Pulsatile release from a flat self-oscillating chitosan macrogel.
Coupling oscillatory chemical reactions to smart materials which can respond to external stimuli is considered an answer to the long-standing issue of pulsatile drug delivery. Although a number of coupled architectures exist, there are no systems reporting pH-controlled pulsed drug release based on chemical oscillators. In this paper, we report for the first time a proof-of-concept self-oscillatory chitosan macrogel, employing the palladium-catalysed oxidative carbonylation reaction as the driving force of its oscillations. The reported hydrogel is composed of highly biocompatible components and a novel imine-functionalised chitosan-palladium catalyst with zero leaching rates. This macrogel was shown to rhythmically release not only the products of the reaction, but also fluorescein, which is used as an FDA-approved model drug. The step-wise release pattern corresponded to the step-wise dynamics of pH decrease in methanol:water, while in pure methanol, the changes in pH had an oscillatory mode, accompanied by mirrored oscillations in fluorescein concentration. This proof-of-concept system significantly expands the horizons of pulsatile delivery materials for future research.


Responsive aqueous foams stabilised by silica nanoparticles hydrophobised in situ with a switchable surfactant.
In the recent past there has been a growing interest in switchable surfactants and stimuli-responsive surface-active particles, since both have surface activity which is either switchable or controllable and they can be recovered and re-used afterwards. Among various triggers the CO2/N2 trigger is particularly environmentally benign. In this paper a facile protocol to obtain switchable surface-active silica nanoparticles using a CO2/N2 trigger is proposed and their utilization in producing responsive aqueous foams with the same trigger is examined. Using a switchable surfactant, N'-dodecyl-N,N-dimethylacetamidinium bicarbonate, which can be switched between a cationic surfactant and a surface-inactive neutral form by bubbling with CO2 and N2 respectively, bare silica nanoparticles can be hydrophobised in situ to become surface-active nanoparticles and the switch of the surfactant can thus be transferred to the particles. Thus responsive particle-stabilised aqueous foams can be prepared. Compared with foams stabilised by specially synthesized switchable or stimuli-responsive particles, the method reported here is much easier, whereas compared with those stabilised by switchable or stimuli-responsive surfactants the method here requires a relatively low concentration.


Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1.
Aurora-A is a centrosomal serine-threonine kinase that regulates mitosis. Over-expression of Aurora-A has been found in a wide range of tumors and has been implicated in oncogenic transformation. However, how Aurora-A over-expression contributes to promotion of carcinogenesis remains elusive. Immunohistochemical analysis of breast tumors revealed that over-expressed Aurora-A is not restricted to the centrosomes but is also found in the cytoplasm. This over-expressed Aurora-A appeared to be phosphorylated on Thr288, which is known to be required for its enzymatic activation. In analogy to Aurora-A's role in oocyte maturation and the early embryonic cell cycle, here we investigated whether ectopically over-expressed Aurora-A can similarly stimulate polyadenylation of mRNA in human somatic cultured cells by interacting with a human ortholog of cytoplasmic polyadenylation element binding protein, h-CPEB. In vitro experiments revealed that Aurora-A binds directly to, and phosphorylates, h-CPEB. We found that polyadenylation of mRNA tails of cyclin B1 and Cdk1 was synergistically stimulated when Aurora-A and h-CPEB were over-expressed, and they were further promoted in the presence of an Aurora-A activator Ajuba. Our results suggest a function of ectopically over-expressed Aurora-A that might be relevant for carcinogenesis.


Insertion reactions of hydridonitrosyltetrakis(trimethylphosphine) tungsten(0).
[W(H)(NO)(PMe3)4] (1) was prepared by the reaction of [W(Cl)(NO)(PMe3)4] with NaBH4 in the presence of PMe3. The insertion of acetophenone, benzophenone and acetone into the W-H bond of 1 afforded the corresponding alkoxide complexes [W(NO)(PMe3)4(OCHR1R2)](R1 = R2 = Me (2); R1 = Me, R2 = Ph (3); R1 = R2 = Ph (4)), which were however thermally unstable. Insertion of CO2 into the W-H bond of yields the formato-O complex trans-W(NO)(OCHO)(PMe3)4 (5). Reaction of trans-W(NO)(H)(PMe3)4 with CO led to the formation of mer-W(CO)(NO)(H)(PMe3)3 (6) and not the formyl complex W(NO)(CHO)(PMe3)4. Insertion of Fe(CO)(5), Re2(CO)10 and Mn2(CO)10 into trans-W(NO)(H)(PMe3)4 resulted in the formation of trans-W(NO)(PMe3)4(mu-OCH)Fe(CO)4 (7), trans-W(NO)(PMe3)4(mu-OCH)Re2(CO)9 (8) and trans-W(NO)(PMe3)4(mu-OCH)Mn2(CO)9 (9). For Re2(CO)10, an equilibrium was established and the thermodynamic data of the equilibrium reaction have been determined by a variable-temperature NMR experiments (K(298K)= 104 L mol(-1), DeltaH=-37 kJ mol(-1), DeltaS =-86 J K(-1) mol(-1)). Both compounds 7 and 8 were separated in analytically pure form. Complex 9 decomposed slowly into some yet unidentified compounds at room temperature. Insertion of imines into the W-H bond of 1 was also additionally studied. For the reactions of the imines PhCH=NPh, Ph(Me)C=NPh, C6H5CH=NCH2C6H5, and (C6H5)2C=NH with only decomposition products were observed. However, the insertion of C10H7N=CHC6H5 into the W-H bond of led to loss of one PMe3 ligand and at the same time a strong agostic interaction (C17-H...W), which was followed by an oxidative addition of the C-H bond to the tungsten center giving the complex [W(NO)(H)(PMe3)3(C10H6NCH2Ph)] (10). The structures of compounds 1, 4, 7, 8 and 10 were studied by single-crystal X-ray diffraction.


Vasopressin Effect on Operation Time and Frequency of Electrocauterization during Laparoscopic Stripping of Ovarian Endometriomas: A Randomized Controlled Clinical Trial.
The purpose of this study was to assess the vasopressin effect on operation time and the need for electrocauterization frequency and ovarian reserve during laparoscopic stripping of ovarian endometriomas. This was a randomized prospective clinical trial, in which twenty patients between 18-35 years with unilateral endometriomas were randomly divided in two groups of cases and controls. Laparoscopic cystectomy was performed by hydrodissection and stripping method in both groups with diluted vasopressin injected in cases, in comparison to only saline injection in controls. Ovarian hemostasis was achieved by bipolar electrocoagulation. The operation time and frequency of electrocoagulation were compared between two groups. The ovarian reserve was determined by ultrasound examination and laboratory assessment one month before and two months after surgery in two groups. Non parametric data was analyzed by Mann-Whitney test. The p-value less than 0.05 was considered statistically significant. The operation time was less in cases than control group, but the difference was not statistically significant (p=0.065). The frequency of electrocoagulation for hemostasis was less in cases than controls but this difference was not statistically significant (p=0.132). The antral follicle count decreased in both groups two months later, while no significant difference was found between two groups. This study shows that diluted vasopressin decreases operation time and electrocauterization frequency during laparoscopic stripping of ovarian endometriomas; however, the difference between case and control group is not statistically significant.


Does Supplementation with Royal Jelly Improve Oxidative Stress and Insulin Resistance in Type 2 Diabetic Patients?
Animal studies have shown antioxidant effects of Royal Jelly (RJ) and its effect on insulin resistance as the most common complication of Type 2 diabetes. This study was conducted to determine the effect of RJ intake on serum total antioxidant capacity, Malondialdehyde and insulin resistance in T2DM. In this randomized controlled trial, forty-six type 2 diabetic patients, aged 25-65 years, with BMI of 20-30 kg/m(2), and HbA1c of 6-8% were included. The patients were randomly assigned to receive 1000 mg of RJ supplement or placebo, 3 times daily for 8 weeks. HOMA-IR, anthropometric measurements, fasting blood glucose, serum insulin, total antioxidant capacity and malondialdehyde level were measured. In comparison with placebo, HOMA-IR decreased (P=0.015) while serum total antioxidant capacity increased significantly in RJ group (P=0.016). No significant difference was detected for serum insulin and MDA in two groups. RJ intake may have favorable effects on serum TAC and HOMA-IR in diabetic patients.


Dynamical simulations of classical stochastic systems using matrix product states.
We adapt the time-evolving block decimation (TEBD) algorithm, originally devised to simulate the dynamics of one-dimensional quantum systems, to simulate the time evolution of nonequilibrium stochastic systems. We describe this method in detail; a system's probability distribution is represented by a matrix product state (MPS) of finite dimension and then its time evolution is efficiently simulated by repeatedly updating and approximately refactorizing this representation. We examine the use of MPS as an approximation method, looking at parallels between the interpretations of applying it to quantum state vectors and probability distributions. In the context of stochastic systems we consider two types of factorization for use in the TEBD algorithm: non-negative matrix factorization (NMF), which ensures that the approximate probability distribution is manifestly non-negative, and the singular value decomposition (SVD). Comparing these factorizations, we find the accuracy of the SVD to be substantially greater than current NMF algorithms. We then apply TEBD to simulate the totally asymmetric simple exclusion process (TASEP) for systems of up to hundreds of lattice sites in size. Using exact analytic results for the TASEP steady state, we find that TEBD reproduces this state such that the error in calculating expectation values can be made negligible even when severely compressing the description of the system by restricting the dimension of the MPS to be very small. Out of the steady state we show for specific observables that expectation values converge as the dimension of the MPS is increased to a moderate size.


Brain abnormalities in neuromyelitis optica.
Neuromyelitis optica (NMO) is a severe demyelinating disease defined principally by its tendency to selectively affect optic nerves and the spinal cord causing recurrent attacks of blindness and paralysis. Contemporary diagnostic criteria require absence of clinical disease outside the optic nerve or spinal cord. We have, however, frequently encountered patients with a well-established diagnosis of NMO in whom either asymptomatic or symptomatic brain lesions develop suggesting that the diagnostic criteria for NMO should be revised. To describe the magnetic resonance image (MRI) brain findings in NMO. Observational, retrospective case series. Patients We ascertained patients through a clinical biospecimens database of individuals with definite or suspected NMO. We included patients who (1) satisfied the 1999 criteria of Wingerchuk et al for NMO except for the absolute criterion of lacking symptoms beyond the optic nerve and spinal cord and the supportive criterion of having a normal brain MRI at onset; (2) had MRI evidence of a spinal cord lesion extending 3 vertebral segments or more (the most specific nonserological feature to differentiate NMO from MS); and (3) were evaluated neurologically and by brain MRI at the Mayo Clinic. Magnetic resonance images were classified as normal or as abnormal with either nonspecific, multiple sclerosis-like or atypical abnormalities. We evaluated whether brain lesions were symptomatic and analyzed the neuropathologic features of a single brain biopsy specimen. Sixty patients (53 women [88%]) fulfilled these inclusion criteria. The mean +/- SD age at onset was 37.2 +/- 18.4 years and the mean +/- SD duration of follow-up was 6.0 +/- 5.6 years. Neuromyelitis optica-IgG was detected in 41 patients (68%). Brain MRI lesions were detected in 36 patients (60%). Most were nonspecific, but 6 patients (10%) had multiple sclerosis-like lesions, usually asymptomatic. Another 5 patients (8%), mostly children, had diencephalic, brainstem or cerebral lesions, atypical for multiple sclerosis. When present, symptoms of brain involvement were subtle, except in 1 patient who was comatose and had large cerebral lesions. Asymptomatic brain lesions are common in NMO, and symptomatic brain lesions do not exclude the diagnosis of NMO. These observations justify revision of diagnostic criteria for NMO to allow for brain involvement.


Microtubule-dependent movement of late endocytic vesicles in vitro: requirements for Dynein and Kinesin.
Our previous studies demonstrated that fluorescent early endocytic vesicles prepared from rat liver after injection of Texas red asialoorosomucoid contain asialoglycoprotein and its receptor and move and undergo fission along microtubules using kinesin I and KIFC2, with Rab4 regulating KIFC2 activity (J. Cell Sci. 116, 2749, 2003). In the current study, procedures to prepare fluorescent late endocytic vesicles were devised. In addition, flow cytometry was utilized to prepare highly purified fluorescent endocytic vesicles, permitting validation of microscopy-based experiments as well as direct biochemical analysis. These studies revealed that late vesicles bound to and moved along microtubules, but in contrast to early vesicles, did not undergo fission. As compared with early vesicles, late vesicles had reduced association with receptor, Rab4, and kinesin I but were highly associated with dynein, Rab7, dynactin, and KIF3A. Dynein and KIF3A antibodies inhibited late vesicle motility, whereas kinesin I and KIFC2 antibodies had no effect. Dynamitin antibodies prevented the association of late vesicles with microtubules. These results indicate that acquisition and exchange of specific motor and regulatory proteins characterizes and may regulate the transition of early to late endocytic vesicles. Flow cytometric purification should ultimately facilitate detailed proteomic analysis and mapping of endocytic vesicle-associated proteins.


Risk-benefit analysis of antidepressant drug treatment in the elderly.
Depression in the elderly is a significant health issue that has the potential to seriously affect physical and emotional well-being. Therefore, the treatment of geriatric depression is necessary. Antidepressant treatment in older depressed patients is efficacious, but differences in the effectiveness of different classes of antidepressants have not been demonstrated. However, differences in tolerability profile are most recognizable in the elderly. With ageing, a series of changes occur in the elderly that modify both the pharmacokinetics and pharmacodynamics of antidepressants and may influence the efficacy, tolerability and safety of treatment in the elderly. Comorbidities require the use of other drugs, which increases the possibility of drug-drug interactions. Given these aspects, individualized therapy for each elderly patient is needed to achieve acceptable risk-benefit ratio. Effective treatment of depression in the elderly, which may require combined pharmacological with psychosocial treatment, can decrease both morbidity and mortality; it also may lead to reduced demands on family members and on health-care and social services.


B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent stromal reaction that has been variably implicated in both tumor growth and tumor suppression. B-lymphocytes have been recently implicated in PDAC progression but their contribution to the characteristic stromal desmoplasia has never been assessed before. In the present work, we aimed to verify whether B-lymphocytes contribute to stromal cell activation in PDAC. CD19+ B-lymphocytes purified from peripheral blood of patients with PDAC were cultivated in the presence of human pancreatic fibroblasts and cancer-associated fibroblasts. Released pro-fibrotic soluble factors and collagen production were assessed by ELISA and Luminex assays. Quantitative RT-PCR was used to assess fibroblast activation in the presence of B cells. The expression of selected pro-fibrotic and inflammatory molecules was confirmed on PDAC tissue sections by multi-color immunofluorescence studies. We herein demonstrate that B-cells from PDAC patients (i) produce the pro-fibrotic molecule PDGF-B and stimulate collagen production by fibroblasts; (ii) express enzymes implicated in extracellular matrix remodeling including LOXL2; and (iii) produce the chemotactic factors CCL-4, CCL-5, and CCL-11. In addition we demonstrate that circulating plasmablasts are expanded in the peripheral blood of patients with PDAC, stimulate collagen production by fibroblasts, and infiltrate pancreatic lesions. Our results indicate that PDAC is characterized by perturbations of the B-cell compartment with expansion of B-lymphocyte subsets that directly contribute to the stromal reaction observed at disease site. These findings provide an additional rationale for modulating B-cell activity in patients with pancreatic cancer.


Accurate classification of MLH1/MSH2 missense variants with multivariate analysis of protein polymorphisms-mismatch repair (MAPP-MMR).
Lynch syndrome, also known as hereditary nonpolyposis colon cancer (HNPCC), is the most common known genetic syndrome for colorectal cancer (CRC). MLH1/MSH2 mutations underlie approximately 90% of Lynch syndrome families. A total of 24% of these mutations are missense. Interpreting missense variation is extremely challenging. We have therefore developed multivariate analysis of protein polymorphisms-mismatch repair (MAPP-MMR), a bioinformatic algorithm that effectively classifies MLH1/MSH2 deleterious and neutral missense variants. We compiled a large database (n>300) of MLH1/MSH2 missense variants with associated clinical and molecular characteristics. We divided this database into nonoverlapping training and validation sets and tested MAPP-MMR. MAPP-MMR significantly outperformed other missense variant classification algorithms (sensitivity, 94%; specificity, 96%; positive predictive value [PPV] 98%; negative predictive value [NPV], 89%), such as SIFT and PolyPhen. MAPP-MMR is an effective bioinformatic tool for missense variant interpretation that accurately distinguishes MLH1/MSH2 deleterious variants from neutral variants.


Macular hole following conventional repair of bullous retinal detachment using air injection (D-ACE procedure).
Sequential drainage of subretinal fluid (D), injection of air (A), cryotherapy (C), and application of local explants (E) (D-ACE) sequence was introduced in order to overcome the problems encountered in managing superior bullous detachments from multiple large equatorial breaks. The authors recently observed the occurrence of a full-thickness macular hole in one patient developing the day after he underwent a D-ACE procedure. A 61-year-old man presented a bullous retinal detachment in the right eye extending from the 9:30 to the 2 o'clock position, and posteriorly to the vascular arcades two retinal tears were noted, at the equator at 11 o'clock, and anterior to the equator at 12 o'clock. The patient underwent a D-ACE procedure. Subretinal fluid was drained above the lateral rectus muscle at the equator. One and a half milliliters of air were injected 3.5 mm from the limbus midway between the superior and the medial rectus insertions. Cryotherapy was applied to the retinal breaks. A 240 encircling band was used in conjunction with a 276 tyre segment at the level of the tears. One day after surgery, the retina was flat, but a full-thickness macular hole could be seen with a surrounding cuff of subretinal fluid. The mechanisms proposed to explain the occurrence of full-thickness macular holes after D-ACE may involve the concurrence of scleral elongation and vitreofoveal traction by means of previous partial posterior vitreous detachment with persistent posterior attachments at the fovea.


Gaussian process modelling of latent chemical species: applications to inferring transcription factor activities.
Inference of latent chemical species in biochemical interaction networks is a key problem in estimation of the structure and parameters of the genetic, metabolic and protein interaction networks that underpin all biological processes. We present a framework for Bayesian marginalization of these latent chemical species through Gaussian process priors. We demonstrate our general approach on three different biological examples of single input motifs, including both activation and repression of transcription. We focus in particular on the problem of inferring transcription factor activity when the concentration of active protein cannot easily be measured. We show how the uncertainty in the inferred transcription factor activity can be integrated out in order to derive a likelihood function that can be used for the estimation of regulatory model parameters. An advantage of our approach is that we avoid the use of a coarsegrained discretization of continuous time functions, which would lead to a large number of additional parameters to be estimated. We develop exact (for linear regulation) and approximate (for non-linear regulation) inference schemes, which are much more efficient than competing sampling-based schemes and therefore provide us with a practical toolkit for model-based inference. The software and data for recreating all the experiments in this paper is available in MATLAB from http://www.cs.man. ac.uk/~neill/gpsim.


Protease inhibitor expression in soybean roots exhibiting susceptible and resistant interactions with soybean cyst nematode.
Protease inhibitors play a role in regulating proteases during cellular development and in plant defense. We cloned and sequenced cDNA encoding six protease inhibitors expressed in soybean roots infected with soybean cyst nematode (SCN) and determined their expression patterns. Four of these protease inhibitors are novel and have not been reported previously. Using RT-PCR, we measured the relative transcript levels of each protease inhibitor in roots of the soybean cv. Peking inoculated with either SCN TN8 to examine the expression of protease inhibitors during the susceptible interaction or with SCN NL1-RHg representing the resistant interaction. Within 12 to 24 hours, mRNA transcripts encoding five of the six protease inhibitors were more highly elevated in soybean roots exhibiting the susceptible interaction than the resistant interaction. Transcripts encoding two protease inhibitors possessing Kunitz trypsin inhibitor domains were induced 37- and 27-fold in the susceptible interaction within 1 dpi, but were induced only 5- to 7-fold in roots displaying the resistant interaction. Our results indicate that soybean roots recognize differences between these two SCN populations before the nematodes initiate a feeding site, and accordingly the roots express transcripts encoding soybean protease inhibitors differentially. These transcripts were generally less abundant in roots exhibiting the resistant interaction.


Vascular endothelial growth factor and spinal cord injury pain.
Vascular endothelial growth factor (VEGF)-A mRNA was previously identified as one of the significantly upregulated transcripts in spinal cord injured tissue from adult rats that developed allodynia. To characterize the role of VEGF-A in the development of pain in spinal cord injury (SCI), we analyzed mechanical allodynia in SCI rats that were treated with either vehicle, VEGF-A isoform 165 (VEGF(165)), or neutralizing VEGF(165)-specific antibody. We have observed that exogenous administration of VEGF(165) increased both the number of SCI rats that develop persistent mechanical allodynia, and the level of hypersensitivity to mechanical stimuli. Our analysis identified excessive and aberrant growth of myelinated axons in dorsal horns and dorsal columns of chronically injured spinal cords as possible mechanisms for both SCI pain and VEGF(165)-induced amplification of SCI pain, suggesting that elevated endogenous VEGF(165) may have a role in the development of allodynia after SCI. However, the neutralizing VEGF(165) antibody showed no effect on allodynia or axonal sprouting after SCI. It is possible that another endogenous VEGF isoform activates the same signaling pathway as the exogenously-administered 165 isoform and contributes to SCI pain. Our transcriptional analysis revealed that endogenous VEGF(188) is likely to be the isoform involved in the development of allodynia after SCI. To the best of our knowledge, this is the first study to suggest a possible link between VEGF, nonspecific sprouting of myelinated axons, and mechanical allodynia following SCI.


Aseptic laboratory techniques: plating methods.
Microorganisms are present on all inanimate surfaces creating ubiquitous sources of possible contamination in the laboratory. Experimental success relies on the ability of a scientist to sterilize work surfaces and equipment as well as prevent contact of sterile instruments and solutions with non-sterile surfaces. Here we present the steps for several plating methods routinely used in the laboratory to isolate, propagate, or enumerate microorganisms such as bacteria and phage. All five methods incorporate aseptic technique, or procedures that maintain the sterility of experimental materials. Procedures described include (1) streak-plating bacterial cultures to isolate single colonies, (2) pour-plating and (3) spread-plating to enumerate viable bacterial colonies, (4) soft agar overlays to isolate phage and enumerate plaques, and (5) replica-plating to transfer cells from one plate to another in an identical spatial pattern. These procedures can be performed at the laboratory bench, provided they involve non-pathogenic strains of microorganisms (Biosafety Level 1, BSL-1). If working with BSL-2 organisms, then these manipulations must take place in a biosafety cabinet. Consult the most current edition of the Biosafety in Microbiological and Biomedical Laboratories (BMBL) as well as Material Safety Data Sheets (MSDS) for Infectious Substances to determine the biohazard classification as well as the safety precautions and containment facilities required for the microorganism in question. Bacterial strains and phage stocks can be obtained from research investigators, companies, and collections maintained by particular organizations such as the American Type Culture Collection (ATCC). It is recommended that non-pathogenic strains be used when learning the various plating methods. By following the procedures described in this protocol, students should be able to: Perform plating procedures without contaminating media. Isolate single bacterial colonies by the streak-plating method. Use pour-plating and spread-plating methods to determine the concentration of bacteria. Perform soft agar overlays when working with phage. Transfer bacterial cells from one plate to another using the replica-plating procedure. Given an experimental task, select the appropriate plating method.


Effectiveness of Adherence Therapy in Adults with Type 2 Diabetes: A Systematic Review.
Adherence therapy has been shown to be an effective adjunct treatment in long-term conditions including hypertension. The purpose of this study is to review and critically appraise evidence on the effectiveness of adherence therapy as an intervention in adults with type 2 diabetes. A systematic search of clinical trials published between 2005 and January 2020 in databases was undertaken in October 2018 and updated in August 2020. Inclusion criteria were any clinical trials where the population under investigation was adults with type 2 diabetes and the experimental intervention was adherence therapy. Version 2 of the Cochrane risk of bias was used to determine the quality of the included studies. No studies met our inclusion criteria. However, four studies that we excluded at full text screening tested some of the components (e.g., problem solving) of adherence therapy. As is recommended when reporting empty reviews, those studies were synthesized to determine if useful information can be extracted. That no trials of adherence therapy have been reported in type 2 diabetes establishes a potentially important gap in knowledge. This review was registered in PROSPERO (registration number: CRD42019115216) after the initial searches were completed.


Prevalence, motivations, and adverse effects of vaginal practices in Africa and Asia: findings from a multicountry household survey.
Women worldwide use various vaginal practices to clean or modify their vulva and vagina. Additional population-level information is needed on prevalence and motivations for these practices, characteristics of users, and their adverse effects. This was a household survey using multistage cluster sampling in Tete, Mozambique; KwaZulu-Natal, South Africa; Yogyakarta, Indonesia; and Chonburi, Thailand. In 2006-2007, vaginal practices and their motivations were examined using structured interviews with women 18-60 years of age (n=3610). Prevalence, frequency, and motivations varied markedly. Two thirds of women in Yogyakarta and Chonburi reported one or more practices. In Yogyakarta, nearly half ingest substances with vaginal effects, and in Chonburi, external washing and application predominate. In Tete, half reported three or four current practices, and a quarter reported five or more practices. Labial elongation was near universal, and 92% of those surveyed cleanse internally. Two third's in KwaZulu-Natal practiced internal cleansing. Insertion of traditional solid products was rare in Chonburi and Yogyakarta, but one tenth of women in KwaZulu-Natal and nearly two thirds of women in Tete do so. Multivariate analysis of the most common practice in each site showed these were more common among less educated women in Africa and young urban women in Asia. Explicit sexual motivations were frequent in KwaZulu-Natal and Tete, intended for pleasure and maintaining partner commitment. Practices in Chonburi and Yogyakarta were largely motivated by femininity and health. Genital irritation was common at African sites. Vaginal practices are not as rare, exotic, or benign as sometimes assumed. Limited evidence of their biomedical consequences remains a concern; further investigation of their safety and sexual health implications is warranted.


Extension of the interacting quantum atoms (IQA) approach to B3LYP level density functional theory (DFT).
An interaction between two atoms, bonded or non-bonded, consists of interatomic contributions: electrostatic energy, exchange energy and electronic correlation energy. Together with the intra-atomic energy of an atom, these contributions are the basic components of the Interacting Quantum Atom (IQA) energy decomposition scheme. Here, we investigate IQA's proper use in conjunction with an explicit implementation of the B3LYP functional. The recovery of the total molecular energy from the IQA components is emphasised, for the first time. A systematic study of three model systems of biological relevance, N-methylacetamide (NMA), the doubly capped tripeptide GlyGlyGly and an alloxan dimer, shows the stabilization effect of B3LYP on most of the interatomic exchange energies (V) compared to their Hartree-Fock values. Diagrams of exchange energies versus interatomic distance show the clustering of interactions, one cluster for each 1,n (n = 1 to 6 where the atoms are separated by n - 1 bonds). The positioning of some V values outside their expected cluster marks interesting interactions.


Socio-economic status, racial composition and the affordability of fresh fruits and vegetables in neighborhoods of a large rural region in Texas.
Little is known about how affordability of healthy food varies with community characteristics in rural settings. We examined how the cost of fresh fruit and vegetables varies with the economic and demographic characteristics in six rural counties of Texas. Ground-truthed data from the Brazos Valley Food Environment Project were used to identify all food stores in the rural region and the availability and lowest price of fresh whole fruit and vegetables in the food stores. Socioeconomic characteristics were extracted from the 2000 U.S. Census Summary Files 3 at the level of the census block group. We used an imputation strategy to calculate two types of price indices for both fresh fruit and fresh vegetables: a high variety and a basic index; and evaluated the relationship between neighborhood economic and demographic characteristics and affordability of fresh produce, using linear regression models. The mean cost of meeting the USDA recommendation of fruit consumption from a high variety basket of fruit types in our sample of stores was just over $27.50 per week. Relying on the three most common fruits lowered the weekly expense to under $17.25 per week, a reduction of 37.6%. The effect of moving from a high variety to a low variety basket was much less when considering vegetable consumption: a 4.3% decline from $29.23 to $27.97 per week. Univariate regression analysis revealed that the cost of fresh produce is not associated with the racial/ethnic composition of the local community. However, multivariate regression showed that holding median income constant, stores in neighborhoods with higher percentages of Black residents paid more for fresh fruits and vegetables. The proportion of Hispanic residents was not associated with cost in either the univariate or multivariate analysis. This study extends prior work by examining the affordability of fresh fruit and vegetables from food stores in a large rural area; and how access to an affordable supply of fresh fruit and vegetables differs by neighborhood inequalities. The approach and findings of this study are relevant and have important research and policy implications for understanding access and availability of affordable, healthy foods.


Fusion of the NUP98 gene with the LEDGF/p52 gene defines a recurrent acute myeloid leukemia translocation.
The NUP98 gene is involved in multiple rearrangements in haematological malignancy. The leukemic cells in an acute myeloid leukemia (AML) patient with a t(9;11)(p22;p15) were recently shown to have a fusion between the NUP98 gene and the LEDGF gene but it was not demonstrated that this fusion was recurrent in other leukaemia patients with the same translocation. We used RT-PCR to analyse the leukemic cells from an AML patient who presented with a cytogenetically identical translocation as the sole chromosomal abnormality. A NUP98-LEDGF fusion transcript was observed and confirmed by sequencing. The reciprocal transcript was also observed. The fusion transcript was not detectable during remission and recurred at relapse. The breakpoints in the NUP98 and LEDGF genes were different to those previously reported. The NUP98 breakpoint occurs in the intron between exons 8 and 9. It is the most 5' breakpoint reported in a translocation involving the NUP98 gene. All of the LEDGF gene is included in the fusion except for exon 1 which codes for the first 24 amino terminal amino acids. Our results show that fusion of the NUP98 and LEDGF genes is a new recurrent translocation in AML.


A supermassive black hole in an ultra-compact dwarf galaxy.
Ultra-compact dwarf galaxies are among the densest stellar systems in the Universe. These systems have masses of up to 2 × 10(8) solar masses, but half-light radii of just 3-50 parsecs. Dynamical mass estimates show that many such dwarfs are more massive than expected from their luminosity. It remains unclear whether these high dynamical mass estimates arise because of the presence of supermassive black holes or result from a non-standard stellar initial mass function that causes the average stellar mass to be higher than expected. Here we report adaptive optics kinematic data of the ultra-compact dwarf galaxy M60-UCD1 that show a central velocity dispersion peak exceeding 100 kilometres per second and modest rotation. Dynamical modelling of these data reveals the presence of a supermassive black hole with a mass of 2.1 × 10(7) solar masses. This is 15 per cent of the object's total mass. The high black hole mass and mass fraction suggest that M60-UCD1 is the stripped nucleus of a galaxy. Our analysis also shows that M60-UCD1's stellar mass is consistent with its luminosity, implying a large population of previously unrecognized supermassive black holes in other ultra-compact dwarf galaxies.


Implementing a podiatry prescribing mentoring program in a public health service: a cost-description study.
In the management of diabetes and high-risk patients, timely treatment with scheduled medicines is critical to prevent severe infections and reduce the risk of lower extremity amputation. However, in Australia, few podiatrists have attained endorsement to prescribe. The aims of this study were to identify the costs associated with developing and implementing a podiatry prescribing mentoring program; and to compare the cost of this program against potential healthcare savings produced. This was a cost-description analysis, involving the calculation of costs associated with the development and implementation of a mentoring program to train podiatrists to become endorsed prescribers. Costs were calculated using the Ingredients Method and examined from the perspective of a public health service provider, and the individual learner podiatrist. Breakeven analysis compared the cost of training a podiatry prescriber for endorsement against the potential benefit (savings) made by averting complications of an infected foot ulcer. A sensitivity analysis was conducted to allow for uncertainty in the results of an economic evaluation. Total start-up cost for the podiatry prescriber mentoring program was $13, 251. The total cost to train one learner podiatrist was $30, 087, distributed between the hospital $17, 046 and the individual learner $13, 041. In the setting studied, a podiatry prescriber must avert 0.40 major amputations arising from an infected foot ulcer through prescribing to recover the cost of training. If in-kind training costs are included, total cost increases to $50, 654, and the breakeven point shifts to 0.68 major amputations averted. The economic benefits (savings) created by an endorsed prescribing podiatrist over their career in a public health service are likely to outweigh the costs to train a podiatrist to attain endorsement. Further research is required to help understand the effectiveness of podiatry prescribing in reducing diabetic foot related complications and the potential economic impact of podiatry prescribers on this health condition.


[Health care networks].
The demographic and epidemiologic transition resulting from aging and the increase of life expectation means an increment related to chronic conditions. The healthcare systems contemporary crisis is characterized by the organization of the focus on fragmented systems turned to the acute conditions care, in spite of the chronic conditions prevalence, and by the hierarchical structure without communication flow among the different health care levels. Brazil health care situation profile is now presenting a triple burden of diseases, due to the concomitant presence of infectious diseases, external causes and chronic diseases. The solution is to restore the consistence between the triple burden of diseases on the health situation and the current system of healthcare practice, with the implantation of health care networks. The conclusion is that there are evidences in the international literature on health care networks that these networks may improve the clinical quality, the sanitation results and the user's satisfaction and the reduction of healthcare systems costs.


The role of Mac-1 (CD11b/CD18) in antigen-induced airway eosinophilia in mice.
Mac-1 (CD11b/CD18) is an important adhesion molecule involved in the migration of leukocytes, cell signaling, and subsequent secretory responses. Its precise role in eosinophil recruitment and activation in vivo is not entirely clear. We wished to directly examine the role of Mac-1 in eosinophil migration in a murine model of allergic pulmonary inflammation. Briefly, wild-type (C57Bl/6) and Mac-1-deficient/knockout (Mac-1 KO) mice were intraperitoneally sensitized with ovalbumin (OVA) and alum (AlOH) on Days 0 and 14, and intranasally challenged with OVA either once on Day 14 or five times on Days 14 and 25 through 28. Control animals were challenged with saline. Bronchial hyperresponsiveness was measured, bronchoalveolar lavage (BAL) fluid was collected, and lungs were harvested for histology 24 h after the last challenge. The data demonstrate that wild-type (WT) mice do not respond to one OVA challenge but do develop bronchial hyperreactivity and airway and tissue eosinophilia after five OVA challenges. Conversely, Mac-1 KO mice develop significant airway eosinophilia after one OVA challenge, and the degree of airway inflammation is comparable to that observed in allergic WT mice after five challenges. In Mac-1 KO mice, after five challenges, bronchial hyperreactivity and airway inflammation was significantly enhanced compared with their wild-type counterparts. Administration of an anti-Mac-1 antibody to WT mice, before each of five intranasal OVA challenges, significantly reduces the airway eosinophilia but has no effect on tissue eosinophilia or bronchial hyperresponsiveness. Intravenous injection of interleukin-5 induced a significant blood eosinophilia in both WT and Mac-1 KO mice. Intranasal eotaxin administration induced similar levels of eosinophil migration into the lung tissues and airways of both WT and Mac-1 KO mice. In conclusion, Mac-1-deficient mice develop enhanced eosinophilic inflammation in the lung in response to allergic antigen challenge.


External Match Workloads During the First Week of Australian Open Tennis Competition.
With a view to informing athlete preparation leading into tournament play, this study examined external hitting and movement workloads during the first week of the 2012-2016 Australian Open tournaments. Using Hawk-Eye, on-court movement and stroke data were captured for 39 players (21 women, 18 men) during the first 4 rounds of singles competition. Hitting and movement workloads were compared between sexes and rounds of competition. On average, men traversed approximately 4 km greater distance and hit 785 more shots than women hit across the first 4 rounds of the Australian Open. Women hit significantly more first serves, forehand returns, and backhand groundstrokes per game than men did. Total distance covered per game did not exhibit a significant sex effect, although men covered a significantly greater proportion of that distance at speeds greater than 3 m/s. Game-level hitting and movement workloads, and effective playing time, increased significantly between rounds 1 and 4 of the tournament in both sexes. When preparing athletes for competition, tennis practitioners should be aware that men may need to withstand aggregated hitting and movement (specifically, high-speed exertion) workloads that are 52% and up to 281% greater than women, respectively. Moreover, the evidence demonstrated that these workloads increased as players progressed deeper into the tournament. These novel insights can be used to improve the specificity of training prescription and physical-testing protocols in professional tennis.


Temporal and Geographic Variations in the Receipt of Colony-Stimulating Factors and Erythropoiesis-Stimulating Agents in a Large Retrospective Cohort of Older Women With Breast Cancer From 2000 to 2009.
The purpose of this study was to use the most recent national data for a large cohort of patients diagnosed with breast cancer to evaluate temporal trend of receiving hematopoietic growth factors from 2000 to 2009 and to examine significant factors associated with increasing trends and geographic variations. We identified 26,130 women aged 65-89 years who were diagnosed with breast cancer and received chemotherapy in 2000-2009 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Colony-stimulating factors (CSFs) were identified if there was a claim from the following procedure codes: filgrastim, pegfilgrastim, or sargramostim. Erythropoiesis-stimulating agents (ESAs) were identified if there was a claim from the following procedure codes: epoetin or darbepoetin. Overall, 51.7% of patients with breast cancer received CSFs, which increased from 21.7% in 2000 to 63.2% in 2009. The percentage of patients receiving pegfilgrastim increased from 2.7% in 2000 to 19.5% in 2003 and then continuously to 49.7% in 2009. The overall percentage of patients receiving ESAs was 39.3%, which increased from 26.4% in 2000 to 60.8% in 2006, and then decreased significantly from 40.7% in 2007 to 12.9% in 2009. The receipt of both CSFs and ESAs differed significantly across different geographic areas. The receipt of CSFs continued to increase from 2000 to 2009, and pegfilgrastim started to replace filgrastim since 2003. The receipt of ESAs increased until 2006 and then declined substantially due to the black box warning. There were substantial geographic variations in the use of these hematopoietic growth factors.


Resolving relationships in an exceedingly young Neotropical orchid lineage using Genotyping-by-sequencing data.
Poor morphological and molecular differentiation in recently diversified lineages is a widespread phenomenon in plants. Phylogenetic relationships within such species complexes are often difficult to resolve because of the low variability in traditional molecular loci. Furthermore, biological phenomena responsible for topological incongruence such as Incomplete Lineage Sorting (ILS) and hybridisation complicate the resolution of phylogenetic relationships among closely related taxa. In this study, we employ a Genotyping-by-sequencing (GBS) approach to disentangle evolutionary relationships within a species complex belonging to the Neotropical orchid genus Cycnoches. This complex includes seven taxa distributed through Central America and the Colombian Chocó, and is nested within a clade estimated to have first diversified in the early Quaternary. Previous phylogenies inferred from few loci failed to provide support for internal relationships within the complex. Our Neighbour-net and coalescent-based analyses inferred from ca. 13,000 GBS loci obtained from 31 individuals belonging to six of the seven traditionally accepted Cycnoches taxa provided a robust phylogeny for this group. The genus Cycnoches includes three main clades that are further supported by morphological traits and geographic distributions. Similarly, a topology reconstructed through maximum likelihood (ML) inference of concatenated GBS loci produced results that are comparable with those reconstructed through coalescence and network-based methods. Our comparative phylogenetic informativeness analyses suggest that the low support evident in the ML phylogeny might be attributed to the abundance of uninformative GBS loci, which can account for up to 50% of the total number of loci recovered. The phylogenomic framework provided here, as well as morphological evidence and geographical patterns, suggest that the six entities previously thought to be different species or subspecies might actually represent only three distinct segregates. We further discuss the limited phylogenetic informativeness found in our GBS approach and its utility to disentangle relationships within recent and rapidly evolving species complexes. Our study is the first to demonstrate the utility of GBS data to reconstruct relationships within young (~2 Ma) Neotropical plant clades, opening new avenues for studies of species complexes that populate the species-rich orchid family.


Multi-channel 100-Gbit/s DQPSK data exchange using bidirectional degenerate four-wave mixing.
We propose a simple approach to performing simultaneous multi-channel data exchange using bidirectional degenerate four-wave mixing (FWM) in a single highly nonlinear fiber (HNLF) assisted by optical filtering. Data exchange between two-channel 100-Gbit/s return-to-zero differential quadrature phase-shift keying (RZ-DQPSK) signals with a variable channel spacing is implemented with a power penalty of less than 4.2 dB at a bit-error rate (BER) of 10(-9). Moreover, simultaneous ITU-grid-compatible four-channel 100-Gbit/s RZ-DQPSK data exchange is demonstrated with a power penalty of less than 4.7 dB at a BER of 10(-9).


Time course of bone screw fixation following a local delivery of Zoledronate in a rat femoral model - a micro-finite element analysis.
A good fixation of osteosynthesis implants is crucial for a successful bone healing but often difficult to achieve in osteoporotic patients. One possible solution to this issue is the local delivery of bisphosphonates in direct proximity to the implants, A critical aspect of this method, that has not yet been well investigated, is the time course of the implant fixation following the drug release. Usual destructive mechanical tests require large numbers of animals to produce meaningful results. Therefore, a micro-finite element (microFE) approach was chosen to analyze implant fixation. In vivo micro computed tomography (microCT) scans were obtained, first weekly and later bi-weekly, after implantation of polymeric screws in the femoral condyles of ovariectomized rats. In one half of the animals, Zoledronate was released from a hydrogel matrix directly in the peri-implant bone stock, the other animals were implanted only with screws as control. The time course of the implant fixation was investigated with linear elastic microFE models that were created based on in vivo microCT scans. The numerical models were validated against experimental pullout-tests measurements in an additional cadaver study. The microFE analysis revealed a significant increase in force at yield of the Zoledronate treated group compared to the control group. The force of the treated group was 28% higher after 17 days of screw implantation, 42% higher after 31 days. The significant difference persisted until the end of the in vivo study at day 58 (p<0.01). The early onset and prolonged duration of the implant anchorage improvement that was found in this study indicates the great potential of Zoledronate-loaded hydrogel for an enhancement of osteosynthesis implant fixation in impaired bone.


The alpha subunit cytoplasmic domain regulates the assembly and adhesiveness of integrin lymphocyte function-associated antigen-1.
The integrin LFA-1 mediates activation-dependent leukocyte adhesion. The beta subunit cytoplasmic domain has been demonstrated previously to modulate the adhesiveness of LFA-1. To investigate whether the alpha subunit cytoplasmic domain is also involved in the regulation of LFA-1-adhesive function, we stably expressed cytoplasmic domain truncated forms of the alpha subunit in a Jurkat mutant (Jurkat-beta2.7) deficient in the endogenous LFA-1 alpha subunit and in K562 cells. Clones expressing similar levels of cell surface LFA-1 were tested for their ability to bind to immobilized ICAM-1. Truncation of the alpha subunit cytoplasmic domain before, but not after, the conserved GFFKR sequence motif resulted in constitutive ICAM-1 binding of both Jurkat-beta2.7 and K562 transfectants. However, truncation after the GFFKR motif reduced sensitivity to stimulation by PMA or stimulatory Abs. Internal deletion of the GFFKR motif, or point mutations of the Gly (G), the two Phe (F), or the Arg (R) in the GFFKR motif to Ala (A) rendered LFA-1 constitutively active. Mutation of the Lys (K) did not affect LFA-1 adhesion to ICAM-1. These findings indicate that the GFFKR motif maintains the low adhesive state of LFA-1, possibly by restraining the receptor conformation. We further demonstrate that the alpha subunit cytoplasmic domain and the conserved GFFKR motif are also required for efficient formation of LFA-1 alphabeta heterodimers.


Treatment patterns and adherence among patients with chronic hepatitis C virus in a US managed care population.
The purpose of this study was to document real-world treatment patterns, medication adherence, and the impact of adherence on disease-specific and all-cause health-care costs among chronic hepatitis C virus (HCV) patients in a US managed care population. Commercial insurance claims data between January 1, 2002 and December 31, 2006 from the Ingenix Impact (formerly Integrated Health Care Information Services) database were retrospectively analyzed. Chronic HCV patients with one or more prescriptions for an HCV-specific treatment within 6 months before or at any time after their first observed diagnosis of chronic HCV were selected. Prescribing patterns, treatment cost, and duration of treatment were assessed over the entire therapy period. Medication adherence rates and the relationship between adherence and health-care costs were assessed over the 24-week period after treatment initiation. The results were stratified by key clinical characteristics such as genotype, sustained virologic attainment, and disease severity. Results showed that peginterferon and ribavirin combination regimens were the most common treatments for chronic HCV. The patients underwent treatment for approximately 30-32 weeks on average, and treatment costs were over $20,000 per patient. Adherence to medication was suboptimal, especially among patients with severe disease. Adherent patients had higher pharmacy costs but significantly lower total costs when pharmacy was excluded. New and improved treatments that promote better adherence and impose a lower cost burden on patients and payers are needed.


Promethazine and Oral Midazolam Preanesthetic Children Medication.
Several kinds of drugs have been investigated in preschool children as a preanesthetic sedation after various routes of administration for surgeries. This study aims to compare the efficacy of promethazine and oral midazolam for premedication in children aged 3 to 9 years who were scheduled for surgeries. This is a double-blind randomized controlled study conducted on 93 patients between the age of 3 and 9 years at Loresten University of Medical Sciences Teaching Hospital, Khoramabad, Iran. The subjects were grouped into P (promethazine), M (midazolam), and C (control). About 0.3 mg/kg of oral promethazine was administered to patients in group P, 0.5 mg/kg of oral midazolam was administered to patients in group M, and 3 mL of normal saline as placebo was administered to patients in group C. Patient satisfaction, sedation and emotional score, systolic blood pressure (SBP), diastolic blood pressure, respiratory rate (RR), and heart rate (HR) were recorded. There was no statistically significant difference among the 3 groups. However, the period after medication, it was observed that SBP, diastolic blood pressure, RR, and HR in group C were statistically significantly higher than those in groups M and P. These 2 groups are similar in terms of SBP, RR, and HR. The emotional scores were comparable for the 2 groups. It was between 3.97 ± 0.6 to 1.7 ± 0.5 in group M and from 3.45 ± 1.17 to 2.745 ± 0.997 in group P in a Kruskal-Wallis test. This study shows that both test groups reduce stress at the time of anesthetic induction and separation from their parents with similar effect. Both of the anesthetics are easily administered without the necessity of an additional equipment. A shorter period to maximal sedation for midazolam is an advantage, thus, making the drug helpful, mostly in the outpatient setting.


Academic Failure in Secondary School: The Inter-Related Role of Health Problems and Educational Context.
This study explores whether the interplay of health problems and school environment predicts academic failure, an individual event with consequences for the life course, as well as for society at large. This exploration proceeds in three steps: 1) we examine whether physical and mental health problems are an academic risk factor during secondary school; 2) we investigate the academic mechanisms underlying this risk status; and 3) we explore whether this risk status varies by school context. A series of logistic regressions reveals that self-rated health and emotional distress are both associated with greater likelihood of failing one or more classes in the next year and that absenteeism, trouble with homework, and student-teacher bonding account for much of these associations. Associations of physical and mental health problems with academic failure vary only slightly across schools, however. We discuss the implications of these findings for both research and policy and argue that the examination of overlap among different domains of adolescent functioning can advance the sociological understanding of health, education, and social problems in general.


Cardiac neural crest is dispensable for outflow tract septation in Xenopus.
In vertebrate embryos, cardiac precursor cells of the primary heart field are specified in the lateral mesoderm. These cells converge at the ventral midline to form the linear heart tube, and give rise to the atria and the left ventricle. The right ventricle and the outflow tract are derived from an adjacent population of precursors known as the second heart field. In addition, the cardiac neural crest contributes cells to the septum of the outflow tract to separate the systemic and the pulmonary circulations. The amphibian heart has a single ventricle and an outflow tract with an incomplete spiral septum; however, it is unknown whether the cardiac neural crest is also involved in outflow tract septation, as in amniotes. Using a combination of tissue transplantations and molecular analyses in Xenopus we show that the amphibian outflow tract is derived from a second heart field equivalent to that described in birds and mammals. However, in contrast to what we see in amniotes, it is the second heart field and not the cardiac neural crest that forms the septum of the amphibian outflow tract. In Xenopus, cardiac neural crest cells remain confined to the aortic sac and arch arteries and never populate the outflow tract cushions. This significant difference suggests that cardiac neural crest cell migration into the cardiac cushions is an amniote-specific characteristic, presumably acquired to increase the mass of the outflow tract septum with the evolutionary need for a fully divided circulation.


Fusion in diffusion MRI for improved fibre orientation estimation: An application to the 3T and 7T data of the Human Connectome Project.
Determining the acquisition parameters in diffusion magnetic resonance imaging (dMRI) is governed by a series of trade-offs. Images of lower resolution have less spatial specificity but higher signal to noise ratio (SNR). At the same time higher angular contrast, important for resolving complex fibre patterns, also yields lower SNR. Considering these trade-offs, the Human Connectome Project (HCP) acquires high quality dMRI data for the same subjects at different field strengths (3T and 7T), which are publically released. Due to differences in the signal behavior and in the underlying scanner hardware, the HCP 3T and 7T data have complementary features in k- and q-space. The 3T dMRI has higher angular contrast and resolution, while the 7T dMRI has higher spatial resolution. Given the availability of these datasets, we explore the idea of fusing them together with the aim of combining their benefits. We extend a previously proposed data-fusion framework and apply it to integrate both datasets from the same subject into a single joint analysis. We use a generative model for performing parametric spherical deconvolution and estimate fibre orientations by simultaneously using data acquired under different protocols. We illustrate unique features from each dataset and how they are retained after fusion. We further show that this allows us to complement benefits and improve brain connectivity analysis compared to analyzing each of the datasets individually.


Specific DNA alterations associated with the environmental induction of heritable changes in flax.
Several flax varieties have been shown to undergo environmentally induced heritable changes resulting in stable lines termed genotrophs. The most notable of these is the variety Stormont Cirrus, also termed "plastic" or Pl. A number of morphological, biochemical and genetic differences are associated with environmental induction of heritable changes in flax. We have studied 5S rDNA alterations as a model system for understanding environmental induction of heritable changes in flax. This paper reports the isolation of a flax 5S rRNA gene variant which identifies genotroph specific restriction fragment length polymorphisms (RFLPs) in flax. Restriction fragment patterns for several enzymes were observed in both large and small genotrophs which consistently differed from the progenitor, Stormont Cirrus. Identical RFLP profiles for all restriction endonucleases tested were observed in four small genotrophs produced from separate environmental induction experiments. Comparison between Stormont Cirrus and these small genotrophs showed at least six differing bands in addition to several high molecular weight polymorphisms. Genetic data indicate that the polymorphisms were all produced from a repetitive 5S rRNA gene cluster at a single chromosomal locus. Similar, but not identical, polymorphisms are also detected in other flax varieties and Linum species suggesting that the induced variation is related to that which occurs naturally. The results are evidence that a specific set of DNA alterations occur in association with the induction of heritable changes in flax. This is the first genetic marker which is altered to an identical state in one type of genotroph. The results are discussed with respect to mechanisms for environmentally induced heritable change in plants.


Developments in Burkitt's lymphoma: novel cooperations in oncogenic MYC signaling.
Burkitt's lymphoma (BL) is an aggressive disorder associated with extremely high rates of cell proliferation tempered by high levels of apoptosis. Despite the high levels of cell death, the net effect is one of rapid tumor growth. The tumor arises within the germinal centers of secondary lymphoid tissues and is identifiable by translocation of the c-MYC gene into the immunoglobulin gene loci, resulting in deregulation of the proto-oncogene. Many of the major players involved in determining the development of BL have been characterized in human BL cell lines or in mouse models of MYC-driven lymphomagenesis. Both systems have been useful so far in characterizing the role of tumor suppressor genes (for example, p53), prosurvival signaling pathways, and members of the B-cell lymphoma-2 family of apoptosis regulators in determining the fate of c-MYC overexpressing B-cells, and ultimately in regulating lymphoma development. Signaling through phosphoinositide (PI)3-kinase stands out as being critical for BL cell survival. Recurrent mutations in ID3 or TCF3 (E2A) that promote signaling through PI3-kinase have recently been identified in human BL samples, and new therapeutic strategies based on coordinately targeting both the prosurvival factor, B-cell lymphoma-XL, and the PI3-kinase/AKT/mammalian target of rapamycin (mTOR) signaling pathway to synergistically induced BL apoptosis have been proposed. Now, engineering both constitutive c-MYC expression and PI3-kinase activity, specifically in murine B-cells undergoing the germinal center reaction, has revealed that there is synergistic cooperation between c-MYC and PI3-kinase during BL development. The resulting tumors phenocopy the human malignancy, and acquire tertiary mutations also present in human tumors. This model may, therefore, prove useful in further studies to identify functionally relevant mutational events necessary for BL pathogenesis. This review discusses these cooperating interactions, the possible influence of BL tumor-associated viruses, and highlights potential new opportunities for therapeutic intervention.


An Integrated Assessment Approach to Address Artisanal and Small-Scale Gold Mining in Ghana.
Artisanal and small-scale gold mining (ASGM) is growing in many regions of the world including Ghana. The problems in these communities are complex and multi-faceted. To help increase understanding of such problems, and to enable consensus-building and effective translation of scientific findings to stakeholders, help inform policies, and ultimately improve decision making, we utilized an Integrated Assessment approach to study artisanal and small-scale gold mining activities in Ghana. Though Integrated Assessments have been used in the fields of environmental science and sustainable development, their use in addressing specific matter in public health, and in particular, environmental and occupational health is quite limited despite their many benefits. The aim of the current paper was to describe specific activities undertaken and how they were organized, and the outputs and outcomes of our activity. In brief, three disciplinary workgroups (Natural Sciences, Human Health, Social Sciences and Economics) were formed, with 26 researchers from a range of Ghanaian institutions plus international experts. The workgroups conducted activities in order to address the following question: What are the causes, consequences and correctives of small-scale gold mining in Ghana? More specifically: What alternatives are available in resource-limited settings in Ghana that allow for gold-mining to occur in a manner that maintains ecological health and human health without hindering near- and long-term economic prosperity? Several response options were identified and evaluated, and are currently being disseminated to various stakeholders within Ghana and internationally.


Stochastic simulation of the spatio-temporal dynamics of reaction-diffusion systems: the case for the bicoid gradient.
Reaction-diffusion systems are mathematical models that describe how the concentrations of substances distributed in space change under the influence of local chemical reactions, and diffusion which causes the substances to spread out in space. The classical representation of a reaction-diffusion system is given by semi-linear parabolic partial differential equations, whose solution predicts how diffusion causes the concentration field to change with time. This change is proportional to the diffusion coefficient. If the solute moves in a homogeneous system in thermal equilibrium, the diffusion coefficients are constants that do not depend on the local concentration of solvent and solute. However, in nonhomogeneous and structured media the assumption of constant intracellular diffusion coefficient is not necessarily valid, and, consequently, the diffusion coefficient is a function of the local concentration of solvent and solutes. In this paper we propose a stochastic model of reaction-diffusion systems, in which the diffusion coefficients are function of the local concentration, viscosity and frictional forces. We then describe the software tool Redi (REaction-DIffusion simulator) which we have developed in order to implement this model into a Gillespie-like stochastic simulation algorithm. Finally, we show the ability of our model implemented in the Redi tool to reproduce the observed gradient of the bicoid protein in the Drosophila Melanogaster embryo. With Redi, we were able to simulate with an accuracy of 1% the experimental spatio-temporal dynamics of the bicoid protein, as recorded in time-lapse experiments obtained by direct measurements of transgenic bicoidenhanced green fluorescent protein.


Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer.
Thyroid cancers are infiltrated with tumor-associated macrophages (TAMs), yet their role in cancer progression is not known. The objectives of this study were to characterize the density of TAMs in well-differentiated (WDTC), poorly differentiated (PDTC), and anaplastic thyroid cancers (ATC) and to correlate TAM density with clinicopathologic parameters. Immunohistochemistry was performed on tissue microarray sections from WDTC (n=33), PDTC (n=37), and ATC (n=20) using macrophage-specific markers. Electronic medical records were used to gather clinical and pathologic data. Follow-up information of PDTC patients was available for 0-12 years. In total, 9 out of 33 WDTC (27%), 20 out of 37 PDTC (54%), and 19 out of 20 ATC (95%) had an increased density of CD68(+) TAMs (> or = 10 per 0.28 mm(2); WDTC versus PDTC, P=0.03; WDTC versus ATC, P<0.0001; PDTC versus ATC, P<0.002). Increased TAMs in PDTC was associated with capsular invasion (P=0.034), extrathyroidal extension (P=0.009), and decreased cancer-related survival (P=0.009) compared with PDTC with a low density of TAMs. In conclusion, the density of TAMs is increased in advanced thyroid cancers. The presence of a high density of TAMs in PDTC correlates with invasion and decreased cancer-related survival. These results suggest that TAMs may facilitate tumor progression. As novel therapies directed against thyroid tumor cell-specific targets are being tested, the potential role of TAMs as potential modulators of the thyroid cancer behavior will need to be considered.


Postoperative 30-day mortality in patients undergoing surgery for colorectal cancer: development of a prognostic model using administrative claims data.
To develop a prognostic model to predict 30-day mortality following colorectal cancer (CRC) surgery using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data and to assess whether race/ethnicity, neighborhood, and hospital characteristics influence model performance. We included patients aged 66 years and older from the linked 2000-2005 SEER-Medicare database. Outcome included 30-day mortality, both in-hospital and following discharge. Potential prognostic factors included tumor, treatment, sociodemographic, hospital, and neighborhood characteristics (census-tract-poverty rate). We performed a multilevel logistic regression analysis to account for nesting of CRC patients within hospitals. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) for discrimination and the Hosmer-Lemeshow goodness-of-fit test for calibration. In a model that included all prognostic factors, important predictors of 30-day mortality included age at diagnosis, cancer stage, and mode of presentation. Race/ethnicity, census-tract-poverty rate, and hospital characteristics were independently associated with 30-day mortality, but they did not influence model performance. Our SEER-Medicare model achieved moderate discrimination (AUC = 0.76), despite suboptimal calibration. We developed a prognostic model that included tumor, treatment, sociodemographic, hospital, and neighborhood predictors. Race/ethnicity, neighborhood, and hospital characteristics did not improve model performance compared with previously developed models.


PKR stimulates NF-kappaB irrespective of its kinase function by interacting with the IkappaB kinase complex.
The interferon (IFN)-induced double-stranded RNA-activated protein kinase PKR mediates inhibition of protein synthesis through phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) and is also involved in the induction of the IFN gene through the activation of the transcription factor NF-kappaB. NF-kappaB is retained in the cytoplasm through binding to its inhibitor IkappaBalpha. The critical step in NF-kappaB activation is the phosphorylation of IkappaBalpha by the IkappaB kinase (IKK) complex. This activity releases NF-kappaB from IkappaBalpha and allows its translocation to the nucleus. Here, we have studied the ability of PKR to activate NF-kappaB in a reporter assay and have shown for the first time that two catalytically inactive PKR mutants, PKR/KR296 and a deletion mutant (PKR/Del42) which lacks the potential eIF2alpha-binding domain, can also activate NF-kappaB. This result indicated that NF-kappaB activation by PKR does not require its kinase activity and that it is independent of the PKR-eIF2alpha relationship. Transfection of either wild-type PKR or catalytically inactive PKR in PKR(0/0) mouse embryo fibroblasts resulted in the activation of the IKK complex. By using a glutathione S-transferase pull-down assay, we showed that PKR interacts with the IKKbeta subunit of the IKK complex. This interaction apparently does not require the integrity of the IKK complex, as it was found to occur with extracts from cells deficient in the NF-kappaB essential modulator, one of the components of the IKK complex. Therefore, our results reveal a novel pathway by which PKR can modulate the NF-kappaB signaling pathway without using its kinase activity.


The ALS Health Profile Study: quality of life of amyotrophic lateral sclerosis patients and carers in Europe.
The measurement of functioning and well-being from the perspective of the patient has in recent years become central to the assessment of health and the evaluation of treatment regimes. The past decade has seen an enormous growth in the application of measures designed to assess quality of life in a vast array of medical specialties. However, the use of such measures in neurology has been relatively limited, and this has certainly been the case in amyotrophic lateral sclerosis (ALS). The European ALS Health Profile Study is a longitudinal survey of patients diagnosed with ALS or other motor neurone diseases in which patients are asked to complete questionnaires concerning their subjective health status. Data from clinical assessments are also collected. It is intended that the information collected will provide more systematic and detailed evidence of the impact of the disease from the perspective of the patient. This contribution documents results from baseline assessment obtained from data supplied by clinicians, carers and patients themselves. Three outcome measures are assessed in this paper: the SF-36, a generic measure of well being and functioning, the ALS Functional Rating Scale and the Carer Strain Index. The evidence presented here suggests that these measures provide a meaningful and valid picture of the impact of the disease. The data indicate that ALS has substantial adverse effects both upon the functioning and well being of patients and carers, as well as an association between the emotional health status of patients and carers, and between the physical health status of patients and carers.


Identity and pharmacognosy of Ruta graveolens Linn.
Ruta graveolens L., is a odoriferous herb belonging to the family Rutaceae. It is the source of Rue or Rue oil, called as Sadab or Satab in Hindi. It is distributed throughout the world and cultivated as a medicinal and ornamental herb. The ancient Greeks and Romans, held the plant in high esteem. It is used in Ayurveda, Homoeopathy and Unani. Phytochemical constituents and pharmacological properties were studied in depth. In 14 species of genus Ruta, R. graveolens and R. chalepensis are available in India and also cultivated in gardens. Taxonomical characters to identify the Indian plants are very clear with fringed and or non-fringed petals. However, references to it are confused in the traditional literature. Due to sharing of regional language name, its identity is confused with Euphorbia dracunculoides. Morphological and anatomical characters were described. Pharmacognostic studies with microscopic characters were also published. Upon reviewing the anatomical characters and pharmacognostic characters one finds that it is highly confused and conflicting. The characters described are opposite of each other and authenticity of the market sample of R. graveolens cannot be guaranteed and able to be differentiated from R. chalepensis. Present work is to describe the pharmacognostic characters of R. graveolens to differentiate it from R. chalepensis. It is concluded that morphologically, R. graveolens can be identified with its non-fringed petals and blunted apices of fruit lobes. Whereas, in R. chalepensis petals are fringed or ciliated and apices of the fruit lobes are sharp and projected. Microscopically, in stem of R. graveolens pericyclic fibers have wide lumen. Whereas, in R. chalepensis, it is narrow. The published pharmacognosy reports do not pertain to authentic plant or some of the characteristic features like glandular trichomes are not observed in our samples.


Nitroso Diels-Alder (NDA) reaction as an efficient tool for the functionalization of diene-containing natural products.
This review describes the use of nitroso Diels-Alder reactions for the functionalization of complex diene-containing natural products in order to generate libraries of compounds with potential biological activity. The application of this methodology to the structural modification of a series of natural products (thebaine, steroidal dienes, rapamycin, leucomycin, colchicine, isocolchicine and piperine) is discussed using relevant examples from the literature from 1973 onwards. The biological activity of the resulting compounds is also discussed. Additional comments are provided that evaluate the methodology as a useful tool in organic, bioorganic and medicinal chemistry.


Humoral and cellular immunity in secondary infection due to murine Chlamydia trachomatis.
A murine model of pneumonia due to the mouse pneumonitis agent (MoPn [murine Chlamydia trachomatis]) in mice deficient in CD4+ T-cell function (major histocompatibility complex [MHC] class II function [class II-/-], CD8+ T-cell function (beta2-microglobulin deficient, MHC class I deficient [Beta2m-/-]), B-cell function (C57BL/10J-Igh(tm1Cgn) [Igh-/-]), and gamma interferon (IFN-gamma) (C57BL/6-Ifg(tm1) [Ifg-/-]) or interleukin-4 (C57BL/6J(tm1Cgn29) [IL4-/-]) production was employed to determine if each of these mechanisms was critical to resistance against reinfection by C. trachomatis or if alternate compensatory mechanisms existed in their absence which could potentially be exploited in vaccine development. Resistance to reinfection with MoPn was heavily dependent on CD4+ T cells. CD4 T-cell-deficient MHC class II-/- mice were very susceptible to reinfection with MoPn, showing the critical importance of this cell to resistance. These mice lacked antibody production but did produce IFN-gamma, apparently by mechanisms involving NK and CD8+ T cells. Neutralization of IFN-gamma in these mice led to a borderline increase in susceptibility, showing a possible role (albeit small) of this cytokine in this setting. Tumor necrosis factor alpha (TNF-alpha) was also present at increased levels in these mice. Igh-/- B-cell-deficient mice which produce no antibody to MoPn were only modestly more susceptible to reinfection than immunized B-cell-intact controls, showing that antibody, including lung immunoglobulin A, is not an absolute requirement for relatively successful host defense in this setting. Levels of lung IFN-gamma and TNF-alpha were elevated in Igh-/- mice compared to those in controls. IL-4-/- mice (deficient in Th2 function) could develop normal resistance to reinfection with MoPn. Conversely, normal mice rendered partially IFN-gamma deficient by antibody depletion were somewhat impaired in their ability to develop acquired immunity to MoPn, again indicating a role for this cytokine in host defense against rechallenge. Of most importance, however, congenitally IFN-gamma-deficient Ifg-/- mice (which have elevated levels of other cytokines, including TNF-alpha and granulocyte-macrophage colony-stimulating factor) are paradoxically more resistant to MoPn rechallenge than controls, showing that IFN-gamma is not an absolute requirement for acquired resistance and implying the presence of very effective compensatory host defense mechanism(s). In vivo depletion of TNF-alpha significantly increased MoPn levels in the lungs in these mice. Thus, resistance to reinfection in this model is flexible and multifactorial and is heavily dependent on CD4+ T cells, with a probable role for IFN-gamma and TNF-alpha and a possible modest role for Th1-dependent antibody. Since IFN-gamma was dispensable in host defense, the highly effective mechanism or mechanisms which can compensate for its absence (which include TNF-alpha) deserve further study.


Documenting the diet in ancient human populations through stable isotope analysis of hair.
Fundamental to the understanding of human history is the ability to make interpretations based on artefacts and other remains which are used to gather information about an ancient population. Sequestered in the organic matrices of these remains can be information, for example, concerning incidence of disease, genetic defects and diet. Stable isotopic compositions, especially those made on isolates of collagen from bones, have been used to help suggest principal dietary components. A significant problem in the use of collagen is its long-term stability, and the possibility of isotopic alteration during early diagenesis, or through contaminating condensation reactions. In this study, we suggest that a commonly overlooked material, human hair, may represent an ideal material to be used in addressing human diets of ancient civilizations. Through the analysis of the amino-acid composition of modern hair, as well as samples that were subjected to radiation (thus simulating ageing of the hair) and hair from humans that is up to 5200 years old, we have observed little in the way of chemical change. The principal amino acids observed in all of these samples are essentially identical in relative abundances and content. Dominating the compositions are serine, glutamic acid, threonine, glycine and leucine, respectively accounting for approximately 15%, 17%, 10%, 8% and 8% of the total hydrolysable amino acids. Even minor components (for example, alanine, valine, isoleucine) show similar constancy between the samples of different ages. This constancy clearly indicates minimal alteration of the amino-acid composition of the hair. Further, it would indicate that hair is well preserved and is amenable to isotopic analysis as a tool for distinguishing sources of nutrition. Based on this observation, we have isotopically characterized modern individuals for whom the diet has been documented. Both stable nitrogen and carbon isotope compositions were assessed, and together provide an indication of trophic status, and principal type (C3 or C4) of vegetation consumed. True vegans have nitrogen isotope compositions of about 7/1000 whereas humans consuming larger amounts of meat, eggs, or milk are more enriched in the heavy nitrogen isotope. We have also analysed large cross-sections of modern humans from North America and Europe to provide an indication of the variability seen in a population (the supermarket diet). There is a wide diversity in both carbon and nitrogen isotope values based at least partially on the levels of seafood, corn-fed beef and grains in the diets. Following analysis of the ancient hair, we have observed similar trends in certain ancient populations. For example, the Coptics of Egypt (1000 BP) and Chinchorro of Chile (5000-800 BP) have diets of similar diversity to those observed in the modern group but were isotopically influenced by local nutritional sources. In other ancient hair (Egyptian Late Middle Kingdom mummies, ca. 4000 BP), we have observed a much more uniform isotopic signature, indicating a more constant diet. We have also recognized a primary vegetarian component in the diet of the Neolithic Ice Man of the Oetztaler Alps (5200 BP). In certain cases, it appears that sulphur isotopes may help to further constrain dietary interpretations, owing to the good preservation and sulphur content of hair. It appears that analysis of the often-overlooked hair in archaeological sites may represent a significant new approach for understanding ancient human communities.


How Involved are Non-VA Chaplains in Supporting Veterans?
In terms of supporting veteran populations, little is known of the experiences of chaplains professionally active outside of Department of Veterans Affairs (VA) healthcare settings. The present study looks to examine how involved non-VA chaplains are in supporting veterans as well as their familiarity with the VA. An online survey was distributed in a convenience sample of chaplains, of which n = 39 met the inclusion criterion for this study (i.e., no past or present VA affiliation). The results find that most of the non-VA chaplains encounter veteran service users either on a weekly or monthly basis. Though familiar with VA services, non-VA chaplains were not sure of their veteran service users' VA enrollment status nor did they feel able to adequately advise their veteran service users on VA enrollment. The results suggest that non-VA chaplains actively support veteran populations. Opportunities for enhancing chaplaincy services and VA outreach programs are discussed.


Beneficial effects of viscous dietary fiber from Konjac-mannan in subjects with the insulin resistance syndrome: results of a controlled metabolic trial.
Dietary fiber has recently received recognition for reducing the risk of developing diabetes and heart disease. The implication is that it may have therapeutic benefit in prediabetic metabolic conditions. To test this hypothesis, we investigated the effect of supplementing a high-carbohydrate diet with fiber from Konjac-mannan (KJM) on metabolic control in subjects with the insulin resistance syndrome. We screened 278 free-living subjects between the ages of 45 and 65 years from the Canadian-Maltese Diabetes Study. A total of 11 (age 55+/-4 years, BMI 28+/-1.5 kg/m2) were recruited who satisfied the inclusion criteria: impaired glucose tolerance, reduced HDL cholesterol, elevated serum triglycerides, and moderate hypertension. After an 8-week baseline, they were randomly assigned to take either KJM fiber-enriched test biscuits (0.5 g of glucomannan per 100 kcal of dietary intake or 8-13 g/day) or wheat bran fiber (WB) control biscuits for two 3-week treatment periods separated by a 2-week washout. The diets were isoenergetic, metabolically controlled, and conformed to National Cholesterol Education Program Step 2 guidelines. Serum lipids, glycemic control, and blood pressure were the outcome measures. Decreases in serum cholesterol (total, 12.4+/-3.1%, P<0.004; LDL, 22+/-3.9%, P<0.002; total/HDL ratio, 15.2+/-3.4%, P<0.003; and LDL/HDL ratio, 22.2+/-4.1%, P< 0.002), apolipoprotein (apo) B (15.1+/-4.3%, P<0.0004), apo B/A-1 ratio (13.1+/-3.4%, P< 0.0003), and serum fructosamine (5.2+/-1.4%, P<0.002) were observed during KJM treatment compared with WB-control. Fasting blood glucose, insulin, triglycerides, HDL cholesterol, and body weight remained unchanged. A diet rich in high-viscosity KJM improves glycemic control and lipid profile, suggesting a therapeutic potential in the treatment of the insulin resistance syndrome.


Predictive Factors for Successful High Myopia Treatment Using High-Frequency Laser-In-Situ Keratomileusis.
To evaluate the predictive factors of LASIK procedure for high myopia with or without astigmatism using a combination of high-frequency femtosecond-assisted LASIK followed by an excimer laser. This study was a retrospective interventional case series study to evaluate myopic eyes undergoing high platform LASIK with FEMTO LDV Z2 intervention, followed by WaveLight®EX500 excimer laser machine. Subjects were divided into 2 groups: high myopia (SE of -6.01 to -9.00 D) and very high myopia (SE of -9.01 D or higher). Myopic eyes (Spherical Equivalent/SE) less than -13 D were included in this study. Visual Acuity (VA) was evaluated 1 day and 60 days after the procedure. Predictive factors, such as age, degree of sphere, degree of astigmatism, keratometric reading and axial length were analyzed to detect any influences affecting the final VA results. A total of 316 myopia eyes underwent intervention, mean age: 25.3±3.8 years. Target treatment was achieved in 96.1% of patients with high myopia and 69.9% of patients with very high myopia. High degree of sphere and astigmatism constitutes an important factor influencing final VA. Modern machines provide a more promising efficacy and success of LASIK procedure in high myopia: important predictive factors were a high degree of sphere and astigmatism for achieving the optimal final outcome.


Enhanced mineralization of polychlorinated biphenyls in soil inoculated with chlorobenzoate-degrading bacteria.
An Altamont soil containing no measurable population of chlorobenzoate utilizers was examined for the potential to enhance polychlorinated biphenyl (PCB) mineralization by inoculation with chlorobenzoate utilizers, a biphenyl utilizer, combinations of the two physiological types, and chlorobiphenyl-mineralizing transconjugants. Biphenyl was added to all soils, and biodegradation of 14C-Aroclor 1242 was assessed by disappearance of that substance and by production of 14CO2. Mineralization of PCBs was consistently greatest (up to 25.5%) in soils inoculated with chlorobenzoate degraders alone. Mineralization was significantly lower in soils receiving all other treatments: PCB cometabolizer (10.7%); chlorobiphenyl mineralizers (8.7 and 14.9%); and mixed inocula of PCB cometabolizers and chlorobenzoate utilizers (11.4 and 18.0%). However, all inoculated soils had higher mineralization than did the uninoculated control (3.1%). PCB disappearance followed trends similar to that observed with the mineralization data, with the greatest degradation occurring in soils inoculated with the chlorobenzoate-degrading strains Pseudomonas aeruginosa JB2 and Pseudomonas putida P111 alone. While the mechanism by which the introduction of chlorobenzoate degraders alone enhanced biodegradation of PCBs could not be elucidated, the possibility that chlorobenzoate inoculants acquired the ability to metabolize biphenyl and possibly PCBs was explored. When strain JB2, which does not utilize biphenyl, was inoculated into soil containing biphenyl and Aroclor 1242, the frequency of isolates able to utilize biphenyl and 2,5-dichlorobenzoate increased progressively with time from 3.3 to 44.4% between 15 and 48 days, respectively. Since this soil contained no measurable level of chlorobenzoate utilizers yet did contain a population of biphenyl utilizers, the possibility of genetic transfer between the latter group and strain JB2 cannot be excluded.


Rapid animal welfare assessment: an archaeological approach.
The welfare of an individual depends on its capacity to overcome suboptimal conditions in its environment; otherwise, its physical and psychological health becomes compromised. A situation that clearly indicates lack of control of the environment is the expression of abnormal behaviours, such as stereotypies. This study aimed to verify the well-being of police horses using a new rapid form of welfare assessment: an archaeological approach. To this end, we sampled and quantified marks found on the stables, deposited as a result of abnormal behaviour. We cross-referenced these physical marks with veterinary records of diseases, such as colic, known to be associated with stress. A total of 46 horses were sampled and the results showed a significant medium-strength, positive correlation between bite mark frequency on stable doors and the incidence of colic. A weak significant positive correlation was found between length of scratch marks (from pawing) and the incidence of lameness. We conclude that these marks reflect the accumulated expression of abnormal behaviour and can provide rapid insight into the welfare of individual animals.


Neural and Behavioral Evidence for Infants' Sensitivity to the Trustworthiness of Faces.
Face evaluation is a key aspect of face processing in humans, serving important functions in regulating social interactions. Adults and preschool children readily evaluate faces with respect to a person's trustworthiness and dominance. However, it is unclear whether face evaluation is mainly a product of extensive learning or a foundational building block of face perception already during infancy. We examined infants' sensitivity to facial signs of trustworthiness (Experiment 1) and dominance (Experiment 2) by measuring ERPs and looking behavior in response to faces that varied with respect to the two facial attributes. Results revealed that 7-month-old infants are sensitive to facial signs of trustworthiness but not dominance. This sensitivity was reflected in infants' behavioral preference and in the modulation of brain responses previously linked to emotion detection from faces. These findings provide first evidence that processing faces with respect to trustworthiness has its origins in infancy and shed light on the behavioral and neural correlates of this early emerging sensitivity.


Using Stereochemistry to Control Mechanical Properties in Thiol-Yne Click-Hydrogels.
The stereochemistry of polymers has a profound impact on their mechanical properties. While this has been observed in thermoplastics, studies on how stereochemistry affects the bulk properties of swollen networks, such as hydrogels, are limited. Typically, changing the stiffness of a hydrogel is achieved at the cost of changing another parameter, that in turn affects the physical properties of the material and ultimately influences the cellular response. Herein, we report that by manipulating the stereochemistry of a double bond, formed in situ during gelation, materials with diverse mechanical properties but comparable physical properties can be obtained. Click-hydrogels that possess a high % trans content are stiffer than their high % cis analogues by almost a factor of 3. Human mesenchymal stem cells acted as a substrate stiffness cell reporter demonstrating the potential of these platforms to study mechanotransduction without the influence of other external factors.


Assessment of multiple cardiac biomarkers in non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 trial.
The aim of this study is to simultaneously evaluate the incremental prognostic value of multiple cardiac biomarkers reflecting different underlying pathophysiological processes in a well-characterized population of patients with non-ST-segment acute coronary syndrome (NSTE-ACS). We measured cardiac troponin I (cTnI), N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein, and myeloperodixase (MPO) among 4352 patients with NSTE-ACS in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischaemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial and followed them for a mean of 343 days. When added individually to a multivariable model adjusted for clinical characteristics, the risk of cardiovascular (CV) death rose in a stepwise fashion with increasing quartiles of each biomarker, and when using their pre-defined cut-points [HR(adj) 2.71 (P < 0.001) for cTnI ≥0.03 ng/mL; HR(adj) 3.01 (P < 0.001) for NT-proBNP ≥400 pg/mL; HR(adj) 1.45 (P = 0.019) for high-sensitivity (hs) C-reactive protein ≥15 mg/L; and HR(adj) 1.49 (P = 0.006) for MPO ≥670 pmol/L]. After including all biomarkers, only NT-proBNP and cTnI were independently associated with CV death, and only cTnI with myocardial infarction (MI). The addition of NT-proBNP to a model adjusted for TIMI risk score incorporating cTnI significantly improved both the discrimination and re-classification of the model for CV death and heart failure (HF) while there was no such improvement after the addition of either MPO or hs-C-reactive protein. In this study of over 4300 patients presenting with NSTEACS, we found that both cTnI and NT-proBNP offer prognostic information beyond that achieved with clinical risk variables for CV death, MI, and HF. Myeloperoxidase and hs-C-reactive protein, while independently associated with some adverse CV outcomes, did not provide substantial incremental prognostic information when evaluated together with cTnI and NT-proBNP.


Diversity in junctional sequences associated with the common human V gamma 9 and V delta 2 gene segments in normal blood and lung compared with the limited diversity in a granulomatous disease.
The T cell receptor (TCR) junctional regions (N regions) of the common human V gamma 9 and V delta 2 gene segments were sequenced from the blood and lung of normal individuals (195 transcripts) and a group of individuals with sarcoidosis (220 transcripts), a granulomatous disease in which increased numbers of V gamma 9+ gamma/delta + T cells are often observed. In normal individuals, the vast majority (86%) of blood V gamma 9 transcripts used the J gamma P gene segment. In contrast to this restriction of J region usage, there was a large diversity of the junctional region, with less than 20% of blood V gamma 9 junctional regions showing identical sequences for any one normal individual. For the blood V delta 2 transcripts in normal individuals, there was restriction of J region usage, with 93% using J delta 1. The junctional regions were even more diverse than for V gamma 9, with a unique sequence observed in each transcript examined. Compared with blood, sequences from the normal lung showed a small increase in identical junctional regions, particularly in one individual where 46% of V gamma 9 transcripts examined were identical, suggesting a response of some gamma/delta T cells to antigens found in the lung in the normal state. In marked contrast to normals, some individuals with sarcoidosis had large numbers of V gamma 9 transcripts, as well as V delta 2 transcripts, sharing identical sequences. For V gamma 9 blood transcripts, two individuals showed 84 and 56% of junctional region sequences to be identical, respectively. Similarly, blood V delta 2 transcripts showed 43, 33, and 25% identical junctional region sequences in three individuals. In the sarcoid patient with the most striking over-representation of blood V gamma 9 junctional sequences, lung V gamma 9 transcripts showed increased (67%) use of the same junctional region sequence as in blood. This limited diversity of TCR junctional regions among some individuals with sarcoidosis suggests a response from specific stimuli, possibly antigenic, and that gamma/delta T cells may play a specific role in granuloma formation in sarcoidosis, as has been suggested in other granulomatous diseases.