Decreased visual acuity from optic disc drusen.
Although visual field defects occur commonly from optic disc drusen, reduction in visual acuity is rare. We describe four patients with reduced visual acuity and one with visual field constriction to the point of legal blindness that resulted from optic disc drusen. The acute episodic and stepwise nature of visual loss in some of the cases in our series suggests a vascular mechanism. Reduced visual acuity from drusen remains a diagnosis of exclusion. It should be considered, however, when visual loss has been acute and nonprogressive or stepwise in a nerve fiber bundle distribution and when visual acuity is not reduced until visual field constriction is severe.


Enterococcal peptide sex pheromones: synthesis and control of biological activity.
The enterococcal pheromone-inducible plasmids such as pCF10 represent a unique class of mobile genetic elements whose transfer functions are induced by peptide sex pheromones. These pheromones are excreted by potential recipient cells and detected by plasmid-containing donor cells at the cell surface, where the pheromone is imported and signals induction of the plasmid transfer system. Pheromone is processed from a chromosomally encoded lipoprotein and excreted by both the donor and recipient cells, but a carefully controlled detection system prevents a response to self-pheromone while still allowing an extremely sensitive response to exogenous pheromone.


Masked symptoms: mid-life women, health, and work.
Data from the Canadian Labour Force Survey (1997) reveal that relatively few mid-life women offer ill health as a reason for leaving their job or downshifting to part-time employment, implying that the role of ill health may be inconsequential in effecting changing patterns in mid-life women's labour force activity. In contrast, interviews with 30 mid-life women (aged 40 to 54 years) illustrate that, although they do not offer illness as their main reason for leaving their job or working part-time, health is a determining factor. This research also maps the complex relationship between work and ill health, showing that stressful working conditions (due to funding cuts and policy changes) affected the mental and physical health of this group of mid-life women, which, in turn, influenced their decision to change their labour force activity. The author concludes that policy makers must recognize that ill health may be under-reported among mid-life women in large surveys and that research is needed that specifically examines women's working conditions as they relate to health. Such research should not be based solely on large surveys but must also include qualitative studies that capture women's experiences.


Dual Role of Vitamin C on the Neuroinflammation Mediated Neurodegeneration and Memory Impairments in Colchicine Induced Rat Model of Alzheimer Disease.
The neurodegeneration in colchicine induced AD rats (cAD) is mediated by cox-2 linked neuroinflammation. The importance of ROS in the inflammatory process in cAD has not been identified, which may be deciphered by blocking oxidative stress in this model by a well-known anti-oxidant vitamin C. Therefore, the present study was designed to investigate the role of vitamin C on colchicine induced oxidative stress linked neuroinflammation mediated neurodegeneration and memory impairments along with peripheral immune responses in cAD. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus of cAD. Administration of vitamin C (200 and 400 mg/kg BW) in cAD resulted in recovery of memory impairments, with prevention of neurodegeneration and neuroinflammation in the hippocampus. The neuroinflammation in the hippocampus also influenced the peripheral immune responses and inflammation in the serum of cAD and all of these parameters were also recovered at 200 and 400 mg dose of vitamin C. However, cAD treated with 600 mg dose did not recover but resulted in increase of memory impairments, neurodegeneration and neuroinflammation in hippocampus along with alteration of peripheral immune responses in comparison to cAD of the present study. Therefore, the present study showed that ROS played an important role in the colchicine induced neuroinflammation linked neurodegeneration and memory impairments along with alteration of peripheral immune responses. It also appears from the results that vitamin C at lower doses showed anti-oxidant effect and at higher dose resulted in pro-oxidant effects in cAD.


Cytotoxic T lymphocyte recognition of a xenogeneic major histocompatibility complex antigen expressed in transgenic mice.
Introduction of a porcine major histocompatability complex (MHC) class I gene (PD1) into the genome of a C57BL/10 (B10) mouse has been shown to lead to cell surface expression of the porcine MHC antigen, SLAPD1 in a transgenic mouse. The PD1 product expressed on spleen cells from the transgenic mice stimulated B10 spleen cells in a mixed lymphocyte culture to generate PD1-specific cytotoxic T lymphocytes (CTL). The CTL were PD1 specific since they lysed transgenic splenic blast cells and PD1-transfected L cells, but not B10 blasts or control L cells. The CTL were L3T4-, Lyt-2+ and their activity was partially inhibited by either anti-Lyt-2 antibody or by anti-swine MHC alloantibodies. The repertoire of responding B10 anti-transgenic CTL was assessed by examining their cross-reactivity on a series of murine allogeneic targets. The B10 anti-transgenic CTL showed some cross-reactivity on conventional allogeneic targets, but reacted strongly on a series of mutant H-2Kbm blast cells. In addition, B10 anti-B6.cH-2bm6 CTL cross-reacted extensively on the transgenic target cells. These results demonstrated that normal B10 CTL possess a repertoire specific for the products of the xenogeneic class I gene PD1, that this repertoire is cross-reactive with the conventional alloreactive CTL repertoire, and that there exists an unanticipated relationship between PD1-specific CTL and CTL specific for Kb mutant determinants.


[Concept and Implementation of ECG Monitoring for Whole-course of Pre-hospital Emergency].
In pre-hospital emergency, it's essential to immediate recognize cardiac arrest, and use real-time ECG monitoring for patients. We propose a concept of whole-course ECG monitoring and implementation in pre-hospital emergency, and design a portable pre-hospital ECG monitor (Pre-ECG). There are two working modes in Pre-ECG, i.e., rapid detection and continuous monitoring modes. In rapid detection mode, ECG waves and heart rate of patients can be displayed in a few seconds by using metal electrodes, which helps to understand the status of patients' cardiac electrical activity. After connecting lead wire to the Pre-ECG, it can automatically switch to working in continous monitoring mode. At this time, ECG waves and heart rate can be displayed in real time, and give an alarm for abnormalities of heart rate, which can well meet the requirement from transfer process of patients. Moreover, all ECG data derived from the two modes can be stored permanently in TranFlash card, which can be printed via bluetooth printer, be used for remote medical consultation through the internet, or be reserved as legal evidence and academic research materials.


Tuning hierarchically aligned structures for high-strength PMIA-MWCNT hybrid nanofibers.
Novel hierarchically aligned PMIA-MWCNT hybrid nanofibers with a robust tensile strength of 316.7 MPa were prepared by a facile electrospinning process. The critical roles of humidity and MWCNT contents in tuning hierarchically aligned structures were first proposed, and a two-step break mechanism upon external stress was confirmed.


Borderline ovarian tumors and fertility.
Borderline ovarian tumors (BOTs) are a distinct diagnostic category of epithelial ovarian tumors, distinguished from both benign and invasive epithelial ovarian tumors. Because they affect young women of childbearing age, are diagnosed at an early stage, and are associated with excellent prognosis, fertility-sparing options are often used. In this review, we discuss recent findings on the outcomes of fertility-sparing treatments in patients with BOTs. Reports on the use of fertility-sparing surgery in patients with advanced-stage BOTs and on the application of laparoscopy in fertility-sparing surgery are increasing. As potential alternative, experiences on ovarian tissue cryopreservation have been reported. Fertility-sparing surgery is the best option to preserve childbearing capacity in young patients with BOTs. Fertility-sparing surgery is well tolerated not only in patients with early-stage BOTs but also in patients with advanced-stage BOTs with noninvasive extraovarian implants, if these implants can be resected completely. After fertility-sparing surgery, pregnancy outcomes are promising and most pregnancies are achieved spontaneously. There are few complications associated with pregnancy, and subsequent pregnancy seems to have little impact on disease course. Fertility drugs are well tolerated in patients with infertility after fertility-sparing surgery for early-stage BOTs, but caution should be exercised when using these drugs after surgery in patients with advanced-stage BOTs. If fertility-sparing surgery is technically not feasible owing to extensive tumor involvement of both ovaries, recent artificial reproductive technologies can be considered, including embryo, oocyte, and ovarian tissue freezing; use of donor oocytes; and surrogacy, but more experience with these options is required.


Heparan sulfate degradation: relation to tumor invasive and metastatic properties of mouse B16 melanoma sublines.
After transport in the blood and implantation in the microcirculation, metastatic tumor cells must invade the vascular endothelium and underlying basal lamina. Mouse B16 melanoma sublines were used to determine the relation between metastatic properties and the ability of the sublines to degrade enzymatically the sulfated glycosaminoglycans present in the extracellular matrix of cultured vascular endothelial cells. Highly invasive and metastatic B16 sublines degraded matrix glycosaminoglycans faster than did sublines of lower metastatic potential. The main products of this matrix degradation were heparan sulfate fragments. Intact B16 cells (or their cell-free homogenates) with a high potential for lung colonization degraded purified heparan sulfate from bovine lung at higher rates than did B16 cells with a poor potential for lung colonization. Analysis of the degradation fragments indicated that B16 cells have a heparan sulfate endoglycosidase. Thus the abilities of B16 melanoma cells to extravasate and successfully colonize the lung may be related to their capacities to degrade heparan sulfate in the walls of pulmonary blood vessels.


Synthesis of highly modified DNA by a combination of PCR with alkyne-bearing triphosphates and click chemistry.
We report the combination of "click chemistry" with PCR by using alkyne-modified triphosphates for efficient and homogeneous labeling of DNA. A series of modified PCR products of different lengths (300, 900, and 2000 base pairs) were prepared by using a variety of alkyne- and azide-containing triphosphates and different polymerases. After intensive screening of real-time PCR methods, protocols were developed that allow the amplification of genes by using these modified triphosphates with similar efficiency to that of standard PCR. The click reaction on the highly modified PCR fragments provided conversion rates above 90 % and resulted in the functionalization of hundreds of alkynes on large DNA fragments with superb selectivity and efficiency.


The in-capillary- 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)-sweeping micellar electrokinetic chromatography - Diode array detector method for screening and quantifying trace natural antioxidants from Schisandra chinensis.
An in-capillary 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)-sweeping micellar electrokinetic chromatography-diode array detector (ABTS+-sweeping MEKC-DAD) method was developed and successfully applied to screening and quantifying antioxidative ingredients from natural products. The parameters affecting sweeping and separation were optimized including components of background electrolyte and sample matrix. Comparing with previously reported MEKC, the sensitivity enhancement factors of trace natural antioxidants obtained by this proposed method were from 17 to 167. The limit of detection was as low as 6 ng·mL-1. The results of other validation parameters including linearity, reproducibility, accuracy and recovery were satisfactory. Seven compounds including schizandrin, schisandrol B, schisantherin B, schisantherin A, schisanhenol, deoxyschizandrin, schisandrin B were identified as the main antioxidants in Schisandra chinensis. It was demonstrated that this developed in-capillary ABTS+-sweeping MEKC-DAD is simple, sensitive, reliable and rapid method for screening and quantifying trace antioxidants from natural products.


Automated structure-based prediction of functional sites in proteins: applications to assessing the validity of inheriting protein function from homology in genome annotation and to protein docking.
A major problem in genome annotation is whether it is valid to transfer the function from a characterised protein to a homologue of unknown activity. Here, we show that one can employ a strategy that uses a structure-based prediction of protein functional sites to assess the reliability of functional inheritance. We have automated and benchmarked a method based on the evolutionary trace approach. Using a multiple sequence alignment, we identified invariant polar residues, which were then mapped onto the protein structure. Spatial clusters of these invariant residues formed the predicted functional site. For 68 of 86 proteins examined, the method yielded information about the observed functional site. This algorithm for functional site prediction was then used to assess the validity of transferring the function between homologues. This procedure was tested on 18 pairs of homologous proteins with unrelated function and 70 pairs of proteins with related function, and was shown to be 94 % accurate. This automated method could be linked to schemes for genome annotation. Finally, we examined the use of functional site prediction in protein-protein and protein-DNA docking. The use of predicted functional sites was shown to filter putative docked complexes with a discrimination similar to that obtained by manually including biological information about active sites or DNA-binding residues.


Strain difference in morphine-induced increase in plasma cyclic AMP and cyclic GMP levels in relation to locomotor activity in male mice.
The effects of morphine on plasma cyclic nucleotide levels and on locomotor activity were investigated in four inbred strains of male mice. Morphine increased both cyclic AMP and cyclic GMP levels as well as locomotor activity in C57BL/6N mice. In BALB/cAnN mice, morphine increased plasma cyclic GMP levels and motor activity without changes in plasma cyclic AMP levels. In C3H/HeN mice, morphine increased plasma cyclic GMP levels without changing cyclic AMP levels and motor activity, but neither plasma cyclic nucleotide levels nor motor activity were increased by morphine in DBA/2N mice. Epinephrine and carbachol increased plasma cyclic AMP and cyclic GMP levels, respectively, in both C57BL and DBA mice. These results show that there is a significant strain difference in the effects of morphine on plasma cyclic nucleotide levels as well as motor activity. The major cause of strain difference in the effects of morphine on cyclic nucleotide levels is unlikely to be due to the difference in the regulation of adenylate cyclase linked to adrenoceptors or that of guanylate cyclase connected with cholinoceptors.


Clinical significance of T.T. virus infection in maintenance hemodialysis patients of an endemic area for hepatitis C infection.
Clinical significance of TTV infection was analyzed in Egyptian hemodialysis (HD) patients. Forty-seven Egyptian patients on maintenance HD and 50 age-matched volunteer blood donors were investigated. TT virus (TTV) DNA detection and genotyping were performed using a semi-nested polymerase chain reaction with specific primers. The prevalence of TTV DNA in patients on HD (66%) was significantly (P<0.001) higher than in blood donors (24%) with genotype 1b predominance (89%) in both. Clinical background including mean age, sex, history of blood transfusion, and positive markers for either hepatitis B virus (HBV) or hepatitis C virus (HCV) did not differ between TTV DNA positive and negative HD patients. However, the mean duration of HD was significantly (P=0.032) shorter in the TTV positive patients (28+/-19 months) than in the negative ones (45+/-34 months). Mean alanine aminotransferase level in patients with HCV infection alone (41+/-24 IU/l) did not differ from that in patients with both co-infection (33+/-28 IU/l), but was significantly higher than that in patients with TTV infection alone (26+/-10 IU/l). Occurrence of chronic hepatic changes in patients with TTV infection alone (7%) was significantly less common than those with HCV infection alone (100%, P<0.001) or those with both co-infection (100%, P<0.001). Serum level of HCV core protein was similar between patients with HCV infection alone and those with co-infection with TTV. In conclusion, the prevalence of TTV infection is high in Egyptian patients on regular HD, especially with shorter duration on HD. No clinical significance of TTV virus could be elicited in HD Egyptian patients; neither it showed any clinical impact as a co-infection with HCV.


First Report of Leek yellow stripe virus in Garlic in Ohio.
Leek yellow stripe virus (LYSV), genus Potyvirus, family Potyviridae, infects a wide range of Allium species worldwide. LYSV is one of several viruses that chronically infect garlic, Allium sativum L. The garlic virus complex, which includes LYSV, Onion yellow dwarf virus, and Garlic common latent virus, is perpetuated by asexual propagation (4) and is transmitted to clean planting material by aphids (3). This virus complex can reduce garlic bulb weight by nearly three quarters (2), and LYSV-only infections can result in approximately a one-quarter reduction in bulb weight (2). Garlic is grown as a small-scale, specialty crop in Ohio. During late May and early June 2013, garlic plants with virus-like symptoms were collected from Medina, Holmes, and Wayne counties, Ohio. Plants exhibited chlorotic streaking, foliar dieback, dwarfing, small bulbs, and cylindrical bulbs that failed to differentiate into cloves. Incidence of affected plants in the fields was up to 5% and all fields had early season aphid infestations. Flexuous rods were observed in TEM micrographs of plant sap from symptomatic leaves. Five symptomatic plants and six asymptomatic plants (from fields with symptomatic plants) were evaluated for LYSV by DAS-ELISA (Agdia, Inc., Elkhart, IN). Reverse transcriptase (RT)-PCR with LYSV-specific primers LYSV-WA and LYSV-WAR (3) was performed with cDNA generated by the High Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Foster City, CA). Both foliar and bulb tissues were tested using both detection methods. Forty percent of symptomatic plants and 67% of asymptomatic plants tested positive for LYSV with both ELISA and RT-PCR. LYSV was detected in both foliar and bulb tissues, including both tissues from asymptomatic plants. Five PCR amplicons generated from both foliar and bulb tissue were sequenced and shown to share 96 to 98% maximum identity with an LYSV polyprotein gene accession in GenBank (AY842136). This provided additional support that the detected virus was LYSV. LYSV was initially difficult to detect in Ohio fields due to low disease incidence and subtle symptom development. Use of virus-tested garlic bulbs can improve yield for several years, even following viral reinfection by aphids, compared to growing garlic from chronically infected bulbs (1). However, many growers routinely save bulbs from year to year and lack access to or knowledge of virus-tested sources of garlic bulbs. Conducive conditions, chronic infections, or co-infections with other viruses enhance the severity of symptoms and yield loss (2). LYSV has previously been reported in garlic producing regions of the northwestern United States (3), and to our knowledge, this is the first report of LYSV in garlic in Ohio. References: (1) V. Conci et al. Plant Dis. 87:1411, 2003. (2) P. Lunello et al. Plant Dis. 91:153, 2008. (3) H. Pappu et al. Plant Health Progress 10, 2008. (4) L. Parrano et al. Phytopathol. Mediterr. 51:549, 2012.


Improved Inhibition of Tumor Growth by Diabody-Drug Conjugates via Half-Life Extension.
Despite some clinical success with antibody-drug conjugates (ADCs) in patients with solid tumors and hematological malignancies, improvements in ADC design are still desirable due to the narrow therapeutic window of these compounds. Tumor-targeting antibody fragments have distinct advantages over monoclonal antibodies, including more rapid tumor accumulation and enhanced penetration, but are subject to rapid clearance. Half-life extension technologies such as PEGylation and albumin-binding domains (ABDs) have been widely used to improve the pharmacokinetics of many different types of biologics. PEGylation improves pharmacokinetics by increasing hydrodynamic size to reduce renal clearance, whereas ABDs extend half-life via FcRn-mediated recycling. In this study, we used an anti-oncofetal antigen 5T4 diabody conjugated with a highly potent cytotoxic pyrrolobenzodiazepine (PBD) warhead to assess and compare the effects of PEGylation and albumin binding on the in vivo efficacy of antibody fragment drug conjugates. Conjugation of 2× PEG20K to a diabody improved half-life from 40 min to 33 h, and an ABD-diabody fusion protein exhibited a half-life of 45 h in mice. In a xenograft model of breast cancer MDA-MB-436, the ABD-diabody-PBD showed greater tumor growth suppression and better tolerability than either PEG-diabody-PBD or diabody-PBD. These results suggest that the mechanism of half-life extension is an important consideration for designing cytotoxic antitumor agents.


Knee injury and Osteoarthritis Outcome Score or International Knee Documentation Committee Subjective Knee Form: which questionnaire is most useful to monitor patients with an anterior cruciate ligament rupture in the short term?
To evaluate which questionnaire, the Knee Injury and Osteoarthritis Outcome Score (KOOS) or the International Knee Documentation Committee Subjective Knee Form (IKDC subjective), is most useful to evaluate patients with recent anterior cruciate ligament (ACL) ruptures or those within 1 year of an ACL reconstruction. Patients with recent (0-6 months) ACL ruptures or those with indications for ACL reconstruction were included. All patients completed the questionnaires shortly after trauma or preoperatively and again 1 year later. The KOOS has 5 subscales, each scored separately. The IKDC subjective consists of one total score. The following measurement properties of the KOOS and IKDC subjective were assessed: content validity (n = 45), construct validity (n = 100), test-retest reliability (n = 50), and responsiveness (n = 50). Regarding content validity, 2 KOOS subscales (Pain and Activities of Daily Living) were scored as nonrelevant. Two of the 18 questions on the IKDC subjective were assessed as nonrelevant. Only the KOOS subscale Sport and Recreation Function had acceptable construct validity (79% confirmation of the predefined hypotheses). None of the KOOS subscales had a sufficient score for responsiveness (<75% confirmation of the predefined hypotheses). The IKDC subjective scored acceptable for construct validity (84% confirmation of the predefined hypotheses) and responsiveness (86% confirmation of the predefined hypotheses). All KOOS subscales and the IKDC subjective had a reliability (intraclass correlation coefficient [ICC]) of 0.81 or higher. The IKDC subjective is more useful than the KOOS questionnaire to evaluate both patients with recent ACL ruptures and those in the first year after ACL reconstruction. Level III, prognostic validation study.


Intestinal Microbiota in Hirschsprung Disease.
The aim of the study was to characterize the microbiota profiles of patients with Hirschsprung disease (HD) and to evaluate this in relation to postoperative bowel function and the incidence of Hirschsprung-associated enterocolitis (HAEC). All patients operated on for HD at our center between 1987 and 2011 were invited to answer questionnaires on bowel function and to participate in a clinical follow-up for laboratory investigations, including fecal DNA extraction, fecal calprotectin (FC), and brush border lactase (LCT) genotyping. The microbiota compositions of patients with HD were compared with those of healthy controls aged between 2 and 7 years. The microbiota composition of eligible patients with HD (n = 34; median age 12 [range, 3-25] years) differed from the healthy controls (n = 141), showing decreased overall microbial richness (P < 0.005). Seventy-seven percent had experienced HAEC. Normal maturation of the intestinal flora was not observed, but patients had a significantly increased abundance of Proteobacteria among other taxa (P < 0.005) resulting in a reduced carbohydrate degradation potential, as predicted by the taxonomic composition. Genetic lactase deficiency was present in 17% and did not correlate with bowel symptoms. No patients reported active HAEC at the time of sampling and FC was within the normal range in all samples. Patients with HD and HAEC had a significantly altered intestinal microbiome compared to healthy individuals, characterized by a lack of richness and pathologic expansions of taxa, particularly Enterobacteria and Bacilli. Further evaluation is needed to identify whether these observations are intrinsic to HD or secondary to the recurrent use of antibiotics during early childhood.


Mathematical Model for MRSA Nasal Carriage.
An interesting biological phenomenon that is a factor for the spread of antibiotic-resistant strains, such as MRSA, is human nasal carriage. Here, we evaluate several biological hypotheses for this problem in an effort to better understand and narrow the scope of the dominant factors that allow these bacteria to persist in otherwise healthy individuals. First, we set up and analyze a simple PDE model created to generally mimic the interactions of the microbes and nasal immune response. This includes looking at different types of diffusion and chemotaxis terms as well as different boundary conditions. Then, using sensitivity analysis, we walk through several biological hypotheses and compare to the model's results looking for persistent infection scenarios indicated by the model's bacteria component surviving over time.


Relationship between the charge distribution and dipole moment functions of CO and the related molecules CS, SiO, and SiS.
The dipole moment functions of the titled molecules are written as the sum of a charge and induced atomic dipole contribution and the distance dependence interpreted in terms of these components. These two contributions have opposite signs over a large range of internuclear distances, and when they have equal magnitudes, the dipole moment vanishes. This happens with CO near the equilibrium bond length and is responsible for its small dipole moment. The dipole moment of CS is 0.770(ea0), rather large for a diatomic in which the two atoms have essentially the same electronegativities; this is because for CS, the two components of the dipole moment have the same sign at equilibrium and reinforce one another.


Probing effects of polymer adsorption in colloidal particle suspensions by light scattering as relevant for the aquatic environment: An overview.
Modification of particle surfaces by adsorption of polymers is a process that governs particle behavior in aqueous environmental systems. The present article briefly reviews the current understanding of the adsorption mechanisms and the properties of the resulting layers, and it discusses two environmentally relevant cases of particle modification by polymers. In particular, the discussion focuses on the usefulness of methods based on light scattering to probe such adsorbed layers together with the resulting properties of the particle suspensions, and it highlights advantages and disadvantages of these techniques. Measurement of the electrophoretic mobility allows to follow the development of the adsorption layer and to characterize the charge of the modified particles. At saturation, the surface charge is governed by the charge of the adsorbed film. Dynamic light scattering provides information on the film thickness and on the behavior of the modified suspensions. The charge and the structure of the adsorbed layer influence the stability of the particles, as well as the applicability of the classical theory of Derjaguin, Landau, Verwey, and Overbeek (DLVO). This fundamental knowledge is presented in the light of environmental systems and its significance for applied systems is underlined. In particular, the article discusses two examples of environmental processes involving adsorption of polymers, namely, the modification of particles by natural adsorption of humic substances and the tailoring of surface properties of iron-based particles used to remediate contaminated aquifers.


Continuous subcutaneous insulin infusion during total parenteral nutrition after gastroscopy complicated by duodenal intramural haematoma in a patient with type 1 diabetes - case repor.
We present the course of the insulin therapy during total parenteral nutrition (TPN) after gastroscopy complicated by duodenal intramural haematoma, in a boy with type 1 diabetes treated with the insulin pump. There is a lack of guidelines regarding the insulin therapy during TPN in children. Additionally, duodenal intramural haematoma is a very rare complication of diagnostic gastroscopy. There are only few cases reported so far.


Malignant melanoma with unknown primary site.
From 1955 to 1976, 129 patients were seen with metastatic malignant melanoma from an unknown primary site, comprising 8.1% of all the referred patients with malignant melanoma. Eighty-two percent of the patients presented with a history of mass or lump. Overall median survival and 5-year survival rates after onset of symptoms were 10 months and 13%, respectively. Patients with lesions of the head and neck area had 5-year disease-free survival of 25%, whereas those with lymph node disease had a survival of 18%. Twenty-nine patients with regional disease had wide excision (usually lymphadenectomy) and their 5-year disease-free survival was 58%. Regional disease in patients with malignant melanoma of unknown primary site should be treated with radical surgical excision, since the survival is comparable or better to that of patients with regional disease having known and excised primary site.


The inhibitory effect of NUCB2/nesfatin-1 on appetite regulation of Siberian sturgeon (Acipenser baerii Brandt).
Since NUCB2 was discovered, the information about NUCB2/nesfatin-1 in appetite regulation in both mammals and teleost has been still limited. The present study aims to determine the effects of nesfatin-1 on food intake and to explore the appetite mechanism in Siberian sturgeon. In this study, nucb2 cDNA sequence of 1571 bp was obtained, and the mRNA expression of nucb2 was abundant in brain and liver. Levels of nucb2 were appreciably increased in brain after feeding 1 and 3 h, while significantly decreased within fasting 15 days. Except for fasting 1 day, the expression pattern of nucb2 in the liver was similar to the brain. Acute intraperitoneal (i.p.) injection of nesfatin-1 inhibited the food intake during 0-1 h in a dose-dependent manner and 50 or 100 ng/g BW nesfatin-1 significantly decreased the cumulative food intake during 3 h. The daily food intake and cumulative food intake were remarkably reduced post chronic (7 days) i.p. injection. Moreover, chronic i.p. injection of nesfatin-1 affected the expression of appetite factors including cart, apelin and pyy in the brain, stomach and liver with the consistent pattern of change, while the levels of cck, ucn3 and nucb2 in these have different patterns. This study demonstrates that nesfatin-1 acts as a satiety factor in reducing the short-term and long-term food intake of Siberian sturgeon. Therefore, the data suggesting nesfatin-1 inhibits the appetite through different signal pathways in the central and peripheral endocrine systems of Siberian sturgeon.


Carotid angiography in conjunction with amytal testing of epilepsy patients.
Angiography is carried out as a basic part of the sodium amobarbital procedure in most institutions in order to predict the distribution of the amobarbital before the procedure itself is performed. This paper presents details of cerebral circulation to provide a framework that will help investigators who are not radiologists to interpret angiography results. The application of angiography specifically to the amobarbital procedure and the implications of different patterns of arterial filling for interpretation of speech and memory test results are discussed.


Novel combination for the treatment of acne differentiated based on gender: a new step towards personalized treatment.
The aim of this study is to evaluate efficacy and tolerability of a complete skin care line consisting of an oral supplement in two distinct formulations for males and females, and a topical cream device in the treatment of mild and moderate acne. Oral supplements contain biotin, probiotic, vitamin E, zinc, nicotinamide; in the formulation for males beta sitosterol and Boswellia serrata were added, the oral supplement for females contains myo-inositol and folic acid. The topical cream device is represented by the association between active plant agents (verbascoside, Ocimum gratissimum) and keratolytic molecules (salicylic acid, gluconolactone, complex alpha-hydroxy acids). An equal number of male and female patients with mild to moderate acne were enrolled in a double-blinded clinical trial. Efficacy and tolerability evaluations were performed at week 4 (T1) and week 12 (T2) by Global acne Grading System (GAGs). Most of patients had satisfactory therapeutic response, in terms of GAGs reduction. All the four groups presented a statistically significant improvement of the mean GAGs at T2 but those assuming the oral supplement improved more, as expected. Our data suggest that this association can be considered a new effective option for mild and moderate acne. This therapeutic line differs from others in the gender matched oral treatment.


Pseudomonas aeruginosa pyocyanin causes airway goblet cell hyperplasia and metaplasia and mucus hypersecretion by inactivating the transcriptional factor FoxA2.
The redox-active exotoxin pyocyanin (PCN) can be recovered in 100 µM concentrations in the sputa of bronchiectasis patients chronically infected with Pseudomonas aeruginosa (PA). However, the importance of PCN within bronchiectatic airways colonized by PA remains unrecognized. Recently, we have shown that PCN is required for chronic PA lung infection in mice, and that chronic instillation of PCN induces goblet cell hyperplasia (GCH), pulmonary fibrosis, emphysema and influx of immune cells in mouse airways. Many of these pathological features are strikingly similar to the mouse airways devoid of functional FoxA2, a transcriptional repressor of GCH and mucus biosynthesis. In this study, we postulate that PCN causes and exacerbates GCH and mucus hypersecretion in bronchiectatic airways chronically infected by PA by inactivating FoxA2. We demonstrate that PCN represses the expression of FoxA2 in mouse airways and in bronchial epithelial cells cultured at an air-liquid interface or conventionally, resulting in GCH, increased MUC5B mucin gene expression and mucus hypersecretion. Immunohistochemical and inhibitor studies indicate that PCN upregulates the expression of Stat6 and EGFR, both of which in turn repress the expression of FoxA2. These studies demonstrate that PCN induces GCH and mucus hypersecretion by inactivating FoxA2.


Copper modulates the large dense core vesicle secretory pathway in PC12 cells.
Copper (Cu) is an essential biometal involved in a number of cell functions. Abnormal Cu homeostasis has been identified as a major factor in a number of neurodegenerative disorders. However, little is known about how cells of brain origin maintain Cu homeostasis and in particular, how they respond to an elevated Cu environment. Understanding these processes is essential to obtaining a greater insight into the pathological changes in neurodegeneration and ageing. Although previous studies have shown that Cu in neurons can be associated with synaptic function, there is little understanding of how Cu modulates the regulated secretory vesicle pathways in these cells. In this study, we examined the effect of elevated intracellular Cu on proteins associated with the regulated secretory vesicle pathway in NGF-differentiated PC12 cells that exhibit neuronal-like properties. Increasing intracellular Cu with a cell-permeable Cu-complex (Cu(II)(gtsm)) resulted in increased expression of synaptophysin and robust translocation of this and additional vesicular proteins from synaptic-like microvesicle (SLMV) fractions to chromogranin-containing putative large dense core vesicle (LDCV) fractions in density gradient preparations. The LDCV fractions also contained substantially elevated Cu levels upon treatment of cells with Cu(II)(gtsm). Expression of the H(+) pump, V-ATPase, which is essential for vesicle maturation, was increased in Cu-treated cells while inhibition of V-ATPase prevented translocation of synaptophysin to LDCV fractions. Cu treatment was found to inhibit release of LDCVs in chromaffin cells due to reduced Ca(2+)-mediated vesicle exocytosis. Our findings demonstrate that elevated Cu can modulate LDCV metabolism potentially resulting in sequestration of Cu in this vesicle pool.


Electrocardiographic reference ranges derived from 79,743 ambulatory subjects.
Reference ranges for electrocardiogram (ECG) intervals, heart rate, and QRS axis in general use by medical personnel and ECG readers are unrepresentative of true age- and sex-related values in large populations and are not based on modern electrocardiographic and ECG reading technology. The results of ECG interpretation by cardiologists using digital technology for viewing and interpreting ECGs were compiled from single, baseline ECGs of 79,743 individuals included in pharmaceutical company-sponsored clinical trials. Women comprised 48% of the total population. Ages ranged from 3 months to 99 years, and the bulk of the population (56%) was aged 40 to 70 years. Striking differences in numerical ECG values based on age and sex were observed. A subgroup of 46,129 individuals with a very low probability of cardiovascular disease was identified. The following were the reference ranges for this subgroup, determined using the 2nd and 98th percentiles: heart rate, 48 to 98 beats/min; PR interval, 113 to 212 milliseconds; QRS interval, 69 to 109 milliseconds; frontal plane QRS axis, -40 degrees to 91 degrees ; QT interval, 325 to 452 milliseconds; QTc-Bazett, 361 to 457 milliseconds; and QTc-Fridericia, 359 to 445 milliseconds. There were marked age- and sex-related variations in the reference ranges of this subgroup, and they differ substantially from previously reported norms. Small differences were observed in ECG values obtained using our digital methods as compared with readings done using paper tracings and values computed by 2 commercial computer algorithms. We observed large differences in electrocardiographic heart rate, interval, and axis reference ranges in this study compared with those reported previously and with reference ranges in general use. We also observed a large influence of age and sex upon normal values. Very large cohorts are required to fully assess age- and sex-related variation of reference ranges. Electrocardiographic reference ranges should be modernized.


Advance care planning documents in nursing facilities: results from a nationally representative survey.
This study assessed clinical, demographic, facility, and regional factors associated with documented do-not-resuscitate (DNR) orders, feeding/medication/other treatment (FMT) restrictions, and living wills among nursing facility residents. Using the Nursing Home Component of the 1996 Medical Expenditure Panel Survey, a nationally representative sample of 815 facilities and 5899 residents, three separate multivariate logistic regression models were developed. DNR orders were more prevalent among residents aged 75+ and those with severe cognitive impairment, dementia, emphysema, and cancer, but less common among African Americans and Latinos than whites. Residents with living children were more likely to have DNR orders. Latinos were less likely to have FMT restrictions. Living wills were more common among residents aged 75+ and those with psychiatric/mood disorders and heart disease, but less prevalent among African Americans. Residents with less social engagement and household incomes below 400% of the Federal Poverty Level were less likely to have a living will. Residents with Medicaid as their largest payer were less likely to have an advance care plan than those with Medicare or other payment mechanisms. To increase the use of advance care plans, interventions should focus on groups with less social engagement and lower household income.


Expression and developmental regulation of the k-FGF oncogene in human and murine embryonal carcinoma cells.
Embryonal carcinoma (EC) cells provide an effective model system for studying growth factor production and regulation during mammalian embryogenesis. Our earlier data indicated that the mouse EC cell lines F9 and PC-13 and the human EC cell line NT2/D1 produce a factor with properties similar to those ascribed to members of the fibroblast growth factor (FGF) family and that production of this FGF-related factor is suppressed when all three EC cell lines are induced to differentiate. Subsequent studies suggested that NT2/D1 EC cells express transcripts for basic FGF (bFGF). The current study confirms and extends these findings using a combination of reverse transcription and polymerase chain reaction (RT-PCR). In this study, the expression of bFGF and other members of the FGF family have been examined in F9 and PC-13 cells in addition to NT2/D1 EC cells. In contrast to NT2/D1 EC cells, bFGF expression could not be detected in F9 and PC-13 EC cells. Additionally, expression of four other members of the FGF family (acidic FGF, int-2, FGF-5, and FGF-6) were not detected in NT2/D1, F9, or PC-13 EC cells. However, expression of another member of the FGF family, the k-FGF oncogene, was detected in NT2/D1, F9, and PC-13 EC cells. Moreover, the expression of this transcript is reduced dramatically when each of the three EC cell lines is induced to differentiate. Taken together, our findings argue that expression of the k-FGF oncogene is predominantly responsible for the FGF-related activity detected in EC cells and that differentiation of these EC cells results in suppression of this oncogene.


A 12-channel, real-time near-infrared spectroscopy instrument for brain-computer interface applications.
A continuous wave near-infrared spectroscopy (NIRS) instrument for brain-computer interface (BCI) applications is presented. In the literature, experiments have been carried out on subjects with such motor degenerative diseases as amyotrophic lateral sclerosis, which have demonstrated the suitability of NIRS to access intentional functional activity, which could be used in a BCI as a communication aid. Specifically, a real-time, multiple channel NIRS tool is needed to realise access to even a few different mental states, for reasonable baud rates. The 12-channel instrument described here has a spatial resolution of 30 mm, employing a flexible software demodulation scheme. Temporal resolution of approximately 100 ms is maintained since typical topographic imaging is not needed, since we are only interested in exploiting the vascular response for BCI control. A simple experiment demonstrates the ability of the system to report on haemodynamics during single trial mental arithmetic tasks. Multiple trial averaging is not required.


Conserved requirement for a plant host cell protein in powdery mildew pathogenesis.
In the fungal phylum Ascomycota, the ability to cause disease in plants and animals has been gained and lost repeatedly during phylogenesis. In monocotyledonous barley, loss-of-function mlo alleles result in effective immunity against the Ascomycete Blumeria graminis f. sp. hordei, the causal agent of powdery mildew disease. However, mlo-based disease resistance has been considered a barley-specific phenomenon to date. Here, we demonstrate a conserved requirement for MLO proteins in powdery mildew pathogenesis in the dicotyledonous plant species Arabidopsis thaliana. Epistasis analysis showed that mlo resistance in A. thaliana does not involve the signaling molecules ethylene, jasmonic acid or salicylic acid, but requires a syntaxin, glycosyl hydrolase and ABC transporter. These findings imply that a common host cell entry mechanism of powdery mildew fungi evolved once and at least 200 million years ago, suggesting that within the Erysiphales (powdery mildews) the ability to cause disease has been a stable trait throughout phylogenesis.


Population balance modelling of ribbon milling with a new mass-based breakage function.
Dry granulation through roll compaction followed by milling is a widely used pharmaceutical process. The material properties of powders and the roll compaction process conditions affect the strength of ribbons, and subsequently the granule size distribution (GSD). Accurate prediction of the granule size distribution from milling of ribbons with different properties is essential for ensuring tablet quality in the final compaction stage. In this study, MCC, PH-102 ribbons with precisely controlled porosities were produced and milled in a cutting mill and granule size distribution was analysed using QicPic. A population balance model with a new breakage function based on the Weibull function was developed to model the ribbon milling process. Eight model parameters were initially obtained for each ribbon porosity and very good agreement between the model and experimental results was obtained. Sensitivity analysis was then performed and thus reduced the number of model parameters that changed with ribbon porosity to two in the breakage function. The refined model was able to predict the granule size distribution both within and outside the experimental boundaries. It was shown that the model developed in this study has a great potential for predicting granule properties and therefore the optimisation of the dry granulation process.


PBPK modeling of complex hydrocarbon mixtures: gasoline.
Petroleum hydrocarbon mixtures such as gasoline, diesel fuel, aviation fuel, and asphalt liquids typically contain hundreds of compounds. These compounds include aliphatic and aromatic hydrocarbons within a specific molecular weight range and sometimes lesser amounts of additives, and often exhibit qualitatively similar pharmacokinetic (PK) and pharmacodynamic properties. However, there are some components that exhibit specific biological effects, such as methyl t-butyl ether and benzene in gasoline. One of the potential pharmacokinetic interactions of many components in such mixtures is inhibition of the metabolism of other components. Due to the complexity of the mixtures, a quantitative description of the pharmacokinetics of each component, particularly in the context of differing blends of these mixtures, has not been available. We describe here a physiologically-based pharmacokinetic (PBPK) modeling approach to describe the PKs of whole gasoline. The approach simplifies the problem by isolating specific components for which a description is desired and treating the remaining components as a single lumped chemical. In this manner, the effect of the non-isolated components (i.e. inhibition) can be taken into account. The gasoline model was based on PK data for the single chemicals, for simple mixtures of the isolated chemicals, and for the isolated and lumped chemicals during gas uptake PK experiments in rats exposed to whole gasoline. While some sacrifice in model accuracy must be made when a chemical lumping approach is used, our lumped PK model still permitted a good representation of the PKs of five isolated chemicals (n-hexane, benzene, toluene, ethylbenzene, and o-xylene) during exposure to various levels of two different blends of gasoline. The approach may be applicable to other hydrocarbon mixtures when appropriate PK data are available for model development.


Enriched environment and spatial learning enhance hippocampal neurogenesis and salvages ischemic penumbra after focal cerebral ischemia.
Enriched environment (EE) has been shown to increase neurogenesis in the adult brain. The aim of this study is to determine the effect of EE and spatial learning on neurogenesis following ischemic stroke. Male adult SD rats were subjected to sham surgery or distal middle cerebral artery occlusion (MCAO). MCAO induced a transient increase followed by a sustained depression of progenitor cell proliferation and neuroblast production below baseline level in both ipsilateral and contralateral DG compared to sham. Increased neuronal differentiation and neurogenesis in the DG were observed in both sham and MCAO rats following 8 weeks in the EE combined with spatial learning, compared to rats housed in the standard environment. EE/Learning also restored the total number of neuroblasts in the DG after MCAO compared to sham. Furthermore, EE/learning enhanced the density of NeuN positive cells in the ischemic penumbra, though no new neurons were detected in this region.


Clinical and biochemical consequences of copper-histidine therapy in Menkes disease.
Menkes disease (MD) is an X-linked recessively inherited neurodegenerative disorder of copper (Cu) metabolism leading to death in early childhood. Symptoms are attributed to deficient activity of Cu-dependent enzymes. Limited experience has been reported concerning clinical and biochemical consequences of parenteral treatment with copper-(histidine)2-complex (Cu-His) in MD. Cu-His was administered in a 13-week-old boy with MD by daily intramuscular injections. After 6 weeks of therapy, Cu and caeruloplasmin in serum and Cu in CSF were normalized. The excessive dopamine level in CSF was corrected after 3 months of treatment. After 6 weeks of Cu supplementation, complete reduction of epileptic discharges, improved muscular tone and increased motor activities were observed. Developmental regression stopped and was replaced by a slight progression. Death at the age of 19 months was caused by septicaemia due to a fulminant urinary tract infection; there was no evidence of chronic Cu toxicity. These findings suggest that Cu-His supplementation may be a promising palliative treatment in MD.


[Cardiac fibrillation in early ontogeny in animals born mature and immature].
The processes of spontaneous reversible fibrillation were compared in mature-born (guinea pigs, hens and cocks) and in immature-born animals (cats, dogs and rats). An increase in duration of the fibrillation in immature-born animals was most significant in the period of recovery of sight which is associated with an increasing parasympathetic influences.


Submental and Anterior Neck Originated Full-Thickness Skin Grafts for Periocular Procedures.
The submental and neck regions share cutaneous features with the face and are suitable donor sites for facial full-thickness skin grafts (FTSGs). Age-related laxity and skin redundancy in the cervicomental region may be an additional motivator to use its skin. We aim to describe, raise awareness, and remind surgeons of the utilization of submental and anterior neck as sources of FTSG for the periocular region, particularly when traditional donor sites are unavailable. Retrospective case series of 5 patients who underwent periocular FTSG from anterior neck and submental regions between January 2017 and January 2019. All patients had contraindications to the usually preferred graft donor sites. Main outcome measures were surgical functional results and cosmesis. Five patients (all female) received FTSGs using anterior neck and submental regions as donor sites. Two patients required skin grafts due to eyelid retraction and anterior lamella shortening; one due to previous multiple basal cell carcinoma excisions with FTSG reconstructions and the other due to chronic Bell's palsy. Three patients required skin grafts for Hughes flap reconstruction after excision of lower eyelid basal cell carcinoma. In all patients, conventional skin donor sites were unavailable or unsuitable due to previous skin grafting, actinic changes, postauricular situated hearing aids or patient's preference. All patients achieved good cosmesis and functional results. None of the patients experienced donor site morbidities. Submental and anterior neck regions are useful FTSG donor sites for periocular procedures, particularly in elderly female patients with submental fullness and neck skin redundancy.


Association between depressive symptoms and morningness-eveningness, sleep duration and rotating shift work in Japanese nurses.
Higher depressive symptoms have been reported in rotating shift workers compared with day workers. Depressive symptoms in adults who do not engage in night work have also been shown to be associated with chronotype and sleep duration. This study examines associations between depressive symptoms, morningness-eveningness (i.e. the degree to which people prefer to be active in the morning or the evening), sleep duration and rotating shift work. Japanese nurses (1252 day workers and 1780 rotating shift workers, aged 20-59) were studied using a self-administered questionnaire. The questionnaire covered depressive symptoms, morningness-eveningness, sleep habits and demographic characteristics of the participants. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to determine the levels of depressive symptoms. A Japanese version of the Morningness-Eveningness Questionnaire (MEQ) was used to measure morningness-eveningness. The CES-D score of shift workers was significantly (p < 0.05) higher than that of day workers. The MEQ score was significantly (p < 0.05) lower (i.e. greater eveningness) in shift workers than in day workers. Sleep duration on the day shift was significantly (p < 0.05) shorter in shift workers than in day workers. Simple linear regression revealed that the MEQ score, sleep duration on the day shift and current work shift (i.e. rotating shift work) were significantly (p < 0.05) associated with the CES-D score. Multivariate linear regression indicated that greater eveningness and shorter sleep duration were independently associated with higher CES-D scores, while rotating shift work was not. These associations between the MEQ score, the sleep duration and the CES-D score were also confirmed in both day workers and shift workers when the groups were analyzed separately. These results suggest that greater eveningness and shorter sleep duration on the day shift were independently associated with higher levels of depressive symptoms, which may explain associations between rotating shift workers and depressive symptoms. These findings have important implications for the development of novel strategies for preventing poor mental health in day workers and rotating shift workers.


Molecular genetic study in Japanese patients with Alexander disease: a novel mutation, R79L.
Since the first report by Brenner et al. of mutations in the glial fibrillary acidic protein (GFAP) gene in patients with Alexander disease, several molecular genetic studies have been performed in different ethnic groups. We previously reported a Japanese patient with a mutation, R239C, which is identical to one commonly found in American patients. Here we have analyzed four additional Japanese patients by screening for known mutations or, if no known mutation was found, by sequencing of all exons of the GFAP gene. We detected three missense mutations; one was a novel mutation, R79L, and two were previously reported mutations, R239C and R79C. All of our patients were heterozygous for their mutations. Together with the novel mutation, R79L, four different nucleotide changes altering the R79 residue have been reported, implying that any alternation of this arginine residue can give the GFAP protein a dominant negative effect, leading to accumulation of GFAP as Rosenthal fibers. We conclude that molecular genetic analysis of the GFAP gene is feasible for antemortem diagnosis of Alexander disease in Japanese patients.


Psychiatric nurses' use of working time.
How nurses spend their time at work is an issue increasingly under scrutiny. This small study, undertaken by a nursing development team, examined the activities of staff and patients on five admission, rehabilitation and continuing care psychiatric wards. The results, sure to stimulate debate and encourage further research, suggest nurses spend less time than might have been expected doing the job for which they were trained.


Reproduction-induced neuroplasticity: natural behavioural and neuronal alterations associated with the production and care of offspring.
As a female transitions into motherhood, many neurobiological adaptations are required to meet the demands presented by her offspring. In addition to the traditional maternal responses (e.g. crouching, nursing, retrieving, grooming), our laboratories have observed several behavioural modifications accompanying parity, especially in the areas of foraging and emotional resilience. Additionally, brain modifications have been observed in the hippocampus and amygdala, providing support for neural plasticity extending beyond the expected hypothalamic alterations. Interestingly, we have observed parenting-induced neuroplasticity to persist into late adulthood, even providing protection against age-related brain and memory deficits. Although the majority of work on the parental brain has been conducted on females, preliminary research suggests similar changes in the biparental male California deer mouse. Taken together, research suggests that the parental brain is dynamic and changeable as it undergoes diverse and, in some cases, long-lasting, modifications to facilitate the production and care of offspring.


Nop10 is a conserved H/ACA snoRNP molecular adaptor.
The H/ACA class of small nucleolar ribonucleoproteins (snoRNPs) is primarily responsible for catalyzing the isomerization of uridine to pseudouridine (Psi) in ribosomal and other cellular RNAs. Each H/ACA snoRNP consist of four conserved proteins, Cbf5 (the Psi-synthase), Gar1, Nhp2 (L7Ae in archaea) and Nop10, that assemble onto a unique RNA component (the snoRNA). The smallest of these proteins, Nop10 ( approximately 7 kDa), has an essential role in the assembly and activity of these particles and binds directly to the Psi-synthase to form the minimal active enzyme in archaea. To better understand the conserved function of this protein, we characterized the NMR structure and dynamics of Nop10 proteins from both archaea and yeast. We show that archaeal Nop10 contains a highly stable Zn2+ binding motif that is replaced in eukaryotes by a smaller meta-stable beta-hairpin, while a highly conserved and conformationally dynamic linker connects these motifs to a nascent alpha-helical structure. Our structural analysis and NMR relaxation data show that these motifs do not interact with each other and tumble independently in solution. Several residues within the archaeal Nop10 Zn2+ binding motif have clear structural and functional roles and are conserved in eukaryotes, yet remain disordered in the free yeast Nop10. We propose that the dynamic structure of Nop10 facilitates an induced-fit recognition with the H/ACA Psi-synthase and allows it to act as a molecular adaptor for guiding snoRNP assembly in similar fashion in all archaea and eukaryotic organisms.


Familiarity Increases Processing Speed in the Visual System.
Familiarity with a stimulus leads to an attenuated neural response to the stimulus. Alongside this attenuation, recent studies have also observed a truncation of stimulus-evoked activity for familiar visual input. One proposed function of this truncation is to rapidly put neurons in a state of readiness to respond to new input. Here, we examined this hypothesis by presenting human participants with target stimuli that were embedded in rapid streams of familiar or novel distractor stimuli at different speeds of presentation, while recording brain activity using magnetoencephalography and measuring behavioral performance. We investigated the temporal and spatial dynamics of signal truncation and whether this phenomenon bears relationship to participants' ability to categorize target items within a visual stream. Behaviorally, target categorization performance was markedly better when the target was embedded within familiar distractors, and this benefit became more pronounced with increasing speed of presentation. Familiar distractors showed a truncation of neural activity in the visual system. This truncation was strongest for the fastest presentation speeds and peaked in progressively more anterior cortical regions as presentation speeds became slower. Moreover, the neural response evoked by the target was stronger when this target was preceded by familiar distractors. Taken together, these findings demonstrate that item familiarity results in a truncated neural response, is associated with stronger processing of relevant target information, and leads to superior perceptual performance.


Analysis of organ-specific effects on metastatic tumor formation by studies in vitro.
After entry into the blood, cells from disseminating malignant tumors are rapidly distributed to many organs, but they only grow to form metastases in certain sites. Clinical and pathologic observations on tumor metastasis in humans and in animals have confirmed that the distribution of these secondary neoplasms is related to the site and type of the primary neoplasm. Numerous studies now indicate that success or failure in producing metastatic deposits is influenced by interaction between the tumor cells and the microenvironment of the organ in which they lodge. In the present investigation, the mechanisms by which the microenvironmental conditions of specific organs may influence tumor cell survival and behavior and hence metastasis distribution were investigated in vitro with the use of spontaneous mouse mammary carcinomas from C3H/Avy mice. Some organs (lung, ovary) promoted the survival and the attachment of the tumor cells to the substratum, while others (liver, thyroid gland) consistently diminished survival of the tumor cells in the flask. These effects were shown to be due to soluble substances diffusing out of the organs, the dose dependency of which was demonstrated. It is known that in vivo murine mammary tumors develop metastases mainly in the lungs and occasionally in the kidneys or ovaries (if inoculated via the aorta). The effects of these same organs on tumor cells in vitro were thus in good agreement with the in vivo observations. The findings are compatible with the hypothesis that normal organs can usually suppress the formation of tumor metastases and that tumors that succeed in establishing metastases have evolved means of escaping the inhibitory effects of organs in which the deposits are found.


Cardiovascular risk in patients with peripheral vascular diseases.
Peripheral arterial disease (PAD) is characterized by increased incidence and prevalence, both of which increasing with age (prevalence about 19% above 70 years versus 2.5% below 60 years); PAD is strongly dependent upon smoking and diabetes mellitus as cardiovascular risk factors. Patients suffering from peripheral arterial disease are patients at high cardiovascular risk, albeit symptomatic patients (intermittent claudication) or asymptomatic patients (added risk for cardiovascular events 4-5%/year); these risks increase in patients needing revascularization surgery (6%), mainly due to association of coronary or cerebro-vascular disease. A fair assessment of preoperative risks (risks depending on patient background, type of surgery, emergency status of surgical procedure) aids in the optimal management of such patient both at the time of performing the procedure and in the long-term patient management. This is why new parameters are required for assessing the risk and identifying a subgroup of patients at high-risk for acute cardiovascular events and for customizing the diagnostic and therapeutic algorithms for such patients.


People with low back pain who have externalised beliefs need to see greater improvements in symptoms to consider exercises worthwhile: an observational study.
Does health locus of control predict the smallest worthwhile effect of motor control exercise or spinal manipulative therapy when adjusted for severity of pain? Cross-sectional observational study. 86 people with non-specific low back pain who had not yet commenced physiotherapy intervention. Predictors were severity of pain measured over the last 7 days using an 11-point scale from 0 to 10, and external and internal health loci of control measured using Form C of the Multidimensional Health Locus of Control scale. The outcome of interest was smallest worthwhile effect which was measured in terms of the percentage perceived change necessary to make two evidence-based physiotherapy interventions for non-specific low back pain (motor control exercise and spinal manipulative therapy) worthwhile. Data were collected before intervention commenced. Multivariate analysis showed that when adjusted for pain and internal locus of control, external locus of control predicted the smallest worthwhile effect for motor control exercise (B 0.79; CI 0.10 to 1.48), explaining 0.07 of the variance. None of the predictors significantly predicted the smallest worthwhile effect for spinal manipulative therapy. Patients with low back pain who have externalised beliefs and agree more strongly with the notion that others are responsible for their condition report higher estimates of smallest worthwhile effect of an active intervention such as motor control exercise than patients who do not have externalised beliefs.


Cloning and Characterization of Lxr and Srebp1, and Their Potential Roles in Regulation of LC-PUFA Biosynthesis in Rabbitfish Siganus canaliculatus.
Rabbitfish Siganus canaliculatus was the first marine teleost demonstrated to have the ability to biosynthesize C20-22 long-chain polyunsaturated fatty acid (LC-PUFA) from C18 PUFA precursors, which is generally absent or low in marine teleosts. Thus, understanding the molecular basis of LC-PUFA biosynthesis in rabbitfish will contribute to efforts aimed at optimizing LC-PUFA biosynthesis in teleosts, especially marine species. In the present study, the importance of the transcription factors liver X receptor (Lxr) and sterol regulatory element-binding protein 1 (Srebp1) in regulation of LC-PUFA biosynthesis in rabbitfish was investigated. First, full-length cDNA of Lxr and Srebp1 were cloned and characterized. The Lxr mRNA displayed a ubiquitous tissue expression pattern while Srebp1 was highly expressed in eyes, brain and intestine. In rabbitfish primary hepatocytes treated with Lxr agonist T0901317, the expression of Lxr and Srebp1 was activated, accompanied by elevated mRNA levels of Δ4 and Δ6/Δ5 fatty acyl desaturase (Fad), key enzymes of LC-PUFA biosynthesis, as well as peroxisome proliferator-activated receptor γ (PPARγ). In addition, Srebp1 displayed higher expression levels in liver of rabbitfish fed a vegetable oil diet or reared at 10 ppt salinity, which were conditions reported to increase the liver expression of Δ4 and Δ6/Δ5 Fad and LC-PUFA biosynthetic ability, than fish fed a fish oil diet or reared at 32 ppt, respectively. These results suggested that Lxr and Srebp1 are involved in regulation of LC-PUFA biosynthesis probably by promoting the expression of two Fad in rabbitfish liver, which, to our knowledge, is the first report in marine teleosts.


Circulating thyroid antibodies in congenital hypothyroidism.
The role of maternal thyroid antibodies in congenital hypothyroidism is controversial. We have analysed serum thyroid antibodies in patients and their mothers. In a bioassay, antibodies interacting with thyroid cells were analysed by measuring of TSH-stimulated cAMP production in a rat thyroid cell line, FRTL5. Serum antibodies against the TSH receptor, thyroid peroxidase and thyroglobulin were determined by radioreceptor assay and enzyme-linked immunosorbent assays. The bioassay was performed with IgG preparations from 89 mothers of children with congenital hypothyroidism. Analyses for TSH receptor antibodies and thyroid peroxidase/thyroglobulin antibodies were performed on 144 and 118 sera of newborn patients respectively. No evidence of an increased prevalence of thyroid antibodies was found on comparison with controls. One infant had transient neonatal hyperthyrotropinaemia because of TSH receptor blocking antibodies transferred from the mother. Our data indicate that, apart from transplacental transfer of TSH receptor antibodies, maternal immunoglobulins have a limited role in the aetiology of congenital thyroid dysfunction.


Effects of ibotenate pedunculopontine tegmental nucleus lesions on exploratory behaviour in the open field.
The pedunculopontine tegmental nucleus (PPTg) as part of the mesencephalic locomotor region is discussed to be involved in motor activity. In this study, we examined whether the PPTg plays a role in exploratory behaviour. Therefore, we compared non-habituated motor behaviour of PPTg lesioned rats with sham lesioned rats under spontaneous, dizocilpine (MK-801) (0.1 and 0.16 mg/kg) and dl-amphetamine (1 and 2 mg/kg) conditions. In order to analyse exploratory behaviour only, session-times were limited to 5 min after placing the rats in an open field. The exploratory motor activity was compared to the motor activity obtained in rats habituated to the environment. PPTg lesions had no effect on spontaneous exploratory behaviour, but it intensified the enhanced motor activity induced by MK-801. However, PPTg lesions blocked the enhanced exploratory behaviour, i.e. horizontal activity, rearing and centre activity induced by amphetamine. These data indicate that the PPTg is involved in behaviour driven by the dopaminergic and glutamatergic systems, when the animals are in a particular motivational state, e.g. a state that increases motor activity for itself, like exploration. This is underlined by the finding that animals exploring their environment show a higher motor activity even after multiple sessions, than animals familiar to the environment.


Role of PDE9 in Cognition.
Inhibition of phosphodiesterases (PDEs) has been demonstrated to enhance performance of animals in various cognition tasks and accordingly PDE inhibitors have been proposed as new approach for treatment of cognitive dysfunction (Reneerkens et al. Psychopharmacology 202:419-443, 2009; Schmidt Curr Top Med Chem 10(2):222-230, 2010). One of the eleven PDE isoforms, showing expression in cognition relevant brain regions across species, is PDE9, which hydrolyzes cGMP only. Furthermore, it is well established that the nitric oxide (NO)/cGMP pathway and NMDA receptor signaling has a crucial function in synaptic plasticity and cognitive function. In this chapter, we will provide an overview on PDE9, its expression and function in the brain, and hence, its relevance for synaptic plasticity and cognitive performance. Moreover, the recent advances of PDE9 inhibition as potential therapeutic approach for treatment of cognitive dysfunction in CNS disorders will be discussed.


Water structure and dynamics at a silica surface: Pake doublets in 1H NMR spectra.
Detailed knowledge about the dynamics and structure of liquids in the vicinity of a solid surface is important in several fields of research. In this study a homogeneous model system of colloidal and nonporous silica particles with a narrow particle size distribution was used to examine such properties of adsorbed water and 1-heptanol. Doublet (1)H water resonances ("Pake doublets") indicate a preferred spatial orientation for the water molecules, as well as a lower molecular density in the surface-induced water structures compared to bulk water. These surface-induced structures are found to extend at least 8 nm from the silica surface. T(1) relaxation measurements at several temperatures indicate weaker H-bonding in the adsorbed water compared to bulk water. T(2) relaxation measurements at several temperatures reveal the presence of two water phases and give quantitative information on the mobility of water molecules and proton exchange processes. The presence of 1-heptanol changes the water characteristics, primarily in the water phase closer to the surface, where water molecules experience decreased translational and increased rotational freedom. In the absence of water, adsorbed 1-heptanol forms surface aggregates encompassing several molecular layers, where the first adsorbed layer shows severe restrictions in mobility and subsequent layers are more mobile.


Determination of the average end-to-end distance of two angiotensin II analogs by resonance energy transfer.
The angiotensin II analogs H . Tyr-Arg-Val-Phe-Val-His-Pro-Trp . OH (I) and H . Trp-Arg-Val-Phe-Val-His-Pro-Tyr . OH (II) were synthesized and their conformations in dilute aqueous solution (3 X 10(-5) M) were studied by fluorescence techniques. Evaluation of singlet-singlet energy transfer between tyrosine (donor) and tryptophan (acceptor) in the biologically active analog I resulted in a low transfer efficiency (E approximately 0.1) Since transposition of the tyrosyl and tryptophanyl residues (analog II) produced a transfer efficiency similar to that observed in compound I, the orientation factor did not present a serious problem for the determination of the intramolecular Tyr-Trp distances in these peptides on the basis of the Förster equation. Similar average Tyr-Trp separations above 15 A were obtained for analogs I and II at pH 5.2 and no drastic titration effects on the distance were observed with compound I in the pH range 1.5-8.5. The observed end-to-end distances indicate that the conformations of analogs I and II are not quite as compact as some of the models which have been proposed for angiotensin II. Furthermore, the results exclude an electrostatic head-to-tail interaction between the terminal NH3+- and COO- groups as well as several proposed beta- and gamma-turn models.


A new way to expose endocervical lesions at colposcopy.
If there are atypical cells on a cytological smear and if the squamo-columnar junction can not be visualized during a colposcopic examination, then in order to exclude an early invasive cancer in the nonvisualized area within the endocervix it is mandatory to perform a diagnostic cone biopsy. A woman with abnormal cervical cytology and an unsatisfactory colposcopic examination who refused a cone biopsy was offered Lamicel in an attempt to expose the entire transformation zone. After 4 hr the sponge was removed and colposcopy repeated. The lesion and the squamo-columnar junction was then fully visible and she was spared a cone biopsy.


[A clinical study on testicular tumor].
The 19 cases of testicular tumors treated at our Hospital between 1974 and 1983, were reviewed retrospectively. The incidence of testicular tumors among the male outpatients in our urologic clinic was 0.31%. The patients ranged in age from 1 to 76 years old (average: 27.8 years old). The affected side was the left side in 11 and the right side in 8 cases. The most frequent symptom was a painless mass of the testis. Histopathological diagnosis according to the classification by Dixon and Moore was type I in 9 cases, type II in 4 cases, type II in 1 case, type IV in 4 cases. Thus germinal tumors accounted for 18 (94.7%) of the cases. One case (5.3%) of malignant lymphoma was non-germinal. As for the age distribution, two peaks were noted in testicular tumors, especially in cases with potential embryonal carcinoma, between 1 and 2 years and between 19 and 32 years. On the other hand, the cases with potential seminoma showed one peak between 25 and 44 years. The treatment consisted of high orchiectomy alone, orchiectomy with radiation, orchiectomy with chemotherapy or orchiectomy with radiation and chemotherapy. Retroperitoneal lymphadenectomy was not done in any case. The over-all 3-year and 5-year actual survival rates were both 92%.


Determination of thickness, dielectric constant of thiol films, and kinetics of adsorption using surface plasmon resonance.
This paper describes the formation of a self-assembled monolayer of 11-mercaptoundecanoic acid (MUA) under different concentrations on a gold sensor disk, monitoring in situ and in real time using surface plasmon resonance spectroscopy (SPR). The film thickness and dielectric constant were determined for a fully formed monolayer using one-color approach SPR. The kinetic studies of the film formation in ethanol solution indicated that the self-assembled monolayer is formed in a two-step adsorption process. In this sense, this unpublished route was applied on the basis of a model where many molecules are adsorbed at an initial step and then can be desorbed and/or rearranged to form a perfect monolayer.


Intratreatment Response Assessment With 18F-FDG PET: Correlation of Semiquantitative PET Features With Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiotherapy.
This prospective study seeks to extract semiquantitative positron emission tomography (PET) features from 18F-fluorodeoxyglucose PET scans performed before and during neoadjuvant chemoradiotherapy for esophageal cancer and to compare their accuracy in predicting histopathologic response. From 2012 to 2016, 26 patients with esophageal cancer underwent pretreatment and intratreatment PET scans during chemoradiotherapy followed by surgery. Median patient age was 63 years (interquartile range, 58-68 years); 26 patients had esophageal adenocarcinoma, and 3 had esophageal squamous cell carcinoma. The intratreatment PET scan was performed at a median of 32.4 Gy (interquartile range, 30.6-32.4 Gy). PET features of the primary site including maximum standardized uptake value (SUV), SUV mean, metabolic tumor volume, and total lesion glycolysis were extracted from the pretreatment and intratreatment PET scans. Patients were histopathologic responders if there was complete or near-complete tumor response by modified Ryan scheme. Mean values of PET features were compared between histopathologic responders and nonresponders. The area under the receiver operating characteristic curve (AUC) was used to compare the accuracy of PET features in predicting histopathologic response. Eleven patients (42%) were histopathologic responders. PET features most discriminatory of histopathologic response on AUC analysis were volumetric PET features from the intratreatment PET including metabolic tumor volume based on manual contour (AUC, 0.73; 95% confidence interval, 0.52-0.93) and total lesion glycolysis based on semiautomatic 40% SUV threshold (AUC, 0.73; 95% confidence interval, 0.53-0.94). Volumetric PET features from the intratreatment PET were the most accurate predictors of histopathologic response.


Syringobulbia: a surgical review.
Syringobulbia is a term which is applied to brain stem symptoms or signs in patients with syringomyelia or hindbrain herniation. Syringobulbia clefts due to a dissection of the CSF under pressure from the fourth ventricle should be differentiated from the ascending syringobulbia which may occur from upward impulsive fluid movements in a syringomyelia. Clinical analysis suggests that the commonest correlation of bulbar features is with neither of the above mechanisms but with pressure differences acting downward upon the hindbrain with distortion of the cerebellum and stem, traction on the cranial nerves or indentation of the brain stem by vascular loops. A review of patients with bulbar symptoms in a neurosurgical practice with an interest in hindbrain herniation in the Midland Centre for Neurosurgery and Neurology (M.C.N.N.) is presented.


[The dependence of the dynamics of the extinction of a temporary connection on the recognizability of a reinforcing stimulus].
Dynamics was studied of the extinction of temporary connection, elaborated by means of motivationally significant word, in patients with chronic alcoholism. Two series of studies were conducted. In the first one the reinforcing stimulus was not recognized by the subject and was perceived as a dull light flash on the screen. In the second one the word was easily read, i.e. it was recognized. It was found that conditioned changes of P300 wave at the elaboration of temporary connection depend on the recognition of the reinforcing stimulus. Temporary connections, elaborated by non-recognized motivationally significant stimulus are considerably stronger that the connections, elaborated by means of recognized reinforcement.


Mini-Stern Trial: A randomized trial comparing mini-sternotomy to full median sternotomy for aortic valve replacement.
Aortic valve replacement (AVR) can be performed either through full median sternotomy (FS) or upper mini-sternotomy (MS). The Mini-Stern trial aimed to establish whether MS leads to quicker postoperative recovery and shorter hospital stay after first-time isolated AVR. This pragmatic, open-label, parallel randomized controlled trial (RCT) compared MS with FS for first-time isolated AVR in 2 United Kingdom National Health Service hospitals. Primary endpoints were duration of postoperative hospital stay and the time to fitness for discharge from hospital after AVR, analyzed in the intent-to-treat population. In this RCT, 222 patients were recruited and randomized (n = 118 in the MS group; n = 104 in the FS group). Compared with the FS group, the MS group had a longer hospital length of stay (mean, 9.5 days vs 8.6 days) and took longer to achieve fitness for discharge home (mean, 8.5 days vs 7.5 days). Adjusting for valve type, sex, and surgeon, hazard ratios (HRs) from Cox models did not show a statistically significant effect of MS (relative to FS) on either hospital stay (HR, 0.874; 95% confidence interval [CI], 0.668-1.143; P = .3246) or time to fitness for discharge (HR, 0.907; 95% CI, 0.688-1.197; P value = .4914). During a mean follow-up of 760 days (745 days for the MS group and 777 days for the FS group), 12 patients (10%) in the MS group and 7 patients (7%) in the FS group died (HR, 1.871; 95% CI, 0.723-4.844; P = .1966). Average extra cost for MS was £1714 during the first 12 months after AVR. Compared with FS for AVR, MS did not result in shorter hospital stay, faster recovery, or improved survival and was not cost-effective. The MS approach is not superior to FS for performing AVR.


Potency and specificity of a growth hormone-releasing factor in a primate and in vitro.
The potency and specificity of the 44-amino acid human pancreatic tumor GRF were tested in six adult female rhesus monkeys and in a perifusion system containing a suspension of rat pituicytes. In vivo, plasma GH levels were elevated in a dose-dependent fashion, with an ED50 of approximately 5 micrograms/kg, a value of the same order of magnitude as other hypothalamic releasing hormones. The magnitude of the GH response after GRF treatment was similar to that observed during insulin-induced hypoglycemia, with peak plasma GH concentrations occurring 5-15 min after GRF administration. High doses of GRF slightly stimulated PRL release, but had no effect on arterial blood pressure, heart rate, or plasma cortisol or glucose concentrations. In vitro, GRF released GH in a dose-dependent manner, but no PRL was released even at the highest GRF concentrations employed (100 nM). It thus appears that stimulation of PRL in vivo may be an indirect effect of GRF. Alternatively, there may be species differences in responsiveness to GRF.


Effects of a physical activity intervention on autonomic and executive functions in obese young adolescents: A randomized controlled trial.
The primary goals of this study were to determine the effects of a physical activity intervention on the set-shifting aspect of executive function and to explore the potential mechanistic role of cardiac autonomic control, as assessed by heart rate variability (HRV), in the relationship between physical activity and executive function in obese young adolescents. Obese young adolescents were randomized either to participate in a physical activity program (n = 25) or to serve as the wait-list control (n = 25) for a 3-month intervention. Outcome measures included physical fitness, obesity status, executive function, and HRV; these measures were assessed at baseline and within 1 week of the conclusion of the intervention. The physical activity program improved the participants' physical fitness and obesity status. The program also improved executive function-related set-shifting performance, as measured by the total number of errors, and increased the HRV indices of normalized low frequency (nLF) and normalized high frequency (nHF). A positive correlation between the nHF time changes and the total number of errors was also observed. These findings suggest that 3 months of a physical activity intervention effectively increase physical fitness and improve the set-shifting aspect of executive function in obese young adolescents. Furthermore, the physical activity-related alterations in cardiac autonomic control, particularly the parasympathetic response, may be associated with enhanced executive function. (PsycINFO Database Record


Long-term results of Nissen fundoplication in reflux esophagitis without strictures. Clinical, endoscopic, and pH-metric evaluation.
The present paper evaluates the efficiency of Nissen fundoplication as an antireflux technique in a series of 51 patients with different grades of esophagitis. Follow-up time averaged 6.6 years. The evaluation includes a clinical assessment, endoscopic study, and 24-hr pH monitoring. The results reveal an acceptable rate of recurrences, with clinical (9.8%) being less frequent than endoscopic (13.7%) or pH-metric (19.6%) recurrences. Side effects appeared in 37.3% of the patients (mainly inability to belch or vomit, and postprandial fullness), which were mild and transitory in most cases. Nissen fundoplication proved effective in controlling long-term gastroesophageal reflux, as over 80% of the patients presented an excellent-to-good clinical situation, without or with minimal digestive consequences.


Extraction and identification of three major aldose reductase inhibitors from Artemisia montana.
Aldose reductase inhibitors (ARIs) provide an important therapeutic and preventive opportunity against hyperglycemia associated diabetic complications. The methanolic extracts of 12 species from the genus Artemisia exhibited significant in vitro rat lens AR (RLAR) inhibitory activities with IC(50) values ranging from 0.51 to 13.45 μg/mL (quercetin, 0.64 μg/mL). Since the whole plant of Artemisia montana showed the highest RLAR inhibitory activity, bioassay-guided fractionation was performed to obtain ethyl acetate and n-butanol fractions. Repeated column chromatography of two active fractions, yielded fifteen compounds, including four chlorogenic acids (3,5-di-O-caffeoylquinic acid, chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid), six flavonoids (apigenin, luteolin, quercetin, isoquercitrin, hyperoside, luteolin 7-rutinoside), and five coumarins (umbelliferone, scoparone, scopoletin, esculetin, and scopolin); their structures were confirmed by spectroscopic methods. 3,5-Di-O-caffeoylquinic acid and chlorogenic acid, as well as test flavonoids, displayed the most potent RLAR inhibitory activities with IC(50) values ranging from 0.19 to 5.37 μM. Furthermore, the HPLC profiles of the ethyl acetate and n-butanol fractions indicated that 3,5-di-O-caffeoylquinic acid, chlorogenic acid, and hyperoside, as major compounds, might play crucial roles in RLAR inhibition. The results suggest that A. montana and three key AR inhibitors therein would clearly be potential candidates as therapeutic or preventive agents for diabetic complications.


Implementation of the care programme approach across health and social services for dual diagnosis clients.
Care for clients with mental health problems and concurrent intellectual disability (dual diagnosis) is currently expected to be provided through the care programme approach (CPA), an approach to provide care to people with mental health problems in secondary mental health services. When CPA was originally introduced into UK mental health services in the 1990s, its implementation was slow and problematic, being hampered in part by problems occurring at a strategic level as health and social service organizations attempted to integrate complex systems. This article reports on a study of a more recent attempt to implement CPA for dual diagnosis clients in one mental health foundation trust, aiming to gauge progress and identify factors at the strategic level that were helping or hindering progress this time round. The study took place in a mental health National Health Service (NHS) Foundation Trust in a large English city, which was implementing a joint mental health and intellectual disability CPA policy across five of its constituent boroughs. Semi-structured interviews with key informants at Trust and borough levels focused on the Trust's overall strategy for implementing CPA and on how it was being put into practice at the front line. Documentary analysis and the administration of the Partnership Assessment Tool were also undertaken. Data were analysed using a framework approach. Progress in implementing CPA varied but overall was extremely limited in all the boroughs. The study identified six key contextual challenges that significantly hindered the implementation progress. These included organizational complexity; arrangements for governance and accountability; competing priorities; financial constraints; high staff turnover and complex information and IT systems. The only element of policy linked to CPA that had been widely taken up was the Greenlight Framework and Audit Toolkit (GLTK). The fact that the toolkit had targets and penalties associated with its implementation appeared to have given it priority. None of the contextual challenges identified in this study were specifically related to CPA as a policy or to the needs and circumstances of dual diagnosis clients. Nevertheless, they inhibited the types of organizational change and partnership working that implementing CPA for a client group of this kind required. Unless these more generic factors are acknowledged and addressed when introducing policies such as CPA, the chances of effective implementation will inevitably be compromised.


[Study on isozymes of farm cultivars of Fructus trichosanthis from Shandong].
To determine different cultivars of Fructus trichosanthis of Shandong, and explore their genetic relationships. The peroxidase isozyme and esterase isozyme of cultivars and wild plant were studied by means of polyarcylamide gel electrophresis, and the finger-prints were established. The zymogram of the peroxidase isozyme and the esterase isozyme of different cultivars and wild plant of Frustus trichosanthis consisted of common bands, but they had more or less difference in the number of isozymic bands, their positions and activity intensity. There are closer genetic relationships between Niuxin Gualou with Ren Gualou, and Xiao Guang-dan with wild sample; Mingpi and Xiao Guang-dan are two different cultivars; The isozyme analysis can provide reliable basis for determining different cultivars of Fructus trichosanthis of Shandong.


Some triphenylmethane dyes as redox indicators in the titration of antimony(III) with cerium(IV) sulphate.
Erioglaucine A, Eriogreen B, Patent Blue and Xylene Cyanol FF work satisfactorily for the titration of Sb(III) with Ce(IV) in 1-2N sulphuric acid medium with iodine as catalyst. In hydrochloric acid medium the colour of the oxidized dye is very evanescent but is very much improved in intensity and stability by the addition of manganese(II) sulphate; no catalyst is needed.


The social construction of drug-related death.
This article invites you to a social constructionist view on the issue of drug-related death. Social constructionism is often misunderstood for denying plain facts. It sure is a fact that there are deadly doses of legal and illegal substances. In this sense it is a truism that drugs kill people. Nonetheless, it is argued that reducing the causes of death to a certain drug as the essential underlying cause of death is a social construction. A case is discussed to demonstrate that a drug-related death can just as well be seen as a free-market death. Free markets kill people at least as much as drugs do. It is argued that drug-related death is a social construction, because attributing a death to a drug is based on unfalsifiable counterfactual thinking. Counterfactual thoughts about what the world would look like if there were no drugs, are seen as expressing one's view of life.


Promoting physical activity: issues in primary health care.
In the past few years, alliances between primary care and leisure services have become a popular strategy for exercise promotion in the England. 'GP Referral Schemes' typically involve referral to a local leisure centre by a General Practitioner (GP), whereupon patients are inducted into a 10-12 week exercise programme at a reduced fee. Referred patients are usually white, middle aged and apparently healthy women, with the main reason for referral being overweight. The schemes are characterised by their lack of formal evaluation, making conclusions about effectiveness impossible. In the US, physicians advice to exercise has been the focus of interventions to date. Two controlled trials, one randomised, have provided some evidence that exercise behaviour can be changed, at least in the short term. The ability to recruit sufficient numbers of patients, who have potentially the most to gain from increased physical activity, is the biggest barrier to primary care based interventions. One contributing factor to this problem, may be doctors and nurses' knowledge about the benefits of physical activity.


Stimulation of adrenocorticotropin secretion by insulin-induced hypoglycemia in the developing rat involves arginine vasopressin but not corticotropin-releasing factor.
In the neonatal rat, the response of the hypothalamo-pituitary-adrenal axis to stressful stimuli is markedly decreased during the first 2 weeks of life. This peculiar period was named "stress hyporesponsive period." In this report, we studied the effect of insulin-induced hypoglycemia, known as a strong stimulator of the corticotroph function in the adult rat. Rats (8- or 20-day-old) were injected ip with 3 IU/kg synthetic insulin and were killed at various times. In 20-day-old rats, hypoglycemia induced a rapid drop in blood glucose concentrations accompanied by a stimulation of ACTH and corticosterone secretion which reached maximal values within 30 min. On the opposite, in 8-day-old rats, despite a rapid decrease in blood glucose levels, insulin injection induced a gradual rise of plasma ACTH and corticosterone concentrations which peaked at 90 min. This delayed response of the hypothalamo-pituitary-adrenal axis to hypoglycemia in the youngest rats does not seem to be due to a difference of sensitivity to insulin-induced hypoglycemia since injection of increasing doses of insulin (0.3, 0.75, or 3 IU/kg body wt) induced a dose-related decrease of blood glucose concentrations and a rise in plasma ACTH and corticosterone levels, comparable in the two age group studied. Basal or hypoglycemia-stimulated absolute corticosterone values were much lower in 8-day-old rats than in 20-day-old animals, suggesting an immaturity of the adrenal glands in the youngest animals. Daily ACTH injection, starting 3 days before the experiment, had a trophic effect on the adrenal glands leading to a more important increase of corticosterone levels after hypoglycemia in 8-day-old rats. Our results confirm that there is an immaturity of the adrenal glands in young rats, probably due to the low plasma ACTH levels during the neonatal period. To determine the respective role of the two major hypothalamic ACTH secretagogues, we studied the effect of passive immunization against CRF or arginine vasopressin (AVP) on plasma ACTH response after hypoglycemia. Passive immunization against AVP decreased significantly hypoglycemia-stimulated ACTH secretion in both 8- and 20-day-old rats, while no change of plasma ACTH response to insulin injection was observed after passive immunization against CRF. This results suggest that CRF does not seem to be involved in the regulation of ACTH secretion after hypoglycemia in the young rat while AVP seems to be the main hypothalamic stimulatory factor for anterior pituitary corticotrophs response to hypoglycemia during the postnatal period.(ABSTRACT TRUNCATED AT 400 WORDS)


Reduced passage of alpha 2-macroglobulin into malignant serous effusions and diminished antifibrinolytic potential of the fluid.
The ratio of the relative concentrations of large and small proteins between effusions and serum was measured in patients with benign and malignant effusions. The ratio of values for a large protein, alpha 2 macroglobulin (alpha 2 M) was significantly (p less than 0.0005) lower in the 22 patients with tumoral effusion (0.436 +/- 0.016) and in the 16 patients with transudates (0.388 +/- 0.017) than in the 21 cases with inflammatory exudates (0.838 +/- 0.036) while the ratios between relative concentrations of the lower molecular weight alpha 1 antitrypsin (alpha 1AT) in serous fluids and sera were similar (close to 1.0) in all the above mentioned conditions. Most inflammatory exudates inhibited fibrinolysis in a urokinase activated system, while the activity of the inhibitors of fibrinolysis was very weak in tumoral effusions and in transudates. These findings suggest a rather selective passage of plasma proteins into a tumoral effusion, a fact that might be relevant for a pathogenic diagnosis.