Allogeneic Transplantation to Treat Therapy-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia in Adults.
Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML), have a poor prognosis. An earlier Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 868 allogeneic hematopoietic cell transplantations (allo-HCTs) performed between 1990 and 2004 showed a 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%, respectively. Modern supportive care, graft-versus-host disease prophylaxis, and reduced-intensity conditioning (RIC) regimens have led to improved outcomes. Therefore, the CIBMTR analyzed 1531 allo-HCTs performed in adults with t-MDS (n = 759) or t-AML (n = 772) between and 2000 and 2014. The median age was 59 years (range, 18 to 74 years) for the patients with t-MDS and 52 years (range, 18 to 77 years) for those with t-AML. Twenty-four percent of patients with t-MDS and 11% of those with t-AML had undergone a previous autologous (auto-) HCT. A myeloablative conditioning (MAC) regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Nonrelapse mortality at 5 years was 34% (95% confidence interval [CI], 30% to 37%) for patients with t-MDS and 34% (95% CI, 30% to 37%) for those with t-AML. Relapse rates at 5 years in the 2 groups were 46% (95% CI, 43% to 50%) and 43% (95% CI, 40% to 47%). Five-year OS and DFS were 27% (95% CI, 23% to 31%) and 19% (95% CI, 16% to 23%), respectively, for patients with t-MDS and 25% (95% CI, 22% to 28%) and 23% (95% CI, 20% to 26%), respectively, for those with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low-risk t-MDS and those with t-AML undergoing HCT with MAC while in first complete remission, but worse for those with previous auto-HCT, higher-risk cytogenetics or Revised International Prognostic Scoring System score, and a partially matched unrelated donor. Relapse remains the major cause of treatment failure, with little improvement seen over the past 2 decades. These data mandate caution when recommending allo-HCT in these conditions and indicate the need for more effective antineoplastic approaches before and after allo-HCT.


Robustness, specificity, and reliability of an in-ear pulse oximetric sensor in surgical patients.
For many years, pulse oximetry has been widely used in the clinical environment for a reliable monitoring of oxygen saturation ( SpO2) and heart rate. But since common sensors are mainly placed to peripheral body parts as finger or earlobe, it is still highly susceptible to reduced peripheral perfusion, e.g., due to centralization. Therefore, a novel in-ear pulse oximetric sensor (placed against the tragus) was presented in a prior work which is deemed to be independent from perfusion fluctuations due to its proximity to the trunk. Having demonstrated the feasibility of in-ear SpO2 measurement with reliable specificity in a laboratory setting, we now report results from a study on in-ear SpO2 in a clinical setting. For this, trials were performed on 29 adult patients undergoing surgery. In-ear SpO2 data are compared with SaO2 data obtained by blood gas analysis, and with three reference pulse oximeters applied to the finger, ear lobe, and forehead. In addition, we derived an SpO2-independent perfusion index by means of the wavelengths used. The feasibility and robustness of in-ear SpO2 measurement is demonstrated under challenging clinical conditions. SpO2 shows good accordance with SaO2, a high level of comparability with the reference pulse oximeters, and was significantly improved by introducing a new algorithm for artifact reduction. The perfusion index also shows a good correlation with the reference data.


Trochanteric-entry long cephalomedullary nailing of subtrochanteric fractures caused by low-energy trauma.
Subtrochanteric fractures of the femur that are caused by low-energy trauma are less common than other proximal femoral fractures, but they occur in a similar population of elderly individuals, who are often socially dependent and medically frail. Although a wide range of operative techniques have been used, cephalomedullary nailing theoretically provides the most minimally invasive and biomechanically stable means of treating these complex fractures. The purpose of the present review was to evaluate the functional outcome and perioperative complications associated with the use of a trochanteric-entry cephalomedullary nail to treat all low-energy subtrochanteric fractures that were seen at a single institution. Over an eight-year period, we used the long Gamma nail to treat a consecutive series of 302 local patients who had sustained a subtrochanteric fracture during low-energy trauma. The mortality, prevalence of complications, and functional outcome were prospectively assessed during the first year after the injury. Survival analysis was used to assess the rates of reoperation and implant revision during the first year after surgery. At one year, seventy-four (24.5%) of the original 302 patients had died and seventeen (5.6%) had been lost to follow-up. The remaining 211 patients (69.9%) were evaluated with regard to the functional outcome and postoperative complications during the first year after the injury. As with other proximal femoral fractures in the elderly, there was an increased level of social dependence, an increase in the use of walking aids, and a reduction in mobility among survivors. Although eighty-eight (41.7%) of the 211 patients who were evaluated at one year after the injury had some degree of hip discomfort, only two described the pain as severe and disabling. Reoperation for the treatment of implant or fracture-related complications was required in twenty-seven (8.9%) of the 302 patients; however, only eighteen of these patients required nail revision, corresponding with a one-year nail-revision rate of 7.1% (95% confidence interval, 4.0% to 10.2%) on survival analysis. Of the 250 patients who survived for six months after the injury, five (2%) had a nonunion that was confirmed at the time of surgical exploration. Complications related to the proximal lag screw were seen in twelve of the original 302 patients, and a fracture distal to the tip of the nail occurred in five. Although superficial wound infection was relatively common, deep infection occurred in only five of the 302 patients. Subtrochanteric fractures caused by low-energy trauma are similar to other proximal femoral fractures, with a high mortality rate during the first year after the injury. Trochanteric-entry cephalomedullary nails are associated with an acceptable rate of perioperative complications and favorable functional outcomes. Therapeutic Level IV.


Shared health governance.
Health and Social Justice (Ruger 2009a ) developed the "health capability paradigm," a conception of justice and health in domestic societies. This idea undergirds an alternative framework of social cooperation called "shared health governance" (SHG). SHG puts forth a set of moral responsibilities, motivational aspirations, and institutional arrangements, and apportions roles for implementation in striving for health justice. This article develops further the SHG framework and explains its importance and implications for governing health domestically.


Molecularly imprinted polymers for cleanup and selective extraction of curcuminoids in medicinal herbal extracts.
This paper describes the synthesis of novel molecularly imprinted polymers (MIPs), prepared by a noncovalent imprinting approach, for cleanup and preconcentration of curcumin (CUR) and bisdemethoxycurcumin (BDMC) from medicinal herbal extracts and further analysis by high-performance liquid chromatography with fluorescence detection (HPLC-FLD). Two molecular mimics, a mixture of reduced BDMCs and 4-(4-hydroxyphenyl)-2-butanone (HPB), have been synthesized and applied as templates for MIP synthesis. The polymers were prepared using N-(2-aminoethyl) methacrylamide (EAMA) as functional monomer, ethylene glycol dimethacrylate (EDMA) as the cross-linker (in a 1:5 molar ratio), and a mixture of acetonitrile/dimethylsulfoxide (90%, v/v) as porogen. MIPs prepared using a mixture of reduced BDMCs as template showed higher selectivity for CUR and BDMC than those obtained with HPB, with imprinting factors of 3.5 and 2.7 for CUR and BDMC, respectively, using H2O/acetonitrile (65:35, v/v) as mobile phase. The adsorption isotherms for CUR in the MIP and the nonimprinted polymer (NIP) were fitted to the Freundlich isotherm model, and the calculated average binding affinities for CUR were (17 ± 2) and (8 ± 1) mM(-1) for the MIP and the NIP, respectively. The polymers were packed into solid-phase extraction (SPE) cartridges, and the optimized molecularly imprinted solid-phase extraction (MISPE-HPLC) with fluorescence detection (FLD) method allowed the extraction of both curcuminoids from aqueous samples (50 mM NH4Ac, pH 8.8) followed by a selective washing with acetonitrile/NH4Ac, 50 mM at pH 8.8 (30:70%, v/v), and elution with 3 × 1 mL of MeOH. Good recoveries and precision ranging between 87 and 92%, with relative standard deviation (RSD) of <5.3% (n = 3), were obtained after the preconcentration of 10-mL solutions containing both CUR and BDMC at concentrations in the range of 0-500 μg L(-1). The optimized method has been applied to the analysis of both curcuminoids in medicinal herbal extracts.


Partisan differences in the relationship between newspaper coverage and concern over global warming.
The effects of news media on public opinion about global warming have been a topic of much interest in both academic and popular discourse. Empirical evidence in this regard, however, is still limited and somewhat mixed. This study used data from the 2006 General Social Survey in combination with a content analysis of newspaper coverage of the same time period to examine the relationship between general news climate and public concern about global warming. Results showed a pattern of political polarization, with increased coverage associated with growing divergence between Democrats and Republicans. Further analysis also showed evidence of reactivity in partisan response to coverage from different news outlets. These findings point to a particular form of politically motivated, biased processing of news information.


Characterising the reproducibility and reliability of dietary patterns among Yup'ik Alaska Native people.
FFQ data can be used to characterise dietary patterns for diet-disease association studies. In the present study, we evaluated three previously defined dietary patterns--'subsistence foods', market-based 'processed foods' and 'fruits and vegetables'--among a sample of Yup'ik people from Southwest Alaska. We tested the reproducibility and reliability of the dietary patterns, as well as the associations of these patterns with dietary biomarkers and participant characteristics. We analysed data from adult study participants who completed at least one FFQ with the Center for Alaska Native Health Research 9/2009-5/2013. To test the reproducibility of the dietary patterns, we conducted a confirmatory factor analysis (CFA) of a hypothesised model using eighteen food items to measure the dietary patterns (n 272). To test the reliability of the dietary patterns, we used the CFA to measure composite reliability (n 272) and intra-class correlation coefficients for test-retest reliability (n 113). Finally, to test the associations, we used linear regression (n 637). All factor loadings, except one, in CFA indicated acceptable correlations between foods and dietary patterns (r>0·40), and model-fit criteria were >0·90. Composite and test-retest reliability of the dietary patterns were, respectively, 0·56 and 0·34 for 'subsistence foods', 0·73 and 0·66 for 'processed foods', and 0·72 and 0·54 for 'fruits and vegetables'. In the multi-predictor analysis, the dietary patterns were significantly associated with dietary biomarkers, community location, age, sex and self-reported lifestyle. This analysis confirmed the reproducibility and reliability of the dietary patterns in the present study population. These dietary patterns can be used for future research and development of dietary interventions in this underserved population.


Tropical forests and the global carbon cycle.
New data on the three major determinants of the carbon release from tropical forest clearing are used in a computer model that simulates land use change and its effects on the carbon content of vegetation and soil in order to calculate the net flux of carbon dioxide between tropical ecosystems and the atmosphere. The model also permits testing the sensitivity of the calculated flux to uncertainties in these data. The tropics were a net source of at least 0.4 x 10(15) grams but not more than 1.6 x 10(15) grams of carbon in 1980, considerably less than previous estimates. Decreases in soil organic matter were responsible for 0.1 x 10(15) to 0.3 x 10(15) grams of the release, while the burning and decay of cleared vegetation accounted for 0.3 x 10(15) to 1.3 x 10(15) grams. These estimates are lower than many previous ones because lower biomass estimates and slightly lower land clearing rates were used and because ecosystem recovery processes were included. These new estimates of the biotic release allow for the possibility of a balanced global budget given the large remaining uncertainties in the marine, terrestrial, and fossil fuel components of the carbon cycle.


Severity of illness and the use of paracetamol in febrile preschool children; a case simulation study of parents' assessments.
Misconceptions and exaggerated fear of fever may divert parents' attention from more predictive symptoms of childhood illness, such as appetite and level of activity. This study aims at exploring how specific predefined characteristics of febrile preschool children affected parents' assessment of the severity of the condition and the perceived need for treatment with paracetamol. Parents judged 24 constructed cases of febrile children with different levels of fever, appetite and activity, occurring at different times of the day. For each case they decided whether the child was moderately or severely ill, and whether or not they would prefer to administer paracetamol. Parents' decision-making was examined by discriminant analyses. Of 466 invited parents, 267 supplied information about their families and 205 accepted to participate in judging constructed cases of febrile children. A total of 159 parents responded to all cases. When evaluating the severity of the illness, 119 parents (75%) responded to one or more of the four cues describing illness. Only one of four cues was used by 80 parents (67%), and 86 (72%) parents emphasized fever. When deciding to give paracetamol, one or more of four cues was used by 102 parents (64%), while 72 parents (71%) used only one cue, and 92 parents (90%) emphasized fever. Parents focus on fever when they evaluate febrile illness and decide whether or not to give paracetamol. Educating parents to focus on their child's level of appetite or activity may improve management, especially when judgement is based on only one or two cues.


Draft genome sequence of carbapenem-resistant Shewanella algae strain AC isolated from small abalone (Haliotis diversicolor).
Shewanella algae is an environmental marine bacterium and an emerging opportunistic human pathogen. Moreover, there are increasing reports of strains showing multidrug resistance, particularly carbapenem-resistant isolates. Although S. algae has been found in bivalve shellfish aquaculture, there is very little genome-wide data on resistance determinants in S. algae from shellfish. The aim of this study was to determine the whole genome sequence of carbapenem-resistant S. algae strain AC isolated from small abalone in Taiwan. Bacterial genomic DNA was sequenced using an Illumina MiSeq platform with 250-bp paired-end reads. De novo genome assembly was performed using Velvet v.1.2.07. The whole genome was annotated and several candidate genes for antimicrobial resistance were identified. The genome size was calculated at 4751156bp, with a mean G+C content of 53.09%. A total of 4164 protein-coding sequences, 7 rRNAs, 85 tRNAs and 5 non-coding RNAs were identified. The genome contains genes associated with resistance to β-lactams, trimethoprim, tetracycline, colistin and quinolones. Multiple efflux pump genes were also detected. Small abalone is a potential source of foodborne drug-resistant S. algae. The genome sequence of carbapenem-resistant S. algae strain AC isolated from small abalone will provide valuable information for further study of the dissemination of resistance genes at the human-animal interface.


Dysregulation of miR-637 is involved in the development of retinopathy in hypertension patients and serves a regulatory role in retinol endothelial cell proliferation.
MicroRNAs (miRNAs) play an important role in the proliferation and migration of retinal endothelial cells in patients with hypertension and hypertensive retinopathy (HR). This study aimed to investigate the clinical value of miR-637 in HR and its role in retinal endothelial cell proliferation and migration. A total of 126 subjects were recruited for the study, including 42 patients with hypertension (male/female 25/17), 42 healthy individuals (male/female 20/22), and 42 cases with HR (male/female 20/22). Except SBP and DBP, there was no significant difference in other indexes among the three groups. qRT-PCR was used to detect the expression of miR-637. The receiver operating curve (ROC) was used for diagnosis value analysis. Logistic regression analysis was used to evaluate the relationship between miR-637 and HR. CCK-8 and Transwell were used to detect the effect of miR-637 on the proliferation and migration of HUVECs. Compared with hypertensive patients, HR patients had the lowest expression of miR-637. The area under the curve (AUC) of miR-637 detected by the ROC curve method is 0.892, which has the ability to distinguish hypertension and HR patients. Logistic regression analysis showed that miR-637 was an independent influence factor in HR. Cell experiment results showed that overexpression of miR-637 significantly inhibited cell proliferation and migration, while downregulation of miR-637 had the opposite effect. Luciferase analysis showed that STAT3 was the target gene of miR-637. Our data indicate that miR-637 is a potential non-invasive marker for patients with HR. The action of miR-637 on STAT3 may inhibit the proliferation and migration of retinal endothelial cells, providing a possible target for the treatment of HR.


Prevention of Soil-transmitted Helminth Infection.
Soil-transmitted helminths (STHs) form one of the most important groups of infectious agents and are the cause of serious global health problems. The most important STHs are roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura) and hookworms (Necator americanus or Ancylostoma duodenale); on a global level, more than a billion people have been infected by at least one species of this group of pathogens. This review explores the general concepts of transmission dynamics and the environment and intensity of infection and morbidity of STHs. The global strategy for the control of soil-transmitted helminthiasis is based on (i) regular anthelminthic treatment, (ii) health education, (iii) sanitation and personal hygiene and (iv) other means of prevention with vaccines and remote sensoring. The reasons for the development of a control strategy based on population intervention rather than on individual treatment are discussed, as well as the costs of the prevention of STHs, although these cannot always be calculated because interventions in health education are difficult to measure. An efficient sanitation infrastructure can reduce the morbidity of STHs and eliminates the underlying cause of most poverty-related diseases and thus supports the economic development of a country.


Anti-pig antibody adsorption efficacy of {alpha}-Gal carrying recombinant P-selectin glycoprotein ligand-1/immunoglobulin chimeras increases with core 2 {beta}1, 6-N-acetylglucosaminyltransferase expression.
We have previously described the construction of a P-selectin glycoprotein ligand-1-mouse immunoglobulin Fc fusion protein, which when transiently coexpressed with the porcine alpha1,3 galactosyltransferase in COS cells becomes a very efficient adsorber of xenoreactive, anti-pig antibodies. To relate the adsorption capacity with the glycan expression of individual fusion proteins produced in different cell lines, stable CHO-K1, COS, and 293T cells producing this fusion protein have been engineered. On alpha1,3 galactosyltransferase coexpression, high-affinity adsorbers were produced by both COS and 293T cells, whereas an adsorber of lower affinity was derived from CHO-K1 cells. Stable coexpression of a core 2 beta1,6 N-acetylglucosaminyltransferase in CHO-K1 cells led to increased alpha-Gal epitope density and improved anti-pig antibody adsorption efficacy. ESI-MS/MS of O-glycans released from PSGL-1/mIgG(2b) produced in an alpha1,3 galactosyl- and core 2 beta1,6 N-acetylglucosaminyltransferase expressing CHO-K1 cell clone revealed a number of structures with carbohydrate sequences consistent with terminal Gal-Gal. In contrast, no O-glycan structures with terminal Gal-Gal were identified on the fusion protein when expressed alone or in combination with the alpha1,3 galactosyltransferase in CHO-K1 cells. In conclusion, the density of alpha-Gal epitopes on PSGL-1/mIgG(2b) was dependent on the expression of O-linked glycans with core 2 structures and lactosamine extensions. The structural complexity of the terminal Gal-Gal expressing O-glycans with both neutral as well as sialic acid-containing structures is likely to contribute to the high adsorption efficacy.


Separating content-specific retrieval from post-retrieval processing.
According to cortical reinstatement accounts, neural processes engaged at the time of encoding are re-engaged at the time of memory retrieval. The temporal precision of event-related potentials (ERPs) has been exploited to assess this possibility, and in this study ERPs were acquired while people made memory judgments to visually presented words encoded in two different ways. There were reliable differences between the scalp distributions of the signatures of successful retrieval of different contents from 300 to 1100 ms after stimulus presentation. Moreover, the scalp distributions of these content-sensitive effects changed during this period. These findings are, to our knowledge, the first demonstration in one study that ERPs reflect content-specific processing in two separable ways: first, via reinstatement, and second, via downstream processes that operate on recovered information in the service of memory judgments.


Coordinated function of cellular DEAD-box helicases in suppression of viral RNA recombination and maintenance of viral genome integrity.
The intricate interactions between viruses and hosts include an evolutionary arms race and adaptation that is facilitated by the ability of RNA viruses to evolve rapidly due to high frequency mutations and genetic RNA recombination. In this paper, we show evidence that the co-opted cellular DDX3-like Ded1 DEAD-box helicase suppresses tombusviral RNA recombination in yeast model host, and the orthologous RH20 helicase functions in a similar way in plants. In vitro replication and recombination assays confirm the direct role of the ATPase function of Ded1p in suppression of viral recombination. We also present data supporting a role for Ded1 in facilitating the switch from minus- to plus-strand synthesis. Interestingly, another co-opted cellular helicase, the eIF4AIII-like AtRH2, enhances TBSV recombination in the absence of Ded1/RH20, suggesting that the coordinated actions of these helicases control viral RNA recombination events. Altogether, these helicases are the first co-opted cellular factors in the viral replicase complex that directly affect viral RNA recombination. Ded1 helicase seems to be a key factor maintaining viral genome integrity by promoting the replication of viral RNAs with correct termini, but inhibiting the replication of defective RNAs lacking correct 5' end sequences. Altogether, a co-opted cellular DEAD-box helicase facilitates the maintenance of full-length viral genome and suppresses viral recombination, thus limiting the appearance of defective viral RNAs during replication.


Role of esterase gp70 and its influence on growth and development of Dictyostelium discoideum.
Gp70 is an esterase originally called crystal protein because of its presence in crystalline structures in aggregation-competent Dictyostelium discoideum cells. Although postulated to break down spore coats, the function of gp70 in vivo was incompletely investigated. Our immunolocalization and biochemical studies of vegetative D. discoideum amoebae show that gp70 was recruited to phagosomes and found in lysosomes. Purified gp70 was effective at hydrolyzing naphthyl substrates with acyl chains typical of lipids and lipopolysaccharides, indicating that the gp70 was involved in digesting endocytosed molecules. The activity of purified gp70 was inhibited by reductants that retarded its electrophoretic mobility and verified the presence of intramolecular disulfide bonds predicted by its amino acid sequence. Compared to wild-type cells, cells overexpressing gp70 were more phagocytically active, had shorter generation times, and produced more fruiting bodies per unit area, while cells lacking gp70 were phagocytically less active with longer doubling times, developed more slowly, and had significantly fewer fruiting bodies per unit area. Consistent with the phenotype of a disrupted metabolism, one-third of the gp70-minus cells were large and multinucleated. Together, these results indicated that despite its crystalline appearance, gp70 was an active esterase involved in both the growth and the development of D. discoideum.


[Changes of the sex hormones in female type II diabetics, coronary heart disease, essential hypertension and its relations with kidney deficiency, cardiovascular complications and efficacy of traditional Chinese medicine or qigong treatment].
In this study 31 normal child-bearing women, 62 postmenopausal women, 93 cases of female type II diabetes (18 child-bearing and 75 postmenopausal cases), 53 cases of coronary heart disease (11 child-bearing and 42 postmenopausal cases) and 38 cases of essential hypertension (8 child-bearing and 30 postmenopausal cases) were investigated. The average score of Kidney deficiency was 22.9-8. 5 before treatment with the combination of TCM and WM. With the treatment of TCM in diabetes and coronary heart disease and of Qigong in essential hypertension, the score decreased to 11.5-4. 4 (P less than 0.001). Serum/saliva estradiol (E2), the ratio of E2 to testosterone (T, E2/T) and progesterone (P) decreased before treatment of TCM or Qigong. After treatment E2 and P value increased; the ovarian endocrine function was improved; the special symptoms of the diseases relieved, fasting blood glucose levels in diabetics, the frequency and severity of angina pectoris in coronary heart disease and the blood pressure in essential hypertension significantly decreased respectively (P less than 0.01). The study suggested that there are certain relations between ovarian endocrine disfunction and Kidney deficiency. The more severe the "Kidney deficiency" was, the more significant the changes of sex hormone were.


Improvement of water barrier property of paperboard by coating application with biodegradable polymers.
Biopolymeric coatings were prepared and applied onto paperboard to improve its water barrier property. To prepare whey protein isolate (WPI)/cellulose-based films, WPI and glycerol were dissolved in water with glutaraldehyde (cross-linking agent) and cellulose xanthate. The solution was cast, dried, and insolubilized by entrapment of WPI in regenerated cellulose. Films were combined with beeswax (BW) into a bilayer coating system and then applied onto paperboard by heating compression. Another coating solution consisting of poly(vinyl butyral) (PVB)/zein was prepared by dissolving poly(vinyl alcohol) (PVA) and zein in 70% ethanol with glutaraldehyde and butyraldehyde (functionalization agent). The PVB/zein solution was applied onto paperboard after BW was sprayed. The structure of the PVB/zein-based coatings was analyzed by Fourier transform infrared spectroscopy (FTIR). The water vapor barrier property of coated paperboards was evaluated by water vapor transmission rate (WVTR) measurements. From the FTIR spectra, PVA functionalization after cross-linking and efficient acetalization into PVB were confirmed. WPI/cellulose and PVB/zein coating treatments improved the water barrier properties of paperboard by decreasing the WVTR by 77-78%. Although the BW coating was more efficient (decrease of WVTR by 89%), bilayer coatings composed of BW and polymer coatings had a stronger barrier effect with a decrease of WVTR to 92-95%, hence approaching commercial attributes required to ensure water vapor barrier in paperboard-based food containers (10 g/m(2).day). These results suggest that surface coating by biodegradable polymers may be utilized for the manufacture of paperboard containers in industrial applications.


Asia, Australia and New Zealand Dyspnoea in Emergency Departments (AANZDEM) study: Rationale, design and analysis.
Shortness of breath is a common reason for ED attendance. This international study aims to describe the epidemiology of dyspnoea presenting to EDs in the South East Asia-Pacific region, to compare disease patterns across regions, to understand how conditions are investigated and treated, and to assess quality of care. This is a prospective, interrupted time series cohort study conducted in EDs in Australia, New Zealand, Singapore, Hong Kong and Malaysia of consecutive adult patients presenting to the ED with dyspnoea as a main symptom. Data were collected over three 72 h periods in May, August and October 2014 (autumn, winter and spring), and included demographics, comorbidities, mode of arrival, usual medications, pre-hospital treatment, initial assessment, ED investigations, treatment in the ED, ED diagnosis, disposition from ED, in-hospital outcome and final hospital diagnosis. The primary outcomes of interest are the epidemiology and outcome of patients presenting to ED with dyspnoea. Secondary outcomes of interest are seasonal and geographic comparisons of diagnoses and outcomes, disease-specific descriptions of epidemiology, investigation, treatment and disposition, and compliance with treatment guidelines. This novel study will explore dyspnoea from the viewpoint of the patient's symptom (shortness of breath) rather than that of a single disease. The results will provide robust data about the epidemiology, investigation, treatment and disposition of this diverse patient group. The obtained data also have the potential to inform service planning and to quantify the proportion of patients with mixed cardiac and respiratory disease.


Calcium supplementation does not augment bone gain in young women consuming diets moderately low in calcium.
In earlier observational work, the dietary calcium:protein ratio was directly related to bone accrual in healthy postadolescent women. In this study, we sought to test the hypothesis that augmented calcium intake would increase postadolescent skeletal consolidation, using a double-blind, randomized, placebo-controlled design. We recruited 152 healthy young women (age 23.1 +/- 2.7 y, BMI 22.5 +/- 3.0 kg/m2); their usual diets, as assessed by 7-d food diaries, were low in calcium (605 +/- 181 mg/d; 15.1 +/- 4.5 mmol/d) and in the calcium:protein ratio (10.1 +/- 2.0 mg/g). The subjects were randomly assigned to supplemental calcium [500 mg calcium (12.5 mmol) as the carbonate, 3 times/d, with meals] or placebo capsules identical in appearance; all participants also took a daily multivitamin, and they were followed for up to 36 mo with bone densitometry (dual energy X-ray absorptiometry; DXA) at 6-mo intervals. A total of 121 subjects remained in the study for at least 12 mo (median time in the study, 35 mo), with a mean compliance level (observed/expected tablet consumption) of 87.7%. DXA data for these 121 subjects indicated modest but significant mean rates of increase (i.e., 0.24 to 1.10%/y) in bone mineral content (BMC; total body, total hip, and lumbar spine) and in lumbar spine bone mineral density (BMD) but no change in total hip BMD. None of these rates of change differed by group, i.e., calcium supplementation did not have any measurable effect on bone mass accrual. By midstudy, the calcium content of the subjects' usual diets for both groups had risen by approximately 15%. The combined effect of improved intakes of dietary calcium and the small amount of calcium added by the multivitamin tablets resulted in a mean calcium intake for the control group > 800 mg (20 mmol)/d, possibly at or near the threshold beyond which additional calcium has no further effect on bone accrual.


Influence of the chemical shift artifact on measurements of compact bone thickness in equine distal limb MR images.
The effect of the chemical shift artifact, resulting from misregistration or phase cancellation at the interface between compact and trabecular bone, on apparent bone thickness was quantified in six isolated equine limbs. Sagittal T1-weighted spin echo (SE) and in-phase three-dimensional spoiled gradient echo (SPGR) images were acquired twice with a 1.5 T magnetic resonance (MR) unit, switching the frequency encoding direction between acquisitions. Out-of-phase SPGR images were also obtained. MR images with different frequency encoding directions were compared with each other and to radiographs made from corresponding 3-mm-bone sections. Compact bone thickness was significantly different when comparing images acquired with different frequency encoding directions for both SE and SPGR sequences. Significant differences were identified in the frequency but not the phase encoding direction when measurements of compact bone in MR images were compared with measurements obtained from thin section radiographs for the majority of surfaces studied (P < 0.05). Correction of MR measurements with the calculated chemical shift abolished these differences (P > 0.05). Measurements of compact bone from out-of-phase SPGR sequences were significantly different than from in-phase sequences (P < 0.001) with out-of-phase measurements greater than in-phase measurements by an average of 0.38mm. These results indicate that the chemical shift artifact results in errors in MR evaluation of compact bone thickness when measurements are performed in the frequency encoding direction or in out-of-phase images. For better accuracy, measurements should be performed parallel to the phase encoding direction and avoiding out-of-phase gradient echo sequences.


Pancreatic growth: interaction of exogenous cholecystokinin, a protease inhibitor, and a cholecystokinin receptor antagonist in mice.
The effects on pancreatic growth and plasma CCK concentration of chronic feeding of camostate (400 mg/kg day for 10 days), a potent inhibitor of serine proteases including trypsin, were assessed in the mouse. For comparison, the trophic effects of chronic exogenous administration of CCK octapeptide (sc injection of 1 microgram/kg day every eight hours for 10 days) were also studied. In addition, the effects of a proglumide-analogue CCK-receptor antagonist (CR1409) on the stimulatory actions of camostate feeding and chronic administration of exogenous CCK were studied. The effects of the combination of chronic camostate feeding and sc injections of CCK, the effects of acute camostate feeding, and the effects of the CCK-receptor antagonist given without camostate or CCK were also studied. The results show that chronic camostate feeding markedly increased CCK plasma concentrations eight-fold over control values, and that acute camostate feeding increased plasma concentration to four fold of control values. Correspondingly, chronic camostate feeding markedly increased pancreatic weight, protein and DNA content. Exogenous CCK-8 also had qualitatively similar, but quantitatively less potent stimulatory effects. The combination of camostate and CCK-8 resulted in an additive stimulatory effect. The trophic actions of exogenous and endogenous CCK grossly increased chymotrypsinogen content, but left amylase content unaffected. The CCK-receptor antagonist CR 1409 completely abolished the trophic effects of exogenous CCK and greatly inhibited the effects of chronic camostate feeding. The CCK antagonist decreased pancreatic weight, DNA and protein content compared to control values when given without any CCK or camostate. We conclude that the protease inhibitor camostate is a very strong release effector of CCK and exerts a powerful trophic effect on mouse pancreas which is probably mediated by CCK. Furthermore, physiological increases of CCK during feeding of regular chow appear to exert trophic effects on the exocrine pancreas.


Association of Air Pollution and Physical Activity With Brain Volumes.
In high-pollution areas, physical activity may have a paradoxical effect on brain health by increasing particulate deposition in the lungs. We examined whether physical activity modifies associations of air pollution (AP) with brain volumes in an epidemiologic framework. The UK Biobank enrolled >500,000 adult participants from 2006 to 2010. Wrist accelerometers, multimodal MRI with T1 images and T2 fluid-attenuated inversion recovery data, and land use regression were used to estimate vigorous physical activity (VigPA), structural brain volumes, and AP, respectively, in subsets of the full sample. We evaluated associations among AP interquartile ranges, VigPA, and brain structure volumes and assessed interactions between AP and VigPA. Eight thousand six hundred participants were included, with an average age of 55.55 (SD 7.46) years. After correction for multiple testing, in overall models, VigPA was positively associated with gray matter volume (GMV) and negatively associated with white matter hyperintensity volume (WMHV), while NO2, PM2.5absorbance, and PM2.5 were negatively associated with GMV. NO2 and PM2.5absorbance interacted with VigPA on WMHV (false discovery rate-corrected interaction p = 0.037). Associations between these air pollutants and WMHVs were stronger among participants with high VigPA. Similarly, VigPA was negatively associated with WMHV for those in areas of low NO2 and PM2.5absorbance but was null among those living in areas of high NO2 and PM2.5absorbance. DISCUSSION: Physical activity is associated with beneficial brain outcomes, while AP is associated with detrimental brain outcomes. VigPA may exacerbate associations of AP with white matter hyperintensity lesions, and AP may attenuate the beneficial associations of physical activity with these lesions.


Methodologic issues in health informatics trials: the complexities of complex interventions.
OBJECTIVE All electronic health (e-health) interventions require validation as health information technologies, ideally in randomized controlled trial settings. However, as with other types of complex interventions involving various active components and multiple targets, health informatics trials often experience problems of design, methodology, or analysis that can influence the results and acceptance of the research. Our objective was to review selected key methodologic issues in conducting and reporting randomized controlled trials in health informatics, provide examples from a recent study, and present practical recommendations. DESIGN For illustration, we use the COMPETE III study, a large randomized controlled clinical trial investigating the impact of a shared decision-support system on the quality of vascular disease management in Ontario, Canada. RESULTS We describe a set of methodologic, logistic, and statistical issues that should be considered when planning and implementing trials of complex e-health interventions, and provide practical recommendations for health informatics trialists. CONCLUSIONS Our recommendations emphasize validity and pragmatic considerations and would be useful for health informaticians conducting or evaluating e-health studies.


Association between plant-based diets and blood pressure in the INTERMAP study.
Plant-based diets are associated with a lower risk of cardiovascular diseases; however, little is known how the healthiness of the diet may be associated with blood pressure (BP). We aimed to modify three plant -based diet indices: overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI) according to country-specific dietary guidelines to enable use across populations with diverse dietary patterns - and assessed their associations with BP. We used cross-sectional data including 4,680 men and women ages 40-59y in Japan, China, the United Kingdom, and the United States from the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP). During four visits, eight BP measurements, and four 24-h dietary recalls were collected. Multivariable regression coefficients were estimated, pooled, weighted, and adjusted extensively for lifestyle/dietary confounders. Modified PDI was not associated with BP. Consumption of hPDI higher by 1SD was inversely associated with systolic (-0.82 mm Hg;95% CI:-1.32,-0.49) and diastolic BP (-0.49 mm Hg; 95% CI:-0.91, -0.28). In contrast, consumption of an uPDI was directly associated with systolic (0.77 mm Hg;95% CI:0.30,1.20). Significant associations between hPDI with BP were attenuated with separate adjustment for vegetables and whole grains; associations between uPDI and BP were attenuated after adjustment for refined grains, sugar-sweetened beverages, and meat. An hPDI is associated with lower BP while a uPDI is adversely related to BP. Plant-based diets rich in vegetables and whole grains and limited in refined grains, sugar-sweetened beverages, and total meat may contribute to these associations. In addition to current guidelines, the nutritional quality of consumed plant foods is as important as limiting animal-based components. The observational INTERMAP study was registered at www.clinicaltrials.gov as NCT00005271.


Molecular mechanism of the tree shrew's insensitivity to spiciness.
Spicy foods elicit a pungent or hot and painful sensation that repels almost all mammals. Here, we observe that the tree shrew (Tupaia belangeri chinensis), which possesses a close relationship with primates and can directly and actively consume spicy plants. Our genomic and functional analyses reveal that a single point mutation in the tree shrew's transient receptor potential vanilloid type-1 (TRPV1) ion channel (tsV1) lowers its sensitivity to capsaicinoids, which enables the unique feeding behavior of tree shrews with regards to pungent plants. We show that strong selection for this residue in tsV1 might be driven by Piper boehmeriaefolium, a spicy plant that geographically overlaps with the tree shrew and produces Cap2, a capsaicin analog, in abundance. We propose that the mutation in tsV1 is a part of evolutionary adaptation that enables the tree shrew to tolerate pungency, thus widening the range of its diet for better survival.


[177Lu]Bz-DTPA-EGF: Preclinical characterization of a potential radionuclide targeting agent against glioma.
Patients with glioblastoma multiforme have a poor prognosis due to recurrences originating from spread cells. The use of radionuclide targeting might increase the chance of inactivating single tumor cells with minimal damage to surrounding healthy tissue. As a target, overexpressed epidermal growth factor receptors (EGFR) may be used. A natural ligand to EGFR, the epidermal growth factor (EGF) is an attractive targeting agent due to its low molecular weight (6 kDa) and high affinity for EGFR. 177Lu (T(1/2) = 6.7 days) is a radionuclide well suited for treatment of small tumor cell clusters, since it emits relatively low-energy beta particles. The goal of this study was to prepare and preclinically evaluate both in vitro and in vivo the [177Lu]Bz-DTPA-EGF conjugate. The conjugate was characterized in vitro for its cell-binding properties, and in vivo for its pharmacokinetics and ability to target EGFR. [177Lu]Bz-DTPA-EGF bound to cultured U343 glioblastoma cells with an affinity of 1.9 nM. Interaction with EGFR led to rapid internalization, and more than 70% of the cell-associated radioactivity was internalized after 30 minutes of incubation. The retention of radioactivity was good, with more than 65% of the 177Lu still cell-associated after 2 days. Biodistribution studies of i.v. injected [177Lu]Bz-DTPA-EGF in NMRI mice demonstrated a rapid blood clearance. Most of the radioactivity was found in the liver and kidneys. The liver uptake was receptor-mediated, since it could be significantly reduced by preinjection of unlabeled EGF. In conclusion, [177Lu]Bz-DTPA-EGF seems to be a promising candidate for locoregional treatment of glioblastoma due to its high binding affinity, low molecular weight, and ability to target EGFR in vivo.


Rails and anchors: guiding and trapping droplet microreactors in two dimensions.
This paper presents a method to control the motion of nanolitre drops in a wide and thin microchannel, by etching fine patterns into the channel's top surface. Such control is possible for drops that are squeezed by the channel roof, by allowing them to reduce their surface energy as they enter into a local depression. The resulting gain in surface energy pulls a drop into the groove such that localized holes can be used as anchors for holding drops, while linear patterns can be used as rails to guide them along complex trajectories. An anchored drop can remain stationary indefinitely, as long as the driving flow rate is below a critical value which depends on the hole and drop sizes. By micro-fabricating holes into a grid pattern, drops can be arrayed and held in the observation field of a microscope against the mean carrier flow. Their contents can then be modulated by gas exchange with the flowing carrier oil. We demonstrate in particular how the pH or the oxygen levels within the drops can be controlled spatially and temporally, either by exposing rows of drops to two streams of oil at different gas concentrations or by periodically switching oil inputs to vary the gas concentration of drops as a function of time. Oxygen control is used to selectively deoxygenate droplets that encapsulate red blood cells from patients suffering from sickle cell disease, in order to study the polymerization of intracellular hemoglobin. Cycles of oxygenation and deoxygenation of anchored droplets induce depolymerization and polymerization of the hemoglobin, thus providing a method to simulate the cycling that takes place in physiological flows.


Two cases of mucinous cystadenoma of the appendix successfully treated by laparoscopy.
Two cases of mucinous cystadenoma of the appendix successfully treated by laparoscopy are reported. An 81-year-old woman with lower right back pain was diagnosed with mucinous cystadenoma of the appendix or appendiceal carcinoma and underwent elective laparoscopic surgery. The other case involved a 70-year-old man with hematochezia who was diagnosed with mucinous cystadenoma. He also underwent elective laparoscopic surgery. In these two cases, gauze was folded around the tumors rather than grasping them directly. The postoperative courses were uneventful, and these patients had no recurrent disease at 2-year follow-up. In such cases, surgical excision of the tumor without rupture is of paramount importance because rupture of the lesion can cause pseudomyxoma peritonei. Though appendiceal mucinous cystadenoma has been considered a contraindication of laparoscopic resection, it was possible to achieve this by using a laparoscopic procedure with a gauze technique.


Human brain and placental choline acetyltransferase: purification and properties.
Choline acetyltransferase (EC 126.96.36.199) catalyzes the biosynthesis of acetylcholine according to the following chemical equation: acetyl-CoA + choline in equilibrium to acetylcholine + CoA. In addition to nervous tissue, primate placenta is the only other animal source which contains appreciable acetylcholine and its biosynthetic enzyme. Human brain caudate nucleus and human placental choline acetyltransferase were purified to electrophoretic homogeneity using ion-exchange and blue dextran-Sepharose affinity chromatography. The molecular weights determined by Sephadex G-150 gel filtration and sodium dodecyl sulfate gel electrophoresis are 67000 plus or minus 3000. N-Ethylmaleimide, p-chloromercuribenzoate, and dithiobis(2-nitrobenzoic acid) inhibit the enzyme. Dithiothreitol reverses the inhibition produced by the latter two reagents. The pKa of the group associated with N-ethylmaleimide inhibition is 8.6 plus or minus 0.3. A chemically competent acetyl-thioenzyme is isolable by Sephadex gel filtration. The enzymes from the brain and placenta are thus far physically and biochemically indistinguishable.


Aromatherapy as treatment for postoperative nausea: a randomized trial.
Postoperative nausea (PON) is a common complication of anesthesia and surgery. Antiemetic medication for higher-risk patients may reduce but does not reliably prevent PON. We examined aromatherapy as a treatment for patients experiencing PON after ambulatory surgery. Our primary hypothesis was that in comparison with inhaling a placebo, PON will be reduced significantly by aromatherapy with (1) essential oil of ginger, (2) a blend of essential oils of ginger, spearmint, peppermint, and cardamom, or (3) isopropyl alcohol. Our secondary hypothesis was that the effectiveness of aromatherapy will depend upon the agent used. A randomized trial of aromatherapy with patients who reported nausea in the postanesthesia care unit was conducted at one ambulatory surgical center. Eligibility criteria were adult, able to give consent, and no history of coagulation problems or allergy to the aromatherapy agents. Before surgery, demographic and risk factors were collected. Patients with a nausea level of 1 to 3 on a verbal descriptive scale (0-3) received a gauze pad saturated with a randomly chosen aromatherapy agent and were told to inhale deeply 3 times; nausea (0-3) was then measured again in 5 minutes. Prophylactic and postnausea antiemetics were given as ordered by physicians or as requested by the patient. A total of 1151 subjects were screened for inclusion; 303 subjects reporting nausea were enrolled (26.3%), and 301 meeting protocol were analyzed (26.2%). The change in nausea level was significant for the blend (P < 0.001) and ginger (P = 0.002) versus saline but not for alcohol (P < 0.76). The number of antiemetic medications requested after aromatherapy was also significantly reduced with ginger or blend aromatherapy versus saline (P = 0.002 and P < 0.001, respectively). The hypothesis that aromatherapy would be effective as a treatment for PON was supported. On the basis of our results, future research further evaluating aromatherapy is warranted. Aromatherapy is promising as an inexpensive, noninvasive treatment for PON that can be administered and controlled by patients as needed.


Histone H3 phosphorylation can promote TBP recruitment through distinct promoter-specific mechanisms.
Histone phosphorylation influences transcription, chromosome condensation, DNA repair and apoptosis. Previously, we showed that histone H3 Ser10 phosphorylation (pSer10) by the yeast Snf1 kinase regulates INO1 gene activation in part via Gcn5/SAGA complex-mediated Lys14 acetylation (acLys14). How such chromatin modification patterns develop is largely unexplored. Here we examine the mechanisms surrounding pSer10 at INO1, and at GAL1, which herein is identified as a new regulatory target of Snf1/pSer10. Snf1 behaves as a classic coactivator in its recruitment by DNA-bound activators, and in its role in modifying histones and recruiting TATA-binding protein (TBP). However, one important difference in Snf1 function in vivo at these promoters is that SAGA recruitment at INO1 requires histone phosphorylation via Snf1, whereas at GAL1, SAGA recruitment is independent of histone phosphorylation. In addition, the GAL1 activator physically interacts with both Snf1 and SAGA, whereas the INO1 activator interacts only with Snf1. Thus, at INO1, pSer10's role in recruiting SAGA may substitute for recruitment by DNA-bound activator. Our results emphasize that histone modifications share general functions between promoters, but also acquire distinct roles tailored for promoter-specific requirements.


The Effectiveness of Functional Family Therapy in Reducing Adolescent Mental Health Risk and Family Adjustment Difficulties in an Irish Context.
To evaluate the effectiveness of Functional Family Therapy (FFT) 42 cases were randomized to FFT and 55 to a waiting-list control group. Minimization procedures controlled the effects of potentially confounding baseline variables. Cases were treated by a team of five therapists who implemented FFT with a moderate degree of fidelity. Rates of clinical recovery were significantly higher in the FFT group than in the control group. Compared to the comparison group, parents in the FFT group reported significantly greater improvement in adolescent problems on the Strengths and Difficulties Questionnaire (SDQ) and both parents and adolescents reported improvements in family adjustment on the Systemic Clinical Outcomes and Routine Evaluation (SCORE). In addition, 93% of youth and families in the treatment condition completed FFT. Improvements shown immediately after treatment were sustained at 3-month follow-up. Results provide a current demonstration of FFT's effectiveness for youth with behavior problems in community-based settings, expand our understanding of the range of positive outcomes of FFT to include mental health risk and family-defined problem severity and impact, and suggests that it is an effective intervention when implemented in an Irish context.


Long-wavelength infrared (~10-15 mm) electroluminescence from Sb-based interband cascade devices.
Electroluminescence in the long-wavelength infrared (10-15 mm) spectrum region was observed from Sb-based type-II interband cascade quantum well structures. The device structure was grown by molecular beam epitaxy on a GaSb substrate and comprises 10 repeated periods of active regions separated by digitally graded multilayer injection regions. The devices have been operated at 300 K and 77 K, with an output optical power up to 50 nW. The emission wavelength, the longest observed in any compound semiconductor material at room temperature, results from tailoring the heterostructure, demonstrating a unique capability of this Sb-family type-II material system.


Identification of small molecule inhibitors of the Lin28-mediated blockage of pre-let-7g processing.
The protein Lin28 and microRNA let-7 play critical roles in mammalian development and human disease. Lin28 inhibits let-7 biogenesis through direct interaction with let-7 precursors (pre-let-7). Accumulating evidence in vitro and in vivo suggests this interaction plays a dominant role in embryonic stem cell self-renewal and tumorigenesis. Thus the Lin28-let-7 interaction might be an attractive drug target, if not for the well-known difficulties in targeting protein-RNA interactions with drugs. The identification and development of suitable probe molecules to further elucidate therapeutic potential, as well as mechanistic details of this pathway will be valuable. We report the development and application of a biophysical high-throughput screening assay for the identification of small molecule inhibitors of the Lin28-pre-let-7 interaction. A library of pharmacologically active small molecules was screened and several small molecule inhibitors were identified and biochemically validated. Of these four validated inhibitors, two compounds successfully restored processing of pre-let-7g in the presence of Lin28, validating the concept. Thus, we have identified examples of small molecule inhibitors of the interaction between Lin28 and pre-let-7. This study provides a proof of concept for small molecule inhibitors that antagonise the effects of Lin28 and enhance processing of let-7 miRNA.


Ozonation of source-separated urine for resource recovery and waste minimization: process modeling, reaction chemistry, and operational considerations.
Bench-scale, semibatch experiments were performed to examine physical-chemical constraints on ozone (O3) absorption and micropollutant oxidation during ozonation of source-separated hydrolyzed urine and the concentrate and diluate streams produced via electrodialysis of hydrolyzed urine. O3 consumption by each matrix was found to occur within a fast pseudo-first-order kinetic regime. Critical constraints on micropollutant oxidation were found through mass transfer modeling to be (i) micropollutant diffusion from the bulk solution into the gas-liquid interfacial film for compounds recalcitrant toward O3 (i.e., k"O3,app < or = 10(3) M(-1) s(-1)), and (ii) aqueous-phase mixing for compounds highly reactive toward O3 (i.e., k"O3,app > 10(3) M(-1) s(-1)). Homogeneous chemical reaction modeling indicated that aqueous reaction chemistry is significantly influenced bythe degree to which incidentally produced hydroxyl radicals are consumed by NH3 in each matrix, in terms of (a) micropollutant oxidation efficiencies, and (b) potential yields of oxidation byproducts. On the basis of the experimental data reported here, per capita energy requirements were estimated for treatment of source-separated urine via (1) ozonation, (2) ozonation with postelectrodialysis, and (3) electrodialysis with postozonation. These estimates indicate that scenario (1) would likely be less energy efficient than ozonation of municipal wastewater effluent in achieving equivalent reductions in urine-derived micropollutant loads, whereas scenarios (2 and 3) could be more efficient than equivalent centralized wastewater treatment strategies in achieving equivalent levels of urine-derived nutrient and micropollutant attenuation. Furthermore, experimental and model data suggest that urine ozonation efficiency may be substantially improved by optimizing aqueous-phase mixing and specific gas-liquid interfacial area.


Coagulopathy: its pathophysiology and treatment in the injured patient.
Hemorrhage continues to be one of the leading causes of death following trauma. Trauma patients are susceptible to the early development of coagulopathy and the most severely injured patients are coagulopathic on hospital admission. Hypothermia, acidosis, and dilution from standard resuscitation can worsen the presenting coagulopathy and perpetuate bleeding. Early identification of coagulopathy is dependent on clinical awareness and point of care laboratory values. Routinely used laboratory coagulation parameters fail to adequately describe this state. Thrombelastography is a test that can be done at the bedside and uses whole blood to provide a functional evaluation of coagulation. Rapid diagnosis of coagulopathy, followed by prevention or correction of hypothermia and acidosis should be a priority during the initial evaluation and resuscitation. Judicious use of resuscitation fluids and early replacement of coagulation factors will help prevent iatrogenic hemodilution. This review covers the pathophysiology as well as the clinical and laboratory diagnosis of coagulopathy. Prevention and treatment strategies are discussed, including early transfusion of coagulation factors during massive transfusion and the use of recombinant factor VIIa. Damage control resuscitation is briefly discussed, and it involves the combination of hypotensive resuscitation and hemostatic resuscitation. Finally, a description of the use of fresh whole blood in the military setting is included. Its use has been proven to be safe and beneficial in this setting and warrants further investigation as an adjunct to the management of civilian trauma patients.


New strategies in the treatment of the thalassemias.
In addition to the severe beta thalassemias, hematologists have begun to recognize the more severe forms of alpha thalassemia, namely hemoglobin (Hb) H disease and Hb H/Hb Constant Spring, as well as the beta compound heterozygote, beta thalassemia/HbE. Clinically, variably severe anemia becomes apparent in the first year accompanied by occasionally massive expansion of erythropoiesis. The most anemic patients require regular red blood cell transfusions to avoid death from cardiac failure. However, the inevitable iron accumulation leads to dysfunction, primarily involving the heart, liver, and endocrine system; thus, regularly transfused patients require iron chelation. A major discovery was that allogeneic bone marrow (stem cell) transplantation in severely affected subjects with both alpha and beta thalassemia could result in cure. Current work deals with specific complications, such as iron overload and endocrine, cardiopulmonary, thrombophilic, and osteopenic problems. The thalassemias are likely to benefit in the future from specific gene therapy. There are also important advances in genetic counseling based on results of early fetal diagnosis.


Intercellular calcium signaling induced by extracellular adenosine 5'-triphosphate and mechanical stimulation in airway epithelial cells.
Airway epithelial cells in culture respond to extracellular adenosine 5'-triphosphate (ATP) by increasing their intracellular Ca2+ concentration ([Ca2+]i). The effective concentration of ATP that elicited a Ca2+ response equal to 50% of the maximal response (EC50) was 0.5 microM. Release of ATP from a pipette to form a local gradient of ATP increased [Ca2+]i of individual cells in a sequential manner. Cells closest to the pipette showed an immediate increase in [Ca2+]i while more distal cells displayed a delayed increase in [Ca2+]i. This response to the local release of ATP appeared as a wave of increasing [Ca2+]i that spread to several cells and, in this respect, was similar to the intercellularly communicated Ca2+ waves initiated by mechanical stimulation in airway epithelial cells (Sanderson et al., Cell Regul. 1, 585-596, 1990). In the presence of a unidirectional fluid flow, the Ca2+ response to a local release of ATP was biased such that virtually all the cells responding with an increase in [Ca2+]i were downstream of the release site. By contrast, an identical fluid flow did not bias the radial propagation of intercellular Ca2+ waves induced by mechanical stimulation. Suramin, a P2-purinergic receptor antagonist, did attenuate the Ca2+ response induced by ATP but did not block the propagation of mechanically induced Ca2+ waves. Cells from young cultures (3-5 days) or those at the leading edge of an outgrowth elevated their [Ca2+]i in response to ATP. However, these cells do not respond to mechanical stimulation by the propagation of a Ca2+ wave. From these results we conclude that the intercellular Ca2+ waves elicited by mechanical stimulation are not the result of ATP or another compound released from the stimulated cell, diffusing through the extracellular fluid. This conclusion is consistent with previous experimental evidence suggesting that intercellular Ca2+ signaling in epithelial cells is mediated by the movement of inositol trisphosphate through gap junctions.


Effectiveness of nutrition centers in Ceará state, northeastern Brazil.
Childhood malnutrition has been a major, long-standing health concern in northeastern Brazil. In response, during 1992-1994, the state government of Ceará, with financial support from the World Bank, established 34 new nutrition centers. During 1996 an evaluation of the centers was conducted to determine their effectiveness in treating children with malnutrition and to identify weaknesses in the system and possible solutions. Also evaluated were the adequacy of resources, admission and discharge criteria, staff training, and community satisfaction. Effectiveness was found to be low. Treatment procedures did not conform with World Health Organization recommendations. Rates of weight gain were inadequate, and the mean duration of rehabilitation--8.7 months--was too long. Case fatality in two centers was unacceptably high, 40% and more. Entry and exit criteria for rehabilitation were ill defined, resulting in some nonmalnourished children being enrolled. Few staff were adequately trained; knowledge was weak, especially about case management; and mothers were not effectively instructed. Recommendations include setting objectives for the centers, improving referral systems, standardizing entry criteria, improving case management, and establishing performance indicators.


Indoor exposure to particulate matter and the incidence of acute lower respiratory infections among children: a birth cohort study in urban Bangladesh.
Approximately half of all children under two years of age in Bangladesh suffer from an acute lower respiratory infection (ALRI) each year. Exposure to indoor biomass smoke has been consistently associated with an increased risk of ALRI in young children. Our aim was to estimate the effect of indoor exposure to particulate matter (PM2.5 ) on the incidence of ALRI among children in a low-income, urban community in Bangladesh. We followed 257 children through two years of age to determine their frequency of ALRI and measured the PM2.5 concentrations in their sleeping space. Poisson regression was used to estimate the association between ALRI and the number of hours per day that PM2.5 concentrations exceeded 100 μg/m(3) , adjusting for known confounders. Each hour that PM2.5 concentrations exceeded 100 μg/m(3) was associated with a 7% increase in incidence of ALRI among children aged 0-11 months (adjusted incidence rate ratio (IRR) 1.07, 95% CI 1.01-1.14), but not in children 12-23 months old (adjusted IRR 1.00, 95% CI 0.92-1.09). Results from this study suggest that reducing indoor PM2.5 exposure could decrease the frequency of ALRI among infants, the children at highest risk of death from these infections.


Extensive changes in the expression of the opioid genes between humans and chimpanzees.
The various means by which the body perceives, transmits, and resolves the experiences of pain and nociception are mediated by a host of molecules, including neuropeptides within the opioid gene signaling pathway. The peptide ligands and receptors encoded by this group of genes have been linked to behavioral disorders as well as a number of psychiatric affective disorders. Our aim was to explore the recent evolutionary history of these two gene families by taking a comparative genomics approach, specifically through a comparison between humans and chimpanzees. Our analyses indicate differential expression of these genes between the two species, more than expected based on genome-wide comparisons, indicating that differential expression is pervasive among the opioid genes. Of the 8 family members, three genes showed significant expression differences (PENK, PNOC, and OPRL1), with two others marginally significant (OPRM1 and OPRD1). Accelerated substitution rates along human and chimpanzee lineages within the putative regulatory regions of OPRM1, POMC, and PDYN between the human and chimpanzee branches are consistent with positive selection. Collectively, these results suggest that there may have been a selective advantage to modulating the expression of the opioid genes in humans compared with our closest living relatives. Information about the cognitive roles mediated by these genes in humans may help to elucidate the trait consequences of these putatively adaptive expression changes.


Regulation of Physical Microglia-Neuron Interactions by Fractalkine Signaling after Status Epilepticus.
Microglia, the resident immune cells of the brain, perform elaborate surveillance in which they physically interact with neuronal elements. A novel form of microglia-neuron interaction named microglial process convergence (MPC) toward neuronal axons and dendrites has recently been described. However, the molecular regulators and pathological relevance of MPC have not been explored. Here, using high-resolution two-photon imaging in vivo and ex vivo, we observed a dramatic increase in MPCs after kainic acid- or pilocarpine-induced experimental seizures that was reconstituted after glutamate treatment in slices from mice. Interestingly, a deficiency of the fractalkine receptor (CX3CR1) decreased MPCs, whereas fractalkine (CX3CL1) treatment increased MPCs, suggesting that fractalkine signaling is a critical regulator of these microglia-neuron interactions. Furthermore, we found that interleukin-1β was necessary and sufficient to trigger CX3CR1-dependent MPCs. Finally, we show that a deficiency in fractalkine signaling corresponds with increased seizure phenotypes. Together, our results identify the neuroglial CX3CL1-CX3CR1 communication axis as a modulator of potentially neuroprotective microglia-neuron physical interactions during conditions of neuronal hyperactivity.


CURRENT CONCEPTS OF PLYOMETRIC EXERCISE.
As knowledge regarding rehabilitation science continues to increase, exercise programs following musculoskeletal athletic injury continue to evolve. Rehabilitation programs have drastically changed, especially in the terminal phases of rehabilitation, which include performance enhancement, development of power, and a safe return to activity. Plyometric exercise has become an integral component of late phase rehabilitation as the patient nears return to activity. Among the numerous types of available exercises, plyometrics assist in the development of power, a foundation from which the athlete can refine the skills of their sport. Therefore, the purpose of this clinical commentary is to provide an overview of plyometrics including: definition, phases, the physiological, mechanical and neurophysiological basis of plyometrics, and to describe clinical guidelines and contraindications for implementing plyometric programs.


Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer.
Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial. Patients with advanced cancer received oral cyclophosphamide 50 mg o.d., celecoxib 400 mg b.d. and methotrexate 2.5 mg b.d. for two consecutive days each week. Response was determined every 8 weeks; toxicity was evaluated according to CTC version 2.0. Plasma markers of inflammation, coagulation and angiogenesis were measured. Sixty-seven of 69 patients were evaluable for response. Twenty-three patients had stable disease (SD) after 8 weeks, but there were no objective responses to therapy. Median time to progression was 57 days. There was a low incidence of toxicities. Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only. There were no changes in other plasma markers. This metronomic approach has negligible activity in advanced cancer albeit with minimal toxicity. Analysis of plasma markers indicates minimal effects on endothelium in this trial. These data for this particular regimen do not support basic tenets of metronomic chemotherapy, such as the ability to overcome resistant tumours by targeting the endothelium.


The importance of tissue segmentation for dose calculations for kilovoltage radiation therapy.
The aim of this work was to evaluate the effect of tissue segmentation on the accuracy of Monte Carlo (MC) dose calculations for kilovoltage radiation therapy, which are commonly used in preclinical radiotherapy studies and are also being revisited as a clinical treatment modality. The feasibility of tissue segmentation routinely done on the basis of differences in tissue mass densities was studied and a new segmentation scheme based on differences in effective atomic numbers was developed. MC dose calculations in a cylindrical mouse phantom with small cylindrical inhomogeneities consisting of 34 ICRU-44 tissues were performed using the EGSnrc/BEAMnrc and DOSXYZnrc codes. The dose to tissue was calculated for five different kilovoltage beams currently used in small animal radiotherapy: a microCT 120 kV beam, two 225 kV beams filtered with either 4 mm of Al or 0.5 mm of Cu, a heavily filtered 320 kV beam, and a 192Ir beam. The mean doses to the 34 ICRU-44 tissues as a function of tissue mass density and effective atomic number and beam energy were studied. A treatment plan for an orthotopic lung tumor model was created, and the dose distribution was calculated for three tissue segmentation schemes using 4, 8, and 39 tissue bins to assess the significance of the simulation results for kilovoltage radiotherapy. In our model, incorrect assignment of adipose tissue to muscle caused dose calculation differences of 27%, 13%, and 7% for the 120 kV beam and the 225 kV beams filtered with 4 mm Al and 0.5 mm Cu, respectively. For the heavily filtered 320 kV beam and a 192Ir source, potential dose calculation differences due to tissue mis-assignment were below 4%. There was no clear relationship between the dose to tissue and its mass density for x-ray beams generated by tube potentials equal or less than 225 kV. A second order polynomial fit approximated well the absorbed dose to tissue as a function of effective atomic number for these beams. In the mouse study, the 120 kV beam dose to bone was overestimated by 100% and underestimated by 10% for the 4 and 8-tissue segmentation schemes compared to the 39-tissue segmentation scheme, respectively. Dose to adipose tissue was overestimated by 30% and underestimated by 10%, respectively. In general, organ at risk (OAR) doses were overestimated in the 4-tissue and the 8-tissue segmentation schemes compared to the 39-tissue segmentation. Tissue segmentation was shown to be a key parameter for dose calculations with kilovoltage beams used in small animal radiotherapy when an x-ray tube with a potential < or = 225 kV is used as a source. A new tissue segmentation scheme with 39 tissues based on effective number differences derived from mass density differences has been implemented.


An Integrated Model of Patient and Staff Satisfaction Using Queuing Theory.
This paper investigates the connection between patient satisfaction, waiting time, staff satisfaction, and service time. It uses a variety of models to enable improvement against experiential and operational health service goals. Patient satisfaction levels are estimated using a model based on waiting (waiting times). Staff satisfaction levels are estimated using a model based on the time spent with patients (service time). An integrated model of patient and staff satisfaction, the effective satisfaction level model, is then proposed (using queuing theory). This links patient satisfaction, waiting time, staff satisfaction, and service time, connecting two important concepts, namely, experience and efficiency in care delivery and leading to a more holistic approach in designing and managing health services. The proposed model will enable healthcare systems analysts to objectively and directly relate elements of service quality to capacity planning. Moreover, as an instrument used jointly by healthcare commissioners and providers, it affords the prospect of better resource allocation.


Gene expression comparison of flow diversion and coiling in an experimental aneurysm model.
Mechanisms of both healing and complications, including spontaneous aneurysm rupture, remain unclear following flow diverter treatment. The aim of this study was to compare gene expression of various key molecules involved in the healing of aneurysms, between aneurysms treated with microcoils and flow diverters. Saccular aneurysms were created in rabbits. Aneurysms were treated with coils (n=6) or flow diverters (n=6). Aneurysms were harvested at 4 weeks following treatment and used for gene expression and zymography experiments. Genes with a fold change of 1.2 or more were considered upregulated whereas those with a fold change of 0.8 or less were considered downregulated. All coil embolized aneurysms were completely occluded at follow-up. Two aneurysms were occluded and the remaining four samples were incompletely occluded in the flow diverter treated group. The following genes were expressed at lower levels in the flow diverter group compared with the coiled aneurysm group: proteinases (matrix metalloproteinases 2 and 9), cellular markers (endothelial nitric oxide synthase and smooth muscle actin), and structural proteins (collagens and fibronectin). Genes related to inflammation (tumor necrosis factor α and monocyte chemoattractant protein 1) were upregulated in flow diverter treated aneurysms compared with coil embolized aneurysms. Notably, the enzymatic activity of active matrix metalloproteinase 9 was high in aneurysms treated with flow diverters. Our findings may provide improved understanding of rupture risk and healing following aneurysm treatment and inform development of therapies aimed at lowering rupture risk and accelerating healing.


First Report of the Golden Potato Cyst Nematode, Globodera rostochiensis, in Bosnia and Herzegovina.
The golden potato cyst nematode, Globodera rostochiensis (Wollenweber, 1923) Behrens, 1975, is the most problematic pest of potato (Solanum tuberosum L. subsp. tuberosum) worldwide and it is recognized as an A1 plant health quarantine species. In Bosnia and Herzegovina, there have been no surveys for the presence of potato cyst nematodes (PCN) in ware potato lands, although they have been documented in the nearby countries of Serbia and Croatia (3). To determine the presence and distribution of PCN and to prevent further spread or increase of PCN populations, a survey in ware potato land was undertaken in 2008, 2009, and 2010. Soil samples consisting of 100 cores of 4 to 5 ml of soil were taken in a grid pattern throughout the plots. Samples of approximately 500 g were processed in the laboratory. The samples were air dried and cysts were extracted using a Spears's flotation method (4) from a 100-ml subsample. Species identification was based on morphometrical characters (2) and real-time PCR where the ribosomal internal transcribed spacer (ITS5, PITSr3) region was amplified and detected by the Sequence Dection Software v1.3 (Applied Biosystems, Carlsbad, CA) (1). In 2008, soil sampling was conducted in five locations and PCN were not detected in any of 10 soil samples taken. In June 2009, 17 soil samples were collected from seven locations. Two viable cysts of G. rostochiensis were detected in one soil sample from Tihaljina (Zaside; E 6447659.560, N 4797392.101, altitude 130 m). A total of 110 soil samples were collected from 90 locations in May and June 2010. Five viable cysts of G. rostochiensis were detected in one soil sample taken from Čapljina (Opličići - Turajlovina; E 6485169, N 4775964, altitude 222 m). On the basis of the survey results, G. rostochiensis is not widely spread but the cysts are detectable, indicating that the infestation is relatively recent and that there is a threat of further spread of this quarantine species. Consequently, producers need to grow resistant potato cultivars and implement additional control measures to keep the nematode populations below damaging levels. References: (1) J. Bacic et al. Russ. J. Nematol. 16:1, 61, 2008. (2) C. C. Fleming and T. O. Powers. Potato Cyst Nematodes: Biology, Distribution and Control. R. J. Marks and B. B. Brodie, eds.CAB International, Wallingford, 1998. (3) D. Grubišic et al. J. Pest Sci. 80:21, 2007. (4) J. F. Spears. Agr. Handb. No. 353. U.S. Dep. Agric., 1968.


An Organic Approach to Health Professions Education and Health Equity: Learning In and With Underserved Communities.
Since the Flexner Report in 1910, medical education has taken a primarily technical approach to preparing students for science-based medical practice. Adequately addressing the complex problems leading to population health disparities and achieving health equity is not possible through a technical approach to education alone. Inspired by Frank Lloyd Wright, who brought organic architecture to the world of building design, the author suggests an organic approach to health equity through education and training of a workforce in and with rural and underserved urban communities. An organic approach can claim many roots-in philosophy, education for social justice, the pedagogy of place, relationship-centered care, patient-centered and community-oriented primary care, community engagement, and complexity science. Though framed in theory, such an approach has a growing evidence base in professional education generally and has practical implications for the location of education and training, emergent curriculum design, and a community-responsive approach to program implementation.


Persistent infection of rhesus monkeys with 'Helicobacter macacae' and its isolation from an animal with intestinal adenocarcinoma.
A novel helicobacter, 'Helicobacter macacae', was previously isolated from a colony of rhesus and cynomolgus monkeys in which diarrhoea from chronic idiopathic colitis was enzootic. A survey performed in a second colony of rhesus monkeys without a history of chronic diarrhoea determined that 57 % were faecal-culture positive for Helicobacter species. Ten years after the survey, one of the animals from which 'H. macacae' had been isolated, a 23-year-old, intact male rhesus monkey (Macaca mulatta), presented with partial inappetence and progressive weight loss. Subsequent evaluation of the monkey revealed anaemia, hypoproteinaemia, hypoalbuminaemia and a palpable abdominal mass. Contrast radiography suggested partial intestinal obstruction. The animal was euthanized and a diagnosis was made of intestinal adenocarcinoma of the ileocaecocolic junction with metastasis to regional lymph nodes and liver. Microaerobic culture of caecal tissue yielded a helicobacter organism identified as 'H. macacae' by 16S rRNA gene sequencing - the same species of bacteria isolated 10 years previously. The liver, small intestine and colon were also positive by PCR for Helicobacter species. Intestinal adenocarcinoma is the most common malignancy of aged macaques. Faeces or caecal tissue from five out of five monkeys that remained from the original cohort and that were colonized with 'H. macacae' in the initial survey were positive for the organism. The apparent persistence of 'H. macacae' in these animals, the isolation of the bacterium from animals with colitis and the recognition of the importance of inflammation in carcinogenesis raise the possibility of an aetiological role in the genesis of intestinal adenocarcinoma in aged rhesus monkeys.


Developmental changes in Na+ conductances in rat neocortical neurons: appearance of a slowly inactivating component.
1. Na+ conductances have been characterized in rat neocortical neurons from the sensorimotor area. Neurons were obtained by acute dissociation from animals at developmental stages from embryonic day 16 (E16) to postnatal day 50 (P50) to quantify any developmental changes in the kinetic properties of the Na+ conductance. 2. Neurons were divided into two classes, based on morphology, to determine whether there are any cell-type specific differences in Na+ conductances that contribute to the different action potential morphologies seen in current-clamp recordings in vitro. 3. Upon isolation, neurons were voltage clamped using the whole-cell variation of the patch-clamp technology. Both cell types, pyramidal and nonpyramidal, demonstrate large increases in Na+ current density during this developmental period (E16-P50). Normalized conductances were near 10 pS/micron2 in neurons from embryonic animals, and increased 6- to 10-fold during the first 2 wk postnatal. The final conductance reached in pyramidal neurons was higher than in non-pyramidal neurons. 4. We found no differences between the two cell types, pyramidal and nonpyramidal, in the voltage dependence of activation, inactivation kinetics, voltage dependence of steady-state inactivation, and recovery from inactivation. 5. The time course of Na+ current in immature neurons were fit with classical Hodgkin-Huxley kinetics. However, in more mature neurons the kinetics of inactivation became more complicated such that two decay components were required to obtain good fit. The slowly decaying component had a time course 5 to 10 times slower than the fast component. 6. Several procedures were used to reduce the magnitude of Na+ conductance in mature neurons to ensure graded, voltage-dependent inward currents. These included reduced extracellular [Na+], submaximal tetrodotoxin concentrations, and reduced holding potential. Under each of these conditions we were able to verify the observation that Na+ current inactivation occurs with two exponentials. 7. Single-channel Na+ currents were obtained from cell-attached patches. The membrane density of active Na+ channels increases with development, and ensemble averages from mature neurons demonstrated two inactivation processes. The slow inactivation process was accounted for by long-latency single-channel openings of the same amplitude as the short-latency openings. 8. We conclude that there are no kinetic differences in the Na+ channels between cell types. Differences in action potentials are then not explained by differences in Na+ current kinetics, but might be partially explained by the different densities.(ABSTRACT TRUNCATED AT 400 WORDS)


Sampling from Determinantal Point Processes for Scalable Manifold Learning.
High computational costs of manifold learning prohibit its application for large datasets. A common strategy to overcome this problem is to perform dimensionality reduction on selected landmarks and to successively embed the entire dataset with the Nyström method. The two main challenges that arise are: (i) the landmarks selected in non-Euclidean geometries must result in a low reconstruction error, (ii) the graph constructed from sparsely sampled landmarks must approximate the manifold well. We propose to sample the landmarks from determinantal distributions on non-Euclidean spaces. Since current determinantal sampling algorithms have the same complexity as those for manifold learning, we present an efficient approximation with linear complexity. Further, we recover the local geometry after the sparsification by assigning each landmark a local covariance matrix, estimated from the original point set. The resulting neighborhood selection .based on the Bhattacharyya distance improves the embedding of sparsely sampled manifolds. Our experiments show a significant performance improvement compared to state-of-the-art landmark selection techniques on synthetic and medical data.


Materiovigilance of unidirectional barbed and poliglecaprone 25 nonbarbed sutures used for intraoral incision closure: An open-label prospective study.
The adverse events of sutures used for the closure of surgical incisions influence clinical outcomes. Literature on the safety profile of the application of unidirectional barbed sutures in oral and maxillofacial surgery is scarce. Hence, focused materiovigilance was done to monitor and compare the adverse events of unidirectional barbed and poliglecaprone 25 nonbarbed sutures for intraoral incision closure. In a prospective randomized comparative study, 64 patients requiring intraoral incision closure were randomized to receive either unidirectional barbed or poliglecaprone 25 nonbarbed sutures. Postoperatively, patients were monitored for any adverse events for 15 days. Causality association of adverse events with sutures was done using the European Commission directives on safety reporting of medical devices. Adverse events observed with unidirectional barbed suture were suture extrusion (n = 7; 21.875%) and suture discomfort (n = 3; 9.375%). While subjects who received poliglecaprone 25 suture experienced suture discomfort (n = 6; 18.75%) and knot unraveling (n = 2; 6.25%). The number of adverse events in both groups was statistically comparable (P = 0.78). Causality assessment of adverse events was probable for suture extrusion and discomfort with nonbarbed and barbed sutures, while it was possible for knot unraveling for nonbarbed sutures. Both types of study sutures were associated with minor severity adverse events when used for the closure of intraoral surgical incisions. Suture extrusion had a probable causal association with barbed suture. Knot unraveling was possibly associated with the nonbarbed suture. Both types of suture materials were equally safe in oral and maxillofacial intraoral surgical incision closure.


Identification of human cytochrome P450 isoforms involved in the stereoselective metabolism of mianserin enantiomers.
To identify cytochrome P450 (CYP) isoform(s) involved in the major metabolic pathways of mianserin (MS) enantiomers in humans, we examined the metabolites formed from S-(+)- and R-(-)-MS using human liver microsomes and eight recombinant human CYP isoforms (i.e., CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4). The mean V(max)/K(m) values of the 8-hydroxylation and N-oxidation were greater for S-(+)- than for R-(-)-MS, whereas that of the N-demethylation gave the opposite observation. When relationships were evaluated in microsomes from 10 human livers between the metabolism of substrates toward the respective CYP isoforms and stereoselective metabolism of MS at a low (5 microM) and at a high (200 microM) MS concentration, significant correlations existed in: 2-hydroxylation of desipramine vs. 8-hydroxylation of S-(+)-MS (r = 0.94, P < .01), O-deethylation of phenacetin vs. N-demethylation of S-(+)-MS (r = 0.85, P < .01) and R-(-)-MS (r = 0.69, P < .05) or N-oxidation of S-(+)-MS (r = 0.94, P < .01) at the low concentration; and 6 beta-hydroxylation of testosterone vs. three metabolic reactions of both MS enantiomers at the high concentration (r = 0.68-0.93, P < .05-.01). Quinidine inhibited the 8-hydroxylation of both enantiomers by < 40% of the respective control values. Furafylline and alpha-naphthoflavone showed a potent inhibitory effect on the N-demethylation and N-oxidation of S-(+)-MS (by up to < 50% of the respective control activities). In addition, troleandomycin inhibited the N-demethylation and N-oxidation of R-(-)-MS by < 50% of the respective control activities. Among the recombinant human CYP isoforms, CYP2D6, 2B6, 3A4 and 1A2 catalyzed the 8-hydroxylation, and CYP1A2 and 3A4 were involved exclusively in the N-oxidation, whereas CYP2B6, 2C19, 1A2, 3A4 and 2D6 showed a catalytic activity for the N-demethylation, for either or both of MS enantiomers. Taken together, the 8-hydroxylation for both MS enantiomers is mediated mainly via CYP2D6, whereas the N-demethylation for both the enantiomers and N-oxidation for S-(+)-MS are catalyzed mainly via CYP1A2. The two in vitro experiments suggested that CYP3A is involved to a certain extent in each of the stereoselective MS metabolic pathways.


High-energy mode-locked fiber lasers using multiple transmission filters and a genetic algorithm.
We theoretically demonstrate that in a laser cavity mode-locked by nonlinear polarization rotation (NPR) using sets of waveplates and passive polarizer, the energy performance can be significantly increased by incorporating multiple NPR filters. The NPR filters are engineered so as to mitigate the multi-pulsing instability in the laser cavity which is responsible for limiting the single pulse per round trip energy in a myriad of mode-locked cavities. Engineering of the NPR filters for performance is accomplished by implementing a genetic algorithm that is capable of systematically identifying viable and optimal NPR settings in a vast parameter space. Our study shows that five NPR filters can increase the cavity energy by approximately a factor of five, with additional NPRs contributing little or no enhancements beyond this. With the advent and demonstration of electronic controls for waveplates and polarizers, the analysis suggests a general design and engineering principle that can potentially close the order of magnitude energy gap between fiber based mode-locked lasers and their solid state counterparts.


Formulations of Rancid and Winey-Vinegary Artificial Olfactory Reference Materials (AORMs) for Virgin Olive Oil Sensory Evaluation.
Sensory assessment of virgin olive oil ("panel test") is the only sensory method included in international regulations of edible oils and its application is compulsory. Even if its application has been a success in quality control, improving the quality of virgin olive oils over the last 30 years, at present, there is no reference material (RM), in the strict sense of the term, to be used as a validated standard for sensory defects of virgin olive oil with which tasters can be trained. Usually, real samples of virgin olive oils assessed by many panels for the International Olive Council (IOC) ring tests are used as materials of reference in panel training and control. The latter are highly representative of the main perceived defects, but availability is limited, samples are not homogeneous year after year, and other secondary defects can be present. Thus, in order to provide solutions, this work describes an analytical procedure for implementing olfactory formulations that emulate rancid and winey-vinegary defects found in virgin olive oils with the aim of providing reproducible RMs that can be prepared on demand. A strategy for designing RMs for aroma is presented and the optimization process to obtain the best formulation is described. Under the criteria of representativeness, verified with the advice of the IOC, aroma persistence, and simplicity in formulation, two RMs for winey-vinegary and rancid were obtained by diluting acetic acid and ethanol (winey-vinegary defect) and hexanal (rancid defect) together with other compounds that are used to modify aroma and avoid non-natural sensory notes.


Chemical orientation to food by the crayfish Orconectes rusticus: influence of hydrodynamics.
Many different organisms orient to chemicals in a variety of habitats. Each of these habitats has a unique hydrodynamic environment that is dependent upon the structure of that habitat. Differences in the hydrodynamics (i.e. turbulence) of an environment will be reflected in the fine-scale structure of chemical signals. To determine what role dispersion dynamics play in influencing orientation behaviour, we studied crayfish searching for food sources in different artificial streams. Streams differed only in substrate composition (sand or cobbles), and the hydrodynamics associated with different substrates were quantified. A detailed analysis of orientation paths showed that crayfish could orient to food sources in streams with either substrate. The most parsimonious explanation is that animals are using information contained in the spatial and temporal distribution of chemicals in the flow to make directional decisions. Crayfish located the source more quickly, spent more time moving, and walked faster while orienting in streams having a cobble substrate compared with those having a sand substrate. These differences between substrates were not seen in control streams. These results show that the hydrodynamics associated with chemical signal structure can greatly influence the temporal properties of orientation to food sources. For crayfish, differences in the turbulent structure of flow may actually increase orientation efficiency by decreasing search time. On a broader scale, these results show that it is important to quantify orientation behaviour in a number of hydrodynamically different environments. Copyright 1999 The Association for the Study of Animal Behaviour.


Tongue and taste organ development in the ontogeny of direct-developing salamander Plethodon cinereus (Lissamphibia: Plethodontidae).
The latest research on direct developing caecilian and anuran species indicate presence of only one generation of taste organs during their ontogeny. This is distinct from indirect developing batrachians studied thus far, which possess taste buds in larvae and anatomically distinct taste discs in metamorphs. This study is a description of the tongue and taste organ morphology and development in direct developing salamander Plethodon cinereus (Plethodontidae) using histology and electron microscopy techniques. The results reveal two distinct stages tongue morphology (primary and secondary), similar to metamorphic urodeles, although only one stage of taste organ morphology. Taste disc sensory zones emerge on the surface of the oropharyngeal epithelium by the end of embryonic development, which coincides with maturation of the soft tongue. Taste organs occur in the epithelium of the tongue pad (where they are situated on the dermal papillae), the palate and the inner surface of the mandible and the maxilla. Plethodon cinereus embryos only possess taste disc type taste organs. Similar to the direct developing anuran Eleutherodactylus coqui (Eleutherodactylidae), these salamanders do not recapitulate larval taste bud morphology as an embryo. The lack of taste bud formation is probably a broadly distributed feature characteristic to direct developing batrachians. J. Morphol. 277:906-915, 2016. © 2016 Wiley Periodicals, Inc.