Coordinate regulation of metabolic enzyme encoding genes during cardiac development and following carvedilol therapy in spontaneously hypertensive rats.
Fuel substrate utilization is highly regulated during cardiac development and with the onset of cardiac hypertrophy. Glucose and lactate are the predominant fuel substrates utilized during cardiac development. Postnatally, a switch occurs so that fatty acids become the chief energy substrate in the nonfed adult mammalian heart. A reversion back towards fetal energy metabolism occurs with the development of cardiac hypertrophy. To evaluate the role of this substrate preference switch in the development of cardiac hypertrophy, the molecular regulation directing these switches is being explored. Thus, we have begun by defining the temporal expression patterns of genes encoding key rate-controlling enzymes directing major fuel substrate metabolism during cardiac development, with pressure-overload-induced cardiac hypertrophy, and following antihypertensive therapy in spontaneously hypertensive rats. The genes encoding the fatty acid and adult enriched rate-controlling glycolytic enzymes are expressed at low levels in the fetal and neonatal rat heart. The genes encoding these enzymes are significantly and coordinately upregulated (> or = 70%) in adult rat hearts compared to the fetal expression patterns. A reciprocal and coordinate downregulation (> or = 40% reduction) of the fatty acid and adult enriched glycolytic enzyme encoding genes are observed with the induction of pressure-overload-induced hypertrophy in spontaneously hypertensive rats compared to Wistar-Furth normotensive control rats. Antihypertensive therapy with carvedilol, a vasodilating alpha- and beta-adrenoreceptor antagonist, attenuates this reversion of the metabolic gene expression pattern towards fetal levels compared to placebo-treated littermate controls. This coordinate developmental and hypertrophy-induced regulation of genes that encode enzymes controlling both fatty acid and glycolytic catabolic pathways in the heart implicates potential mutual/overlapping regulatory signaling proteins within their gene regulatory programs. These gene regulatory pathways need to be identified and modulated in order to characterize the functional role of fuel substrate metabolism in cardiac development and with the induction of cardiac hypertrophy.


Military Family Physicians' Practices and Perceptions About Reproductive Health Services for Deploying Women.
Incomplete or inadequate provision of contraceptive services to servicewomen can have a profound impact on military health, readiness, and financial outcomes. This study examined the reproductive health practices and perceptions among family medicine physicians caring for servicewomen. We conducted an anonymous survey of 568 registered attendees at the March, 2018 Uniformed Services Academy of Family Physicians annual meeting. The response rate was 52.8% and 69% of responders met inclusion criteria. Our sample of family medicine physicians was 58.3% male and 85.3% Caucasian. In all, 18.3% were current residents, 42.9% graduated between 2008 and 2017, and 38.7% graduated before 2008. A previous deployment was reported by 55.1%.Among physicians with a deployment history, 20.8% reported difficulty prescribing contraception during deployment because they were unable to obtain a patient's desired method, 2.6% reported servicewomen not accessing contraception because of fear and stigma associated with sexual activity in the deployed setting, and 22.1% reported problems with both factors.Among physicians performing pre-deployment and other readiness visits for active duty servicewomen, 17.4% reported not discussing contraception at these encounters because of competing priorities and 1.5% because of ethical/religious concerns. Physicians who could offer more rapid access to subdermal implants (within 2 weeks) were more likely to discuss contraception (87.0% versus 64.7%, p = 0.005).When discussing the use of contraception in the deployed environment, 15.8% of physicians would not prescribe oral contraceptives, 12.3% would not prescribe intrauterine methods, and 14.3% would not prescribe subdermal implants. Physicians who previously deployed were more likely to report they would offer oral contraceptives (91% versus 75.0%, OR 3.4 [95% CI 1.44-8.48], p = 0.002) for women in the deployed setting compared to those who have not deployed. More timely (<2 weeks) access to subdermal implant insertion was associated with a greater rate of offering subdermal implants (91.9% versus 79.6%, p = 0.02).When discussing contraceptive options with all women, 27.3% of physicians do not prescribe emergency contraception because of training, ethical, and/or religious reasons. Some reported they would neither prescribe nor refer women for the following methods: emergency contraception (4.5%), intrauterine contraception (9.3%), and subdermal implants (7.3%). The results of this study support the need to develop a consistent, standardized, and evidence-based pre-deployment process and expanded resources in deployed environments for services related to the provision of reproductive health. Optimal strategies may aim to reduce barriers to care and enable the highest quality of health care through provider education, resource allocation, revised appointment times and content, and diversity among provider experience. Further research is needed to determine the influence of physician practice patterns on patient reproductive health outcomes and interventions to modify these practices to improve patient outcomes and military readiness.


Technical Note: A model-based sinogram correction for beam hardening artifact reduction in CT.
This study aims to propose a physics-based method of reducing beam-hardening artifacts induced by high-attenuation materials such as metal stents or other metallic implants. The proposed approach consists of deriving a sinogram inconsistency formula representing the energy dependence of the attenuation coefficient of high-attenuation materials. This inconsistency formula more accurately represents the inconsistencies of the sinogram than that of a previously reported formula (called the MAC-BC method). This is achieved by considering the properties of the high-attenuation materials, which include the materials' shapes and locations and their effects on the incident X-ray spectrum, including their attenuation coefficients. Numerical simulation and phantom experiment demonstrate that the modeling error of MAC-BC method are nearly completely removed by means of the proposed method. The proposed method reduces beam-hardening artifacts arising from high-attenuation materials by relaxing the assumptions of the MAC-BC method. In doing so, it outperforms the original MAC-BC method. Further research is required to address other potential sources of metal artifacts, such as photon starvation, scattering, and noise.


An innovative calibration based integral photography rendering algorithm for medical application and its evaluation.
Autostereoscopic has long been proposed to fulfill medical display in image-guided surgery and clinical education to provide more intuitive position information of clinical interest zone thus improving surgery safety and accuracy. As one category of flexible autostereoscopic 3D display, computer generated integral photography (CGIP) has been studied in medical application by many researches for its convenience and cost-efficiency. However, IP still suffers from inaccurate light field reconstruction, which limits its practicality in surgery. In this paper, we propose and apply a flexible fish-eye model based micro lens array (MLA) distortion calibration method and pre-distorted retracing rendering algorithm to render elemental image array (EIA) of CGIP. Furthermore, we also evaluate light field of the proposed algorithm in depth cue, and signal noise ratio of IP images by phantom experiment.


Cost-Effectiveness Analysis of Tyrosine Kinase Inhibitors for Patients with Advanced Gastrointestinal Stromal Tumors.
The management of advanced gastrointestinal stromal tumors (GISTs) has been modified considerably by the availability of costly tyrosine kinase inhibitors (TKIs); however, the best therapeutic sequence in terms of cost and effectiveness remains unknown. The aim of this study was to compare four potential strategies (reflecting the potential daily practice), each including imatinib 400 mg/day, as first-line treatment: S1 (imatinib400/best supportive care [BSC]); S2 (imatinib400/imatinib800/BSC); S3 (imatinib400/sunitinib/BSC); and S4 (imatinib400/imatinib800/sunitinib/BSC). A Markov model was developed with a hypothetical cohort of patients and a lifetime horizon. Transition probabilities were estimated from the results of clinical trials. The analysis was performed from the French payer perspective, and only direct medical costs were included. Clinical and economic parameters were discounted, and the robustness of results was assessed. The least costly and effective strategy was S1, at a cost of €65,744 for 32.9 life months (reference). S3 was the most cost-effective strategy, with an incremental cost-effectiveness ratio (ICER) of €48,277/life-year saved (LYS). S2 was dominated, and S4 yielded an ICER of €363,320/LYS compared with S3. Sensitivity analyses confirmed the robustness of these results; however, when taking into account a price reduction of 80 % for imatinib, S2 and S4 become the most cost-effective strategies. Our approach is innovative to the extent that our analysis takes into account the sequential application of TKIs. The results suggest that the S1 strategy is the best cost-effective strategy, but a price reduction of imatinib impacts on the results. This approach must continue, including new drugs and their impact on the quality of life of patients with advanced GISTs.


[Pectus excavatumn and carinatum in children and adolescents : what to say, what to do ?]
In children presenting with a pectus excavatum (PE) or pectus carinatum (PC) an underlying syndrome including Marfan's syndrome needs to be excluded. In adolescents, severe chest wall deformities may cause cardiac or respiratory problems but most commonly they have a psychological impact. The conservative treatment is a Vacuum Bell for PE, and a Dynamic Compression System for PC ; they play an increasing role in young patients. These devices need to be worn multiple hours per day for several months for an optimal result. Surgery is usually reserved for adolescents. The Nuss procedure for PE, also known as minimal invasive repair of PE offers excellent results. Sterno-chondro-plasty with stabilisation of the sternum with struts clipped to the ribs offers the same good results for PC. In our opinion, a multidisciplinary approach is preferable.


Equilibrium lines and barriers to phase transitions: the cubic diamond to beta-tin transition in Si from first principles.
The phase transition between the cubic diamond (cd) and beta-tin (β-Sn) phases of Si under pressure and the region of interaction of the two phases are studied by first-principles total energy calculations. For a non-vibrating crystal we determine the pressure of the thermodynamic phase transition p(t) = 96 kbar, the Gibbs free energy barrier at p(t) of ΔG = 19.6 mRyd/atom that stabilizes the phases against a phase transition and the finite pressure range in which both phases are stable. We show that the phases in that pressure range are completely described by three equilibrium lines of states along which the structure, the total energy E, the hydrostatic pressure p that would stabilize the structure and the values of G all vary. Two equilibrium lines describe the two phases (denoted the ph-eq line, ph is cd or β-Sn phase); a third line is a line of saddle points of G with respect to structure (denoted the sp-eq line) that forms a barrier of larger G against instability of the metastable ranges of the phase lines. An important conclusion is that the sp-eq line merges with the two ph-eq lines: one end of the sp-eq line merges with the cd-eq line at high pressure, the other end merges with the β-Sn-eq line at low pressure. The mergers end the barrier protecting the metastable ranges of the two ph-eq lines, hence the lines go unstable beyond the mergers. The mergers thus simplify the phase diagram by providing a natural termination to the stable parts of all metastable ranges of the ph-eq lines. Although 96 kbar is lower than the experimental transition pressure, we note that phonon pressure raises the observed transition pressure.


Experimental evidence for allosteric modifier saturation as predicted by the bi-substrate Hill equation.
The cooperative enzyme reaction rates predicted by the bi-substrate Hill equation and the bi-substrate Monod-Wyman-Changeux (MWC) equation when allosterically inhibited are compared in silico. Theoretically, the Hill equation predicts that when the maximum inhibitory effect at a certain substrate condition has been reached, an increase in allosteric inhibitor concentration will have no effect on reaction rate, that is the Hill equation shows allosteric inhibitor saturation. This saturating inhibitory effect is not present in the MWC equation. Experimental in vitro data for pyruvate kinase, a bi-substrate cooperative enzyme that is allosterically inhibited, are presented. This enzyme also shows inhibitor saturation, and therefore serves as experimental evidence that the bi-substrate Hill equation predicts more realistic allosteric inhibitor behaviour than the bi-substrate MWC equation.


An update on squamous carcinoma of the oral cavity, oropharynx, and maxillary sinus.
There are more than 45,000 new cancer cases involving the head and neck diagnosed each year within the United States. Squamous cell carcinoma accounts for the majority of cases, often occurring within the oral cavity and oropharynx. This article reviews current literature and various controversial topics involving the diagnosis and treatment strategies for patients with oral cavity/oropharyngeal cancers. Although not considered cancer within the oral cavity, maxillary sinus squamous cell carcinoma is discussed.


The accuracy of transcranial Doppler in the diagnosis of stenosis or occlusion of the terminal internal carotid artery.
Transcranial Doppler (TCD) can detect intracranial stenoses and occlusions that can help in the diagnosis and management of ischemic stroke. The accuracy parameters for lesions located in the terminal internal carotid artery (TICA) are less known, unlike other basal cerebral vessels. The authors studied consecutive patients referred for TCD who underwent contrast angiography or magnetic resonance angiography. They calculated the sensitivity, specificity, positive and negative predictive values (PPV and NPV), and likelihood ratios. Forty-three patients had TCD and angiography: mean age was 57 +/- 20 years, and 65% were men. Twenty-two patients were diagnosed with TICA stenosis or occlusion on TCD underwent angiography. Four patients had abnormal TCD findings that were not confirmed by angiography. Two of 21 patients with normal TCD showed moderate (< 50%) stenosis of the TICA and cavernous segment of the internal carotid artery at angiography. Accuracy parameters for TCD were as follows: sensitivity = 90% (confidence interval [CI], 63%-96%), specificity = 83% (CI, 61%-94%), PPV = 82%, NPV = 86%, positive likelihood ratio = 5, and negative likelihood ratio = 0.17. TCD is a sensitive screening tool for the lesions in the TICA. Specificity is likely affected by a wide spectrum of the stenosis severity shown at angiography and time lags between the studies.


Thy-1 (CD90) promotes bone formation and protects against obesity.
Osteoporosis and obesity result from disturbed osteogenic and adipogenic differentiation and present emerging challenges for our aging society. Because of the regulatory role of Thy-1 in mesenchyme-derived fibroblasts, we investigated the impact of Thy-1 expression on mesenchymal stem cell (MSC) fate between osteogenic and adipogenic differentiation and consequences for bone formation and adipose tissue development in vivo. MSCs from Thy-1-deficient mice have decreased osteoblast differentiation and increased adipogenic differentiation compared to MSCs from wild-type mice. Consistently, Thy-1-deficient mice exhibited decreased bone volume and bone formation rate with elevated cortical porosity, resulting in lower bone strength. In parallel, body weight, subcutaneous/epigonadal fat mass, and bone fat volume were increased. Thy-1 deficiency was accompanied by reduced expression of specific Wnt ligands with simultaneous increase of the Wnt inhibitors sclerostin and dickkopf-1 and an altered responsiveness to Wnt. We demonstrated that disturbed bone remodeling in osteoporosis and dysregulated adipose tissue accumulation in patients with obesity were mirrored by reduced serum Thy-1 concentrations. Our findings provide new insights into the mutual regulation of bone formation and obesity and open new perspectives to monitor and to interfere with the dysregulated balance of adipogenesis and osteogenesis in obesity and osteoporosis.


Non-pericyclic cycloaddition of gem-difluorosubstituted azomethine ylides to the C[double bond, length as m-dash]O bond: computational study and synthesis of fluorinated oxazole derivatives.
The cycloaddition of arenecarbaldehydes and α,α,α-trifluoroacetophenones with gem-difluoro-substituted azomethine ylides, generated from N-benzhydrylideneamines and difluorocarbene, occurs regioselectively to give, after hydrolysis, oxazolidin-4-ones. The primary cycloadducts of trifluoroacetophenones, 4,4-difluoro-5-trifluoromethyloxazolidine derivatives, are sufficiently stable to be isolated in reasonable to excellent yields. The results of correlation analysis and DFT calculations reveal a non-pericyclic step-wise mechanism of the reaction. The replacement of the two geminal hydrogen atoms in the azomethine ylide intermediate for fluorine atoms results in a dramatic change in the reaction mechanism from pericyclic to step-wise, proceeding via a zwitterion-like transition state in which no C-O bonding is observed.


Inhibitory mechanisms of two Uncaria tomentosa extracts affecting the Wnt-signaling pathway.
Uncaria tomentosa ("uña de gato"; "cat's claw"), a woody vine native to the Amazon rainforest, is commonly used in South American traditional medicine to treat a broad spectrum of diseases. Although recent studies have reported anti-inflammatory and anti-proliferative properties of different alkaloids extracted from this plant, the underlying molecular mechanisms of these effects have not been elucidated yet. Our study investigates the inhibitory mechanisms of Uncaria tomentosa extracts on the Wnt-signaling pathway, a central regulator of development and tissue homoeostasis. A modified cell-based luciferase assay for screening inhibitors of the Wnt-pathway was used for analysis. Three cancer cell lines displaying different levels of aberrant Wnt-signaling activity were transfected with Wnt-signaling responsive Tcf-reporter plasmids and treated with increasing concentrations of two Uncaria tomentosa bark extracts. Wnt-signaling activity was assessed by luciferase activity and by expression of Wnt-responsive target genes. We show that both, an aqueous and an alkaloid-enriched extract specifically inhibit Wnt-signaling activity in HeLa, HCT116 and SW480 cancer cells resulting in reduced expression of the Wnt-target gene: c-Myc. The alkaloid-enriched extract (B/S(rt)) was found to be more effective than the aqueous extract (B/W(37)). The strongest effect was observed in SW480 cells, displaying the highest endogenous Wnt-signaling activity. Downregulation of Wnt-signaling by a dominant negative-TCF-4 variant in non-cancer cells rendered the cells insensitive towards treatment with B/S(rt). B/Srt was less toxic in non-cancer cells than in cancer cells. Our data suggest that the broad spectrum of pharmacological action of Uncaria tomentosa involves inhibition of the Wnt-signaling pathway, downstream of beta-Catenin activity.


Religion, Health, and Life Satisfaction: Evidence from Australia.
In this article, we examine the influence of religion on health and life satisfaction while controlling for an extensive range of demographic characteristics and life conditions-marital satisfaction, job satisfaction, financial stress, and social resources-using data drawn from the Household, Income and Labour Dynamics in Australia (HILDA) survey. Our findings suggest that, on average, high levels of faith and attendance at religious services are associated with lower health. In contrast, however, we find no relationship between high levels of faith, attendance, and life satisfaction. Further research is required to unravel how faith and attendance influence health and life satisfaction.


Idiopathic pulmonary fibrosis will increase the risk of lung cancer.
To review the studies investigating the increased risk of lung cancer in patients with idiopathic pulmonary fibrosis (IPF). Data cited in this review were obtained mainly from PubMed and Medline from 1999 to 2013 and highly regarded older publications were also included. We identified, retrieved and reviewed the information on the frequency, risk factors, anatomical features, histological types, clinical manifestations, computed tomography findings and underlying mechanisms of lung cancer in IPF patients. The prevalence rates of lung cancer in patients with IPF (4.8% to 48%) are much higher than patients without IPF (2.0% to 6.4%). The risk factors for lung cancer in IPF include smoking, male gender, and age. Lung cancers often occur in the peripheral lung zones where fibrotic changes are predominant. Adenocarcinoma and squamous cell carcinoma are the most common types of lung cancer in patients with IPF. Radiologic features of these patients include peripherally located, ill-defined mass mimicking air-space disease. The underlying mechanisms of the development of lung cancer in patients with IPF have not been fully understood, but may include the inflammatory response, epithelial injury and/or abnormalities, aberrant fibroblast proliferation, epigenetic and genetic changes, reduced cell-to-cell communication, and activation of specific signaling pathways. These findings suggest that IPF is associated with increased lung cancer risk. It is necessary to raise the awareness of lung cancer risk in IPF patients among physicians and patients.


Adaptive evolution after gene duplication.
One of the two ribonuclease genes in a leaf-eating monkey has adapted to a role in the digestion of bacterial RNA. Following duplication of the ancestral ribonuclease gene, adaptation occurred through a series of changes in the amino acid sequence of the protein it encodes. This example is a good illustration of how specialization of protein function after gene duplication can be as source of novel protein functions.


Molecular detection and characterization of unclassified bovine enteric caliciviruses in South Korea.
The unclassified bovine enteric calicivirus (BEC) is a new bovine enteric calicivirus that is different from bovine norovirus, and causes diarrhea and pathologies in the small intestine of calves. This virus includes Nebraska (NB)- and Newbury agent 1 (NA1)-like strains. The prevalence of this BEC and its genetic characterization has only been reported in the UK and the USA. This study examined the prevalence and genetic diversity of these BECs in diarrheic calves in South Korea. Among a total of 645 diarrheic fecal specimens obtained from 629 cattle herds, these unclassified BECs were detected in 59 (9.1%) diarrheic fecal samples from 57 herds (9.3%) by either RT-PCR or nested PCR. Sequence and phylogenetic analyses of the partial RdRp gene showed that all the Korean BECs clustered together and were closely related to the NB-like viruses (80.9-88.1% nucleotide and 84.5-98.4% amino acid) but not to the NA1-like viruses (75.8-78.4% nucleotide and 79.7-82.8% amino acid). Although these viruses could not be classified into NA1- and NB-like viruses from the sequence and phylogenetic data of the entire capsid gene, all the Korean BECs clustered together on a branch separate from the other known BECs. These results show that these BEC infections are endemic in diarrheic calves in South Korea. The infecting strains are genetically closer to the NB-like viruses but have a distinct evolutionary pathway.


CCND1 rearrangements and cyclin D1 overexpression in renal oncocytomas: frequency, clinicopathologic features, and utility in differentiation from chromophobe renal cell carcinoma.
Renal oncocytoma is a benign tumor occurring singly or as multiple synchronous lesions. The histologic features of renal oncocytoma may overlap with those of chromophobe renal cell carcinoma. Chromosomal translocations involving the CCND1 locus at 11q13 and overexpression of cyclin D1 occur in a subset of renal oncocytomas. We evaluated a series of 63 renal oncocytomas and 36 chromophobe renal cell carcinomas and assessed the clinical features, cyclin D1 overexpression by immunohistochemistry, and alterations of the CCND1 gene by fluorescence in situ hybridization. All 36 chromophobe renal cell carcinomas were negative for cyclin D1 overexpression and alterations of CCND1. Of the 63 renal oncocytomas, 21 (33%) showed cyclin D1 overexpression. Of 21 renal oncocytomas with cyclin D1 overexpression, a CCND1 rearrangement was detected in 12 (57%). A CCND1 rearrangement was also identified in 1 (2%) of the 42 renal oncocytomas without cyclin D1 overexpression. Of 42 renal oncocytomas without cyclin D1 overexpression, 16 (38%) were from patients with multiple renal oncocytomas at nephrectomy. Of 21 renal oncocytomas with cyclin D1 overexpression, only 1 (5%) patient had multiple renal oncocytomas (P = .006). Of the 25 patients whose original tumor showed no cyclin D1 overexpression, 8 (32%) developed a subsequent renal oncocytoma. None of 15 patients whose original tumor showed cyclin D1 overexpression had a subsequent renal oncocytoma (P = .016). The findings of this study suggest that renal oncocytomas lacking cyclin D1 overexpression may be associated with the development of multiple renal oncocytomas and that these patients are more likely to develop subsequent renal oncocytomas suggesting the need for more frequent clinical for these patients and little need for follow-up in patients with renal oncocytomas overexpressing cyclin D1. The data also show that cyclin D1 overexpression and CCND1 rearrangements by fluorescence in situ hybridization are absent in chromophobe renal cell carcinoma, suggesting that these are useful when differentiating between renal oncocytoma and chromophobe renal cell carcinoma.


Heat shock protein inhibition is associated with activation of the unfolded protein response pathway in myeloma plasma cells.
Plasma cells producing high levels of paraprotein are dependent on the unfolded protein response (UPR) and chaperone proteins to ensure correct protein folding and cell survival. We hypothesized that disrupting client-chaperone interactions using heat shock protein 90 (Hsp90) inhibitors would result in an inability to handle immunoglobulin production with the induction of the UPR and myeloma cell death. To study this, myeloma cells were treated with Hsp90 inhibitors as well as known endoplasmic reticulum stress inducers and proteasome inhibitors. Treatment with thapsigargin and tunicamycin led to the activation of all 3 branches of the UPR, with early splicing of XBP1 indicative of IRE1 activation, upregulation of CHOP consistent with ER resident kinase (PERK) activation, and activating transcription factor 6 (ATF6) splicing. 17-AAG and radicicol also induced splicing of XBP1, with the induction of CHOP and activation of ATF6, whereas bortezomib resulted in the induction of CHOP and activation of ATF6 with minimal effects on XBP1. After treatment with all drugs, expression levels of the molecular chaperones BiP and GRP94 were increased. All drugs inhibited proliferation and induced cell death with activation of JNK and caspase cleavage. In conclusion, Hsp90 inhibitors induce myeloma cell death at least in part via endoplasmic reticulum stress and the UPR death pathway.


Application of Fast-Track Recovery Protocols in Single-Port Laparoscopic Surgery Versus Multiport Laparoscopic Surgery for Colon Resection.
The aim of this study is to analyze whether fast-track (FT) recovery protocols can be applied to single-port laparoscopic surgery for colon resection, as they are in multiport laparoscopic surgery. Retrospective study comparing single-port laparoscopic surgery (SP-FT) versus multiport laparoscopic surgery (MP-FT) for colon resection, and the applicability of our FT recovery protocol in all patients between 2013 and 2014. Variables evaluated were American Society of Anesthesiologists (ASA) score, tumor size, number of nodes, surgery performed, postoperative morbidity, and length of hospital stay. A total of 83 patients (28 SP-FT group and 55 MP-FT group) underwent FT recovery. The median age was 62 (11-85) years in SP-FT group and 72 (57-84) in MP-FT group. ASA score showed no significant difference (P = .973). The surgical procedures performed were as follows: SP-FT group 20 right hemicolectomy, 5 left hemicolectomy, and 3 subtotal colectomy and MP-FT group were 26 right hemicolectomy, 28 left hemicolectomy, and 1 subtotal colectomy. Mean operative time (minutes) was shorter in SP-FT group (151 ± 47.9 versus 182 ± 50.7), but no significant difference was observed. Regarding the tumor size (SP-FT 4.2 [2-7] cm versus MP-FT 4 [3-12] cm) and postoperative morbidity Clavien-Dindo ≥2 (SP-FT 10 patients versus MP-FT 20 patients), there were no significant differences (P = .535; P = .383). The median length of hospital stay was statistically significant: SP-FT 4.5 (3-53) days versus MP-FT 7 (4-33) days (P = .005). FT rehabilitation is safe and reproducible in single-port laparoscopic surgery for colon pathologies, with postoperative results comparable with conventional laparoscopic surgery.


Prevention of high-dose-methotrexate neurotoxicity by adequate folinic acid rescue is possible even after central nervous system irradiation.
Neurotoxicity, especially associated with therapy for acute lymphatic leukemia, has been attributed by many to the use of methotrexate (MTX). After radiotherapy this has been reported even more frequently but no explanation has been suggested apart from "a complex interaction". The hypothesis presented here is as follows: (1) Inadequate folinic acid rescue alone accounts for MTX-induced neurotoxicity. (2) Adequate folinic acid after MTX can prevent neurotoxicity. (3) Higher doses of MTX require a disproportionately higher dose of folinic acid than MTX to prevent toxicity. Doubling the dose of MTX has required tripling and quadrupling the folinic acid dose to prevent neurotoxicity. Assuming that central nervous system radiotherapy increases the cerebrospinal fluid levels of MTX and folinic acid proportionally, the folinic acid level may now not be enough to prevent neurotoxicity. This neurotoxicity occurs when MTX is given after (but not before) radiotherapy, and can be prevented by appropriate doses of folinic acid. (4) There is no evidence that within the dose range currently being used, the administration of larger quantities of folinic acid to prevent neurotoxicity compromises prognosis. This hypothesis is supported by a large amount of published data. Critical reanalysis of studies that ostensibly contradict parts of the hypothesis showed that they, in fact, support it.


An enzyme-linked immunosorbent assay (ELISA) for the detection of IgG and IgM anti-idiotypes directed against anti-HBs molecules.
A simple and specific enzyme-linked immunosorbent assay (ELISA) has been developed to detect circulating IgG and IgM anti-idiotypic antibodies directed against anti-HBs molecules using 96-well polyvinyl microtitre plates as the solid phase and HRPO-labelled goat anti-HBs as conjugate. Anti-idiotype reactions were observed in the supernatant portion after precipitation of immune complexes from sera with polyethylene glycol 6000 (PEG). Both IgG and IgM with anti-idiotype activity were detected concurrently in HBsAg-positive sera from HBV-infected patients and asymptomatic HBV carriers. Anti-idiotype activity was absent in HBsAg-negative sera from healthy persons, and in patients with non-A, non-B hepatitis and viral hepatitis A. However, such antibodies could be demonstrated in the sera of two out of eight HBsAg vaccine recipients negative for anti-HBs but in none of 11 recipients positive for anti-HBs after receiving a booster immunising dose of HBsAg vaccine. Those sera showing positive anti-idiotype reactions were free from rheumatoid factor and HBsAg/IgM or HBsAg/IgG complex activity. An analysis of anti-idiotype positive sera for anti-HBs, HBeAg and HBV-specific DNA-polymerase activity demonstrated these markers in 20%, 30% and 60% of cases, respectively. The presence of anti-idiotypic antibodies was presumed to permit a more active multiplication of hepatitis B virus.


The calibration of ultrasound transducers used to monitor motion of the residual femur within a trans-femoral socket during gait.
During gait the motion of the residual femur within a trans-femoral socket may be estimated using video recorded data from two ultrasound transducers attached to the socket wall. This paper reviews possible measurement errors and identifies the magnitude of the inaccuracies. Inaccuracies due to equipment limitations and those due to human error are identified and quantified. Ranges of flexion/extension and abduction/adduction of the residual femur within the socket during gait have been estimated with a cumulative level of inaccuracy of <1 degree.


Aneurysm surgery in Pakistan.
The purpose of this study was to find out the incidence and outcome of aneurysms being operated in Pakistan. The data was collected from various neurosurgical centers in Pakistan where facilities for aneurysm surgery are available. The population of Pakistan is 130 million, with 28 neurosurgical centers in the country but only eight are equipped with facilities for performing aneurysm surgery. The period of study extended from January 1994 to December 1996. During this period 350 patients presented with subarachnoid hemorrhage (SAH). Diagnosis of SAH was confirmed by computed tomography (CT) brain scan, diagnostic lumbar puncture was performed in few patients only where CT scan was negative. After angiography, 240 patients had intracranial aneurysms, 79 had arteriovenous malformations, and three had bled in brain tumors. Of the 240 patients with proven intracranial aneurysms, 122 (51%) were male and 118 (49%) were female. The mean age at presentation was 40.5 years with a range from 7 to 68 and a peak incidence between 41 and 50 years. Subarachnoid bleeding was noticed in 179 (74.6%) patients, 52 (21.7%) had SAH associated with intracerebral hemorrhage, and nine (4%) patients presented with the third cranial nerve palsy. Anterior communicating artery was the commonest site for aneurysms (120, 50%), followed by posterior communicating artery (46, 19%) and middle cerebral artery (45, 19%). Aneurysm surgery was performed in 134 (56%) patients. Operative mortality was about 10%. At 3 months follow up 49% patients were in grade I Glasgow Outcome Scale. We conclude that intracranial aneurysms occur with equal frequency in both sexes with a peak incidence between 41-50 years and anterior communicating artery is the commonest site. SAH is the most common mode of presentation and is still a neglected from of stroke in Pakistan. Medical specialists and family physicians require education for early diagnosis and timely referral of patients with SAH to neurosurgical centers.


[Development of New Biologics through Creation of a Functional Cytokine Mutant].
The clinical use of cytokines is fairly limited because of their characteristics of having significant bioactivity and low stability, although some are useful biopharmaceuticals, such as interferon. Cytokines, which are secreted from various immune cells, show many kinds of bioactivities including unexpected activities; thus it would be desirable to regulate cytokine activity. Recently, we have developed a new drug delivery system (DDS) to create structural mutant cytokines using a phage display system. This system can produce functional mutant proteins that can bind their objective targets specifically. In this study, tumor necrosis factor (TNF) was used as a model cytokine to create agonist and antagonist activities against two TNF receptors TNFR1 and TNFR2, respectively. We created a phage library expressing mutant TNF, where the amino acids in the binding interface between TNF and TNF receptors were alternately exchanged. Affinity panning was performed at the optimum condition and the bioactivities of these mutant TNFs were analyzed to obtain the objective agonists or antagonists. The pharmacological activity and toxicity of these engineered TNF mutants could indicate their potential use as novel biopharmaceutical agents.


A case of congenital soft tissue chondroma.
Soft tissue chondromas are rare benign tumors unrelated to bone that arise primarily in the distal extremities, especially in the fingers of middle-aged adults. We report an extremely rare case of congenital soft tissue chondroma, arising in the left great toe of a new-born infant. The present case is, to our knowledge, the first to be described in the dermatologic literature and the second reported case of congenital soft tissue chondroma.


Relationships between bone mass and dietary/lifestyle habits in Japanese women at 3-4 months postpartum.
The relationships between calcaneal bone mass and dietary/lifestyle habits in women at 3-4 months postpartum were examined in the context of osteoporosis prevention. Cross-sectional survey. We measured bone mass using calcaneal ultrasound in mothers who brought their 3- to 4-month-old babies to healthcare centers in Japan for health examination and administered a self-report questionnaire on physical characteristics and dietary/lifestyle habits to those who agreed to participate in the survey. Valid data were available for 1220 women (valid response rate, 97.5%). Based on their stiffness score, a measure of bone mass, 70.9% (n = 865) of the participants were classified as 'no apparent abnormality (stiffness score ≥78.8)' (low-risk group), 18.2% (n = 222) as 'guidance required (≥70.1-<78.8)' (intermediate-risk group), and 10.9% (n = 133) as 'complete examination required (<70.1)' (high-risk group), according to the criteria for osteoporosis screening test results. The percentage of individuals with a history of fracture was higher in the guidance required/complete examination required than in the no apparent abnormality group (P = 0.016). The analysis of relationships between the consumption frequency of certain foods, such as calcium-rich foodstuffs, and bone mass found that women who reported lower frequencies of milk and dark-colored (beta-carotene rich) vegetables for breakfast consumption had a significantly lower bone mass than those who consumed these foods more often. Furthermore, the guidance required/complete examination required group had a significantly lower calcium intake than the no apparent abnormality group (P = 0.022). These results indicate the need to provide postpartum women with dietary education programs to promote healthy eating habits, such as increased consumption of calcium-rich foods, and prevent osteoporosis.


Carcinoma of the nasopharynx: factors affecting prognosis.
This is a retrospective analysis of 143 patients with histologically confirmed epidermoid carcinoma of the nasopharynx treated with definitive irradiation. Patients were treated with a combination of Cobalt-60, 4 to 6 MV X rays, and 18 to 25 MV X rays to the primary tumor and the upper necks, excluding the spinal cord at 4000 to 4500 cGy to total doses of 6000 to 7000 cGy. At 10 years the actuarial primary tumor failure rate was 15% in T1, 25% in T2, 33% in T3, and 60% in T4 lesions. The corresponding failure rate in the neck was 18% for N0, 14% for N1, and 33% for N2 and N3 lymphadenopathy. The incidence of distant metastasis was related to the stage of the cervical lymphadenopathy: 16% in patients with N0-N1 nodes compared with 40% in the N2-3 node group. The actuarial 10-year disease-free survival rate was 55% to 60% for T1-3N0-1 tumors, 45% for T1-3N2-3 tumors, 35% for T4N0-1, and 20% for T4N2-3 lesions. The overall 10-year survival rate was about 40% for patients with T1-2N0-1 tumors, 30% for those with T3 any N stage tumors, and only 10% for the patients with T4 lesions. Multivariate analysis showed that tumor stage and histological type, cranial nerve involvement, patient age, and doses of irradiation to the nasopharynx were significant prognostic factors for local/regional tumor control. Increasing doses of irradiation resulted in nasopharynx tumor control in 80% of the patients receiving 6600 to 7000 cGy and 100% of those receiving over 7000 cGy in the T1, T2, and T3 tumors. However, the tumor control rate did not rise above 55% even for doses over 7000 cGy in the T4 lesions. Local tumor control was higher in patients who had simulation (55/78 = 71%) compared with those on whom simulation was not performed (34/61 = 56%) (p = 0.10). Moreover, patients with more than 75% of the reviewed films judged as adequate had 69% primary tumor control (66/96) compared with 53% (23/43) for those with fewer than 75% adequate portal films (p = 0.07).


Hereditary cerebellar degeneration in Scottish terriers.
Hereditary cerebellar degeneration is described in several dog breeds. This heterogeneous group of diseases causes cerebellar ataxia associated with cerebellar cortical degeneration. To report the clinical and histopathological features, and describe the mode of inheritance of hereditary cerebellar degeneration in Scottish Terriers. Sixty-two affected dogs recruited through the Scottish Terrier Club of America. Prospective, observational study: Owners of affected dogs were contacted for a description of clinical signs, age of onset, and disease progression. Medical records, videotapes of gait, and brain imaging were evaluated. When possible, necropsy was performed and the brain examined histopathologically. Prevalence of the disease was estimated and a pedigree analysis was performed to determine mode of inheritance. Gait abnormalities were noted in the 1st year of life in 76% of dogs, and progressed slowly; only 1 of 27 dogs dead at time of writing was euthanized because of cerebellar degeneration. Clinical signs included wide based stance, dysmetria, intention tremor, and difficulty negotiating stairs and running. Cerebellar atrophy was detected on magnetic resonance imaging. On histopathological examination, there was segmental loss of Purkinje neurons, thinning of molecular and granular layers, and polyglucosan bodies in the molecular layer. Prevalence of disease was estimated at 1 in 1,335 American Kennel Club registered Scottish Terriers. Genetic analysis results are consistent with an autosomal recessive mode of inheritance. A hereditary cerebellar degenerative disorder with a relatively mild phenotype has emerged in the Scottish Terrier. Genetic studies are needed.


Improved accuracy of the transcriptional profiling method of age grading in Aedes aegypti mosquitoes under laboratory and semi-field cage conditions and in the presence of Wolbachia infection.
Transcriptional profiling is an effective method of predicting age in the mosquito Aedes aegypti in the laboratory, however, its effectiveness is limited to younger mosquitoes. To address this we used a microarray to identify new gene candidates that show significant expression changes in older mosquitoes. These genes were then used to create a revised model, which upon evaluation in both laboratory and semi-field conditions, proved to have improved accuracy overall and for older mosquitoes. In association with the development of symbiont-based control strategies for Ae. aegypti, we also tested the model's accuracy for Wolbachia-infected mosquitoes and found no decline in performance. Our findings suggest that the new model is a robust and powerful tool for age determination in Australian Ae. aegypti populations.


Regulation of p63 function by Mdm2 and MdmX.
p63, a p53-related protein, has been shown to activate p53-responsive genes and induce apoptosis in certain cell types. In this study, we examined the effects of Mdm2 and MdmX proteins on p63 transactivation, apoptosis, and protein levels. The isoforms of p63 most structurally similar to p53, p63gamma (p51A) and p63alpha (p51B), were chosen for study. Our results confirm earlier reports demonstrating that although both p63 isoforms can transactivate p53-responsive promoters and induce apoptosis, p63gamma has a stronger transactivation potential and is a more potent inducer of apoptosis than is p63alpha. In addition, both Mdm2 and MdmX were able to inhibit the transactivation induced by p63gamma and p63alpha. However, only Mdm2 overexpression led to a detectable decrease in p63-induced apoptosis. Although Mdm2 binding to p53 triggers ubiquitin-mediated proteosome degradation, p63 protein levels were unaltered by association with either Mdm2 or MdmX. Finally, immunofluorescence experiments showed that both p63 isoforms were localized in the nucleus and could be exported when coexpressed with Mdm2 but not with MdmX. These findings suggest that both Mdm2 and MdmX can downregulate p63 transactivation potential; however, only Mdm2 is capable of inhibiting the apoptotic function of p63 by removing it from the nucleus.


Colorectal Cancer Screening.
Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality in the Western world. Advances in surgical and medical management have led to improved outcomes; however, the prognosis of CRC is often poor when detected at a symptomatic stage. Most cases of CRC develop over years from removable well-defined precursor lesions, and asymptomatic, curable disease may be detected by convenient noninvasive tests. These features make CRC a suitable candidate for screening, and several options are available. This article outlines the evidence for established CRC screening tests along with a discussion on newer tests and ongoing research.


Acute splenic complications and implications of splenectomy in hemoglobin SC disease.
Splenectomy indications and outcome were evaluated in 124 adults with hemoglobin SC disease (Hb SC). Twelve patients (9.6%) required splenectomy. There was a significant difference between the splenectomy group and the non-splenectomy group, respectively, regarding Hb levels (median 7.2 g/dL vs. 12.5 g/dL, P < 0.0001), platelet counts (median 146 x 10(6)/L vs. 275 x 10(6)/L, P = 0.031), palpable spleen rate (66% vs. 16%, P = 0.0003%), acute chest syndrome frequency (75% vs. 12%P = 0.0004) and cholecystectomy rate (66% vs. 13%, P = 0.0004). No significant morbidity or mortality occurred postsplenectomy. There is a subgroup of Hb SC patients requiring splenectomy, in which splenectomy is effective. Although it appears to be safe regarding short-term complications of surgery, long-term adverse effects such as infections have to be evaluated cautiously.


Putting down the scalpel in rectal cancer management - a historical perspective.
The surgical management of rectal cancer has evolved from a disease without any possibility of cure in the early 1700s where surgical management consisted of the palliative drainage of disease related abscesses to the present day where surgical cure is not only possible but also possible with sphincter or even organ preservation. Prof Habr-Gama's lecture describes the evolution of the surgical management of rectal cancer and the current focus on organ preservation.


Amino acids in spinal dorsal horn of patients during surgery for neuropathic pain or spasticity.
A specific microdialysis probe combined with high performance liquid chromatography analysis was used to compare the basal levels of extracellular amino acids (AAs) in the dorsal horn (DH) between two groups of patients undergoing spinal surgery for the treatment of peripheral neuropathic pain (n = 5) or disabling spasticity (n = 5). A stabilized concentration was reached in the dialysates 45 min after probe implantation for excitatory AAs (glutamate and aspartate) and inhibitory AAs (GABA and glycine). A significant increase in the ratios aspartate/GABA and aspartate/glycine was found in the group of patients suffering from neuropathic pain. This study shows the feasibility of a microdialysis investigation in the DH of patients during a neurosurgical operation and supports in humans the hypothesis of an imbalance between excitatory AAs and inhibitory AAs within the DH in neuropathic pain states, as suggested by previous animal studies.


[Effect of microenvironment on the conformation of m-cholinoreceptors in brain synaptic membranes].
Sensitivity of m-cholinergic receptor of synaptic membranes to SH-reagents (PChMB and NEM) was compared before and after its solubilization with detergents. PChMB blocked specific binding of m-antagonist QNB to both forms of the receptor in equal extent, while NEM was effective only after solubilization. After the membranes modification with butanol or arachidonic acid the membrane-bound receptor became sensitive to NEM. The solubilized receptor lost its ability to allosteric inhibition by acid. It is suggested that the receptor conformation is under the control of the membrane microenvironment.


Phenazopyridine associated acute interstitial nephritis and review of literature.
Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange discoloration of urine, methemoglobinemia, yellowish skin discoloration, hepatitis and acute renal failure. Various case reports with phenazopyridine associated acute renal failure secondary to acute tubular necrosis have been reported in the literature. Acute kidney injury in these patients is caused by either direct injury to renal tubular epithelial cells or secondary to pigment induced nephropathy from hemolytic anemia. Hypoxic injury from phenazopyridine-induced methemoglobinemia has been well documented. We report a case of biopsy proven acute interstitial nephritis, associated with therapeutic doses of phenazopyridine without any evidence of methemoglobinemia or other mechanism of renal injury. Clinicians should be aware of the toxicity of this commonly used drug and should look closely for signs of renal insufficiency. Identifying and stopping the offending medication stays as the first step, but recent studies indicate that early steroid administration improves renal recovery, as well as decreasing the risk of progression to chronic kidney disease with fibrosis and consequent permanent renal damage.


Circular dichroism studies of 6-N-methylated adenylyladenosine and adenylyluridine and their parent compounds. Thermodynamics of stacking.
The temperature dependence of the circular dichroism spectra of two adenylyladenosine and three adenylyluridine dinucleotides in aqueous solution have been studied. The effect of methylation of the N-6 position of the adenylyl moieties on the thermodynamic parameters of the stacking equilibrium was investigated applying a two-state model for the thermodynamic analysis of the experimental data. It is shown that the methylated compounds allow a more accurate analysis of the data and that methylation stabilizes the stacking interaction by a relative decrease of the entropy of unstacking.


Gamma-glutamyltransferase-friend or foe within?
Gamma-glutamyltransferase (GGT) is a liver enzyme, which is located on the plasma membranes of most cells and organ tissues, but more commonly in hepatocytes, and is routinely used in clinical practice to help indicate liver injury and as a marker of excessive alcohol consumption. Among the liver enzymes, important advances have especially been made in understanding the physiological functions of GGT. The primary role of GGT is the extracellular catabolism of glutathione, the major thiol antioxidant in mammalian cells, which plays a relevant role in protecting cells against oxidants produced during normal metabolism; GGT, therefore, plays an important role in cellular defence. Beyond its physiological functions, circulating serum GGT has been linked to a remarkable array of chronic conditions and diseases, which include nonalcoholic fatty liver disease, vascular and nonvascular diseases and mortality outcomes. This review summarizes the available epidemiological and genetic evidence for the associations between GGT and these adverse outcomes, the postulated biologic mechanisms underlying these associations, outlines areas of outstanding uncertainty and the implications for clinical practice.


Massive pulmonary embolism with liver injury associated with chest compressions during cardiac resuscitation.
A 34-year-old man was admitted to our hospital because of sudden respiratory failure caused by massive pulmonary embolism. After arrival in the hospital, the patient experienced cardiopulmonary arrest, and we promptly initiated percutaneous cardiopulmonary support, in addition to sternal compressions for cardiopulmonary resuscitation. Computed tomography revealed massive pulmonary embolisms and intraperitoneal bleeding due to liver injury. After interventional hemostasis of the hepatic arteries, we performed emergent pulmonary embolectomy and hemostasis of the liver with gauze packing. Absence of further intraperitoneal bleeding was confirmed 2 days later on a second look. The patient was discharged 2 month later without neurologic sequelae.


Effect of chronic amiodarone therapy on excitable gap during typical human atrial flutter.
Class I antiarrhythmic drugs increase duration of the excitable gap (EG) during typical atrial flutter whereas intravenous class III drugs decrease the EG. The effect of chronic oral amiodarone therapy on the EG is unknown. EG was prospectively determined by introducing a premature stimulus and analyzing the response pattern during typical atrial flutter in 30 patients without antiarrhythmic drugs and in 20 patients under chronic oral amiodarone therapy. EG was calculated by the difference between the longest coupling interval leading to resetting and the effective atrial refractory period (EARP). A fully EG was defined by the portion of EG where the response curve of the return cycles was flat. A partially EG was defined by the portion of EG where the return cycle increases while coupling interval decreases. A resetting response curve was constructed by plotting the duration of the return cycle against the value of the coupling interval. Cycle length (CL; 222 +/- 17 vs 267 +/- 20 msec, P < 0.0001), EARP (128 +/- 16 vs 152 +/- 18 msec, P < 0.0001), and EG (54 +/- 19 vs 70 +/- 21 msec, P = 0.01) were significantly longer in patients taking amiodarone than in controls. Compared to CL, the relative part of the EARP (57 +/- 7 vs 57 +/- 6%, P = 0.96) and EG (24 +/- 7 vs 26 +/- 8%, P = 0.41) were comparable in both groups. The fully EG was larger in patients under chronic amiodarone therapy than in controls (39 +/- 21 vs 26 +/- 20 msec, P = 0.03). Neither duration of the partially EG (28 +/- 15 vs 31 +/- 15 msec, P = 0.42) nor slope of the ascending portion of the resetting response curve (1.15 +/- 0.5 vs 1.13 +/- 0.4 msec/msec, P = 0.71) differed between the two groups. EG in patients under chronic amiodarone therapy is significantly larger than in controls, mainly because of a longer fully EG. This observation may be explained by opposite effects on conduction velocity and refractoriness.


Exercise-induced second-degree atrioventricular block.
In this report we describe the case of a 56-year-old woman with normal 1:1 AV conduction at rest who developed 2:1 AV block during treadmill exercise testing. Electrophysiological study documented 2:1 AV block proximal to the His bundle with reappearance of 1:1 AV conduction at a higher pacing atrial rate. A gap phenomenon involving a proximal and distal part of the AV node may be a likely explanation of paradoxical AV conduction in our case.


Efficacy of cypermethrin for the control of mosquito larvae and pupae, and impact on non-target organisms, including fish.
In laboratory tests, cypermethrin was highly toxic to mosquito larvae and pupae. It was more toxic at low temperatures after a 24 hr exposure. Larvae of Aedes stimulans were less susceptible than Culex restuans. Technical cypermethrin was more toxic than an emulsifiable concentrate formulation. In outdoor simulated pools cypermethrin 40% EC was consistently effective against larvae and pupae of Ae. stimulans at 10 g AI/ha and Culex spp. at 50 g AI/ha. When stickleback fish were tested, no mortality occurred at the lowest effective dosage in each trial. The residual toxicity of cypermethrin increased with dosage and was much higher in a test at 8 degrees C than at 20 degrees C. In natural snowmelt pools, cypermethrin at 20 g AI/ha provided 92-100% control of Aedes spp. larvae and pupae by 7 days after treatment. Non-target amphipod, anostracan, cladoceran and insect populations were usually reduced 80-100% while copepods, ostracods and hydracarinid mites were generally less affected. No significant mortality of caged stickleback fish occurred in these pools.


[Incorrect use and complications of negative pressure therapy].
The specific training of teams as recommended by the French National Authority for Health in its document drawn up in January 2011 relating to the use of negative pressure therapy (NPT) is unfortunately rarely effective. The recognition of expertise in wounds and cicatrisation, the constitution of a multidisciplinary network as well as the use of information and communication technologies in the field of healthcare can provide nurses with the teaching and supervision required to master this technique.


Population genetics of cis-regulatory sequences that operate during embryonic development in the sea urchin Strongylocentrotus purpuratus.
Despite the fact that noncoding sequences comprise a substantial fraction of functional sites within all genomes, the evolutionary mechanisms that operate on genetic variation within regulatory elements remain poorly understood. In this study, we examine the population genetics of the core, upstream cis-regulatory regions of eight genes (AN, CyIIa, CyIIIa, Endo16, FoxB, HE, SM30 a, and SM50) that function during the early development of the purple sea urchin, Strongylocentrotus purpuratus. Quantitative and qualitative measures of segregating variation are not conspicuously different between cis-regulatory and closely linked "proxy neutral" noncoding regions containing no known functional sites. Length and compound mutations are common in noncoding sequences; conventional descriptive statistics ignore such mutations, under-representing true genetic variation by approximately 28% for these loci in this population. Patterns of variation in the cis-regulatory regions of six of the genes examined (CyIIa, CyIIIa, Endo16, FoxB, AN, and HE) are consistent with directional selection. Genetic variation within annotated transcription factor binding sites is comparable to, and frequently greater than, that of surrounding sequences. Comparisons of two paralog pairs (CyIIa/CyIIIa and AN/HE) suggest that distinct evolutionary processes have operated on their cis-regulatory regions following gene duplication. Together, these analyses provide a detailed view of the evolutionary mechanisms operating on noncoding sequences within a natural population, and underscore how little is known about how these processes operate on cis-regulatory sequences.


A chemical analysis of the clogging process of polymeric biliary endoprostheses.
Insertion of polymeric biliary endoprostheses is widely used as a method of palliation of malignant strictures of the biliary tree. Despite the success of this technique, clogging of the stent in a few months is still an existing problem. The aim of the present study has been to investigate the causes of the obstruction, considering both the stent material and the composition of the obstructing deposit. 16 ready-to-implant and 33 occluded retrieved prostheses were analysed by ATR-FTIR spectroscopy. The clogging sludge was recovered and studied by FTIR spectroscopy and pyrolysis derivatisation/gas chromatography/mass spectrometry (Py/GC/MS). The results of the analyses showed that the deposit was mainly formed by proteins, bilirubin, calcium palmitate and bilirubinate, cholesterol and its fatty acids salts. It was found that approximately 50% of the examined ready-to-implant samples were made of ethylene-vinylacetate copolymer (EVA) instead of polyethylene (PE), as was stated in the producer declaration. Moreover, 94% of the retrieved samples were found to be made of EVA indicating that this material is less suitable than PE for this application. All retrieved PE and EVA stents showed a protein-like black layer strongly absorbed on the surface.


Noninvasive detection of nonsteroidal anti-inflammatory drug-induced gastropathy in dogs.
Nonsteroidal anti-inflammatory drugs (NSAID) are widely used for treatment of people and animals. Their use is limited by frequent side effects commonly involving the gastrointestinal tract, most important of which is development of ulcerating lesions principally in the stomach. Unfortunately, presence of such lesions is often unsuspected because clinical signs may be overlooked until a complication develops. We reported that such damage can be detected by measuring the increase in gastric permeability that is a hallmark of this condition. Sucrose is a novel probe molecule for determination of site-specific gastric permeability. As a disaccharide, it is large enough to be effectively excluded by the intact gastric epithelium, and because it is rapidly digested within the small intestine, absorption of the intact molecule implies damage proximal to this site. Recently, we found that increased sucrose permeability is useful in predicting presence of endoscopically relevant gastric damage in people. We extended these results to the detection of NSAID-induced gastropathy in dogs. Dogs treated with aspirin developed NSAID-induced gastropathy (including gastric ulceration), and the degree of endoscopically detectable damage correlated well with sucrose permeability. Furthermore, healing of these lesions could also be monitored by sequential measurements of sucrose permeability. Sucrose permeability decreased more rapidly than the disappearance of gastric ulcers, suggesting that this technique is more sensitive to generalized mucosal damage than is the presence of discrete, endoscopically visible ulceration. This was confirmed by creating artificial ulcers in the antrum and observing that sucrose permeability was not increased in the setting.(ABSTRACT TRUNCATED AT 250 WORDS)


Vogt-Koyanagi-Harada Syndrome in a Group of Patients in Two Ophthalmology Referral Centers in Bogotá, Colombia.
To describe the clinical presentation of Vogt-Koyanagi-Harada (VKH) syndrome in a group of patients in Colombia. Retrospective review of 2638 medical records of patients with uveitis in two centers during 17 years. A total of 25 patients with uveitis were diagnosed with VKH syndrome (0.95%), 23 patients were included in the data analysis (0.87%), 78.3% females, and mean age of diagnosis was 37 years (SD ± 29). Main complaints: blurred vision (87%), headaches (47.8%), tinnitus (26.1%), and hearing impairments (21.7%). Ophthalmic findings: bilateral serous retinal detachment (73.9%) and non-granulomatous uveitis (52.3%). Most of the patients were diagnosed with probable disease (56.5%). Mean duration of follow-up was 14 months; disease relapse was encountered in 26% of patients despite treatment. Patients in Colombia with VKH had clinical features similar to those reported in other Hispanic populations, except for the non-granulomatous uveitis. This disease may be considered as having variation of clinical manifestations across population groups.


The structural identification of a methyl analog of methaqualone via 2-dimensional NMR techniques.
A submission to the Drug Enforcement Administration North Central Laboratory of a substance believed to be a structural analog of methaqualone hydrochloride precipitated an interest in being able to obtain a rapid and positive identification of such compounds. Both mass spectrometry and proton NMR spectroscopy (1-dimensional) provided evidence to suggest that the structural analog possessed a second methyl group in the molecule, relative to methaqualone, and that the methyl group was attached to the existing methyl-substituted phenyl ring. By application of proton 2-dimensional (2-D) NMR techniques, specifically the homonuclear shift correlation spectroscopy (COSY) and 2-D NOE (NOESY), the precise location of the methyl group in this unknown methaqualone analog was established and shown to have the structure 2.


Muscle pain in neuromuscular disorders and primary fibromyalgia.
Muscle fibre degeneration and regeneration, inflammation in intramuscular connective tissue and hypoxia in resting muscle are not necessarily associated with pain. However, when sustained or dynamic muscle contractions are performed in an ischaemic muscle, severe pain develops. In the chronic muscle pain syndrome called fibromyalgia (or fibrositis) the most likely cause of the pain is a combination of muscle tension and muscle hypoxia. This conclusion is supported by the finding of a pathological distribution of tissue oxygen tension in painful muscles and a subjective feeling of muscle tension and muscle stiffness in the majority of patients. A decrease in high energy phosphates is found in biopsies from painful muscle. The most characteristic morphological finding is the so called ragged red fibre, which is a finding that can been seen in mitochondrial disorders. The morphological and chemical findings are possibly a consequence of a long standing hypoxia. The possibility that activity in muscle sympathetic nerves is important for the development of chronic muscle pain is discussed.


[Chemoembolization of liver tumors (VX-2) using lyophilized Spherex].
Chemoembolisation is a new promising approach. Until now no standardized procedures exist for the production of the embolisate-cytostatics mixture. A main technical problem when doing chemoembolisation is the proof of the complete peripheral vascular occlusion. By using lyophilized Spherex and cytostatics, diluted in x-ray contrast media, frozen pictures can be obtained and the complete proof of the embolisation is possible. Therefore the conventional x-ray examination can be used to monitor the embolisation treatment instead of the much more sophisticated DSA technique.


Titanium dioxide nanoparticles relieve biochemical dysfunctions of fifth-instar larvae of silkworms following exposure to phoxim insecticide.
Phoxim insecticide is widely used in agriculture, which is toxic to insect pests and nontarget organisms. The phoxim poisoning is hard to prevent for silkworms. TiO(2) NPs have been widely applied in whitening, brightening foods, toothpaste or sunscreens, and orally-administered drugs. However, whether TiO(2) NPs can increase resistance of silkworm to phoxim poisoning has not been reported. The results demonstrated that added TiO(2) NPs significantly decreased reduction of protein, glucose and pyruvate contents, lactate dehydrogenase, succinate dehydrogenase and malate dehydrogenase activities, and attenuated increases of free amino acids, urea, uric acid and lactate levels, activities of protease, alanine aminotransferase and aspartate aminotransferase in the hemolymph of silkworms caused by phoxim exposure. From the present study, it is clearly evident that added TiO(2) NPs may relieve toxic impacts of phoxim insecticide on silkworm metabolism, which in turn may result in an increase in silk yield.


Prosthetic valve endocarditis: what is the evidence for anticoagulant therapy?
The use of anticoagulant therapy in prosthetic valve endocarditis is a controversial management issue. Some authorities believe that anticoagulation increases the potential risk of cerebral haemorrhage after a thromboembolism whereas others, however, affirm that cessation of anticoagulation itself increases the risk of thromboembolism and subsequent morbidity and mortality. We reviewed the association of anticoagulant therapy and cerebral complications in patients with prosthetic valve endocarditis. Our results suggest that anticoagulant therapy reduces the risk of thromboembolism and is not associated with increased risk of intracranial haemorrhage.


Immunoglobulin A and Protein Content of Low-Fat Human Milk Prepared for the Treatment of Chylothorax.
Several case studies report successful recovery from chylothorax while infants were fed low-fat human milk. The reported growth rates were inadequate despite milk supplementation with added medium-chain triglycerides (MCTs). The objective was to determine the effect that various human milk fat separating methods, refrigerated centrifuge, room temperature centrifuge, and refrigeration have on the loss of immunoglobulin A (IgA) and protein in the preparation of low-fat human milk. Protein and IgA were measured in 31 samples of reduced-fat human milk. Reduced-fat breastmilk samples were prepared by separating the fat using 3 methods (refrigerated centrifuge, room temperature centrifuge, and a refrigeration method), followed by lower fat milk extraction by syringe. The refrigeration method decreased IgA concentration by 17% (P = .035) while centrifugation and fat removal from the human milk samples led to a 38% decline in IgA concentration in both the nonrefrigerated and refrigerated centrifuge samples (P < .0001 for both). Protein declined by 11% with refrigeration and fat removal (P < .0001) while centrifugation and fat removal decreased protein concentration by 31% (P < .0001) in both nonrefrigerated centrifuge and refrigerated centrifuge samples. Preparing low-fat human milk for patients with chylothorax decreased the IgA and protein contents. As well as fat (in the form of MCTs), protein likely needs to be supplemented for infants fed low-fat human milk to support adequate growth.


Determination of individual hydroxyethyl rutosides in various animal body fluids by thin-layer chromatography and scanning densitometry.
A method is described for the accurate determination in plasma of the beta-hydroxyethylrutosides by measurement of the fluorescence of their borocitrate complexes by scanning densitometry following separation by thin-layer chromatography. A modification is also described for estimation of individual hydroxyethylrutosides and their glucuronide conjugates in samples of bile and urine.


[The history of the elimination of guinea worm infection in Uzbekistan].
Dracunculiasis was mainly spread in Bukhara. Control was made in two directions: 1) timely detection of patients, their registration, treatment and parasitic decontamination; 2) elimination of Dracunculus larvae-infected Cyclops in the water reservoirs. The prevalence of the disease is as high as 20% and a total of 1116 patients were identified. Only one patient was notified in 1931. In 1932, foci of Dracunculus stopped its existence in Old Bukhara and 56 neighboring inhabited areas.


Two-photon absorption and photoluminescence of europium based emissive probes for bioactive systems.
Observation of two-photon excitation (760 nm) and emission of two responsive water soluble europium complexes is reported with cross-sections of up to 2 GM. Two-photon excitation spectra have also been measured, acquisition being achieved by the use of a cavity-dumped mode locked Ti-sapphire laser. Time-gated detection is used to differentiate the ligand fluorescence and metal centred emission in these europium complexes.


[Clinicopathological study of six cases of primary pulmonary lymphoma diagnosed by gene rearrangement analysis].
We report six cases of primary pulmonary lymphoma in which a gene-rearranged band was shown by Southern blot analysis of transbronchial or surgical biopsy specimens. The cases were 3 mens and 4 women with an average age of 59.6, who had abnormal pulmonary shadows on chest X-ray. Two cases had Sjögren's syndrome and one case had monoclonal gammopathy (IgM-lambda type). Histopathologic and immunologic examination revealed diffuse infiltration of small lymphocytes (B-cell type) in all cases, and histological features of lymphoepithelial lesion or lympho-cytic interstitial pneumonia (LIP) in three cases. CT revealed an ill-defined margin, air-space consolidation, and air-bronchogram in all cases. A CT-angiogram sign was apparent in 2 cases. In all cases, Southern blot analysis of the tissue obtained from transbronchial or surgical biopsy revealed a gene re-arranged band, supporting the diagnosis of primary pulmonary lymphoma. We infer that an ill-defined margin, air-bronchogram and air space consolidation on CT were associated with the histopathological features of primary pulmonary lymphoma.


Microcapsule of sweet orange essential oil changes gut microbiota in diet-induced obese rats.
Obesity is associated with the changes in gut microbiota. The aim of present study was to investigate the effects of sweet orange essential oil (SOEO) microcapsules on body weight and gut microbiota in obese rats induced by high-fat diet. By analyzing the body weight, fat rate and the sequence of cloned microbial small-subunit ribosomal RNA genes (16S rDNA) in rats fecal samples, we found that SOEO microcapsules decreased the body weight and increased the relative abundance of Bifidobacterium (genus-level) in gut microbiota. The analysis of endotoxin content proved that SOEO microcapsules protected gut barrier and decreased gut endotoxin levels by increasing the content of Bifidobacterium, then ameliorated low-grade inflammation, achieving the goal of losing weight. This might be the mechanism of SOEO microcapsules to lose body weight and provided a novel anti-obesity dietary supplement.


[Community-acquired pneumonias, complicated with pathology of the urological system].
The article presents the results of studying the characteristics of clinical course, diagnostics and treatment of outhospital pneumonias, combined with pathology of urinary bodies in the interest of optimizing medical-diagnostic ensure this category of patients in an environment of pulmonologikal department of multidisciplinary hospital facility. Optimization of the full survey of patients with pneumonia, combined with diseases and pathological changes of urinary system, in the initial period of their treatment in the pulmonologikal department environment allows to make early, proved correction of etiotropic, pathogenetic and symptomatic therapy of their polimorbidycal pathology, that will reduce their terms of being in hospital without damage to quality of diagnostics and treatment.


Role of Helicobacter pylori in common rosacea subtypes: a genotypic comparative study of Egyptian patients.
Helicobacter pylori was incriminated as an etiological factor of rosacea. However, there is still controversy about this association. We conducted a comparative study in order to assess the role of H. pylori in rosacea patients who had dyspeptic symptoms. The study included 68 patients and 54 controls. Screening for H. pylori was performed and positive cases were referred for gastric endoscopy. The inflammatory response and bacterial density were evaluated in gastric biopsy. H. pylori vacA alleles, cagA and iceA genotypes were assessed by polymerase chain reaction. We found that 49 rosacea (72%) and 25 controls (46.3%) were infected with H. pylori. Thirty-one rosacea cases were papulopustular (PPR) while 18 were erythematotelangiectatic (ETR). Gastric ulceration was higher in PPR cases (38.7%) than ETR (11.1%) and controls (12%). A significant inflammatory reaction was observed more in PPR cases (74.2%) compared with 44.4% in ETR (P = 0.04) and 44% in controls (P = 0.02). Analysis of H. pylori genotypes revealed that vacA s1m1 was more identified in PPR cases (54.8%) compared with 22.2% in ETR (P = 0.03) and 16% in controls (P = 0.003). There was a significant elevation of cagA/vacA s1m1 positivity in PPR cases. After the eradication regimen of H. pylori, a significant improvement (P < 0.05) was observed in 15 out of 27 PPR cases (55.6%) compared with three out of 17 ETR (17.6%). We concluded that H. pylori has a significant role in rosacea patients who had dyspeptic symptoms. The PPR type is more influenced by H. pylori and this is regarded as being because of certain virulent strains that increase the inflammatory response in gastric mucosa and also in cutaneous lesions.


Oral fluid collection by post for viral antibody testing.
The objective of this study was to estimate the prevalence of hepatitis B virus exposure (HBV) in the population of the Republic of Ireland, by using oral fluid (saliva) collection by post for hepatitis B anti-core antibody (anti-HBc). This paper discusses the methodological approach used and the strategies that were adopted to improve response rates. The sampling frame used was the Register of Electors for Irish parliamentary elections. A multistage stratified cluster sample was taken, and a total of 962 households were selected nationally. A four-letter approach was employed for sample collection. Households received an initial letter outlining the purpose of the study. This was followed by a letter containing six swabs for oral fluid collection, along with easy-to-follow instructions. Non-respondents received two reminder letters, and were also telephoned where possible. A telephone helpline was provided. All testing was anonymous and unlinked. The study achieved a good household response rate (60.4%), and more than 98% of the 1738 specimens received were suitable for testing. The prevalence of anti-HBc in the Irish population was estimated to be 0.51%. The observed design effect was 1.29. From a review of the literature, this is the first study where a representative sample of a national population was asked to self-collect oral fluid samples and return these by post for serological testing. The technique may have many future applications in epidemiological research.


Penetrating keratoplasty for unilateral corneal disease: outcomes from a tertiary care hospital in Australia.
To assess the visual outcome after unilateral penetrating keratoplasty (PKP) in a heterogenous group of patients with unilateral corneal disease. A retrospective analysis of hospital records of patients who had undergone PKP at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, over a 10-year period, was performed. All cases with a history of corneal transplantation surgery in one eye and a best-corrected visual acuity (BCVA) more than or equal to 0.5 in the fellow eye with no corneal pathologic condition were included. Outcome measures included BCVA at 2 years, and overall graft survival. Of the 498 grafts performed during the study period, 30 eyes (6%) met the inclusion criteria. The most common indications for PKP in the study group were bullous keratopathy (40%) and keratoconus (34%). The mean postoperative BCVA at 2 years (0.31 +/- 0.25; range, 0.033-1) was less than the mean BCVA of the fellow eye (0.77 +/- 0.20; range, 0.5-1) (P<0.00). Although there was a significant difference between the preoperative and postoperative BCVA (P<0.00), only 22% of patients could attain BCVA of more than or equal to 0.5. The major complications encountered were graft rejection (40%) and secondary graft failure (20%). Unilateral PKP is most commonly performed to treat bullous keratopathy and keratoconus in Australia and may be associated with suboptimal visual outcome as compared to the normal fellow eye.


Local and remote ischemia-reperfusion injury is mitigated in mice overexpressing human C1 inhibitor.
Activation of the classical complement pathway is crucially involved in complement-mediated endothelial cell damage in ischemia-reperfusion injury. C1 inhibitor is the only known physiological inhibitor of classical complement pathway activation. Transgenic mice overexpressing human C1 inhibitor were used in a surgical lower torso and a liver ischemia-reperfusion model. Organ-specific endothelial disruption was determined by 125I-tagged albumin extravasation. In the lower torso ischemia-reperfusion model, transgenic mice overexpressing the C1 inhibitor were protected in the muscle and the lungs from endothelial cell damage. In the liver ischemia-reperfusion model, endothelial cell integrity was preserved in transgenic animals in the liver, the gut and the lungs. Our data indicate that inhibiting complement activation by a transgenic approach is effective in protection against ischemia-reperfusion injury.


A Novel Platform for High-Throughput Gene Synthesis to Maximize Recombinant Expression in Escherichia coli.
Gene synthesis is becoming an important tool in many fields of recombinant DNA technology, including recombinant protein production. De novo gene synthesis is quickly replacing the classical cloning and mutagenesis procedures and allows generating nucleic acids for which no template is available. Here, we describe a high-throughput platform to design and produce multiple synthetic genes (<500 bp) for recombinant expression in Escherichia coli. This pipeline includes an innovative codon optimization algorithm that designs DNA sequences to maximize heterologous protein production in different hosts. The platform is based on a simple gene synthesis method that uses a PCR-based protocol to assemble synthetic DNA from pools of overlapping oligonucleotides. This technology incorporates an accurate, automated and cost-effective ligase-independent cloning step to directly integrate the synthetic genes into an effective E. coli expression vector. High-throughput production of synthetic genes is of increasing relevance to allow exploring the biological function of the extensive genomic and meta-genomic information currently available from various sources.


Statistical physics of crime: a review.
Containing the spread of crime in urban societies remains a major challenge. Empirical evidence suggests that, if left unchecked, crimes may be recurrent and proliferate. On the other hand, eradicating a culture of crime may be difficult, especially under extreme social circumstances that impair the creation of a shared sense of social responsibility. Although our understanding of the mechanisms that drive the emergence and diffusion of crime is still incomplete, recent research highlights applied mathematics and methods of statistical physics as valuable theoretical resources that may help us better understand criminal activity. We review different approaches aimed at modeling and improving our understanding of crime, focusing on the nucleation of crime hotspots using partial differential equations, self-exciting point process and agent-based modeling, adversarial evolutionary games, and the network science behind the formation of gangs and large-scale organized crime. We emphasize that statistical physics of crime can relevantly inform the design of successful crime prevention strategies, as well as improve the accuracy of expectations about how different policing interventions should impact malicious human activity that deviates from social norms. We also outline possible directions for future research, related to the effects of social and coevolving networks and to the hierarchical growth of criminal structures due to self-organization.


In vitro efficacy of a povidone-iodine 0.4% and dexamethasone 0.1% suspension against ocular pathogens.
To assess the efficacy of a povidone-iodine 0.4%-dexamethasone 0.1% suspension against bacterial, fungal, and Acanthamoeba clinical isolates. Bascom Palmer Eye Institute, McKnight Research Building, Miami, Florida, USA. Experimental study. One hundred milliliters of 10(4) colony-forming units/mL of ocular isolates of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Serratia marcescens, Candida albicans, Fusarium solani, and Acanthamoeba castellanii were inoculated into 100 μL of a povidone-iodine 0.4%-dexamethasone 0.1% suspension in a 96-well microtiter plate incubated at room temperature. Organism viability was assessed at 15, 30, and 60 seconds by removing 10 μL aliquots and streaking onto a 5.0% sheep blood agar plate (fungi and bacteria) and agar-agar (Acanthamoeba) using a 0.001 calibrated loop. The plates were then incubated at 35 °C and monitored for up to 7 days. Isolates were inoculated into 200 μL of trypticase soy broth as controls. The number of colonies was counted and compared with controls to determine the kill rate. A 99.9% kill was observed for MRSA, P aeruginosa, S marcescens, and C albicans after 15 seconds of exposure and for F solani after 60 seconds. Acanthamoeba castellanii cyst viability was not inhibited by exposure to the povidone-iodine and dexamethasone suspension. Organism growth was achieved on all control broth. Povidone-iodine 0.4%-dexamethasone 0.1% suspension killed all bacterial and candida isolates within 15 seconds of exposure. It killed Fusarium isolates at 60 seconds but was ineffective against Acanthamoeba cysts. Drs. Pelletier and Miller have no financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.


Regulation of TRAIL-induced apoptosis by XIAP in pancreatic carcinoma cells.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapy because of its relative tumor selectivity. However, many cancers including pancreatic cancer remain resistant towards TRAIL. To develop TRAIL for cancer therapy of pancreatic carcinoma, it will therefore be pivotal to elucidate the molecular mechanisms of TRAIL resistance. Here, we identify X-linked inhibitor of apoptosis (XIAP) as a regulator of TRAIL sensitivity in pancreatic carcinoma cells. Full activation of effector caspases, loss of mitochondrial membrane potential and cytochrome c release following TRAIL treatment were markedly impaired in pancreatic carcinoma cell lines, which poorly responded to TRAIL (PaTuII, PancTu1, ASPC1, DanG), compared to TRAIL-sensitive Colo357 pancreatic carcinoma cells. Stable downregulation of XIAP by RNA interference significantly reduced survival and enhanced TRAIL-induced apoptosis in pancreatic carcinoma cells. Also, downregulation of XIAP significantly increased CD95-induced cell death. Importantly, knockdown of XIAP strongly inhibited clonogenicity of pancreatic cancer cells treated with TRAIL indicating that XIAP promotes clonogenic survival of pancreatic carcinoma cells. Thus, our findings for the first time indicate that targeting XIAP represents a promising strategy to enhance the antitumor activity of TRAIL in pancreatic cancer, which has important clinical implications.


Age-related changes in membrane fluidity of erythrocytes in essential hypertension.
In the present study, age- and calcium-related changes in the membrane fluidity of erythrocytes were examined in patients with essential hypertension by use of electron spin resonance method (ESR). The erythrocytes were obtained from patients with essential hypertension. We examined the ESR spectra for a fatty acid spin label agent (5-nitroxy stearate) incorporated into the erythrocyte membranes. The values of outer hyperfine splitting and order parameter (S) were significantly higher in subjects with essential hypertension than in the normotensive subjects. This finding indicates that the membrane fluidity of erythrocytes was lower in essential hypertension. Calcium-loading of erythrocytes with the Ca-ionophore A23187 decreased the membrane fluidity (S value was increased) more strongly in essential hypertension than in the normotensive subjects. Furthermore, this Ca-induced change in membrane fluidity was significantly correlated with age in essential hypertension. These results demonstrate that the membrane fluidity of erythrocytes is markedly decreased by calcium, especially in essential hypertension in older patients. This suggests an increased calcium-sensitivity of cell membranes in the aged hypertensive patient.


Comparing multidrug-resistant tuberculosis patient costs under molecular diagnostic algorithms in South Africa.
Ten primary health care facilities in Cape Town, South Africa, 2010-2013. A comparison of costs incurred by patients in GenoType MDRTBplus line-probe assay (LPA) and Xpert MTB/RIF-based diagnostic algorithms from symptom onset until treatment initiation for multidrug-resistant tuberculosis (MDR-TB). Eligible patients identified from laboratory and facility records were interviewed 3-6 months after treatment initiation and a cost questionnaire completed. Direct and indirect costs, individual and household income, loss of individual income and change in household income were recorded in local currency, adjusted to 2013 costs and converted to $US. Median number of visits to initiation of MDR-TB treatment was reduced from 20 to 7 (P < 0.001) and median costs fell from US$68.1 to US$38.3 (P = 0.004) in the Xpert group. From symptom onset to being interviewed, the proportion of unemployed increased from 39% to 73% in the LPA group (P < 0.001) and from 53% to 89% in the Xpert group (P < 0.001). Median household income decreased by 16% in the LPA group and by 13% in the Xpert group. The introduction of an Xpert-based algorithm brought relief by reducing the costs incurred by patients, but loss of employment and income persist. Patients require support to mitigate this impact.


The association of Trisomy 13 and 18 and hospital discharge outcomes among neonates in California: A retrospective cohort study.
Despite Trisomy 13 and 18 being among the most fatal congenital anomalies, limited information exists about resource utilization and factors associated with length of stay (LOS) and total hospital charges (THC) for these anomalies. We studied data sets of the patient discharge data set from the California Office of Statewide Health Planning and Development from 2006 to 2010, to determine differences in resource utilization for survivors and non-survivors and identify the predictors of LOS and total hospital charges. Descriptive statistics were assessed for demographic and clinical characteristics. General linear regression models were used to identify predictors of LOS and THC. Seventy-six Trisomy 13 and 115 Trisomy 18 patients were identified, for whom inpatient mortality was 27.6% and 20.9%, respectively. In patients with Trisomy 13, after adjusting for gender, ethnicity, advanced directive (DNR), insurance and co-morbidities on multivariate analysis, the provision of more than 96 h of mechanical ventilation was associated with significantly increased LOS (standard error, SE) by 18.0 ± 5.3 days and THC (SE) by $399,000 ± $85,000. In terms of insurance type, patients with private coverage had 10.8 ± 4.9 days more than patients with Medicaid. In patients with Trisomy 18, on multivariate analysis, after adjusting for gender, ethnicity, DNR, insurance and co-morbidities, more than 96 h of mechanical ventilation was associated with increased LOS (SE) by 36.8 ± 6.8 days and THC (SE) by $365,000 ± $59,000. Understanding predictors that are associated with longer LOS and higher THC may be associated in hospital resource allocation for this vulnerable population of infants.


Potential ecotoxicity of metals leached from antifouling paint particles under different salinities.
Antifouling paint particles (APPs) are residues generated during maintenance of vessels. In boat maintenance areas of South America, waste generation and disposal are not completely regulated. Therefore, APPs can enter into the aquatic environment and act as a source of contamination by metals and other biocides. Thus, the aim of the present study was to evaluate the potential ecotoxicity of the metal mixture present in APPs leached under different salinities. Therefore, the copepod Acartia tonsa was exposed to different concentrations of a leachate solution prepared by the addition of APPs (1.25g/L) in artificial saline water (salinities 5, 15 and 30). Thereafter, complexing agents (EDTA and sodium thiosulfate) were added to the experimental media in order to evaluate metal influence in APPs toxicity. APPs leachate solutions were very toxic to A. tonsa, reaching an estimated LC50 of 1% at salinities 5% and 15%, and 2% at salinity 30. The addition of the chelators in leachate solutions showed that metals are the major responsible compounds for the observed toxicity. Moreover, results from the calculated toxic units suggested a slightly synergic effect between Cu and Zn in the paint formulation. A metal speciation modelling showed that Zn was predominant as a free ion at all salinities, therefore, explaining the high leachate toxicity. Furthermore, the release of Zn was observed more at lower salinities, whereas Cu was observed at higher salinities. APPs are frequently released in estuarine systems, under conditions of salinity gradients. Therefore, navigated estuaries might be under the threat of this neglected residue.


A critical evaluation of cystic features in primary glioblastoma as a prognostic factor for survival.
The presence of cystic features in glioblastoma (GBM) has been described as a favorable prognostic factor. The aim of this study was to determine the survival outcome in patients undergoing surgery for newly diagnosed primary GBM with a large cystic component as compared with a large cohort of patients with noncystic GBM, while controlling for well-characterized prognostic factors. A retrospective review of 354 consecutive patients treated with resection of primary GBM was performed using medical records and imaging information obtained at the University of California, San Francisco from 2005 to 2009. Within this cohort, 37 patients with large cysts (≥ 50% of tumor) were identified. Clinical presentations and surgical outcomes were statistically compared between the cystic and noncystic patients. There were no statistically significant differences in clinical presentation between groups, including differences in age, sex, presenting symptoms, tumor location, or preoperative functional status, with the exception of tumor size, which was marginally larger in the cystic group. Surgical outcomes, including extent of resection and postoperative functional status, were equivalent. The median actuarial survival for the patients with cystic GBM was 17.0 months (95% CI 12.6-21.3 months), and the median survival for patients with noncystic GBM was 15.9 months (95% CI 14.6-17.2 months). There was no significant between-groups difference in survival (p = 0.99, log-rank test). A Cox multivariate regression model was constructed, which identified only age and extent of resection as independent predictors of survival. The presence of a cyst was not a statistically significant prognostic factor. This study, comprising the largest series of cases of primary cystic GBM reported in the literature to date, demonstrates that the presence of a large cyst in patients with GBM does not significantly affect overall survival as compared with survival in patients without a cyst. Preoperative discussions with patients with GBM should focus on validated prognostic factors. The presence of cystic features does not confer a survival advantage.


Enhancement of europium emission band of europium tetracycline complex in the presence of cholesterol.
We report here the observation, for the first time, of the enhancement of Europium-Tetracycline complex emission in cholesterol solutions. This enhancement was initially observed with the addition of the enzyme cholesterol oxidase, which produces H(2)O(2), the agent driver of the Europium tetracycline complex, to the solution. However, it was found that the enzyme is not needed to enhance the luminescence. A calibration curve was determined, resulting in a simple method to measure the cholesterol quantity in a solution. This method shows that the complex can be used as a sensor to determine cholesterol in biological systems.


The Mindful Attention Awareness Scale: Further Examination of Dimensionality, Reliability, and Concurrent Validity Estimates.
We examined the factor structure and psychometric properties of the Mindful Attention Awareness Scale (MAAS) in a sample of 810 undergraduate students. Using common exploratory factor analysis (EFA), we obtained evidence for a 1-factor solution (41.84% common variance). To confirm unidimensionality of the 15-item MAAS, we conducted a 1-factor confirmatory factor analysis (CFA). Results of the EFA and CFA, respectively, provided support for a unidimensional model. Using differential item functioning analysis methods within item response theory modeling (IRT-based DIF), we found that individuals with high and low levels of nonattachment responded similarly to the MAAS items. Following a detailed item analysis, we proposed a 5-item short version of the instrument and present descriptive statistics and composite score reliability for the short and full versions of the MAAS. Finally, correlation analyses showed that scores on the full and short versions of the MAAS were associated with measures assessing related constructs. The 5-item MAAS is as useful as the original MAAS in enhancing our understanding of the mindfulness construct.


Sensitivity of human gamma interferon assay and tuberculin skin testing for detecting infection with Mycobacterium tuberculosis in patients with culture positive tuberculosis.
Nine university-affiliated chest clinics in Australia. To evaluate the sensitivity of a whole blood human gamma-interferon assay (HGIA, QuantiFERON-TB) for specific T lymphocyte responses and Tuberculin skin testing (TST) for the detection of Mycobacterium tuberculosis infection in subjects with culture-proven M. tuberculosis disease (TBCP). Prospective testing of 129 patients with recent TBCP and 100 patients with non-tuberculosis lung disease (NTBLD). Using a defined level of specific IFN-gamma production and TST 10mm as positive cut-offs, the sensitivity of HGIA was 81% compared to 89% for TST (p=0.06). When positive responses in both TST and HGIA were combined, 96% of TB patients were detected. For the NTBLD group, 43% of whom were born overseas, 73% were negative for both the HGIA and TST. Prior immunization with M. bovis (bacille Calmette-Guerin) (BCG) or the type of TB had no effect on the sensitivities of the assays. For those treated for <2 months, the sensitivities for both assays were 84%, but for those treated for >2 months the sensitivity of TST (90%) tended to be higher than for HGIA (81%) (p=0.07). The distribution of TST results in TB patients showed a broad peak between 10 and 25 mm, while the results in the HGIA were bimodal in both TB and NTBLD patients. HGIA may prove an alternative to skin testing for detecting M. tuberculosis infection in certain settings.