[A SURGICAL CASE OF MYCOBACTERIUM KANSASII LUNG DISEASE MIMICKING PRIMARY LUNG CANCER].
We report a rare surgical case of a solitary pulmonary nodule due to Mycobacterium kansasii. A 59-year-old man was admitted to our hospital for examination of an abnormal shadow in the left upper lobe incidentally found on a chest radiogram. Computed tomography of the chest showed that the nodule was located in the left segment 1+2 and was irregularly shaped with a diameter of 35 mm. Thoracic fluorine-18 fluoro-deoxy-glucose positron emission tomography showed a high metabolic pulmonary lesion, with a maximum standardized uptake value of 5.1, consistent with findings for lung cancer. A bronchoscopy was performed to establish the diagnosis of lung cancer; however, it failed to show malignant cells. Because we could not confirm the diagnosis by bronchoscopic examination, video-assisted thoracoscopic surgery was performed. The intraoperative rapid diagnosis of the nodule was epithelioid cell granuloma. Smear test of the resected specimen was positive for acid-fast bacilli, and a culture was also positive for mycobacteria, which were identified as Mycobacterium kansasii. Antibiotic treatment for M. kansasii infection was administered for a year after the surgical resection. Few cases of Mycobacterium kansasii infection present with solitary pulmonary nodules.


Surgery for full-thickness macular hole in patients with idiopathic macular telangiectasia type 2.
The authors report surgical outcomes of full-thickness macular hole repair in two patients with idiopathic macular telangiectasia in a non-comparative case series. Both patients underwent pars plana vitrectomy with indocyanine green-assisted internal limiting membrane peeling and injection of 16% C(3)F(8) gas. Patients were imaged with optical coherence tomography (OCT) before and after surgery. The first patient demonstrated macular hole closure on examination and OCT with visual improvement from 20/50 preoperatively to 20/30 after macular hole surgery and subsequent cataract surgery. The second patient's hole closed per OCT immediately after surgery but reopened 4 months later, and visual acuity remained 20/70. Macular hole surgery may be an effective treatment in patients with idiopathic macular telangiectasia and full-thickness macular holes and should be further investigated.


Analysis and modeling of dialect information in Ao, a low resource language.
Ao is a Tibeto-Burman language spoken in Nagaland, India. It is a low resource, tonal language with three lexical tones, namely, high, mid, and low. However, tone assignment on lexical words may differ among the three dialects of Ao, namely, Chungli, Mongsen, and Changki. In this work, an acoustic study is conducted on the three tones in the three dialects of Ao. It was found that the acoustic characteristics of the tones in the Changki dialect are markedly different from that of the Chungli and the Mongsen dialects. Hence, in the latter part of the work, automatic dialect identification (DID) in the Ao dialects is attempted with Mel Frequency Cepstral Coefficients, Shifted Delta Cepstral coefficients, and F0 features using the Gaussian Mixture models. It is confirmed that in both text-dependent and text-independent DID, the F0 features improve the accuracy of classification.


[Features of Professor Ma Kun's medication in treating ovulatory infertility].
In order to analyze Professor Ma Kun's medication in treating anovulatory infertility, her prescriptions for treating anovulatory infertility in 2012-2015 were collected. The medication features and the regularity of prescriptions were mined by using traditional Chinese medicine inheritance support system, association rules, complex system entropy clustering and other mining methods. Finally, a total of 684 prescriptions and 300 kinds of herbs were screened out, with a total frequency of 11 156 times; And 68 core combinations and 8 new prescriptions were mined. The top three frequently used herbs by effect were respectively tonic herb, blood circulation promoting herb, and Qi-circulation promoting herb. The top three tastes were sweetness, bitterness and pungent flavor. The results showed 28 herbs with a high frequency of ≥100.The top 10 frequently used herbs were respectively Angelica Sinensis Radix, Cyperi Rhizoma, Chuanxiong Rhizome, Paeoniae Radix Rubra, Cyathulae Radix, Taxilli Herba, Cuscutae Semen, Codonopsis Radix, Ligustri Lucidi Fructus, Paeoniae Albaand Paeoniae Radix Alba. The association rules analysis showed commonly used herbal pairs, including Rehmanniae Radix Preparata-Chuanxiong Rhizome, Rehmanniae Radix Preparata-Angelica Sinensis Radix, Cuscutae Semen-Dipsaci Radix. In conclusion, Professor Ma has treated anovulatory infertility by nourishing the kidney and activating blood throughout the treatment course, and attached the importance to the relationship between Qi and blood and there gulation of liver, spleen and kidney in treating anovulatory infertility.


Primary Sclerosing Cholangitis in a Young Female.
Primary sclerosing cholangitis (PSC) is a liver disease characterized by inflammation and fibrosis of both intrahepatic and extrahepatic bile ducts resulting in cholestasis. Due to nonspecific symptoms it is difficult to diagnose until complication arises. It is common in male and usually associated with other autoimmune diseases. Here, we report a case of PSC in a young female which was initially thought to be drug induced cholestasis without presence of any other autoimmunity.


The safety of vedolizumab in a patient with Crohn's disease who developed anti-TNF-alpha agent associated latent tuberculosis infection reactivation: A case report.
Latent tuberculosis (TB) infection screening before inducing anti-tumor necrosis factor (anti-TNF) alpha agents is important to prevent TB reactivation. However, latent TB infection reactivation may still occur, and the ideal therapeutic strategy for patients with inflammatory bowel disease (IBD) who develop active TB infection has not been established. Vedolizumab (VDZ) has a good safety profile, with low incidence rates of serious infections. However, its safety in patients with latent TB infection reactivation associated with anti-TNF-alpha agents remains unknown. A 21-year-old Vietnamese male patient presented to our hospital with hemorrhagic stool. He had no personal or family history of IBD or TB. Colonoscopy revealed multiple longitudinal ulcers and a cobblestone appearance in the terminal ileum, as well as multiple small erosions and aphtha throughout the colon. Computed tomography revealed a right lung nodular lesion. Serological interferon-gamma release assay and several culture tests were all negative. Thus, he was diagnosed with ileocolonic Crohn's disease (CD) without TB. The intravenous anti-TNF-alpha agent administration with an immunomodulator was initiated. Computed tomography revealed nodular lesion expansion at the right lung, and serological interferon-gamma release assay was positive. He was diagnosed with latent TB infection reactivation. Anti-TNF-alpha agent with an immunomodulator was immediately discontinued, and anti-TB therapy was initiated. His endoscopic findings were still active, and VDZ was selected for maintenance therapy because VDZ has a favorable safety profile with low incidence rates of serious infections. Consequently, mucosal healing was achieved without active TB relapse. This case report presented a patient in whom VDZ was continued as maintenance therapy without inducing TB relapse in a patient with CD who developed latent TB infection reactivation associated with anti-TNF-alpha agents and summarized the safety profile of VDZ for patients with IBD with active or latent TB infection. VDZ may be a safe option for induction and maintenance therapy in patients with CD, even in cases with latent TB infection reactivation.


Cloning and characterization of a cDNA encoding a protein synthesis initiation factor-2alpha (eIF-2alpha) kinase from Drosophila melanogaster. Homology To yeast GCN2 protein kinase.
Phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eIF-2alpha) is one of the best-characterized mechanisms for downregulating protein synthesis in mammalian cells in response to various stress conditions. In Drosophila, such a regulatory mechanism has not been elucidated. We report the molecular cloning and characterization of DGCN2, a Drosophila eIF-2alpha kinase related to yeast GCN2 protein kinase. DGCN2 contains all of the 12 catalytic subdomains characteristic of eukaryotic Ser/Thr protein kinases and the conserved sequence of eIF-2alpha kinases in subdomain V. A large insert of 94 amino acids, which is characteristic of eIF-2alpha kinases, is also present between subdomains IV and V. It is particularly notable that DGCN2 possesses an amino acid sequence related to class II aminoacyl-tRNA synthetases, a unique feature of yeast GCN2 protein kinase. DGCN2 expression is developmentally regulated. During embryogenesis, DGCN2 mRNA is dynamically expressed in several tissues. Interestingly, at later stages this expression becomes restricted to a few cells of the central nervous system. Affinity-purified antibodies, raised against a synthetic peptide based on the predicted DGCN2 sequence, specifically immunoprecipitated an eIF-2alpha kinase activity and recognized an approximately 175 kDa phosphoprotein in Western blots of Drosophila embryo extracts.


Quantum magneto-transport properties of monolayers MoSi2N4, WSi2N4, and MoSi2As4.
We study the transport properties of monolayers MoSi2N4, WSi2N4, and MoSi2As4in a perpendicular magnetic field. The Landau level (LL) band structures including spin and exchange field effects are derived and discussed using a low-energy effective model. We show that the LLs band structures of these materials are similar to those of phosphorene and transition-metal dichalcogenides rather than graphene or silicene. The combination of strong spin-orbit coupling and exchange fields reduces the degradation of the LLs, leading to new plateaus in the Hall conductivity and Hall resistivity and new peaks in the longitudinal conductivity and longitudinal resistivity. The effect of the exchange field, carrier density, and LLs band structure on the conductivities and resistivities have been investigated. At high temperatures, the steps in Hall conductivity and resistivity plateaus disappear and reduce to their corresponding classical forms.


Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases.
Immune thrombocytopenic purpura (ITP) is an autoimmune condition characterized by low platelet count with mucocutaneous and other bleedings. Clinical manifestations may range from spontaneous formation of purpura and petechiae, especially on the extremities, to epistaxis, bleeding at the gums or menorrhagia, any of which occur usually if the platelet count is below 20,000 per μl. A very low count may result in the spontaneous formation of hematomas in the mouth or on other mucous membranes. Fatal complications, including subarachnoid or intracerebral, lower gastrointestinal or other internal bleeding can arise due to an extremely low count. Vaccines may induce ITP by several mechanisms. Vaccine-associated autoimmunity may stem not only from the antigen-mediated responses but also from other constituents of the vaccine, such as yeast proteins, adjuvants, and preservatives diluents. The most likely is through virally induced molecular mimicry. The binding of pathogenic autoantibodies to platelet and megakaryocytes may cause thrombocytopenia by different mechanisms, such as opsonization, direct activation of complement, or apoptotic pathways. The autoantibodies hypothesis is not sufficient to explain all ITP cases: In the anti-platelet antibody-negative cases, a complementary mechanism based on T cell immune-mediated mechanism has been suggested. In particular, T cell subsets seem dysregulated with an increased production of pro-inflammatory cytokines, as IFN-γ and TNF, and chemokines, as CXCL10. Vaccines are one of the most striking discoveries in human history that changed dramatically life expectancy. Nonetheless, the occurrence of adverse events and autoimmune phenomena has been described following vaccination, and ITP may represent one of this.


Interaction of a new fluorescent ATP analogue with skeletal muscle myosin subfragment-1.
A new fluorescent ribose-modified ATP analogue, 2'(3')-O-[6-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoic]-ATP (NBD-ATP), was synthesized and its interaction with skeletal muscle myosin subfragment-1 (S-1) was studied. NBD-ATP was hydrolysed by S-1 at a rate and with divalent cation-dependence similar to those in the case of regular ATP. Skeletal HMM supported actin translocation using NBD-ATP and the velocity was slightly higher than that in the case of regular ATP. The addition of S1 to NBD-ATP resulted in quenching of NBD fluorescence. Recovery of the fluorescence intensity was noted after complete hydrolysis of NBD-ATP to NBD-ADP. The quenching of NBD-ATP fluorescence was accompanied by enhancement of intrinsic tryptophan fluorescence. These results suggested that the quenching of NBD-ATP fluorescence reflected the formation of transient states of ATPase. The formation of S-1.NBD-ADP.BeF(n) and S-1.NBD-ADP.AlF(4)(-) complexes was monitored by following changes in NBD fluorescence. The time-course of the formation fitted an exponential profile yielding rate constants of 7.38 x 10(-2) s(-1) for BeF(n) and 1.1 x 10(-3) s(-1) for AlF(4)(-). These values were similar to those estimated from the intrinsic fluorescence enhancement of trp due to the formation of S-1.ADP.BeF(n) or AlF(4)(-) reported previously by our group. Our novel ATP analogue seems to be applicable to kinetic studies on myosin.


Production of copper-64 using a hospital cyclotron: targetry, purification and quality analysis.
To construct and evaluate a 64Cu production system that minimises the amount of costly 64Ni, radionuclidic impurities and nonradioactive metal contamination and maximises radiochemical and radionuclidic purity and molar activity; and to report analytical and quality control methods that can be used within typical PET radiochemistry production facilities to measure metal ion concentrations and radiometal molar activities. Low volume was ensured by dissolving the irradiated nickel in a low volume of hydrochloric acid (<1 mL) using the concave gold target backing as a reaction vessel in a custom-built target holder. Removal of contaminating 55Co and nonradioactive trace metals was ensured by adding an intermediate hydrochloric acid concentration step during the conventional ion-exchange elution process. The radionuclidic purity of the product was determined by half-life measurements, gamma spectroscopy and ion radiochromatography. Trace metal contamination and molar activity were determined by ion chromatography. On a small scale, suitable for preclinical research, the process produced typically 3.2 GBq 64Cu in 2 mL solution from 9.4 ± 2.1 mg nickel-64 electroplated onto a gold target backing. The product had high molar activity (121.5 GBq/µmol), was free of trace metal contamination detectable by ion chromatography and has been used for many preclinical and clinical PET imaging applications.


The penetration of lincomycin into normal human bone. Determination of penetration into compact bone, spongy bone and bone marrow.
The penetration of lincomycin into normal bone was studied in 10 patients with fracture of the neck of the femur, a separate determination being made of the lincomycin concentration in serum, bone marrow, spongy bone and compact bone. The concentration of lincomycin in bone marrow was found to be at the same level as that in the serum. The concentration in spongy bone amounted in most cases to 50 to 75 percent of the concentration in the serum, whereas the concentration in compact bone varied from 0 to 15 percent of that in the serum.


Emotion Processing Dysfunction in Alzheimer's Disease: An Overview of Behavioral Findings, Systems Neural Correlates, and Underlying Neural Biology.
We described behavioral studies to highlight emotional processing deficits in Alzheimer's disease (AD). The findings suggest prominent deficit in recognizing negative emotions, pronounced effect of positive emotion on enhancing memory, and a critical role of cognitive deficits in manifesting emotional processing dysfunction in AD. We reviewed imaging studies to highlight morphometric and functional markers of hippocampal circuit dysfunction in emotional processing deficits. Despite amygdala reactivity to emotional stimuli, hippocampal dysfunction conduces to deficits in emotional memory. Finally, the reviewed studies implicating major neurotransmitter systems in anxiety and depression in AD supported altered cholinergic and noradrenergic signaling in AD emotional disorders. Overall, the studies showed altered emotions early in the course of illness and suggest the need of multimodal imaging for further investigations. Particularly, longitudinal studies with multiple behavioral paradigms translatable between preclinical and clinical models would provide data to elucidate the time course and underlying neurobiology of emotion processing dysfunction in AD.


Cost-effectiveness of combination daclatasvir-sofosbuvir for treatment of genotype 3 chronic hepatitis C infection in the United States.
A phase III trial evaluated the efficacy and safety of Daklinza (daclatasvir or DCV) in combination with sofosbuvir (SOF) for treatment of genotype (GT) 3 hepatitis C virus (HCV) patients. This study evaluated the cost-effectiveness of DCV + SOF vs SOF in combination with ribavirin (RBV) over a 20-year time horizon from the perspective of a United States (US) payer. A published Markov model was adapted to reflect US demographic characteristics, treatment patterns, costs of drug acquisition, monitoring, disease and adverse event management, and mortality risks. Clinical inputs came from the ALLY-3 and VALENCE trials. The primary outcome was the incremental cost-utility ratio. Life-years, incidence of complications, number of patients achieving sustained virological response (SVR), and the total cost per SVR were secondary outcomes. Costs (2014 USD) and quality-adjusted life years (QALYs) were discounted at 3% per year. Deterministic, probabilistic, and scenario sensitivity analyses were conducted. DCV + SOF was associated with lower costs and better effectiveness than SOF + RBV in the base case and in almost all scenarios (i.e. treatment-experienced, non-cirrhotic, time horizons of 5, 10, and 80 years). DCV + SOF was less costly, but also slightly less effective than SOF + RBV in the cirrhotic and treatment-naïve population scenarios. Results were sensitive to variations in the probability of achieving SVR for both treatment arms. DCV + SOF costs less than $50,000 per QALY gained in 79% of all probabilistic iterations compared with SOF + RBV. DCV + SOF is a dominant option compared with SOF + RBV in the US for the overall GT 3 HCV patient population.


Astrocyte-derived CCL2 participates in surgery-induced cognitive dysfunction and neuroinflammation via evoking microglia activation.
Neuroinflammation induced by peripheral trauma plays a key role in the development of postoperative cognitive dysfunction (POCD). Substantial evidence points to reactive glia as a pivotal factor during the inflammation process. However, little is known about the functional interactions between astrocytes and microglia. Recent evidence suggests the involvement of the CCL2-CCR2 pathway in CNS inflammation-related diseases. Our previous studies have suggested that astrocyte-derived CCL2 can induce microglial activation in vitro. Within this context, we sought to determine if the CCL2/CCR2 axis is involved in the crosstalk between astrocytes and microglia, contributing to increased neuroinflammation. Here, we show that tibial fracture surgery promoted CCL2 upregulation in activated astrocytes, increased CCR2 expression in activated microglia, and induced deficits in learning and memory. Site-directed pre-injection of RS504393, a CCR2 antagonist, inhibited this effect by reducing microglial activation, M1 polarization, inflammatory cytokines, and neuronal injury and death and improving cognitive function. Taken together, these data implicate CCL2-CCR2 signaling in astrocyte-mediated microglial activation in central nervous system (CNS) inflammation and suggest that interference with CCL2 signaling could constitute another potential therapeutic target for POCD.


Servicemembers' Group Life Insurance Traumatic Injury Protection Program--genitourinary losses. Final rule.
The Department of Veterans Affairs (VA) is issuing this final rule that amends the regulations governing the Servicemembers' Group Life Insurance Traumatic Injury Protection (TSGLI) program by adding certain genitourinary (GU) system losses to the TSGLI Schedule of Losses and defining terms relevant to these new losses. This amendment is necessary to make qualifying GU losses a basis for paying TSGLI benefits to servicemembers with severe GU injuries. The intended effect is to expand the list of losses for which TSGLI payments can be made. This document adopts as a final rule, without change, the interim final rule published in the Federal Register on December 2, 2011.


Finite-Horizon $H_{\infty }$ Tracking Control for Unknown Nonlinear Systems With Saturating Actuators.
In this paper, a neural network (NN)-based online model-free integral reinforcement learning algorithm is developed to solve the finite-horizon optimal tracking control problem for completely unknown nonlinear continuous-time systems with disturbance and saturating actuators (constrained control input). An augmented system is constructed with the tracking error system and the command generator system. A time-varying Hamilton-Jacobi-Isaacs (HJI) equation is formulated for the augmented problem, which is extremely difficult or impossible to solve due to its time-dependent property and nonlinearity. Then, an actor-critic-disturbance NN structure-based scheme is proposed to learn the time-varying solution to the HJI equation in real time without using the knowledge of system dynamics. Since the solution to the HJI equation is time-dependent, the form of NNs representation with constant weights and time-dependent activation functions is considered. Furthermore, an extra error is incorporated in order to satisfy the terminal constraints in the weight update law. Convergence and stability proofs are given based on the Lyapunov theory for nonautonomous systems. Two simulation examples are provided to demonstrate the effectiveness of the designed algorithm.


Factors influencing health-related quality of life in chronic liver disease.
To investigate the factors contributing to health-related quality of life (HRQL) in chronic liver disease (CLD). Patients with CLD and age- and sex-matched normal subjects performed the validated Thai versions of the short-form 36 (SF-36) by health survey and chronic liver disease questionnaire (CLDQ). Stepwise multiple regression analysis was used to assess the impact of disease severity, demography, causes of CLD, socioeconomic factors, and self-rating health perception on HRQL. Two-hundred and fifty patients with CLD and fifty normal subjects were enrolled into the study. Mean age and the numbers of low educated, unemployed, blue-collar career and poor health perception increased significantly from chronic hepatitis to Child's Classes A to B to C. Advanced stage of CLD was related to deterioration of HRQL. Increasing age and female reduced physical health area. Low socioeconomic factors and financial burden affected multiple areas of HRQL. In overall, the positive impact of self-rating health perception on HRQL was consistently showed. Advanced stages of chronic liver disease, old age, female sex, low socioeconomic status and financial burden are important factors reducing HRQL. Good health perception improves HRQL regardless of stages of liver disease.


Proposition of New Testing Procedure for the Mechanical Properties of Bulk-Fill Materials.
This study analysed flexural properties, microhardness, and the degree of conversion (DC) of five bulk-fill composites under clinically relevant conditions (4 mm thick specimens) in comparison to 2 mm specimens according to ISO 4049. Additionally, the effect of rapid polymerisation on 4 mm specimens was evaluated after accelerated aging. DC was measured using Fourier transform infrared spectrometry at 2 and 4 mm thick layers, while flexural properties and Vickers microhardness were tested using 16 × 2 × 2 mm or 16 × 2 × 4 mm specimens. Three polymerisation protocols were used: (I) "ISO": 2 mm thickness, 1000 mW/cm2, double-sided; (II) "10 s": 4 mm thickness, 1000 mW/cm2, one-sided; and (III) "3 s": 4 mm thickness, 2600 mW/cm2, one-sided. Mechanical properties were tested after 1 day, after 10,000 thermocycles, and after 10,000 thermocycles followed by a 7-day immersion in absolute ethanol. The "ISO" protocol produced a higher DC and microhardness of all materials. Elastic modulus was significantly higher for the "ISO" protocol compared to the 4 mm specimens. The differences in flexural strength for all polymerisation protocols were equalised after thermocycling and immersion in absolute ethanol. All tested materials met the ISO 4049 flexural strength requirement (80 MPa) for all polymerisation methods and all aging conditions. Rapid polymerisation achieved nearly optimal properties (ISO), except for elastic modulus, which was significantly reduced in 4 mm samples.


Nonsteroidal peptic damage in rheumatoid patients receiving second-line drugs.
Using endoscopy, we assessed the prevalence of peptic ulceration in 281 rheumatoid patients receiving nonsteroidal antiinflammatory drugs alone, or in combination with second-line agents. Ulcers were found in 33 of 96 patients who took nonsteroidals only (33/96, 34%), compared with 8/33 (24%) on hydroxychloroquine, 10/30 (33%) on penicillamine, 13/46 (28%) on sulphasalazine, but only 11/76 (14%) on intramuscular gold plus nonsteroidals (chi 2 = 7.95, 0.001 less than p less than 0.01, p less than 0.05 using Bonferroni correction). Second-line drugs do not seem to increase the prevalence of ulcers related to nonsteroidal antiinflammatory drugs; on the contrary, fewer ulcers were found in patients receiving gold therapy, and this might have therapeutic implications.


Surviving, not thriving: a qualitative study of newly qualified midwives' experience of their transition to practice.
The study explored the experiences of newly qualified midwives and described the factors that facilitated or constrained their development during the transition from student to registered midwife. Knowledge of the transition to midwifery practice remains limited. A qualitative descriptive approach was used. Sixteen graduates from one Australian University participated in a tape-recorded interview. Thematic analysis was used to analyse the data set. The metaphor of 'The Pond', an environment that consists of layers of life and can be both clear and peaceful or murky and infested, was used to describe new midwives perceptions of the context and culture of hospital-based maternity care. For some, 'The Pond' was a harsh environment that often became toxic. The 'Life-raft' metaphor was used to describe the importance of midwife-to-midwife relationships. The theme of 'Swimming' captured the consequence of positive interactions with colleagues and a supportive environment, whilst 'Sinking' described the consequence of poor relationships with midwives and a difficult working environment. The study highlights the importance of positive midwife-to-midwife relationships on the transition from student to registered midwife. There was also evidence that continuity with women and midwifery colleagues enhanced confidence and restored faith in normal birth. At the same time, it was clear that the midwifery culture of some institutions remains highly contested with midwives struggling to provide woman-centred care and often challenged by the risk-averse nature of maternity care. Whilst further work is required, the findings provide a deeper understanding of individual midwives' transition period. The importance of forming longitudinal relationships not only with women but with midwifery colleagues is highlighted. Developing continuity models that adequately support graduates and student's needs are likely to assist in addressing practices issues in both the academic and clinical setting.


[Fibronectin (FN) concentrations in plasma and cerebrospinal fluid (CSF) from guinea pigs with experimental allergic encephalomyelitis (EAE) induced by myelin basic proteins].
The aim of this study was to ascertain whether the FN concentrations in plasma and in CSF are related to the symptomatic status of EAE induced in guinea pigs by myelin basic protein. Guinea pigs were immunized with myelin basic proteins in Freund's complete adjuvant, and after the appearance of neurological symptoms, the plasmas and CSFs from these animals were individually collected. The FN concentrations in these specimens were determined by a solid-phase inhibitory radioimmunoassay using a rabbit antibody specific for guinea pig FN. In plasmas from EAE induced animals, the average value of FN concentrations was lower than that from control animals, but in CSFs from EAE induced animals the average value was slightly higher than that from control animals. The FN concentration in plasma from individual animals with or without EAE was not related to that in the respective CSF, and no direct correlation between the symptomatic severity of EAE and the FN concentration in CSF from the respective animals was observed. These results indicate that the FN concentrations in CSFs probably increase in association with the induction of EAE in guinea pigs, but the levels are highly variable in individual cases, and that the FN concentration in CSF is not available to use as a consistent indicator for EAE in guinea pigs.


[Noradrenaline role in regulation of dopamine-producing neurons in rat arcuate nucleus].
Among most important functions of the neuroendocrine system is the regulation of reproduction, including the inhibitory control of prolactin secretion by dopamine (DA) synthesized in the arcuate nucleus (AN). Besides DA, noradrenaline (NA) contributes to this regulation though, in contrast DA, its concrete functional role remains to be uncertain. In the previous studies, it has been suggested that NA inhibits compensatory synthesis of DA in DA-producing neurons of AN under the failure of the dopaminergic system though no evidence were obtained. Therefore, the goal of this study was to specify the role of NA in the regulation of DA-producing neurons in AN. Two pharmacological models were used to this aim: a) switching off dopaminergic and noradrenergic neurons and their afferents in An or b) switching of only dopaminergic neurons and afferents that allowed us to recognize NA role in the complex catecholaminergic regulation of prolactin secretion. According to our data, the maintaining of the noradrenergic innervation of AN under the neurotoxin-induced failure of dopaminergic neurons resulted in the decrease of the expression of tyrosine hydroxylase (TH), the first enzyme ofDA synthesis, thereby enhancing DA deficit. This is considered as direct evidence of noradrenergic inhibitory control of TH expression in the neurons of AN.


[Progress in the study of ophthalmic molecular biology].
Abundant progress has been made in the study of molecular biology in the last decade, which included the practical application of RNA interference, proteomic, molecular image and nano technology. The communication between bioscience with other branches (including ophthalmology) enhanced the further development of bioscience. This review briefly summarizes these new cutting age information in the field of molecular biology related with eye research to help us to acquire a deeper understanding of the pathogenesis and mechanism of treatment for systemic and eye diseases.


RANKS: a flexible tool for node label ranking and classification in biological networks.
RANKS is a flexible software package that can be easily applied to any bioinformatics task formalizable as ranking of nodes with respect to a property given as a label, such as automated protein function prediction, gene disease prioritization and drug repositioning. To this end RANKS provides an efficient and easy-to-use implementation of kernelized score functions, a semi-supervised algorithmic scheme embedding both local and global learning strategies for the analysis of biomolecular networks. To facilitate comparative assessment, baseline network-based methods, e.g. label propagation and random walk algorithms, have also been implemented. The package is available from CRAN: https://cran.r-project.org/ The package is written in R, except for the most computationally intensive functionalities which are implemented in C. email@example.com Supplementary data are available at Bioinformatics online.


Influence of afferent synaptic innervation on the discharge variability of cat abducens motoneurones.
The discharge variability of abducens motoneurones was studied after blocking inhibitory synaptic inputs or both excitatory and inhibitory inputs by means of an intramuscular (lateral rectus) injection of either a low (0.5 ng kg(-1)) or a high dose (5 ng kg(-1)) of tetanus neurotoxin (TeNT), respectively. Motoneuronal firing increased after low-dose TeNT. High-dose treatment, however, produced a firing depression, and in some cells, a total lack of modulation in relation to eye movements. Firing became increasingly more regular with larger TeNT doses as shown by significant reductions in the coefficient of variation after low- and high-dose treatments. Similarly, autocorrelation histograms of interspike intervals increased the number of resolvable peaks twofold in low-dose-treated motoneurones and sevenfold in high-dose-treated motoneurones. The plots of standard deviation versus the mean instantaneous firing frequency showed an upward deflexion with low firing frequencies. The upward deflexion occurred in controls at 39.9 +/- 4.9 ms, an interval similar to the mean afterhyperpolarisation (AHP) duration (48.4 +/- 8.8 ms). Low-dose TeNT treatment shifted the deflexion point to 20.9 +/- 3.9 ms, whereas the high dose increased it to 60.7 +/- 6.1 ms, in spite of the fact that no differences in AHP parameters between groups were found. The density of synaptophysin-immunoreactive boutons decreased by 14 % after the low-dose treatment and 40.5 % after the high-dose treatment, indicating that protracted synaptic blockade produces elimination of synaptic boutons. It is concluded that abducens motoneurone spike variability during spontaneous ocular fixations depends largely on the balance between inhibitory and excitatory synaptic innervation.


Hepatitis B and C seroprevalence in patients with diabetes mellitus and its relationship with microvascular complications.
Diabetic patients are susceptible to bacterial, viral and fungal infections because of various deficiencies in the immune system. To investigate a possible link between hepatitis B/C prevalence and microvascular complications as well as duration of diabetes. In total 1263 diabetic patients (1149 type 2, 114 type 1) were enrolled in the study. The control group consisted of 1482 healthy blood donors who were over 40 years old. All diabetic patients were tested for HBsAg, anti-HBs and anti-HCV beside routine laboratory tests. Diabetic patients were divided into three groups according to their diabetes duration, and all of the patients were scanned for microvascular complications. Demographic data of all patients were recorded. HBsAg seropositivity was 3.7% in diabetic patients and 1.08% in the control group; this difference was statistically significant (p < 0.001). HBsAg positivity rates in type 1 and type 2 diabetics were 0.8% and 4%, respectively (p = 0.09). HCV seropositivity was 2.2% for diabetics and 0.5% for the control group; this difference was statistically significant (p < 0.001). Anti-HCV seropositivity in type 1 and type 2 diabetics was 1.75% and 2.26%, respectively. There was no relationship between diabetes duration and hepatitis B-C prevalence (p > 0.05). Also, no relationship was found between microvascular complications of diabetes and hepatitis B/C seropositivity. Hepatitis B and C seroprevalence was found to be increased in diabetes mellitus; however, there was no relationship between hepatitis seroprevalence and the duration or microvascular complications of diabetes.


Analysis of anions in alkaline solutions by ion chromatography after solid-phase extraction.
An Ion Chromatographic (IC) method for the determination of six organic acids and three inorganic anions in alkaline solutions was reported. Formic, acetic, propionic, oxalic, succinic, glutaric acid, F-, Cl-, and SO4(2-) were separated and determined in 33 min. The analytes were removed from Bayer liquor by using an ion-exchange resin column. The chromatographic separation was achieved with only one IonPac AS11-HC column thermostated at 30 degrees C. Organic acids and inorganic anions were detected with a suppressed conductance detector. The precision results' showed that the repeatability and reproducibility were < 2.94 and < 1.37%, respectively. The accuracy of the method was assessed by the recoveries ranging from 86.3 to 105.6%. Under optimum conditions the detection limits ranged from 0.008 to 0.053 mg/l.


Noncollinear third-harmonic generation with large angular acceptance by noncritical phase matching in KDP crystal.
The scheme of prefocusing to focus sum frequency generation (SFG) without a lens is proposed and experimentally verified in this study. Noncollinear type-I noncritical phase-matching SFG to generate a third-harmonic wave with large angular acceptance is presented. The principle of broad angular acceptance and the advantages of this PM configuration are also described in detail. External angular bandwidth of 7.33° for noncollinear SFG was measured in a 2 mm long KH2PO4 (KDP) crystal, which is in reasonably good agreement with the theoretical calculation. The mechanism of broadband SFG and the prefocusing scheme make it possible for the realization of convergent third-harmonic generation without involving a lens, which provides a promising way to avoid damage to optical components during the focusing of high-energy UV light in high-power laser facilities.


[Histopathological comparison of stage A prostatic adenocarcinoma in Japan and the United States].
Histopathological characteristics of stage A prostatic adenocarcinoma from Japan (137 cases) and the United States (51 cases) were comparatively evaluated by retrospective analysis. All cases were examined by one referee pathologist (MH) using classification based on Japanese General Rules for Prostatic Cancer (JGRPC), nuclear grading by Mostofi-WHO system and Gleason grading. The incidences of the cases with well differentiated, low nuclear anaplasia and Gleason grade 1 or 2 on primary and secondary grades as well as histologic score 2-4 were much more higher in the cases from Japan as compared with those from the US. In the cases from the US proportion of the cases with moderately differentiated adenocarcinoma and grade 2 nuclear anaplasia exceeded those with well differentiated and grade 1 anaplasia. Adenocarcinomas with Gleason grade 3 in primary and secondary grade and 6-8 of histologic score were also more frequently observed in the cases from the US. No different distribution of each histologic grade could be obtained among the Japanese cases classified stage A2 and entire cases from the US. These results suggest that much more stage A adenocarcinoma in the US might fall into A2 if strict criteria was applied for subcalssification of stage A, which may reflected in the remarkable difference in the incidence of clinical prostatic carcinoma.


Inflammatory bowel disease activity assessment with biologic markers and 99mTc-WBC scintigraphy: are there different trends in ileitis versus colitis?
To evaluate whether scintigraphy with (99m)Tc-labeled white blood cells (WBC) can assess the intensity of bowel inflammation, a large dataset of laboratory values and clinical activity indices was correlated with (99m)Tc-WBC scintigraphy in children with Crohn's disease (CD), ulcerative colitis (UC), and miscellaneous colitis (MC). Also evaluated was whether stratification of children with CD as ileitis versus colitis results in different correlation coefficients for laboratory values versus (99m)Tc-WBC scintigraphy. Over a 6-y period, 313 (99m)Tc-WBC studies were performed. A dataset of 2,714 laboratory values is available for analysis. There is a positive correlation between the erythrocyte sedimentation rate (ESR) and large bowel uptake of (99m)Tc-WBC (P < 0.05) and a negative trend with small bowel uptake of (99m)Tc-WBC in children with CD. Similarly, there is a correlation between WBC counts and scintigraphy in most segments of the large bowel and a negative correlation with the small bowel (R = -0.32, P = 0.01) in children with CD. There is a correlation between platelets and (99m)Tc-WBC in children with CD or UC. There is no correlation between the ESR and (99m)Tc-WBC in children with UC or MC. Many clinical activity indices correlate (P < 0.001) with (99m)Tc-WBC in children with CD, but none correlates in children with UC. Numerous laboratory values correlate with each other. There is a negative correlation between protein, albumin, hemoglobin, and hematocrit versus (99m)Tc-WBC scintigraphy in children with CD. In children with UC, there is a negative correlation between hemoglobin and hematocrit versus (99m)Tc-WBC. (99m)Tc-WBC scintigraphy, ESR, and WBC counts are good indicators of the inflammatory activity in CD if the inflammation is limited to the large bowel. There is a trend toward an inverse relationship when the inflammation is limited to the small bowel; thus, scintigraphy and the aforementioned markers may be of limited value. This report also demonstrates that (99m)Tc-WBC scintigraphy correlates with clinical activity indices in CD and with numerous biologic markers. In children with UC, scintigraphy with (99m)Tc-WBC and most laboratory markers are of limited value in assessing disease activity.


Sex, Race, and HIV Risk Disparities in Discontinuity of HIV Care After Antiretroviral Therapy Initiation in the United States and Canada.
Disruption of continuous retention in care (discontinuity) is associated with HIV disease progression. We examined sex, race, and HIV risk disparities in discontinuity after antiretroviral therapy (ART) initiation among patients in North America. Adults (≥18 years of age) initiating ART from 2000 to 2010 were included. Discontinuity was defined as first disruption of continuous retention (≥2 visits separated by >90 days in the calendar year). Relative hazard ratio (HR) and times from ART initiation until discontinuity by race, sex, and HIV risk were assessed by modeling of the cumulative incidence function (CIF) in the presence of the competing risk of death. Models were adjusted for cohort site, baseline age, and CD4+ cell count within 1 year before ART initiation; nadir CD4+ cell count after ART, but before a study event, was assessed as a mediator. Among 17,171 adults initiating ART, median follow-up time was 3.97 years, and 49% were observed to have ≥1 discontinuity of care. In adjusted regression models, the hazard of discontinuity for patients was lower for females versus males [HR: 0.84; 95% confidence interval (CI): 0.79-0.89] and higher for blacks versus nonblacks (HR: 1.17; 95% CI: 1.12-1.23) and persons with injection drug use (IDU) versus non-IDU risk (HR: 1.33; 95% CI: 1.25-1.41). Sex, racial, and HIV risk differences in clinical retention exist, even accounting for access to care and known competing risks for discontinuity. These results point to vulnerable populations at greatest risk for discontinuity in need of improved outreach to prevent disruptions of HIV care.


Direct refolding of recombinant human growth differentiation factor 5 for large-scale production process.
An efficient downstream process for the production of recombinant human growth differentiation factor 5 (rhGDF5) has been developed for industrial application utilizing a novel "direct refolding" method. In this method, the starting material is an inclusion body produced in Escherichia coli, and the critical step is the direct refolding step that follows directly after solubilization of the inclusion body. rhGDF5 can be refolded at a markedly high concentration of 2.4 mg.ml(-1), which is 24 times that hitherto achieved by the proteins of the TGF-beta superfamily. The refolding yield is 63%, and after purification by diafiltration, isoelectric precipitation and reverse-phase chromatography, the final purification yield is 20% with purity higher than 99%. The yield is more than twice that of a conventionally established process having three chromatography steps and the purity is equivalent. The first pilot-scale trial shows a refolding yield of 51% and a final yield of 11%. The final yield is 1.4 times that of the conventional process, and further optimization at pilot-scale is expected to bring this figure up to or above that of laboratory-scale. As a result, the calculated production cost of rhGDF5 has been reduced dramatically. This type of efficient and simple process is beneficial particularly in the large-scale production of recombinant proteins in which high yield and quality are required.


Is fibre supplementation in paediatric sip feeds beneficial?
The usefulness of a paediatric fibre containing sip feeds specifically formulated for paediatrics has not been evaluated. In an open, prospective, parallel study the efficacy, safety and tolerance of a paediatric fibre-containing sip feed designed for children weighing 8-20 kg (1-6 years) was compared with a fibre-free sip feed in 60 children with chronic illness. The subjects either received a trial sip feed containing 150 kcal (100 ml)(-1) and 2.0 g (100 ml)(-1) of fibre or a fibre-free equivalent control sip feed for 12 weeks. Blood biochemistry, haematology, anthropometry, tolerance and food intake data were estimated during week 1 and 12. The fibre intake was higher (P < 0.0001) and laxative usage decreased in the fibre-containing sip feed group. The sip feed provided almost 50% of fibre intake in the trial group. There were no differences in sip feed tolerance, anthropometry, nutritional biochemistry or haematology between the two groups. Sip feeds provide an important source of fibre for sick children with normal gut function requiring nutritional support.


A Compartmental Model for Zika Virus with Dynamic Human and Vector Populations.
The Zika virus (ZIKV) outbreak in South American countries and its potential association with microcephaly in newborns and Guillain-Barré Syndrome led the World Health Organization to declare a Public Health Emergency of International Concern. To understand the ZIKV disease dynamics and evaluate the effectiveness of different containment strategies, we propose a compartmental model with a vector-host structure for ZIKV. The model utilizes logistic growth in human population and dynamic growth in vector population. Using this model, we derive the basic reproduction number to gain insight on containment strategies. We contrast the impact and influence of different parameters on the virus trend and outbreak spread. We also evaluate different containment strategies and their combination effects to achieve early containment by minimizing total infections. This result can help decision makers select and invest in the strategies most effective to combat the infection spread. The decision-support tool demonstrates the importance of "digital disease surveillance" in response to waves of epidemics including ZIKV, Dengue, Ebola and cholera.


Performance of membrane fixed biocatalyst reactors. I: Membrane reactor systems and modelling.
Enzymatic membrane reactors are discussed according to the state of biocatalyst and driving force of reaction. Particular attention is given to the Capillary Membrane Fixed Enzyme Reactor (CAMFER) for its favorable characteristics. It is shown that, for a practical range of operation conditions, both kinetic and mass transfer effects must be considered simultaneously. Three modes of operation were investigated in detail using enzymatic lactose hydrolysis as a model reaction: Diffusional reactor, Recycle reactor, and Backflush reactor. In the comparison, superior performance of the CAMFER in diffusional mode was clearly demonstrated.


Progress of Statin Therapy in the Treatment of Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease (ILD) characterized by the proliferation of fibroblasts and aberrant accumulation of extracellular matrix. These changes are accompanied by structural destruction of the lung tissue and the progressive decline of pulmonary function. In the past few decades, researchers have investigated the pathogenesis of IPF and sought a therapeutic approach for its treatment. Some studies have shown that the occurrence of IPF is related to pulmonary inflammatory injury; however, its specific etiology and pathogenesis remain unknown, and no effective treatment, with the exception of lung transplantation, has been identified yet. Several basic science and clinical studies in recent years have shown that statins, the traditional lipid-lowering drugs, exert significant antifibrotic effects, which can delay the progression of IPF and impairment of pulmonary function. This article is aimed at summarizing the current understanding of the pathogenesis of IPF, the progress of research on the use of statins in IPF models and clinical trials, and its main molecular targets.


Stroke in rural Ecuador: a three-phase, door-to-door survey.
The authors carried out a three-phase door-to-door survey in Atahualpa, Ecuador to assess epidemiologic and pathogenetic mechanisms of stroke. They found 10 stroke patients among 1,568 individuals aged > or =15 years (crude prevalence, 638 per 100,000). There was only one incident case (incidence, 64 per 100,000). Six of the 10 patients had hypertensive arteriolopathy (five with ischemic and one with hemorrhagic stroke). Additional work is needed to increase knowledge on stroke in developing countries.


Macropinoscope: Real-Time Simultaneous Tracking of pH and Cathepsin B Activity in Individual Macropinosomes.
A fluorescent sensor that allows simultaneous analysis of environmental factors in a limited cellular space is useful for understanding precise molecular interactions in live cells and their biological responses. Macropinocytosis is a ubiquitous endocytic pathway for massive uptake of extracellular fluids, resulting in the formation of macropinosomes. Although macropinocytosis may impact intracellular delivery and cancer proliferation, information on the intracellular behaviors of macropinosomes is limited. Here, we aimed to develop a macropinoscope, a sensor that simultaneously detects pH and cathepsin B activity in individual macropinosomes. A macropinosome-specific marker, dextran (70 kDa), was employed as a platform, onto which fluorescein, Oregon Green, and tetramethylrhodamine were loaded for ratiometric pH sensing and imaging. A cathepsin-B-cleavable peptide sequence bearing sulfo-Cy5 and the quencher BHQ-3 was also mounted; cleavage of the sequence was detected as an increase in sulfo-Cy5 fluorescence. A steep decrease in pH was observed 5-10 min after macropinosome formation, which was accompanied by an immediate increase in cathepsin B activity. Our design concept will lead to the development of other macropinoscopes for the simultaneous detection of other parameters in individual macropinosomes.


Hemofiltration during cardiopulmonary bypass for high risk adult cardiac surgery.
The role of hemofiltration (HF) during cardiopulmonary bypass (CPB) in adult cardiac surgery is controversial. It may be beneficial during prolonged CPB in high-risk surgery. Accordingly, we sought to compare two groups of patients undergoing high-risk cardiac surgery with or without HF. One hundred and eighteen patients who underwent complex cardiac surgical procedures during a 12-month period were divided into two groups. Group I (n=61) comprised patients who were treated with hemofiltration during CPB. Group II (n=57) were not filtered. Estimated risk of death, standard demographic, clinical and surgical features were obtained and predetermined outcomes were studied. Statistical comparisons were made. Age, procedure times and mortality rates were similar in both groups. The mean volume of fluid removed in group I was 3.4 L. The preoperative mean Parsonnet score was 24.8 in group I and 22.5 in group II (ns). Postoperative serum hemoglobin, hematocrit, platelet, and albumin levels were all significantly higher in group I patients (p=0.0015) indicating hemoconcentration. Post-operative chest drainage showed a trend toward decreased post-operative bleeding in group I (p=0.065). Postoperative pleural effusions requiring chest tube drainage were significantly less in group I (9.8% vs. 29.8% 6; p = 0.0062). The incidence of lung infection was also decreased from 26.3% to 13.1% (p=0.05). Operative mortality was similar in both groups (11.4% in group 1, 10.5% in group II, ns). Hemofiltration during CPB attenuates postoperative anemia, thrombocytopenia and hypoalbuminemia, may reduce post-operative bleeding and appears to decrease post-operative pulmonary complications.


Prevalence of metabolic syndrome in Saudi adult soldiers.
To estimate the prevalence of metabolic syndrome in Saudi male soldiers aged 20 years and above using the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). We performed a cross-sectional survey involving a group of 2250 Saudi male soldiers aged 20-60 years residing in a military city in Northern Saudi Arabia in 2004. Participants were recruited from a primary care setting. Anthropometric data together with a brief medical history were obtained from the subjects at initial contact. Laboratory investigations were performed on the following day after fasting for 12 hours. Data on all variables required to define the metabolic syndrome according to NCEP ATP III criteria were available only for 1079 subjects who attended the laboratory for investigations (response rate: 47.9%). Data obtained from these subjects were analyzed excluding the non-respondents from the study sample. The age-adjusted prevalence of metabolic syndrome was found to be 20.8%. Abdominal obesity was the most common component in the study population (33.1%) closely followed by raised serum triglycerides (32.2%) and elevated systolic blood pressure (29.5%). Over two-thirds of the subjects (71%) exhibited at least one criterion for metabolic syndrome. Prevalence of individual factors and mean values of the components of the syndrome showed a steady increase with increase in age and body fat. The estimated prevalence conforms to the rates found in other studies performed in the Middle East and elsewhere. High rates of this syndrome predict an increased burden of cardiovascular disease and diabetes among Saudis over the next few years and call for effective healthcare planning to contain this epidemic.


Partial DiGeorge syndrome at the age of thirty-four.
A 34-year-old man with partial DiGeorge syndrome suffered from seizures and mental retardation from the age of three years. He was diagnosed as having primary hypoparathyroidism by the Ellsworth-Howard test at the age of 22. He was also found to have a right aortic arch. Immunological studies revealed the presence of immature T cells (CD 38+, OKT 9+), although the subsets and function of his T cells were almost normal. The facts that the cardiovascular anomaly and immunodeficiency were mild and the hypoparathyroidism was well controlled, may account for his survival to this age.


Lymph node size in uterine cancer: A revisit.
To study whether lymph node size is a good predictor of lymph node metastasis in uterine cancer, we reviewed the pathologic sections of pelvic and para-aortic lymph node removed from uterine cancer patients who underwent surgical staging in our institution from January 1994 to December 2004. The long axis of each individual node was measured. Out of 4280 total nodes obtained (178 cases), 86 nodes (28 cases) were positive for metastatic cancer (2.0% of total nodes or 15.7% of cases). Among the positive nodes, 11 nodes (12.8%) had nodal long axis <5 mm, 34 nodes (39.5%) had long axis of 5-9 mm, and 32 (37.2%) and 9 nodes (10.5%) had long axes of 10-19 mm and >20 mm, respectively. More than half (52.3%) of these positive nodal long axes were less than 10 mm. At lymph node size of 10 mm that was the common point of reference for pathologic enlargement, the sensitivity, specificity, negative and positive predictive value of lymph node to predict metastatic cancer were 47.7%, 76.7%, 98.6%, and 4.0%, respectively. From these findings, we tended to conclude that lymph node size is not a good predictor of lymph node metastasis in uterine cancer.


An inducible transgenic mouse model for familial hypertension with hyperkalaemia (Gordon's syndrome or pseudohypoaldosteronism type II).
Mutations in the novel serine/threonine WNK [With No lysine (=K)] kinases WNK1 and WNK4 cause PHAII (pseudohypoaldosteronism type II or Gordon's syndrome), a rare monogenic syndrome which causes hypertension and hyperkalaemia on a background of a normal glomerular filtration rate. Current animal models for PHAII recapitulate some aspects of the disease phenotype, but give no clues to how rapidly the phenotype emerges or whether it is reversible. To this end we have created an inducible PHAII transgenic animal model that expresses a human disease-causing WNK4 mutation, WNK4 Q565E, under the control of the Tet-On system. Several PHAII inducible transgenic mouse lines were created, each with differing TG (transgene) copy numbers and displaying varying degrees of TG expression (low, medium and high). Each of these transgenic lines demonstrated similar elevations of BP (blood pressure) and plasma potassium after 4 weeks of TG induction. Withdrawal of doxycycline switched off mutant TG expression and the disappearance of the PHAII phenotype. Western blotting of microdissected kidney nephron segments confirmed that expression of the thiazide-sensitive NCC (Na⁺-Cl⁻ co-transporter) was increased, as expected, in the distal convoluted tubule when transgenic mice were induced with doxycycline. The kidneys of these mice also do not show the morphological changes seen in the previous transgenic model expressing the same mutant form of WNK4. This inducible model shows, for the first time, that in vivo expression of a mutant WNK4 protein is sufficient to cause the rapid and reversible appearance of a PHAII disease phenotype in mice.


Path towards home: Exploring pathways to the development of a sense of home in residential care settings in China.
To understand different pathways leading to older adults' sense of home in residential care environments in China. This research adopted the qualitative comparative analysis method to analyse data from 29 interviews. Qualitative comparative analysis is an analytic strategy to systematically analyse potential causal pathways in small-to-medium-sized qualitative datasets. Findings uncovered four different pathways that older adults followed in their process of constructing a sense of home in residential care environments in China. This study adds to the body of literature by analysing how a sense of home in residential care environments can be achieved with pathways that contain a combination of sets of necessary, substitutive and absent conditions. It concludes that even though older adults may not live at home, they may achieve a sense of home by the joint effort at institutional, social and personal levels that facilitates older adults to find a sense of home.


Single and mixture impacts of two pyrethroids on damselfly predatory behavior and physiological biomarkers.
Direct mortality due to toxicity of single pesticide exposure along a concentration gradient, while the most common, is only one important parameter for assessing the effects of pesticide contamination on aquatic ecosystems. Sub-lethal toxicity can induce changes in an organism's behavior and physiology that may have population-level ramifications and consequences for ecosystem health. Additionally, the simultaneous detection of multiple contaminants in monitored watersheds stresses the importance of gaining a greater understanding of the toxicities of combined exposures, particularly at low, environmentally relevant concentrations. Using larvae of the Azure Damselfly (Coenagrion puella), we conducted a combined exposure investigation of two widely-used pyrethroid insecticides presumed to share the same neurotoxic mechanism of action, and estimated their effect on predatory ability, mobility and three physiological biomarkers (Glutathione S-transferase; GST, respiratory electron transport system; ETS, and malondialdehyde; MDA). Deltamethrin exposure (0.065μg/L and 0.13μg/L) was found to reduce the predatory ability, but it did not affect the larvae's mobility. Esfenvalerate exposure (0.069μg/L and 0.13μg/L), on the other hand, induced no significant changes in predatory ability or mobility. The decrease in predatory ability after the combination exposure (0.067μg/L deltamethrin and 0.12μg/L esfenvalerate) did not significantly differ from the impact of the single deltamethrin exposures. Glutathione-S-transferase was induced after single esfenvalerate exposure and the lower deltamethrin concentration exposure, but seemingly inhibited after exposure to the higher concentration of deltamethrin as well as the combination of both pyrethroids. Our data indicate that sub-lethal exposure to deltamethrin reduces predatory ability and suggest that sub-lethal combined exposure to deltamethrin and esfenvalerate inhibits the GST detoxification pathway. These effects can eventually result in a lower emergence of adults from contaminated ponds.


Maternal Salvage With Extracorporeal Life Support: Lessons Learned in a Single Center.
The American Heart Association scientific statement on cardiac arrest in pregnancy did not endorse extracorporeal life support for lack of cohort data. We studied all pregnancy and peripartum cases of extracorporeal life support in 1 medical center (n = 11), including collapse due to infection (n = 6, 55%), thromboembolism (n = 3, 27%), and cardiac disease (n = 2, 18%). Half of the cases (n = 5, 45%) involved extracorporeal cardiopulmonary resuscitation. Most mothers survived (n = 7, 64% [95% confidence interval, 32%-88%]). Deaths were attributable to oxygenator blockage (n = 1) and late sepsis (n = 3). The 2 unique clinical challenges were maintenance of high peripartum cardiac outputs and balancing anticoagulation with hemostasis.


Randomized Trial of a Mobile Personal Health Record for Behavioral Health Homes.
Behavioral health homes, which provide onsite primary medical care in mental health clinics, face challenges in integrating information across multiple health records. This study tested whether a mobile personal health record application improved quality of medical care for individuals treated in these settings. This randomized study enrolled 311 participants with a serious mental illness and one or more cardiometabolic risk factors across two behavioral health homes to receive a mobile personal health record application (N=156) or usual care (N=155). A secure mobile personal health record (mPHR) app provided participants in the intervention group with key information about diagnoses, medications, and laboratory test values and allowed them to track health goals. The primary study outcome was a chart-derived composite measure of quality of cardiometabolic and preventive services. At 12-month follow-up, participants in the mPHR group maintained high quality of care (70% of indicated services at baseline and at 12-month follow-up), in contrast to a decline in quality for the usual-care group (71% at baseline and 67% at follow-up), resulting in a statistically significant but clinically modest differential impact between the groups. No differences between the study groups were found in secondary self-reported outcomes, including delivery of chronic illness care, patient activation, and quality of life related to mental or general medical health. Use of a mPHR app was associated with a statistically significant but clinically modest differential benefit for quality of medical care among individuals with serious mental illness and comorbid cardiometabolic conditions.


A Simple and Efficient Protocol for the Catalytic Insertion Polymerization of Functional Norbornenes.
Norbornene can be polymerized by a variety of mechanisms, including insertion polymerization whereby the double bond is polymerized and the bicyclic nature of the monomer is conserved. The resulting polymer, polynorbornene, has a very high glass transition temperature, Tg, and interesting optical and electrical properties. However, the polymerization of functional norbornenes by this mechanism is complicated by the fact that the endo substituted norbornene monomer has, in general, a very low reactivity. Furthermore, the separation of the endo substituted monomer from the exo monomer is a tedious task. Here, we present a simple protocol for the polymerization of substituted norbornenes (endo:exo ca. 80:20) bearing either a carboxylic acid or a pendant double bond. The process does not require that both isomers be separated, and proceeds with low catalyst loadings (0.01 to 0.02 mol%). The polymer bearing pendant double bonds can be further transformed in high yield, to afford a polymer bearing pendant epoxy groups. These simple procedures can be applied to prepare polynorbornenes with a variety of functional groups, such as esters, alcohols, imides, double bonds, carboxylic acids, bromo-alkyls, aldehydes and anhydrides.


Use of human cancer cell lines mitochondria to explore the mechanisms of BH3 peptides and ABT-737-induced mitochondrial membrane permeabilization.
Current limitations of chemotherapy include toxicity on healthy tissues and multidrug resistance of malignant cells. A number of recent anti-cancer strategies aim at targeting the mitochondrial apoptotic machinery to induce tumor cell death. In this study, we set up protocols to purify functional mitochondria from various human cell lines to analyze the effect of peptidic and xenobiotic compounds described to harbour either Bcl-2 inhibition properties or toxic effects related to mitochondria. Mitochondrial inner and outer membrane permeabilization were systematically investigated in cancer cell mitochondria versus non-cancerous mitochondria. The truncated (t-) Bid protein, synthetic BH3 peptides from Bim and Bak, and the small molecule ABT-737 induced a tumor-specific and OMP-restricted mitochondrio-toxicity, while compounds like HA-14.1, YC-137, Chelerythrine, Gossypol, TW-37 or EM20-25 did not. We found that ABT-737 can induce the Bax-dependent release of apoptotic proteins (cytochrome c, Smac/Diablo and Omi/HtrA2 but not AIF) from various but not all cancer cell mitochondria. Furthermore, ABT-737 addition to isolated cancer cell mitochondria induced oligomerization of Bax and/or Bak monomers already inserted in the mitochondrial membrane. Finally immunoprecipatations indicated that ABT-737 induces Bax, Bak and Bim desequestration from Bcl-2 and Bcl-xL but not from Mcl-1L. This study investigates for the first time the mechanism of action of ABT-737 as a single agent on isolated cancer cell mitochondria. Hence, this method based on MOMP (mitochondrial outer membrane permeabilization) is an interesting screening tool, tailored for identifying Bcl-2 antagonists with selective toxicity profile against cancer cell mitochondria but devoid of toxicity against healthy mitochondria.


Epidemiological surveillance methods for vector-borne diseases.
Compared with many other diseases, the ever-increasing threat of vector-borne diseases (VBDs) represents a great challenge to public and animal health managers. Complex life cycles, changing distribution ranges, a variety of potential vectors and hosts, and the possible role of reservoirs make surveillance for VBDs a grave concern in a changing environment with increasing economic constraints. Surveillance activities may have various specific objectives and may focus on clinical disease, pathogens, vectors, hosts and/or reservoirs, but ultimately such activities should improve our ability to predict, prevent and/or control the diseases concerned. This paper briefly reviews existing and newly developed tools for the surveillance of VBDs. A range of examples, by no means exhaustive, illustrates that VBD surveillance usually involves a combination of methods to achieve its aims, and is best accomplished when these techniques are adapted to the specific environment and constraints of the region. More so than any other diseases, VBDs respect no administrative boundaries; in addition, animal, human and commodity movements are increasing dramatically, with illegal or unknown movements difficult to quantify. Vector-borne disease surveillance therefore becomes a serious issue for local and national organisations and is being conducted more and more at the regional and international level through multidisciplinary networks. With economic and logistical constraints, tools for optimising and evaluating the performance of surveillance systems are essential and examples of recent developments in this area are included. The continuous development of mapping, analytical and modelling tools provides us with an enhanced ability to interpret, visualise and communicate surveillance results. This review also demonstrates the importance of the link between surveillance and research, with interactions and benefits in both directions.


Accessory urethra in a male. Case report.
A 19-year-old man presented with an unusual accessory urethra located on the shaft of the penis. The diagnosis was stated by biopsy.


Basal insulin combined incretin mimetic therapy with glucagon-like protein 1 receptor agonists as an upcoming option in the treatment of type 2 diabetes: a practical guide to decision making.
The combination of basal insulin and glucagon-like protein 1 receptor agonists (GLP-1 RAs) is a new intriguing therapeutic option for patients with type 2 diabetes. In our daily practice we abbreviate this therapeutic concept with the term BIT (basal insulin combined incretin mimetic therapy) in a certain analogy to BOT (basal insulin supported oral therapy). In most cases BIT is indeed an extension of BOT, if fasting, prandial or postprandial blood glucose values have not reached the target range. In our paper we discuss special features of combinations of short- or prandial-acting and long- or continuous-acting GLP-1 RAs like exenatide, lixisenatide and liraglutide with basal insulin in relation to different glycemic targets. Overall it seems appropriate to use a short-acting GLP-1 RA if, after the near normalization of fasting blood glucose with BOT, the prandial or postprandial values are elevated. A long-acting GLP-1 RA might well be given, if fasting blood glucose values are the problem. Based on pathophysiological findings, recent clinical studies and our experience with BIT and BOT as well as BOTplus we developed chart-supported algorithms for decision making, including features and conditions of patients. The development of these practical tools was guided by the need for a more individualized antidiabetic therapy and the availability of the new BIT principle.


Study protocol for investigating the clinical performance of an automated blood test for glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase L1 blood concentrations in elderly patients with mild traumatic BRAIN Injury and reference values (BRAINI-2 Elderly European study): a prospective multicentre observational study.
Two blood brain-derived biomarkers, glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), can rule out intracranial lesions in patients with mild traumatic brain injury (mTBI) when assessed within the first 12 hours. Most elderly patients were excluded from previous studies due to comorbidities. Biomarker use in elderly population could be affected by increased basal levels. This study will assess the performance of an automated test for measuring serum GFAP and UCH-L1 in elderly patients to predict the absence of intracranial lesions on head CT scans after mTBI, and determine both biomarkers reference values in a non-TBI elderly population. This is a prospective multicentre observational study on elderly patients (≥65 years) that will be performed in Spain, France and Germany. Two patient groups will be included in two independent substudies. (1) A cohort of 2370 elderly patients (1185<80 years and 1185≥80 years; BRAINI2-ELDERLY DIAGNOSTIC AND PROGNOSTIC STUDY) with mTBI and a brain CT scan that will undergo blood sampling within 12 hours after mTBI. The primary outcome measure is the diagnostic performance of GFAP and UCH-L1 measured using an automated assay for discriminating between patients with positive and negative findings on brain CT scans. Secondary outcome measures include the performance of both biomarkers in predicting early (1 week) and midterm (3 months) neurological status and quality of life after trauma. (2) A cohort of 480 elderly reference participants (BRAINI2-ELDERLY REFERENCE STUDY) in whom reference values for GFAP and UCHL1 will be determined. Ethical approval was obtained from the Institutional Review Boards of Hospital 12 de Octubre in Spain (Re#22/027) and Southeast VI (Clermont Ferrand Hospital) (Re# 22.01782.000095) in France. The study's results will be presented at scientific meetings and published in peer-review publications. NCT05425251.


Microfilariae in the cerebrospinal fluid, and neurological complications, during treatment of onchocerciasis with diethylcarbamazine.
Microfilariae of Onchocerca volvulus were found in the cerebrospinal fluid (CSF) of 5/8 heavily infected onchocerciasis patients. During treatment with diethylcarbamazine citrate 10/11 patients showed increased numbers of 0. volvulus microfilariae in the CSF. Patients with concentrations of 8-31 mf/ml CSF developed severe vertigo, and some other neurological manifestations, during treatment. A hypothesis is put forward to account for this clinical piciture, and its importance in relation to the treatment of onchocerciasis is discussed.


Changing children's intergroup attitudes toward refugees: testing different models of extended contact.
The present research evaluated an intervention, derived from the "extended contact hypothesis," which aimed to change children's intergroup attitudes toward refugees. The study (n=253) tested 3 models of extended contact among 5- to 11-year-old children: dual identity, common ingroup identity, and decategorization. Children read friendship stories based upon these models featuring in- and outgroup members. Outgroup attitudes were significantly more positive in the extended contact conditions, compared with the control, and this was mediated by "inclusion of other in self." The dual identity intervention was the most effective extended contact model at improving outgroup attitudes. The effect of condition on outgroup intended behavior was moderated by subgroup identity. Implications for theoretically based prejudice-reduction interventions among children are discussed.


Relationship of nutrient intakes and bone mineral density of elderly women in Daegu, Korea.
The purpose of this study was to examine the relationship between nutrient intake and bone mineral density (BMD) of elderly women in Daegu, Korea. In this study, the bone mineral densities of 101 elderly women in Daegu were measured, and their nutrient intake, dietary habits, and maternal factors were determined through a survey. The subjects were divided into the normal group, the osteopenia group, and osteoporosis group to find out if there is a correlation between bone mineral density and maternal factors, dietary habits, and nutrient intake through their T-scores, analyzed according to the standards of WHO. Classification by T-scores of the participants were the normal group 25.7%, the osteopenia group 39.6%, the osteoporosis group 34.7%. Menopause age of the osteoporosis group was lower, postmenopausal period was longer, and last delivery age was significantly higher than the normal group (p<0.05). Osteoporosis group had a lower percentage of 'everyday' fruit and vegetable intakes and higher percentage of 'never' dairy intake than of the normal group. Vitamin A, vitamin B(1), and vitamin B(2) intakes of participants in the osteoporosis group were lower than those in the normal group (p<0.05). In conclusion, nutritional education is necessary to encourage high intake of milk and vegetables and fruits along with calcium, vitamin A, B(1), and B(1) intakes and low intake of sodium for the prevention of elderly women's osteoporosis.


Role and regulation of ferritin-like proteins in iron homeostasis and oxidative stress survival of Caulobacter crescentus.
Iron is an essential nutrient that is poorly available to living organisms but can be harmful when in excess due to the production of reactive oxygen species. Bacteria and other organisms use iron storage proteins called ferritins to avoid iron toxicity and as a safe iron source in the cytosol. The alpha-proteobacterium Caulobacter crescentus has two putative ferritins, Bfr and Dps, and some other proteins belonging to the ferritin-like superfamily, among them the one encoded by CC_0557. In this work, we have analyzed the role and regulation of these three putative ferritin-like proteins. Using lacZ-transcriptional fusions, we found that bfr expression is positively regulated (2.5-fold induction) by the Fe-responsive regulator Fur in iron sufficiency, as expected for an iron storage protein. Expression of dps was induced 1.5-fold in iron limitation in a Fur-independent manner, while the expression of the product of CC_0557 was unaffected by either iron supply or Fur. With respect to growth phase, while bfr expression was constant during growth, expression of dps (1.4-fold) and CC_0557 (around seven times) increased in the transition from exponential to stationary phase. Deletion mutant strains for each gene and a double dps/bfr mutant were obtained and tested for oxidative stress resistance. The dps mutant was very sensitive to H2O2, and this phenotype was not relieved by the addition of the iron chelator 2',2-dipyridyl in the conditions tested. While bfr and CC_0557 showed no phenotype as to H2O2 resistance, the double dps/bfr mutant had a similar phenotype to the dps mutation alone. These findings indicate that in C. crescentus Bfr contributes to iron homeostasis and Dps has a role in protection against oxidative stress. The role of the protein CC_0557 containing a ferritin-like fold remains unclear.


[Endemic enterovirus meningitis in 4 newborn infants].
Four infants acquired meningitis within ten days in the same maternity unit. They were not severely ill. Fever was neither high nor long-lasting, and sedimentation rate, leukocyte count and C-reactive protein did not suggest bacterial infection, In contrast, there was a marked pleocytosis in the cerebrospinal fluid in three children with leukocyte counts between 2660 and 5000 cells, predominantly granulocytes. As pathogens enteroviruses were identified. One father and one brother of the infants had mild fever and had identical enteroviruses in their stools, and one other father and two further neonates were unaffected carriers.


A C. trachomatis cloning vector and the generation of C. trachomatis strains expressing fluorescent proteins under the control of a C. trachomatis promoter.
Here we describe a versatile cloning vector for conducting genetic experiments in C. trachomatis. We successfully expressed various fluorescent proteins (i.e. GFP, mCherry and CFP) from C. trachomatis regulatory elements (i.e. the promoter and terminator of the incDEFG operon) and showed that the transformed strains produced wild type amounts of infectious particles and recapitulated major features of the C. trachomatis developmental cycle. C. trachomatis strains expressing fluorescent proteins are valuable tools for studying the C. trachomatis developmental cycle. For instance, we show the feasibility of investigating the dynamics of inclusion fusion and interaction with host proteins and organelles by time-lapse video microscopy.


Sustained Epigenetic Drug Delivery Depletes Cholesterol-Sphingomyelin Rafts from Resistant Breast Cancer Cells, Influencing Biophysical Characteristics of Membrane Lipids.
Cell-membrane lipid composition can greatly influence biophysical properties of cell membranes, affecting various cellular functions. We previously showed that lipid synthesis becomes altered in the membranes of resistant breast cancer cells (MCF-7/ADR); they form a more rigid, hydrophobic lipid monolayer than do sensitive cell membranes (MCF-7). These changes in membrane lipids of resistant cells, attributed to epigenetic aberration, significantly affected drug transport and endocytic function, thus impacting the efficacy of anticancer drugs. The present study's objective was to determine the effects of the epigenetic drug, 5-aza-2'-deoxycytidine (DAC), delivered in sustained-release nanogels (DAC-NGs), on the composition and biophysical properties of membrane lipids of resistant cells. Resistant and sensitive cells were treated with DAC in solution (DAC-sol) or DAC-NGs, and cell-membrane lipids were isolated and analyzed for lipid composition and biophysical properties. In resistant cells, we found increased formation of cholesterol-sphingomyelin (CHOL-SM) rafts with culturing time, whereas DAC treatment reduced their formation. In general, the effect of DAC-NGs was greater in changing the lipid composition than with DAC-sol. DAC treatment also caused a rise in levels of certain phospholipids and neutral lipids known to increase membrane fluidity, while reducing the levels of certain lipids known to increase membrane rigidity. Isotherm data showed increased lipid membrane fluidity following DAC treatment, attributed to decrease levels of CHOL-SM rafts (lamellar beta [Lβ] structures or ordered gel) and a corresponding increase in lipids that form lamellar alpha-structures (Lα, liquid crystalline phase). Sensitive cells showed marginal or insignificant changes in lipid profile following DAC-treatment, suggesting that epigenetic changes affecting lipid biosynthesis are more specific to resistant cells. Since membrane fluidity plays a major role in drug transport and endocytic function, treatment of resistant cells with epigenetic drugs with altered lipid profile could facilitate anticancer drug transport to overcome acquired drug resistance in a combination therapy.


[Multidrug resistance of malignant tumors].
The development of resistance to chemotherapy is a major problem in the treatment of malignant tumors. Clinically, this is characterized by short periods of remission and failure to respond to subsequent therapy. Multidrug-resistance or pleiotropic resistance describes the simultaneous expression of cellular resistance to a vide range of structurally unrelated drugs (e.g. alkaloids, anthracyclines, antibiotics, etc.). The most frequently reported alteration of multidrug-resistant cells is the overexpression of a 170 kD glycoprotein (P--170 or P-glycoprotein) encoding by the MDR gene family. A great deal of evidence has suggested that the P-glycoprotein is, in fact, an energy-dependent drug efflux pump. Pharmacological overcome of MDR may indicate to circumvent clinically observed drug resistance.


Rank-based permutation approaches for non-parametric factorial designs.
Inference methods for null hypotheses formulated in terms of distribution functions in general non-parametric factorial designs are studied. The methods can be applied to continuous, ordinal or even ordered categorical data in a unified way, and are based only on ranks. In this set-up Wald-type statistics and ANOVA-type statistics are the current state of the art. The first method is asymptotically exact but a rather liberal statistical testing procedure for small to moderate sample size, while the latter is only an approximation which does not possess the correct asymptotic α level under the null. To bridge these gaps, a novel permutation approach is proposed which can be seen as a flexible generalization of the Kruskal-Wallis test to all kinds of factorial designs with independent observations. It is proven that the permutation principle is asymptotically correct while keeping its finite exactness property when data are exchangeable. The results of extensive simulation studies foster these theoretical findings. A real data set exemplifies its applicability.


A cost-effectiveness analysis of the diagnostic strategies for differentiating focal nodular hyperplasia from hepatocellular adenoma.
We evaluated the cost-effectiveness of a gadoxetic acid-enhanced MRI (EOB-MRI) strategy compared with conventional MRI strategy and biopsy to differentiate focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA). A decision tree model was constructed to compare the cost-effectiveness of EOB-MRI, conventional MRI with extracellular contrast agents, and biopsy as the initial diagnostic modality in patients with incidentally detected focal liver lesions suspected of being FNH or HCA. We analysed the cost and effectiveness, i.e. probability of successful diagnosis of each strategy. Costs were based on utilisation rates and Medicare reimbursements in the USA and South Korea. In the base case analysis of our decision tree model, the effectiveness of the three strategies was similar. The cost of the EOB-MRI strategy ($1283 in USA, $813 in South Korea) was lowest compared with the biopsy strategy ($1725 in USA, $847 in South Korea) and the conventional MRI strategy ($1750 in USA, $962 in South Korea). One-way, two-way and probabilistic sensitivity analysis showed unchanged results over an acceptable range. EOB-MRI strategy is the most cost-effective strategy for differentiating FNH from HCA in patients with incidentally detected focal liver lesions in a non-cirrhotic liver. • The effectiveness of the three strategies was similar. • The cost of the EOB-MRI strategy was lowest. • EOB-MRI strategy is the most cost-effective for differentiating FNH from HCA.


Management of chronic hypertension in older men: an exploration of patient goal-setting.
Goal-setting is an approach to collaborative chronic care that involves clinicians and patients working together to set goals and to initiate and maintain specific self-care behaviors. Using patients' own perspectives, this study describes how goals for the self-management of hypertension are developed and whether or not they conform to the characteristics of effective goal-setting. Qualitative methodology was used to explore the process of setting self-management goals for hypertensive patients. Thirty patients participated in semi-structured interviews that ascertained the detail and specificity of self-care goals, timing and quality of feedback for setting and monitoring goals and the role of family members and caregivers in setting goals. Patients understood the risks associated with hypertension, had intentions to control their disease, reported conducting at least one self-care task and set informal goals for themselves; however, these goals lacked the characteristics needed to initiate and maintain behavior change. Patient goal-setting is underdeveloped and poorly supported in chronic hypertension care. Future studies need to examine ways to support effective goal-setting. As part of chronic hypertension care, health care providers should incorporate time and support for dedicated goal-setting to improve the effectiveness of self-management behaviors.


Intestinal obstruction due to spontaneous intramural hematoma of the small intestine during warfarin use: a report of two cases.
Warfarin-dependent spontaneous intramural hematoma of the small intestine is a rare complication. The first symptom is usually abdominal pain, frequently accompanied by nausea and vomiting. In some cases, concomitant gastrointestinal bleeding might be seen. Ultrasonography and computed tomography are the most useful radiographic methods for the diagnosis of an intramural hematoma of the intestines. Although it is usually treated conservatively, surgical intervention is required in cases involving active bleeding, intestinal obstruction, or acute abdominal symptoms. Here we present two patients who were treated surgically. Both patients had intestinal obstruction and ischemia, and one had concomitant gastrointestinal bleeding and intussusception due to an intramural hematoma.


Proline porter II is activated by a hyperosmotic shift in both whole cells and membrane vesicles of Escherichia coli K12.
Proline porter II is rapidly activated when nongrowing bacteria are subjected to a hyperosmotic shift (Grothe, S., Krogsrud, R. L., McClellan, D. J., Milner, J. L., and Wood, J. M. (1986) J. Bacteriol. 166, 253-259). Proline porter II was active in membrane vesicles prepared from bacteria grown under optimal conditions, nutritional stress, or osmotic stress. That activity was: (i) dependent on the presence of the energy sources phenazine methosulphate plus ascorbate or D-lactate; (ii) observed only when a hyperosmotic shift accompanied the transport measurement; (iii) inhibited by glycine betaine in a manner analogous to that observed in whole cells; and (iv) eliminated by lesions in proP. Membrane vesicles were able to transport serine but not glutamine and serine transport was reduced by the hyperosmotic shift. In whole cells, proline porter II activity was supported by glucose and by D-lactate in a strain defective for proline porters I and III and the F1F0-ATPase. Glucose energized proline uptake was eliminated by carbonyl cyanide m-chlorophenylhydrazone and KCN as was serine uptake. These results suggested that proline porter II was respiration-dependent and probably ion-linked. Activation of proline porter II in whole cells by sucrose or NaCl was sustained over 30 min, whereas activation by glycerol was transient. Proline porter II was activated by NaCl and sucrose with a half-time of approximately 1 min in both whole cells and membrane vesicles. Thus, activation of proline porter II was reversible. It occurred at a rate comparable to that of K+ influx and much more rapid than the genetic regulatory responses that follow a hyperosmotic shift.


The identification of up-regulated ebv-miR-BHRF1-2-5p targeting MALT1 and ebv-miR-BHRF1-3 in the circulation of patients with multiple sclerosis.
Epstein-Barr virus (EBV) is a well-documented aetiological factor for multiple sclerosis (MS). EBV encodes at least 44 microRNAs (miRNAs) that are readily detectable in the circulation of human. Previous studies have demonstrated that EBV-encoded miRNAs regulate host immune response and may serve as biomarkers for EBV-associated diseases. However, the roles of EBV miRNAs in MS are still unknown. To fill the gap, we conducted a comprehensive profiling of 44 mature EBV miRNAs in 30 relapsing-remitting MS (RRMS) patients at relapse and 30 matched healthy controls. Expression levels of ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-3 were elevated significantly in the circulation and correlated positively with the expanded disability status scale (EDSS) scores of MS patients. Receiver operating characteristic (ROC) analyses confirmed that the expression of these two miRNAs distinguished MS patients clearly from healthy controls. Luciferase assays revealed that ebv-miR-BHRF1-2-5p may directly target MALT1 (mucosa-associated lymphoid tissue lymphoma transport protein 1), a key regulator of immune homeostasis. In conclusion, we described the expression of EBV miRNAs in MS and preliminarily validated the potential target genes of significantly altered EBV miRNAs. The findings may pave the way for prospective study about the pathogenesis of MS.


High- versus low-dose methylprednisolone for acute rejection episodes in renal transplantation.
A double-blind, randomized trial was conducted to compare the efficacy and safety of two doses of methylprednisolone (MP) in reversing acute rejection episodes in renal allograft recipients. 18 subjects were randomized to receive either 250 mg (group 1) or 1,000 mg (group 2) MP daily for 4 days. The two groups were similar with regard to HLA matching, number of cadaveric grafts, number of second transplants, and transfusion history. 6 of 10 patients in group 1 and 4 of 8 in group 2 responded to treatment with MP, i.e., serum creatinine returned to baseline. 1-year follow-up has demonstrated a similar graft survival, 70% in group 1 and 50% in group 2. There were no significant differences in mortality, infectious complications, blood glucose, and blood pressure between the two groups. We conclude that (1) 250 mg MP is as effective as 1,000 mg in reversing acute rejection in renal allografts; (2) 1,000 mg MP does not result in a greater incidence of adverse effects, and (3) 250 mg MP does not adversely affect 1-year graft survival.


Bioinformatic analysis of circadian gene oscillation in mouse aorta.
Circadian rhythmicity of many aspects of cardiovascular function-blood pressure, coagulation and contractile function-is well established, as is diurnal variation in important clinical events, such as myocardial infarction and stroke. Here, we undertake studies to globally assess circadian gene expression in murine aorta. Aortae from mice were harvested at 4-hour intervals for 2 circadian cycles (48 hours). Gene expression was assessed by expression profiling and subjected to a gene ontology bioinformatics analysis. Three hundred thirty transcripts exhibited a circadian pattern of oscillation in mouse aorta, including those intrinsic to the function of the molecular clock. In addition, many genes relevant to protein folding, protein degradation, glucose and lipid metabolism, adipocyte maturation, vascular integrity, and the response to injury are also included in this subset of roughly 7000 genes screened for circadian oscillation. Detection of functional cassettes of vascular genes that exhibit circadian regulation in the mouse will facilitate elucidation of the mechanisms by which the molecular clock may interact with environmental variables to modulate cardiovascular function and the response to therapeutic interventions.


[Cloning of human KIAA1173 gene and biological characterization of transfected 6-10B cells].
To establish a 6-10B cell line with stable expression of KIAA1173 gene and study the biological behaviors of the cells. The total RNA was extracted from normal skeletal muscular tissues for cloning of KIAA1173 gene by means of RT-PCR which was subsequently introduced into pcDNA3.1 (+) vector. The recombinant eukaryotic expression vector pcDNA 3.1(+)-KIAA1173 was constructed and identified by endonuclease digestion and sequencing before transfection into 6-10B cells via lipofectamine with the empty vector as the control. The positive cell clones were obtained by G418 selection. Stable expression of KIAA1173 gene in the transfected 6-10B cells was determined by RT-PCR, in situ hybridization and immunocytochemistry, and the biological behaviors of the transfected cells were observed by MTT assay, cell invasion assay and tumorigenesis assay in nude mice. High expression of KIAA1173 at both mRNA and protein levels was observed in the transfected 6-10B cells. The capability of proliferation, invasion and tumorgenicity of the KIAA1173-transfected cells in nude mice was lowered in comparison with those of the cells transfected with pcDNA3.1 (+) vector (P<0.05). KIAA1173 genes may function as a potential tumor suppressor of nasopharyngeal carcinoma both in vitro and in vivo. The 6-10B cell line expressing KIAA1173 has been obtained, which can be helpful for further study of KIAA1173 gene.


[Treatment of chronic hip dislocation in adults by recentered total prosthesis. Apropos of 43 cases].
Forty-three total hip prostheses were inserted in 33 adults suffering from a chronic high dislocation of the hip. Ten patients had a bilateral arthroplasty. The authors decided to keep in this series only hips presenting with a very considerable upward displacement of the femoral head of type IV in Crowe, Maini and Ranawat's classification. All the hips were treated in the same way with pre-operative planning using template tracings to anticipate problems of length and choice of implant. The acetabular cup was placed in the old acetabulum with downward displacement of the femur. The results were studied in 39 prostheses with a mean follow-up of five-and-a-half years (two years to nine-and-a-half years). The mean age of the patients was 48 and-a-half years (28 to 76 years). A satisfactory result was obtained in 79.5 per cent of cases. The mean downward displacement of the femur was 4.8 cm. Complications included one death from pulmonary embolus, two phlebitides, two fractures of the femoral shaft and four dislocations. There were nos cases of sepsis or neurological complications. The authors advise the use of custom-made implants, consider the tactical problems relative to the opposite hip. It is concluded that the value of the method often lies in the transformation of the life of these young patients by a "functional miracle", but the operative indications need to be considered carefully, since the procedures are sometimes extensive, often difficult and always require technical skill.