Endothelial cells of different organs exhibit heterogeneity in von Willebrand factor expression in response to hypoxia.
We have previously demonstrated that in response to hypoxia, von Willebrand factor (VWF) expression is upregulated in lung and heart endothelial cells both in vitro and in vivo, but not in kidney endothelial cells. The aim of our current study was to determine whether endothelial cells of different organs employ distinct molecular mechanisms to mediate VWF response to hypoxia. We used cultured human primary lung, heart and kidney endothelial cells to determine the activation of endogenous VWF as well as exogenously expressed VWF promoter in response to hypoxia. Chromatin immunoprecipitation and siRNA knockdown analyses were used to determine the roles of VWF promoter associated transacting factors in mediating its hypoxia response. Platelet aggregates formations in vascular beds of mice were used as a marker for potential functional consequences of hypoxia-induced VWF upregulation in vivo. Our analyses demonstrated that while Yin Yang 1 (YY1) and specificity protein 1 (Sp1) participate in the hypoxia-induced upregulation of VWF specifically in lung endothelial cells, GATA6 mediates this process specifically in heart endothelial cells. In both cell types, the response to hypoxia involves the decreased association of the NFIB repressor with the VWF promoter, and the increased acetylation of the promoter-associated histone H4. In mice exposed to hypoxia, the upregulation of VWF expression was concomitant with the presence of thrombi in heart and lung, but not kidney vascular beds. Heart and lung endothelial cells demonstrated VWF upregulation in response to hypoxia, using distinct mechanisms, while this response was lacking in kidney endothelial cells.


cAMP attenuates autacoid release from endothelial cells: relation to internal calcium.
The effects of elevated levels of adenosine 3',5'-cyclic monophosphate (cAMP), in cultured endothelial cells from bovine aorta, on the ATP-induced increases in the intracellular free calcium concentration [( Ca2+]i) and the release of prostaglandin I2 (PGI2) and endothelium-derived relaxant factor (EDRF) were investigated. Endothelial cAMP production was assessed in terms of cAMP release in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine; this release was increased fivefold by isoproterenol (1 microM), 1.6-fold by isoproterenol (0.1 microM), and 1.5-fold by the stable PGI2 analogue iloprost (10 microM). [Ca2+]i, measured with the fluorescent probe indo-1, was increased by ATP (1 microM) from 150 +/- 20 (SE) to 410 +/- 50 nM. Neither isoproterenol nor iloprost changed [Ca2+]i in unstimulated cells, but they significantly reduced [Ca2+]i levels in the presence of ATP. Similar inhibitions of increases in [Ca2+]i as by iloprost and isoproterenol (0.1 microM) were evoked by dibutyryl-cAMP (100 microM). Release of PGI2 was enhanced from 3.9 +/- 0.5 to 34.6 +/- 6 ng.min-1.5 x 10(6) cells-1 by ATP (3 microM); in the presence of isoproterenol, the ATP-stimulated release was reversibly reduced to 18.1 +/- 4.9 ng/min. Release of EDRF was assayed in terms of its stimulatory action on purified soluble guanylate cyclase. EDRF release in the first minute after stimulation with ATP (10 microM) was significantly attenuated by isoproterenol from 32.3 +/- 4.8 to 23.0 +/- 4.6 nmol.min-1.mg-1 (activity of soluble guanylate cyclase).(ABSTRACT TRUNCATED AT 250 WORDS)


A limb to stand on? A scoping review of employability assessment in Australian total and permanent disability insurance claims.
Purpose: Employability assessment helps in deciding to pay or decline Australian total and permanent disability insurance claims, yet it has not been critically examined. This paper reviews employability assessment from forensic vocational assessment, life insurance/superannuation, and legal perspectives.Methods: In a scoping review, we searched six multidisciplinary databases and various industry-specific resources. Items pertinent to forensic employability/vocational assessment and life insurance total and permanent disability claims were included. Return-to-work assessment, the vocational assessor, medical or functional evaluation, and case law items were excluded. Quality appraisal measures were used for research studies and other items. From 104 full-text reviews, 39 items were included for thematic synthesis from the three perspectives of interest.Results: Our review found that employability assessment is derived from forensic vocational assessment, but methodology differs in claimant contact and psychosocial aspects. Employability assessment practice is informed by policy, market changes, and legal interpretation. Assessors may work for opposing sides in forensic or indirect settings therefore high standards and credentials must prevail.Conclusions: Foundational research into the effectiveness of employability assessment and the experience of claimants is warranted. Future research into methodology, assessor credentials, and legal aspects will broaden understanding of this relatively new topic.Implications for rehabilitationEmployability assessment is an emergent and hitherto unexamined model that operates in the multi-billion-dollar Australian total and permanent disability insurance market.Total and permanent disability insurance policies and their legal interpretation are ever-changing and substantially inform employability assessment practice.Employability assessment lacks methodology and variables that are common elements in proven forensic vocational assessment models in the United States.Training and credentialing of rehabilitation professionals who conduct employability assessments are required to withstand legal scrutiny and meet international forensic standards.


Serological Investigation of Peste Des Petits Ruminants in East Shewa and Arsi Zones, Oromia Region, Ethiopia.
Peste des petits ruminant (PPR) is an economically important disease of small ruminants with a rapidly expanding geographical distribution. There are fragmented reports to the occurrence and distribution of the disease in Ethiopia. A total of 700 serum samples were collected from goats and sheep to detect the presence of antibody against PPR virus using Competitive Enzyme-Linked Immunosorbent Assay (C-ELISA). An overall PPR seropositivity was reported to be 48.43% in the area. There is no statistically significant difference in the seroprevalence of the disease between sheep and goats (50.85% and 46.68%), respectively. However, there was statistically significant variation (P < 0.05) in the seroprevalence of the disease in young (33.9%) and adult (55.8%) age categories. The seroprevalence in male and female was 42.07% and 50.09%, respectively, where the variation was statistically not significant (P > 0.05). High seroprevalence of Peste des petites ruminants in the study area indicated the virus circulation and endemicity of the disease. The disease causes substantial economic losses by affecting the livelihood of the farmers. Therefore, control measures should be put in place to minimize the loss associated with the disease.


Fasciola hepatica mucin-encoding gene: expression, variability and its potential relevance in host-parasite relationship.
Fasciola hepatica is the causative agent of fasciolosis, a zoonosis with significant impact both in human and animal health. Understanding the basic processes of parasite biology, especially those related to interactions with its host, will contribute to control F. hepatica infections and hence liver pathology. Mucins have been described as important mediators for parasite establishment within its host, due to their key roles in immune evasion. In F. hepatica, mucin expression is upregulated in the mammalian invasive newly excysted juvenile (NEJ) stage in comparison with the adult stage. Here, we performed sequencing of mucin cDNAs prepared from NEJ RNA, resulting in six different cDNAs clusters. The differences are due to the presence of a tandem repeated sequence of 66 bp encoded by different exons. Two groups of apomucins one with three and the other with four repeats, with 459 and 393 bp respectively, were identified. These cDNAs have open reading frames encoding Ser-Thr enriched proteins with an N-terminal signal peptide, characteristic of apomucin backbone. We cloned a 4470 bp gene comprising eight exons and seven introns that encodes all the cDNA variants identified in NEJs. By real time polymerase chain reaction and high-resolution melting approaches of individual flukes we infer that fhemuc-1 is a single-copy gene, with at least two different alleles. Our data suggest that both gene polymorphism and alternative splicing might account for apomucin variability in the fhemuc-1 gene that is upregulated in NEJ invasive stage. The relevance of this variation in host-parasite interplay is discussed.


Preparation and properties of thyroxine-binding alpha globulin (TBG).
Thyroxine-binding alpha globulin (TBG) in human serum was isolated from Cohn fractions IV-5,6 and IV-4 by (1) chromatography on carboxymethyl (CM) cellulose, (2) gel filtration on Sephadex G-200, (3) chromatography on diethylaminoethyl-Sephadex, (4) a novel procedure of "double-gel" electrophoresis, and (5) preparative polyacrylamide gel electrophoresis. The protein was homogeneous by analytical disc gel electrophoresis, immunoelectrophoresis, and ultracentrifugal analyses (sedimentation velocity and sedimentation equilibrium), and after addition of thyroxine-(125)I showed a constant specific radioactivity on polyacrylamide electrophoresis. The sedimentation and diffusion coefficients were s(20, w), 3.0 x 10(-13) sec, and D(20, w), 8.05 x 10(-7) cm(2).sec(-1), and the molecular weight obtained by sedimentation equilibrium was 36,500. Gel filtration studies on Sephadex G-200 demonstrated that the protein had the same elution volume as that of native TBG in serum, apparently excluding the possibility of a subunit of the native protein. Chemical composition was ascertained by amino acid and carbohydrate analyses. The maximal thyroxine (T4)-binding capacity measured by reverse flow paper electrophoresis was 15,000 mug per g of protein, representing more than 2100 times that of the starting material, or about 5000 times that of whole serum. Based on the molecular weight obtained, the TBG preparation could bind 0.7 mole T4 per mole of protein, suggesting a single binding site. The association constant for T4 was estimated to be of the order of 10(10) by competitive binding studies employing TBG and T4-binding prealbumin (TBPA).


The effect of the visceral adiposity index on the severity of COVID-19 disease: results of a cross-sectional study.
Obesity has been identified as a contributing factor that exacerbates the severity of COVID-19 and is associated with an increased risk of mortality among hospitalized patients. Assessing visceral adipose tissue cannot be solely determined by obesity and body mass index (BMI) alone. In our study, we investigated the relationship between the visceral adiposity index (VAI) and the clinical severity of COVID-19. A total of 315 adult patients hospitalized with COVID-19 were included in the study. The cohort consisted of 146 male patients, and the median age was 60 (48-74) years. Comparative analyses were conducted to evaluate gender-based differences in VAI levels and the impact of VAI on the extent of radiological lung involvement. The median VAI level was significantly higher in women compared to men (6.1 vs. 4.0, p<0.001). Furthermore, patients with radiologically severe lung involvement demonstrated a higher median VAI level compared to those with mild involvement (5.7 vs. 4.2, p=0.003). This difference was particularly notable among male patients, where the median VAI level was significantly higher. Logistic regression analysis revealed that each integer increase in the median VAI value was associated with a 1.1-fold (1.01-1.14) increase in the severity of radiological lung involvement (p=0.011). Our study highlights a significant correlation between VAI and the clinical severity of COVID-19, particularly among male patients. The findings suggest that VAI, as an indicator of visceral adiposity, holds potential as a valuable tool for assessing COVID-19 severity and identifying high-risk individuals, particularly males.


Nutrition in space: lessons from the past applied to the future.
From the basic impact of nutrient intake on health maintenance to the psychosocial benefits of mealtime, the role of nutrition in space is evident. In this discussion, dietary intake data from three space programs, Apollo, Space Shuttle, and Skylab, are presented. Data examination reveals that energy and fluid intakes are almost always lower than predicted. Nutrition in space has many areas of impact, including provision of required nutrients and maintenance of endocrine, immune, and musculoskeletal systems. Long-duration missions will require quantitation of nutrient requirements for maintenance of health and protection against the effects of microgravity. Psychosocial aspects of nutrition will also be important for more productive missions and crew morale. Realization of the full role of nutrition during spaceflight is critical for the success of extended-duration missions. Research conducted to determine the impact of spaceflight on human physiology and subsequent nutritional requirements will also have direct and indirect applications in Earth-based nutrition research.


Time-dose-mortality data and modeling for the entomopathogenic fungus Aschersonia placenta against the whitefly Bemisia tabaci.
The fungus Aschersonia placenta FJSM was evaluated for control of the sweet potato whitefly, Bemisia tabaci. Bemisia tabaci nymphs (1st-4th instars) on tomato plants in the greenhouse (25-27 °C, 70%-85% relative humidity) were sprayed with suspensions containing 0, 10(4), 10(5), 10(6), 10(7), or 10(8) A. placenta FJSM conidia/mL. Mortality of fungus-treated 1st to 3rd instar nymphs ranged from 93% to 100% but was <25% for 4th instar nymphs; the fungus sporulated from 70% to 80% of the fungus-treated B. tabaci cadavers. LD50 and LD90 values decreased with time after treatment and increased with instar. LT50 values decreased with conidial concentration. The data were then described with time-dose-mortality models. The results indicate that A. placenta FJSM has potential as a mycoinsecticide for control of B. tabaci.


Impulsivity in the prediction of suicidal behavior in adolescent populations.
Impulsivity has been identified as a key factor in risk of suicidal behavior in adolescent and adult patients. However, a lack of consensus about the definition of impulsivity has led to difficulty in its measurement. Impulsivity self-report scales exhibit low intercorrelations, are subject to response bias, and incorporate multiple subfactors. Performance tests may be less sensitive to response biases, as well as be more precise measures of dimensions of impulsivity, but each test alone does not provide a comprehensive measure of the trait. Assessing impulsivity in child and adolescent groups presents additional methodological problems, such as an overlap between limited impulse control due to developmental factors and psychopathology. A multiple measures approach to assessing impulsivity is suggested.


Abdominal tuberculosis: CT findings.
The computed tomographic (CT) characteristics of intraabdominal tuberculosis are not specific. A recent article from South Africa proposed a set of criteria that included high density ascites and mesenteric involvement, consisting of thickening and adenopathy, as possible criteria for the diagnosis of tuberculous peritonitis by CT. Review of three additional cases of abdominal tuberculosis showing these findings supports the criteria defined in the earlier study. Although not definitive, these findings in the appropriate clinical setting should suggest the possibility of tuberculosis.


Ontogenetic criteria to distinguish vertebral types on the debated xenarthran synsacrum.
The presence of a synsacrum formed by the fusion of vertebrae that come into closed contact with the ilium and ischium is a feature that characterizes the clade Xenarthra. Nevertheless, the proper identity of each vertebral element that forms it is a matter of discussion. In this article, we provide ontogenetic information about skeletal ossification of the xenarthran synsacrum and define the position of the sacrocaudal limit within it. We analyzed the synsacrum of 25 specimens of nonadult and 101 adult armadillos and anteaters: Dasypus hybridus, D. novemcinctus, Chaetophractus vellerosus, C. villosus, Tamandua tetradactyla, and Myrmecophaga tridactyla. Two sets of vertebrae were identified: an anterior set, often attached to the iliac bones, in which transverse processes are originated mainly from an expansion of the base of the neural arches, and secondarily from a lateroventral ossification center. A posterior set is characterized by a series of vertebrae along which extra lateral ossifications (described here for the first time) are developed and form exclusively the transverse processes. Among armadillos, the sacrocaudal limit is set between the last vertebrae attached to the iliac bones and the first vertebrae that form the dorsal border of the sacroischial fenestra. In addition, anterior free caudals also showed extra lateral ossifications forming exclusively the transverse processes, supporting the notion that more posterior synsacrals are in fact caudal vertebrae that were incorporated to the synsacrum. In pilosans, the sacrocaudal limit is set between the first vertebrae that come into contact with the ischial bones and the immediately anterior one. However, the pattern of homologies is obscured by the low resolution in the ontogenetic sequence when compared to that of armadillos.


Apelin, plasmatic osmolality and hypotension in dialyzed patients.
To evaluate the balance between arginine-vasopressin (AVP) and apelin during hemodialysis and its role in hypotension onset and in the inflammation status. We enrolled 50 patients chronically treated with hemodialysis. We assessed plasmatic osmolality, AVP, apelin, mean blood pressure (BP), high-sensitivity C-reactive protein (hsCRP) and β(2)-microglobulin. Apelin rises during dialytic treatment (from 0.68 ± 0.34 to 1.89 ± 0.56 pg/ml, p < 0.0001), while plasmatic osmolality (from 325 ± 4.54 to 311 ± 1.20 mosm/kg H(2)O, p < 0.0001), AVP (from 4.28 ± 1.12 to 2.48 ± 0.50 pg/ml, p < 0.0001) and mean BP (from 124 ± 6 to 110 ± 7 mm Hg, p < 0.0001) decrease. At multivariate regression with respect to apelin, only mean BP remains (r = -0.95, p < 0.0001). We also correlated the AVP/apelin ratio with BP. Moreover, apelin is inversely related to hsCRP (r = -0.79, p < 0.0001). The AVP/apelin balance changes with plasmatic osmolality variations induced by hemodialytic sessions and could represent a physiopathological marker of arterial hypo- and hypertension. Finally, apelin appears inversely related to inflammation markers.


Factors affecting responsivity of unilamellar liposomes to 20 kHz ultrasound.
Ultrasound is commonly used in the preparation of unilamellar liposome dispersions and is often considered for cell membrane disruption for drug delivery or DNA transfection applications. To better understand the physical and chemical properties of lipid membranes that render them susceptible to ultrasonic permeabilization, the roles of temperature, lipid composition (cholesterol and PEG-lipid content), and liposome size have been studied. The results of these studies suggest that lipid packing is very important to ultrasound responsiveness; surprisingly, cohesive energy and tensile strength are not. Taken together, the experimental results implicate a defect-mediated permeabilization mechanism, rather than pore formation or membrane tearing. The implications of this work for drug release from liposomes and ultrasound-mediated DNA transfection are discussed.


Effects of 1,25-dihydroxyvitamin D3 on the local bone renin-angiotensin system in a murine model of glucocorticoid-induced osteoporosis.
Active vitamin D is closely related to the circulating renin-angiotensin system (RAS) in experimental animal models and humans; however, corresponding local bone data remain limited. The present study examined whether 1,25-dihydroxyvitamin D3 supplementation altered local bone RAS elements in a murine model of glucocorticoid-induced osteoporosis (GIOP). A total of 36 8-week-old mice were randomized into three equal-sized groups: The sham, GIOP and 1,25-dihydroxyvitamin D3 treatment groups. After 12 weeks, the cancellous bone microstructure of the third lumbar vertebra and left femur from the mice from each group were examined using micro-computed tomography. To access the impact of glucocorticoid use, the effect of 1,25-dihydroxyvitamin D3 on cancellous bone microstructure, the expression of bone turnover markers, circulation and expression of the main RAS components was assessed. Results demonstrated that bone volume fraction, trabecular number and trabecular thickness of the treatment and sham groups were significantly higher than the GIOP group (P<0.05). Furthermore, the structure model index, trabecular separation and bone surface to bone volume ratio of the sham and treatment groups were significantly reduced compared with the GIOP group (P<0.05). All assessed parameters exhibited no significant differences between the treatment and sham groups. mRNA expression levels of local bone angiotensin type 1 and 2 receptors and receptor activator of nuclear factor-κB ligand were significantly lower in the treatment group than in the GIOP group (P<0.05); however, there were no significant differences in circulating protein levels between the groups (P>0.05). In conclusion, 1,25-dihydroxyvitamin D3 may modulate bone metabolism by downregulating the local bone RAS in mice with GIOP.


Characterization of a human foamy virus 170-kilodalton Env-Bet fusion protein generated by alternative splicing.
Primate foamy viruses (FVs) express, in addition to the 130-kDa envelope protein, a 170-kDa glycoprotein, which reacts with antisera specific for the envelope and Bel proteins. We determined the exact nature of this 170-kDa glycoprotein by using the molecularly cloned human FV (HFV). Radioimmunoprecipitation analysis of 293T cells transfected with appropriate expression constructs by using antisera specific for the HFV Env, Bel1, and Bel2 proteins, as well as reverse transcription-PCR analysis of HFV-infected cells, demonstrated that this protein is an Env-Bet fusion protein that is secreted into the supernatant. However, it is only loosely associated, or not associated, with viral particles. gp170 is generated by an alternatively spliced Env mRNA using a splice donor and splice acceptor pair localized within the env open reading frame (ORF), which is normally used to generate Bell and Bet transcripts derived from the internal promoter within the env ORF. gp170 is expressed at a level 30 to 50% of the Env precursor gp130. However, it alone does not confer infectivity to HFV particles, because capsids derived from proviruses expressing only the gp170 were not released into the supernatant. In contrast, viruses derived from proviral clones deficient in gp170 expression showed similar in vitro infectivity and replication kinetics to wild-type virus. Furthermore, both types of viruses were inactivated to a similar extent by neutralizing sera, indicating that shedding of gp170 probably does not affect the humoral immune response in the infected host.


[Differential diagnosis of inflammation-induced arterial vascular diseases].
The clarification of non-arteriosclerotic inflammatory vascular diseases is based on angiological, angiographical, immunological and immunohistological methods and parameters. As causes of the arterial occlusive disease of younger patients are taken into consideration the obliterating endangiitis and Takayasu's aortoarteriitis. To the clinical manifestations of the giant cell arteriitis belong the temporal arteriitis and the rheumatic polymyalgia. Hypersensitivity and panangiitides are to be delimited from the group of the pathergic granulomatoses. The secondary Raynaud's syndrome on the basis of a digital arteriitis is of differential-diagnostic and prognostic importance in collagenoses and rheumatoid arthritis.


Activated and inactivated renin-angiotensin system in transgenic animals: from genes to blood pressure.
Much of our knowledge about blood pressure regulation has come from a huge number of biochemical, endocrinologic, pharmacologic, clinical, and physiologic studies. The renin-angiotensin system, composed of enzymatic and signal-transduction cascades, has a key role in regulating arterial blood pressure and in developing certain forms of experimentally induced hypertension and hypertension in human beings. Angiotensin peptides, the products of this system, exert a wide range of physiologically important effects on many tissues, including those of the cardiovascular system, through their actions on angiotensin receptors. Recently, several groups have succeeded in generating animals transgenic for the renin or angiotensinogen genes, or with a targeted disruption of the component genes of the renin-angiotensin system. This brief review describes advances of the in vivo analysis of blood pressure regulation by focusing on the renin-angiotensin system.


Tetraspanin CD9 is involved in the migration of retinal microvascular endothelial cells.
Members of the tetraspanin protein family are modulators of several fundamental cellular processes in various cell types. However, expression and function of these proteins have not been studied in microvascular endothelial cells despite their (patho-)physiological importance. Western blotting, FACS or RT-PCR analyses confirmed that CD9 and other tetraspanins are expressed in immortalized microvascular endothelial cells of the bovine retina (iBREC). In subconfluent cultures, most of the detected CD9 was located intracellularly as well as in the plasma membrane at cell-cell contact sites and in long spike-like extensions, whereas cells in confluent cultures predominantly showed plasma membrane staining. In wound healing assays, CD9 delocalized from the plasma membrane to its intracellular compartment in cells located at the gap border, and the gap closure was retarded by the addition of an anti-CD9 antibody. Migration of iBREC towards fibronectin and their adhesion to fibronectin were also strongly inhibited in the presence of an anti-CD9 antibody whereas other anti-tetraspanin antibodies had no effect. In summary, iBREC express members of the tetraspanin family of which CD9 was demonstrated to have a function in migration and adhesion of these cells.


Patterning and regulatory associations of DNA methylation are mirrored by histone modifications in insects.
Epigenetic information is an important mediator of the relationship between genotype and phenotype in eukaryotic organisms. One of the most important and widely conserved forms of epigenetic information is the methylation of genes. However, the function of intragenic DNA methylation remains poorly understood. The goal of this study was to gain greater understanding of the nature of intragenic methylation by determining its role in the multilayered epigenetic landscape of insects. We first investigated the evolutionary lability of DNA methylation by examining whether methylation patterns were conserved in the fire ant and honey bee. We found that DNA methylation was targeted to largely overlapping sets of orthologs in both species. Next, we compared intragenic DNA methylation levels in the fire ant and honey bee to comprehensive epigenetic and gene-regulatory data from Drosophila melanogaster orthologs. We observed striking evidence of a conserved association between DNA methylation in fire ants and honey bees, and several active histone modifications, constitutive gene expression, and "broad" promoter architecture in D. melanogaster. Overall, our study illustrates that DNA methylation is a single component of a conserved, integrated, multilayered epigenetic and regulatory landscape in insect genomes.


Arrow injuries in North East Nigeria.
Arrow injuries are an extinct form of injury in most parts of the developed world but constitute 0.1% of emergency admissions in the University of Maiduguri Teaching Hospital annually. This is a retrospective study of arrow injuries carried out over a ten-year period (1989-1999) in order to study the reasons for its continued incidence the presentation and the experiences in the management of these injuries. There were 73 cases of arrow injuries and were all males with a peak age incidence of 31-40 years of age. Majority were farmers, cattle herdsmen and traders from the northeast region of Nigeria and the neighbouring republic of Cameroon, Chad and Niger. The various reasons for the injuries were armed robbery in 41%, communal clashes 20.5%, dispute between farmers and cattle herdsmen 13%, and cattle theft 8%. Majority were clinically stable on presentation with arrows in the head, neck, chest and abdomen this resulted in various surgical procedures in order to remove the arrows and repair damaged viscera. Unstable presentations resulted in mortalities (4.1%) preoperatively. Wound infection was the most common complication in patients who presented late. Improvements in the socio-economic conditions in the region and legislation on the use of these weapons would reduce the incidence of these injuries.


Lithium treatment of acute mania in adolescents: a placebo-controlled discontinuation study.
There are no published placebo-controlled studies of any agent in the treatment of acute mania in children or adolescents. This is the first placebo-controlled study of lithium's efficacy in the treatment of acute mania in adolescents. In this discontinuation study, participants received open treatment with lithium at therapeutic serum levels (mean 0.99 mEq/L) for at least 4 weeks. Responders were randomly assigned to continue or discontinue lithium during a 2-week double-blind, placebo-controlled phase. This study had 80% power to detect a 40% difference in exacerbation rates between groups (10% on lithium versus 50% on placebo). Twenty-three of 40 protocol participants (57.5%) experienced a clinically significant symptom exacerbation during the 2-week double-blind phase. However, the slightly lower exacerbation rate in the group maintained on lithium (10/19 or 52.6%) versus the group switched to placebo (13/21 or 61.9%) did not reach statistical significance. This study does not support a large effect for lithium continuation treatment of adolescents with acute mania, mostly due to the unexpectedly high rate of exacerbations in the group that continued on lithium. Further studies are warranted to clarify whether acute mania in adolescents is lithium responsive.


Dissociating Medial Temporal and Striatal Memory Systems With a Same/Different Matching Task: Evidence for Two Neural Systems in Human Recognition.
The medial temporal lobe and striatum have both been implicated as brain substrates of memory and learning. Here, we show dissociation between these two memory systems using a same/different matching task, in which subjects judged whether four-letter strings were the same or different. Different RT was determined by the left-to-right location of the first letter different between the study and test string, consistent with a left-to-right comparison of the study and test strings, terminating when a difference was found. This comparison process results in same responses being slower than different responses. Nevertheless, same responses were faster than different responses. Same responses were associated with hippocampus activation. Different responses were associated with both caudate and hippocampus activation. These findings are consistent with the dual-system hypothesis of mammalian memory and extend the model to human visual recognition.


Effect of sequential comparison on active processing of sound duration.
Previous studies on active duration processing on sounds showed opposing results regarding the predominant involvement of the left or right hemisphere. Duration of an acoustic event is normally judged relative to other sounds. This requires sequential comparison as auditory events unfold over time. We hypothesized that increasing the demand on sequential comparison in a task increases the involvement of the left auditory cortex. With the current fMRI study, we investigated the effect of sequential comparison in active duration discrimination by comparing a categorical with a comparative task. During the categorical task, the participant had to categorize the tones according to their duration (short vs long). During the comparative task, they had to decide for each tone whether its length matched the tone presented before. We used the contralateral noise procedure to reveal the degree of participation of the left and right auditory cortex during these tasks. We found that both tasks more strongly involve the left than the right auditory cortex. Furthermore, the left auditory cortex was more strongly involved during comparison than during categorization. Together with previous studies, this suggests that additional demand for sequential comparison during processing of different basic acoustic parameters leads to an increased recruitment of the left auditory cortex. In addition, the comparison task more strongly involved several brain areas outside the auditory cortex, which may also be related to the demand for additional cognitive resources as compared to the more efficient categorization of sounds. Hum Brain Mapp 38:4459-4469, 2017. © 2017 Wiley Periodicals, Inc.


The Glycogen Synthase Kinase-3 in the Regulation of Ion Channels and Cellular Carriers.
Glycogen synthase kinase-3 (GSK-3) is a highly evolutionarily conserved and ubiquitously expressed serine/threonine kinase, an enzyme protein profoundly specific for glycogen synthase (GS). GSK-3 is involved in various cellular functions and physiological processes, including cell proliferation, differentiation, motility, and survival as well as glycogen metabolism, protein synthesis, and apoptosis. There are two isoforms of human GSK-3 (named GSK-3α and GSK-3β) encoded by two distinct genes. Recently, GSK-3β has been reported to function as a powerful regulator of various transport processes across the cell membrane. This kinase, GSK-3β, either directly or indirectly, may stimulate or inhibit many different types of transporter proteins, including ion channel and cellular carriers. More specifically, GSK-3β-sensitive cellular transport regulation involves various calcium, chloride, sodium, and potassium ion channels, as well as a number of Na+-coupled cellular carriers including excitatory amino acid transporters EAAT2, 3 and 4, high-affinity Na+ coupled glucose carriers SGLT1, creatine transporter 1 CreaT1, and the type II sodium/phosphate cotransporter NaPi-IIa. The GSK-3β-dependent cellular transport regulations are a part of the kinase functions in numerous physiological and pathophysiological processes. Clearly, additional studies are required to examine the role of GSK-3β in many other types of cellular transporters as well as further elucidating the underlying mechanisms of GSK-3β-mediated cellular transport regulation.


Deep-sea echinoderm oxygen consumption rates and an interclass comparison of metabolic rates in Asteroidea, Crinoidea, Echinoidea, Holothuroidea and Ophiuroidea.
Echinoderms are important components of deep-sea communities because of their abundance and the fact that their activities contribute to carbon cycling. Estimating the echinoderm contribution to food webs and carbon cycling is important to our understanding of the functioning of the deep-sea environment and how this may alter in the future as climatic changes take place. Metabolic rate data from deep-sea echinoderm species are, however, scarce. To obtain such data from abyssal echinoderms, a novel in situ respirometer system, the benthic incubation chamber system (BICS), was deployed by remotely operated vehicle (ROV) at depths ranging from 2200 to 3600 m. Oxygen consumption rates were obtained in situ from four species of abyssal echinoderm (Ophiuroidea and Holothuroidea). The design and operation of two versions of BICS are presented here, together with the in situ respirometry measurements. These results were then incorporated into a larger echinoderm metabolic rate data set, which included the metabolic rates of 84 echinoderm species from all five classes (Asteroidea, Crinoidea, Echinoidea, Holothuroidea and Ophiuroidea). The allometric scaling relationships between metabolic rate and body mass derived in this study for each echinoderm class were found to vary. Analysis of the data set indicated no change in echinoderm metabolic rate with depth (by class or phylum). The allometric scaling relationships presented here provide updated information for mass-dependent deep-sea echinoderm metabolic rate for use in ecosystem models, which will contribute to the study of both shallow water and deep-sea ecosystem functioning and biogeochemistry.


Effect of poly(ethylene glycol) content and formulation parameters on particulate properties and intraperitoneal delivery of insulin from PLGA nanoparticles prepared using the double-emulsion evaporation procedure.
Size, encapsulation efficiency and stability affect the sustained release from nanoparticles containing protein-type drugs. Insulin was used to evaluate effects of formulation parameters on minimizing diameter, maximizing encapsulation efficiency and preserving blood glucose control following intraperitoneal (IP) administration. Homogenization or sonication was used to incorporate insulin into poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles with increasing poly(ethylene glycol) (PEG) content. Effects of polymer type, insulin/polymer loading ratio and stabilizer in the internal aqueous phase on physicochemical characteristics of NP, in vitro release and stability of encapsulated insulin were investigated. Entrapment efficiency and release were assessed by radioimmunoassay and bicinconnic acid protein assay, and stability was evaluated using SDS-PAGE. Bioactivity of insulin was assessed in streptozotocin-induced, insulin-deficient Type I diabetic mice. Increasing polymeric PEG increased encapsulation efficiency, while the absence of internal stabilizer improved encapsulation and minimized burst release kinetics. Homogenization was shown to be superior to sonication, with NP fabricated from 10% PEG-PLGA having higher insulin encapsulation, lower burst release and better stability. Insulin-loaded NP maintained normoglycaemia for 24 h in diabetic mice following a single bolus, with no evidence of hypoglycemia. Insulin-loaded NP prepared from 10% PEG-PLGA possessed therapeutically useful encapsulation and release kinetics when delivered by the IP route.


Cation-induced monolayer collapse at lower surface pressure follows specific headgroup percolation.
A Langmuir monolayer can be considered as a two-dimensional (2D) sheet at higher surface pressure which structurally deform with mechanical compression depending upon the elastic nature of the monolayer. The deformed structures formed after a certain elastic limit are called collapsed structures. To explore monolayer collapses at lower surface pressure and to see the effect of ions on such monolayer collapses, out-of-plane structures and in-plane morphologies of stearic acid Langmuir monolayers have been studied both at lower (≈6.8) and higher (≈9.5) subphase pH in the presence of Mg^{2+},Ca^{2+},Zn^{2+},Cd^{2+}, and Ba^{2+} ions. At lower subphase pH and in the presence of all cations, the stearic acid monolayer remains as a monolayer before collapse, which generally takes place at higher surface pressure (π_{c}>50mN/m). However, at higher subphase pH, structural changes of stearic acid monolayers occur at relatively lower surface pressure depending upon the specific dissolved ions. Among the same group elements of Mg^{2+},Ca^{2+}, and Ba^{2+}, only for Ba^{2+} ions does monolayer to multilayer transition take place from a much lower surface pressure of the monolayer, remaining, however, as a monolayer for Mg^{2+} and Ca^{2+} ions. For another same group elements of Zn^{2+} and Cd^{2+} ions, a less covered bilayer structure forms on top of the monolayer structure at lower surface pressure, which is evidenced from both x-ray reflectometry and atomic force microscopy. Fourier transform infrared spectroscopy confirms the presence of two coexisting conformations formed by the two different metal-headgroup coordinations and the monolayer to trilayer or multilayer transformation takes place when the coverage ratio of the two molecular conformations changes from the critical value (p_{c}) of ≈0.66. Such ion-specific monolayer collapses are correlated with the 2D lattice percolation model.


Current and future perspectives of chimeric antigen receptors against glioblastoma.
Glioblastoma multiforme (GBM) is the most malignant form of cancer in the central nervous system; even with treatment, it has a 5-year survival rate of 7.2%. The adoptive cell transfer (ACT) of T cells expressing chimeric antigen receptors (CARs) has shown a remarkable success against hematological malignancies, namely leukemia and multiple myeloma. However, CAR T cell therapy against solid tumors, and more specifically GBM, is still riddled with challenges preventing its widespread adoption. Here, we first establish the obstacles in ACT against GBM, including on-target/off-tumor toxicity, antigen modulation, tumor heterogeneity, and the immunosuppressive tumor microenvironment. We then present recent preclinical and clinical studies targeting well-characterized GBM antigens, which include the interleukin-13 receptor α2 and the epidermal growth factor receptor. Afterward, we turn our attention to alternative targets in GBM, including less-explored antigens such as B7-H3 (CD276), carbonic anhydrase IX, and the GD2 ganglioside. We also discuss additional target ligands, namely CD70, and natural killer group 2 member D ligands. Finally, we present the possibilities afforded by novel CAR architectures. In particular, we examine the use of armored CARs to improve the survival and proliferation of CAR T cells. We conclude by discussing the advantages of tandem and synNotch CARs when targeting multiple GBM antigens.


Standard immunohistochemistry efficiently screens for anaplastic lymphoma kinase rearrangements in differentiated thyroid cancer.
The anaplastic lymphoma kinase (ALK) gene is frequently rearranged in various types of cancer and is highly responsive to targeted therapeutics. We developed a system to detect rearrangement of ALK in a large group of Korean thyroid cancer patients. We screened 474 malignant or benign thyroid tumor cases to identify ALK fusions. Expression and translocation of the ALK gene were analyzed by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and digital multiplexed gene expression (DMGE) analysis in formalin-fixed paraffin-embedded tissues. Four cases of rearrangement of ALK were detected by IHC, and these cases were validated with FISH on 189 samples. On the other hand, DMGE analysis using Nanostring detected three out of four IHC-positive cases. Two rearrangements of ALK were striatin (STRN)-ALK fusions, which were identified by 5' RACE analysis. Rearrangements of ALK were found exclusively in v-raf murine sarcoma viral oncogene homolog B (BRAF) WT papillary carcinomas. Given the wide availability and accuracy of IHC for detecting ectopic expression of ALK in the thyroid, we suggest that IHC-based screening can be a practical method for identifying patients with ALK rearrangements in differentiated thyroid cancer.


Pharmacotherapeutic options for visceral leishmaniasis-current scenario.
Visceral leishmaniasis (VL) or Kala-azar is a protozoal disease, which was previously regarded as one of the most neglected tropical diseases. Management of this disease is quite difficult, because it is said to affect the poorest of the poor. Previously Sodium Stibogluconate (SSG) was regarded as the gold standard treatment for VL. But due to the increasing unresponsiveness, to this drug various other drugs were tried and are still being tried. Pentamidine is very toxic and has been discarded of late. Amphotericin B and its lipid formulations are very effective but require hospital admission and monitoring. Oral drugs like Miltefosine have already been launched. An amino glycoside Paromomycin and another oral drug Sitamaquine are in the pipe line. Interferon gamma has been used with discouraging results.


Water policy differences between a western democracy and a country in economic transition.
Where environmental policy is concerned Western democracies and transition economies share more similarities than differences. Sound environmental policies require substantial investment. Public-private cooperation can play a major role in the search for solutions, but politicians, environmentalists and academics must act vigorously to ensure that big business does not acquire a final say in the implementation of environmental policy. Lithuania as a transition economy faces major environmental challenges, but international collaboration, including working with the European Union and cross-border cooperation with neighbouring states, is bringing good results. A major unifying factor for the Baltic Sea states is the continuing struggle to purify and protect the Baltic Sea.


Doxycycline vs Hydroxychloroquine + Azithromycin in the Management of COVID-19 Patients: An Open-Label Randomized Clinical Trial in Sub-Saharan Africa (DOXYCOV).
Objective We aimed to compare the safety and efficacy of a doxycycline-based regimen against Cameroon National Standard Guidelines (hydroxychloroquine plus azithromycin) for the treatment of mild symptomatic COVID-19. Methods We conducted an open-label, randomized, non-inferiority trial in Cameroon comparing doxycycline 100 mg, twice daily for seven days versus hydroxychloroquine 400 mg daily for five days and azithromycin 500 mg at day 1 and 250 mg from day 2 through 5 in mild COVID-19 patients. Clinical recovery, biological parameters, and adverse events were assessed. The primary outcome was the proportion of clinical recovery on days 3, 10, and 30. Non-inferiority was determined by the clinical recovery rate between protocols with a 20-percentage points margin. Results One hundred and ninety-four participants underwent randomization and were treated either with doxycycline (n = 97) or hydroxychloroquine-azithromycin (n = 97). On day 3, 74/92 (80.4%) participants on doxycycline versus 77/95 (81.1%) on hydroxychloroquine-azithromycin-based protocols were asymptomatic (p = 0.91). On day 10, 88/92 (95.7%) participants on doxycycline versus 93/95 (97.9%) on hydroxychloroquine-azithromycin were asymptomatic (p = 0.44). On day 30, all participants were asymptomatic. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) polymerase chain reaction (PCR) test was negative on day 10 in 60/92 (65.2%) participants who were assigned to doxycycline and in 63/95 (66.3%) participants who were assigned to hydroxychloroquine-azithromycin. None of the participants were admitted for worsening of the disease after treatment initiation. Conclusion Doxycycline 100 mg twice daily for seven days proved to be safe and non-inferior in terms of efficacy when compared to hydroxychloroquine-azithromycin for preventing clinical worsening of mild symptomatic or asymptomatic COVID-19 and achieving virological suppression.


Hsa_circ_0001946 Inhibits Lung Cancer Progression and Mediates Cisplatin Sensitivity in Non-small Cell Lung Cancer via the Nucleotide Excision Repair Signaling Pathway.
Background: Despite great advances in the diagnosis and treatment of non-small cell lung cancer (NSCLC), early diagnosis remains a challenge because patients usually have advanced lung cancer at the time they are diagnosed. The limited efficacy of conventional chemotherapy is another major problem in the treatment of NSCLC. Based on a published set of sequencing data, we find that hsa_circ_0001946 is a circRNA molecule with a significantly different expression level in three cell lines (human normal lung fibroblasts cell line MRC-5, human NSCLC cell line A549, cisplatin-resistant cell line A549/DDP), NSCLC tissues and paired adjacent normal tissues. We believe that hsa_circ_0001946 may have an effect on the progression of NSCLC and its sensitivity to cisplatin. Methods: We focused on investigating the circular RNA, hsa_circ_0001946. RNA interference of hsa_circ_0001946 was carried out in A549 cell lines to determine the effect of reduced hsa_circ_0001946 expression on lung cancer progression and was analyzed by Cell Counting Kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine, clone formation, Hoechst, wound healing, and transwell assays. The nucleotide excision repair (NER) signaling pathway was identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Moreover, cellular responses to cisplatin were assessed through CCK-8 and flow cytometry assays. Western blot analysis and host-cell reactivation assay were used to determine the effect of hsa_circ_0001946 on NER signaling. Results: In this study, we found that the reduced expression of hsa_circ_0001946 promoted the viability, proliferation, migration, and invasion of NSCLC cells, as well as inhibition of cell apoptosis. Our findings suggest that hsa_circ_0001946 can affect the sensitivity of NSCLC cells to the chemotherapeutic drug cisplatin via modulation of the NER signaling pathway. Conclusions: Our study demonstrated the role of hsa_circ_0001946 in NSCLC pathogenesis, development, and chemosensitivity, and suggests that hsa_circ_0001946 may serve as a novel biomarker for the diagnosis and prediction of platinum-based chemosensitivity in patients with NSCLC.


Ozone Therapy on Reduction of Bacterial Colonies and Acceleration of Diabetic Foot Ulcer Healing.
Diabetic foot ulcers (DFUs) are highly vulnerable to infection and pose risk for limb amputations. Studies have shown that ozone therapy reduces wound size and improves wound healing time better than standard treatments. We examined the effectiveness of combining standard wound care with ozone therapy to reduce bacterial colonization and accelerate healing of DFUs in the home care setting. The control group (n = 12) received standard wound care with antimicrobial dressings every 3 days for 21 days, and the intervention group (n = 15) received the same as control group plus ozone bagging therapy at 70 μg/mL for 10 minutes every 3 days for 21 days. Combining standard wound care with ozone therapy significantly decreased the number of bacterial colonies (p = 0.001). However, no significant difference in DFU assessment score was found between the intervention and control groups (p > 0.05). Combining standard wound care with ozone therapy reduced the number of bacteria in the DFUs but exerted no significant effect on wound healing. Future studies should examine the administration of ozone therapy with different concentrations and times of exposure to explore the right dose for healing DFUs.


T Lymphocytes in the Pathogenesis and Progression of Alzheimer's Disease: Pursuing Direct Neuropathological Evidence.
Multiple studies have proposed important roles of T cells in the pathogenesis of Alzheimer's disease. Given the successful application of immune-based therapy for cancer and a variety of diseases, T cell-modifying therapy becomes an attractive way to develop new therapies for Alzheimer's disease and perhaps neurodegenerative diseases in general. However, most of these studies address peripheral T cell responses, while direct pathological evidence documenting T cell infiltration relative to Alzheimer's disease pathological markers (i.e., amyloid plaque and neurofibrillary tangle) is sparse and at best, very preliminary in both human subjects and relevant animal models. Here, we concisely summarize the available pathological data that directly corresponds to T cell infiltration, critically analyze the current knowledge gaps, and thoughtfully propose several key recommendations for future research.


Catabolism of secretin by the liver and kidney.
We have investigated the roles of the liver and the kidney in the catabolism of secretin, using a specific and sensitive radioimmunoassay. Dogs were prepared with sampling catheters in the aorta, hepatic vein, portal vein, and renal vein and with electromagnetic flow probes on the portal vein, hepatic artery, and renal artery. Secretin levels in the vessels entering and leaving the liver and kidney were determined by radioimmunoassay and the total mass of secretin [concentration (picograms per milliliter) X plasma flow rate (milliliter per minute)] was calculated during an intravenous infusion of exogenous secretin and during release of endogenous secretin by acidification of the proximal intestine. The total masses of secretin entering and leaving the liver were the same during secretin infusion and during the release of endogenous secretin. Under conditions of elevation of plasma secretin, however, the kidney extracted 30 percent of arterial secretin during secretin infusion and 45 percent during release of endogenous secretin. Clearly the kidney is a major site of secretin catabolism.


Modeling and Analyzing the Transmission Dynamics of HBV Epidemic in Xinjiang, China.
Hepatitis B is an infectious disease caused by the hepatitis B virus (HBV) which affects livers. In this paper, we formulate a hepatitis B model to study the transmission dynamics of hepatitis B in Xinjiang, China. The epidemic model involves an exponential birth rate and vertical transmission. For a better understanding of HBV transmission dynamics, we analyze the dynamic behavior of the model. The modified reproductive number σ is obtained. When σ < 1, the disease-free equilibrium is locally asymptotically stable, when σ > 1, the disease-free equilibrium is unstable and the disease is uniformly persistent. In the simulation, parameters are chosen to fit public data in Xinjiang. The simulation indicates that the cumulated HBV infection number in Xinjiang will attain about 600,000 cases unless there are stronger or more effective control measures by the end of 2017. Sensitive analysis results show that enhancing the vaccination rate for newborns in Xinjiang is very effective to stop the transmission of HBV. Hence, we recommend that all infants in Xinjiang receive the hepatitis B vaccine as soon as possible after birth.


[Safeguarding herds from the animal hygiene point of view].
One of the most important concepts for the protection of herd health is the implementation of structural and organisational measures to prevent infective agents and other adverse compounds from entering the farm. Safeguarding health, well-being and production efficiency is part of the overall management concept of hygiene in animal production systems. This paper presents an overview of the most important rules and recommendations to protect livestock production facilities from the intrusion of infectious pathogens, beginning with the right choice of the site for the farm and the animal housing ("safe distances" to neighbouring farm animal houses), solid fencing and control and disinfecting places at the entrance gate. The traffic of vehicles and people transporting animals, feedstuff, equipment and slurry or manure to and from the facility should be reduced to a minimum. Fallen animals should be stored in separate and safe containers until removed by specialised companies. Regular control of rodents, insects and wild birds is crucial to avoid the transfer of infectious agents from farm to farm and between herds within a farm. Equally important factors are the health status of personnel to avoid transmission of zoonotic diseases, the application of the all-in-all-out system and a strict cleaning and disinfecting regime. The internal and external organisational measures for preventing the spread of infections in animal production will gain increasing importance in the future because the farm animal producer bears the responsibility for the production of safe and healthy food at the primary segment of the food chain. Increasing restrictions on the use of veterinary drugs for food delivering animals will increase the importance of prophylaxis, prevention and protection of production units as the keys for safeguarding health, well-being and efficiency of farm animals. Only the application of strict hygiene principles in animal production will make it possible to meet the consumer demand for safe and high quality food of animal origin.


Anesthetic Management of a Patient With Multiple Previous Episodes of Postanesthesia Care Unit Delirium: A Case Report.
We report the case of a 37-year-old female patient who required 22 surgeries following a pedestrian versus car accident. She was enrolled in a clinical study investigating emergence from anesthesia. In 10 of her 22 surgeries, we assessed her cognitive status in the postanesthesia care unit (PACU) using the Confusion Assessment Method. We observed PACU delirium in all 4 cases in which the patient received sevoflurane, but only in 1 of 6 cases in which she received propofol. The patient showed EEG α-band activity similar to that of an elderly patient who may reflect a greater risk of PACU delirium.


The 21st annual SOHN congress.
In a recent Presidential Perspectives column (see ORL-Head and Neck Nursing, Vol. 15, No. 3, Fall 1997, p. 4), Mary LeGrand described the impact that volunteerism can have on the success of an organization. The following article lends a prime example of how one SOHN member volunteers her services at both the local and national levels, donating her time and talents, reaping the rewards of her experiences, and ultimately sharing her thoughts in the following article.


Macroscopic Hematuria due to Placenta Percreta: Report of Two Cases and Short Review.
Herein we present two cases of pregnant women with placenta percreta and severe hematuria during the 24th and 35th weeks of pregnancy, respectively. A timely sonographic diagnosis was feasible in the first case and cesarean section was performed during the 29th week. During the operation, the placenta was invading the bladder wall and concomitant hysterectomy with cystotomy and bladder wall reconstruction was performed. The second case presented in our emergency department with vaginal bleeding during the 35th weeks of pregnancy. She underwent an emergency cesarean section with uterine preservation, cystotomy, and bladder reconstruction.


Malaria chemoprophylaxis with a proguanil-chloroquine-maloprim combination in Papua New Guinea.
Proguanil 200mg daily and chloroquine base 300mg weekly along with maloprim 1 tablet weekly was used as malaria chemoprophylaxis for 140 Hong Kong based soliders on a seven-week jungle exercise in a holoendemic malarial area of Papua New Guinea. On return from exercise all personnel were treated with primaquine 7.5mg three times daily for a two week period. One solider developed P. falciparum on the exercise whilst taking chemoprophylaxis and four subsequently developed P. vivax malaria after cessation of chemoprophylaxis.


Correlation between LH secretion in castrated rats with cellular proliferation and synthesis of DNA in the anterior pituitary gland.
The relationship between the release of LH and the synthesis of DNA was studied in the anterior pituitary gland of castrated rats. Cell types were characterized immunocytochemically. Castration significantly (P less than 0.01) increased the concentration of LH in serum (1326%) and the incorporation of [3H]thymidine into pituitary DNA (72%). This was accompanied by an increment in the activity of the enzyme DNA polymerase-alpha (58%) and in the number of mitoses (from 2 +/- 0.1/mm2 in intact rats to 21 +/- 0.8/mm2 15 days after castration). Only 20% of the mitoses found in the pituitary gland of castrated rats were positively stained with the antiserum against the beta-subunit of LH. The other 80% did not stain either with LH antiserum or with antisera against the other pituitary hormones. There was a significant (P less than 0.01) increase in the number of LH cells in castrated rats (48%). All the changes produced in the anterior pituitary gland after castration were prevented by the administration of dihydrotestosterone. The results demonstrate that a stimulation of LH release is followed by an increase of DNA synthesis and cell proliferation of gonadotrophs in the anterior pituitary gland.


Low rates of sustained virologic response with peginterferon plus ribavirin for chronic hepatitis C virus infection in HIV infected patients in Rio de Janeiro, Brazil.
The standard treatment for chronic hepatitis C virus (HCV) infection in HIV-infected subjects is the combination of alfapeginterferon (PEG-IFN) plus ribavirin. We designed this study to evaluate the rate of SVR and predictors of SVR in a public health setting in Rio de Janeiro, Brazil. Retrospective cohort study of HCV/HIV co-infected patients treated with PEG-IFN plus ribavirin from 2004 to 2011 in 3 outpatient units in Rio de Janeiro. Exposure variables included age, sex, CD4+ cell count, HCV genotype, HCV and HIV viral loads, liver histology (METAVIR fibrosis scoring system) and previous treatment. The main outcome measurement was SVR. 100 patients were included in this analysis. Median age was 47 years and 68% were male. 80%, 4%, 14% and 2% were infected with HCV genotypes 1, 2, 3 and 4, respectively. At baseline, 77% had HCV viral load greater than 800,000 IU/ml, 99% had CD4+ greater than 200 cells/mm(3) and 10% had a diagnosis of cirrhosis. The treatment was withdrawn in 9% of the subjects (5% with adverse effects and 4% dropped out). SVR was observed in 27 (27%) of the 100 patients included. 13 (13%) subjects were classified as null-responders, 33(33%) as non-responders, 9 (9%) as breakthrough and 9(9%) as relapsers. In the multivariate model only being infected with genotype 2 or 3 (p<0.01) and having low levels of gamma glutamyl transferase (GGT) at baseline (p = 0.04), were predictive of SVR. SVR in HCV/HIV co-infected subjects in a public health setting is similar to that observed in clinical trials, albeit very low. A delay in therapy initiation should be considered until new therapies as direct acting antiviral drugs (DAA) become widely available and tested in coinfected subjects.


Key role of bacterial NH(4)(+) metabolism in Rhizobium-plant symbiosis.
Symbiotic nitrogen fixation is carried out in specialized organs, the nodules, whose formation is induced on leguminous host plants by bacteria belonging to the family Rhizobiaceae: Nodule development is a complex multistep process, which requires continued interaction between the two partners and thus the exchange of different signals and metabolites. NH(4)(+) is not only the primary product but also the main regulator of the symbiosis: either as ammonium and after conversion into organic compounds, it regulates most stages of the interaction, from the production of nodule inducers to the growth, function, and maintenance of nodules. This review examines the adaptation of bacterial NH(4)(+) metabolism to the variable environment generated by the plant, which actively controls and restricts bacterial growth by affecting oxygen and nutrient availability, thereby allowing a proficient interaction and at the same time preventing parasitic invasion. We describe the regulatory circuitry responsible for the downregulation of bacterial genes involved in NH(4)(+) assimilation occurring early during nodule invasion. This is a key and necessary step for the differentiation of N(2)-fixing bacteroids (the endocellular symbiotic form of rhizobia) and for the development of efficient nodules.


Zataria multiflora Boiss and Carvacrol Affect β(2)-Adrenoceptors of Guinea Pig Trachea.
The stimulatory effect of Zataria multiflora Boiss (Labiatae) and carvacrol on β-adrenoceptors was examined on guinea pig trachea. The effects of three concentrations of aqueous-ethanolic extract, carvacrol, and propranolol (β-receptor antagonist) on β-adrenoceptors were tested in nonincubated (group 1, n = 8) and incubated tracheal chains with 1 μM chlorpheniramine (histamine H1 receptor antagonist) (group 2, n = 5). Isoprenaline (β-receptor agonist) curves obtained in the presence of all concentrations of the extract and carvacrol showed leftward shifts compared with that of saline in both groups. In both groups, the EC50 (the effective concentration of isoprenaline, causing 50% of maximum response) obtained in the presence of all concentrations of the extract and carvacrol was significantly lower compared to that of saline (P < .01 to P < .001). All values of (CR-1: (EC50 in the presence of active substances/EC50 obtained in the presence of saline)-1) obtained in the presence of concentrations of the extract and carvacrol in both groups were negative and significantly different from that of propranolol (P < .001 for all cases). The results indicated a stimulatory effect of Zataria multiflora Boiss extract on β(2)-adrenoceptors which is perhaps due to its constituent, carvacrol.


English News Text Recommendation Method Based on Hypergraph Random Walk Label Expansion.
With the rapid development of multimedia and Internet technology, English news text summary technology has received widespread attention as a way to quickly obtain English news text content. The existing method of English news text summarization based on graph model usually takes English news text as the vertices of the graph, and the relationship between the two vertices is represented by the edge. Although it has achieved good results, it cannot quickly sort out the English Complex relationships between news texts. In order to solve this problem, this paper uses the hypergraph model to model the relationship between English news text, and conducts in-depth research on the application of the hypergraph model in the field of English news text summarization. The high popularity of the Internet has brought about earth-shaking changes to the news industry, which makes the news on the Internet a great way for netizens to get news. However, the public cannot pick out satisfactory events from a large amount of news. In order to solve this problem, news event discovery technology that can help users quickly discover and understand hot news is produced. In addition, user personalized recommendation technology will rely on customer operation habits to provide customers with hot events of interest. The personalized news recommendation method adopted in this article has the advantages of integrating discovery and personalized news recommendation, and provides users with a better experience. Compared with the traditional hierarchical clustering algorithm, the algorithm proposed in this paper significantly improves the accuracy.


Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats.
Cadmium (Cd) is an environmental toxic metal implicated in lipid abnormalities. The present study was designed to elucidate the possible association between chronic exposure to Cd concentration and alterations in plasma lipid, lipoprotein, and oxidative stress indices in rats. Sixteen male rats were assigned to 2 groups of 8 rats each (test and control). The Cd-exposed group obtained drinking water containing cadmium chloride (CdCl2) in the concentration of 2.0 mg Cd/L in drinking water for 3 months. At the end of the experimental period, blood samples were obtained to determine the changes of serum triglycerides (TG), total cholesterol (TC), highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), reduced glutathione (GSH), malondialdehyde (MDA) and also serum Cd contents. The results of the present study indicated that Cd administration significantly increased the serum levels of TG, TC, LDL-C, MDA and Cd with reduction in the HDL-C and GSH levels. In conclusion, evidence is presented that chronic exposure to low Cd concentration can adversely affect the lipid and lipoprotein profile via lipid peroxidation.


Efficacy and tolerability of etodolac in aged patients affected by degenerative joint disease (osteoarthritis) in its active phase.
Three-hundred-and-fifteen patients, aged 60 or more years, affected by degenerative joint disease (DJD) in the active stage, the majority with concomitant pathological conditions of various organs and systems and undergoing various combined drug treatments, were treated with 300 mg b.i.d. etodolac in order to assay its efficacy and safety profile in an aged population more exposed to the occurrence of adverse events. In a subset of these patients, the impact of etodolac treatment on cognitive function and mood was studied. All clinical assessments revealed highly significant improvement after etodolac treatment. Significant improvement was found also for what concerns mood, whereas only the less aged patients showed improvement in cognitive abilities after treatment with etodolac. Only 30 patients (9.5%) showed side-effects, resulting in suspension of treatment in 10 cases (3.17%). In all cases, adverse reactions subsided with no consequences. Laboratory tests performed at the end of the study yielded mean values comprised within the normal range and were not statistically different from the same examinations performed before starting treatment. Occult blood in stool turned positive after treatment with etodolac only in six patients (2%). In conclusion, etodolac proved to be effective and well-tolerated in the treatment of risk-aged patients with active DJD.


[Open heart surgery in patients with a tracheostoma].
From April 1992 to May 1997 six patients underwent open heart surgery, who had tracheostoma at the time of operation. The sternum was divided completely in three patients whose tracheostoma lay highly on the neck, and it was cut transversely on the manubrium at the level of the first intercostal space, below which it was split longitudinally in two patients (partial median sternotomy). In one patient right anterolateral thoracotomy was used. There were no operative death and no complication related to infection. A left internal thoracic artery (LITA) was used successfully for a bypass conduit in two patients who underwent partial median sternotomy. Dissection of the proximal portion of the LITA through the second intercostal space prior to the sternotomy made the graft procurement feasible in this particular situation. In conclusion, full-length sternotomy is performable safely when the tracheostoma lies highly on the neck, and the partial sternotomy up to the midmanubrium is applicable, including LITA harvesting, even if it is just at the sternal angle.


Fluorescamine in cytodiagnosis of thyroid carcinomas.
Fluorescamine, which reacts with primary amino groups yielding intensely fluorescent products, was found to induce intense fluorescence in cells from medullary and papillary thyroid carcinoma. No fluorescence was detected in cells from follicular or undifferentiated carcinoma or from benign thyroid lesions, except Hürthle cell adenomas, the cells of which exhibited moderate fluorescamine-induced fluorescence. This was demonstrated on fine needle aspiration biopsy smears pretreated with formaldehyde gas. Since the fluorescamine technique is simple and rapid, it may be of value as an aid in the cytodiagnosis of thyroid neoplasms.


Stable, Fluorescent Polymethylmethacrylate Particles for the Long-Term Observation of Slow Colloidal Dynamics.
Suspensions of solid micron-scale colloidal particles in liquid solvents are a foundational model system used to explore a wide range of phase transitions, including crystallization, gelation, spinodal decomposition, and the glass transition. One of the most commonly used systems for these investigations is the fluorescent spherical particles of polymethylmethacrylate (PMMA) suspended in a mixture of nonpolar solvents that match the density and the refractive index of the particles to minimize sedimentation and scattering. However, the particles can swell in these solvents, changing their size and density, and may leak the fluorescent dye over days to weeks; this constrains the exploration of slow and kinetically limited processes, such as near-boundary phase separation or the glass transition. In this paper, we produce PMMA colloidal particles that employ polymerizable and photostable cyanine-based fluorescent monomers spanning the range of visible wavelengths and a polymeric stabilizer prepared from polydimethylsiloxane, PDMS-graft-PMMA. Using microcalorimetry, we characterize the thermodynamics of an accelerated equilibration process for these dispersions in the buoyancy- and refractive-index-matching solvents. We use confocal differential dynamic microscopy to demonstrate that they behave as hard spheres. The suspended particles are stable for months to years, maintaining fixed particle size and density, and do not leak dye. Thus, these particles enable longer term experiments than may have been possible earlier; we demonstrate this by observing spinodal decomposition in a mixture of these particles with a depletant polymer in the microgravity environment of the International Space Station. Using fluorescence microscopy, we observe coarsening over several months and measure the growth of the characteristic length scale to be a fraction of a picometer per second; this rate is among the slowest observed in a phase-separating system. Our protocols should facilitate the synthesis of a variety of particles.


Impact of lesion preparation strategies on outcomes of left main PCI: The EXCEL trial.
We examined outcomes according to lesion preparation strategy (LPS) in patients with left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in the EXCEL trial. The optimal LPS for LMCA PCI is unclear. We categorized LPS hierarchically (high to low) as: (a) rotational atherectomy (RA); (b) cutting or scoring balloon (CSB); (c) balloon angioplasty (BAL); and d) direct stenting (DIR). The primary endpoint was 3-year MACE; all-cause death, stroke, or myocardial infarction. Among 938 patients undergoing LMCA PCI, RA was performed in 6.0%, CSB 9.5%, BAL 71.3%, and DIR 13.2%. In patients treated with DIR, BAL, CSB, and RA, respectively, there was a progressive increase in SYNTAX score, LMCA complex bifurcation, trifurcation or calcification, number of stents, and total stent length. Any procedural complication occurred in 10.4% of cases overall, with the lowest rate in the DIR (7.4%) and highest in the RA group (16.1%) (ptrend = .22). There were no significant differences in the 3-year rates of MACE (from RA to DIR: 17.9%, 20.2%, 14.5%, 14.7%; p = .50) or ischemia-driven revascularization (from RA to DIR: 16.8%, 10.8%, 12.3%, 14.2%; p = .65). The adjusted 3-year rates of MACE did not differ according to LPS. The comparable 3-year outcomes suggest that appropriate lesion preparation may be able to overcome the increased risks of complex LMCA lesion morphology.


Protein phosphatase 5 promotes hepatocarcinogenesis through interaction with AMP-activated protein kinase.
The serine-threonine protein phosphatase family members are known as critical regulators of various cellular functions, such as survival and transformation. Growing evidence suggests that pharmacological manipulation of phosphatase activity exhibits therapeutic benefits. Ser/Thr protein phosphatase 5 (PP5) is known to participate in glucocorticoid receptor (GR) and stress-induced signaling cascades that regulate cell growth and apoptosis, and has been shown to be overexpressed in various human malignant diseases. However, the role of PP5 in hepatocellular carcinoma (HCC) and whether PP5 may be a viable therapeutic target for HCC treatment are unknown. Here, by analyzing HCC clinical samples obtained from 215 patients, we found that overexpression of PP5 is tumor specific and associated with worse clinical outcomes. We further characterized the oncogenic properties of PP5 in HCC cells. Importantly, both silencing of PP5 with lentiviral-mediated short hairpin RNA (shRNA) and chemical inhibition of PP5 phosphatase activity using the natural compound cantharidin/norcantharidin markedly suppressed the growth of HCC cells and tumors in vitro and in vivo. Moreover, we identified AMP-activated protein kinase (AMPK) as a novel downstream target of oncogenic PP5 and demonstrated that the antitumor mechanisms underlying PP5 inhibition involve activation of AMPK signaling. Overall, our results establish a pathological function of PP5 in hepatocarcinogenesis via affecting AMPK signaling and suggest that PP5 inhibition is an attractive therapeutic approach for HCC.


Arsenic determination in marine sediment using ultrasound for sample preparation.
This work deals with As determination in marine sediment using ultrasound for sample preparation. It is shown that As can be quantitatively extracted from marine sediment using 20% (v/v) HCl and sonication. The slurry is centrifuged and the analyte is determined in the supernatant by hydride generation atomic absorption spectrometry (HG AAS). A flow injection (FI) system is employed for hydride generation, with 0.5% (m/v) NaBH(4) used as reducdant and a 20% (v/v) HCl used as sample carrier. The limit of quantification is 1.6 microg g(-1) of As, which is based on 800 microl of sample solution and 0.200 g of sample mass in a volume of 50 mL. Certified and non certified marine sediment samples were analyzed; the results were in accordance with the certified or reference values. Speciation analysis by HPLC-ICP-MS showed that As(V) is the only detectable As species present in the supernatant of the centrifuged sample.


[Comparative analysis of the promoting blood effects of the combination of different proportions of danggui and honghua by the principal component analysis and multi-attribute comprehensive index methods].
The combination of Danggui and Honghua (GH) is a popular herb pair commonly used in clinic for the treatment of blood stasis syndrome in China. To evaluate the activating blood circulation and dissipating blood stasis effects of the combination of different proportions of Danggui and Honghua on acute blood stasis rats, and optimize the proportion of GH to have the best activating blood circulation and dissipating blood stasis effect. Acute blood stasis rat model was induced by subcutaneous injection of adrenaline and ice water bath. The blood stasis rats were administrated intragastrically with GH (1 : 0, 4 : 1, 2 : 1, 3 : 2, 1 : 1, 2 : 3, 1: 2, 1 : 4 and 0 : 1) extracts. The whole blood viscosity (WBV), plasma viscosity (PV), and high shear whole blood relative index (HSWBRI), low shear whole blood relative index (LSWBRI), and erythrocyte aggregation index (EAI) were tested to observe the effects of GH on hemorheology of blood stasis rats. And the maximum aggregation induced by adenosine diphosphate (ADP) was tested to observe the effect of GH on platelet aggregation index of blood stasis rats. In addition, the prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT) and plasma fibrinogen (FIB) were tested to observe the effects of GH on blood coagulation function of blood stasis rats. Then principal component analysis and multi-attribute comprehensive index methods were both used to comprehensively evaluate the total activating blood circulation and dissipating blood stasis effects of GH. The results showed that the hemorheological indexes and coagulation parameters of model group both had significant differences with normal group. Compared with model group, GH (1 : 0, 4 : 1, 2: 1, 3 : 2, 1 : 1, 2 : 3, 1 : 2, 1 : 4 and 0 : 1) could improve all the blood hemorheology indexes and regulate part indexes of blood coagulation function and platelet aggregation in acute blood stasis rats. Based on principal component analysis and multi-attribute comprehensive index methods, GH 1 : 1 and GH 3 : 2 both had the best effect of blood circulation and dissipating blood stasis, and the effect of GH 1 : 1 was slightly better than GH 3 : 2. These results suggest that GH could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats. The optimized proportion of GH was consistent with regulations of medicine usage that GH 1 : 1 had the highest frequency used in traditional Chinese formulae. It could provide scientific basis for more effective application of the compatibility between Danggui and Honghua in modern clinic medicine.


XIST promotes apoptosis and the inflammatory response in CSE-stimulated cells via the miR-200c-3p/EGR3 axis.
Chronic obstructive pulmonary disease (COPD) is a disease that causes obstructed airways and abnormal inflammatory responses in the lungs. Early growth response 3 (EGR3) has been revealed to play a vital role in the regulation of the inflammatory response in certain diseases. We aimed to explore the role of EGR3 and its upstream mechanism in COPD. In the present study, 16HBE cells were treated with cigarette smoke extract (CSE) to mimic the inflammatory response in vitro. RT-qPCR revealed that the expression of EGR3 was upregulated in lungs from COPD patients. EGR3 expression in 16HBE cells was increased by CSE treatment. Moreover, flow cytometry analysis and western blot analysis showed that EGR3 downregulation inhibited 16HBE cell apoptosis. EGR3 silencing decreased the protein levels of IL-6, TNF-α, IL-1β and COX2 in CSE-stimulated 16HBE cells. In addition, EGR3 was targeted by microRNA-200c-3p (miR-200c-3p) in 16HBE cells. MiR-200c-3p expression was significantly decreased in lung tissues from COPD patients compared to that in healthy controls. Furthermore, miR-200c-3p bound to lncRNA X-inactive specific transcript (XIST) in 16HBE cells. Additionally, XIST expression was elevated in lung tissues from COPD patients. Rescue assays indicated that EGR3 overexpression counteracted the effects of XIST downregulation on apoptosis and inflammation in CSE-stimulated 16HBE cells. The XIST/miR-200c-3p/EGR3 axis facilitated apoptosis and inflammation in CSE-stimulated 16HBE cells. These findings may provide novel insight for treating COPD by alleviating lung inflammation.


Using the constrained DFT approach in generating diabatic surfaces and off diagonal empirical valence bond terms for modeling reactions in condensed phases.
The empirical valence bond (EVB) model provides an extremely powerful way for modeling and analyzing chemical reactions in solutions and proteins. However, this model is based on the unverified assumption that the off diagonal elements of the EVB Hamiltonian do not change significantly upon transfer of the reacting system from one phase to another. This ad hoc assumption has been rationalized by its consistency with empirically observed linear free energy relationships, as well as by other qualitative considerations. Nevertheless, this assumption has not been rigorously established. The present work explores the validity of the above EVB key assumption by a rigorous numerical approach. This is done by exploiting the ability of the frozen density functional theory (FDFT) and the constrained density functional theory (CDFT) models to generate convenient diabatic states for QM/MM treatments, and thus to examine the relationship between the diabatic and adiabatic surfaces, as well as the corresponding effective off diagonal elements. It is found that, at least for the test case of S(N)()2 reactions, the off diagonal element does not change significantly upon moving from the gas phase to solutions and thus the EVB assumption is valid and extremely useful.


RNA deep sequencing analysis reveals that nicotine restores impaired gene expression by viral proteins in the brains of HIV-1 transgenic rats.
Persons infected with HIV-1 often develop neurologic disorders despite receiving highly active anti-retroviral therapy. Although the underlying mechanism is largely undetermined, our previous RNA-seq-based study showed that the expression of many genes was altered in the central nervous system (CNS) of HIV-1 transgenic (HIV-1Tg) rats. Because nicotine, a natural agonist of nicotinic acetylcholine receptors, exhibits a neuroprotective effect, we presently tested the hypothesis that nicotine restores the expression of altered genes in the CNS of HIV-1Tg rats. Adult male HIV-1Tg and F344 control strain rats were injected with either nicotine (0.25 mg/kg) or saline subcutaneously twice a day for 17 days. Gene expression in the prefrontal cortex (PFC), dorsal hippocampus (HIP), and dorsal striatum (STR) was evaluated using the RNA deep sequencing technique. We found that about 20% of the altered genes in the HIV-1Tg rat were affected by nicotine in each brain region, with the expression of most restored. Analysis of the restored genes showed distinct pathways corrected by nicotine in different brain regions of HIV-1Tg rats. Specifically, the two most significantly restored pathways were Wnt/β-catenin signaling and ephrin B signaling in the PFC, cAMP-responsive element-binding protein (CREB) signaling and glutathione metabolism pathway in the HIP, and tricarboxylic acid (TCA) cycle and calcium signaling in the STR. Together, our findings indicate that cholinergic modulators such as nicotine have beneficial effects on HIV-1-induced neurologic deficits.


Manufacturing-Enabled Tunability of Linear and Nonlinear Epsilon-Near-Zero Properties in Indium Tin Oxide Nanofilms.
Epsilon-near-zero (ENZ) materials have attracted great interest due to their exotic linear and nonlinear responses, which makes it significant to tune ENZ wavelengths for wavelength-dependent applications. However, studies to achieve tunability in a wide spectral range and link the fabrication parameters with linear and nonlinear ENZ properties have been uncovered. ENZ indium tin oxide (ITO) nanofilms are fabricated by magnetron sputtering, through which the control of ENZ properties is demonstrated. Factors in the sputtering process, such as the gas ratio and annealing, have a great impact on the ITO samples. Tunable ENZ parameters are listed to provide a beneficial database for ENZ ITO, mainly attributed to the change of carrier concentration. The influence of ENZ parameters on optical characteristics via annealing treatment is further explored. The ENZ wavelength is blue-shifted by 609 nm, and the intrinsic loss is reduced by 63.2%, while the ITO samples exhibit better linear scattering properties and stronger field intensity enhancement. Additionally, the laser testing system illustrates the change from reverse saturable absorption to saturable absorption with an absolute modulation depth of 21.9%, improved by 222.1%, and the nonlinear refractive index n2 and nonlinear absorption coefficient β are 2.07 × 10-16 m2 W-1 and -3.16 × 10-10 m W-1 for post-annealed ITO samples, respectively. The proposed sputtering protocol offers a feasible technique to control the linear and nonlinear ENZ performance, which has great potential in laser technology and nanophotonics.


Deceased, disabled or depressed--a population-based 6-year follow-up study of elderly people with depression.
The prognosis of depression in elderly people is reported as poor, with high mortality and high rate of non-recovery. The aim of this study was to investigate the outcome after 6 years in a broader perspective. In addition to the risk of dying, we also estimated the risk of moving to long-term care, and having a depression in a re-screening event after 6 years. In 1993, a screening event for depressive symptoms using the Hopkins Symptom Checklist (HSCL-25) was carried out on 1215 subjects aged 65 years and older living in a health care district in Karlstad, Sweden. The study population was divided into a high score, a low score and a dropout group. A re-screening of the same population was carried out in 1999. Logistic regression analysis was used for calculating odds ratios for the selected end-points adjusted for age, gender, civil status and occurrence of physical illness. The adjusted odds ratios for dying for the high score group were 2.5 (95% CI 1.5-4.4) and for any of the end-points 6.1 (95% CI 3.5-10.8) compared with the low score group. Nearly three-quarters of the subjects in the high score group were deceased, depressed or had moved to long-term care after 6 years. The prognosis was poor for depressed elderly people despite not having more physical illness. It is believed that the poor outcome is due to an additive effect of depression on the total medical disease burden.


Evolving concepts in the quantitative analysis of the determinants of the plasma water sodium concentration and the pathophysiology and treatment of the dysnatremias.
The physiologic and clinical implications of the empirical formula originally discovered by Edelman et al [J Clin Invest 37:1236-1256, 1958] relating the plasma water sodium concentration ([Na(+)](pw)) to the total exchangeable sodium (Na(e)), total exchangeable potassium (K(e)), and total body water (TBW) have recently been elucidated. It is quite remarkable that the full significance of the Edelman equation discovered almost 50 years ago had remained unrecognized by clinicians and physiologists until recently. Although Edelman and colleagues had shown that the [Na(+)](pw) is proportional to the magnitude of (Na(e)+ K(e))/TBW, the linear equation relating [Na(+)](pw) to (Na(e)+ K(e))/TBW had a slope greater than unity of 1.11, and a non-zero y intercept of -25.6 whose significance was unrecognized and more often than not ignored. It has recently been demonstrated that the slope and y intercept in this equation are quantitatively determined by several additional physiologic parameters, which in addition to (Na(e)+ K(e))/TBW, play a role both in modulating the [Na(+)](pw) and in the generation of the dysnatremias. Even more remarkably, based only on the theoretical principles of Gibbs-Donnan and osmotic equilibrium, all the physiologic parameters that determine the magnitude of the [Na(+)](pw) can be incorporated into a simple conceptual and mathematical framework that sheds light on a broad of range of seemingly unrelated topics that have heretofore been treated separately clinically, including (1) effect of changes in the mass balance of Na(+), K(+), and H(2)O on the [Na(+)](pw); (2) modulation of [Na(+)](pw) in hyperglycemic states; (3) definition of an isonatric solution; (4) current formulas used to quantitate electrolyte-free water excretion; (5) complex role of K(+) in modulating the [Na(+)](pw); and (6) quantitative analysis of the generation and treatment of the dysnatremias. Moreover, this analysis has also proven to be an indispensable tool for deriving new formulas to aid the clinician in both interpreting the pathogenesis and treating the dysnatremias.


High-resolution Episcopic Microscopy (HREM) - Simple and Robust Protocols for Processing and Visualizing Organic Materials.
We provide simple protocols for generating digital volume data with the high-resolution episcopic microscopy (HREM) method. HREM is capable of imaging organic materials with volumes up to 5 x 5 x 7 mm3 in typical numeric resolutions between 1 x 1 x 1 and 5 x 5 x 5 µm3. Specimens are embedded in methacrylate resin and sectioned on a microtome. After each section an image of the block surface is captured with a digital video camera that sits on the phototube connected to the compound microscope head. The optical axis passes through a green fluorescent protein (GFP) filter cube and is aligned with a position, at which the bock holder arm comes to rest after each section. In this way, a series of inherently aligned digital images, displaying subsequent block surfaces are produced. Loading such an image series in three-dimensional (3D) visualization software facilitates the immediate conversion to digital volume data, which permit virtual sectioning in various orthogonal and oblique planes and the creation of volume and surface rendered computer models. We present three simple, tissue specific protocols for processing various groups of organic specimens, including mouse, chick, quail, frog and zebra fish embryos, human biopsy material, uncoated paper and skin replacement material.


Parents' consent to the post-mortem removal and retention of organs.
Parents of children who died following complex heart surgery have recently discovered that organs were removed and retained in post-mortem investigations to which they consented. It has been established that many of these parents did not give informed consent to the retention of organs. The Bristol Royal Infirmary Inquiry which examined these practices drafted codes of practice to govern future post-mortem activities. It is argued that these codes of practice may be onerous to some parents, yet effectively disbar them from dissenting to their application whilst they might otherwise agree to the post-mortem removal and retention of organs for purposes of medical audit, research or training. This consequence arises from employing an over-rigorous concept of informed consent in the immediate circumstances of bereavement. That concept is discussed in detail. An alternative proposal is canvassed which improves on the status quo but does not impose a practice of consent which may be burdensome and distressing to many.


Histological characteristics of biliary intraepithelial neoplasia-3 and intraepithelial spread of cholangiocarcinoma.
The increasing grades of biliary intraepithelial neoplasia (BilIN) reflect multistep carcinogenesis of cholangiocarcinoma, BilIN-3 representing the carcinoma in situ stage. A different form of in situ growth form of cancer cells is the intraepithelial spreading of cholangiocarcinoma cells. We examined the histological characteristics of carcinoma in situ in the biliary tract on 64 partial hepatectomy specimens with a diagnosis of hepatolithiasis. We distinguished two forms of carcinoma in situ: BilIN-3 and intraepithelial spread of carcinoma (IES). BilIN-3 is defined by epithelial atypia gradually decreasing towards the transition to adjacent normal biliary epithelium. In IES, the lesion shows an abrupt transition to normal biliary epithelium, in which the intraepithelial carcinoma then tends to spread. BilIN-3 and IES were observed in 17 (94 %) and seven (39 %), respectively, in cases of invasive cholangiocarcinoma (n = 18), and neither of them was observed in cases without invasive cholangiocarcinoma (n = 46). Most lesions of BilIN-3 and IES microscopically showed a flat or pseudopapillary pattern. The less frequent micropapillary configuration was noted more often in BilIN-3. BilIN-3 was not observed in septal and small intrahepatic bile ducts, while IES was regularly observed in such bile ducts. Immunohistochemical analysis showed p53 to be expressed significantly more frequently in IES (29 %) than in BilIN-3 (8 %). In conclusion, carcinoma in situ in the biliary tract is morphologically heterogeneous, and it is important to distinguish BilIN-3 and intraepithelial carcinoma spreading as distinct lesions, to better understand their biology.


Clinical manifestations in a Chinese girl with heterozygous de novo NAA10 variant c. 247C > T, p. (Arg83Cys): a case report.
The NAA10 gene encodes the catalytic subunit of the N-terminal acetyltransferase protein complex A (NatA), which is supposed to acetylate approximately 40% of the human proteins. After the advent of next-generation sequencing, more variants in the NAA10 gene and Ogden syndrome (OMIM# 300855) have been reported. Individuals with NAA10-related syndrome have a wide spectrum of clinical manifestations and the genotype-phenotype correlation is still far from being confirmed. Here, we report a three years old Chinese girl carrying a heterozygous de novo NAA10 [NM_003491: c. 247C > T, p. (Arg83Cys)] variant (dbSNP# rs387906701) (ClinVar# 208664) (OMIM# 300013.0010). The proband not only has some mild and common clinical manifestations, including dysmorphic features, developmental delay, obstructive hypertrophic cardiomyopathy, and arrhythmia, but also shows some rare clinical features such as exophthalmos, blue sclera, cutaneous capillary malformations, and adenoid hypertrophy. Our attempt is to expand the clinical phenotype associated with NAA10-related syndrome and explore genotype-phenotype correlation with such syndrome.


Genomic organization of tRNA and aminoacyl-tRNA synthetase genes for two amino acids in Saccharomyces cerevisiae.
The genomic organization in Saccharomyces cerevisiae of the tRNA and aminoacyl-tRNA synthetase genes for two amino acids was investigated. Aspartic acid and serine were chosen for the study because of the number and diversity of their tRNA gene sequences and the availability of cloned tRNA and aminoacyl-tRNA synthetase genes. Chromosome assignments were determined by hybridization to DNA gel blots of chromosomal DNA resolved by contour-clamped homogeneous electric field gel electrophoresis. Our results show that the tRNA and the cognate synthetase genes in such a family are dispersed and, therefore, cannot be regulated via a mechanism dependent on close proximity of genes. In general, the genome of S. cerevisiae contains randomly dispersed tRNA genes that are transcribed individually. We have supported and expanded this view by applying the facile method of contour-clamped homogeneous electric field gel electrophoresis to the investigation of these small multigene families.


Electrokinetic Thin-Film Model for Electrowetting: The Role of Bulk Charges.
The electrowetting behavior of a charge-carrying sessile droplet is relevant to applications such as point-of-care diagnostics. Often biomedical assays involve droplets that contain charged molecules such as dissolved ions, proteins, and DNA. In this work, we develop a reduced-order electrokinetic model for electrowetting of such a charge-carrying droplet under a parallel-plate electrode configuration. An inertial-lubrication model based on the weighted residual integral boundary layer (WRIBL) technique is used to obtain evolution equations that describe the spatiotemporal evolution of the fluid-air interface and the depth-integrated flow rate. The solutions to the evolution equations are obtained numerically by using the spectral collocation method. We investigate the role of domain and surface charges, characterized by the Debye length, on droplet wetting. Under low relaxation timescales, both droplet deformation and wetting alteration under an AC field are shown to be equivalent to that under a root-mean-square (RMS) DC field. We show that an electrolytic sessile droplet can exhibit a larger deformation in comparison to the two asymptotic limits of a perfect conductor and a perfect dielectric droplet, corresponding, respectively, to very low and high Debye lengths. The effects of several other parameters such as the inherent equilibrium wettability, permittivity ratio, and electric field strength are also investigated.