Surgery for scoliosis in Duchenne muscular dystrophy.
Scoliosis in patients with Duchenne muscular dystrophy (DMD) is usually progressive and is treated with surgery. However, it is unclear whether the existing evidence is sufficiently scientifically rigorous to support a recommendation for spinal surgery for most patients with DMD and scoliosis. This is an updated review, and an updated search was undertaken in which no new studies were found for inclusion. To determine the effectiveness and safety of spinal surgery in patients with DMD with scoliosis. We intended to test whether spinal surgery is effective in increasing survival and improving respiratory function, quality of life, and overall functioning, and whether spinal surgery is associated with severe adverse effects. On 16 June 2015 we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL Plus. We also searched ProQuest Dissertation and Thesis database (January 1980 to June 2015), the National Institutes of Health Clinical Trials Database (6 January 2015), and the WHO International Clinical Trials Registry Platform (17 June 2015), and checked references. We imposed no language restrictions. We planned to include controlled clinical trials using random or quasi-random allocation of treatment evaluating all forms of spinal surgery for scoliosis in patients with DMD in the review. The control interventions would have been no treatment, non-operative treatment, or a different form of spinal surgery. We used standard methodological procedures expected by The Cochrane Collaboration. Two review authors independently examined the search results and evaluated the study characteristics against inclusion criteria in order to decide which studies to include in the review. Of the 49 relevant studies we found, none met the inclusion criteria for the review because they were not clinical trials, but prospective or retrospective reviews of case series. Since no randomized controlled clinical trials were available to evaluate the effectiveness of scoliosis surgery in patients with DMD, we can make no good evidence-based conclusion to guide clinical practice. Patients with scoliosis should be informed as to the uncertainty of benefits and potential risks of surgery for scoliosis. Randomized controlled trials are needed to investigate the effectiveness of scoliosis surgery, in terms of quality of life, functional status, respiratory function, and life expectancy.


Bacteremia in diabetic patients with infected lower extremities.
Eleven cases of bacteremia in diabetic patients with infected lower extremities at Rancho Los Amigos Hospital (RLAH) were observed over a 34-mo period. The yearly incidence was 0.6% of admissions to the Ortho-Diabetes service. Aerobic bacteria were recovered in six cases and anaerobic bacteria in five. Bacteroides fragilis was isolated four times, Staphylococcus aureus three times, and nonfragilis Bacteroides sp., Escherichia coli, group B streptococcus, and viridans streptococcus were each seen once. Ten of the 11 patients were febrile at the time of bacteremia. Clinical, laboratory, radiologic, and ultrasonographic parameters were comparable in patients with aerobic and anaerobic bacteremia, and between bacteremic patients and nonbacteremic controls. Fever, however, was significantly more frequent in bacteremic patients. Foul-smelling lesions were seen in two of the five patients with anaerobic bacteremia, and in none of the patients with aerobic bacteremia. Postoperative B. fragilis bacteremia was observed to be transient and resolved without definitive therapy in one patient. Appropriate antibiotic therapy in 10 patients together with surgical intervention in eight cases resulted in resolution of the infection in the remaining patients.


Trial of remote telemedicine support for patients with chronic respiratory failure at home through a multistation communication system.
To create and test a multistation telemedicine support system, three remote locations were connected: the homes of two patients with chronic respiratory failure, the hospital of the attending physician, and the hospital of the pulmonary specialist. Real-time connections were set up between the three locations. Medical history and biologic variables were noninvasively recorded, including blood pressure, arterial oxygen saturation, three-lead electrocardiogram, and end-tidal carbon dioxide. Both physicians shared in these data real-time. If necessary, the respiratory specialist could provide medical advice to the attending physician based on the patient's condition. The trial program resulted in the same information being exchanged remotely using the multi-station telemedicine system that would be exchanged in a direct, face-to-face encounter. This result, together with the improvement in quality of life and the establishment of appropriate treatment and cooperation between the respiratory specialist and attending physician, suggests our system can be considered useful and promising for further use.


Conceptualizing the neurobiology of non-suicidal self-injury from the perspective of the Research Domain Criteria Project.
Non-suicidal self-injury (NSSI) commonly starts in adolescence and is associated with an array of negative outcomes. Neurobiological research investigating NSSI is in its early stages and most studies have examined this behavior within the context of specific diagnoses. However, the Research Domain Criteria (RDoC) initiative encourages researchers to examine brain-behavior relationships across diagnoses. This review on the neurobiology associated with NSSI is organized using the domains proposed by RDoC: Negative Valence, Positive Valence, Cognitive, Social Processes, and Arousal/Regulatory Systems. Evidence of neurobiological anomalies is found in each of these domains. We also propose future research directions, especially in regard to human development. Future NSSI studies should address this behavior independent of diagnosis, examine relevant constructs across multiple units of analysis, and assess how systems change across development and course of illness. These advances will be essential for guiding neurobiologically informed intervention and prevention strategies to target NSSI. In doing so, we may prevent the associated negative outcomes across the lifespan.


Isolation of Brucella abortus biovar 1 from human lumbar disc bulging: a case report of brucellar discitis.
Brucellosis is an endemic zoonotic disease with rising health and economic concerns in many areas worldwide. Musculoskeletal pains are among the main complications of human brucellosis, which are often difficult to diagnose due to the variability of clinical symptoms. Brucellar discitis is a very disabling problem in some chronic forms of the disease which may lead to serious vertebral and neurological consequences. In this case report, we reported the isolation of Brucella abortus from lumbar disc bulging in a woman who had rheumatoid arthritis and diabetes mellitus as underlying conditions. The patient had several negative brucellosis serological tests and dorsolumbar pains with urinary incontinence over a 2-month period. The diagnosis was confirmed by magnetic resonance imaging (MRI) examination of lumbar spine as well as disc culture. MRI examination was performed without intravenous contrast and revealed the presence of disc bulging, left foraminal narrowing at L5-S1, left foraminal narrowing, anterolisthesis grade II at L4-L5. The diagnosis was also confirmed by isolation of B. abortus biovar 1 from bulging disc culture. The isolate was characterized by AMOS PCR, Bruce-ladder PCR and biotyping, resulting in the identification of B. abortus from L4-L5 and L5-S1 disc bulging regions. The patient was treated with two drugs i.e. doxycycline and rifampin for 3 months. In the follow-up, in addition to improving the patient's general condition, low-back pain was also significantly reduced. MRI, serology, cultural and molecular test along with patient history are important to make a rapid diagnosis of brucellosis' discitis, thereby decreasing the delay for the brucellosis treatment. The present report suggests that the infection by Brucella spp. should be fundamentally considered among the causative agents of back pain especially in the endemic areas of Brucella infections.


Congenital hemophilia A diagnosed with postoperative hemorrhage after thyroidectomy for papillary thyroid carcinoma: a case report.
Postoperative bleeding in thyroid surgery is a serious complication with fatal outcomes. Risk factors for postoperative hemorrhage have been reported as old age, male sex, Graves' disease, use of anticoagulants, and hematological disorders. Among the hematological diseases, congenital hemophilia is an inherited bleeding disorder characterized by absence or reduced levels of clotting factors VIII or IX. Most patients with hemophilia display bleeding symptoms during infancy or childhood, but diagnosis could be delayed in mild cases. We report a case of congenital hemophilia A that was diagnosed after three episodes of postoperative bleeding after thyroid surgery. A 46-year-old man developed repeated postoperative hemorrhage after thyroid surgery for thyroid cancer. In this case, several irregularities were seen in the postoperative course, such as a relatively long interval between surgery and bleeding, the lack of an obvious bleeding point, fresh red blood dripping from the drain insertion site on the second postoperative day, and repeated bleeding three times. We therefore considered that the cause of postoperative hemorrhage might be other than the surgical operations. After a thorough examination, hemophilia A was diagnosed. Hemophilia is a risk factor for postoperative bleeding in thyroid surgery. However, mild hemophilia shows normal prothrombin time and activated partial thromboplastin time. We encountered a case of papillary thyroid carcinoma associated with congenital hemophilia A, which was diagnosed after repeated bleeding.


The economic value of health care data.
The amount of health care data in our world has been exploding, and the ability to store, aggregate, and combine data and then use the results to perform deep analyses have become ever more important. "Big data," large pools of data that can be captured, communicated, aggregated, stored, and analyzed, are now part of every sector and function of the global economy. While most research into big data thus far has focused on the question of their volume, there is evidence that the business and economic possibilities of big data and their wider implications are important for consideration. It is even offering the possibility that health care data could become the most valuable asset over the next 5 years as "secondary use" of electronic health record data takes off.


In vivo kinetics of thymidylate synthetase inhibition of 5-fluorouracil-sensitive and -resistant murine colon adenocarcinomas.
The predictive utility of several biochemical parameters of 5-fluorouracil (5-FUra) action was evaluated in four murine colonic adenocarcinomas: 5-FUra-sensitive Tumor 38 and 5-FUra-resistant Tumors 07/A, 51 and 06/A. Thymidylate synthetase (TS) was determined by a tritiated 5-fluoro-2'-deoxyuridylate (FdUMP)-binding assay. Bolus 5-FUra (80 mg/kg, i.p.) administrated caused in all tumors a rapid decrease in free TS levels. Only Tumor 38, however, showed inhibition of TS to undetectable (less than 0.05 pmol/g) levels, which lasted up to 6 hr after treatment; correction for dissociation of endogenous TS: FdUMP:folate ternary complex during the TS assay was required. Total TS (free enzyme plus ternary complex) was determined with experimental conditions that achieved quantitative recovery of free TS from ternary complex. By 48 hr after 5-FUra, Tumor 38 showed a decrease in total TS proportional to the estimated log kill/dose of 5-FUra; in contrast, the resistant tumors showed no such decrease from pretreatment levels. Assay of FdUMP showed that the free nucleotide was formed rapidly in all tumors in excess over available TS-binding sites. However, tumor sensitivity did not correlate with peak or residual FdUMP levels or with deoxyuridylate levels, which were low and remained so in all tumors. Tumor sensitivity to 5-FUra also could not be explained by the small differences among the tumors in total perchloric acid-soluble metabolites of 5-FUra or drug incorporation into RNA. We conclude from these data that levels of free TS in the tumor after 5-FUra treatment are predictive of chemotherapeutic response in these murine models of human colonic adenocarcinoma.


SELID: Selective Event Labeling for Intrusion Detection Datasets.
A large volume of security events, generally collected by distributed monitoring sensors, overwhelms human analysts at security operations centers and raises an alert fatigue problem. Machine learning is expected to mitigate this problem by automatically distinguishing between true alerts, or attacks, and falsely reported ones. Machine learning models should first be trained on datasets having correct labels, but the labeling process itself requires considerable human resources. In this paper, we present a new selective sampling scheme for efficient data labeling via unsupervised clustering. The new scheme transforms the byte sequence of an event into a fixed-size vector through content-defined chunking and feature hashing. Then, a clustering algorithm is applied to the vectors, and only a few samples from each cluster are selected for manual labeling. The experimental results demonstrate that the new scheme can select only 2% of the data for labeling without degrading the F1-score of the machine learning model. Two datasets, a private dataset from a real security operations center and a public dataset from the Internet for experimental reproducibility, are used.


A positive feedback loop promotes HIF-1α stability through miR-210-mediated suppression of RUNX3 in paraquat-induced EMT.
Irreversible pulmonary fibrosis induced by paraquat (PQ) poisoning is the major cause of death in patients with PQ poisoning. The epithelial-mesenchymal transition (EMT) is postulated to be one of the main mechanisms of pulmonary fibrosis. Here, we investigated the role of miR-210 in PQ-induced EMT and its relationship with hypoxia-inducible factor-1α (HIF-1α). Western blotting, immunofluorescence, immunoprecipitation and other methods were used in this study. We found that miR-210 expression was significantly increased after PQ poisoning, and it may be regulated by HIF-1α. Overexpression of miR-210 further increased the HIF-1α protein level and promoted EMT. Moreover, miR-210 knock-down reduced the HIF-1α protein level and decreased the degree of EMT. Runt-related transcription factor-3 (RUNX3), a direct target of miR-210, was inhibited by miR-210 in response to PQ poisoning. RUNX3 increased the hydroxylation ability of prolyl hydroxylase domain-containing protein 2 (PHD2), a key enzyme that promotes HIF-1α degradation. PHD2 immunoprecipitated with RUNX3 and its level changed similarly to that of RUNX3. The expression of the HIF-1α protein was significantly reduced when RUNX3 was overexpressed. HIF-1α protein levels were markedly increased when RUNX3 was silenced. Based on these results, a positive feedback loop may exist between miR-210 and HIF-1α. The mechanism may function through miR-210-mediated repression of RUNX3, which further decreases the hydroxylation activity of PHD2, enhances the stability of HIF-1α, and promotes PQ-induced EMT, aggravating the progression of pulmonary fibrosis. This study further elucidates the mechanism of PQ-induced pulmonary fibrosis and may provide a new perspective for the future development of therapies.


TNF-induced beta2 integrin activation involves Src kinases and a redox-regulated activation of p38 MAPK.
We previously demonstrated that the TNF-alpha-induced inside-out signaling leading to beta(2) integrin activation is redox regulated. To identify kinases involved in this pathway, the effects of kinase inhibitors on the expression of beta(2) integrin activation neoepitope (clone 24) were investigated. We show that both p38 MAPK (inhibited by SB203580) and Src kinases (inhibited by PP2) are involved in beta(2) integrin activation by TNF and oxidants in human neutrophils. Src kinases appeared constitutively active in resting neutrophils and not further activated by TNF or oxidants in nonadherent conditions. However, PP2 blocked both TNF-induced expression of the 24 epitope and cell adhesion promoted by the integrin activating anti-CD18 KIM185 mAb, showing that both the inside-out and the outside-in signaling involve Src kinases. p38 MAPK was activated by TNF and oxidants in nonadherent conditions i.e., with 10 mM EDTA. This activation in EDTA resulted in CD11b, CD35 and CD66 up-regulation and in an oxidative response, all blocked by SB203580 and PP2. p38 MAPK was not activated upon direct integrin activation by KIM185 mAb. Thus, p38 activation allows the study to distinguish the initial transduction pathway leading to beta(2) integrin activation from the signaling resulting from integrin engagement. Finally, p38 MAPK activation by TNF was blocked by diphenylene iodonium, an inhibitor of flavoprotein oxidoreductase, and by the free radical scavenger N-acetylcystein. Taken together, these results demonstrate, for the first time, that constitutively activated Src tyrosine kinases and a redox-regulated activation of p38 MAPK are involved in TNF inside-out signaling leading to beta(2) integrin activation.


Personal exposure of traffic police officers to particulate matter, carbon monoxide, and benzene in the city of Milan, Italy.
The aim of this work was to quantify the personal exposure of traffic police officers to particulate matter (PM), carbon monoxide (CO), benzene, toluene, ethylbenzene, and xylenes. The contributions of some behavioral, occupational, and meteorological determinants of exposure also were evaluated. Personal exposure to airborne contaminants was measured on 130 selected volunteers in four seasonal sampling sessions. CO was measured with high sampling frequency. A time-activity diary was completed by traffic police officers during their work shift. Mean (median) personal exposure levels of carbon monoxide, respirable particles (PM(resp)), and benzene were 3.51 (3.22) mg/m(3), 128 (115) microg/m(3) and 11.5 (9.6) microg/m(3), respectively. The highest ambient mean levels of PM(resp), CO, and benzene were found during cold seasons. Measurements taken where traffic is directed, schools are guarded, and other outdoor tasks are performed showed the highest median CO concentrations. As expected, wind decreased exposure to CO and benzene. Exposure was not significantly affected by active tobacco smoke. A key finding was that airborne concentrations determined by fixed measurement stations reported in other studies greatly underestimated traffic officers' exposure to airborne contaminants. The proximity to an emission source determined by the occupational activity was the factor that most affected exposure. For this reason, fixed stations are poor predictors of roadside exposures to airborne pollutants.


Quasiperiodic forcing of coupled chaotic systems.
We study the manner in which the effect of quasiperiodic modulation is transmitted in a coupled nonlinear dynamical system. A system of Rössler oscillators is considered, one of which is subject to driving, and the dynamics of other oscillators which are, in effect, indirectly forced is observed. Strange nonchaotic dynamics is known to arise only in quasiperiodically driven systems, and thus the transmitted effect is apparent when such motion is seen in subsystems that are not directly modulated. We also find instances of imperfect phase synchronization with forcing, where the system transits from one phase synchronized state to another, with arbitrary phase slips. The stability of phase synchrony for arbitrary initial conditions with identical forcing is observed as a general property of strange nonchaotic motion.


Hyperacusis in Children with Attention Deficit Hyperactivity Disorder: A Preliminary Study.
The association between hyperacusis and developmental disorders such as autism spectrum disorders has been extensively reported in the literature; however, the specific prevalence of hyperacusis in attention deficit hyperactivity disorder (ADHD) has never been investigated. In this preliminary study, we evaluated the presence of hyperacusis in a small sample of children affected by ADHD compared to a control group of healthy children. Thirty normal hearing children with a diagnosis of ADHD and 30 children matched for sex and age were enrolled in the study. All children underwent audiological and multidisciplinary neuropsychiatric evaluation. Hearing was assessed using pure tone audiometry and immittance test; ADHD was diagnosed following the Diagnostic and Statistical Manual of Mental Disorder criteria. Hyperacusis was assessed through the administration of a questionnaire to parents and an interview with children. Hyperacusis was diagnosed in 11 children (36.7%) in the study group and in four children (13.3%) in the control group; this difference was statistically significant (p = 0.03). The preliminary results of this study suggest a higher presence of hyperacusis in children with attention deficit hyperactivity disorder compared to control children. More studies on larger samples are necessary to confirm these results.


Nitrogen incorporation in saturated aliphatic C6-C8 hydrocarbons and ethanol in low-pressure nitrogen plasma generated by a hollow cathode discharge ion source.
Ion/molecule reactions of saturated hydrocarbons (n-hexane, cyclohexane, n-heptane, n-octane and isooctane) in 28-Torr N2 plasma generated by a hollow cathode discharge ion source were investigated using an Orbitrap mass spectrometer. It was found that the ions with [M+14](+) were observed as the major ions (M: sample molecule). The exact mass analysis revealed that the ions are nitrogenated molecules, [M+N](+) formed by the reactions of N3 (+) with M. The reaction, N3 (+) + M → [M+N](+) + N2 , were examined by the density functional theory calculations. It was found that N3 (+) abstracts the H atom from hydrocarbon molecules leading to the formation of protonated imines in the forms of R'R″CNH2 (+) (i.e. C-H bond nitrogenation). This result is in accord with the fact that elimination of NH3 is the major channel for MS/MS of [M+N](+) . That is, nitrogen is incorporated in the C-H bonds of saturated hydrocarbons. No nitrogenation was observed for benzene and acetone, which was ascribed to the formation of stable charge-transfer complexes benzene⋅⋅⋅⋅N3 (+) and acetone⋅⋅⋅⋅N3 (+) revealed by density functional theory calculations. Copyright © 2016 John Wiley & Sons, Ltd.


The radiological anatomy of the anterior skull base.
Two complications dominate the thoughts of any surgeon undertaking functional endoscopic sinus surgery (FESS), namely damage to orbital structures and fractures of the fovea ethmoidalis. To avoid these complications, a detailed knowledge of the paranasal sinus anatomy of the patient is essential. This is usually assessed using preoperative computerized tomography (CT) scans of the paranasal sinuses. Analysis of 151 CT scans, measuring the height of cribriform plate below a supraorbital horizontal and above the hard palate was performed. Variation of shape and take-off angle of the fovea ethmoidalis was also measured. Comparison between left and right sides, and between scans showing radiological features of sinonasal disease and normal scans, was undertaken. Five patterns of fovea ethmoidalis were identified. No statistically significant difference between left and right sides was demonstrable for any parameter, irrespective of pathological status.


Snack food consumption of 12 year old inner-city children and its relationship to oral health.
The relations between reported frequency of consumption of 18 common snack foods, SES variables, and oral health scores were studied in 92 12-year-old children from three inner-city schools in Rochester, New York. The group was composed of 44 males and 48 females who were either black or had a Spanish surname. The study documented only a few significant relations between consumption of snack foods and DMF scores or overall oral health. Reported cake consumption correlated positively with total debris and gingivitis, and consumption of chewy candy and ice cream was positively related to DMF scores. Black females exhibited the greatest number of decayed and DMF teeth, and both male and female black children had significantly greater amounts of total debris, gingivitis and decayed teeth.


Chemistry of marine ligands and siderophores.
Marine microorganisms are presented with unique challenges to obtain essential metal ions required to survive and thrive in the ocean. The production of organic ligands to complex transition metal ions is one strategy to both facilitate uptake of specific metals, such as iron, and to mitigate the potential toxic effects of other metal ions, such as copper. A number of important trace metal ions are complexed by organic ligands in seawater, including iron, cobalt, nickel, copper, zinc, and cadmium, thus defining the speciation of these metal ions in the ocean. In the case of iron, siderophores have been identified and structurally characterized. Siderophores are low molecular weight iron-binding ligands produced by marine bacteria. Although progress has been made toward the identity of in situ iron-binding ligands, few compounds have been identified that coordinate the other trace metals. Deciphering the chemical structures and production stimuli of naturally produced organic ligands and the organisms they come from is fundamental to understanding metal speciation and bioavailability. The current evidence for marine ligands, with an emphasis on siderophores, and discussion of the importance and implications of metal-binding ligands in controlling metal speciation and cycling within the world's oceans are presented.


Insurance effects on employer group dental expenditures.
As the number of dental insureds and the amount of insured expenditures have increased over the past decade, so has interest in determining insurance effects on dental demand among employer groups and their insureds. Using Pennsylvania Blue Shield (PBS) employer group data representing 50-65% of all PBS insureds, the authors estimate the own-effect of basic insurance rates (diagnostic, preventive, restorative, endodontic, extraction services) and the cross-effects of riders A (crowns and oral surgery), B (prosthodontics), C (periodontics), and D (orthodontics) insurance rates on annual basic expenditures for 1975-1979. Results indicate a consistently positive relationship between basic insurance rates and expenditures. Orthodontic insurance rates have positive cross-effects on basic expenditures, suggesting basic-orthodontic complementarities. Although not statistically significant, potential substitution relationships may exist between basic and oral surgery, prosthodontic, and periodontic services. The implications of these findings for plan design and public oral health are discussed.


Characterization of Skeletal Muscle Strain Lesion Induced by Stretching in Rats: Effects of Laser Photobiomodulation.
Unusual and exhaustive physical exercise can lead to muscle lesions depending on the type of contraction, intensity, duration, age, and level of conditioning. Different therapies have been proposed to prevent or reduce exercise-induced muscle damage. In this study, we investigate the effects of low-level laser therapy on skeletal muscle strain in an experimental model in rats. Male Wistar rats (200 g) were used. The animals were randomized into groups of six animals. We performed tibialis muscle elongation using a previously described protocol. The animals were anesthetized and submitted to passive stretching of the anterior tibial muscle attached to a weight corresponding to 150% of the body mass of the animal for 20 min, rested for 3 min, and received a second traction for 20 min. The cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10, edema, and C-reactive protein (CRP) levels were determined in the tibialis anterior muscle. Plasma extravasation of groups treated with different doses of laser energy, lesion +1 J (2.61 ± 0.46), lesion +3 J (2.33 ± 0.13), lesion +6 J (2.92 ± 0.91), and lesion +9 J (2.80 ± 0.55), shows a significant reduction of extravasation when compared with the injury group (5.46 ± 1.09). Laser therapy was able to significantly reduce CRP and cytokine levels (TNF-α, IL-1β, IL-6, and IL-10). Laser photobiomodulation reduced skeletal muscle edema as well as cytokines and CRP, leading to a significant reduction in inflammatory markers.


Physically active academic lessons and effect on physical activity and aerobic fitness. The Active School study: A cluster randomized controlled trial.
The Active School program was designed to positively impact health and academic-related outcomes in school. The core intervention component was physically active academic lessons, a teaching activity that combines physical activity and educational content. The purpose of this study was to investigate the effect of a 10-month, cluster-randomized controlled trial on physical activity level and aerobic fitness conducted in the city of Stavanger, Norway, in 2014-15. The physical activity level during physically active academic lessons was also studied. A total of 447 children (9-10 years) participated. The weekly intervention consisted of physically active academic lessons, physically active homework and physically active recess. Physical activity level and aerobic fitness were measured objectively by accelerometry and a 10-minute interval running test. Intervention effects were found for time in moderate to vigorous physical activity (MVPA) (adjusted mean difference of 8 min/day, 95% CI: 3.4-13, p < 0.001) and total physical activity (60 counts/min, 95% CI: 15-105, p = 0.009). Children with low aerobic fitness increased their running distance compared to controls (d = 0.46; p = 0.001). During physically active academic lessons children spent 26% of the time in MVPA, which was comparable to physical education lessons. The Active School program successfully increased physical activity for the intervention group and aerobic fitness for the least fit children. The activity level during physically active academic lessons was as high as in physical education lessons. Clinicaltrail.gov ID identifier: NCT03436355.


Long-term survival of Escherichia coli O157:H7 and Salmonella enterica on butterhead lettuce seeds, and their subsequent survival and growth on the seedlings.
The long-term survival of enteric pathogens on butterhead lettuce seeds, and their subsequent survival and growth on seedlings were investigated. Lettuce seeds were inoculated at a high level with two Salmonella enterica and two Escherichia coli O157:H7 strains each (±8 log₁₀ CFU/g seed) and the survival of the pathogens was monitored over two years using standard plating techniques on selective medium. The Salmonella strains (serovars Typhimurium and Thompson) survived significantly better on the seeds than the E. coli O157:H7 strains (MB3885 and NCTC12900). When individual seeds were tested two years after inoculation, Salmonella was recovered from each individual seed, whereas E. coli O157:H7 only from 4% to 14% of the seeds, depending on the recovery method. When contaminated stored seeds were germinated and the seedlings examined for presence of the pathogens, it was clear that both pathogens were able to proliferate on the seedlings. Pathogen counts up to 5.92 log₁₀ CFU and 4.41 log₁₀ CFU per positive seedling were observed for Salmonella and E. coli O157:H7, respectively. Our study not only confirms the long-term survival of enteric pathogens on seeds but also shows that the pathogens maintain their ability to resuscitate and proliferate on the seedlings. Seeds or seedlings should be considered as contamination sources for the cultivation of leafy vegetables such as butterhead lettuce grown in greenhouses.


A mitochondria-targeted chemiluminescent probe for detection of hydrogen sulfide in cancer cells, human serum and in vivo.
Hydrogen sulfide (H2S) as a critical messenger molecule plays vital roles in regular cell function. However, abnormal levels of H2S, especially mitochondrial H2S, are directly correlated with the formation of pathological states including neurodegenerative diseases, cardiovascular disorders, and cancer. Thus, monitoring fluxes of mitochondrial H2S concentrations both in vitro and in vivo with high selectivity and sensitivity is crucial. In this direction, herein we developed the first ever example of a mitochondria-targeted and H2S-responsive new generation 1,2-dioxetane-based chemiluminescent probe (MCH). Chemiluminescent probes offer unique advantages compared to conventional fluorophores as they do not require external light irradiation to emit light. MCH exhibited a dramatic turn-on response in its luminescence signal upon reacting with H2S with high selectivity. It was used to detect H2S activity in different biological systems ranging from cancerous cells to human serum and tumor-bearing mice. We anticipate that MCH will pave the way for development of new organelle-targeted chemiluminescence agents towards imaging of different analytes in various biological models.


Metastasis Seeding Cells: Lone Invaders or Mass Migrators?
Lymph node metastases are among the best predictors of recurrence and of cancer-related death in early-stage colorectal cancers. Yet, despite their clinical and biological relevance, it remains elusive how lymph node metastases develop and whether metastatic seeding is a major bottleneck that restrains genetic heterogeneity of metastatic disease. Clin Cancer Res; 24(9); 2032-4. ©2018 AACRSee related article by Ulintz et al., p. 2214.


Double aortic arch anomalies in Children: A Systematic 20-Year Single Center Study.
Aortic arch anomalies underlie numerous congenital disorders. Effectively diagnosing and treating them requires close understanding of cardiovascular embryology. As our Center serves the entire pediatric population of our country, we performed a comprehensive retrospective analysis of all aortic arch anomalies diagnosed at our Center over the past 20 years. We analyzed 40 children with aortic arch anomalies, distinguishing two defect types: Group 1 displayed ring-forming anomalies, and Group 2 other types of aortic arch anomalies that did not form a vascular ring. We performed detailed morphological analyses using echocardiography, angiography, computed tomography, or magnetic resonance imaging and generated a catalog of all aortic arch anomalies present. Group 1 was represented by 25 patients; 40% with persistent both aortic arches, and 60% with various forms of right aortic arch and an incomplete left aortic arch. Group 2 was represented by 15 patients with complex heart defects. On the basis of our dataset, the incidence of all aortic arch anomalies was 0.033%, and of ring-forming pathologies 0.021%. Although aortic arch anomalies are rare, it is important to diagnose them correctly. It is critical to distinguish ring-forming types. Although in complex defects the aortic arch anomaly represents only an additive diagnosis, its correct definition could be crucial for further management. Cumulatively, this unique, long-term study provides a systematic patient registry and offers critical epidemiological data to aid the study of rare congenital cardiovascular defects. Clin. Anat. 30:929-939, 2017. © 2017 Wiley Periodicals, Inc.


MicroRNA prediction with a novel ranking algorithm based on random walks.
MicroRNA (miRNAs) play essential roles in post-transcriptional gene regulation in animals and plants. Several existing computational approaches have been developed to complement experimental methods in discovery of miRNAs that express restrictively in specific environmental conditions or cell types. These computational methods require a sufficient number of characterized miRNAs as training samples, and rely on genome annotation to reduce the number of predicted putative miRNAs. However, most sequenced genomes have not been well annotated and many of them have a very few experimentally characterized miRNAs. As a result, the existing methods are not effective or even feasible for identifying miRNAs in these genomes. Aiming at identifying miRNAs from genomes with a few known miRNA and/or little annotation, we propose and develop a novel miRNA prediction method, miRank, based on our new random walks- based ranking algorithm. We first tested our method on Homo sapiens genome; using a very few known human miRNAs as samples, our method achieved a prediction accuracy greater than 95%. We then applied our method to predict 200 miRNAs in Anopheles gambiae, which is the most important vector of malaria in Africa. Our further study showed that 78 out of the 200 putative miRNA precursors encode mature miRNAs that are conserved in at least one other animal species. These conserved putative miRNAs are good candidates for further experimental study to understand malaria infection. MiRank is programmed in Matlab on Windows platform. The source code is available upon request.


Defective production of monocyte-activating cytokines in lepromatous leprosy.
We have examined the capacity of monocytes from patients with leprosy to undergo activation and the capacity of mononuclear cells from these patients to incorporate [3H]thymidine and produce monocyte-activating cytokines. Monocytes from patients with either lepromatous or tuberculoid leprosy were activated by concanavalin A (Con A)-induced mononuclear cell supernatants generated from the leukocytes of a normal person. Monocytes activated by these supernatants strongly inhibited L. pneumophila multiplication, and the degree of inhibition was comparable in both groups of patients. Mononuclear cells from patients with either form of leprosy responded comparably to Con A with vigorous [3H]thymidine incorporation. Mononuclear cells from patients with tuberculoid leprosy also vigorously incorporated [3H]thymidine in response to M. leprae antigens. In contrast, mononuclear cells from patients with lepromatous leprosy did not exhibit significant [3H]thymidine incorporation in response to M. leprae antigens. The capacity of mononuclear cells to generate monocyte-activating cytokines generally paralleled their capacity to incorporate [3H]thymidine in response to Con A and M. leprae. Mononuclear cells from patients with either form of leprosy responded to Con A with the production of cytokines (supernatants) able to activate normal monocytes, expressed by inhibition of L. pneumophila multiplication. However Con A-induced supernatants from patients with lepromatous leprosy were less potent than Con A-induced supernatants from patients with tuberculoid leprosy. Mononuclear cells from patients with tuberculoid leprosy responded to M. leprae antigens with the production of potent monocyte-activating supernatants. In contrast, mononuclear cells from patients with lepromatous leprosy did not produce monocyte-activating cytokines in response to M. leprae antigens. These studies support the hypothesis that the immunological defect in lepromatous leprosy results from a failure to activate mononuclear phagocytes rather than from an intrinsic inability of these cells to be activated. We suggest that the failure to activate mononuclear phagocytes stems from defective production of monocyte-activating cytokines in response to M. leprae antigens.


Achieving tunable Kerker-type invisibility for a radiation-enhanced electrically small antenna.
Low-temperature gaseous plasmas exhibit great potential in designing tunable and reconfigurable electromagnetic devices. In this paper, based on an overdense-underdense core-shell plasma structure, tunable Kerker-type invisibility for a radiation-enhanced electrically small antenna is achieved, where dominant scattering direction can be mutated between backward and forward while omnidirectional invisibility and signal enhancement are maintained. Moreover, by electromagnetic multipole decompositions, it is shown that the underdense outer plasma with a negative polarizability is able to weaken the strength and modulate the phase of the electric dipolar scattering component (a_{1}), while the magnetic dipolar term (b_{1}) nearly remains unchanged. Consequently, quasi-first and -second Kerker conditions are fulfilled near the cutoff band of a_{1}.


The potential role of microbes in oncogenesis with particular emphasis on oral cancer.
For over a century, non-virus microorganisms, notably bacteria have been implicated as causal agents of cancers, a relatively small number of researchers have provided evidence to support the so-called "cancer germ" hypothesis. With the exception of the link between Helicobacter pylori and stomach cancer, other supposed links have been ignored. A wide range of bacteria and other non-virus microbes, including fungi, have been implicated over the years in oncogenesis, as well as the ability to induce inflammation, which may cause cancer. It seems that there is no single "cancer germ," as most bacteria can apparently induce cancer. Here, the role of bacteria and other non-virus microorganisms and oral cancers will be discussed. By ignoring bacteria as a causal agent of cancer, we set back our understanding of this crucially important disease and, as a result, have hindered the development of potential cures.


A major difference between the divergence patterns within the lines-1 families in mice and voles.
L1 retroposons are represented in mice by subfamilies of interspersed sequences of varied abundance. Previous analyses have indicated that subfamilies are generated by duplicative transposition of a small number of members of the L1 family, the progeny of which then become a major component of the murine L1 population, and are not due to any active processes generating homology within preexisting groups of elements in a particular species. In mice, more than a third of the L1 elements belong to a clade that became active approximately 5 Mya and whose elements are > or = 95% identical. We have collected sequence information from 13 L1 elements isolated from two species of voles (Rodentia: Microtinae: Microtus and Arvicola) and have found that divergence within the vole L1 population is quite different from that in mice, in that there is no abundant subfamily of homologous elements. Individual L1 elements from voles are very divergent from one another and belong to a clade that began a period of elevated duplicative transposition approximately 13 Mya. Sequence analyses of portions of these divergent L1 elements (approximately 250 bp each) gave no evidence for concerted evolution having acted on the vole L1 elements since the split of the two vole lineages approximately 3.5 Mya; that is, the observed interspecific divergence (6.7%-24.7%) is not larger than the intraspecific divergence (7.9%-27.2%), and phylogenetic analyses showed no clustering into Arvicola and Microtus clades.


Protein universe containing a PUA RNA-binding domain.
Here, we review current knowledge about pseudouridine synthase and archaeosine transglycosylase (PUA)-domain-containing proteins to illustrate progress in this field. A methodological analysis of the literature about the topic was carried out, together with a 'qualitative comparative analysis' to give a more comprehensive review. Bioinformatics methods for whole-protein or protein-domain identification are commonly based on pairwise protein sequence comparisons; we added comparison of structures to detect the whole universe of proteins containing the PUA domain. We present an update of proteins having this domain, focusing on the specific proteins present in Homo sapiens (dyskerin, MCT1, Nip7, eIF2D and Nsun6), and explore the existence of these in other species. We also analyze the phylogenetic distribution of the PUA domain in different species and proteins. Finally, we performed a structural comparison of the PUA domain through data mining of structural databases, determining a conserved structural motif, despite the differences in the sequence, even among eukaryotes, archaea and bacteria. All data discussed in this review, both bibliographic and analytical, corroborate the functional importance of the PUA domain in RNA-binding proteins.


Outcome of calcaneoplasty in insertional achilles tendinopathy.
Insertional Achilles tendinopathy may be associated with Haglund's deformity and result in chronic pain. It is usually refractory to conservative management. The aim of this study was to assess the outcome of calcaneoplasty performed in our hospital. Eight patients were prospectively evaluated pre- and postoperatively using the American Orthopaedic Foot and Ankle Society (AOFAS) Hindfoot Score, Visual Analogue Scale (VAS) and Short Form (SF) 36, as well as satisfaction rate. Average follow-up duration was 12.4 months. The mean pre and post-operative AOFAS scores were significantly improved at three and six months. SF 36 improved in most parameters. The postoperative VAS score improved significantly and was 0 at 2 years. The procedure was rated as good to excellent by seven of the subjects. We recommend calcaneoplasty for the treatment of insertional Achilles tendinopathy. Calcaneoplasty, Insertional Achilles tendinopathy, Haglund's deformity.


Cloning and expression of an iron-containing superoxide dismutase in the parasitic protist, Trichomonas vaginalis.
A superoxide dismutase (SOD) gene of the parasitic protist Trichomonas vaginalis was cloned, sequenced, expressed in Escherichia coli, and its gene product characterized. It is an iron-containing dimeric protein with a monomeric mass of 22,067 Da. Southern blots analyses suggested the presence of seven iron-containing (FeSOD) gene copies. Hydrophobic cluster analysis revealed some peculiarities in the 2D structure of the FeSOD from T. vaginalis and a strong structural conservation between prokaryotic and eukaryotic FeSODs. Phylogenetic reconstruction of the SOD sequences confirmed the dichotomy between FeSODs and manganese-containing SODs. FeSODs of protists appeared to group together with homologous proteobacterial enzymes suggesting a possible origin of eukaryotic FeSODs through an endosymbiotic event.


Interventions minimizing fatigue in children/adolescents with cancer: An integrative review.
Fatigue is among the most common, debilitating, and distressing symptoms associated with chronic condition in pediatric population. The purpose of this study was to identify non-pharmacological fatigue interventions in children and adolescents with cancer. For this, we carried out an integrative review of the literature from January 2000 to December 2016. A comprehensive search of four databases was conducted: Cumulative Index to Nursing and Allied Health Literature, Psychology Information, Medline via PubMed, and Web of Science. Randomized controlled trial, quasi-experimental, case-control and cohort studies were included in this review. Thirteen relevant studies were included for analysis. Seven papers reported positive outcomes for exercise, exercise plus leisure activities, healing touch and acupressure. In another six papers using exercise, exercise plus psychological intervention and massage, no effectiveness was found. Effective management of fatigue in children and adolescents is important but research in this area is limited, so the results of this review should be interpreted cautiously. Future researchers are encouraged to test the effective interventions in homogenous cancer populations and in other groups where fatigue is a common concern.


Skeletal 18F-PSMA-1007 uptake in prostate cancer patients.
Accurate and uniform interpretation and reporting of metastatic prostate cancer (PCa) lesions on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) are indispensable. 18F-PSMA-1007 is increasingly used because of its favorable imaging characteristics. However, increased non-specific skeletal uptake may be an important pitfall of this radioligand. Therefore, we aimed to assess the interobserver variation in reporting skeletal 18F-PSMA-1007 uptake on PET/CT. In total, 33 18F-PSMA-1007 PET/CT scans of 21 patients with primary PCa and 12 patients with biochemical recurrence were included, and a total of 85 skeletal lesions were evaluated by three independent observers. The primary endpoint was the interobserver variability of the likelihood of malignancy of the skeletal lesions on both patient and lesion level (kappa analysis). Observers qualified most lesions as not malignant (81-91%) and the overall mean interobserver agreement was moderate on both patient (κ: 0.54) and lesion level (κ: 0.55). In 52 lesions without corresponding CT substrate, the rating resulted in not malignant in 95-100%. Availability of additional imaging (60% of lesions) did not improve interobserver agreement (κ: 0.39 on lesion level) and resulted in unchanged rating for all observers in 78%. This interobserver analysis of skeletal 18F-PSMA-1007 uptake resulted in moderate agreement, in line with rates reported in literature. Importantly, the presence of non-specific skeletal uptake without CT substrate, as a potential shortcoming of 18F-PSMA-1007, did not impair interobserver agreement.


Multicenter comparison of calibration and cross calibration of PET scanners.
The purpose of this study was to compare the calibration of PET scanners and their cross calibration to peripheral devices in a multicenter study. Twenty-three dedicated PET scanners were investigated, applying standardized protocols. To ensure exact determination of the activity used, dose calibrators were checked using (68)Ge standards. Nine of 19 and 11 of 20 scanners displayed an error of <5% in 3-dimensional and 2-dimensional acquisition modes, respectively. Four and 5 scanners displayed an error of 10% in 3-dimensional and 2-dimensional modes, respectively. All other scanners yielded errors of 5% to <10%. Because of hardware and software problems, the measurements performed on 1 scanner could not be adequately analyzed. An investigation of calibration is mandatory. Especially for quantitative analyses in clinical multicenter trials, identification of potentially miscalibrated scanners is necessary.


Procyanidin C1 from apple extracts inhibits Fc epsilon RI-mediated mast cell activation.
Polyphenol-enriched fractions, which are extracted from unripe apples (Rosaceae, Malus spp.), consisting of procyanidins (polymers of catechins) are known to have an anti-allergenic effect on patients with various allergic diseases. Although it has been reported that apple extracts inhibit histamine release from mast cells, the molecular mechanisms for this anti-allergenic effect are not well understood. To elucidate the molecular mechanisms by which apple extracts induce their anti-allergenic effects, the effects of purified apple extract components on high-affinity receptors for IgE (Fc epsilon RI)-mediated mast cell activation were investigated. The anti-allergic effect of oral administration of apple procyanidin extracts on passive cutaneous anaphylactic responses of BALB/c mice was assessed. We evaluated the effects of procyanidin C1 (PC1) [epicatechin-(4beta-->8)-epicatechin-(4beta-->8)-epicatechin], a component of the procyanidin fraction, on mouse bone-marrow-derived mast cell degranulation, cytokine production, protein tyrosine phosphorylation and on the generation of intracellular reactive oxygen species (ROS) of cells stimulated by Fc epsilon RI cross-linking in vitro. In an in vivo study, oral administration of the procyanidin fraction suppressed the mast-cell-dependent allergic reaction. In in vitro studies, PC1 dose-dependently decreased Fc epsilon RI-mediated degranulation and cytokine production of mast cells. Furthermore, PC1 inhibited tyrosine phosphorylation of Syk and linker for activation of T cells, and the ROS generation in stimulated mast cells. PC1 suppresses Fc epsilon RI-mediated mast cell activation by inhibiting intracellular signaling pathways. These observations provide evidence for the anti-allergenic effects of the procyanidin-enriched apple extract.


Circ_0080940 Regulates miR-139-5p/CTGF Pathway to Promote the Proliferation, Migration, Extracellular Matrix Deposition of Human Tenon's Capsule Fibroblasts.
Circular RNA (circRNA) has been identified as an important regulator for glaucoma progression. Our study aims to reveal the circ_0080940 roles in glaucoma progression. Transforming growth factor β1 (TGF-β1) was used to treat human Tenon's capsule fibroblasts (HTFs) to mimic glaucoma cell models. Cell function was determined by cell counting kit 8 assay, EdU assay and wound healing assay. Protein levels were determined by western blot analysis. Quantitative real-time PCR was used to measure RNA expression. Dual-luciferase reporter assay was performed to evaluate RNA interaction. Our data confirmed that TGF-β1 induced HTFs proliferation, migration and extracellular matrix (ECM) deposition. Circ_0080940 was highly expressed in glaucoma patients, and its knockdown inhibited TGF-β1-induced proliferation, migration and ECM deposition in HTFs. Circ_0080940 sponged miR-139-5p, and anti-miR-139-5p revoked the effect of si-circ_0080940 on the biological functions of TGF-β1-induced HTFs. CTGF was targeted by miR-139-5p, and overexpressed CTGF overturned the inhibition effect of miR-139-5p on the biological functions of TGF-β1-induced HTFs. Furthermore, CTGF expression could be positively regulated by circ_0080940. To sum up, we confirmed that circ_0080940 contributed to glaucoma progression by miR-139-5p/CTGF axis.


Dysbindin Deficiency Modifies the Expression of GABA Neuron and Ion Permeation Transcripts in the Developing Hippocampus.
The neurodevelopmental factor dysbindin is required for synapse function and GABA interneuron development. Dysbindin protein levels are reduced in the hippocampus of schizophrenia patients. Mouse dysbindin genetic defects and other mouse models of neurodevelopmental disorders share defective GABAergic neurotransmission and, in several instances, a loss of parvalbumin-positive interneuron phenotypes. This suggests that mechanisms downstream of dysbindin deficiency, such as those affecting GABA interneurons, could inform pathways contributing to or ameliorating diverse neurodevelopmental disorders. Here we define the transcriptome of developing wild type and dysbindin null Bloc1s8sdy/sdy mouse hippocampus in order to identify mechanisms downstream dysbindin defects. The dysbindin mutant transcriptome revealed previously reported GABA parvalbumin interneuron defects. However, the Bloc1s8sdy/sdy transcriptome additionally uncovered changes in the expression of molecules controlling cellular excitability such as the cation-chloride cotransporters NKCC1, KCC2, and NCKX2 as well as the potassium channel subunits Kcne2 and Kcnj13. Our results suggest that dysbindin deficiency phenotypes, such as GABAergic defects, are modulated by the expression of molecules controlling the magnitude and cadence of neuronal excitability.


Lessons learned from using linked administrative data to evaluate the Family Nurse Partnership in England and Scotland.
"Big data" - including linked administrative data - can be exploited to evaluate interventions for maternal and child health, providing time- and cost-effective alternatives to randomised controlled trials. However, using these data to evaluate population-level interventions can be challenging. We aimed to inform future evaluations of complex interventions by describing sources of bias, lessons learned, and suggestions for improvements, based on two observational studies using linked administrative data from health, education and social care sectors to evaluate the Family Nurse Partnership (FNP) in England and Scotland. We first considered how different sources of potential bias within the administrative data could affect results of the evaluations. We explored how each study design addressed these sources of bias using maternal confounders captured in the data. We then determined what additional information could be captured at each step of the complex intervention to enable analysts to minimise bias and maximise comparability between intervention and usual care groups, so that any observed differences can be attributed to the intervention. Lessons learned include the need for i) detailed data on intervention activity (dates/geography) and usual care; ii) improved information on data linkage quality to accurately characterise control groups; iii) more efficient provision of linked data to ensure timeliness of results; iv) better measurement of confounding characteristics affecting who is eligible, approached and enrolled. Linked administrative data are a valuable resource for evaluations of the FNP national programme and other complex population-level interventions. However, information on local programme delivery and usual care are required to account for biases that characterise those who receive the intervention, and to inform understanding of mechanisms of effect. National, ongoing, robust evaluations of complex public health evaluations would be more achievable if programme implementation was integrated with improved national and local data collection, and robust quasi-experimental designs.


Assessing Similarity Among Individual Tumor Size Lesion Dynamics: The CICIL Methodology.
Mathematical models of tumor dynamics generally omit information on individual target lesions (iTLs), and consider the most important variable to be the sum of tumor sizes (TS). However, differences in lesion dynamics might be predictive of tumor progression. To exploit this information, we have developed a novel and flexible approach for the non-parametric analysis of iTLs, which integrates knowledge from signal processing and machine learning. We called this new methodology ClassIfication Clustering of Individual Lesions (CICIL). We used CICIL to assess similarities among the TS dynamics of 3,223 iTLs measured in 1,056 patients with metastatic colorectal cancer treated with cetuximab combined with irinotecan, in two phase II studies. We mainly observed similar dynamics among lesions within the same tumor site classification. In contrast, lesions in anatomic locations with different features showed different dynamics in about 35% of patients. The CICIL methodology has also been implemented in a user-friendly and efficient Java-based framework.


The embryology of spinal dysraphism.
The theories of abnormal embryogenesis suggested as explanations for the various forms of SBA and occult spinal dysraphism appear in some instances too all encompassing, as in Gardner's hydrodynamic theory or Padget's neuroschisis theory, or too limited, as in the theory of arrested development proposed by Daniel and Strich for the ACM, or just too speculative in many cases. The observation of a completed defect does not allow one to venture backwards in development to a specific time and cause with any accuracy. Perhaps several different causes striking different tissues at different times can set up a series of aberrations that lead to morphologically similar mature anomalies. The ability of developmental processes to heal themselves, as shown experimentally, may obscure the true mechanism and timing of occurrence although the final morphological expression may be dramatic. Since the study of human embryogenesis in the experimental laboratory is ethically unacceptable although technically feasible, the elucidation of the mechanisms of these neural defects will be long in coming.


Effects of neuropeptide FF and related peptides on the antinociceptive activities of VD-hemopressin(α) in naive and cannabinoid-tolerant mice.
Neuropeptide FF (NPFF) system has recently been reported to modulate cannabinoid-induced antinociception. The aim of the present study was to further investigate the roles of NPFF system in the antinociceptive effects induced by intracerebroventricular (i.c.v.) administration of mouse VD-hemopressin(α), a novel endogenous agonist of cannabinoid CB1 receptor, in naive and VD-hemopressin(α)-tolerant mice. The effects of NPFF system on the antinociception induced by VD-hemopressin(α) were investigated in the radiant heat tail-flick test in naive mice and VD-hemopressin(α)-tolerant mice. The cannabinoid-tolerant mice were produced by given daily injections of VD-hemopressin(α) (20 nmol, i.c.v.) for 5 days and the antinociception was measured on day 6. In naive mice, intracerebroventricular injection of NPFF dose-dependently attenuated central analgesia of VD-hemopressin(α). In contrast, neuropeptide VF (NPVF) and D.NP(N-Me)AFLFQPQRF-NH2 (dNPA), two highly selective agonists for Neuropeptide FF1 and Neuropeptide FF2 receptors, enhanced VD-hemopressin(α)-induced antinociception in a dose-dependent manner. In addition, the VD-hemopressin(α)-modulating activities of NPFF and related peptides were antagonized by the Neuropeptide FF receptors selective antagonist 1-adamantanecarbonyl-RF-NH2 (RF9). In VD-hemopressin(α)-tolerant mice, NPFF failed to modify VD-hemopressin(α)-induced antinociception. However, both neuropeptide VF and dNPA dose-dependently potentiated the antinociception of VD-hemopressin(α) and these cannabinoid-potentiating effects were reduced by RF9. The present works support the cannabinoid-modulating character of NPFF system in naive and cannabinoid-tolerant mice. In addition, the data suggest that a chronic cannabinoid treatment modifies the pharmacological profiles of NPFF, but not the cannabinoid-potentiating effects of neuropeptide VF and dNPA.


Dexanabinol: a novel cannabinoid with neuroprotective properties.
Dexanabinol was developed as a synthetic analog of the cannabinoid tetrahydrocannabinol, however, the action of the drug is as a weak, uncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. Dexanabinol is an effective neuroprotectant in animal models of hypoxemia/ischemia, neurotoxin exposure and nerve crush. Unlike some other uncompetitive NMDA receptor antagonists, dexanabinol does not produce psychotrophic effects and is generally well tolerated in humans. In this respect it is similar to the uncompetitive NMDA receptor antagonist memantine. Dexanabinol is currently in phase III clinical trials for severe head injury. It is a promising drug that appears to be able to provide the therapeutic benefits of uncompetitive NMDA-receptor antagonists without the adverse side effects associated with some of the earlier drugs of this type.


Optical phase contrast imaging for absolute, quantitative measurements of ultrasonic fields with frequencies up to 20 MHz.
The technique of phase contrast imaging, combined with tomographic reconstructions, can rapidly measure ultrasonic fields propagating in water, including ultrasonic fields with complex wavefront shapes, which are difficult to characterize with standard hydrophone measurements. Furthermore, the technique can measure the absolute pressure amplitudes of ultrasonic fields without requiring a pressure calibration. Absolute pressure measurements have been previously demonstrated using optical imaging methods for ultrasonic frequencies below 2.5 MHz. The present work demonstrates that phase contrast imaging can accurately measure ultrasonic fields with frequencies up to 20 MHz and pressure amplitudes near 10 kPa. Accurate measurements at high ultrasonic frequencies are performed by tailoring the measurement conditions to limit optical diffraction as guided by a simple dimensionless parameter. In some situations, differences between high frequency measurements made with the phase contrast method and a calibrated hydrophone become apparent, and the reasons for these differences are discussed. Extending optical imaging measurements to high ultrasonic frequencies could facilitate quantitative applications of ultrasound measurements in nondestructive testing and medical therapeutics and diagnostics such as photoacoustic imaging.


Combining protein-shelled platinum nanoparticles with graphene to build a bionanohybrid capacitor.
The electronic properties of biomolecules and their hybrids with inorganic materials can be utilized for the fabrication of nanoelectronic devices. Here, we report the charge transport behavior of protein-shelled inorganic nanoparticles combined with graphene and demonstrate their possible application as a bionanohybrid capacitor. The conductivity of PepA, a bacterial aminopeptidase used as a protein shell (PS), and the platinum nanoparticles (PtNPs) encapsulated by PepA was measured using a field effect transistor (FET) and a graphene-based FET (GFET). Furthermore, we confirmed that the electronic properties of PepA-PtNPs were controlled by varying the size of the PtNPs. The use of two poly(methyl methacrylate) (PMMA)-coated graphene layers separated by PepA-PtNPs enabled us to build a bionanohybrid capacitor with tunable properties. The combination of bioinorganic nanohybrids with graphene is regarded as the cornerstone for developing flexible and biocompatible bionanoelectronic devices that can be integrated into bioelectric circuits for biomedical purposes.


Biological activity during co-composting of sludge issued from the OMW evaporation ponds with poultry manure-Physico-chemical characterization of the processed organic matter.
Olive mill sludge (OMS), a by-product resulting from natural evaporation of olive oil processing effluent, poses a major environmental threat. A current cost-effective practice of OMS management is composting. A mixture of OMS (60%) with poultry manure (PM) was successfully composted for 210 days. During the process, effluents of olive oil mill and confectionary were used to keep moisture at optimal level (40-60%). Biological indicators reflecting stability of the compost (microbial biota respiration and enumeration, and germination index) were analysed for the assessment of the product quality. The composted mixture showed a high microbial activity with a succession of microbial populations depending on the temperature reached during the biodegradation. The pathogen content from PM decreased with composting as did phytotoxic compounds. Phenols and lipids were reduced, respectively, by 40% and 84% while germination index increased with composting progress. Fourier transform infrared (FTIR) spectroscopic analysis revealed that the final compost improved the aromatic content compared to the starting materials, with a decrease in aliphatic groups and a reduction in the easily assimilated components by the microflora acting during the biological process. The final compost was characterized by relatively high organic matter content (26.21%), a low C/N ratio (16.21), an alkaline pH (8.32), a relatively high electrical conductivity (9.21mS/cm) and a high level of nutrients. The germination index for Lepidium sativum L. was 87.71% after 210 days of composting, showing that the final compost was not phytotoxic.


Mechanism of O-antigen distribution in lipopolysaccharide.
O-antigen units are nonuniformly distributed among lipid A-core molecules in lipopolysaccharide (LPS) from gram-negative bacteria, as revealed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate; the actual distribution patterns are complex, multimodal, and strain specific. Although the basic biochemical steps involved in synthesis and polymerization of O-antigen monomers and their subsequent attachment to lipid A-core are known, the mechanism by which specific multimodal distribution patterns are attained in mature LPS has not been previously considered theoretically or experimentally. We have developed probability equations which completely describe O-antigen distribution among lipid A-core molecules in terms of the probability of finding a nascent polymer (O antigen linked to carrier lipid) of length k (Tk) and the probability that a nascent polymer of length k will be extended to k + 1 by polymerase (pk) or transferred to lipid A-core by ligase (qk). These equations were used to show that multimodal distribution patterns in mature LPS cannot be produced if all pk are equal to p and all qk are equal to q, conditions which indicate a lack of selectivity of polymerase and ligase, respectively, for nascent O-antigen chain lengths. A completely stochastic model (pk = p, qk = q) of O-antigen polymerization and transfer to lipid A-core was also inconsistent with observed effects of mutations which resulted in partial inhibition of O-antigen monomer synthesis, lipid A-core synthesis, or ligase activity. The simplest explanation compatible with experimental observations is that polymerase or ligase, or perhaps both, have specificity for certain O-antigen chain lengths during biosynthesis of LPS. Our mathematical model indicates selectively probably was associated with the polymerase reaction. Although one may argue for a multimodal distribution pattern based on a kinetic mechanism i.e., varying reaction parameters in space or in time during cell growth, such a model requires complex sensory and regulatory mechanisms to explain the mutant data and mechanisms for sequestering specific components of LPS biosynthesis to explain the distribution pattern in normal cells. We favor the simple alternative of enzyme specificity and present generalized equations which should be useful in analysis of other analogous biochemical systems.


The Relationship between Mitochondrial Respiratory Chain Activities in Muscle and Metabolites in Plasma and Urine: A Retrospective Study.
The relationship between 114 cases with decreased enzymatic activities of mitochondrial respiratory chain (MRC) complexes I-V (C I-V) in muscle and metabolites in urine and plasma was retrospectively examined. Less than 35% disclosed abnormal plasma amino acids and acylcarnitines, with elevated alanine and low free carnitine or elevated C4-OH-carnitine as the most common findings, respectively. Abnormal urine organic acids (OA) were detected in 82% of all cases. In CI and CII defects, lactic acid (LA) in combination with other metabolites was the most common finding. 3-Methylglutaconic (3MGA) acid was more frequent in CIV and CV, while Tyrosine metabolites, mainly 4-hydroxyphenyllactate, were common in CI and IV defects. Ketones were present in all groups but more prominent in combined deficiencies. There was a significant strong correlation between elevated urinary LA and plasma lactate but none between urine Tyrosine metabolites and plasma Tyrosine or urinary LA and plasma Alanine. All except one of 14 cases showed elevated FGF21, but correlation with urine OA was weak. Although this study is limited, we conclude that urine organic acid test in combination with plasma FGF21 determination are valuable tools in the diagnosis of mitochondrial diseases.


Towards the use of ion mobility mass spectrometry derived collision cross section as a screening approach for unambiguous identification of targeted pesticides in food.
Mass spectrometry (MS) is the reference method for the screening of ultra-trace residues of pesticides in food because MS offers the required selectivity/sensitivity to gather information and enable the analyst to make informed decisions during the identification process. Here we present and discuss the use of collision cross section (CCS) values in addition to mass accuracy and retention times in a pesticide screening method that integrates all the features offered by coupling ultra-performance liquid chromatography (UPLC) with ion mobility mass spectrometry (IMS-MS). All experiments were carried out using UHPLC coupled to a travelling wave ion mobility mass spectrometer equipped with an electrospray ionization (ESI) source working in positive mode. An in-house library containing 200 pesticides was built using standard solutions and used as reference for a TWCCS calibration study. Matrix extracts were analyzed to evaluate the performance of different screening workflows based on TWCCS, mass accuracy and retention times. The results proved that TWCCS values are very consistent, as the measured values do not differ more than 1% from the in-house reference data library and emphasized the importance of the first low m/z mobility calibration point to guarantee full independence from instrument parameters and calibrant. The screening procedure was simplified to a single step by fully exploiting the content of ion mobility without generating any false detections, either positive or negative, from spiked samples and a previous proficiency test. The screening approach proposed in this study is unconventional and based on large mass accuracy (20 ppm) and retention time windows (0.5 min) to capture, in a first step, a maximum of detected compounds. Compounds of interest are then identified by comparing measured collision cross sections with the measured reference library collision cross sections (with relative error tolerance lower than 2%).


Racemization in human lens: evidence of rapid insolubilization of specific polypeptides in cataract formation.
After early life, the dry weight of normal human lenses increases at a relatively constant rate with time. Transformation from soluble to insoluble material appears to occur at a comparable rate, resulting in a constant amount of soluble material. However, in cataract the insolubilization rate is accelerated. These observations are supported by determination of D-aspartic acid/L-aspartic acid ratios. The abundance of D-aspartic acid increases with aging at a constant rate in the insoluble fraction of normal lenses but does not change in the soluble fraction. However, in cataractous lenses there is a significant decrease in the ratio in the insoluble fraction. Examination of polypeptides isolated from reduced and alkylated soluble and insoluble cataractous lens proteins as well as other data suggest the following additional conclusions: (i) the 10,000-dalton polypeptide in the insoluble fraction is derived in part from degradation of an already insoluble precursor; and (ii) the lowered abundance of D-aspartic acid in the insoluble fraction of cataractous lenses is primarily due to the rapid insolubilization of the 43,000- and 20,000-dalton range components.


Effects of sodium valproate on the growth of human ovarian cancer cell line HO8910.
To explore a possible new treatment for human ovarian cancer, we studied the effects of sodium valproate on the growth of the HO8910 human cell line. HO8910 cells were cultured in vitro and treated with different concentrations of sodium valproate. Cell proliferation, cell cycling, and apoptosis were measured by flow cytometry, cell morphology under a microscope, and expression levels of WWOX and P27 by Western blotting and RT-PCR. Tumor xenografts were established to determine in vivo effects of sodium valproate. Our results showed that cell proliferation was decreased with increasing concentration of sodium valproate, with features of cytoplasmic retraction and floating cells. Moreover, cell cycle analysis revealed a higher apoptosis rate and G0/ G1 phase in the sodium valproate experimental group than in the control group. In addition, protein expression levels of WWOX and P27 were elevated. Importantly, sodium valproate decreased in vivo xenograft tumor burden and up-regulated WWOX and P27 expression in nude mice. In conclusion, sodium valproate might play a role in inhibition and control of ovarian cancer cell line HO8910 by inhibiting cell proliferation, interfering with the cell cycle and promoting apoptosis, so that it may be effective in the clinical treatment of ovarian cancer.


Extensive characterisation of bioactive phenolic constituents from globe artichoke (Cynara scolymus L.) by HPLC-DAD-ESI-QTOF-MS.
The aim of this work was to characterise the phenolic compounds in artichoke (hearts) by using HPLC coupled to DAD-ESI-QTOF-MS, which proved useful in characterising 61 phenolic and other polar compounds. Notably, of the 61 compounds characterised, 34 new phenolic compounds with their isomers have been tentatively characterised in artichoke for the first time, namely: 3 hydroxybenzoic acids, 17 hydroxycinnamic acids, 4 lignans, 7 flavones, 2 flavonols, and 1 phenol derivative. Moreover, a total of 28 isomers of previously described phenolics have also been detected. The data compiled from the qualitative polyphenol characterisation indicate that the artichoke extract analysed (Blanca de Tudela variety) could be regarded as a bioactive functional food and also as a promising source of antioxidant phenolic compounds.


Contact activation of prekallikrein and of fibrinolysis by heparinoids and heparin.
Contact activation of plasma prekallikrein (PPK) assayed by a tripeptide chromogenic substrate, and surface-mediated fibrinolysis by the euglobulin test (both tests being insensitive to the anticoagulant effect of heparin and heparinoids) were studied. The following substances were tested: Dextran solutions of different molecular weight (M.W.), heparinoids such as dextran sulphate, pentosan and mannuronate sulphuric polyesters. Liquoid and Moranyl and various commercial therapeutic preparations of heparin. Most of these anionic polyesters are able to activate both PPK and fibrinolysis, dextran sulphate (500,000 M.W.) being the most active. Factor XII, PPK and HMWK are necessary for full activation. Besides dextran sulphate, other heparinoids such as Na pentosan polysulphate, or Na polyanhydromannuronic sulphuric acid, are also contact activators. This may explain some of their side effects observed in vivo. Non-sulphated dextrans used in therapy have no activating effect. Nine therapeutic commercial preparations of heparin were tested. They appear to have a slight activating effect on PPK but an uncertain effect on fibrinolysis. Such factor XII activability has until now been unnoticed, being masked by the anticoagulant activity of heparinoids and heparins on later phases of blood coagulation. It appears that heparin is unable to prevent contact activation in vivo as well as in vitro. This allows PPK assays during extracorporeal circulation in the presence of circulating heparin.


Analysis of multiple shear wave modes in a nonlinear soft solid: Experiments and finite element simulations with a tilted acoustic radiation force.
Tissue nonlinearity is conventionally measured in shear wave elastography by studying the change in wave speed caused by the tissue deformation, generally known as the acoustoelastic effect. However, these measurements have mainly focused on the excitation and detection of one specific shear mode, while it is theoretically known that the analysis of multiple wave modes offers more information about tissue material properties that can potentially be used to refine disease diagnosis. This work demonstrated proof of concept using experiments and finite element simulations in a uniaxially stretched phantom by tilting the acoustic radiation force excitation axis with respect to the material's symmetry axis. Using this unique set-up, we were able to visualize two propagating shear wave modes across the stretch direction for stretches larger than 140%. Complementary simulations were performed using material parameters determined from mechanical testing, which enabled us to convert the observed shear wave behavior into a correct representative constitutive law for the phantom material, i.e. the Isihara model. This demonstrates the potential of measuring shear wave propagation in combination with shear wave modeling in complex materials as a non-invasive alternative for mechanical testing.


Analysis of the biomechanical properties of the mandible after unilateral distraction osteogenesis.
The purpose of this study was to establish biomechanical outcomes measures to evaluate how mandibular distraction osteogenesis affects the overall quality of bone healing. Strength and functional integrity of the regenerate were determined quantitatively after unilateral mandibular distraction osteogenesis in comparison with the contralateral mandible and a partially reduced fracture. The authors hypothesized that the breaking load, yield, and stiffness of mandibular distraction osteogenesis would be significantly reduced in comparison with both the contralateral mandible and a partially reduced fracture. Sprague-Dawley rats underwent mandibular distraction osteogenesis (n = 8) or a partially reduced fracture (n = 6). Distraction was performed using 4 days' latency and then 0.3 mm every 12 hours for 8 days (5.1 mm). Partially reduced fractures had gaps fixed postoperatively at 2.1 mm. Both groups underwent 4 weeks of consolidation. The contralateral mandibles were used as controls (n = 14). Mandibles were tension tested at 0.5 mm/second to failure, and then breaking load, yield, and stiffness were determined. Mandibular distraction osteogenesis had significantly lower breaking load, yield, and stiffness than contralateral mandible, by 40, 30, and 60 percent, respectively. Breaking load was reduced in partially reduced mandibular fractures by 40 percent when compared with distraction osteogenesis. Using a standard Ilizarov protocol, the biomechanical properties of breaking load, yield, and stiffness in mandibular distraction osteogenesis were significantly lower than those in contralateral mandibles. Surprisingly, the breaking load of mandibular distraction osteogenesis was significantly greater than that of partially reduced mandibular fracture. These verifiable metrics of regenerate integrity can be used to discern optimal outcomes of mandibular distraction osteogenesis, potentially enhancing the clinical applications of this powerful technique.


A modified Glenn shunt reduces venous congestion during acute right ventricular failure due to pulmonary banding: a randomized experimental study.
Right ventricular failure after left ventricular assist device implantation is a serious complication with high rates of mortality and morbidity. It has been demonstrated in experimental settings that volume exclusion of the right ventricle with a modified Glenn shunt can improve haemodynamics during ischaemic right ventricular failure. However, the concept of a modified Glenn shunt is dependent on a normal pulmonary vascular resistance, which can limit its use in some patients. The aim of this study was to explore the effects of volume exclusion with a modified Glenn shunt during right ventricular failure due to pulmonary banding, and to study the alterations in genetic expression in the right ventricle due to pressure and volume overload. Experimental right ventricular failure was induced in pigs (n = 11) through 2 h of pulmonary banding. The pigs were randomized to either treatment with a modified Glenn shunt and pulmonary banding (n = 6) or solely pulmonary banding (n = 5) as a control group. Haemodynamic measurements, blood samples and right ventricular biopsies for genetic analysis were sampled at baseline, at right ventricular failure (i.e. 2 h of pulmonary banding) and 1 h post-right ventricular failure in both groups. Right atrial pressure increased from 10 mmHg (9.0-12) to 18 mmHg (16-22) (P < 0.01) and the right ventricular pressure from 31 mmHg (26-35) to 57 mmHg (49-61) (P < 0.01) after pulmonary banding. Subsequent treatment with the modified Glenn shunt resulted in a decrease in right atrial pressure to 13 mmHg (11-14) (P = 0.03). In the control group, right atrial pressure was unchanged at 19 mmHg (16-20) (P = 0.18). At right heart failure, there was an up-regulation of genes associated with heart failure, inflammation, angiogenesis, negative regulation of cell death and proliferation. Volume exclusion with a modified Glenn shunt during right ventricular failure reduced venous congestion compared with the control group. The state of right heart failure was verified through genetic expressional changes.


Percutaneous coronary intervention for the management of stable ischemic heart disease.
The purpose of this review is to summarize landmark studies and recent evidence in support for and against benefits of routine percutaneous coronary intervention (PCI) in the management of patients with stable ischemic heart disease (SIHD). Randomized controlled trials have raised uncertainty regarding the prognostic benefits of routine PCI in patients with SIHD. The benefits of PCI to improve symptoms and quality of life (QOL), thought to be more established, was brought into question recently by the ORBITA trial. Two hundred participants with single vessel SIHD optimized first on antianginal therapy were randomized to PCI or sham PCI procedure. At 6 weeks, there was no significant difference in the primary endpoint of exercise time increment (PCI minus sham PCI 16.6 s, 95% confidence interval -8.9 to 42.0 s, P = 0.20), or secondary endpoints of change in angina or QOL scores between the groups. Findings from this first placebo-controlled trial of PCI in patients with single vessel SIHD suggest that PCI need not necessarily be the first line or default strategy for symptomatic improvement. Results from the ongoing ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial will provide further guidance regarding symptomatic and prognostic benefits of early angiography and revascularization for higher risk SIHD patients with moderate-severe ischemia.


Antihypertensive effects of Gynura procumbens extract in spontaneously hypertensive rats.
Aqueous extracts of Gynura procumbens (Lour.) Merr. were orally administered to spontaneously hypertensive (SHR) rats for 4 weeks, and antihypertensive effects were determined. Oral administration of 500 mg/kg of G. procumbens (Lour.) Merr. extract (GPE) resulted in significantly lower blood pressure in SHR rats compared with SHR rats not given GPE (P < .05). Furthermore, GPE-administered rats had significantly lower serum lactate dehydrogenase, creatine phosphate kinase, and increased nitric oxide (NO), a known vasodilator, compared with the non-GPE-administered SHR group (P < .05). These results suggest that oral administration of aqueous GPE may be useful for prevention and treatment of hypertension through increasing NO production in blood vessels.


Nisin Z Production by Wild Strains of Lactococcus lactis Isolated from Brazilian (Italian Type) Fermented Sausage.
In this study, five bacteriocin-producing Lactococcus lactis strains were identified from different naturally fermented Brazilian sausages. Ion exchange and reversed-phase chromatographies were used to purify the bacteriocins from culture supernatant of the five strains. Mass spectrometry (MALDI-TOF/TOF) showed that the molecular masses of the bactericoins from L. lactis ID1.5, ID3.1, ID8.5, PD4.7, and PR3.1 were 3330.567 Da, 3330.514 Da, 3329.985 Da, 3329.561 Da, and 3329.591 Da, respectively. PCR product sequence analysis confirmed that the structural genes of bacteriocins produced by the five isolates are identical to the lantibiotic nisin Z. Optimal nisin Z production was achieved in tryptone and casein peptone, at pH 6.0 or 6.5. The most favorable temperatures for nisin Z production were 25°C and 30°C, and its production was better under aerobic than anaerobic condition. The type of carbon source appeared to be an important factor for nisin Z production. While sucrose was found to be the most efficient carbon source for nisin Z production by four L. lactis isolates, fructose was the best for one isolate. Lactose was also a good energy source for nisin Z production. Surprisingly, glucose was clearly the poorest carbon source for nisin Z production. The five isolates produced different amounts of the bacteriocin, L. lactis ID1.5 and ID8.5 isolates being the best nisin Z producers. DNA sequence analysis did not reveal any sequence differences in the nisZ and nisF promoter regions that could explain the differences in nisin Z production, suggesting that there should be other factors responsible for differential nisin Z production by the isolates.


Granulocyte and monocyte apheresis can control juvenile generalized pustular psoriasis with mutation of IL36RN.
Patients with deficiency of interleukin-36 receptor antagonist (DITRA), due to mutation of IL36RN, exhibit psoriatic phenotypes, typically generalized pustular psoriasis (GPP). We report a paediatric patient with DITRA, whose cutaneous lesions varied from psoriasis vulgaris in infancy to annular pustular psoriasis with acute exacerbation to GPP at 13 years of age. Conventional systemic treatments for GPP, which include oral retinoids, ciclosporin and methotrexate, are controversial in paediatric cases, because of their adverse effects and uncertain long-term consequences. Granulocyte monocyte apheresis, a process associated with few adverse events, promptly controlled the GPP of our paediatric patient, and has potential as a suitable alternative treatment for paediatric patients with DITRA.


Double Fascicular Nerve Transfer to Musculocutaneous Branches for Restoration of Elbow Flexion in Brachial Plexus Injury.
Background Restriction of elbow flexion significantly limits upper extremity function following brachial plexus injuries. In recent years, the double fascicular nerve transfer procedure utilizing ulnar and median nerve transfer to musculocutaneous branches has shown promising functional outcomes. Objective To evaluate restoration of elbow flexion following a double fascicular transfer in patients with brachial plexus injuries and identify predictors of poor outcomes. Methods This retrospective review included 10 consecutive patients with brachial plexus injuries involving C5-C6 root avulsions who underwent the double nerve transfer procedure. The mean follow-up was 12 months and the primary outcome was assessment of elbow flexion with the use of the Medical Research Council (MRC) scale. Results This procedure achieved elbow flexion of MRC grade M3 or higher in 50% of our cohort. Time interval from injury to surgery showed a statistically significant inverse association with functional recovery (r = -0.73, p = 0.016). Patients who had the surgery within six months of the injury, demonstrated higher MRC grades during the follow-up (p = 0.048). There was no association between elbow flexion recovery and age, body mass index (BMI), gender, hypertension, diabetes or smoking status. Conclusions The double fascicular transfer to musculocutaneous may be a safe and effective treatment for restoration of elbow flexion. The procedure is associated with superior functional outcomes when performed within the first six months from the injury.


Enforced expression of Bcl-2 partially restores cell numbers but not functions of TCRgammadelta intestinal intraepithelial T lymphocytes in IL-15-deficient mice.
IL-15 knockout (KO) mice have severely reduced numbers of TCRgammadelta intestinal intraepithelial T lymphocytes (i-IEL), suggesting requirements of IL-15 signaling in the development or maintenance of i-IEL. To determine an involvement of survival signals via Bcl-2 in IL-15-mediated homeostasis of TCRgammadelta i-IEL, we introduced a bcl-2 transgene into IL-15 KO mice. In situ apoptosis of TCRgammadelta i-IEL was decreased in Bcl-2 transgenic (Tg) x IL-15 KO mice compared with IL-15 KO mice. The enforced expression of Bcl-2 partially restored the numbers of TCRgammadelta i-IEL in IL-15 KO mice. However, effector functions of TCRgammadelta i-IEL, including cytokine production and cytotoxic activity, were not recovered in Bcl-2 Tg x IL-15 KO mice. Importantly, TCRgammadelta i-IEL in Bcl-2 Tg x IL-15 KO mice expressed a reduced level of eomesodermin, a transcription factor critical for effector functions of NK cells and CD8(+) T cells. Similar to the case of TCRgammadelta i-IEL, enforced expression of Bcl-2 restored the numbers but not the functions of NK cells in IL-15 KO mice. These results suggest that Bcl-2-mediated survival signal is involved in the IL-15-mediated homeostasis of TCRgammadelta i-IEL and NK cells, but other signals from IL-15 are critical for inducing transcription factors, such as eomesodermin for their effector functions.


Local government conservation and management of native vegetation in urban Australia.
Reflecting a worldwide trend of devolution of power and responsibilities to local authorities, metropolitan local governments in Australia now have a role in protecting and managing native vegetation (bushland). Reporting on questionnaire and interview results for Sydney, Melbourne, Perth, and Adelaide, this research examines the main disturbances in local government bushlands, local governments' efforts in bushland conservation, and universality of issues and responses among the cities and between urban and urban-rural local authorities. A number of disturbances in bushlands are common among the cities, with weeds, development impacts, and urban run off perceived to be the most threatening. Management efforts focus on weed control, whereas other main disturbances are receiving less attention. Community involvement in management is prevalent, although regional coordination among local governments is limited. Local governments are willing to be involved in biodiversity conservation and their capacity would be enhanced with increased funding, staffing, and regional coordination.


Two new Hamacantha (Vomerula) from the Rio Grande Rise (SW Atlantic (Hamacanthidae, Porifera).
Hamacantha occurs worldwide and frequently in deep-waters. It is easily distinguished from any other sponge by the possession of conspicuous diancistra microscleres. Here we describe two new species from the Rio Grande Rise. Hamacantha (Vomerula) jeanvaceleti sp. nov. is the sole Hamacantha with styles, diancistras in two categories with the smaller ones cyrtancistra-like; and H. (V.) klausruetzleri sp. nov., the sole with two types of megascleres (styles and strongyles), two categories of diancistras, and two categories of sigmas.


Epidemiology of needlestick and sharps injuries in a tertiary care center in Saudi Arabia.
Health care workers (HCWs) are frequently exposed to the danger of infectious agents through needlestick and sharps injury (NSSI). In Saudi Arabia, the hepatitis B and C viruses pose a great threat to the HCW because of their high prevalence rate (8%-10% and 2%-6%, respectively). A prospective study on the management of NSSI at King Fahad National Guard Hospital from 1996 to 2000. Data relating to the epidemiology of NSSI were collected with the Exposure Prevention Information Network (EPIN(et)) data collection tool, 1997. The results were compared with data as reported by EPIN(et) 1998. Consistency was demonstrated between King Fahad National Guard Hospital and EPIN(et) 1998 for the occupational categories, locations, and the devices involved. Three anomalies were noted: (1) housekeeping staff injuries ranked third at our facility and eighth as reported by EPIN(et) 1998; (2) injuries caused by devices discarded inappropriately commonly occurred at this facility but were not reported by EPIN(et); and (3) injuries due to unsafe practices ranked third at our hospital but ranked seventh in EPIN(et). To date, only 1 employee in our hospital had a seroconversion to hepatitis C. This surveillance highlighted risky practices and demonstrated employees and locations frequently involved in NSSIs. An education program was designed for all staff at risk of exposure, targeting higher-risk employees.


Submerged aerated bio-filter (SAB)--a post treatment option for UASB effluent treating sewage.
This paper presents exploratory results of the performance of submerged aerated bio-filter (SAB-1.5 L) for the post treatment of UASB effluent treating sewage in order to bring the effluent quality in compliance with discharge standards. The study was carried out in three stages with varied dissolved oxygen (DO) levels of 0 to 2.0, 2.0 to 4.0, 4.0 to 6.0 and > 6.0 mg/L. The hydraulic retention time (HRT) and hydraulic loading rate (HLR) were maintained 0.67 h & 0.1 m3/ m2 x h respectively in all stage of study. The performance in terms of BOD removal efficiency was increased with increase in DO levels. Results revealed that the average BOD and SS removal efficiencies in phases 3 and 4 were 51.3 and 59.5% and 58.8 and 67.5% respectively. Significant ammonical nitrogen (NH4-N) removal of 60% was observed in phase 4. The BOD and SS in phases 3 and 4 were reduced to well below the effluent disposal standards. The SAB at DO ≥ 4 mg/L can be considered a viable alternative for the post treatment of effluent from UASB treating domestic wastewater.


Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis.
Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.