Discrimination of bacteria by rapid sensing their metabolic volatiles using an aspiration-type ion mobility spectrometer (a-IMS) and gas chromatography-mass spectrometry GC-MS.
The objective of our study was to investigate whether one may quickly and reliably discriminate different microorganism strains by direct monitoring of the headspace atmosphere above their cultures. Headspace samples above a series of in vitro bacterial cultures were directly interrogated using an aspiration type ion mobility spectrometer (a-IMS), which produced distinct profiles ("fingerprints") of ion currents generated simultaneously by the detectors present inside the ion mobility cell. Data processing and analysis using principal component analysis showed net differences in the responses produced by volatiles emitted by various bacterial strains. Fingerprint assignments were conferred on the basis of product ion mobilities; ions of differing size and mass were deflected in a different degree upon their introduction of a transverse electric field, impacting finally on a series of capacitors (denominated as detectors, or channels) placed in a manner analogous to sensor arrays. Three microorganism strains were investigated - Escherichia coli, Bacillus subtilis and Staphylococcus aureus; all strains possess a relatively low pathogenic character. Samples of air with a 5 cm3 volume from the headspace above the bacterial cultures in agar growth medium were collected using a gas-tight chromatographic syringe and injected inside the closed-loop pneumatic circuit of the breadboard a-IMS instrument model ChemPro-100i (Environics Oy, Finland), at a distance of about 1 cm from the ionization source. The resulting chemical fingerprints were produced within two seconds from the moment of injection. The sampling protocol involved to taking three replicate samples from each of 10 different cultures for a specific strain, during a total period of 72 h after the initial incubation - at 24, 48 and 72 h, respectively. Principal component analysis (PCA) was used to discriminate between the IMS fingerprints. PCA was found to successfully discriminate between bacteria at three levels in the experimental campaign: 1) between blank samples from growth medium and samples from bacterial cultures, 2) between samples from different bacterial strains, and 3) between time evolutions of headspace samples from the same bacterial strain over the 3-day sampling period. Consistent classification between growth medium samples and growth medium inoculated with bacteria was observed in both positive and negative detection/ionization modes. In parallel, headspace air samples of 1 dm3 were collected from each bacterial culture and loaded onto Tenax™-Carbograph desorption tubes, using a custom built sampling unit based on a portable sampling pump. One sample was taken for each of 10 different cultures of a strain, at 24, 48 and 72 h after the initial incubation. These adsorption tubes were subsequently analyzed using thermal desorption - gas chromatography - mass spectrometry (TD-GC-MS). This second dataset was intended to produce a qualitative analysis of the volatiles present in the headspace above the bacterial cultures.


Depressed during the depression: has the economic crisis affected mental health inequalities in Europe? Findings from the European Social Survey (2014) special module on the determinants of health.
Economic crises constitute a shock to societies with potentially harmful effects to the mental health status of the population, including depressive symptoms, and existing health inequalities. With recent data from the European Social Survey (2006–14), this study investigates how the economic recession in Europe starting in 2007 has affected health inequalities in 21 European nations. Depressive feelings were measured with the CES-D eight-item depression scale. We tested for measurement invariance across different socio-economic groups. Overall, depressive feelings have decreased between 2006 and 2014 except for Cyprus and Spain. Inequalities between persons whose household income depends mainly on public benefits and those who do not have decreased, while the development of depressive feelings was less favorable among the precariously employed and the inactive than among the persons employed with an unlimited work contract. There are no robust effects of the crisis measure on health inequalities. Negative implications for mental health (in terms of depressive feelings) have been limited to some of the most strongly affected countries, while in the majority of Europe persons have felt less depressed over the course of the recession. Health inequalities have persisted in most countries during this time with little influence of the recession. Particular attention should be paid to the mental health of the inactive and the precariously employed.


Relative biological effectiveness of negative pi mesons for the immune response in mice.
Immunologically competent mouse spleen cells were exposed to negative pi mesons in the entrance plateau or at the peak of the dose distribution at a maximum dosage of 5 rads/min. or to 60Co gamma rays at 4.96 rads/min. Survival curves from cells irradiated in vitro but incubated in vivo yielded RBE values of 2.15 for the peak and 1.84 for the entrance plateau at a surviving fraction of 0.1. The dose-rate dependence of antibody-forming spleen cells for both 60Co gamma rays and the lot-LET components of the pion beam is discussed. The authors suggest that these RBE values constitute an upper limit for normal mammalian cells exposed to pions and tha the RBE with clinically useful dose rates may be significantly lower than those reported here.


'Free to be' peer group supports patients with MPD/DD.
1. During the last decade, dissociative identity disorder increasingly has been recognized as a relatively common post-traumatic syndrome. 2. Individuals with MPD/DD often are estranged from abusive families and have difficulty with social connection; an urgent therapeutic task is the re-creation of a sense of human interdependency and community. 3. Group therapy can be a useful and successful adjunct to individual psychotherapy for relatively stable clients with MPD/DD; the group's focus should be here-and-now, supportive, and psychoeducative in nature.


Pathophysiology of coronary thrombosis: role of plaque rupture and plaque erosion.
Coronary artery disease is the leading cause of death in much of the western world. Atherosclerotic plaques in the coronary arteries contribute to luminal obstruction leading to myocardial ischemia; however, abrupt coronary artery occlusion most frequently results from superimposition of a thrombus on a disrupted plaque, leading to the most serious clinical manifestations of coronary artery disease, ie, unstable angina, acute myocardial infarction, and sudden death. Plaque that have undergone disruption and, by inference, plaques at risk for disruption (vulnerable plaques), tend to demonstrate outward vessel remodeling, contain a large lipid core, thinned out fibrous cap, reduced collagen content, and increased inflammatory cell infiltration. Plaque stabilization through change in plaque composition may be responsible for reduced frequency of acute vaso-occlusive events observed with lipid and other risk-factor modifying interventions.


Relating airway diameter distributions to regular branching asymmetry in the lung.
We study the distribution Pi(n)(D) of airway diameters D as a function of generation N in asymmetric airway trees of mammalian lungs. We find that the airway bifurcations are self-similar in four species studied. Specifically, the ratios of diameters of the major and minor daughters to their parent are constants independent of N until a cutoff diameter is reached. We derive closed form expressions for Pi(N)(D) and examine the flow resistance of the tree based on an asymmetric flow division model. Our findings suggest that the observed diameter heterogeneity is consistent with an underlying regular branching asymmetry.


Increased progesterone/estradiol ratio on the day of HCG administration adversely affects success of in vitro fertilization-embryo transfer in patients stimulated with gonadotropin-releasing hormone agonist and recombinant follicle-stimulating hormone.
We investigated the influence of premature luteinization in in vitro fertilization using a long protocol of gonadotropin-releasing hormone agonist (GnRHa) and recombinant follicle-stimulating hormone (rFSH), taking ovarian response into account in the definition of premature luteinization. A total of 339 cycles of controlled ovarian hyperstimulation with rFSH and GnRHa were performed in 311 infertile couples. Premature luteinization was defined as a progesterone (P) to estradiol (E2) ratio of > 1 on the day of human chorionic gonadotropin (hCG) administration. The P/E2 ratio is calculated as: P (ng/mL) 1,000/E2 (pg/mL). Clinical outcomes were compared for the prematurely luteinized and non-prematurely luteinized groups. The mean number of retrieved oocytes, recovered mature oocytes, embryos and top quality embryos were significantly higher in the non-prematurely luteinized group than in the prematurely luteinized group. Although fertilization rates and implantation rates were similar between the two groups, the clinical pregnancy rate was higher in the non-prematurely luteinized group than in the prematurely luteinized group. Premature luteinization, defined as late follicular P/E2 ratio of > 1 in long GnRHa cycles with rFSH stimulation, adversely affected ovarian responses and clinical outcomes. It seems unrelated to preovulatory luteinizing hormone (LH) elevation and LH/hCG content of gonadotropins and could be associated with poor ovarian response and the presence of dysmature follicles.


Design, synthesis, and evaluation of cisplatin-containing EGFR targeting bioconjugates as potential therapeutic agents for brain tumors.
The aim of this study was to evaluate four different platinated bioconjugates containing a cisplatin (cis-diamminedichloroplatinum [cis-DDP]) fragment and epidermal growth factor receptor (EGFR)-targeting moieties as potential therapeutic agents for the treatment of brain tumors using a human EGFR-expressing transfectant of the F98 rat glioma (F98EGFR) to assess their efficacy. The first two bioconjugates employed the monoclonal antibody cetuximab (C225 or Erbitux(®)) as the targeting moiety, and the second two used genetically engineered EGF peptides. C225-G5-Pt was produced by reacting cis-DDP with a fifth-generation polyamidoamine dendrimer (G5) and then linking it to C225 by means of two heterobifunctional reagents. The second bioconjugate (C225-PG-Pt) employed the same methodology except that polyglutamic acid was used as the carrier. The third and fourth bioconjugates used two different EGF peptides, PEP382 and PEP455, with direct coordination to the Pt center of the cis-DDP fragment. In vivo studies with C225-G5-Pt failed to demonstrate therapeutic activity following intracerebral (ic) convection-enhanced delivery (CED) to F98EGFR glioma-bearing rats. The second bioconjugate, C225-PG-Pt, failed to show in vitro cytotoxicity. Furthermore, because of its high molecular weight, we decided that lower molecular weight peptides might provide better targeting and microdistribution within the tumor. Both PEP382-Pt and PEP455-Pt bioconjugates were cytotoxic in vitro and, based on this, a pilot study was initiated using PEP455-Pt. The end point for this study was tumor size at 6 weeks following tumor cell implantation and 4 weeks following ic CED of PEP455-Pt to F98 glioma-bearing rats. Neuropathologic examination revealed that five of seven rats were either tumor-free or only had microscopic tumors at 42 days following tumor implantation compared to a mean survival time of 20.5 and 26.3 days for untreated controls. In conclusion, we have succeeded in reformatting the toxicity profile of cis-DDP and demonstrated the therapeutic efficacy of the PEP455-Pt bioconjugate in F98 glioma-bearing rats.


Combined carbon and hydrogen isotope fractionation investigations for elucidating benzene biodegradation pathways.
Recently, combined carbon and hydrogen isotope fractionation investigations have emerged as a powerful tool for the characterization of reaction mechanisms relevant for the removal of organic pollutants. Here, we applied this approach in order to differentiate benzene biodegradation pathways under oxic and anoxic conditions in laboratory experiments. Carbon and hydrogen isotope fractionation of benzene was studied with four different aerobic strains using a monooxygenase or a dioxygenase for the initial benzene attack, a facultative anaerobic chlorate-reducing strain as well as a sulfate-reducing mixed culture. Carbon and hydrogen enrichment factors (epsilon(C), epsilon(H)) varied for the specific pathways and degradation conditions, respectively, so that from the individual enrichment factors only limited information could be obtained for the identification of benzene biodegradation pathways. However, using the slope derived from hydrogen vs carbon isotope discriminations or the ratio of hydrogen to carbon enrichment factors (lambda = deltaH/ deltaC approximately epsilon(H)/epsilon(C)), benzene degradation mechanisms could be distinguished. Although experimentally determined lambda values partially overlapped, ranges could be determined for different benzene biodegradation pathways. Specific lambda values were < 2 for dihydroxylation, between 7 and 9 for monohydroxylation, and > 17 for anaerobic degradation. Moreover, variations in lambda values suggest that more than one reaction mechanism exists for monohydroxylation as well as for anaerobic benzene degradation under nitrate-reducing, sulfate-reducing, or methanogenic conditions. Our results show that the combined carbon and hydrogen isotope fractionation approach has potential to elucidate biodegradation pathways of pollutants in field and laboratory microcosm studies.


Formulation of hydrophobic peptides for skin delivery via coated microneedles.
Microneedles (MNs) have been investigated as a minimally-invasive delivery technology for a range of active pharmaceutical ingredients (APIs). Various formulations and methods for coating the surface of MNs with therapeutics have been proposed and exemplified, predominantly for hydrophilic drugs and particulates. The development of effective MN delivery formulations for hydrophobic drugs is more challenging with dosing restrictions and the use of organic solvents impacting on both the bioactivity and the kinetics of drug release. In this study we propose a novel formulation that is suitable for MN coating of hydrophobic auto-antigen peptides currently being investigated for antigen specific immunotherapy (ASI) of type 1 diabetes. The formulation, comprising three co-solvents (water, 2-methyl-2-butanol and acetic acid) and polyvinylalcohol 2000 (PVA2000) can dissolve both hydrophilic and hydrophobic peptide auto-antigens at relatively high, and clinically relevant, concentrations (25mg/ml or 12.5mg/ml). The drug:excipient ratio is restricted to 10:1 w/w to maximise dose whilst ensuring that the dry-coated payload does not significantly impact on MN skin penetration performance. The coating formulation and process does not adversely affect the biological activity of the peptide. The delivery efficiency of the coated peptide into skin is influenced by a number of parameters. Electropolishing the metal MN surface increases delivery efficiency from 2.0±1.0% to 59.9±6.7%. An increased mass of peptide formulation per needle, from 0.37μg to 2μg peptide dose, resulted in a thicker coating and a 20% reduction in the efficiency of skin delivery. Other important performance parameters for coated MNs include the role of excipients in assisting dissolution from the MNs, the intrinsic hydrophobicity of the peptide and the species of skin model used in laboratory studies. This study therefore both exemplifies the potential of a novel formulation for coating hydrophobic and hydrophilic peptides onto MN devices and provides new insight into the factors that influence delivery efficiency from coated MNs. Importantly, the results provide guidance for identifying critical attributes of the formulation, coating process and delivery device, that confer reproducible and effective delivery from coated MNs, and thus contribute to the requirements of the regulators appraising these devices.


Routine follow-up care for head and neck cancer after curative treatment: A 3-year experience of measuring patients' self-reported needs, preferences, quality of life and attitudes towards follow-up.
To evaluate and describe attitudes, quality of life (Qol), needs and preferences of patients with head and neck cancer after 3 years of follow-up care. This is an exploratory prospective study of recurrence-free patients. Survey results were compared between 1-, 2- and 3-year post-treatment and by disease characteristics. A total of 116 patients were included with 46% oropharyngeal cancer, 66% early stage disease and 41% having had surgery. After 3 years, most patients reported good to excellent health (88%), however expressed uncertainty regarding recurrence (66%), multiple needs (information on prognosis 91%, long-term sequalae 72%) and wanted to continue with follow-up (96%). Few changes were observed over time, with exceptions. Patients with more advanced disease, oral cancer or who had surgery experienced declining Qol (p < 0.050). Women experienced improvements in Qol domains (pain p = 0.028, speech p = 0.009) over time. Attitudes towards communication with oncologists demonstrated improved patient comfort (p = 0.044) over the 3 years; however, patients' beliefs about their prognosis did not (71% vs. 73% vs. 77% did not believe they were cured, p = 0.581). Although patients' needs, preferences and attitudes towards follow-up did not change drastically, important needs persist. This work supports identifying individual patient needs and the challenges in addressing prognostic expectations.


Fetal facial standard plane recognition via very deep convolutional networks.
The accurate recognition of fetal facial standard plane (FFSP) (i.e., axial, coronal and sagittal plane) from ultrasound (US) images is quite essential for routine US examination. Since the labor-intensive and subjective measurement is too time-consuming and unreliable, the development of the automatic FFSP recognition method is highly desirable. Different from the previous methods, we leverage a general framework to recognize the FFSP from US images automatically. Specifically, instead of using the previous hand-crafted visual features, we utilize the recent developed deep learning approach via very deep convolutional networks (DCNN) architecture to represent fine-grained details of US image. Also, very small (3×3) convolution filters are adopted to improve the performance. The evaluation of our FFSP dataset shows the superiority of our method over the previous studies and achieves the state-of-the-art FFSP recognition results.


Autophagy impairment in human bile duct carcinoma cells.
Bile duct epithelial cells, named cholangiocytes, may undergo a neoplastic transformation leading to cholangiocarcinoma. The role autophagy plays in cancer is still debated and few information are available in cholangiocarcinoma. We report in vitro data, at least in part validated in vivo,i ndicating that autophagy is impaired in intrahepatic cholangiocarcinoma cells, as compared to healthy cholangiocytes, evaluated through LC3II and p62 Western blot analyses. Autophagy impairment was found to be associated with low expression of TFEB protein and high expression of three proteins i.e., c-FLIP, caspase-10 and cleaved BCLAF-1, as compared to healthy cholangiocytes. We highlight biological effects of autophagy impairment in cholangiocarcinoma showing that autophagy induction, via rapamycin, as well as caspase inhibition, via Q-VD-OPh, are able to reduce proliferation marker PCNA level, colony size and protein content of cultured cholangiocarcinoma cells. The increased protein expression of p62, c-FLIP, caspase-10 observed in vitro in cholangiocarcinoma cells was paralleled by significant increase at gene expression levels in vivo; in fact, significant increase of transcript levels of p62, c-FLIP and caspase-10 was observed in 34 biopsies from human cholangiocarcinoma patients compared to 9 biopsies from 9 healthy controls, as reported in the GEPIA2 public database. The significant increase of p62 level in cholangiocarcinoma was found as a relatively uncommon finding in solid cancers, since it was also found in only 7 cancer types out of 31 cancer types investigated, including melanoma and hepatocarcinoma. In conclusion, we present data suggesting a molecular machinery controlling autophagy in cholangiocytes and autophagy impairment in cholangiocarcinoma.


Extramedullary relapse confirmed by fluorescence in situ hybridization study of an ear mass in acute promyelocytic leukemia.
A 40-year-old man with acute promyelocytic leukemia (APL) achieved complete remission after induction chemotherapy combined with all-trans-retinoic acid. A mass developed in the left ear 24 months later. Relapse of APL was suspected at morphologic examination of the biopsy specimen of the ear mass, but t(15;17) and PML/RAR alpha rearrangement were not detected by chromosomal, fluorescence in situ hybridization (FISH), or reverse transcription polymerase chain reaction analysis of bone marrow samples. FISH performed on the ear mass revealed t(15;17). To our knowledge, this case is the first reported case of extramedullary relapse of APL confirmed by FISH study of a biopsy specimen of extramedullary tissue.


Treatment of chronic osteomyelitis with muscle flaps.
This article discusses a study of 36 patients with chronic osteomyelitis that had local or free muscle flaps. Reconstruction of chronic osteomyelitis requires infection control and assessment of soft tissue and bone. In patients with osteomyelitis with an ununited fracture or nonunion, stabilization of the fracture is needed.


Development and Validation of the Real-World Progression in Diabetes (RAPIDS) Model.
To develop and validate the first real-world data-based type 2 diabetes progression model (RAPIDS) employing econometric techniques that can study the comparative effects of complex dynamic patterns of glucose-lowering drug use. The US Department of Veterans Affairs (VA) electronic medical record and claims databases were used to identify over 500,000 diabetes patients in 2003 with up to 9-year follow-up. The RAPIDS model contains interdependent first-order Markov processes over quarters for each of the micro- and macrovascular events, hypoglycemia, and death, as well as predictive models for 8 biomarker levels. Model parameters varied by static demographic factors and dynamic factors, such as age, duration of diabetes, 13 possible glucose-lowering treatment combinations, any blood pressure and any cholesterol-lowering medications, and cardiovascular history. To illustrate model capabilities, a simple comparative study was set up to compare observed treatment use patterns to alternate patterns if perfect adherence is assumed following initiating the use of any of these medications. Data were randomly split into 307,288, 105,195, and 105,081 patients to perform estimation, out-of-sample calibration, and validation, respectively. Model predictions in the validation sample closely aligned with the observed longitudinal trajectory of biomarkers and outcomes. Perfect adherence among initiators increased proportion of days covered by only 6 months. Most of this increase came from increased adherence to monotherapies and did not lead to meaningful changes in any of the outcomes over the 9-year period. Future value of increasing medication adherence among VA patients with diabetes may lie among those who never initiate treatment or are late in initiating treatment. The first-of-its-kind real-world data-based model has the potential to carry out many complex comparative-effectiveness research (CER) studies of dynamic glucose-lowering drug regimens.


On the right path.
The RCN has re-formed its ethics committee to help nurses deal with the moral dilemmas that they face in their day-to-day practice.


Increased insulin receptors in carbohydrate-sensitive subjects: a mechanism for hyperlipaemia in these subjects?
Twenty male subjects, 11 normal and 9 carbohydrate-sensitive, participated in a study in which the effect of feeding diets low in copper (1.03 mg/d) on the number and affinity of insulin receptors was determined. Since carbohydrate-sensitive subjects are hyperinsulinaemic, it was anticipated that they would demonstrate a down-regulation of insulin receptors. The subjects were fed a low copper diet for 11 weeks and then replenished with copper (3 mg/d) for 3 weeks. Regardless of diets fed, carbohydrate-sensitive subjects showed increased insulin binding. The increase was due to the number of receptors without any change in their affinity. This unusual and unexpected observation in carbohydrate-sensitive subjects suggests an altered response of the insulin receptor, namely the failure of plasma insulin to down-regulate the number of receptors. It is possible that such an alteration could lead to a shift of the biological response curve of insulin to the left in some target tissues thereby causing hyperlipaemia by diverting glucose into triglyceride. The exact mechanism of hyperlipaemia in carbohydrate-sensitive subjects remains to be clarified.


Randomized trial of adjuvant zoledronic acid in postmenopausal women with high-risk breast cancer.
We present the results of a randomized multicenter clinical trial of adjuvant zoledronic acid (ZA) in postmenopausal women with high-risk breast cancer. The primary objective was change in bone mineral density (BMD) at the lumbar spine and femoral neck at 1 year. Secondary objectives included change in calcaneal BMD, disease-free survival (DFS), overall survival (OS), and toxicity. Postmenopausal women with stage II/III breast cancer diagnosed up to 5 years previous were eligible and randomized to either observation or ZA 4 mg intravenous every 3 months. Bone mineral density testing was performed at 0, 6, and 12 months. Sixty-eight women were enrolled (36 ZA and 32 observation). The population was a median of 2 years from diagnosis and the majority received tamoxifen during the study. There was a significant difference in the mean change from baseline to 1 year follow-up for lumbar spine (increased by 4.28% ± 0.62%; P = .01), total femur (increased by 1.9% ± 0.4%; P = .03), trochanter (increased by 2.97% ± 0.69%; P = .03), and calcaneal BMD (increased by 2% ± 0.57%; P = .01) in favor of the ZA arm. No significant difference in the mean change for the femoral neck was seen. No significant differences in DFS or OS were observed. Zoledronic acid significantly improved the BMD at multiple skeletal sites in postmenopausal women largely on tamoxifen. No new safety signals were noted. There were insufficient events to comment on DFS or OS.


Influence of High Shear Dispersion on the Production of Cellulose Nanofibers by Ultrasound-Assisted TEMPO-Oxidation of Kraft Pulp.
Cellulose nanofibers can be produced using a combination of TEMPO, sodium bromide (NaBr) and sodium hypochlorite, and mechanical dispersion. Recently, this process has been the subject of intensive investigation. However, studies on the aspects of mechanical treatment of this process remain marginal. The main objective of this study is to evaluate the high shear dispersion parameters (e.g., consistency, stator-rotor gap, recirculation rate and pH) and determine their influences on nanocellulose production using ultrasound-assisted TEMPO-oxidation of Kraft pulp. All nanofiber gels produced in this study exhibited rheological behaviors known as shear thinning. From all the dispersion parameters, the following conditions were identified as optimal: 0.042 mm stator-rotor gap, 200 mL/min recycle rate, dispersion pH of 7 and a feed consistency of 2%. High quality cellulose gel could be produced under these conditions. This finding is surely of great interest for the pulp and paper industry.


Foxk proteins repress the initiation of starvation-induced atrophy and autophagy programs.
Autophagy is the primary catabolic process triggered in response to starvation. Although autophagic regulation within the cytosolic compartment is well established, it is becoming clear that nuclear events also regulate the induction or repression of autophagy. Nevertheless, a thorough understanding of the mechanisms by which sequence-specific transcription factors modulate expression of genes required for autophagy is lacking. Here, we identify Foxk proteins (Foxk1 and Foxk2) as transcriptional repressors of autophagy in muscle cells and fibroblasts. Interestingly, Foxk1/2 serve to counter-balance another forkhead transcription factor, Foxo3, which induces an overlapping set of autophagic and atrophic targets in muscle. Foxk1/2 specifically recruits Sin3A-HDAC complexes to restrict acetylation of histone H4 and expression of critical autophagy genes. Remarkably, mTOR promotes the transcriptional activity of Foxk1 by facilitating nuclear entry to specifically limit basal levels of autophagy in nutrient-rich conditions. Our study highlights an ancient, conserved mechanism whereby nutritional status is interpreted by mTOR to restrict autophagy by repressing essential autophagy genes through Foxk-Sin3-mediated transcriptional control.


Finite-size scaling for quantum criticality above the upper critical dimension: Superfluid-Mott-insulator transition in three dimensions.
The validity of modified finite-size scaling above the upper critical dimension is demonstrated for the quantum phase transition whose dynamical critical exponent is z=2. We consider the N -component Bose-Hubbard model, which is exactly solvable and exhibits mean-field type critical phenomena in the large- N limit. The modified finite-size scaling holds exactly in that limit. However, the usual procedure, taking the large system-size limit with fixed temperature, does not lead to the expected (and correct) mean-field critical behavior because of the limited range of applicability of the finite-size scaling form. By quantum Monte Carlo simulation, it is shown that the modified finite-size scaling holds in the case of N=1.


Traumatic renal artery occlusion in the pediatric age group: a case and review of the literature.
Blunt trauma represents a major cause of death in children. The incidence of renal arterial injuries in these cases is less than 1%. Traumatic renal artery occlusion is a rare occurrence in the pediatric age group. However, there is lack of information on the exact incidence and results of the management of these rare cases in the pediatric age group. We report herein a case and we review the available literature of this severe injury in the pediatric age group.


Clinical Characteristics of Late Gadolinium Enhancement in Patients with Cardiac Sarcoidosis.
The presence of cardiac involvement in sarcoidosis, a multisystem granulomatous disease of unknown etiology, is associated with very poor prognosis. Therefore, early detection of cardiac sarcoidosis (C-sar) is very important for effective treatment. Recently, the value of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR), which allows visualization of even minute amounts of myocardial damage, has been emphasized in diagnosing C-sar. Although the presence of LGE has been added as a minor criterion for diagnosing C-sar in the most recent Japan Ministry of Health and Welfare (JMHW) guidelines, its clinical utility remains unknown. A total of 17 patients with biopsy-proven extracardiac sarcoidosis, who underwent CMR and examinations using a sufficient number of modalities to diagnose or exclude C-sar in accordance with the JMHW diagnostic criteria, were retrospectively enrolled in this study. Among these 17 patients, 7 patients were diagnosed with C-sar and 10 with non-C-sar. We investigated the clinical performance of LGE in the detection of cardiac involvement, compared the distribution of LGE with perfusion defects of iodine-123-labeled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (BMIPP) or thallium-201 (201Tl) scintigraphy, and evaluated the prognostic value of LGE on CMR in identifying adverse clinical events. All patients diagnosed with C-sar were positive for LGE and all diagnosed with non-C-sar patients were negative. Evaluation of LGE revealed a broader range of abnormalities than the evaluation of the defects shown by either BMIPP or 201Tl scintigraphy. All adverse events occurred in the C-sar patients with LGE. This study showed that LGE is useful for the detection of cardiac involvement, and it might be a promising tool for determining the prognosis of patients with biopsy-proven extracardiac sarcoidosis.


Standardized application of yeast bioluminescent reporters as endocrine disruptor screen for comparative analysis of wastewater effluents from membrane bioreactor and traditional activated sludge.
A standardized protocol is demonstrated for bioluminescent strains Saccharomyces cerevisiae BLYES, BLYAS and BLYR as high-throughput screening tools to monitor the estrogenic, androgenic and toxic potencies in wastewater. The sensitivity and reproducibility of the assay in wastewater monitoring was evaluated for 7 day semi-continuous batch reactor using activated sludge with hormones spiked raw sewage. Yeast bioluminescent assay successfully captured the rapid removal of estrogenic and androgenic activities in the bioreactors, and demonstrated rapid response (≤4 h) with good reproducibility. This standardized protocol was then applied in a 12 months monitoring of the effluent of a WWTP located at Powell, TN, USA featuring parallel-operated full-scale membrane bioreactor (MBR) and traditional activated sludge (TAS) treatment. Monitoring results showed that estrogenic activity was persistent in all TAS and most MBR effluent samples, while residual androgenic activity was non-detectable throughout the monitored period. The estrogenic equivalents (EEQ) in TAS effluent ranged from 21.61 ng/L to 0.04 pg/L and averaged 3.25 ng/L. The EEQ in MBR effluent ranged from 2.88 ng/L to 0.0134 pg/L and averaged ~10 fold less (0.32 ng/L) than TAS. Despite the large temporal variation, MBR effluent EEQ was consistently lower than TAS on any given sampling date. Most MBR effluent samples also exhibited less cytotoxicity than TAS. Further analysis did not demonstrate significant correlation between effluent EEQ level and WWTP operational parameters including MLSS, SRT, HRT and BOD.


[Biodegradation of lignin in wheat straw by alkaliphilic ligninolytic bacteria with compounded carbons].
The article researched enzymes production, the degradation rate of lignin and strain growth of alkaliphilic ligninolytic bacteria strain No. 6 in alkaline liquid medium (pH approximately 10.5) with compounded carbons. The results showed that the highest activities of laccase and MnP were 2915.37 U/L (4th d) and 1152.88 U/L (8th d), respectively, and the strain degraded 49.84% lignin of wheat straw during ten days cultivation. The changes of ultrastructure of wheat straw caused by strain No. 6 attack were investigated with SEM (scan electron microscopy).


Genomic and molecular mechanisms for efficient biodegradation of aromatic dye.
Understanding the molecular mechanisms for aromatic compound degradation is crucial for the development of effective bioremediation strategies. We report the discovery of a novel phenomenon for improved degradation of Direct Red 5B azo dye by Irpex lacteus CD2 with lignin as a co-substrate. Transcriptomics analysis was performed to elucidate the molecular mechanisms of aromatic degradation in white rot fungus by comparing dye, lignin, and dye/lignin combined treatments. A full spectrum of lignin degradation peroxidases, oxidases, radical producing enzymes, and other relevant components were up-regulated under DR5B and lignin treatments. Lignin induced genes complemented the DR5B induced genes to provide essential enzymes and redox conditions for aromatic compound degradation. The transcriptomics analysis was further verified by manganese peroxidase (MnP) protein over-expression, as revealed by proteomics, dye decolorization assay by purified MnP and increased hydroxyl radical levels, as indicated by an iron reducing activity assay. Overall, the molecular and genomic mechanisms indicated that effective aromatic polymer degradation requires synergistic enzymes and radical-mediated oxidative reactions to form an effective network of chemical processes. This study will help to guide the development of effective bioremediation and biomass degradation strategies.


Rates of cerebral palsy in Victoria, Australia, 1970 to 2004: has there been a change?
The aim of this study was to assess overall and gestational age-specific trends in the rate of cerebral palsy (CP) in Victoria, Australia, and to compare these findings with other population data. Individuals born in Victoria from 1970 to 2004 with non-postneonatally acquired CP were identified from a population register; 3491 were included in the study (1963 males, 1528 females). After a literature review, comparison data were extracted from publications using previously devised inclusion criteria. Rates were calculated per 1000 live births for all CP and by gestational age group: these were tabulated and plotted by year of birth. Data from nine registries, including the Victorian register, showed an increase in the rates of CP over the 1970s and 1980s, consistently seen in extremely preterm (<28 wks) survivors but also in those born at term (≥37 wks). Since the early 1990s, CP rates either stabilized or decreased, particularly for children born extremely preterm. Increases in the rates of CP during the 1970s and 1980s are in part because of the increasing survival of extremely preterm infants that occurred without a concomitant improvement in neurological outcomes. Evidence from population samples now suggests that this trend has been reversed since the mid- to late 1990s.


Rudimentary expression of RYamide in Drosophila melanogaster relative to other Drosophila species points to a functional decline of this neuropeptide gene.
RYamides are arthropod neuropeptides with unknown function. In 2011 two RYamides were isolated from D. melanogaster as the ligands for the G-protein coupled receptor CG5811. The D. melanogaster gene encoding these neuropeptides is highly unusual, as there are four RYamide encoding exons in the current genome assembly, but an exon encoding a signal peptide is absent. Comparing the D. melanogaster gene structure with those from other species, including D. virilis, suggests that the gene is degenerating. RNAseq data from 1634 short sequence read archives at NCBI containing more than 34 billion spots yielded numerous individual spots that correspond to the RYamide encoding exons, of which a large number include the intron-exon boundary at the start of this exon. Although 72 different sequences have been spliced onto this RYamide encoding exon, none codes for the signal peptide of this gene. Thus, the RNAseq data for this gene reveal only noise and no signal. The very small quantities of peptide recovered during isolation and the absence of credible RNAseq data, indicates that the gene is very little expressed, while the RYamide gene structure in D. melanogaster suggests that it might be evolving into a pseudogene. Yet, the identification of the peptides it encodes clearly shows it is still functional. Using region specific antisera, we could localize numerous neurons and enteroendocrine cells in D. willistoni, D. virilis and D. pseudoobscura, but only two adult abdominal neurons in D. melanogaster. Those two neurons project to and innervate the rectal papillae, suggesting that RYamides may be involved in the regulation of water homeostasis.


Camera scheduling and energy allocation for lifetime maximization in user-centric visual sensor networks.
We explore camera scheduling and energy allocation strategies for lifetime optimization in image sensor networks. For the application scenarios that we consider, visual coverage over a monitored region is obtained by deploying wireless, battery-powered image sensors. Each sensor camera provides coverage over a part of the monitored region and a central processor coordinates the sensors in order to gather required visual data. For the purpose of maximizing the network operational lifetime, we consider two problems in this setting: a) camera scheduling, i.e., the selection, among available possibilities, of a set of cameras providing the desired coverage at each time instance, and b) energy allocation, i.e., the distribution of total available energy between the camera sensor nodes. We model the network lifetime as a stochastic random variable that depends upon the coverage geometry for the sensors and the distribution of data requests over the monitored region, two key characteristics that distinguish our problem from other wireless sensor network applications. By suitably abstracting this model of network lifetime and utilizing asymptotic analysis, we propose lifetime-maximizing camera scheduling and energy allocation strategies. The effectiveness of the proposed camera scheduling and energy allocation strategies is validated by simulations.


The Patient Protection and Affordable Care Act: the victory of unorthodox lawmaking.
The 2010 Patient Protection and Affordable Care Act was a major legislative achievement of the 111th Congress. This law structurally reforms the US health care system by encouraging universal health care coverage through regulated competition among private insurance companies. When looking at the process for reform, what strikes an observer of US health care policy in the first place is that the Democratic majority was able to enact something in a political field characterized by strong resistance to change. This article builds on that observation. Arguments concentrate on the legislative process of the reform and support the idea that it may be partly explained by considering an evolution of US legislative institutions, mostly in the sense of a more centralized legislative process. Based on approximately one hundred semidirected interviews, I argue that the Democratic majority, building on lessons from both President Bill Clinton's health care reform attempt and the Republicans' strategy of using strong congressional leadership to pass social reforms, was able to overcome institutional constraints that have long prevented comprehensive change. A more centralized legislative process, which has been described as "unorthodox lawmaking," enabled the Democratic leadership to overcome multiple institutional and political veto players.


Effect of Copper Nanoparticles on the Flexural Strength of Heat Polymerized Acrylic Resin.
The aim of this study was to investigate the flexural strength of heat cure acrylic resin reinforced with varying concentration copper nanoparticles. The study followed ISO 20795-1-2013 guidelines for estimating the flexural strength. Hundred samples of heat cure acrylic resin of dimension were fabricated. The study had five groups and each group had 20 samples. The samples were grouped as per the concentration of copper (Cu) nanoparticles in acrylic. Three-point bending flexural strength was evaluated with universal testing machine. The load was directed at the midpoint of the sample at a cross-sectional speed of 5 mm/min. The fractured load was recorded and flexural strength was estimated. The data were statistically analyzed with analysis of variance and the post hoc test. The results displayed improved flexural strength in lower Cu concentrations. The increase in flexural strength was observed in 1% (78.38 MPa), 2% (73.08 MPa), and 3% (73.08 MPa) of Cu nanoparticles and it decreased beyond 3% increase in Cu nanoparticles. The tests were statistically insignificant (P <.05). The results concluded that the optimal concentration of Cu nanoparticles to be reinforced with heat cure PMMA is 1 gm. The flexural strength decreased with an increase in concentration of Cu nanoparticles.


Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment.
This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1-42, tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive impairment (MCI). The recommendations were developed by a multidisciplinary working group and based on the available evidence and consensus from focused group discussions for 1) prediction of clinical progression to Alzheimer's disease (AD) dementia, 2) cost-effectiveness, 3) interpretation of results, and 4) patient counseling. The working group recommended using CSF AD biomarkers in the diagnostic workup of MCI patients, after prebiomarker counseling, as an add-on to clinical evaluation to predict functional decline or conversion to AD dementia and to guide disease management. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Furthermore, the working group provided recommendations for interpretation of ambiguous CSF biomarker results and for pre- and post-biomarker counseling.


Cross-talk between CXC chemokine ligand 10-CXC chemokine receptor 3 axis and CC chemokine ligand 17-CC chemokine receptor 4 axis in the pathogenesis of oral lichen planus.
This study aimed to determine whether a correlation existed between CXC chemokine ligand 10 (CXCL10)-CXC chemokine receptor 3 (CXCR3) and CC chemokine ligand 17 (CCL17)-CC chemokine receptor 4 (CCR4) in the pathogenesis of oral lichen planus (OLP). Peripheral blood of OLP patients (non-erosive and erosive groups) and healthy controls were collected, and T cells were isolated and purified. T cells were co-cultured with three groups: blank, anti-CXCR3, and anti-CCR4. CXCR3 and CCR4 expression were detected by flow cytometry, and CXCL10 and CCL17 were detected by enzyme-linked immunosorbent assay, respectively. The purities of T cells were all >95% in the three groups (P>0.05). Receptor expression showed that CXCR3 and CCR4 in the anti-CXCR3 group was downregulated in OLP compared with the blank group (P>0.05). The level of CCR4 in the anti-CCR4 group was significantly downregulated (P<0.05), and CXCR3 was upregulated (P>0.05). Ligand analysis results showed that CXCL10 in the anti-CXCR3 group was significantly downregulated in OLP compared with the blank group (P<0.05), and CCL17 was also downregulated (P>0.05). CCL17 in the anti-CCR4 group was significantly downregulated (P<0.05), and CXCL10 was upregulated (P>0.05). The trend of receptors and ligands in controls was consistent with OLP, but no significant difference existed between the antagonistic and the blank groups (P>0.05). Two axes interact with each other in the pathogenesis of OLP and may play different roles in its occurrence and development.


Quantifying temporal ventriloquism in audiovisual synchrony perception.
The integration of visual and auditory inputs in the human brain works properly only if the components are perceived in close temporal proximity. In the present study, we quantified cross-modal interactions in the human brain for audiovisual stimuli with temporal asynchronies, using a paradigm from rhythm perception. In this method, participants had to align the temporal position of a target in a rhythmic sequence of four markers. In the first experiment, target and markers consisted of a visual flash or an auditory noise burst, and all four combinations of target and marker modalities were tested. In the same-modality conditions, no temporal biases and a high precision of the adjusted temporal position of the target were observed. In the different-modality conditions, we found a systematic temporal bias of 25-30 ms. In the second part of the first and in a second experiment, we tested conditions in which audiovisual markers with different stimulus onset asynchronies (SOAs) between the two components and a visual target were used to quantify temporal ventriloquism. The adjusted target positions varied by up to about 50 ms and depended in a systematic way on the SOA and its proximity to the point of subjective synchrony. These data allowed testing different quantitative models. The most satisfying model, based on work by Maij, Brenner, and Smeets (Journal of Neurophysiology 102, 490-495, 2009), linked temporal ventriloquism and the percept of synchrony and was capable of adequately describing the results from the present study, as well as those of some earlier experiments.


Estuarine fish health assessment: evidence of wastewater impacts based on nitrogen isotopes and histopathology.
Sewage effluent is a powerful agent of ecological change in estuaries. While the effects of sewage pollution on water quality are usually well documented, biological responses of exposed organisms are not. We quantified health impacts in the form of pathological tissue changes across multiple organs in estuarine fish exposed to elevated levels of treated wastewater. Structural pathologies were compared in wild populations of four fish species from two subtropical estuaries on the east coast of Australia that differ substantially in the amount of direct wastewater loadings. Uptake of sewage-derived nitrogen by fish was traced with stable nitrogen isotopes. Pathologies were common in the liver, spleen, gill, kidney and muscle tissues, and included granulomas, melanomacrophage aggregates, and multiple deformities of the gill epithelia. Tissue deformities were more frequent in fish exposed directly to wastewater discharges. Mullet (Valamugil georgii) were most affected, with only a single specimen free of pathologies in the sewage-impacted estuary. Similarly, in those fish that had structural abnormalities, more deformities were generally found in individuals from sites receiving sewage. These spatial contrasts in impaired fish health correspond to significantly enriched delta15N values in fish muscle as a consequence of fish assimilating sewage-N. Overall, the pattern of lower health and enriched delta15N values in fish from sewage-impacted areas suggests that organism health is lowered by sewage inputs to estuaries. Measurements of organism health are required to understand the effects of sewage on estuarine ecosystems, and histopathology of fishes is a powerful tool to achieve this.


Green Fluorescent Terbium (III) Complex Doped Silica Nanoparticles.
The low photostability of conventional organic dyes and the toxicity of cadmium-based luminescent quantum dots have prompted the development of novel probes for in vitro and in vivo labelling. Here, a new fluorescent lanthanide probe based on silica nanoparticles is fabricated and investigated for optically traceable in vitro translocator protein (TSPO) targeting. The targeting and detection of TSPO receptor, overexpressed in several pathological states, including neurodegenerative diseases and cancers, may provide valuable information for the early diagnosis and therapy of human disorders. Green fluorescent terbium(III)-calix[4]arene derivative complexes are encapsulated within silica nanoparticles and surface functionalized amine groups are conjugated with selective TSPO ligands based on a 2-phenylimidazo[1,2-a]pyridine acetamide structure containing derivatizable carboxylic groups. The photophysical properties of the terbium complex, promising for biological labelling, are demonstrated to be successfully conveyed to the realized nanoarchitectures. In addition, the high degree of biocompatibility, assessed by cell viability assay and the selectivity towards TSPO mitochondrial membrane receptors, proven by subcellular fractional studies, highlight targeting potential of this nanostructure for in vitro labelling of mitochondria.


Differential expression of protease-activated receptors 1, 2, and 4 on human endothelial cells from different vascular sites.
Protease-activated receptors (PARs) mediate DNA synthesis in endothelial cells when activated by serine proteases. However, despite the existence of heterogeneity among endothelial cells from each tissue, the responses to PAR-1, PAR-2, and PAR-4 activation are poorly defined and compared between endothelial cells from different sites. The aim of this study was to investigate whether PAR-mediated DNA synthesis differed in various endothelial cell types. We examined the incorporation of BrdU by human pulmonary artery endothelial cells (HPAECs), human aortic endothelial cells (HAECs), and human umbilical vein endothelial cells (HUVECs). When the endothelial cells were treated with the selective PAR-1-activating peptide, SFLLRN, HAECs showed the highest BrdU incorporation rate (182 +/- 28%). In contrast, treatment with the PAR-2-activating peptide, SLIGKV, resulted in the highest BrdU incorporation rate (173 +/- 37%) in HPAECs, when pretreated with TNF-alpha. The PAR-4-activating peptide, GYPGQV, induced DNA synthesis in HPAECs and HAECs, but not in HUVECs. These findings suggest that each PAR preferentially targets an endothelial cell type, and thus plays a distinct role in diverse physiological or pathological conditions.


Passive emission colorimetric sensor (PECS) for measuring emission rates of formaldehyde based on an enzymatic reaction and reflectance photometry.
A coin-sized passive emission colorimetric sensor (PECS) based on an enzymatic reaction and a portable reflectance photometry device were developed to determine the emission rates of formaldehyde from building materials and other materials found indoors in only 30 minutes on-site. The color change of the PECS linearly correlated to the concentration of formaldehyde aqueous solutions up to 28 microg/mL. The correlation between the emission rates measured by using the PECS and those measured by using a desiccator method or by using a chamber method was fitted with a linear function and a power function, and the determination coefficients were more than 0.98. The reproducible results indicate that the emission rates could be obtained with the correlation equations from the data measured by using the PECS and the portable reflectance photometry device. Limits of detection (LODs) were 0.051 mg/L for the desiccator method and 3.1 microg/m2/h for the chamber method. Thus, it was confirmed that the emission rates of formaldehyde from the building materials classified as F four-star (< 0.3 mg/L (desiccator method) or < 5.0 microg/m2/h (chamber method)), based on Japanese Industrial Standards (JIS), could be measured with the PECS. The measurement with PECS was confirmed to be precise (RSD < 10%). Other chemicals emitted from indoor materials, such as methanol, ethanol, acetone, toluene, and xylene, interfered little with the measurement of formaldehyde emission rates by using the PECS.


Central Nervous System Inflammation and Infection during Early, Nonaccelerated Simian-Human Immunodeficiency Virus Infection in Rhesus Macaques.
Studies utilizing highly pathogenic simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) have largely focused on the immunopathology of the central nervous system (CNS) during end-stage neurological AIDS and SIV encephalitis. However, this may not model pathophysiology in earlier stages of infection. In this nonaccelerated SHIV model, plasma SHIV RNA levels and peripheral blood and colonic CD4+ T cell counts mirrored early human immunodeficiency virus (HIV) infection in humans. At 12 weeks postinfection, cerebrospinal fluid (CSF) detection of SHIV RNA and elevations in IP-10 and MCP-1 reflected a discrete neurovirologic process. Immunohistochemical staining revealed a diffuse, low-level CD3+ CD4- cellular infiltrate in the brain parenchyma without a concomitant increase in CD68/CD163+ monocytes, macrophages, and activated microglial cells. Rare SHIV-infected cells in the brain parenchyma and meninges were identified by RNAScope in situ hybridization. In the meninges, there was also a trend toward increased CD4+ infiltration in SHIV-infected animals but no differences in CD68/CD163+ cells between SHIV-infected and uninfected control animals. These data suggest that in a model that closely recapitulates human disease, CNS inflammation and SHIV in CSF are predominantly mediated by T cell-mediated processes during early infection in both brain parenchyma and meninges. Because SHIV expresses an HIV rather than SIV envelope, this model could inform studies to understand potential HIV cure strategies targeting the HIV envelope.IMPORTANCE Animal models of the neurologic effects of HIV are needed because brain pathology is difficult to assess in humans. Many current models focus on the effects of late-stage disease utilizing SIV. In the era of antiretroviral therapy, manifestations of late-stage HIV are less common. Furthermore, new interventions, such as monoclonal antibodies and therapeutic vaccinations, target HIV envelope. We therefore describe a new model of central nervous system involvement in rhesus macaques infected with SHIV expressing HIV envelope in earlier, less aggressive stages of disease. Here, we demonstrate that SHIV mimics the early clinical course in humans and that early neurologic inflammation is characterized by predominantly T cell-mediated inflammation accompanied by SHIV infection in the brain and meninges. This model can be utilized to assess the effect of novel therapies targeted to HIV envelope on reducing brain inflammation before end-stage disease.


Single and double scattering event analysis for ultraviolet communication channels.
This paper presents a channel analysis method for single and double scattering events in non-line-of-sight (NLOS) ultraviolet (UV) communication systems. In general, the calculations of path loss and impulse response of such systems require Monte Carlo random number generations. However, the high computational costs of Monte Carlo methods impose severe limitations on quick reliable evaluations of system performance under complex atmospheric conditions. This paper proposes a sample-based UV channel characterization approach that improves computational performance by multiple orders of magnitude. The proposed novel approach uses fixed probability-based sampling. The method focuses only on single and double scattering events which dominate the received signal. The effects of various fog and dust aerosols are discussed under non-planar realistic conditions. The results demonstrate reliable channel characterization with significantly lower complexity using the proposed approach.


Exploring Synthetic and Systems Biology at the University of Edinburgh.
The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme.


Epigenetic inactivation and aberrant transcription of CSMD1 in squamous cell carcinoma cell lines.
The p23.2 region of human chromosome 8 is frequently deleted in several types of epithelial cancer and those deletions appear to be associated with poor prognosis. Cub and Sushi Multiple Domains 1 (CSMD1) was positionally cloned as a candidate for the 8p23 suppressor but point mutations in this gene are rare relative to the frequency of allelic loss. In an effort to identify alternative mechanisms of inactivation, we have characterized CSMD1 expression and epigenetic modifications in head and neck squamous cell carcinoma cell lines. Only one of the 20 cell lines examined appears to express a structurally normal CSMD1 transcript. The rest express transcripts which either lack internal exons, terminate abnormally or initiate at cryptic promoters. None of these truncated transcripts is predicted to encode a functional CSMD1 protein. Cell lines that express little or no CSMD1 RNA exhibit DNA methylation of a specific region of the CpG island surrounding CSMD1's first exon. Correlating methylation patterns and expression suggests that it is modification of the genomic DNA preceding the first exon that is associated with gene silencing and that methylation of CpG dinucleotides further 3' does not contribute to inactivation of the gene. Taken together, the cell line data suggest that epigenetic silencing and aberrant splicing rather than point mutations may be contributing to the reduction in CSMD1 expression in squamous cancers. These mechanisms can now serve as a focus for further analysis of primary squamous cancers.


International partnerships in nursing education.
As economies are shrinking, international partnerships in nursing education are growing, with the more established educational institutions launching not only on-site internationally focused programmes but also educational partnerships that cross borders, regions, societies, cultures, languages and educational and nursing traditions. Below, some issues related to initiating and maintaining partnerships, as well as the benefits and problems based on personal experience with these partnerships in developing countries.


Differential Effects of Wedelia chinensis on Human Glioblastoma Multiforme Cells.
Glioblastoma multiforme (GBM) is the most aggressive glioma, and its diffuse nature makes resection of it difficult. Moreover, even with the administration of postoperative radiotherapy and chemotherapy, prolonged remission is often not achieved. Hence, innovative or alternative treatments for GBM are urgently required. Traditional Chinese herbs and their functional components have long been used in the treatment of various cancers, including GBM. The current study investigated the antitumor activity of Wedelia chinensis and its major functional components, luteolin and apigenin, on GBM. MTT assay, Transwell migration assay, and flow cytometry analysis were adopted to assess the cell viability, invasive capability, and cell cycle. Immunofluorescence staining and Western blotting were used to detect the expressions of apoptotic and autophagy-related signaling molecules. The W. chinensis extract (WCE) significantly inhibited the proliferation and invasive ability of both GBM8401 and U-87MG cells in a dose-dependent manner. Moreover, differential effects of WCE on GBM8401 and U-87MG cells were observed: WCE induced apoptosis in GBM8401 cells and autophagy in U-87MG cells. Notably, WCE had significant effects in reducing the cell survival and invasive capability of both GBM8401 and U-87MG cells than the combination of luteolin and apigenin. Taken together, these findings indicate the potential of using WCE and the combination of luteolin and apigenin for GBM treatment. However, further investigations are warranted before considering recommending the clinical use of WCE or the combination of luteolin and apigenin as the standard for GBM treatment.


[Morphology of sweat glands].
There are two types of sweat glands: eccrine glands, which do not show cytological changes during secretion and apocrine glands, characterised by decapitation secretion, in which part of the cell is pinched off and released into the lumen. Eccrine glands play a major role in thermoregulation and electrolyte balance. They are present everywhere in the human skin and are composed of a secretory portion, an intradermal duct and an upper intraepidermal part, called acrosyringium. The acrosyringium has a unique symmetrical and helicoidal course, which length is correlated to the thickness of the epidermis. Apocrine glands are located only on genital, axillary and mammary areas, where they are always connected to a hair follicle. Their exact role in humans is unknown. A third type of intermediate sweat glands, the apoeccrine glands, was recently described in axillary areas. Sweat glands can be involved in various inflammatory processes and can lead to a large range of both benign and malignant tumors.


An efficient method for conjugation of a lipopolysaccharide from Salmonella enterica sv. Minnesota with probes bearing hydrazine or amino functional groups.
A conjugation method for coupling probes bearing hydrazine or primary amino groups to a lipopolysaccharide (LPS) is described. LPS is modified through the hydroxyl groups present in its O-antigen moiety by activation with cyanogen bromide in aqueous acetone using triethylamine to enhance the electrophilicity of CNBr. The method yields conjugates with good labeling ratios, preserving the endotoxic activity of the lipid A moiety, which in blood exerts pleiotropic effects on many tissues and organs, resulting in multiple-organ damage, circulatory collapse, and death. Conjugation of smooth-form LPS from Salmonella enterica sv. Minnesota to dansyl hydrazine yielded a labeling ratio of 330 nmol dansyl/mg LPS, with nearly no loss of the original endotoxic activity. In the case of horseradish peroxidase, in which a spacer was introduced, the ratio was 28 nmol HRP/mg of LPS, preserving 65% of the original endotoxic activity. This work shows that under these conditions of CNBr activation, the labeling process has practically no effect on the endotoxic behavior of LPS. The method can be used effectively for the conjugation of LPS to probes bearing primary amino, hydrazine, or hydrazide functional groups.


Use of microsatellite markers in molecular analysis of segregating populations of papaya (Carica papaya L.) derived from backcrossing.
Brazil is the world leader in papaya production. However, only a small number of cultivars are registered for commercial planting, mainly owing to delays in obtaining cultivars and the high costs of the field phase of breeding programs. These costs can be reduced when molecular tools are combined with conventional breeding methods. In the present study, we conducted a molecular analysis of a self-fertilized population of a first backcrossing generation of BC1S1 papaya plants via microsatellite markers both to monitor the level of homozygosity and the gene/allele transfer that confers the Golden trait (fruit color) and to assess the parental genomic proportion in the genotypes studied. Based on the analysis of 20 polymorphic microsatellite loci, 19 genotypes with the Golden trait belonging to BC1S1 were evaluated in addition to the parental genotypes. Genetic distance was estimated through weighted index. The genotypes were then grouped using the hierarchical nearest neighbor method, and the analysis of principal coordinates was used to measure the proportion of parental genomes in the segregating genotypes. The mean value of the inbreeding coefficient was 0.36. The analysis of the principal coordinates revealed that on average, 64% of the recurrent parent genome was present in the population. Together, the analyses allowed the selection of 3 individuals for the next backcross cycle (33BC1S1-18, 34BC1S1-16, and 37BC1S1-10). These individuals had a higher proportion of the recurrent parent and were grouped close to the recurrent parent in the cluster analysis.


Inhibition of Fat Accumulation by Hesperidin in Caenorhabditis elegans.
Hesperidin, abundant in citrus fruits, has a wide range of pharmacological effects, including anticarcinogenic, anti-inflammatory, antioxidative, radioprotective, and antiviral activities. However, relatively few studies on the effects of hesperidin on lipid metabolism have been reported. Here, using Caenorhaditis elegans as a model animal, we found that 100 μM hesperidin significantly decreased fat accumulation in both high-fat worms cultured in nematode growth medium containing 10 mM glucose (83.5 ± 1.2% versus control by Sudan Black B staining and 87.6 ± 2.0% versus control by Oil Red O staining; p < 0.001) and daf-2 mutant worms (87.8 ± 1.4% versus control by Oil Red O staining; p < 0.001). Furthermore, 50 μM hesperidin decreased the ratio of oleic acid/stearic acid (C18:1Δ9/C18:0) (p < 0.05), and supplementation of oleic acid could restore the inhibitory effect of hesperidin on fat accumulation. Hesperidin significantly downregulated the expression of stearoyl-CoA desaturase, fat-6, and fat-7 (p < 0.05), and mutation of fat-6 and fat-7 reversed fat accumulation inhibited by hesperidin. In addition, hesperidin decreased the expression of other genes involved in lipid metabolism, including pod-2, mdt-15, acs-2, and kat-1 (p < 0.05). These results suggested that hesperidin reduced fat accumulation by affecting several lipid metabolism pathways, such as fat-6 and fat-7. This study provided new insights into elucidating the mechanism underlying the regulation of lipid metabolism by hesperidin.


Tailgut cyst (retrorectal cystic hamartoma): report of a case and review of the literature.
Tailgut cysts are rare congenital lesions arising from remnants of normally regressing postanal primitive gut. They often present in middle-aged women with perirectal symptoms and a retrorectal multicystic mass. These cysts have occasionally shown malignant transformation. We report a case of a tailgut cyst occurring in a 25-year-old African-American female. The differential diagnosis of a retrorectal mass is briefly explored, and the etiology, diagnostic strategy, and surgical approach for tailgut cysts is examined. We also report an extensive literature review to examine clinical characteristics and surgical data for 43 cases of tailgut cysts spanning 16 years.


Effects of alcohol on biliary lipids in the presence of a chronic biliary fistula.
To investigate the effects of alcohol on bile volume and bile composition, dogs with a Thomas cannula and cannulated common ducts were given loading and maintenance doses of alcohol. Bile was analyzed for total bile salts, phospholipids and cholesterol. In dogs with partial interruption of the enterohepatic circulation, alcohol caused significant diminution of volume and outputs of bile salts and cholesterol. However, when a high bile flow was maintained by intravenous infusion of taurocholate sodium, the effects of alcohol on volume and total bile salts were no longer demonstrated. Fall in cholesterol output, nevertheless, persisted. These results show that alcohol causes significant changes in bile flow and biliary lipid composition and support the existence of a bile salt independent fraction of cholesterol secretion in the dog.


When Is Thyroidectomy the Right Choice? Comparison between Fine-Needle Aspiration and Final Histology in a Single Institution Experience.
The aim of this study was to compare SIAPEC-IAP-based cytological reports with their corresponding histological diagnoses to establish when thyroidectomy is the right choice in the management of thyroid diseases. This is a retrospective review of all the consecutive thyroidectomies/lobectomies performed at Maria Vittoria Hospital during the 10-year period between January 2005 and December 2015. Patients who underwent both fine-needle aspiration (FNA) and surgical procedures in our institution were included in the study. A total of 260 patients underwent both FNA and a thyroid surgical procedure at Maria Vittoria Hospital; 111 (42.69%) had a malignant histological report. The final cytological diagnosis was nondiagnostic (TIR-1) in 19 cases (7.31%), benign (TIR-2) in 83 cases (31.92%), indeterminate (TIR-3) in 96 cases (36.92%), suspicious for malignancy (TIR-4) in 22 cases (8.46%), and diagnostic for malignancy (TIR-5) in 40 cases (15.38%). Among the 96 cases with TIR-3 cytology, after the review, 44 (16.92%) were classified as TIR-3A and 52 (20%) as TIR-3B. The prevalence of malignancy among TIR-3A cases was 20.45% (9/44) and among TIR-3B cases 53.85% (28/52). The difference was statistically significant (p = 0.0007). Our data suggest that follow-up alone is not sufficient in TIR-3A patients given the high prevalence of malignancy within that diagnostic category (20.45%) and the low sensitivity (75.68%) and specificity (59.32%) in the distinction between TIR-3A and TIR-3B. Regarding patients with a multinodular goiter and TIR-2 at FNA, the surgical approach should not be excluded.


Glial cell line-derived neurotrophic factor promotes β-catenin phosphorylation and nuclear translocation in glioma cells.
Glial cell line-derived neurotrophic factor (GDNF) and N-cadherin interact to transduce intracellular signals. However, the specific molecular mechanisms of this interaction are unclear. This study attempted to detect changes in GDNF-induced β-catenin phosphorylation and nuclear translocation in C6 glioma cells. C6 glioma cells were treated with GDNF (70 ng/mL) and membrane and cytoplasmic proteins were extracted. A N-cadherin antibody was used for co-immunoprecipitation (co-IP). Western blot analysis using the co-IP protein was completed using antibodies for β-catenin, Src and β-actin. Immunocytochemistry was conducted with the same antibodies. To determine if Src induced phosphorylation of β-catenin Tyr-654, Western blot analysis was also performed on nuclear proteins from C6 cells treated with tyrosine kinase inhibitor PP2 using then p- β-catenin antibody. After induced by GDNF, C6 cell membrane β-catenin was phosphorylated at Tyr-654 and subsequently separated from the N-cadherin/β-catenin complex. Further study confirmed that the induction by GDNF significantly increased cytoplasmic and nuclear expression of phospho-β-catenin (Tyr-654) in C6 glioma cells. There was also an increase in the binding of non-receptor protein kinase Src with N-cadherin on the inner cell membrane surface. Src induced phosphorylation of β-catenin Tyr-654 induced by GDNF decreased significantly. The results of our study demonstrate that GDNF increases the intracellular phosphorylation level of β-catenin through N-cadherin/Src signaling, which subsequently stimulates the nuclear translocation of β-catenin. This study provides a theoretical basis for us to reveal the role of biological mechanisms on glioma cell by GDNF.


Synthesis, theoretical studies, and effect on the photosynthetic electron transport of trifluoromethyl arylamides.
The photosynthetic apparatus is targeted by various herbicides, including several amides such as diuron and linuron. Considering the need for the discovery of new active ingredients to cope with weed resistance, the synthesis of a series of trifluoromethyl aryl amides is herein described whose inhibitory properties were assessed in vitro on the photosynthetic electron transport chain, and in vivo on the growth of a model cyanobacterial strain. Theoretical studies were also carried out. Starting with 1-fluoro-2-nitro-4-(trifluoromethyl) benzene, the preparation of the amides was achieved via a three-step sequence, namely nucleophilic aromatic substitution, reduction with SnCl2 /HCl, and acylation reactions. The measurement of ferricyanide reduction by functionally intact spinach chloroplasts showed that several derivatives are capable of inhibiting the photosynthetic apparatus. The most active amides presented IC50 values close to 1 μmol L-1 , and showed the presence of a 4-bromophenyl group as a common structural feature. The addition of these brominated amides to the culture medium of a model cyanobacterial strain, Synechococcus elongatus PCC 6301, caused various degrees of growth inhibition. Theoretical studies (molecular modeling and quantitative structure-activity relationship) of all amides and their comparison with some known herbicides confirmed these experimental findings and provided more in-depth information about the possible molecular target of these compounds. Trifluoromethyl amides herein described, which were shown to act at the PSII level, may represent a novel scaffold to be exploited aiming at the development of new active ingredients for weed control. © 2017 Society of Chemical Industry.


Mutations in the small subunit of ribulose-1,5-bisphosphate carboxylase/ oxygenase increase the formation of the misfire product xylulose-1,5-bisphosphate.
The small subunit (S) increases the catalytic efficiency of ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 18.104.22.168) by stabilizing the active sites generated by four large subunit (L) dimers. This stabilization appears to be due to an influence of S on the reaction intermediate 2,3-enediol, which is formed after the abstraction of a proton from the substrate ribulose-1,5-bisphosphate. We tested the functional significance of residues that are conserved among most species in the carboxy-terminal part of S and analyzed their influence on the kinetic parameters of Synechococcus holoenzymes. The replacements in S (F92S, Q99G, and P108L) resulted in catalytic activities ranging from 95 to 43% of wild type. The specificity factors for the three mutant enzymes were little affected (90-96% of wild type), but Km(CO2) values increased 0.5- to 2-fold. Mutant enzymes with replacements Q99G and P108L showed increased mis-protonation, relative to carboxylation, of the 2,3-enediol intermediate, forming 2 to 3 times more xylulose-1,5-bisphosphate per ribulose-1,5-bisphosphate utilized than wild-type or F92S enzymes. The results suggest that specific alterations of the L/S interfaces and of the hydrophobic core of S are transmitted to the active site by long-range interactions. S interactions with L may restrict the flexibility of active-site residues in L.


Effects of sodium butyrate on X-ray and bleomycin-induced chromosome aberrations in human peripheral blood lymphocytes.
Peripheral blood lymphocytes from normal human volunteers or from Down syndrome patients were pre-treated with sodium butyrate (a compound which is known to induce structural modifications in the chromatin through hyperacetylation of nucleosomal core histones) and exposed to X-irradiation or treated with bleomycin in vitro in the G0 and/or G1 stage(s) of the cell cycle. The frequencies of chromosomal aberrations in the first mitosis after treatment were scored. The results show an enhancement in the yield of aberrations in the butyrate pre-treated groups. However, the absolute frequencies of chromosomal aberrations as well as the relative increases with butyrate pre-treatment varied between blood samples from different donors suggesting the existence of inter-individual variations. There is a parallelism between the effects of X-irradiation or of combined treatments in G0 and G1 stages and between effects observed in the X-ray and bleomycin series. The increase in the yields of chromosomal aberrations in butyrate-treated and X-irradiated lymphocytes (relative to those which received X-irradiation alone) is interpreted as a consequence of the inhibition of repair of DNA damage by butyrate.


Lipid synthesis and ultrastructure of isolated barley chloroplasts.
The cell organelle contents of chloroplast preparations made from barley leaves with salt and sucrose isolation media at pH 6 and 8 were determined and compared with the acetate incorporating activity of these preparations. A chloroplast preparation obtained with 0.5 m sucrose at pH 8 gave the highest number of intact chloroplasts (with envelope and stroma), the lowest number of contaminating mitochondria, and the highest activity in light dependent acetate incorporation into lipids. In the preparations observed, the light induced lipid synthesizing capacity correlates well with the percentage of intact chloroplasts. It is suggested that the intact chloroplasts are responsible for the light induced lipid synthesis of the preparations and that the synthesizing enzymes are localized in the chloroplast stroma. Acetate is mainly incorporated into palmitic and oleic acids. The low yield of intact chloroplasts and of light induced lipid synthesis in preparations isolated at pH 6 seem to result from the action of galactolipid lipase(s).


Syntheses and kinetic studies of cyclisation-based self-immolative spacers.
Kinetic analysis of the disassembly of self-immolative spacers based on cyclisation processes was performed. Five compounds were synthesized belonging to two different series, and their kinetic constants were determined. Electron-donating substituents gave a slight acceleration but the main effect was steric, and the Thorpe-Ingold effect was indeed particularly effective. Comparison with the self-immolative spacers based on elimination processes showed that cyclisations gave comparable or lower rate, but the corresponding spacers are more difficult to modulate.


Relationship between premature brain injury and multiple biomarkers in cord blood and amniotic fluid.
The purpose of this study is to investigate the relationship between premature brain injury and multiple biomarkers in cord blood and amniotic fluid, identify potential biomarkers for early monitoring of premature brain injury. One hundred and thirty cases of singleton premature infants with gestational age less than 34 weeks were evaluated. Based on brain imaging examination, all cases were divided into the brain injury group and the no brain injury group. Eleven biomarkers in cord blood and amniotic fluid were measured. Levels of interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), S100B, and activin A were higher in the brain injury group than those in the no brain injury group, in addition to S100B in amniotic fluid (p > .05), the differences were all statistically significant (p < .05). In the value of predicting brain injury, S100B had the highest sensitivity in cord blood, IL-1β had the highest sensitivity in amniotic fluid, and activin A owned the highest specificity both in cord blood and amniotic fluid. Levels of IL-4 and IL-17A were too low and had no predictive value to brain injury. A variety of biomarkers in umbilical blood and amniotic fluid can predict preterm brain injury.


Comparison of recapture patterns of marked and released Aedes vexans and Ae. melanimon (Diptera: Culicidae) in the Sacramento Valley of California.
Recapture patterns of Aedes vexans (Meigen) and Aedes melanimon Dyar were compared in a mark-release-recapture study conducted on the Colusa National Wildlife Refuge, Colusa County, California, from 15 August to 2 September 1988. The 2.0% recapture rate for Ae. vexans females was significantly greater than the 0.9% rate for Ae. melanimon females. Daily survivorship of 0.70 for Ae. vexans females was significantly lower than the 0.84 estimate for Ae. melanimon. The two species had different patterns of dispersal. On day 1, when the majority of marked females of both species were recaptured, the mean dispersal distance for Ae. vexans females was significantly greater than that for Ae. melanimon. The cumulative dispersal distance for Ae. vexans females decreased over the study period. In contrast, Ae. melanimon dispersal distances increased gradually over time.


MnTBAP treatment ameliorates aldosterone-induced renal injury by regulating mitochondrial dysfunction and NLRP3 inflammasome signalling.
Aldosterone plays an important role in the pathogenesis of chronic kidney disease (CKD) by directly damaging renal tubular cells. However, the treatment against aldosterone-induced renal injury is still limited. The present study was performed to examine the protection role of MnTBAP in modulating aldosterone-induced renal tubular injury both in vitro and vivo. MtD is induced by aldosterone in HK-2 cells, as evidenced by decreased expression of mtDNA and reduced mitochondrial membrane potential (MMP), which was markedly ameliorated by treatment with MnTBAP. HK-2 cells treated with MnTBAP demonstrated a reduction in cell apoptosis and improvements in cell phenotypic alterations following aldosterone challenge. Treatment with MnTBAP also inhibited the activation of the NLRP3 inflammasome and subsequent release of pro-inflammatory cytokines, IL-1β and IL-18. In addition, MnTBAP treatment of aldosterone-infused mice significantly improved mitochondrial morphology and function, suppressed the activation of NLRP3 inflammasome, reduced renal tubular cell apoptosis, decreased phenotypic alterations, and ameliorated renal apoptosis. We conclude that MnTBAP treatment ameliorates aldosterone-induced renal injury through regulating MtD and NLRP3 inflammsome signalling axis.


Regions of very low H3K27me3 partition the Drosophila genome into topological domains.
It is now well established that eukaryote genomes have a common architectural organization into topologically associated domains (TADs) and evidence is accumulating that this organization plays an important role in gene regulation. However, the mechanisms that partition the genome into TADs and the nature of domain boundaries are still poorly understood. We have investigated boundary regions in the Drosophila genome and find that they can be identified as domains of very low H3K27me3. The genome-wide H3K27me3 profile partitions into two states; very low H3K27me3 identifies Depleted (D) domains that contain housekeeping genes and their regulators such as the histone acetyltransferase-containing NSL complex, whereas domains containing moderate-to-high levels of H3K27me3 (Enriched or E domains) are associated with regulated genes, irrespective of whether they are active or inactive. The D domains correlate with the boundaries of TADs and are enriched in a subset of architectural proteins, particularly Chromator, BEAF-32, and Z4/Putzig. However, rather than being clustered at the borders of these domains, these proteins bind throughout the H3K27me3-depleted regions and are much more strongly associated with the transcription start sites of housekeeping genes than with the H3K27me3 domain boundaries. While we have not demonstrated causality, we suggest that the D domain chromatin state, characterised by very low or absent H3K27me3 and established by housekeeping gene regulators, acts to separate topological domains thereby setting up the domain architecture of the genome.


Redefinition of two little known mirine plant bug genera Babacoris and Paramiridius (Hemiptera: Heteroptera: Miridae: Mirinae).
A long neglected plant bug genus Babacoris Miyamoto, 1994 (Mirinae: Mirini), proposed for a single Taiwanese species, B. striatus Miyamoto, is redefined and redescribed as a valid genus, based on recent rediscovery of the type species from Hengchun, Taiwan; the neotype is designated for B. striatus. The genus is now presumed to be closely related to Paramiridius Miyamoto Yasunaga which also has been poorly known since the original description. A species recently described from Laos, Babacoris laomontanus (Oh, Yasunaga Lee) comb. n., is transferred from Paramiridius. An updated checklist of the tribe Mirini in Taiwan is incorporated, with proposition of a new combination, Adelphocorisella minutum (Poppius) comb. n., having been left in Megacoelum Fieber as incertae sedis.


Validation of the French Women Abuse Screening Tool to routinely identify intimate partner violence.
Health care professionals strongly underestimate the prevalence of intimate partner violence (IPV), and a few of them think that they screen and refer victims appropriately for assistance. The aim of this study was to cross-culturally validate a French version of the Woman Abuse Screening Tool (WAST). A multicenter case-control study was performed in the forensic medicine unit of the University Hospital and two offices of the women's rights association in France. Abused and non-abused women self-completed the WAST and a questionnaire assessing their level of comfort in responding to the WAST during the study and during a hypothetical consultation with a physician in primary care. We analyzed the psychometric properties and screening performance of the WAST. Respondent acceptability was very good, with response rates exceeding 95%. The WAST had a good internal consistency (Cronbach α coefficient = 0.95). Its screening performance with a cut-off score of 5 was excellent: area under the ROC curve was 0.99, sensitivity 97.7%, specificity 97.1%, positive predictive value 97.2% and negative predictive value 97.7%. The levels of comfort were significantly lower among abused compared with non-abused women. Both groups of women were more comfortable answering the WAST during the study than in a hypothetical consultation. The French version of the WAST was found to be a well-accepted and valid screening tool for routine use in IPV. It may help health care professionals to detect women experiencing abuse early and to refer them more quickly to specific assistance.


Hypotension in a woman with a metastatic dopamine-secreting carotid body tumor.
To describe a woman with metastatic carotid body tumor in whom hypotension occurred in the setting of exceedingly high plasma dopamine levels. We present a case report and review the literature on the topic of dopamine-secreting paraganglioma or pheochromocytoma. A previously healthy 40-year-old Asian woman noted difficulty with swallowing and hoarseness. No neck mass was visible, and she had no symptoms of catecholamine excess and no family history of endocrine disorders or malignant disease. Indirect laryngoscopy revealed a paralyzed left vocal cord and a nonulcerating mass in the left parapharyngeal space. An initial needle biopsy was interpreted as undifferentiated carcinoma. After a second biopsy, this mass was diagnosed as a neuroendocrine tumor, consistent with paraganglioma. The patient underwent surgical resection and radiation therapy (total dose, 40 Gy), after which she remained asymptomatic for 11 years. Then loss of weight, fatigue, nausea, and hypotensive episodes (blood pressures as low as 70/35 mm Hg) prompted whole-body imaging with bone scans, computed tomography, and magnetic resonance imaging, which disclosed several lesions in the liver, lungs, and spine, suggestive of metastatic disease. The adrenal glands were unremarkable. A metaiodobenzylguanidine scan with use of (131)I was negative. Liver biopsy of a hypodense lesion revealed a neuroendocrine tumor by histologic and immunohistochemical studies. Because of the patient's history, malignant paraganglioma was diagnosed. The tumor secreted predominantly dopamine at extraordinary levels (plasma concentration 27,942 pg/mL; normal, <30). The patient died before further treatment could be initiated. Carotid body tumors usually do not secrete catecholamines but frequently metastasize. During progression, these neuroendocrine tumors may become able to produce and secrete selected catecholamines such as dopamine. Dopamine can lower the blood pressure rather than causing hypertension, even though hypertension is one of the main symptoms of a pheochromocytoma.


Symptom Recognition and Diagnosis of Cerebral Palsy in Nepal.
Cerebral palsy (CP) is the most common movement disorder of childhood. Parents recognized the symptoms of CP at mean age of 13 months. However there was a mean delay of going to a doctor by 23 months and the mean age of diagnosis was 5½ years. Less than half of the CP children were diagnosed by a pediatrician and were receiving treatment methods with weak evidence base of efficacy. Delay in recognition of symptoms and help seeking due to lack of awareness and access to proper medical care and prevalent false beliefs were the leading reason for late diagnosis of CP in Nepal and thus children loose valuable time for intervention in their early developmental stage.


The effect of proteolytic activity of starter cultures on technologically important properties of yogurt.
In this study, the effects of proteolytic activity of yogurt starter bacteria on physicochemical and technological properties of yogurt were investigated. Moreover, impact of proteolytic activity and production of exopolysaccharide (EPS) on the performance of each strain were screened. In order to compare the textural properties of yogurt samples, four parameters were evaluated: syneresis, water-holding capacity, cohesiveness, and hardness. Results showed that strains with high proteolytic activity had lower acidifying activity during fermentation and storage. Samples containing EPS-producing starter cultures had low proteolytic activity except samples K, L, and M. These differences related to nature and characteristics of each strain. Counts of starter cultures in samples produced using strains with high proteolytic activity were higher than other samples. Textural analysis data showed significant differences (p < .05) among strains in the four tested parameters. Strains with high proteolytic activity showed lower texture properties than other samples. Evaluation of sensory characteristics also showed samples prepared using strains with low or medium proteolytic activity and produced with EPS-producing strains have higher overall acceptability than other samples. Accordingly, microbial, physicochemical, and sensory properties of produced yogurts confirm that proteolytic activity is one of the most effective factors in quality of product and performance of each strain.


[Findings of digital intensive or bed lung radiographs at the monitor vs. hard copy: a clinical ROC study].
45 bedside chest examinations acquired with storage phosphorus radiography, were displayed on a viewing box as single-format hard copies and at a high-performance digital reporting console. 6 observers performed an ROC study. For the pathologies under question, significantly better results were shown in monitor reporting due to pneumonic infiltration whereas no significant differences were found for pulmonary or mediastinal masses, or for pneumothoraces.


Characterization of Novel Paclitaxel Nanoparticles Prepared by Laser Irradiation.
The antitumor drug paclitaxel has low water solubility, and its bioavailability is limited by the dissolution rate. To overcome this low water solubility, the currently marketed drug, Taxol, is formulated in a vehicle including Cremophor EL and ethanol mixture (1/1, v/v). However, Cremophor EL has been shown to have serious adverse side effects, such as hypersensitivity reactions and neurotoxicity. Improving the solubility of paclitaxel makes it possible to reduce side effects and enhance drug efficacy during antitumor therapy. One way to improve the solubility of poorly soluble drugs is to decrease their particle size to the nano-range to increase the surface area and dissolution rate. In the present study, we aimed to develop a new method for paclitaxel nanoparticle production. Polymeric nanoparticles of paclitaxel were prepared by laser irradiation at 1064 nm, which is the wavelength in the near-IR region. The prepared nanoparticles had a mean size of 57.9 nm and were spherical in shape. X-ray powder diffraction analysis showed that paclitaxel in the nanoparticles was in an amorphous state. These results demonstrate that the preparation of nanoparticles by laser irradiation is effective in improving the solubility of paclitaxel. Furthermore, the nanoparticles had an equivalent efficacy to Taxol in cell growth inhibition against breast cancer MCF-7 cells and drug efficacy in MCF-7 tumor-bearing mice as determined using positron emission tomography. Our method for preparing paclitaxel nanoparticles may be more effective in treating tumors with fewer adverse side effects than conventional Taxol.


Microwave ablation of colorectal liver metastases: Impact of a 10-mm safety margin on local recurrence in a tertiary care hospital.
Microwave ablation (MWA) for colorectal liver metastasis (CLM) has been traditionally considered inferior to surgery due to the higher rate of local recurrence. The study investigated whether a safety margin of 10 mm can improve local control in patients undergoing surgical MWA. Surgical MWA was used to treat 53 lesions in 22 patients with CLM at our Institution from June 2012 to June 2017. The patients' mean age was 64.5 years, and the median size of the lesion was 16.5 mm (9-34 mm). MWA was associated with liver resection in 16 patients (72.7%). The median follow-up was 32.4 months. Univariate and multivariate analyses were performed to identify factors associated with tumor recurrence. Median ablation area was 36.6 mm2 (30-50 mm2). The complication rate was 22.7%. No local recurrence was observed during follow-up. Disease-free survival was 20 months (4.8-55.2 months). Univariate analysis revealed that the number of liver metastases and node-positive primary tumors were associated with tumor recurrence. Multivariate analysis revealed that node-positive primary tumor was the only factor significantly associated with tumor recurrence (p = 0.049; odds ratio, 12; 95% confidence interval, 1-143). When performed with a 10-mm safety margin, surgical MWA can lead to acceptable oncological outcomes with low morbidity. Therefore, it represents a good option in selected patients with CLM.