Exploring Expressive Communication Skills in a Cross-Sectional Sample of Children and Young Adults With Angelman Syndrome.
This study explores data on expressive communication skills of 300 individuals aged 0.0-21.11 years with Angelman syndrome (AS). These data provide a composite portrait of communication skills in a large sample of children and young adults with this rare disorder, specifying new detailed information about expressive communication. The database associated with the Communication Matrix assessment (Rowland, 2004, 2011; Rowland & Fried-Oken, 2010) was mined for data regarding individuals with AS. We extracted data on the reasons for communicating, level of communication achieved, and use of various expressive communication modes to convey 24 specific messages. The performance of children and young adults in 5 age groups in the cross-sectional sample were contrasted. Results confirmed earlier studies showing that few individuals with AS use natural speech. However, in addition to using presymbolic modes, many children used alternative symbolic modes such as picture symbols, object symbols, and manual signs. Assessment scores increased slightly with age, F(4, 295) = 2.416, p = .049. Aggregating data on a large sample of individuals with AS provides a reference point for practitioners and family members and a basis for future investigations.


Rehabilitation for hamstring injuries.
Hamstring injuries are a common musculoskeletal disorder, particularly amongst athletes. Many factors have been associated with these injuries, including motor control and strength, soft tissue length and postural alignment. Well-established rehabilitation protocols are commonly used in the treatment of this condition, but their effectiveness remains questionable. This is an update of a Cochrane review first published in 2007. To evaluate the effectiveness of all rehabilitation strategies employed to promote the return to full strength, range of movement and function of those individuals presenting with all forms of hamstring injury, regardless of site, severity, onset or level of chronicity. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (to September 2011), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2011 Issue 3), MEDLINE (including in-process & other non-indexed citations: 1966 to August 2011), EMBASE (1980 to September 2011), PEDro (2006 to June 2012), CINAHL (1937 to September 2011), AMED (1985 to September 2011), SPORTDiscus (1859 to February 2006), and the World Health Organisation International Clinical Trials Registry platform (April 2012). Randomised clinical trials investigating the effect of at least one rehabilitation strategy, in isolation or combination with another, compared with another strategy or control, performed on individuals presenting with hamstring injuries. Two review authors performed study selection. All review authors performed data extraction and assessed risk of bias. Any disagreement was resolved by discussion. Two trials were included in the review, totaling 104 participants. One trial assessed additional (four times a day) versus once daily stretching and the other assessed exercise for movement dysfunction versus stretching and strengthening. The first trial, involving 80 elite athletes, suggested additional stretching could reduce time to return to full activity (mean difference (MD) -1.8 days, 95% confidence interval (CI) -2.1 to -1.5, P < 0.001). The second trial, involving 24 participants from a diverse sporting background, did not find conclusive evidence of a difference (MD -14.5 days, 95% CI -30.64 to 1.64, P = 0.08). It did, however, report reduced re-injury rates using exercise for movement dysfunction of 8% versus 64% (odds ratio (OR) 0.05, 95% CI 0.00 to 0.52, P = 0.01). No other outcomes relevant to this review were reported by either study: most notably pain and participant satisfaction. Most proposed physiotherapy techniques for rehabilitation of hamstring injuries have not been assessed using randomised trials. Those that have only have single studies with a limited range of participants and outcomes. There is limited evidence to suggest that time to recovery for elite athletes can be reduced with an increased daily frequency of hamstring stretching exercises. There is preliminary evidence from another small study of mixed ability athletes to suggest that exercise to correct movement dysfunction could reduce time to return to full activity and the risk of re-injury. Further studies are required to check these findings. Until further evidence is available, current practice and widely published rehabilitation protocols cannot either be supported or refuted.


The normal appearing grey matter in primary progressive multiple sclerosis: a magnetisation transfer imaging study.
In 10-15 % of patients with multiple sclerosis (MS), the clinical course is characterized by slow progression in disability without relapses (primary progressive (PP) MS). The mechanism of disability in this form of MS is poorly understood. Using magnetization transfer ratio (MTR) imaging, we investigated normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) in PPMS and explored the relationship of MTR measures with disability. Thirty patients with PPMS and 30 age matched controls had spin echo based MTR imaging to study lesions and normal appearing tissues. The brain was segmented into NAWM and NAGM using SPM99 with lesions segmented using a semiautomated local thresholding technique. A 75% probability threshold for classification of NAWM and NAGM was used to diminish partial volume effects. From normalized histograms of MTR intensity values, six MTR parameters were measured. Mean lesion MTR and T2 lesion volume were also measured. Disability was assessed using Kurtzke's expanded disability status scale (EDSS). Compared with controls, patients exhibited a significant reduction in mean NAWM (p = 0.001) and NAGM (p = 0.004) MTR. Spearman's rank correlation of EDSS with the six MTR parameters in NAWM and NAGM, mean lesion MTR, and T2 lesion volume, was only significant with mean NAGM MTR (r = -0.41, p = 0.02), the 25th percentile of NAGM MTR intensity (r = -0.37, p = 0.05), and T2 lesion volume (r = 0.39, p = 0.04). Multiple regression analysis of the relationship between EDSS and 4 MR parameters representing each tissue type (mean NAWM MTR, mean NAGM MTR, mean lesion MTR, T2 lesion volume) showed that the association of EDSS with mean NAGM MTR remained significant. There appear to be significant abnormalities in the NAGM in PP MS. Further investigation of the pathological basis and functional significance of grey matter abnormality in PPMS is warranted.


Review of the 2012 Epizootic Hemorrhagic Disease Outbreak in Domestic Ruminants in the United States.
An unusually large number of cases of Epizootic hemorrhagic disease (EHD) were observed in United States cattle and white-tailed deer in the summer and fall of 2012. USDA APHIS Veterinary Services area offices were asked to report on foreign animal disease investigations and state diagnostic laboratory submissions which resulted in a diagnosis of EHD based on positive PCR results. EHD was reported in the following species: cattle (129 herds), captive white-tailed deer (65 herds), bison (8 herds), yak (6 herds), elk (1 herd), and sheep (1 flock). A majority of the cases in cattle and bison were found in Nebraska, South Dakota, and Iowa. The majority of cases in captive white-tailed deer were found in Ohio, Iowa, Michigan, and Missouri. The most common clinical sign observed in the cattle and bison herds was oral lesions. The major observation in captive white-tailed deer herds was death. Average within-herd morbidity was 7% in cattle and bison herds, and 46% in captive white-tailed deer herds. The average within-herd mortality in captive white-tailed deer herds was 42%.


The comparative retention of National Health Service Corps and other rural physicians. Results of a 9-year follow-up study.
To contrast the retention of physicians serving National Health Service Corps (NHSC) Scholarship Program obligations in rural settings to that of non-NHSC physicians working in the same or similar practices, and to identify promising retention-enhancing strategies. Cohort study. Four hundred twelve primary care physicians initially identified during an earlier study as working in a national stratified random sample of 178 externally subsidized rural clinics in 1981. Thirty-six percent were serving obligations to the NHSC, nearly all through the NHSC's Scholarship Program. The NHSC and non-NHSC inception cohorts (those first coming to their 1981 [or "index"] practices from May 1979 through December 1981) were created from within the entire group for use in most analyses. In 1990, physicians were resurveyed to learn of their backgrounds, experiences in their index practices, and their subsequent career moves. By 1984 and in each year thereafter, fewer NHSC than non-NHSC physicians of the entire respondent cohort remained (1) in their index practices, (2) in their index communities, and (3) in practice in any rural county (P less than .001). In the inception cohort, fewer NHSC than non-NHSC physicians were retained within all three settings by the third year after their initial dates of employment (P less than or equal to .01). After 8 years of employment, group retention rates for NHSC and non-NHSC inception cohort physicians were 12% vs 39% in the index practice and 29% vs 52% in nonmetropolitan practice. Physicians in both NHSC and non-NHSC groups who left their index practices generally left rural practice altogether. When compared to non-NHSC physicians working in comparable rural settings, the retention of rural NHSC physicians is seen to be poor and only partially explained by fixed physician, practice, or community variables. Long-term retention of NHSC providers is now receiving much needed attention at the federal level.


A fixed-dose randomized controlled trial of olanzapine for psychosis in Parkinson disease.
Psychosis is a common and debilitating side effect of long-term dopaminergic treatment of Parkinson disease (PD). While clozapine is an effective treatment, the need for blood monitoring has limited its first-line use. Since olanzapine shows similar receptor affinity to clozapine, we hypothesized that it might be an effective alternative to clozapine for treatment of drug-induced psychosis (DIP) in PD, and that lower doses than usual might make it tolerable. In 1998-2003 we conducted a four-week, double-blind, placebo-controlled, parallel group, fixed-dose trial of olanzapine (0, 2.5mg, or 5mg) in 23 PD patients with DIP while allowing for clinically realistic dose adjustments of dopaminomimetic mid-study. The primary outcome measures were Brief Psychiatric Rating Scale (BPRS) ratings scored from videotaped interviews after study termination by an observer blinded to dose assignment and to interview timing, and CGI (Clinical Global Impression). The Unified Parkinson's Disease Rating Scale motor subscale (UPDRS) was the primary measure of tolerability. Intention-to-treat analysis found no significant differences among treatment groups in study completion or serious adverse events. However, a disproportionate number of olanzapine vs. placebo subjects reported mild side effects (p<0.04), many citing motor worsening. Fourteen patients completed the study (seven on placebo, two on 2.5mg olanzapine, five on 5mg olanzapine). In study completers, analysis by repeated measures ANOVA revealed no significant difference between olanzapine and placebo groups in BPRS psychosis reduction (p=0.536), parkinsonism (p=0.608), or any other measured parameters (CGI, MMSE, Beck Depression Inventory, Hamilton Depression score, PDQ‑39, Schwab-England ADL assessment, and sleep scores). This study adds to other evidence that olanzapine is ineffective in treating medication-induced psychosis in Parkinson disease.


[Tissue engineering of peripheral nerves].
In spite of considerable progress in microsurgical techniques, the treatment of long distance defects in peripheral nerves remains challenging for the surgeon. Autologous nerve grafting has been the only applicable procedure to overcome such defects in the past. Due to the known disadvantages of this procedure (neuroma formation and sensory deficits at the donor-site, limited availability of donor-material, etc.) and impaired regenerative results, different tubulisation techniques are discussed more frequently as alternatives to the autologous nerve grafts. In this work, the authors summarise their experiences and results with different synthetically developed materials, cellular and acellular tubes and venous conduits for the reconstruction of peripheral nerve defects. To analyse peripheral nerve regeneration, we utilised a median nerve model in rats. In these studies nerve gaps up to 40 mm were induced. Guiding tubes of various materials (trimethylene carbonate-epsilon-caprolactone, polyethylene, veins, and collagen) were employed. Furthermore, we introduced Schwann cells as cellular elements into some of the trimethylene carbonate-epsilon-caprolactone tubes. The longest postoperative observation period was nine months. The results demonstrated that only in the case of cellular filled tubes (syngenic Schwann cells) did regeneration occur across the 20 mm gap. This regeneration was comparable to that induced after autologous grafting. Across a 40 mm gap the autologous graft demonstrated the best results.


Intimate partner violence and unwanted pregnancy, miscarriage, induced abortion, and stillbirth among a national sample of Bangladeshi women.
To estimate (1) lifetime prevalence of physical and sexual victimisation from husbands among a national sample of Bangladeshi women, (2) associations of unwanted pregnancy and experiences of husband violence, and (3) associations of miscarriage, induced abortion, and fetal death/stillbirth and such victimisation. Cross-sectional, nationally representative study utilizing matched husband-wife data from the 2004 MEASURE Bangladesh Demographic Health Survey. Bangladesh. Married Bangladeshi women ages 13-40 years old (n = 2677). Bivariate and multivariate logistic regression analysis. Relations of intimate partner violence to unwanted pregnancy, miscarriage, induced abortion and stillbirth. Three out of four (75.6%) Bangladeshi women experienced violence from husbands. Less educated, poorer, and Muslim women were at greatest risk. Women experiencing violence from husbands were more likely to report both unwanted pregnancy (ORs(adj) 1.46-1.54) and a pregnancy loss in the form of miscarriage, induced abortion, or stillbirth (ORs(adj) 1.43-1.69). Assessed individually, miscarriage was more likely among victimised women (OR(adj) 1.81). A nonsignificant trend was detected for increased risk of induced abortion (OR(adj) 1.64); stillbirth was unrelated to violence from husbands. Intimate partner violence is extremely prevalent and relates to unwanted pregnancy and higher rates of pregnancy loss or termination, particularly miscarriages, among Bangladeshi women. Investigation of mechanisms responsible for these associations will be critical to developing interventions to improve maternal, fetal, and neonatal health. Such programmes may be vital to reducing the significant health and social costs associated with both husband violence and unwanted and adverse pregnancy outcomes.


Experimental demonstration of multiple pulse nonlinear optoacoustic signal generation and control.
Generating underwater acoustic signals from a remote, aerial location by use of a high-energy pulsed infrared laser has been demonstrated. The laser beam is directed from the air and focused onto the water surface, where the optical energy was converted into a propagating acoustic wave. Sound pressure levels of 185 dB re microPa (decibel re microPa) were consistently recorded under freshwater laboratory conditions at laser-pulse repetition rates of up to 1000 pulses/s. The nonlinear optoacoustic transmission concept is outlined, and the experimental results from investigation of the time-domain and frequency-domain characteristics of the generated underwater sound are provided. A high repetition rate, high-energy per pulse laser was used in this test under freshwater laboratory conditions. A means of deterministically controlling the spectrum of the underwater acoustic signal was investigated and demonstrated by varying the laser-pulse repetition rate.


Effects of ethanol extract of Ficus bengalensis (bark) on inflammatory bowel disease.
The present study was designed to evaluate the effects of ethanol extract of Ficus bengalensis Linn. bark (AEFB) on inflammatory bowel disease (IBD). Effects of AEFB were studied on 2,4,6-trinitrobenzenesulfonic acid (TNBS, 0.25 ml 120 mg/ml in 50% ethanol intrarectally, on first day only) induced IBD in rats. The effects of co-administration of prednisolone (2 mg/kg) and AEFB (250, 500 mg/kg) for 21 days were evaluated. Animals sacrificed at end of the experiment and various histopathological parameters like colon mucosal damage index (CMDI) and disease activity index (DAI) were assessed. In the colon homogenate malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and nitric oxide (NO) levels and in mesentery % mast cell protection was also measured. Rats treated with only TNBS showed more score of CMDI and DAI, higher MDA, NO, MPO, and lower SOD activity as compared to the control group. Treatment with AEFB significantly declined both indices scores and decreased the MPO, MDA, NO, and increased the SOD activity. AEFB also increased the % mast cell protection compared to alone TNBS-treated animals. In our study, we found that AEFB has a significant protective effect in the IBD in rats that is comparable to that of prednisolone and may be because of the presence of flavonoids, terpenoids, and phenolic compounds.


[Video-assisted thoracoscopy for resecting solitary pulmonary nodules].
The objective of this study was to evaluate the usefulness of video assisted thoracoscopy in the resection of solitary pulmonary nodules. Thirty-three patients with solitary pulmonary nodules diagnosed by video assisted thoracoscopy were enrolled prospectively. A preoperative computed tomography scan was obtained for each patient. Harpoons were implanted preoperatively to locate the lesion in patients whose tumors were in the parenchyma. When endoscopic resection proved impossible in five patients, the surgeon resorted to thoracotomy. All were diagnosed after the procedure. One was a case of pulmonary lymphoma, 2 were primary adenocarcinomas of the lung, 2 were oat-cell cancers, 1 was Wegener's disease, 4 were tuberculomas, 3 involved pulmonary infarction and 20 were single pulmonary metastases. Patients who needed thoracotomy required more days of postsurgical drainage (p < 0.05). The size of resected nodules ranged from 0.4 to 6 centimeters. Preoperative positron emission tomographs were available for four patients. No perioperative (< 30 days) mortality occurred and morbidity consisted of one case of prolonged airway leak (> 7 days). Use of video-assisted thoracoscopy reduced perioperative morbidity and hospital stay.


Dinophysis toxins: causative organisms, distribution and fate in shellfish.
Several Dinophysis species produce diarrhoetic toxins (okadaic acid and dinophysistoxins) and pectenotoxins, and cause gastointestinal illness, Diarrhetic Shellfish Poisoning (DSP), even at low cell densities (<103 cells·L⁻¹). They are the main threat, in terms of days of harvesting bans, to aquaculture in Northern Japan, Chile, and Europe. Toxicity and toxin profiles are very variable, more between strains than species. The distribution of DSP events mirrors that of shellfish production areas that have implemented toxin regulations, otherwise misinterpreted as bacterial or viral contamination. Field observations and laboratory experiments have shown that most of the toxins produced by Dinophysis are released into the medium, raising questions about the ecological role of extracelular toxins and their potential uptake by shellfish. Shellfish contamination results from a complex balance between food selection, adsorption, species-specific enzymatic transformations, and allometric processes. Highest risk areas are those combining Dinophysis strains with high cell content of okadaates, aquaculture with predominance of mytilids (good accumulators of toxins), and consumers who frequently include mussels in their diet. Regions including pectenotoxins in their regulated phycotoxins will suffer from much longer harvesting bans and from disloyal competition with production areas where these toxins have been deregulated.


Evaluation of stress response in black-tailed prairie dogs (Cynomys ludovicianus) in arid regions from colonies in Chihuahua Mexico.
Among all the regulatory homeostatic networks in vertebrates, the activation of the hypothalamic-pituitaryadrenal axis during the stress response, has gained considerable attention, and the measurement of fecal glucocorticoids (FGC) has become an invaluable tool to assess adrenocortical activity related to stressful events in wild and captive animals. However, the use of FGC requires the validation of measurement techniques and the proper selection of the specific hormone according to the study species. The main objective of this study was to identify the dominant glucocorticoid (GC) hormone in the stress response of black-tailed prairie dogs (Cynomys ludovicianus) in an arid grassland of Chihuahua, Mexico. A capture stress challenge in the field was developed to determine if the levels of glucocorticoids (cortisol and corticosterone) both in serum and fecal samples could be attributed to stress in Cynomys ludovicianus. The samples were analysed with the technique of liquid phase radioimmunoassay , and this study showed that both cortisol and corticosterone are present at measurable levels in serum and fecal samples of black-tailed prairie dogs. We found that both GCs were present in similar concentrations in serum, however, corticosterone concentration in fecal samples was higher than cortisol. Likewise, biochemical validations performed in this study to test the assay reached acceptable levels of reliability. Therefore, we confirm that fecal analysis can be implemented as a method to measure stress responses in wild prairie dogs.


Effects of dopamine on reinforcement learning and consolidation in Parkinson's disease.
Emerging evidence suggests that dopamine may modulate learning and memory with important implications for understanding the neurobiology of memory and future therapeutic targeting. An influential hypothesis posits that dopamine biases reinforcement learning. More recent data also suggest an influence during both consolidation and retrieval. Eighteen Parkinson's disease patients learned through feedback ON or OFF medication, with memory tested 24 hr later ON or OFF medication (4 conditions, within-subjects design with matched healthy control group). Patients OFF medication during learning decreased in memory accuracy over the following 24 hr. In contrast to previous studies, however, dopaminergic medication during learning and testing did not affect expression of positive or negative reinforcement. Two further experiments were run without the 24 hr delay, but they too failed to reproduce effects of dopaminergic medication on reinforcement learning. While supportive of a dopaminergic role in consolidation, this study failed to replicate previous findings on reinforcement learning.


The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure.
Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy. To assess the effect of GC replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition. We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body composition (clinical parameters and full body DXA) of 53 patients (19 female, median age 46 years) with hypopituitarism (33 ACTH-deficient/20 ACTH-replete) (study A). The corticosteroid metabolite profile of ten patients with ACTH deficiency was then assessed prospectively in a cross over study using three hydrocortisone (HC) dosing regimens (20/10 mg, 10/10 mg and 10/5 mg) (study B) each for 6 weeks. 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity was assessed by urinary THF+5α-THF/THE. Endocrine Centres within University Teaching Hospitals in the UK and Ireland. Urinary corticosteroid metabolite profile and body composition assessment. In study A, when patients were divided into three groups - patients not receiving HC and patients receiving HC≤20 mg/day or HC>20 mg/day - patients in the group receiving the highest daily dose of HC had significantly higher waist-to-hip ratio (WHR) than the ACTH replete group. They also had significantly elevated THF+5α-THF/THE (P=0.0002) and total cortisol metabolites (P=0.015). In study B, patients on the highest HC dose had significantly elevated total cortisol metabolites and all patients on HC had elevated THF+5α-THF/THE ratios when compared to controls. In ACTH-deficient patients daily HC doses of >20 mg/day have increased WHR, THF+5α-THF/THE ratios and total cortisol metabolites. GC metabolism and induction of 11β-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype.


Impact of postpartum hospital-stay legislation on newborn length of stay, readmission, and mortality in California.
The objectives of this study were to examine the impact of postpartum hospital-stay legislation on newborns' length of stay, neonatal readmissions, and 1-year mortality in California, and whether this legislation had differential impacts by demographics and complications during delivery or pregnancy. This study used linked birth certificates, death certificates and hospital discharge records for all full-term, normal birth weight, and singleton-birth newborns during 1991-2000 in California (n = 662,753). Interrupted time-series analyses were used to examine changes in newborns' length of stay and outcomes after 1 year, 2 years, and 3 years since the passage of postpartum laws. Multivariate linear and logistic regressions were estimated separately by maternal characteristics (race, education, age, and partity), delivery type, and complications during pregnancy or delivery. Length of stay increased by 9.5, 12, and 14 hours in years 1, 2, and 3, respectively, after the passage of the law. Increases were larger for newborns of white mothers, more educated mothers, mothers >35 years of age, primaparous mothers, cesarean deliveries, and Medicaid recipients, but there were no differences by pregnancy or delivery complications. The odds of neonatal readmission declined by 9.3%, 11.8%, and 19.7% in years 1, 2 and 3 after the law, respectively. The odds of infection-related readmissions declined by 21.5% and 30.3% in years 2 and 3, respectively. The odds of jaundice-related readmissions increased by 7% in year 1. There was no significant change in either the odds of readmission due to respiratory problems or the odds of 1-year mortality in the postlaw years. Demographic differences in the impact of the law on readmissions and mortality could not be detected because of lack of statistical power. Postpartum length of stay legislation was associated with increased length of stay among all births in California, with significant variation in the law's impact across demographic groups. After the law's passage, there was a significant decline in neonatal readmissions but not in 1-year mortality.


Extracorporeal membrane oxygenation and cytokine adsorption.
Extracorporeal membrane oxygenation (ECMO) is an increasingly used technology for mechanical support of respiratory and cardio-circulatory failure. Excessive systemic inflammatory response is observed during sepsis and after cardiopulmonary bypass (CPB) with similar clinical features. The overwhelming inflammatory response is characterized by highly elevated pro- and anti-inflammatory cytokine levels. The excessive cytokine release during the overwhelming inflammatory response may result in multiple organ damage and failure. During ECMO therapy activation of complement and contact systems occur which may be followed by cytokine release. Controlling excessively increased cytokines may be considered as a valuable treatment option. Hemoadsorption therapy may be used to decrease cytokine levels in case of excessive inflammatory response and due to its unspecific adsorptive characteristics also substances like myoglobin, free hemoglobin or bilirubin. Controlling pro-inflammatory response with hemoadsorption may have positive impact on the endothelial glycocalix and also may be advantageous for maintenance of the vascular barrier function which plays a pivotal role in the development of tissue edema and oxygen mismatch. Hemoadsorption therapy seems to offer a promising new option for the treatment of patients with overwhelming inflammatory response leading to faster hemodynamic and metabolic stabilization finally resulting in preserved organ functions.


Pancreatic cancer risk and ABO blood group alleles: results from the pancreatic cancer cohort consortium.
A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18-1.62], 1.47 (95% CI, 1.07-2.02), and 1.53 (95% CI, 1.21-1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13-1.58) and 1.61 (95% CI, 1.22-2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14-1.85) and 2.42 (1.28-4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03-3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk.


Connectivity to the surface determines diversity patterns in subsurface aquifers of the Fennoscandian shield.
Little research has been conducted on microbial diversity deep under the Earth's surface. In this study, the microbial communities of three deep terrestrial subsurface aquifers were investigated. Temporal community data over 6 years revealed that the phylogenetic structure and community dynamics were highly dependent on the degree of isolation from the earth surface biomes. The microbial community at the shallow site was the most dynamic and was dominated by the sulfur-oxidizing genera Sulfurovum or Sulfurimonas at all-time points. The microbial community in the meteoric water filled intermediate aquifer (water turnover approximately every 5 years) was less variable and was dominated by candidate phylum OD1. Metagenomic analysis of this water demonstrated the occurrence of key genes for nitrogen and carbon fixation, sulfate reduction, sulfide oxidation and fermentation. The deepest water mass (5000 year old waters) had the lowest taxon richness and surprisingly contained Cyanobacteria. The high relative abundance of phylogenetic groups associated with nitrogen and sulfur cycling, as well as fermentation implied that these processes were important in these systems. We conclude that the microbial community patterns appear to be shaped by the availability of energy and nutrient sources via connectivity to the surface or from deep geological processes.


Insulin-associated weight gain in obese type 2 diabetes mellitus patients: What can be done?
Insulin therapy (IT) is initiated for patients with type 2 diabetes mellitus when glycaemic targets are not met with diet and other hypoglycaemic agents. The initiation of IT improves glycaemic control and reduces the risk of microvascular complications. There is, however, an associated weight gain following IT, which may adversely affect diabetic and cardiovascular morbidity and mortality. A 3 to 9 kg insulin-associated weight gain (IAWG) is reported to occur in the first year of initiating IT, predominantly caused by adipose tissue. The potential causes for this weight gain include an increase in energy intake linked to a fear of hypoglycaemia, a reduction in glycosuria, catch-up weight, and central effects on weight and appetite regulation. Patients with type 2 diabetes who are receiving IT often have multiple co-morbidities, including obesity, that are exacerbated by weight gain, making the management of their diabetes and obesity challenging. There are several treatment strategies for patients with type 2 diabetes, who require IT, that attenuate weight gain, help improve glycaemic control, and help promote body weight homeostasis. This review addresses the effects of insulin initiation and intensification on IAWG, and explores its potential underlying mechanisms, the predictors for this weight gain, and the available treatment options for managing and limiting weight gain.


Evolution of a novel lysine decarboxylase in siderophore biosynthesis.
Structural backbones of iron-scavenging siderophore molecules include polyamines 1,3-diaminopropane and 1,5-diaminopentane (cadaverine). For the cadaverine-based desferroxiamine E siderophore in Streptomyces coelicolor, the corresponding biosynthetic gene cluster contains an ORF encoded by desA that was suspected of producing the cadaverine (decarboxylated lysine) backbone. However, desA encodes an l-2,4-diaminobutyrate decarboxylase (DABA DC) homologue and not any known form of lysine decarboxylase (LDC). The only known function of DABA DC is, together with l-2,4-aminobutyrate aminotransferase (DABA AT), to synthesize 1,3-diaminopropane. We show here that S. coelicolor desA encodes a novel LDC and we hypothesized that DABA DC homologues present in siderophore biosynthetic clusters in the absence of DABA AT ORFs would be novel LDCs. We confirmed this by correctly predicting the LDC activity of a DABA DC homologue from a Yersinia pestis siderophore biosynthetic pathway. The corollary was confirmed for a DABA DC homologue, adjacent to a DABA AT ORF in a siderophore pathway in the cyanobacterium Anabaena variabilis, which was shown to be a bona fide DABA DC. These findings enable prediction of whether a siderophore pathway will utilize 1,3-diaminopropane or cadaverine, and suggest that the majority of bacteria use DABA AT and DABA DC for siderophore, rather than norspermidine/polyamine biosynthesis.


Nanocomposites with graft copolymer-templated mesoporous MgTiO3 perovskite for CO2 capture applications.
Mesoporous MgTiO3 perovskite with a high porosity and interfacial properties were synthesized via a solvothermal reaction at 150 °C for 10 h using a graft copolymer, i.e., poly(vinyl chloride)-g-poly(oxyethylene methacrylate) (PVC-g-POEM) with a well-ordered micellar morphology as a structure-directing agent. A PVC-g-POEM graft copolymer with a wormlike morphology was utilized as a soft matrix to prepare a mixed matrix membrane (MMM) with mesoporous MgTiO3 perovskite through a solution-casting method. The structure and morphology of PVC-g-POEM graft copolymer was carefully tuned by controlling polymer-solvent interactions, as characterized by transmission electron microscopy (TEM). The average pore diameter of the MgTiO3 perovskite was 10.4 nm, which is effective in facilitating gas transport via Knudsen diffusion through mesopores as well as improving interfacial contact with the organic polymer matrix. Because of a high porosity (0.56), the density of mesoporous MgTiO3 (1.75 g/cm(3)) was much lower than that of dense nonporous MgTiO3 (4 g/cm(3)) and not significantly higher than that of PVC-g-POEM (1.25 g/cm(3)), leading to a uniform distribution of MgTiO3 in MMM. The permeability of MMM with MgTiO3 was greater than those of MMM with only MgO or TiO2, indicating the simultaneous improvement of solubility and diffusivity in the former, as supported by CO2 temperature-programmed desorption (TPD) measurements. The MMM with MgTiO3 25 wt % exhibited a CO2 permeability improvement of 140% up to 138.7 Barrer (1 Barrer = 1 × 10(-10) cm(3)(STP) cm cm(-2) s(-1) cmHg(-1)) without a large loss of CO2/N2 selectivity.


Simulations to demonstrate reduction of the Gordon-Haus effect.
The superposition of spontaneous emission noise on a train of soliton pulses produces a random change of the center frequency of the soliton spectrum that causes a change of the group velocity of individual solitons, which in long-light-wave systems translates into a random jitter of the position of the pulses at the receiver. This phenomenon is known as the Gordon-Haus effect. If uncontrolled, the Gordon-Haus effect sets a definite limit on the permissible data rate or on the length of soliton-based light-wave systems. Recently Kodama and Hasegawa [Opt. Lett. 17, 31 (1992)] have shown that the Gordon-Haus effect can be suppressed by placing filters along the fiber that reduce the frequency jitter and the concomitant group-velocity changes. We demonstrate the reduction of the Gordon-Haus effect by computer simulations.


Flow measurements in a blood-perfused collagen vessel using x-ray micro-particle image velocimetry.
Blood-perfused tissue models are joining the emerging field of tumor engineering because they provide new avenues for modulation of the tumor microenvironment and preclinical evaluation of the therapeutic potential of new treatments. The characterization of fluid flow parameters in such in-vitro perfused tissue models is a critical step towards better understanding and manipulating the tumor microenvironment. However, traditional optical flow measurement methods are inapplicable because of the opacity of blood and the thickness of the tissue sample. In order to overcome the limitations of optical method we demonstrate the feasibility of using phase-contrast x-ray imaging to perform microscale particle image velocimetry (PIV) measurements of flow in blood perfused hydrated tissue-representative microvessels. However, phase contrast x-ray images significantly depart from the traditional PIV image paradigm, as they have high intensity background, very low signal-to-noise ratio, and volume integration effects. Hence, in order to achieve accurate measurements special attention must be paid to the image processing and PIV cross-correlation methodologies. Therefore we develop and demonstrate a methodology that incorporates image preprocessing as well as advanced PIV cross-correlation methods to result in measured velocities within experimental uncertainty.


Endotoxin contamination of engineered nanomaterials.
Endotoxin has established health impacts and may be a potential confounding factor in toxicity studies of engineered nanomaterials (ENM). We aimed to characterize endotoxin contamination for a representative set of carbon-based ENM. The established method for quantifying endotoxin relies on its activity in a complex biochemical assay system. Because of their physical and chemical properties, measurement of endotoxin associated with many ENM presents non-trivial technical challenges. We have made progress in identifying and implementing methods for ENM analysis with respect to endotoxin content, revealing varying levels of endotoxin contamination in the ENM examined here. The physical association of ENM and endotoxin and their shared physiological effects suggest the possibility that contaminating endotoxin may contribute to the toxicity that is ascribed to ENM. We found in this small number of samples that endotoxin levels were not related to type of ENM or surface area but may be introduced randomly during manufacture.


Isoenzyme patterns of Entamoeba histolytica isolates from asymptomatic carriers: use of gradient acrylamide gels.
A vertical polyacrylamide gradient gel (3% to 7%) was designed to facilitate the electrophoretic resolution and classification of isoenzyme patterns of Entamoeba histolytica isolates. The following enzyme systems were used: phosphoglucomutase (PGM), hexokinase (HX), glucosephosphate isomerase (GPI), and malate dehydrogenase (ME). The modifications in the electrophoretic procedure and sample preparation allowed the reproducible comparison of enzyme patterns of axenic, monoxenic, and mixed cultures of E. histolytica isolated from humans. The clear distinction obtained in gradient polyacrylamide gels, between amebic isoenzyme bands and those from bacteria, renders this technique adequate for application to epidemiological studies where mixed cultures are used. The isoenzyme patterns of eight isolates from asymptomatic carriers, rigorously characterized by the absence of clinical, endoscopic, and serological findings were studied and compared with three well characterized pathogenic strains, cultured under axenic conditions. Our observations confirm the existence of distinct isoenzyme patterns for PGM, HX, and GPI in pathogenic and nonpathogenic strains, and reveal the consistent presence of more than one band for GPI. In addition, a previously undescribed band for GPI with an Rf of 0.64 in a carrier strain was found. The results suggest that while carriers usually harbor amebas with nonpathogenic isoenzyme patterns, pathogenic patterns also may be found in carriers.


Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management.
Heterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management. Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease. Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics. To explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management. To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people). Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena. (1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering. The results indicate the high potential of a systems approach to address COPD heterogeneity. Significant knowledge gaps were identified that are relevant to shape strategies aiming at fostering 4P Medicine for patients with COPD.


First Report of Bacterial Leaf Spot of Parsley Caused by Pseudomonas syringae pv. coriandricola in Ohio.
A severe leaf spot of parsley (Petroselinum crispum L. cvs. Dark Green Italian and Gigante) was observed on ∼1.5 ha in 2007 and 8 ha in 2012 on three vegetable farms in northern Ohio. Tiny, water-soaked spots that enlarged to necrotic lesions (∼5 mm wide) were first observed in June of each year. Lesions often coalesced and leaf marginal necrosis was common. Disease incidence initially ranged from 20 to 50%, and a 1.5-ha field was completely lost in 2012 as a result of the disease. Bacterial streaming was observed microscopically from leaf lesions. Diseased leaf tissue was dipped briefly in 70% ethanol, rinsed in sterile water, and blotted dry. Bacteria were isolated by plating 10-fold serial dilutions of diseased tissue extracts onto yeast dextrose carbonate and Pseudomonas F (PF) agar media. Whitish, opaque, circular colonies were isolated consistently from all samples. One isolate was purified from each of four fields. They were all gram-negative, non-fluorescent on PF medium, levan positive, oxidase negative, arginine dihydrolase negative, potato rot negative, and tobacco hypersensitive reaction positive. Repetitive extragenic palindromic sequence (Rep)-PCR fingerprint profiles using the BOXA1R primer (4) were identical for the four isolates. A pathogenicity test was conducted with strain SM69-07 isolated in 2007. A bacterial culture was suspended in sterile potassium phosphate buffer (0.01M, pH 7.4) and adjusted to 108 CFU/ml. Four 4-week-old plants each of parsley and cilantro (Ferry-Morse Seed Co.) were inoculated by spraying the bacterial suspension on the leaves until runoff. Potassium phosphate buffer was applied as a negative control treatment for each plant species. Plants were kept in a mist room with 100% humidity for 4 h, then transferred to a greenhouse with average maximum and minimum temperatures of 30 and 25°C. Leaf symptoms similar to those on the original plants were observed on the inoculated parsley and cilantro plants within 14 days of inoculation, whereas no symptoms developed on the negative control plants. One bacterial isolate obtained from each inoculated host using the isolation method described above was confirmed to be identical to the original isolates using the LOPAT tests and Rep-PCR DNA fingerprint profiles; no target bacteria were isolated from the negative control plants. Multilocus sequence typing (MLST) of the housekeeping genes gap1, gltA, gyrB, and rpoD was conducted for strain Sm69-07 (2,3). Sequence data were subjected to BLASTn searches in the Plant-Associated Microbes Database (PAMDB, http://genome.ppws.vt.edu/cgi-bin/MLST/home.pl ) (1). The sequences aligned with those of Pseudomonas syringae pv. coriandricola with 100% identity to alleles 101 (gyrB), 123 (rpoD), 7 (gap1), and 64 (gltA). Strain information and sequence alignment results for SM69-07 were submitted to PAMDB and assigned as isolate ID 1138. Based on bacterial culture morphology, LOPAT profile, pathogenicity test results, and MLST, the pathogen was confirmed as P. syringae pv. coriandricola. To our knowledge, this is the first report of bacterial spot of parsley caused by P. syringae pv. coriandricola in Ohio. Due to stringent quality requirements for fresh market parsley, this disease may pose a threat to the economic sustainability of parsley production in Ohio. References: (1) N. F. Almeida et al. Phytopathology 100:208, 2010. (2) C. T. Bull et al. Phytopathology 101:847, 2011. (3) M. S. Hwang et al. Appl. Environ. Microbiol. 71:5182, 2002. (4) J. Versalovic et al. Methods Mol. Cell Biol. 5:25, 1994.


Regulation and symbiotic role of nirK and norC expression in Rhizobium etli.
Rhizobium etli CFN42 is unable to use nitrate for respiration and lacks nitrate reductase activity as well as the nap or nar genes encoding respiratory nitrate reductase. However, genes encoding proteins closely related to denitrification enzymes, the norCBQD gene cluster and a novel nirKnirVnnrRnnrU operon are located on pCFN42f. In this study, we carried out a genetic and functional characterization of the reductases encoded by the R. etli nirK and norCB genes. By gene fusion expression analysis in free-living conditions, we determined that R. etli regulates its response to nitric oxide through NnrR via the microaerobic expression mediated by FixKf. Interestingly, expression of the norC and nirK genes displays a different level of dependence for NnrR. A null mutation in nnrR causes a drastic drop in the expression of norC, while nirK still exhibits significant expression. A thorough analysis of the nirK regulatory region revealed that this gene is under both positive and negative regulation. Functional analysis carried out in this work demonstrated that reduction of nitrite and nitric oxide in R. etli requires the reductase activities encoded by the norCBQD and nirK genes. Levels of nitrosylleghemoglobin complexes in bean plants exposed to nitrate are increased in a norC mutant but decreased in a nirK mutant. The nitrate-induced decline in nitrogenase-specific activity observed in both the wild type and the norC mutant was not detected in the nirK mutant. This data indicate that bacterial nitrite reductase is an important contributor to the formation of NO in bean nodules in response to nitrate.


Identifying potential survival strategies of HIV-1 through virus-host protein interaction networks.
The National Institute of Allergy and Infectious Diseases has launched the HIV-1 Human Protein Interaction Database in an effort to catalogue all published interactions between HIV-1 and human proteins. In order to systematically investigate these interactions functionally and dynamically, we have constructed an HIV-1 human protein interaction network. This network was analyzed for important proteins and processes that are specific for the HIV life-cycle. In order to expose viral strategies, network motif analysis was carried out showing reoccurring patterns in virus-host dynamics. Our analyses show that human proteins interacting with HIV form a densely connected and central sub-network within the total human protein interaction network. The evaluation of this sub-network for connectivity and centrality resulted in a set of proteins essential for the HIV life-cycle. Remarkably, we were able to associate proteins involved in RNA polymerase II transcription with hubs and proteasome formation with bottlenecks. Inferred network motifs show significant over-representation of positive and negative feedback patterns between virus and host. Strikingly, such patterns have never been reported in combined virus-host systems. HIV infection results in a reprioritization of cellular processes reflected by an increase in the relative importance of transcriptional machinery and proteasome formation. We conclude that during the evolution of HIV, some patterns of interaction have been selected for resulting in a system where virus proteins preferably interact with central human proteins for direct control and with proteasomal proteins for indirect control over the cellular processes. Finally, the patterns described by network motifs illustrate how virus and host interact with one another.


Roles of extracellular nucleotides and P2 receptors in ectodomain shedding.
Ectodomain shedding of integral membrane receptors results in the release of soluble molecules and modification of the transmembrane portions to mediate or modulate extracellular and intracellular signalling. Ectodomain shedding is stimulated by a variety of mechanisms, including the activation of P2 receptors by extracellular nucleotides. This review describes in detail the roles of extracellular nucleotides and P2 receptors in the shedding of various cell surface molecules, including amyloid precursor protein, CD23, CD62L, and members of the epidermal growth factor, immunoglobulin and tumour necrosis factor families. This review discusses the mechanisms involved in P2 receptor-mediated shedding, demonstrating central roles for the P2 receptors, P2X7 and P2Y2, and the sheddases, ADAM10 and ADAM17, in this process in a number of cell types.


What automaticity deficit? Activation of lexical information by readers with dyslexia in a rapid automatized naming Stroop-switch task.
Reading fluency is often predicted by rapid automatized naming (RAN) speed, which as the name implies, measures the automaticity with which familiar stimuli (e.g., letters) can be retrieved and named. Readers with dyslexia are considered to have less "automatized" access to lexical information, reflected in longer RAN times compared with nondyslexic readers. We combined the RAN task with a Stroop-switch manipulation to test the automaticity of dyslexic and nondyslexic readers' lexical access directly within a fluency task. Participants named letters in 10 × 4 arrays while eye movements and speech responses were recorded. Upon fixation, specific letter font colors changed from black to a different color, whereupon the participant was required to rapidly switch from naming the letter to naming the letter color. We could therefore measure reading group differences on "automatic" lexical processing, insofar as it was task-irrelevant. Readers with dyslexia showed obligatory lexical processing and a timeline for recognition that was overall similar to typical readers, but a delay emerged in the output (naming) phase. Further delay was caused by visual-orthographic competition between neighboring stimuli. Our findings outline the specific processes involved when researchers speak of "impaired automaticity" in dyslexic readers' fluency, and are discussed in the context of the broader literature in this field.


Substrate specificity of the rabbit lung flavin-containing monooxygenase for amines: oxidation products of primary alkylamines.
Substrate activity of a flavin-containing monooxygenase isolated from rabbit lung microsomes has been examined with a number of primary, secondary, and tertiary amines. Of the secondary and tertiary amines tested, trifluoperazine, prochlorperazine, N, N-dimethyloctylamine, desmethylperazine, and N-methyloctylamine half-saturate the enzyme at concentrations less than 100 microM. Although the lung enzyme does not exhibit detectable substrate activity with primary arylamines, it catalyzes N-oxygenation of alkylamines to oximes. Studies on the mechanism for the oxidation of n-dodecylamine suggest that the amine is first oxidized to the hydroxylamine which is then further oxidized to the oxime. This interpretation is based on product identification, kinetic studies, and changes in the ratio of hydroxylamine to oxime formed as a function of initial substrate concentration. Kinetic constants calculated for the oxidation of n-dodecylamine and n-dodecylhydroxylamine indicate that the latter saturates the enzyme at a 100-fold lower concentration than that required for the parent amine, and the hydroxylamine is the dominant product only at saturating concentrations of the amine. The ratio of substrate-dependent NADPH and O2 consumption and product formation (hydroxylamine + 2 X oxime) is approximately 1.0:0.9:0.7. Although the reason for the less than stoichiometric yield of products is not known, uncoupling of the enzyme by primary amines does not appear to be a major factor since substrate-dependent increase in H2O2 formation is never more than 3% of substrate-dependent O2 consumption.


Rasch analysis of the ADL scale of the A-ONE.
The ADL-focused Occupation-based Neurobehavioral Evaluation (A-ONE; Arnadóttir, 1990) can be used to evaluate both performance of activities of daily living (ADL) tasks and neurobehavioral problems that interfere with ADL task performance among clients with neurological disorders. This study examined the rating scale structure and aspects of validity and reliability of the A-ONE's ordinal ADL scale by applying Rasch analysis methods (Bond & Fox, 2001). Rasch analysis of 209 clients' A-ONE assessments indicated that misfit of items to the ADL scale could be reduced by removing the two communication items. Threshold disordering could be corrected by combining two adjacent scoring categories (supervision and verbal assistance), thus supporting four response categories. Separation reliability for item calibrations (.98) was high and acceptable for people (.90). Finally, principal components analysis of the residuals supported unidimensionality. The study provided support for converting the ordinal ADL scale to an interval scale that has potential to be used to measure changes in ADL task performance over time.


Neurological manifestations of intracranial dural arteriovenous malformations.
The authors describe their experience with four cases of dural arteriovenous malformation (AVM) which led them to analyze the clinical aspects of these lesions in an attempt to understand their pathophysiology. An additional 191 previously reported cases of dural AVM's were reviewed with special attention to the mechanism of intradural, central, and peripheral nervous system manifestations. Apart from the peripheral cranial nerve symptoms, which are most likely due to arterial steal, the central nervous system (CNS) symptoms appear to be related to passive venous hypertension and/or congestion. Generalized CNS symptoms can be related to cerebrospinal fluid malabsorption due either to increased pressure in the superior sagittal sinus, to venous sinus thrombosis, or to meningeal reaction resulting from minimal subarachnoid hemorrhages. These phenomena are not related to the anatomical type of venous drainage. On the other hand, focal CNS symptoms are specifically indicative of cortical venous drainage. Seizures, transient ischemic attacks, motor weakness, and brain-stem and cerebellar symptoms can be encountered depending on the territory of the draining vein or veins. Therefore, the localizing value of focal CNS symptomatology relates to the venous territory and not to the nidus or to the arterial supply characteristics of dural AVM's. Furthermore, the venous patterns of various dural AVM's at the base of the skull are expressed by differences in their clinical presentation. Dural AVM's of the floor of the anterior cranial fossa and of the tentorium are almost always drained by the cortical veins and, therefore, have a high risk of intradural bleeding. The remarkable similarities in the manifestations of dural and brain AVM's and the differences in the manifestations of dural and spinal dural AMV's are pointed out. High-quality angiograms and a multidisciplinary approach to the study of dural AVM's will provide the best understanding of their symptoms and, therefore, the most appropriate treatment strategy.


OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance.
Mitochondrial dynamics is a conserved process by which mitochondria undergo repeated cycles of fusion and fission, leading to exchange of mitochondrial genetic content, ions, metabolites, and proteins. Here, we examine the role of the mitochondrial fusion protein optic atrophy 1 (OPA1) in differentiated skeletal muscle by reducing OPA1 gene expression in an inducible manner. OPA1 deficiency in young mice results in non-lethal progressive mitochondrial dysfunction and loss of muscle mass. Mutant mice are resistant to age- and diet-induced weight gain and insulin resistance, by mechanisms that involve activation of ER stress and secretion of fibroblast growth factor 21 (FGF21) from skeletal muscle, resulting in increased metabolic rates and improved whole-body insulin sensitivity. OPA1-elicited mitochondrial dysfunction activates an integrated stress response that locally induces muscle atrophy, but via secretion of FGF21 acts distally to modulate whole-body metabolism.


The role of motion and number of element locations in mirror symmetry perception.
The human visual system has specialised mechanisms for encoding mirror-symmetry and for detecting symmetric motion-directions for objects that loom or recede from the observers. The contribution of motion to mirror-symmetry perception has never been investigated. Here we examine symmetry detection thresholds for stationary (static and dynamic flicker) and symmetrically moving patterns (inwards, outwards, random directions) with and without positional symmetry. We also measured motion detection and direction-discrimination thresholds for horizontal (left, right) and symmetrically moving patterns with and without positional symmetry. We found that symmetry detection thresholds were (a) significantly higher for static patterns, but there was no difference between the dynamic flicker and symmetrical motion conditions, and (b) higher than motion detection and direction-discrimination thresholds for horizontal or symmetrical motion, with or without positional symmetry. In addition, symmetrical motion was as easy to detect or discriminate as horizontal motion. We conclude that whilst symmetrical motion per se does not contribute to symmetry perception, limiting the lifetime of pattern elements does improve performance by increasing the number of element-locations as elements move from one location to the next. This may be explained by a temporal integration process in which weak, noisy symmetry signals are combined to produce a stronger signal.


Linking appearance to neural activity through the study of the perception of lightness in naturalistic contexts.
The present paper deals with the classical question how a psychological experience, in this case apparent lightness, is linked by intervening neural processing to physical variables. We address two methodological issues: (a) how does one know the appropriate physical variable (what is the right x?) to look at, and (b) how can behavioral measurements be used to probe the internal transformation that leads to psychological experience. We measured so-called lightness transfer functions (LTFs), that is the functions that describe the mapping between retinal luminance and perceived lightness for naturalistic checkerboard stimuli. The LTFs were measured for different illumination situations: plain view, a cast shadow, and an intervening transparent medium. Observers adjusted the luminance of a comparison patch such that it had the same lightness as each of the test patches. When the data were plotted in luminance-luminance space, we found qualitative differences between mapping functions in different contexts. These differences were greatly diminished when the data were plotted in terms of contrast. On contrast-contrast coordinates, the data were compatible with a single linear generative model. This result is an indication that, for the naturalistic scenes used here, lightness perception depends mostly on local contrast. We further discuss that, in addition to the mean adjustments, one may find it useful to consider also the variability of an observer's adjustments in order to infer the true luminance-to-lightness mapping function.


Increased in vivo angiogenic effect of glioma stromal mesenchymal stem-like cells on glioma cancer stem cells from patients with glioblastoma.
The presence of glioma stromal mesenchymal stem‑like cells (GS-MSLCs) in tumors from glioma patients has been previously reported. The mechanisms through which these cells function as a part of the glioma microenvironment, however, remain incompletely understood. We investigated the biological effects of GS-MSLCs on glioma cancer stem cells (gCSCs), testing the hypothesis that GS-MSLCs alter the biological characteristics of gCSCs. GS-MSLCs and gCSCs were isolated from different glioblastoma (GBM) specimens obtained from patients. In in vitro experiments, gCSCs were cultured alone or co-cultured with GS-MSLCs, and gCSCs cell counts were compared between the two groups. In addition, two groups of orthotopic GBM xenografts in mice were created, one using gCSCs from the monoculture group and one using gCSCs isolated from the co-culture group, and tumor volume and survival were analyzed. Furthermore, in vivo proliferation, apoptosis and vessel formation were examined using immunohistochemical analyses. In vitro cell counts for gCSCs co-cultured with GS-MSLCs increased 3-fold compared to gCSCs cultured alone. In orthotopic xenograft experiments, mice injected with gCSCs isolated from the co-culture group had significantly larger tumor volume, measured on day 40 after injection, and their survival times were shorter. Immunohistochemical analysis showed increased tumor expression of CD31, indicative of enhanced microvessel formation in mice injected with gCSCs co-cultured with GS-MSLCs compared to mice injected with gCSCs cultured alone. However, proliferation (PCNA) and apoptosis (TUNEL) markers showed no significant difference between the two groups. In conclusion, GS-MSLCs may influence the biological properties of gCSCs, shifting them towards a more aggressive status; moreover, increased angiogenesis may be a critical component of this mechanism.


A multiscale in situ high temperature high resolution transmission electron microscopy study of ThO2 sintering.
Two-grain model systems formed by ThO2 nanospheres have been used to experimentally study for the first time the initial stage of sintering from room temperature to 1050 °C using high temperature high resolution transmission electron microscopy. In each grain, oriented attachment drove the reorganization and growth of the crystallites up to 300 °C to form a pseudo single crystal. Crystallite size kept growing up to 950 °C. At this temperature, a fast transformation probably corresponding to the elimination of stacking faults or dislocation walls led to the formation of single-crystals. The contact formed at room temperature between the two grains was stabilized during heat treatment by a slight reorientation of the crystallographic planes (T≈ 400 °C), leading the neck to be formed by numerous boundaries between the crystallites. At higher temperatures, the neck evolved and stabilized in the form of a plane of crystallographic orientation mismatch between the grains, which corresponds to the usual definition of the grain boundary. The growth of the neck by the addition of atomic columns was further observed in real time and quantified. At T = 950 °C, the evolution of the microscopic sintering parameter λ was obtained from HT-HRTEM images and indicated that the neck formation mostly proceeded through volume diffusion.


Possessions and memories.
People often acquire souvenirs and photographs to facilitate remembering, but possessions and memories can relate to each other in a variety of ways. This review paper presents four different connection types found between meaningful things in our everyday lives and our personal memories. Each connection type either focuses on possessions or memories and the connection between the two is either active or lost. These perspectives will be detailed through examples of studies and design cases from different fields and research areas. More studies have been found focusing on existing connections between possessions and memories, such as in human-computer interaction, design, material culture, psychology and marketing, than those lost, which were specifically focused around ageing, forgetting, heirlooms, identity and hoarding behaviour. Our review of connections between possessions and memories accumulate to suggest the attachment people ascribe to certain possessions is mirrored by the ability of objects to fulfil people's desire to preserve, embody, showcase and recollect certain memories.


Gender discrimination facilitates fMRI responses and connectivity to thermal pain.
Gender discrimination is a serious social issue that has been shown to increase negative consequences, especially in females when accompanied by acute or chronic pain. Experiencing social pain through discrimination can increase an individual's evaluation of evoked physical pain. However, few studies have explored the mechanism underlying how gender discrimination modulates brain responses when individuals experience physical pain evoked by noxious stimuli. In this study, we addressed this issue using a gender discrimination fMRI paradigm with thermal pain stimulation. We found that discrimination indeed affected participants' own behavioral self-evaluation of noxious stimuli. Discrimination-encoded brain activations were identified in the temporopolar cortex, while brain activations to thermal stimuli after viewing pictures of discrimination were found in the dorsal anterior cingulate cortex (dACC). Brain activations in the temporopolar cortex and the dACC were correlated. Furthermore, pain perception-specific functional connectivity of the dACC-SII in the cue stage and the dACC-frontal in the pain stage were identified, suggesting a facilitative effect of gender discrimination on females' experience of physical pain. Our results indicate that the dACC may play a central role in mediating the affective aspect of physical pain after experiencing discrimination. These findings provide novel insights into the underlying mechanism of how gender discrimination facilitates females' experience of physical pain.


A meta-analysis of experiments testing the effects of a neonicotinoid insecticide (imidacloprid) on honey bees.
Honey bees provide important pollination services to crops and wild plants. The agricultural use of systemic insecticides, such as neonicotinoids, may harm bees through their presence in pollen and nectar, which bees consume. Many studies have tested the effects on honey bees of imidacloprid, a neonicotinoid, but a clear picture of the risk it poses to bees has not previously emerged, because investigations are methodologically varied and inconsistent in outcome. In a meta-analysis of fourteen published studies of the effects of imidacloprid on honey bees under laboratory and semi-field conditions that comprised measurements on 7073 adult individuals and 36 colonies, fitted dose-response relationships estimate that trace dietary imidacloprid at field-realistic levels in nectar will have no lethal effects, but will reduce expected performance in honey bees by between 6 and 20%. Statistical power analysis showed that published field trials that have reported no effects on honey bees from neonicotinoids were incapable of detecting these predicted sublethal effects with conventionally accepted levels of certainty. These findings raise renewed concern about the impact on honey bees of dietary imidacloprid, but because questions remain over the environmental relevance of predominantly laboratory-based results, I identify targets for research and provide procedural recommendations for future studies.


Regulation of surface coat exchange by differentiating African trypanosomes.
African trypanosomes (Trypanosoma brucei) have a digenetic lifecycle that alternates between the mammalian bloodstream and the tsetse fly vector. In the bloodstream, replicating long slender parasites transform into non-dividing short stumpy forms. Upon transmission into the fly midgut, short stumpy cells differentiate into actively dividing procyclics. A hallmark of this process is the replacement of the bloodstream-stage surface coat composed of variant surface glycoprotein (VSG) with a new coat composed of procyclin. Pre-existing VSG is shed by a zinc metalloprotease activity (MSP-B) and glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC). We now provide a detailed analysis of the coordinate and inverse regulation of these activities during synchronous differentiation. MSP-B mRNA and protein levels are upregulated during differentiation at the same time as proteolysis whereas GPI-PLC levels decrease. When transcription or translation is inhibited, VSG release is incomplete and a substantial amount of protein stays cell-associated. Both modes of release are still evident under these conditions, but GPI hydrolysis plays a quantitatively minor role during normal differentiation. Nevertheless, GPI biosynthesis shifts early in differentiation from a GPI-PLC sensitive structure to a resistant procyclic-type anchor. Translation inhibition also results in a marked increase in the mRNA levels of both MSP-B and GPI-PLC, consistent with negative regulation by labile protein factors. The relegation of short stumpy surface GPI-PLC to a secondary role in differentiation suggests that it may play a more important role as a virulence factor within the mammalian host.


Alternative techniques for left ventricular pacing in cardiac resynchronization therapy.
Cardiac resynchronization therapy (CRT) is an important treatment modality for a well-defined subgroup of heart failure patients. Coronary sinus (CS) lead placement is the first-line clinical approach but the insertion is unsuccessful in about 5-10% of the patients. In recent years, the number of CRT recipients and the considerable need for left ventricular (LV) lead revisions increased enormously. Numerous techniques and technologies have been specifically developed to provide alternatives for the CS LV pacing. Currently, the surgical access is most frequently used as a second choice by either minithoracotomy or especially the video-assisted thoracoscopy. The transseptal or transapical endocardial LV lead implantations are being developed but there are no longer follow-up data in larger patient cohorts. These new techniques should be reserved for patients failing conventional or surgical CRT implants. In the future, randomized studies are needed to asses the potential benefits of some alternative LV pacing techniques and other new technologies for LV lead placement are expected.


Cultivation, proliferation and characterization of thymic macrophages.
Successful long-term culture of murine thymic macrophages was achieved by plating adherent thymic cells, in the presence of L cell-conditioned medium, on dishes coated with an extracellular matrix. Adherent thymic cells in normal conditions of in-vitro culture do not proliferate. Those maintained on plastic tissue-culture dishes, and exposed to L cell-conditioned medium, proliferate slowly to a limited degree and form very small colonies. In contrast, when cultured in dishes coated with an extracellular matrix formed by corneal endothelial cells, in the presence of L cell-conditioned medium, adherent thymic cells proliferate rapidly and after 12-21 days in culture form large colonies (about 3-5 mm in diameter). The proliferating cells were identified to be mononuclear phagocytes by their morphological appearance, their ability to ingest both bacteria and antibody-coated erythrocytes and by their nonspecific esterase activity. These cells were also shown to exhibit cell surface antigens that are characteristic of differentiated macrophages, e.g. Fc receptors and the specific macrophage cell surface marker F4/80. A high percentage of these cultured cells were found to bear I-A antigens. The adherent thymic mononuclear phagocytes could be trypsinized and passaged while maintaining both their ability to proliferate and their specific macrophage characteristics for a period of 70 days. Thus, monocyte-macrophage stem cells ae present in the thymus, and under appropriate in-vitro conditions, can be made to proliferate and mature to I-A-bearing macrophages.


The regulation and evolution of a genetic switch controlling sexually dimorphic traits in Drosophila.
Sexually dimorphic traits play key roles in animal evolution and behavior. Little is known, however, about the mechanisms governing their development and evolution. One recently evolved dimorphic trait is the male-specific abdominal pigmentation of Drosophila melanogaster, which is repressed in females by the Bric-à-brac (Bab) proteins. To understand the regulation and origin of this trait, we have identified and traced the evolution of the genetic switch controlling dimorphic bab expression. We show that the HOX protein Abdominal-B (ABD-B) and the sex-specific isoforms of Doublesex (DSX) directly regulate a bab cis-regulatory element (CRE). In females, ABD-B and DSX(F) activate bab expression whereas in males DSX(M) directly represses bab, which allows for pigmentation. A new domain of dimorphic bab expression evolved through multiple fine-scale changes within this CRE, whose ancestral role was to regulate other dimorphic features. These findings reveal how new dimorphic characters can emerge from genetic networks regulating pre-existing dimorphic traits.


Optical monitoring of chemical processes in turbid biogenic liquid dispersions by Photon Density Wave spectroscopy.
In turbid biogenic liquid material, like blood or milk, quantitative optical analysis is often strongly hindered by multiple light scattering resulting from cells, particles, or droplets. Here, optical attenuation is caused by losses due to absorption as well as scattering of light. Fiber-based Photon Density Wave (PDW) spectroscopy is a very promising method for the precise measurement of the optical properties of such materials. They are expressed as absorption and reduced scattering coefficients (μ a and μ s', respectively) and are linked to the chemical composition and physical properties of the sample. As a process analytical technology, PDW spectroscopy can sense chemical and/or physical processes within such turbid biogenic liquids, providing new scientific insight and process understanding. Here, for the first time, several bioprocesses are analyzed by PDW spectroscopy and the resulting optical coefficients are discussed with respect to established mechanistic models of the chosen processes. As model systems, enzymatic casein coagulation in milk, temperature-induced starch hydrolysis in beer mash, and oxy- as well as deoxygenation of human donor blood were investigated by PDW spectroscopy. The findings indicate that also for very complex biomaterials (i.e., not well-defined model materials like monodisperse polymer dispersions), obtained optical coefficients allow for the assessment of a structure/process relationship and thus for a new analytical access to biogenic liquid material. This is of special relevance as PDW spectroscopy data are obtained without any dilution or calibration, as often found in conventional spectroscopic approaches.


Migration strategies of insects.
Physiological and ecological results from a variety of species are consistent with what seem to be valid general statements concerning insect migration. These are as follows: (i)During migration locomotory functions are enhanced and vegetative functions such as feeding and reproduction are suppressed. (ii) Migration usually occurs prereproductively in the life of the adult insect (the oogenesis-flight syndrome). (iii)Since migrant individuals are usually prereproductive, their reproductive values, and hence colonizing abilities, are at or near maximum. (iv) Migrants usually reside in temporary habitats. (v)Migrants have a high potential for population increase, r, which is also advantageous for colonizers. (vi)Both the physiological and ecological parameters of migration are modifiable by environmental factors (that is, phenotypically modifiable)to suit the prevailing conditions. Taken together, these criteria establish a comprehensive theory and adumbrate the basic strategy for migrant insects. This basic strategy is modified to suit the ecological requirements of individual species. Comparative studies of these modifications are of considerable theoretical and practical interest, the more so since most economically important insects are migrants. No satisfactory general statements can as yet be made with respect to the genotype and migration. Certainly we expect colonizing populiations to possess genotypes favoring a high r, but genotypic variation in r depends on the heritabilities of life table statistics, and such measurements are yet to be made (10, 53). The fact that flight duration can be increased by appropriate selection in Oncopeltus fasciatus, and the demonstration of additive genetic variance for this trait in Lygaeus kalmii, suggest that heritability studies of migratory behavior would also be worth pursuing. Most interesting of course, will be possible genetic correlations between migration and life history parameters. Also, migration often transports genotypes across long distances with considerable mixing of populations. An understanding of its operation therefore carries with it implications for population genetics, zoogeography, and evolutionary theory. Finally, at least parts of the above general theory would seem to be applicable to forms other than insects. Bird and insect migrations, for example, are in many respects ecologically and physiologically similar. Birds, like insects, emphasize locomotory. as opposed to vegetative functions during long-distance flight; the well-known Zugenruhe or migratory restlessness is a case in point. Further, many birds migrateat nigt at a time when they would ordinarily roost(vegetative activity). Because their life spans exceed single seasons, bird migrants are not prereproductive in the same sense that insect migrants are, and hence reproductive values do not have the same meaning(but note that some insects are also interreproductive migrants). The situaion is complicated further by the fact that in many birds adult survivorship is virtually independent of age so that colonizing ability tends to be also (10, 54). Nevertheless, birds arrive on their nesting grounds in reproductive condition with the result that migration is a colonizing episode. It is also phenotypically modifiable by environmental factors, some of which, for example, photoperiod, influence insects as well (55). The similarities between birds and insects thus seem sufficient to indicate, at least provisionally, that the theory developed for insects applies also to birds with appropriate modifications for longer life span and more complex social behavior; comparisons between insects and fish (56) lead to the same conclusion. In birds especially, and also in other forms, various functions accessory to migration such as reproductive endocrinology, energy budgets, and orientation mechanisms have been studied extensively (55, 56). But there is need in vertebrates for more data andtheoy on the ecology and physiology of migratory behavior per se in order tobetter understand its evolution and its role in ecosystem function (5, 57). Migration in any animal cannot be understood until viewed in its entirety as a physiological, behavioral, and ecological syndrome.


Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 7: A one-month, randomized, ambulatory, controlled clinical study in Poland.
This randomized, open-label, ambulatory, controlled clinical study investigated biomarkers associated with cardiovascular risk and biomarkers of exposure to 10 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke in 316 male and female Polish smokers. Subjects were randomized to continue smoking conventional cigarettes (CC; N=79) or switch to smoking the Electrically Heated Cigarette Smoking System series-K cigarette (EHCSS-K6; N=237). Biomarker assessments were performed at several time points during the study at baseline and during the 1-month investigational period. The primary biomarkers were high-sensitivity C-reactive protein and white blood cell counts. No statistically significant differences in the two primary biomarkers were found between the study groups at the end of the study. End-of-study comparisons of secondary biomarkers between study groups indicated an increase in high-density lipoprotein cholesterol, and reductions in red blood cell count, hemoglobin, and hematocrit levels in the EHCSS-K6 group. All biomarkers of exposure to cigarette smoke HPHC were decreased in the EHCSS-K6 group, despite an increase in cigarette consumption, compared to the CC group. There were no apparent differences in any of the safety assessment parameters between the groups, and the overall incidence of study-related adverse events was low.


A chemical genomic approach identifies matrix metalloproteinases as playing an essential and specific role in Xenopus melanophore migration.
To dissect the function of matrix metalloproteinases (MMPs) involved in cellular migration in vivo, we undertook both a forward chemical genomic screen and a functional approach to discover modulators of melanophore (pigment cell) migration in Xenopus laevis. We identified the 8-quinolinol derivative NSC 84093 as affecting melanophore migration in the developing embryo and have shown it to act as a MMP inhibitor. Potential targets of NSC 84093 investigated include MMP-14 and MMP-2. MMP-14 is expressed in migrating neural crest cells from which melanophores are derived. MMP-2 is expressed at the relevant time of development and in a pattern that suggests it contributes to melanophore migration. Morpholino-mediated knockdown of both MMPs demonstrates they play a key role in melanophore migration and partially phenocopy the effect of NSC 84093.


Optical glucose sensing using ethanolamine-polyborate complexes.
Wound monitoring is essential to tackle chronic complications at their infancy and thus objectively scrutinize any delay in the epithelization process. Since glucose in wound exudates is recognized as key bio-marker in wound monitoring, the development of a cost-efficient detection method for glucose would aid at tackling early-stage infections in wounds. For the first time, we present a novel platform for one-step synthesis of non-enzymatic, cost-efficient optical glucose sensors. These are based on complexes formed by the interactions between polyborates and ethanolamines. The complexes, synthesized by just heating a solution of boric acid and ethanolamines at 150 °C, were characterized using 13C-NMR, 1H-NMR, 11B-NMR, analytical ultracentrifugation and DFT. The results show that the complexes in solution are extremely small (hydrodynamic diameter of around 0.5 nm) and that the polyborates species interact with the ethanolamines via both moderate and weak hydrogen bondings. These complexes were then tested on glucose concentrations ranging from 0 to 10 mM, showing significant changes in the fluorescent emission between the glucose level expressed in an healable wound (5.0-7.6 mM) and a chronic one (0.3-1.0 mM).


Variation in anastrozole metabolism and pharmacodynamics in women with early breast cancer.
Aromatase inhibitors play a prominent role in the management of postmenopausal women with endocrine-sensitive breast cancer, but there is large variability in both efficacy and tolerability. The purpose of our study was to define interindividual variation in anastrozole metabolism and pharmacodynamics among patients treated with the approved daily dose of 1 mg in a standard practice setting as adjuvant therapy for resected early breast cancer. This study was performed in 191 women in whom pretreatment and during anastrozole plasma concentrations of estrone (E1), estradiol (E2), estrone conjugates, androstenedione, and testosterone were determined and correlated with plasma concentrations of anastrozole and anastrozole metabolites. There were large interindividual variations in plasma anastrozole and anastrozole metabolite concentrations, as well as pretreatment and postdrug plasma E1, E2, and E1 conjugate and estrogen precursor (androstenedione and testosterone) concentrations. E1 and E2 concentrations were below the lower limit of quantitation (LLQ) in most patients after anastrozole therapy (83% for both), but those with detectable concentrations had a broad range (1.58-45.2 and 0.635-97.0 pg/mL, respectively). E1 conjugates after anastrozole therapy were above the LLQ in most patients (93%), with wide interpatient variability (3.50-2,990 pg/mL). Two patients seemed to extensively metabolize anastrozole and failed to display substantial decreases in estrogens. Acknowledging the potential factor of variable compliance, our results showed large interindividual variation in anastrozole metabolism and its effect on circulating estrogens in postmenopausal patients. These findings may have implications with regard to efficacy and adverse events and may indicate the need to "individualize" therapy with this drug.


Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan.
Observational studies and fatal case reports raise concern about the safety of severe dysglycemia associated with fluoroquinolone use. The objective of this study was to assess the risk of severe dysglycemia among diabetic patients who received different fluoroquinolones. In a population-based inception cohort study of diabetic patients covering the period from January 2006 to November 2007, outpatient new users of levofloxacin, ciprofloxacin, moxifloxacin, cephalosporins, and macrolides orally were identified. Study events were defined as emergency department visits or hospitalization for dysglycemia within 30 days following the initiation of antibiotic therapy. Results were analyzed with adjusted multinomial propensity score. A total of 78 433 diabetic patients receiving the antibiotics of interest were included in the study. The absolute risk of hyperglycemia per 1000 persons was 6.9 for moxifloxacin and 1.6 for macrolides. In contrast, the risk of hypoglycemia was 10.0 for moxifloxacin and 3.7 for macrolides. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) of levofloxacin, ciprofloxacin, and moxifloxacin compared with macrolides were 1.75 (1.12-2.73), 1.87 (1.20-2.93), and 2.48 (1.50-4.12), respectively, for hyperglycemia and 1.79 (1.33-2.42), 1.46 (1.07-2.00), and 2.13 (1.44-3.14), respectively, for hypoglycemia. Patients taking moxifloxacin faced a significantly higher risk of hypoglycemia than those receiving ciprofloxacin. A significant increase in the risk of hypoglycemia was also observed among patients receiving moxifloxacin concomitantly with insulin (AOR, 2.28; 95% CI, 1.22-4.24). Diabetics using oral fluoroquinolones faced greater risk of severe dysglycemia. The risk of hypoglycemia varied according to the type of fluoroquinolone administered, and was most commonly associated with moxifloxacin.


Apparent culture-negative prosthetic valve endocarditis caused by Peptostreptococcus magnus.
In two patients with prosthetic valve endocarditis due to Peptostreptococcus magnus, blood cultures in the BacT/Alert and BACTEC 9240 systems were signal negative. The capability of the BacT/Alert system to detect various Peptostreptococcus species was assessed. P. magnus and P. anaerobius could not be detected, and subcultures remained negative. The growth in conventional media of these two species and other Peptostreptococcus species was similar.


First Complete Genome Sequence of Salmonella enterica subsp. enterica Serovar Worthington Strain CFSAN051295, Isolated from Pistachio.
We report here, using third-generation, single-molecule, real-time DNA sequencing, the first complete genome sequence of Salmonella enterica serovar Worthington CFSAN051295, isolated from pistachios in the United States. The genome consists of a single 4.9-Mb chromosome.


Epidermal stem cells cultured on collagen-modified chitin membrane induce in situ tissue regeneration of full-thickness skin defects in mice.
A Large scale of full-thickness skin defects is lack of auto-grafts and which requires the engineered skin substitutes for repair and regeneration. One major obstacle in skin tissue engineering is to expand epidermal stem cells (ESCs) and develop functional substitutes. The other one is the scaffold of the ESCs. Here, we applied type I collagen-modified chitin membrane to form collagen-chitin biomimetic membrane (C-CBM), which has been proved to have a great biocompatibility and degraded totally when it was subcutaneously transplanted into rat skin. ESCs were cultured, and the resulting biofilm was used to cover full-thickness skin defects in nude mice. The transplantation of ESCs- collagen- chitn biomimetic membrane (ESCs-C-CBM) has achieved in situ skin regeneration. In nude mice, compared to controls with collagen-chitin biomimetic membrane (C-CBM) only, the ESCs-C-CBM group had significantly more dermatoglyphs on the skin wound 10 w after surgery, and the new skin was relatively thick, red and elastic. In vivo experiments showed obvious hair follicle cell proliferation in the full-thickness skin defect. Stem cell markers examination showed active ESCs in repair and regeneration of skin. The results indicate that the collagen-modified chitin membrane carry with ESCs has successfully regenerated the whole skin with all the skin appendages and function.


New azidotetrazoles: structurally interesting and extremely sensitive.
The treatment of triaminoguanidinium chloride with two equivalents of sodium nitrite under acidic conditions, followed by the cyclization with stoichiometric amounts of either sodium hydroxide solution or solid sodium carbonate yielded 1-amino-5-azidotetrazole (1), 5-azido-1-diazidocarbamoyltetrazole (2), and 1-(aminoazidocarbamoyl)-5-azidotetrazole (3). The three novel compounds could be isolated by short-column liquid chromatography by using chloroform in reasonable yields. The mechanism of the formation as well as the decomposition pathway of the materials was investigated and a full characterization of all three compounds is presented. Compounds 1-3 have been characterized by means of Raman and IR as well as multinuclear NMR spectroscopy, mass spectrometry, and X-ray diffraction studies. Thermal stabilities have been evaluated by differential scanning calorimetry. Theoretical calculations have been performed to ensure the assignment of the vibrational modes obtained from Raman and IR measurements. The sensitivity values obtained from our measurements reflect the behavior of the compounds, which show an extremely high sensitivity toward mechanical as well as thermal stimuli.


Effectiveness of early orthopaedic treatment with headgear: a systematic review and meta-analysis.
Although the headgear appliance has been used extensively to correct anteroposterior discrepancies, its treatment effects have not yet been adequately assessed in an evidence-based manner. Aim of this systematic review was to assess the therapeutic and adverse effects of early headgear treatment from controlled clinical trials on human patients in an evidence-based manner. An unrestricted electronic search of six databases from inception to December 2015. Randomized and prospective non-randomized controlled trials assessing the effects of headgear treatment on human patients. After duplicate study selection, data extraction, and risk of bias assessment according to the Cochrane guidelines, random-effects meta-analyses of mean differences (MDs) and relative risks (RRs), including their 95% confidence intervals (CIs) were performed, followed by subgroup and sensitivity analyses. A total of 18 unique studies with a total of 930 (56% male/44% female) patients were included. Headgear treatment was associated with a posterior translation of the anterior maxilla border in the short term, as seen by the mean annualized change in the SNA angle (MD = -1.63°/year; 95% CI = -2.20 to -1.06°/year; high quality evidence) compared to untreated patients. This effect was independent of the rotation of the palatal plane and the inclination of the upper incisors, while a proportional relationship with the initial discrepancy in SNA was seen. The clinical significance of this improvement diminished in the long term, although only limited evidence existed. Additionally, early headgear treatment might decrease the risk of dental trauma during the following years (RR = 0.34; 95% CI = 0.14 to 0.80; moderate quality evidence). Low quality evidence on the effect of headgear on the rotation of the palatal plane, the nasolabial angle, the occlusal outcome, and signs of temporomandibular disorders precluded robust assessments, due to risk of bias, inconsistency, imprecision, and small-study effects. Based on existing trials, headgear is a viable treatment option to modify sagittal growth of the maxilla in the short term in Class II patients with maxillary prognathism. PROSPERO (CRD42015029837). None.


Amblyomma cajennense (Fabricius, 1787) (Acari: Ixodidae), the Cayenne tick: phylogeography and evidence for allopatric speciation.
Amblyomma cajennense F. is one of the best known and studied ticks in the New World because of its very wide distribution, its economical importance as pest of domestic ungulates, and its association with a variety of animal and human pathogens. Recent observations, however, have challenged the taxonomic status of this tick and indicated that intraspecific cryptic speciation might be occurring. In the present study, we investigate the evolutionary and demographic history of this tick and examine its genetic structure based on the analyses of three mitochondrial (12SrDNA, d-loop, and COII) and one nuclear (ITS2) genes. Because A. cajennense is characterized by a typical trans-Amazonian distribution, lineage divergence dating is also performed to establish whether genetic diversity can be linked to dated vicariant events which shaped the topology of the Neotropics. Total evidence analyses of the concatenated mtDNA and nuclear + mtDNA datasets resulted in well-resolved and fully congruent reconstructions of the relationships within A. cajennense. The phylogenetic analyses consistently found A. cajennense to be monophyletic and to be separated into six genetic units defined by mutually exclusive haplotype compositions and habitat associations. Also, genetic divergence values showed that these lineages are as distinct from each other as recognized separate species of the same genus. The six clades are deeply split and node dating indicates that they started diverging in the middle-late Miocene. Behavioral differences and the results of laboratory cross-breeding experiments had already indicated that A. cajennense might be a complex of distinct taxonomic units. The combined and congruent mitochondrial and nuclear genetic evidence from this study reveals that A. cajennense is an assembly of six distinct species which have evolved separately from each other since at least 13.2 million years ago (Mya) in the earliest and 3.3 Mya in the latest lineages. The temporal and spatial diversification modes of the six lineages overlap the phylogeographical history of other organisms with similar extant trans-Amazonian distributions and are consistent with the present prevailing hypothesis that Neotropical diversity often finds its origins in the Miocene, after the Andean uplift changed the topology and consequently the climate and ecology of the Neotropics.