Action relations facilitate the identification of briefly-presented objects.
The link between perception and action allows us to interact fluently with the world. Objects which 'afford' an action elicit a visuomotor response, facilitating compatible responses. In addition, positioning objects to interact with one another appears to facilitate grouping, indicated by patients with extinction being better able to identify interacting objects (e.g. a corkscrew going towards the top of a wine bottle) than the same objects when positioned incorrectly for action (Riddoch, Humphreys, Edwards, Baker, & Willson, Nature Neuroscience, 6, 82-89, 2003). Here, we investigate the effect of action relations on the perception of normal participants. We found improved identification of briefly-presented objects when in correct versus incorrect co-locations for action. For the object that would be 'active' in the interaction (the corkscrew), this improvement was enhanced when it was oriented for use by the viewer's dominant hand. In contrast, the position-related benefit for the 'passive' object was stronger when the objects formed an action-related pair (corkscrew and bottle) compared with an unrelated pair (corkscrew and candle), and it was reduced when spatial cues disrupted grouping between the objects. We propose that these results indicate two separate effects of action relations on normal perception: a visuomotor response to objects which strongly afford an action; and a grouping effect between objects which form action-related pairs.


SAMMD: Staphylococcus aureus microarray meta-database.
Staphylococcus aureus is an important human pathogen, causing a wide variety of diseases ranging from superficial skin infections to severe life threatening infections. S. aureus is one of the leading causes of nosocomial infections. Its ability to resist multiple antibiotics poses a growing public health problem. In order to understand the mechanism of pathogenesis of S. aureus, several global expression profiles have been developed. These transcriptional profiles included regulatory mutants of S. aureus and growth of wild type under different growth conditions. The abundance of these profiles has generated a large amount of data without a uniform annotation system to comprehensively examine them. We report the development of the Staphylococcus aureus Microarray meta-database (SAMMD) which includes data from all the published transcriptional profiles. SAMMD is a web-accessible database that helps users to perform a variety of analysis against and within the existing transcriptional profiles. SAMMD is a relational database that uses MySQL as the back end and PHP/JavaScript/DHTML as the front end. The database is normalized and consists of five tables, which holds information about gene annotations, regulated gene lists, experimental details, references, and other details. SAMMD data is collected from the peer-reviewed published articles. Data extraction and conversion was done using perl scripts while data entry was done through phpMyAdmin tool. The database is accessible via a web interface that contains several features such as a simple search by ORF ID, gene name, gene product name, advanced search using gene lists, comparing among datasets, browsing, downloading, statistics, and help. The database is licensed under General Public License (GPL). SAMMD is hosted and available at http://www.bioinformatics.org/sammd/. Currently there are over 9500 entries for regulated genes, from 67 microarray experiments. SAMMD will help staphylococcal scientists to analyze their expression data and understand it at global level. It will also allow scientists to compare and contrast their transcriptome to that of the other published transcriptomes.


Roles of cell adhesion and cytoskeleton activity in Entamoeba histolytica pathogenesis: a delicate balance.
The protozoan parasite Entamoeba histolytica colonizes the human large bowel. Invasion of the intestinal epithelium causes amoebic colitis and opens the route for amoebic liver abscesses. The parasite relies on its dynamic actomyosin cytoskeleton and on surface adhesion molecules for dissemination in the human tissues. Here we show that the galactose/N-acetylgalactosamine (Gal/GalNAc) lectin clusters in focal structures localized in the region of E. histolytica that contacts monolayers of enterocytes. Disruption of myosin II activity impairs the formation of these structures and renders the trophozoites avirulent for liver abscess development. Production of the cytoplasmic domain of the E. histolytica Gal/GalNAc lectin in engineered trophozoites causes reduced adhesion to enterocytes. Intraportal delivery of these parasites to the liver leads to the formation of a large number of small abscesses with disorganized morphology that are localized in the vicinity of blood vessels. The data support a model for invasion in which parasite motility is essential for establishment of infectious foci, while the adhesion to host cells modulates the distribution of trophozoites in the liver and their capacity to migrate in the hepatic tissue.


Who support open access publishing? Gender, discipline, seniority and other factors associated with academics' OA practice.
This paper presents the findings from a survey study of UK academics and their publishing behaviour. The aim of this study is to investigate academics' attitudes towards and practice of open access (OA) publishing. The results are based on a survey study of academics at 12 Russell Group universities, and reflect responses from over 1800 researchers. This study found that whilst most academics support the principle of making knowledge freely available to everyone, the use of OA publishing among UK academics was still limited despite relevant established OA policies. The results suggest that there were differences in the extent of OA practice between different universities, academic disciplines, age and seniorities. Academics' use in OA publishing was also related to their awareness of OA policy and OA repositories, their attitudes towards the importance of OA publishing and their belief in OA citation advantage. The implications of these findings are relevant to the development of strategies for the implementation of OA policies.


Spatial and temporal variations of two cyanobacteria in the mesotrophic Miyun reservoir, China.
Spatial variations in phytoplankton community within a large mesotrophic reservoir (Miyun reservoir, North China) were investigated in relation to variations in physico-chemical properties, nutrient concentrations, temperature and light conditions over a 5 month period in 2009. The dynamics of phytoplankton community was represented by the dominance of cyanobacteria through summer and fall, following with a short-term dominance of chlorophyta in late fall, and a relatively high abundance of diatom in October; on the other hand, maximum phytoplankton biomass was recorded in the north shallow region of Miyun reservoir with a higher nutrients level. Particular attention was paid to the impacts of environmental conditions on the growth of two cyanobacteria genera, the toxin-producing Microcystis and the taste & odor-producing Oscillatoria. Microcystis biomass was in general greatly affected by water temperature and mixing depth/local water depth ratio in this reservoir, while the Oscillatoria biomass in the surface and middle layers was greatly affected by total dissolved phosphorus, and that in the bottom layer was related with the Secchi depth/local water depth ratio. Abundant Oscillatoria biomass was observed only in late September when Microcystis biomass decreased and allowed sufficient light go through.


Excitotoxicity in the pathogenesis of autism.
Autism is a debilitating neurodevelopment disorder characterised by stereotyped interests and behaviours, and abnormalities in verbal and non-verbal communication. It is a multifactorial disorder resulting from interactions between genetic, environmental and immunological factors. Excitotoxicity and oxidative stress are potential mechanisms, which are likely to serve as a converging point to these risk factors. Substantial evidence suggests that excitotoxicity, oxidative stress and impaired mitochondrial function are the leading cause of neuronal dysfunction in autistic patients. Glutamate is the primary excitatory neurotransmitter produced in the CNS, and overactivity of glutamate and its receptors leads to excitotoxicity. The over excitatory action of glutamate, and the glutamatergic receptors NMDA and AMPA, leads to activation of enzymes that damage cellular structure, membrane permeability and electrochemical gradients. The role of excitotoxicity and the mechanism behind its action in autistic subjects is delineated in this review.


Genome-wide diversity in the levant reveals recent structuring by culture.
The Levant is a region in the Near East with an impressive record of continuous human existence and major cultural developments since the Paleolithic period. Genetic and archeological studies present solid evidence placing the Middle East and the Arabian Peninsula as the first stepping-stone outside Africa. There is, however, little understanding of demographic changes in the Middle East, particularly the Levant, after the first Out-of-Africa expansion and how the Levantine peoples relate genetically to each other and to their neighbors. In this study we analyze more than 500,000 genome-wide SNPs in 1,341 new samples from the Levant and compare them to samples from 48 populations worldwide. Our results show recent genetic stratifications in the Levant are driven by the religious affiliations of the populations within the region. Cultural changes within the last two millennia appear to have facilitated/maintained admixture between culturally similar populations from the Levant, Arabian Peninsula, and Africa. The same cultural changes seem to have resulted in genetic isolation of other groups by limiting admixture with culturally different neighboring populations. Consequently, Levant populations today fall into two main groups: one sharing more genetic characteristics with modern-day Europeans and Central Asians, and the other with closer genetic affinities to other Middle Easterners and Africans. Finally, we identify a putative Levantine ancestral component that diverged from other Middle Easterners ∼23,700-15,500 years ago during the last glacial period, and diverged from Europeans ∼15,900-9,100 years ago between the last glacial warming and the start of the Neolithic.


Inhibition of ammonium oxidation by nitrapyrin in soil and liquid culture.
Inhibition of growth of axenic cultures of Nitrosomonas europaea by nitrapyrin was investigated in liquid culture and in soil. In liquid culture, exponentially growing cells were more sensitive than stationary-phase cells, possibly due to a requirement for uptake of nitrapyrin, metabolism of nitrapyrin, or both before inhibition. Differences in sensitivity were observed between the parent strain and two strains, sp1 and sp2, that were selected through repeated subculturing. These differences were reflected in the length of the lag period induced by nitrapyrin and in the specific growth rate and were due to different bactericidal and bacteriostatic effects. Soil provided significant protection from inhibition, with concentrations of nitrapyrin approximately one order of magnitude greater than those required for equivalent inhibition in liquid culture. The data show that strain differences alone do not explain differences in sensitivity between nitrification in soil and in liquid culture and suggest that the inhibitor may be more effective against actively nitrifying soils.


Subtype-specific suppression of Shiga toxin 2 released from Escherichia coli upon exposure to protein synthesis inhibitors.
Shiga toxins (Stx) are important virulence factors in the pathogenesis of severe disease including hemolytic-uremic syndrome, caused by Stx-producing Escherichia coli (STEC). STEC strains increase the release of Stx in vitro following the addition of fluoroquinolones, whereas protein synthesis inhibitors previously have been reported to suppress the release of Stx. The amount of Stx released from wild-type STEC strains incubated with protein synthesis inhibitors was examined by a Vero cell cytotoxicity assay. The amounts released were compared to the Stx type (Stx1 or Stx2) and additionally to the individual subtypes and toxin variants of Stx2. In general, Stx2 release was suppressed significantly upon exposure to protein synthesis inhibitors at MICs, which was not observed in the case of Stx1. Also, the average amount of different Stx2 toxin variants released was suppressed to various levels ranging from 14.0% (Stx2-O157-EDL933) to 94.7% (Stx2d-O8-C466-01B). Clinical studies exploring protein synthesis inhibitors as future candidates for treatment of intestinal infections caused by Stx2-producing STEC should therefore include knowledge of the toxin variant in addition to the subtype.


The role of primary care in service provision for people with severe mental illness in the United Kingdom.
Severe mental illness is a serious and potentially life changing set of conditions. This paper describes and analyses patient characteristics and service usage over one year of a representative cohort of people with a diagnosis of severe mental illness across England, including contacts with primary and secondary care and continuity of care. Data were collected from primary care patient notes (n = 1150) by trained nurses from 64 practices in England, covering all service contacts from 1(st) April 2008 to 31st March 2009. The estimated national rate of patients seen only in primary care in the period was 31.1% (95% C.I. 27.2% to 35.3%) and the rates of schizophrenia and bipolar disorder were 56.8% (95% C.I. 52.3% to 61.2%) and 37.9% (95% C.I. 33.7% to 42.2%). In total, patients had 7,961 consultations within primary care and 1,993 contacts with mental health services (20% of the total). Unemployed individuals diagnosed more recently were more likely to have contact with secondary care. Of those seen in secondary care, 61% had at most two secondary care contacts in the period. Median annual consultation rates with GPs were lower than have been reported for previous years and were only slightly above the general population. Relational continuity in primary care was poor for 21% of patients (Modified Modified Continuity Index = <0.5), and for almost a third of new referrals to mental health services the primary care record contained no information on the referral outcome. Primary care is centrally involved in the care of people with serious mental illness, but primary care and cross-boundary continuity is poor for a substantial proportion. Research is needed to determine the impact of poor continuity on patient outcomes, and above all, the impact of new collaborative ways of working at the primary/secondary care interface.


Developing neocortex organization and connectivity in cats revealed by direct correlation of diffusion tractography and histology.
The immature cortex (cortical plate [CP]) and underlying subplate (SP), a transient cell layer just below the CP, play critical roles in the formation of intracerebral connections. The purpose of this study was to examine the diffusion characteristics of the developing cortex and subcortical structures and compare to histology. We obtained high-resolution diffusion spectrum images of postnatal day (P) 0 (newborn), P35 (pediatric), and P100 (adult) cat brains, performed tractography analysis, and correlated with histological findings. Tractography revealed radial organization and radial afferent/efferent tracts not only in the CP but also in external SP at P0. Radial organization persisted only in the cortex but decreased at P35 and P100. Radial organization correlated with radial cellular organization, with highest cellular density at P0 (Cresyl Violet staining). At P0, the internal SP contained abundant corticocortical and projection tractography pathways, crossing at wide angles in areas with no myelination by Luxol Fast Blue staining. At P35 and P100, increased directional coherence of white matter was observed, with fewer local tracts, but more long association pathways. These results suggest that diffusion tractography can differentially characterize internal and external SP zones and their transition into mature cortical pathways.


Fast and Quantitative Phospholipidomic Analysis of SH-SY5Y Neuroblastoma Cell Cultures Using Liquid Chromatography-Tandem Mass Spectrometry and 31P Nuclear Magnetic Resonance.
Global lipid analysis still lags behind proteomics with respect to the availability of databases, experimental protocols, and specialized software. Determining the lipidome of cellular model systems in common use is of particular importance, especially when research questions involve lipids directly. In Parkinson's disease research, there is a growing awareness for the role of the biological membrane, where individual lipids may contribute to provoking α-synuclein oligomerisation and fibrillation. We present an analysis of the whole cell and plasma membrane lipid isolates of a neuroblastoma cell line, SH-SY5Y, a commonly used model system for research on this and other neurodegenerative diseases. We have used two complementary lipidomics methods. The relative quantities of PC, PE, SMs, CL, PI, PG, and PS were determined by 31P NMR. Fatty acid chain composition and their relative abundances within each phospholipid group were evaluated by liquid chromatography-tandem mass spectrometry. For this part of the analysis, we have developed and made available a set of Matlab scripts, LipMat. Our approach allowed us to observe several deviations of lipid abundances when compared to published reports regarding phospholipid analysis of cell cultures or brain matter. The most striking was the high abundance of PC (54.7 ± 1.9%) and low abundance of PE (17.8 ± 4.8%) and SMs (2.7 ± 1.2%). In addition, the observed abundance of PS was smaller than expected (4.7 ± 2.7%), similar to the observed abundance of PG (4.5 ± 1.8%). The observed fatty acid chain distribution was similar to the whole brain content with some notable differences: a higher abundance of 16:1 PC FA (17.4 ± 3.4% in PC whole cell content), lower abundance of 22:6 PE FA (15.9 ± 2.2% in plasma membrane fraction), and a complete lack of 22:6 PS FA.


Systematic review of trial-based analyses reporting the economic impact of heart failure management programs compared with usual care.
The cost-effectiveness of heart failure management programs (HF-MPs) is highly variable. We explored intervention and clinical characteristics likely to influence cost outcomes. A systematic review of economic analyses alongside randomized clinical trials comparing HF-MPs and usual care. Electronic databases were searched for English peer-reviewed articles published between 1990 and 2013. Of 511 articles identified, 34 comprising 35 analyses met the inclusion criteria. Eighteen analyses (51%) reported a HF-MP as more effective and less costly; four analyses (11%), and five analyses (14%) also reported they were more effective but with no significant or an increased cost difference, respectively. Alternatively, five analyses (14%) reported no statistically significant difference in effects or costs, and one analysis (3%) reported no statistically significant effect difference but was less costly. Finally, two analyses (6%) reported no statistically significant effect difference but were more costly. Interventions that reduced hospital admissions tended to result in favorable cost outcomes, moderated by increased resource use, intervention cost and/or the durability of the intervention effect. The reporting quality of economic evaluation assessed by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist varied substantially between 5% and 91% (median 45%; 34 articles) of the checklist criteria adequately addressed. Overall, none of the study, patient or intervention characteristics appeared to independently influence the cost-effectiveness of a HF-MP. The extent that HF-MPs reduce hospital readmissions appears to be associated with favorable cost outcomes. The current evidence does not provide a sufficient evidence base to explain what intervention or clinical attributes may influence the cost implications.


Lipids rich in phosphatidylethanolamine from natural gas-utilizing bacteria reduce plasma cholesterol and classes of phospholipids: a comparison with soybean oil.
We compared the effects of three different high-lipid diets on plasma lipoproteins and phospholipids in mink (Mustela vison). The 18 mink studied were fed one of the three diets during a 25-d period in a parallel group design. The compared diets had 0, 17, and 67% extracted lipids from natural gas-utilizing bacteria (LNGB), which were rich in PE. The group with 0% LNGB was fed a diet for which the lipid content was 100% soybean oil. The total cholesterol, LDL cholesterol, and HDL cholesterol of animals consuming a diet with 67% LNGB (67LNGB-diet), were significantly lowered by 35, 49, and 29%, respectively, and unesterified cholesterol increased by 17% compared with the animals fed a diet of 100% lipids from soybean oil (SB-diet). In addition, the ratio of LDL cholesterol to HDL cholesterol was 27% lower in mink fed the 67LNGB-diet than those fed the SB-diet. When the mink were fed the 67LNGB-diet, plasma PC, total phospholipids, lysoPC, and PI were lowered significantly compared with the mink fed a SB-diet. Plasma total cholesterol was correlated with total phospholipids as well as with PC (R = 0.8, P< 0.001). A significantly higher fecal excretion of unesterified cholesterol, cholesteryl ester, PC, lysoPC, and PE was observed in the 67LNGB-fed mink compared with the SB-fed mink. We conclude that phospholipids from the 67LNGB-diet decreased plasma lipoprotein levels, the LDL/HDL cholesterol ratio, and plasma phospholipid levels, especially lysoPC and PC, compared with the highly unsaturated soybean oil. Our findings indicate that the decrease of plasma cholesterol is mainly caused by a specific mixture of phospholipids containing a high level of PE, and not by the dietary FA composition. The lack of significant differences in the level of plasma PE due to the diets indicates that most of the PE from LNGB has been converted to PC in the liver. Thus, plasma cholesterol may at least be partly regulated by phospholipid methylation from PE to PC in the liver.


Habitat-related benthic macrofaunal assemblages of bays and estuaries of the western United States.
Data from 7 coastwide and regional benthic surveys were combined and used to assess the number and distribution of estuarine benthic macrofaunal assemblages of the western United States. Q-mode cluster analysis was applied to 714 samples and site groupings were tested for differences in 4 habitat factors (latitude, salinity, sediment grain size, and depth). Eight macrofaunal assemblages, structured primarily by latitude, salinity, and sediment grain size, were identified: (A) Puget Sound fine sediment, (B) Puget Sound coarse sediment, (C) southern California marine bays, (D) polyhaline central San Francisco Bay, (E) shallow estuaries and wetlands, (F) saline very coarse sediment, (G) mesohaline San Francisco Bay, and (H) limnetic and oligohaline. The Puget Sound, southern California, and San Francisco Bay assemblages were geographically distinct, while Assemblages E, F and H were distributed widely along the entire coast. A second Q-mode cluster analysis was conducted after adding replicate samples that were available from some of the sites and temporal replicates that were available for sites that were sampled in successive years. Variabilities due to small spatial scale habitat heterogeneity and temporal change were both low in Puget Sound, but temporal variability was high in the San Francisco estuary where large fluctuations in freshwater inputs and salinity among years leads to spatial relocation of the assemblages.


Simultaneous Fluorescence and Phosphorescence Lifetime Imaging Microscopy in Living Cells.
In living cells, there are always a plethora of processes taking place at the same time. Their precise regulation is the basis of cellular functions, since small failures can lead to severe dysfunctions. For a comprehensive understanding of intracellular homeostasis, simultaneous multiparameter detection is a versatile tool for revealing the spatial and temporal interactions of intracellular parameters. Here, a recently developed time-correlated single-photon counting (TCSPC) board was evaluated for simultaneous fluorescence and phosphorescence lifetime imaging microscopy (FLIM/PLIM). Therefore, the metabolic activity in insect salivary glands was investigated by recording ns-decaying intrinsic cellular fluorescence, mainly related to oxidized flavin adenine dinucleotide (FAD) and the μs-decaying phosphorescence of the oxygen-sensitive ruthenium-complex Kr341. Due to dopamine stimulation, the metabolic activity of salivary glands increased, causing a higher pericellular oxygen consumption and a resulting increase in Kr341 phosphorescence decay time. Furthermore, FAD fluorescence decay time decreased, presumably due to protein binding, thus inducing a quenching of FAD fluorescence decay time. Through application of the metabolic drugs antimycin and FCCP, the recorded signals could be assigned to a mitochondrial origin. The dopamine-induced changes could be observed in sequential FLIM and PLIM recordings, as well as in simultaneous FLIM/PLIM recordings using an intermediate TCSPC timing resolution.


The heterosexual human immunodeficiency virus type 1 epidemic in Thailand is caused by an intersubtype (A/E) recombinant of African origin.
Since 1989, human immunodeficiency virus type 1 (HIV-1) has spread explosively through the heterosexual population in Thailand. This epidemic is caused primarily by viruses classified as "subtype E", which, on the basis of limited sequence comparisons, appear to represent hybrids of subtypes A (gag) and E (env). However, the true evolutionary origins of "subtype E" viruses are still obscure since no complete genomes have been analyzed, and only one full-length subtype A sequence has been available for phylogenetic comparison. In this study, we determined full-length proviral sequences for "subtype E" viruses from Thailand (93TH253) and the Central African Republic (90CR402) and for a subtype A virus from Uganda (92UG037). We also sequenced the long terminal repeat (LTR) regions from 16 virus strains representing clades A, C, E, F, and G. Detailed phylogenetic analyses of these sequences indicated that "subtype E" viruses do indeed represent A/E recombinants with multiple points of crossover along their genomes. The extracellular portion of env, parts of vif and vpr, as well as most of the LTR are of subtype E origin, whereas the remainder of the genome is of subtype A origin. The possibility that the discordant phylogenetic positions of "subtype E" viruses in gag- and env-derived trees are the result of unusual rates or patterns of evolution was also considered but was ruled out on the basis of two lines of evidence: (i) phylogenetic trees constructed for synonymous and nonsynonymous substitutions yielded the same discordant branching orders for "subtype E" gag and env gene sequences, thus excluding selection-driven evolution, and (ii) multiple crossovers in the viral genome are most consistent with the copy choice model of recombination and have been observed in other documented examples of HIV-1 intersubtype recombination. Thai and CAR "subtype E" viruses exhibited the same pattern of A/E mosaicism, indicating that the recombination event occurred in Africa prior to the spread of virus to Asia. Finally, all "subtype E" viruses were found to contain a distinctive two-nucleotide bulge in their transactivation response (TAR) elements. This feature was present only in viruses which also contained a subtype A 5' pol region (i.e., subtype A viruses or A/D and A/E recombinants), raising the possibility of a functional linkage between the TAR region and the polymerase. The implications of epidemic spread of a recombinant HIV-1 strain to viral natural history and vaccine development are discussed.


The interactome of Streptococcus pneumoniae and its bacteriophages show highly specific patterns of interactions among bacteria and their phages.
Although an abundance of bacteriophages exists, little is known about interactions between their proteins and those of their bacterial hosts. Here, we experimentally determined the phage-host interactomes of the phages Dp-1 and Cp-1 and their underlying protein interaction network in the host Streptococcus pneumoniae. We compared our results to the interaction patterns of E. coli phages lambda and T7. Dp-1 and Cp-1 target highly connected host proteins, occupy central network positions, and reach many protein clusters through the interactions of their targets. In turn, lambda and T7 targets cluster to conserved and essential proteins in E. coli, while such patterns were largely absent in S. pneumoniae. Furthermore, targets in E. coli were mutually strongly intertwined, while targets of Dp-1 and Cp-1 were strongly connected through essential and orthologous proteins in their immediate network vicinity. In both phage-host systems, the impact of phages on their protein targets appears to extend from their network neighbors, since proteins that interact with phage targets were located in central network positions, have a strong topologically disruptive effect and touch complexes with high functional heterogeneity. Such observations suggest that the phages, biological impact is accomplished through a surprisingly limited topological reach of their targets.


Cyst fluid from human autosomal dominant polycystic kidneys promotes cyst formation and expansion by renal epithelial cells in vitro.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive renal enlargement, culminating in renal insufficiency in over one half of affected individuals. The highly variable onset and clinical course of ADPKD may be due to factors extrinsic to the genetically defined renal cysts. In this study, cyst fluid samples from 12 nonazotemic and 18 azotemic ADPKD subjects were examined for in vitro biologic activity that promotes cellular proliferation and the secretion of fluid by renal epithelial monolayers, two pathogenetic mechanisms that have critical roles in the formation and the rate of expansion of renal cysts. Cyst fluid added to culture medium (final concentrations, 1 to 20%) caused Madin-Darby canine kidney cells and human kidney cortex (HKC) cells derived from primary cultures to form cysts in Type I collagen matrix. Cyst fluid stimulated the net transepithelial secretion of fluid by polarized monolayers composed of these same cells. Absolute levels of fluid secretory activity determined by MDCK bioassay were correlated directly with the rate of fluid secretion by HKC cell monolayers and with the extent of cyst formation by MDCK and HKC cells embedded in collagen matrix. The secretory activity of urine was negligible; secretory activity was detectable in the serum of normal and ADPKD subjects, but the levels were much lower than in cyst fluid. cAMP agonists prostaglandins E1 and E2, arginine vasopressin, and 8-Br-cAMP stimulated fluid secretion by MDCK and HKC monolayers, but these substances did not cause HKC cells to form cysts in collagen matrix, whereas cyst fluid did. Among other naturally occurring growth factors and autacoids, only epidermal growth factor and transforming growth factor alpha stimulated cyst formation by HKC cells; however, the capacity of cyst fluid to stimulate fluid secretion was not affected by treatment with antiserum to epidermal growth factor. It was concluded that potent, and possibly unique, substances in the cyst fluids of individuals with ADPKD support and augment biologic processes in renal epithelial cells that may be important in the promotion of progressive cyst expansion.


Swedish Diabetes Register, a tool for quality development in primary health care.
Introduction In Sweden, quality indicators in health care have been the basis for developing National Quality Registers. The Swedish National Diabetes Register (NDR) - one of the largest diabetes registers globally - was introduced in primary health care (PHC) in the county of Östergötland by an implementation project, 2002-2005. Aim The aim of the present paper was to investigate, by using the results of the NDR, whether the registration led to sustained outcomes of medical results of diabetes care in PHC in the county during the period 2005-2009. Method HbA1c, blood pressure (BP), albuminuria and low-density lipoprotein-cholesterol were registered online in the NDR. In 2005 and 2006, goal achievement for HbA1c was measured and compared between PHC centres (PHCC) within the county. In 2007, achievements to national goals were compared between the PHCCs within the county and with those Swedish counties that had attained a sufficiently high registration rate. In 2008 and 2009, the average county results were compared with the corresponding national average measurements for all 21 Swedish counties combined. Result In 2005, a clear improvement trend for HbA1c and BP was shown within the county. In 2007-2009, goal achievements in the county studied were slightly better than the other counties measured and the country as a whole in almost every comparison. Discussion The present study has shown association between medical results and registration in the NDR. As the project was primarily a quality improvement work, the results have continuously influenced the development of diabetes care. Both the health professions and the county council now have - in the NDR - an effective and rapid method for evaluation and follow-up of diabetes care. The systematic documentation, followed by comparisons and analyses, create ideas for care improvements.


A role for action-potential activity in the development of neuronal connections in the kitten retinogeniculate pathway.
The role of action potentials in the development of proper synaptic connections in the mammalian CNS was studied in the kitten retinogeniculate pathway. Our basic finding is that there is improper segregation of retinal inputs onto LGN cells after prolonged retinal action-potential blockade. Retinal ganglion cell firing was silenced from birth by repeated monocular injections of TTX. The resulting ganglion cell connections in the LGN were studied electrophysiologically after the action-potential blockade was ended. Most cells in the deprived LGN layers received excitatory input from both ON-center and OFF-center type ganglion cells, whereas LGN cells normally receive inputs only from ON-center or OFF-center ganglion cells, but not from both types. Improper segregation of ON and OFF inputs has never been reported after other types of visual deprivation that do not block ganglion cell activity. Control experiments showed that receptive fields in the nondeprived LGN layers were normal, that ganglion cell responses remained normal, and that there was no obvious ganglion cell loss. We also showed that individual LGN cells with ON and OFF excitatory inputs were not present in normal neonatal kittens. Two other types of improper input segregation in response to action-potential blockade were also found in the deprived LGN layers. (1) A greater than normal number of LGN cells received both X- and Y-type ganglion cell input. (2) Almost half of the cells at LGN layer borders were excited binocularly. Recovery of LGN normality was rapid and complete after blockade that lasted for only 3 weeks from birth, but little recovery was seen after about 11 weeks of blockade. The susceptibility to action-potential blockade decreased during the first 3 postnatal weeks. These findings may result from axon-terminal sprouting or from the failure of axon terminals to retract. The results are consistent with the idea that normally synchronous activity of neighboring ganglion cells of like center-type may be used in the refinement of retinogeniculate synaptic connections.


Efficient inorganic-organic hybrid perovskite solar cells based on pyrene arylamine derivatives as hole-transporting materials.
A set of three N,N-di-p-methoxyphenylamine-substituted pyrene derivatives have successfully been synthesized and characterized by (1)H/(13)C NMR spectroscopy, mass spectrometry, and elemental analysis. The optical and electronic structures of the pyrene derivatives were adjusted by controlling the ratio of N,N-di-p-methoxyphenylamine to pyrene, and investigated by UV/vis spectroscopy and cyclic voltammetry. The pyrene derivatives were employed as hole-transporting materials (HTMs) in fabricating mesoporous TiO2/CH3NH3PbI3/HTMs/Au solar cells. The pyrene-based derivative Py-C exhibited a short-circuit current density of 20.2 mA/cm(2), an open-circuit voltage (Voc) of 0.886 V, and a fill factor of 69.4% under an illumination of 1 sun (100 mW/cm(2)), resulting in an overall power conversion efficiency of 12.4%. The performance is comparable to that of the well-studied spiro-OMeTAD, even though the Voc is slightly lower. Thus, this newly synthesized pyrene derivative holds promise as a HTM for highly efficient perovskite-based solar cells.


Associations between musculoskeletal pain and work-related factors among public service sector computer workers in Kaunas County, Lithuania.
Information technologies in occupational activities have been developing very rapid. Epidemiological studies have shown that musculoskeletal disorders are widely prevalent among employees working with a computer. The aim of this study was to evaluate the prevalence of musculoskeletal pain in various anatomical areas and its associations with individual, ergonomic, and psychosocial factors among computer workers of the public sector in Kaunas County, Lithuania. The investigation consisting of two parts - questionnaire study (Nordic Musculoskeletal Questionnaire and Copenhagen Psychosocial Questionnaire) and direct observation (evaluation of work ergonomics using the Rapid Upper Limb Assessment [RULA]) - was carried out in three randomly selected public sector companies of Kaunas County. The representative study sample comprised 513 public service office workers. The prevalence of musculoskeletal pain in five anatomical areas of the body (shoulders, elbows, wrists/hands, as well as upper and low back) was evaluated. The prevalence rates of shoulder, elbow, wrist/hand, upper and low back pain were 50.5 %, 20.3 %, 26.3 %, 44.8 %, and 56.1 %, respectively. Individual factors such as gender, age, computer work experience, and body mass index were found as significant for musculoskeletal pain in various musculoskeletal regions. The respondents reporting pain in shoulder, wrist/hand, upper back, and low back areas had a statistically significantly higher mean RULA score. The duration of working with a computer was found as a significant factor for shoulder pain. High quantitative demands were related to musculoskeletal pain in all investigated anatomical areas expect for the low back; weak social support was a significant predictor for complaints in upper and low back areas. This study confirmed associations between musculoskeletal pain and work ergonomics; therefore, preventive measures at the workplace should be directed to the improvement in ergonomic work environment, education, and workload optimization.


Family members of cancer patients: Needs, quality of life and symptoms of anxiety and depression.
Family members of cancer patient's have multiple needs, many of which are not adequately met. Unmet needs may affect psychological distress and quality of life (QOL). The purpose of this study was to assess needs and unmet needs, QOL, symptoms of anxiety and depression, and the relationship between those variables in a large sample of family members of cancer patients in different phases of illness. Of 332 family members invited to participate, 330 accepted and 223 (67%) completed a cross-sectional, descriptive study. Data was collected with the Family Inventory of Needs (FIN), Quality of Life Scale (QOLS) and the Hospital Anxiety and Depression Scale (HADS). Of 20 needs assessed the mean (SD) number of important needs and unmet needs was 16.4 ± 4.3 and 6.2 ± 5.6, respectively. Twelve important needs were unmet in 40-56% of the sample. The mean number of unmet needs was significantly higher among women than men, other relatives than spouses, younger family members, those currently working and those of patients with metastatic cancer. QOL was similar to what has been reported for healthy populations and cancer caregivers in advanced stages. The prevalence of symptoms of anxiety and depression was high (20-40%). Anxiety scores were higher among women than men and both anxiety and depression scores were highest during years 1-5 compared to the first year and more than five years post diagnosis. There was a positive relationship between number of important needs and QOL, and between needs met and QOL. Additionally, there was a significant relationship between anxiety and unmet needs. Finally, there was a significant relationship between QOL and symptoms of anxiety and depression. The results support the importance of screening needs and psychological distress among family members of cancer patients in all phases of illness.


Global distribution, host range and prevalence of Trypanosoma vivax: a systematic review and meta-analysis.
Trypanosomosis caused by Trypanosoma vivax is one of the diseases threatening the health and productivity of livestock in Africa and Latin America. Trypanosoma vivax is mainly transmitted by tsetse flies; however, the parasite has also acquired the ability to be transmitted mechanically by hematophagous dipterans. Understanding its distribution, host range and prevalence is a key step in local and global efforts to control the disease. The study was conducted according to the methodological recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. A systematic literature search was conducted on three search engines, namely PubMed, Scopus and CAB Direct, to identify all publications reporting natural infection of T. vivax across the world. All the three search engines were screened using the search term Trypanosoma vivax without time and language restrictions. Publications on T. vivax that met our inclusion criteria were considered for systematic review and meta-analysis. The study provides a global database of T. vivax, consisting of 899 records from 245 peer-reviewed articles in 41 countries. A total of 232, 6277 tests were performed on 97 different mammalian hosts, including a wide range of wild animals. Natural infections of T. vivax were recorded in 39 different African and Latin American countries and 47 mammalian host species. All the 245 articles were included into the qualitative analysis, while information from 186 cross-sectional studies was used in the quantitative analysis mainly to estimate the pooled prevalence. Pooled prevalence estimates of T. vivax in domestic buffalo, cattle, dog, dromedary camel, equine, pig, small ruminant and wild animals were 30.6%, 6.4%, 2.6%, 8.4%, 3.7%, 5.5%, 3.8% and 12.9%, respectively. Stratified according to the diagnostic method, the highest pooled prevalences were found with serological techniques in domesticated buffalo (57.6%) followed by equine (50.0%) and wild animals (49.3%). The study provides a comprehensive dataset on the geographical distribution and host range of T. vivax and demonstrates the potential of this parasite to invade other countries out of Africa and Latin America.


First documented case of human granulocytic ehrlichiosis in Austria.
We report the first documented case of human granulocytic ehrlichiosis (HGE) in Austria. The infection was acquired near Arzl in the surroundings of Innsbruck in northern Tyrol. Except for a biphasic course of illness, presentation in this 33-year-old female patient was comparable to clinical findings observed in other European adults with high fever, transient thrombocytopenia, elevated levels of CRP and LDH, arthralgias, myalgias, fatigue and subfebrile temperature. Flu-like symptoms started about seven days after a tick bite and lasted for ten days, followed by an asymptomatic interval of three days and an acute onset of fever up to 39.5 degrees C on day 20. On admission, the patient showed high antibody titres against Anaplasma phagocytophilum (IgG 1:1024, IgM 1:640); six weeks later the IgG-titre had risen to 1:2048, and IgM-levels had fallen below 1:40. The demonstration of anti-platelet antibodies in acute-phase serum was noteworthy. We conclude that also in Austria HGE should be considered in patients with febrile thrombocytopenia, especially when the medical history reveals recent tick exposure.


Galileo encounter with 951 gaspra: first pictures of an asteroid.
Galileo images of Gaspra reveal it to be an irregularly shaped object (19 by 12 by 11 kilometers) that appears to have been created by a catastrophic collisional disruption of a precursor parent body. The cratering age of the surface is about 200 million years. Subtle albedo and color variations appear to correlate with morphological features: Brighter materials are associated with craters especially along the crests of ridges, have a stronger 1-micrometer absorption, and may represent freshly excavated mafic materials; darker materials exhibiting a significantly weaker 1-micrometer absorption appear concentrated in interridge areas. One explanation of these patterns is that Gaspra is covered with a thin regolith and that some of this material has migrated downslope in some areas.


Are parents of young children practicing healthy nutrition and physical activity behaviors?
Although parenthood is a common life event in early adulthood, little is known about whether parenthood is associated with weight and weight-related health behaviors, including dietary intake and physical activity. In this article we examine whether parents of young children (aged ≤5 years) report different dietary intake, physical activity, and BMIs compared with young adults without children. Data for this analysis were drawn from the second and third waves of Project EAT (Eating and Activity in Teens and Young Adults), a longitudinal population-based cohort study. Young adults (838 women, 682 men) from diverse ethnic and socioeconomic backgrounds were included. Gender-stratified linear regression models were used to examine associations between parental status and dietary intake, hours of physical activity, and BMI. Results were adjusted for each health behavior outcome level 5 years earlier (time 2). Results indicate that although many dietary behaviors were the same between parents and nonparents, mothers reported greater consumption of sugar-sweetened beverages, total energy, and percent saturated fat compared with women without children. Both mothers and fathers had lower amounts of physical activity compared with nonparents. Mothers had higher mean BMIs than women without children. No difference was observed in BMIs between fathers and men without children. Our findings suggest that pediatricians and health care providers may want to consider discussing dietary intake and physical activity with new parents to identify ways to engage in healthful behaviors given the daily demands of parenthood, both to improve parents' own health and to help them model healthful behavior for their children.


Novel trends in transrectal ultrasound imaging of prostate gland carcinoma.
Carcinoma of the prostate gland is the most common neoplasm in men. Its treatment depends on multiple factors among which local staging plays a significant role. The basic method is transrectal ultrasound imaging. This examination enables imaging of the prostate gland and its abnormalities, but it also allows ultrasound-guided biopsies to be conducted. A conventional gray-scale ultrasound examination enables assessment of the size, echostructure and outlines of the anatomic capsule, but in many cases, neoplastic lesions cannot be observed. For this reason, new sonographic techniques are implemented in order to facilitate detectability of cancer. The usage of contrast agents during transrectal ultrasound examination must be emphasized since, in combination with color Doppler, it facilitates detection of cancerous lesions by visualizing flow which is not observable without contrast enhancement. Elastography, in turn, is a different solution. It uses the differences in tissue elasticity between a neoplastic region and normal prostatic parenchyma that surrounds it. This technique facilitates detection of lesions irrespective of their echogenicity and thereby supplements conventional transrectal examinations. However, the size of the prostate gland and its relatively far location from the transducer may constitute limitations to the effectiveness of elastography. Moreover, the manner of conducting such an examination depends on the examiner and his or her subjective assessment. Another method, which falls within the novel, popular trend of combining imaging methods, is fusion of magnetic resonance imaging and transrectal sonography. The application of multidimensional magnetic resonance imaging, which is currently believed to be the best method for prostate cancer staging, in combination with the availability of a TRUS examination and the possibility of monitoring biopsies in real-time sonography is a promising alternative, but it is associated with higher costs and longer duration of the examination. This paper presents the most important novel trends in transrectal imaging in prostate cancer diagnosis based on the review of the articles available in the PubMed base and published after 2010.


Preventive effects of astaxanthin on diethylnitrosamine-induced liver tumorigenesis in C57/BL/KsJ-db/db obese mice.
Obesity and its related metabolic abnormalities, including oxidative stress and adipokine imbalance, are involved in liver carcinogenesis. The aim of the present study was to examine the effects of astaxanthin, a powerful biological antioxidant, on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were given a single i.p. injection of DEN (25 mg/kg bodyweight) at 2 weeks of age, and, subsequently, from 4 weeks of age, they were fed a diet containing 200 p.p.m. astaxanthin throughout the experiment. Twenty weeks of astaxanthin administration significantly inhibited the development of hepatocellular neoplasms (liver cell adenoma and hepatocellular carcinoma) and the hepatic expression of cyclin D1 mRNA compared with the basal diet group in DEN-treated db/db mice. Astaxanthin administration in DEN-treated experimental mice markedly reduced the derivatives of reactive oxygen metabolites/biological antioxidant potential ratio, which is a serum marker of oxidative stress, while increasing the mRNA expression of the antioxidant enzymes superoxide dismutase 2 and glutathione peroxidase 1 in the liver and white adipose tissue. The serum levels of adiponectin increased after astaxanthin administration in these mice. Dietary astaxanthin prevented the development of liver tumorigenesis in obese mice by improving oxidative stress and ameliorating serum adiponectin level. Therefore, astaxanthin may be useful in the chemoprevention of liver tumorigenesis in obese individuals.


Tumor necrosis serum induces a serologically distinct population of NK cells.
Murine spleen cells generate nonspecific cytotoxic cells, referred to as natural killer (NK) cells, within 4 d of incubation in Mishell-Dutton cultures. This NK cell type does not arise in cultures of BALB/c.nu spleen cells or in cultures of T-cell depleted C57BL/6 spleen cells, indicating that its activation depends on T cells. Another type of NK cells is induced by tumor necrosis serum in murine spleen-cell cultures. It arises within 24 h and its activation does not depend on T cells. This cell type (and its precursor) expresses the recently discovered cell-surface marker Qa5 (controlled by the Q region of chromosome 17) that distinguishes this NK cell from the NK cell that depends for its activation on thymic function. Qa5+ NK cells are also induced by interferon.


Use of customized polyetheretherketone (PEEK) implants in the reconstruction of complex maxillofacial defects.
Extensive maxillofacial defects resulting from trauma or oncologic resection present reconstructive challenges. Various autografts and alloplastic materials in conjunction with standard soft-tissue techniques have been used in the reconstruction of these types of defects. Polyetheretherketone (PEEK) is a semicrystalline polyaromatic linear polymer exhibiting an excellent combination of strength, stiffness, durability, and environmental resistance. Recent investigations of PEEK as a biomaterial resulted in the successful treatment of cervical disk disease. We describe a series of 4 patients whose defects were reconstructed using customized PEEK implants. All had excellent postoperative aesthetic and functional results without complications such as infections or extrusions. Because PEEK implants are customizable, easily workable, inert, and nonporous, they represent an ideal alloplastic material for maxillofacial reconstruction.


Adipocytes fail to maintain cellular identity during obesity due to reduced PPARγ activity and elevated TGFβ-SMAD signaling.
Obesity due to overnutrition causes adipose tissue dysfunction, which is a critical pathological step on the road to type 2 diabetes (T2D) and other metabolic disorders. In this study, we conducted an unbiased investigation into the fundamental molecular mechanisms by which adipocytes transition to an unhealthy state during obesity. We used nuclear tagging and translating ribosome affinity purification (NuTRAP) reporter mice crossed with Adipoq-Cre mice to determine adipocyte-specific 1) transcriptional profiles (RNA-seq), 2) promoter and enhancer activity (H3K27ac ChIP-seq), 3) and PPARγ cistrome (ChIP-seq) profiles in mice fed chow or a high-fat diet (HFD) for 10 weeks. We also assessed the impact of the PPARγ agonist rosiglitazone (Rosi) on gene expression and cellular state of adipocytes from the HFD-fed mice. We integrated these data to determine the transcription factors underlying adipocyte responses to HFD and conducted functional studies using shRNA-mediated loss-of-function approaches in 3T3-L1 adipocytes. Adipocytes from the HFD-fed mice exhibited reduced expression of adipocyte markers and metabolic genes and enhanced expression of myofibroblast marker genes involved in cytoskeletal organization, accompanied by the formation of actin filament structures within the cell. PPARγ binding was globally reduced in adipocytes after HFD feeding, and Rosi restored the molecular and cellular phenotypes of adipocytes associated with HFD feeding. We identified the TGFβ1 effector protein SMAD to be enriched at HFD-induced promoters and enhancers and associated with myofibroblast signature genes. TGFβ1 treatment of mature 3T3-L1 adipocytes induced gene expression and cellular changes similar to those seen after HFD in vivo, and knockdown of Smad3 blunted the effects of TGFβ1. Our data demonstrate that adipocytes fail to maintain cellular identity after HFD feeding, acquiring characteristics of a myofibroblast-like cell type through reduced PPARγ activity and elevated TGFβ-SMAD signaling. This cellular identity crisis may be a fundamental mechanism that drives functional decline of adipose tissues during obesity.


Sensitivity of California Isolates of Uncinula necator to Trifloxystrobin and Spiroxamine, and Update on Triadimefon Sensitivity.
Sensitivities of Uncinula necator to spiroxamine and trifloxystrobin were established by assay of 36 and 35 isolates, respectively, recovered from California grape vineyards in 2002 and increased as single-spore lines for laboratory testing. Twenty-nine single-spore isolates also were evaluated for levels of sensitivity to the fungicide triadimefon to determine if there had been a reversion to sensitivity following the development of resistance in 1986. Although triadimefon use was limited after 1992, other demethylation inhibitor (DMI) fungicides (fenarimol and myclobutanil) were used extensively in California vineyards. For spiroxamine, the sample mean value of the median effective concentration (EC50 value) was 365 μg/liter (95% confidence interval [CI] from 251 to 531 μg/liter) and values were distributed log-normally. The corresponding mean for trifloxystrobin was 12.8 μg/liter bounded by 8.9 to 18.5 μg/liter for the 95% CI. State-wide, the triadimefon mean EC50 was 8.8 mg/liter, bounded by a 5.3 to 14.5 mg/liter 95% CI, and those values were significantly higher than those obtained in the last assay 12 years earlier. Significant differences in sensitivity of U. necator to triadimefon were detected at a regional scale by comparison of mean EC50 values of frequency distributions representative of regions within California, although the relations between those regions were different from the prior survey.


Using the theory of planned behavior to predict mothers' intentions to vaccinate their daughters against HPV.
This study assessed mothers' intentions to vaccinate their daughters against human papillomavirus (HPV) using the theory of planned behavior (TPB). Experience with sexually transmitted infections (STIs), beliefs about the vaccine encouraging sexual activity, and perception of daughters' risk for HPV were also examined for a relationship with intention. A random sample of mothers in a rural, Midwestern state were mailed a survey with questions pertaining to the intention to vaccinate. Attitudes were the strongest predictor of mothers' intentions to vaccinate, but intentions were not high. Subjective norms also influence intention. Mothers' risk perceptions, experience with STIs, and beliefs about the vaccine encouraging sexual activity were not related to intention. Mothers' perceptions of the daughters' risks for HPV were surprisingly low. This research provides a foundation for designing interventions to increase HPV vaccination rates. Further research should explore ways to influence mothers' attitudes and to uncover the referent groups mothers refer to for vaccination behavior.


Digestive efficiency mediated by serum calcium predicts bone mineral density in the common marmoset (Callithrix jacchus).
Two health problems have plagued captive common marmoset (Callithrix jacchus) colonies for nearly as long as those colonies have existed: marmoset wasting syndrome and metabolic bone disease. While marmoset wasting syndrome is explicitly linked to nutrient malabsorption, we propose metabolic bone disease is also linked to nutrient malabsorption, although indirectly. If animals experience negative nutrient balance chronically, critical nutrients may be taken from mineral stores such as the skeleton, thus leaving those stores depleted. We indirectly tested this prediction through an initial investigation of digestive efficiency, as measured by apparent energy digestibility, and serum parameters known to play a part in metabolic bone mineral density of captive common marmoset monkeys. In our initial study on 12 clinically healthy animals, we found a wide range of digestive efficiencies, and subjects with lower digestive efficiency had lower serum vitamin D despite having higher food intakes. A second experiment on 23 subjects including several with suspected bone disease was undertaken to measure digestive and serum parameters, with the addition of a measure of bone mineral density by dual-energy X-ray absorptiometry (DEXA). Bone mineral density was positively associated with apparent digestibility of energy, vitamin D, and serum calcium. Further, digestive efficiency was found to predict bone mineral density when mediated by serum calcium. These data indicate that a poor ability to digest and absorb nutrients leads to calcium and vitamin D insufficiency. Vitamin D absorption may be particularly critical for indoor-housed animals, as opposed to animals in a more natural setting, because vitamin D that would otherwise be synthesized via exposure to sunlight must be absorbed from their diet. If malabsorption persists, metabolic bone disease is a possible consequence in common marmosets. These findings support our hypothesis that both wasting syndrome and metabolic bone disease in captive common marmosets are consequences of inefficient nutrient absorption.


Distribution of Cu, Zn, and Fe in the soluble fraction of the kidney in normal, copper-poisoned, and thiomolybdate-treated sheep.
Twenty-seven sheep were used in two experiments to study the distribution of copper (Cu), zinc (Zn), and iron (Fe) in the kidney cytosol of control, Cu-loaded, and thiomolybdate (TM)-treated sheep. A comparison was made of the patterns of distribution on Sephadex G-75 of Cu, Zn, and Fe from the cytosol of fresh and frozen kidneys and after thawing of frozen cytosol. In both Cu-dosed and TM-treated sheep, the absolute level of Cu increased in the cytosol, but the percent of Cu decreased. The percent recovery of Cu from the frozen kidney was comparable to that from fresh kidney, but the extraction of Cu from the supernatant of frozen cytosol was approximately 10% less. This was due to a loss of Cu in a precipitate that formed when the frozen cytosol was thawed. Most of the Cu in the cytosol from the kidney of Cu-loaded sheep was in a metallothionein (MT)-like protein fraction and was trichloroacetic acid (TCA) soluble. In contrast, that from the cytosol of TM-treated sheep was mostly in a high molecular weight fraction that was TCA insoluble. The chromatograms obtained from cytosol derived from frozen kidneys, or cytosol that had itself been frozen, contained a similar distribution of Cu, Zn, and Fe, but the peak heights were lower in the latter samples.


Collapsing glomerulopathy in a renal transplant recipient: potential molecular mechanisms.
In this case report, we describe a predisposed renal transplant patient who developed FSGS with cellular and collapsing features after sirolimus exposure and discuss the potential molecular mechanisms. A 35-year old African American female with end stage renal disease due to lupus nephritis received a living related renal transplant from a brother. She had immediate function achieved serum creatinine level of 1.7 mg/dl post day 4. Following a slow rise in the creatinine, first renal allograft biopsy performed on post op day 14 that showed thrombotic microangiopathy (TMA) involving arterioles and glomerular capillaries without any sign of rejection. The serological work up was negative for donor specific and antiphospholipid antibodies. The TMA was attributed to tacrolimus which was subsequently discontinued. It was replaced with sirolimus with loading dose of 10mg once and then 5 mg daily maintenance dose at day 21. At day 35, the patient was noted to have nephrotic range proteinuria, 12 gm/24 hrs. A second renal biopsy performed that revealed de novo focal segmental glomerulosclerosis with cellular and collapsing features, mild mesangial proliferative glomerulonephritis with immunoflourescence consistent with early recurrence of lupus nephritis ISN/RPS class 2. The etiology of cellular and collapsing FSGS was thought to be related to sirolimus based on timing of exposure and negative work up for secondary causes of collapsing FSGS. Sirolimus was switched to cyclosporine. At day 105, proteinuria decreased to 1.6 grams/day and serum creatinine leveled off 1.6 mg/dL. We report a case of possible sirolimus-induced collapsing FSGS in a renal transplant recipient who may have been predisposed to develop a podocytopathy possibly due to TMA and altered WT1 expression resulting from m-TOR exposure.


Psychopathy in a forensic sample - the factor structure of the PCL:SV in a Danish forensic sample.
The research literature reveals an ongoing debate regarding the most appropriate conceptualization of psychopathic personality disorder. Specifically, it is discussed to what degree antisocial behavior is part of the conceptualization of the psychopathy construct and what constitutes the best factor model of the Psychopathy Checklist scales. The aim of the present study is to consider the underlying factor structure of the PCL:SV (Psychopathy Checklist Screening Version) in a Danish sample as well as considering the role of antisocial behavior in the psychopathy construct. Data from a Danish forensic patient sample (N = 225) was used and item response theory (IRT), aonfirmatory factor analyses (CFA) and structural equations model (SEM) analyses were carried out. Overall, the findings suggest appropriate item and model fit for the PCL:SV as well as superiority of the three-factor model over the four-factor model. The results are discussed in relation to the broader concept of personality disorder as well as clinical practice in regards to violence risk assessments and treatment of psychopathy.


Metrics for evaluating 3D medical image segmentation: analysis, selection, and tool.
Medical Image segmentation is an important image processing step. Comparing images to evaluate the quality of segmentation is an essential part of measuring progress in this research area. Some of the challenges in evaluating medical segmentation are: metric selection, the use in the literature of multiple definitions for certain metrics, inefficiency of the metric calculation implementations leading to difficulties with large volumes, and lack of support for fuzzy segmentation by existing metrics. First we present an overview of 20 evaluation metrics selected based on a comprehensive literature review. For fuzzy segmentation, which shows the level of membership of each voxel to multiple classes, fuzzy definitions of all metrics are provided. We present a discussion about metric properties to provide a guide for selecting evaluation metrics. Finally, we propose an efficient evaluation tool implementing the 20 selected metrics. The tool is optimized to perform efficiently in terms of speed and required memory, also if the image size is extremely large as in the case of whole body MRI or CT volume segmentation. An implementation of this tool is available as an open source project. We propose an efficient evaluation tool for 3D medical image segmentation using 20 evaluation metrics and provide guidelines for selecting a subset of these metrics that is suitable for the data and the segmentation task.


Improving Primary Care After Stroke (IPCAS) randomised controlled trial: protocol for a multidimensional process evaluation.
Primary care interventions are often multicomponent, with several targets (eg, patients and healthcare professionals). Improving Primary Care After Stroke (IPCAS) is a novel primary care-based model of long-term stroke care involving a review of stroke-related needs, a self-management programme, a direct point of contact in general practice, enhanced communication between care services, and a directory of national and local community services, currently being evaluated in a cluster randomised controlled trial (RCT). Informed by Medical Research Council guidance for complex interventions and the Behaviour Change Consortium fidelity framework, this protocol outlines the process evaluation of IPCAS within this RCT. The process evaluation aimed to explore how the intervention was delivered in context and how participants engaged with the intervention. Mixed methods will be used: (1) design: intervention content will be compared with 'usual care'; (2) training: intervention training sessions will be audio/video-recorded where feasible; (3) delivery: healthcare professional self-reports, audio recordings of intervention delivery and observations of My Life After Stroke course (10% of reviews and sessions) will be coded separately; semistructured interviews will be conducted with a purposive sample of healthcare professionals; (4) receipt and (5) enactment: where available, structured stroke review records will be analysed quantitatively; semistructured interviews will be conducted with a purposive sample of study participants. Self-reports, observations and audio/video recordings will be coded and scored using specifically developed checklists. Semistructured interviews will be analysed thematically. Data will be analysed iteratively, independent of primary endpoint analysis. Favourable ethical opinion was gained from Yorkshire & The Humber-Bradford Leeds NHS Research Ethics Committee (19 December 2017, 17/YH/0441). Study results will be published in a peer-reviewed journal and presented at relevant conferences. NCT03353519; Pre-results.


A preclinical evaluation of alternative synthetic biomaterials for fascial defect repair using a rat abdominal hernia model.
Fascial defects are a common problem in the abdominal wall and in the vagina leading to hernia or pelvic organ prolapse that requires mesh enhancement to reduce operation failure. However, the long-term outcome of synthetic mesh surgery may be unsatisfactory due to post-surgical complications. We hypothesized that mesh fabricated from alternative synthetic polymers may evoke a different tissue response, and provide more appropriate mechanical properties for hernia repair. Our aim was to compare the in vivo biocompatibility of new synthetic meshes with a commercial mesh. We have fabricated 3 new warp-knitted synthetic meshes from different polymers with different tensile properties polyetheretherketone (PEEK), polyamide (PA) and a composite, gelatin coated PA (PA+G). The rat abdominal hernia model was used to implant the meshes (25 × 35 mm, n = 24/ group). After 7, 30, 60, 90 days tissues were explanted for immunohistochemical assessment of foreign body reaction and tissue integration, using CD31, CD45, CD68, alpha-SMA antibodies. The images were analysed using an image analysis software program. Biomechanical properties were uniaxially evaluated using an Instron Tensile® Tester. This study showed that the new meshes induced complex differences in the type of foreign body reaction over the time course of implantation. The PA, and particularly the composite PA+G meshes, evoked a milder early inflammatory response, and macrophages were apparent throughout the time course. Our meshes led to better tissue integration and new collagen deposition, particularly with the PA+G meshes, as well as greater and sustained neovascularisation compared with the PP meshes. PA, PA+G and PEEK appear to be well tolerated and are biocompatible, evoking an overlapping and different host tissue response with time that might convey mechanical variations in the healing tissue. These new meshes comprising different polymers may provide an alternative option for future treatment of fascial defects.


Economics of low-molecular weight heparins.
Low-molecular weight heparins (LMWHs) have become attractive alternatives to standard unfractionated heparin (UFH) for the treatment and prophylaxis of deep vein thrombosis (DVT), and for the management of acute coronary syndrome (ACS). The economic impact of the use of LMWHs has been studied in randomized controlled studies, in demonstration projects in managed care institutions, and in decision models. These studies provide valuable insight into the ways LMWHs can be economically attractive despite higher per unit costs compared with UFH. For the treatment of DVT, the cost benefit of using LMWHs results primarily from the cost shifting from inpatient to outpatient care, and might be limited by the eligibility of patients for outpatient management. In contrast, the attractiveness of LMWHs for ACS and DVT prophylaxis hinges on the increased effectiveness of LMWHs compared with standard UFH.


Synaptic transmission between individual pyramidal neurons of the rat visual cortex in vitro.
Synaptic transmission between pairs of neurons in layer 2/3 of in vitro slices from the rat visual cortex was studied by dual intracellular recording. The intrinsic electrophysiological properties of these neurons suggested that they were pyramidal cells. More than 1/3 of the total number of synaptically connected neurons were stained by intracellular iontophoresis of biocytin, and all had pyramidal morphology. Postsynaptic potentials (PSPs) were evoked by single action potentials (elicited by current injection) in presynaptic cells. Measurements of PSP latency, amplitude, and shape were made on spike-triggered averages. Forty-eight synaptic connections were found out of a possible total of 549, equivalent to a probability of about 0.09. For these 48 connections, the distance between the 2 impalement sites ranged from 50 to 340 microns. All PSPs were depolarizing at rest (-74 +/- 5 mV, mean +/- SD), and all 14 of the PSPs that were also recorded with the postsynaptic cell depolarized to around action potential threshold (about -55 mV) remained depolarizing. PSPs had short latencies (1.2 +/- 0.6 msec, mean +/- SD), suggesting that they were mediated by monosynaptic pathways. Peak amplitudes of the averaged PSPs varied widely (range, 0.05-2.08 mV), but the majority were less than 0.5 mV. PSPs decayed exponentially with time constants that were correlated with, but slightly longer than, the membrane time constants of the postsynaptic cells measured using injected current pulses. Four cell pairs were connected reciprocally, and 6 examples of convergent input were found in which a single cell was postsynaptic to more than 1 presynaptic cell. Trial-to-trial fluctuations in PSP amplitude were analyzed for 16 synaptic connections. The amplitude of the PSP evoked by a presynaptic action potential fluctuated more than could be accounted for by the background noise.


Mitochondrial dysfunction in distal axons contributes to human immunodeficiency virus sensory neuropathy.
Accumulation of mitochondrial DNA (mtDNA) damage has been associated with aging and abnormal oxidative metabolism. We hypothesized that in human immunodeficiency virus-associated sensory neuropathy (HIV-SN), damaged mtDNA accumulates in distal nerve segments, and that a spatial pattern of mitochondrial dysfunction contributes to the distal degeneration of sensory nerve fibers. We measured levels of common deletion mutations in mtDNA and expression levels of mitochondrial respiratory chain complexes of matched proximal and distal nerve specimens from patients with and without HIV-SN. In mitochondria isolated from peripheral nerves of simian immunodeficiency virus (SIV)-infected macaques, a model of HIV-SN, we measured mitochondrial function and generation of reactive oxygen species. We identified increased levels of mtDNA common deletion mutation in postmortem sural nerves of patients with HIV-SN as compared to uninfected patients or HIV patients without sensory neuropathy. Furthermore, we found that common deletion mutation in mtDNA was more prevalent in distal sural nerves compared to dorsal root ganglia. In a primate model of HIV-SN, freshly isolated mitochondria from sural nerves of macaques infected with a neurovirulent strain of SIV showed impaired mitochondrial function compared to mitochondria from proximal nerve segments. Our findings suggest that mtDNA damage accumulates in distal mitochondria of long axons, especially in patients with HIV-SN, and that this may lead to reduced mitochondrial function in distal nerves relative to proximal segments. Although our findings are based on HIV-SN, if confirmed in other neuropathies, these observations could explain the length-dependent nature of most axonal peripheral neuropathies.


Magnetic bead-based isolation of exosomes.
Exosomes are here defined as extracellular vesicles (EVs) in the approximate size range of 30-100 nm in diameter, and are observed in most body fluids containing typical exosomal markers such as CD9, CD63, and CD81. Potential subpopulations of exosomes can be captured by targeting these markers using magnetic beads. Magnetic beads are versatile tools for exosome isolation and downstream analysis. Here, we describe the workflow of immuno magnetic isolation and analysis of exosomes by flow cytometry, Western immunoblotting, and electron microscopy.


A Survey of Viewpoint Selection Methods for Polygonal Models.
Viewpoint selection has been an emerging area in computer graphics for some years, and it is now getting maturity with applications in fields such as scene navigation, scientific visualization, object recognition, mesh simplification, and camera placement. In this survey, we review and compare twenty-two measures to select good views of a polygonal 3D model, classify them using an extension of the categories defined by Secord et al., and evaluate them against the Dutagaci et al. benchmark. Eleven of these measures have not been reviewed in previous surveys. Three out of the five short-listed best viewpoint measures are directly related to information. We also present in which fields the different viewpoint measures have been applied. Finally, we provide a publicly available framework where all the viewpoint selection measures are implemented and can be compared against each other.


Structure and dynamics of the actin filament.
The structures of filamentous Mg-ATP-actin (F actin) in the presence and absence of KCl have been mapped with hydroxyl radicals (*OH) generated by synchrotron X-ray radiolysis. Proteolysis and mass spectrometry (MS) analysis revealed 52 reactive side-chain sites from 27 distinct peptides within actin. The reactivities of these probe sites with *OH in the F-actin states are compared with those of Mg-ATP-G-actin (monomers) analyzed previously [Guan, J.-Q. et al. (2003) Biochemistry 42, 11992-12000]. Filament-dependent protection within subdomains 2, 3, and 4 and at the C terminus is consistent with longitudinal contacts of monomers within the filament helical structure as predicted by the Holmes model. In the absence of KCl, the extent of filament-dependent protection rarely reached 3-fold, consistent with a highly dynamic filament characterized by relatively weak interactions between actin protomers. However, in the presence of KCl, the extents of protection are significantly increased, consistent with a well-ordered, more tightly packed filament structure. Filament-dependent enhancements of reactivity not predicted by the Holmes model are seen for a peptide that overlaps the "hydrophobic plug" (H-plug) region and for a peptide that forms contacts with the polyphosphate moiety of the bound nucleotide. Overall, these data are both consistent with and complementary to a recent deuterium-exchange MS study of filamentous actin [Chik, J. K., and Schriemer, D.C. (2003) J. Mol. Biol. 334, 373-385], which also did not detect any burial of the H plug upon formation of filaments.


Designing metallodrugs with nuclease and protease activity.
The accidental discovery of cisplatin some 50 years ago generated renewed interest in metallopharmaceuticals. Beyond cisplatin, many useful metallodrugs have been synthesized for the diagnosis and treatment of various diseases, but toxicity concerns, and the propensity to induce chemoresistance and secondary cancers make it imperative to search for novel metallodrugs that address these limitations. The Amino Terminal Cu(ii) and Ni(ii) (ATCUN) binding motif has emerged as a suitable template to design catalytic metallodrugs with nuclease and protease activities. Unlike their classical counterparts, ATCUN-based metallodrugs exhibit low toxicity, employ novel mechanisms to irreversibly inactivate disease-associated genes or proteins providing in principle, a channel to circumvent the rapid emergence of chemoresistance. The ATCUN motif thus presents novel strategies for the treatment of many diseases including cancers, HIV and infections caused by drug-resistant bacteria at the genetic level. This review discusses their design, mechanisms of action and potential for further development to expand their scope of application.


Growth retardation--an unexpected outcome from growth hormone gene therapy in normal mice with microencapsulated myoblasts.
Recently, we have succeeded in using nonautologous myoblasts engineered to secrete mouse growth hormone (GH) to correct partially the growth retardation of the Snell dwarf mice, which suffer from pituitary GH deficiency. The allogeneic myoblasts were protected from immune rejection by enclosure in permselective microcapsules fabricated from alginate, thus validating the clinical efficacy of using universal nonautologous cells for somatic gene therapy. Because GH therapy is considered also for treating patients with normal pituitary function, we now apply this protocol to treat normal mice to evaluate the potential consequences of using GH gene therapy in subjects with no demonstrated GH deficiency. When microencapsulated allogeneic myoblasts engineered to secrete mouse GH were implanted into normal male and female mice, contrary to expectation, the treated animals became significantly shorter and lost weight; their internal organs became smaller and their tibial growth plates were less differentiated, indicating reduced skeletal growth. Females were more severely affected than males and 2 animals died by day 13 of unknown cause. By day 70, most of the abnormalities were restored to normal except for body weights, which remained below normal. In conclusion, although somatic gene therapy for GH delivery is beneficial for pituitary dwarfism, it may have adverse metabolic consequences in those with normal hypothalamic-pituitary functions, and the female mice were more severely affected than males.


Genetic diversity and connectivity remain high in Holothuria polii (Delle Chiaje 1823) across a coastal lagoon-open sea environmental gradient.
Coastal lagoons represent habitats with widely heterogeneous environmental conditions, particularly as regards salinity and temperature, which fluctuate in both space and time. These characteristics suggest that physical and ecological factors could contribute to the genetic divergence among populations occurring in coastal lagoon and open-coast environments. This study investigates the genetic structure of Holothuria polii at a micro-geographic scale across the Mar Menor coastal lagoon and nearby marine areas, estimating the mitochondrial DNA variation in two gene fragments, cytochrome oxidase I (COI) and 16S rRNA (16S). Dataset of mitochondrial sequences was also used to test the influence of environmental differences between coastal lagoon and marine waters on population genetic structure. All sampled locations exhibited high levels of haplotype diversity and low values of nucleotide diversity. Both genes showed contrasting signals of genetic differentiation (non-significant differences using COI and slight differences using 16S, which could due to different mutation rates or to differential number of exclusive haplotypes. We detected an excess of recent mutations and exclusive haplotypes, which can be generated as a result of population growth. However, selective processes can be also acting on the gene markers used; highly significant generalized additive models have been obtained considering genetic data from 16S gene and independent variables such as temperature and salinity.


Cognitive processes in insulin-dependent diabetes.
Cognitive processes in a group of neurologically asymptomatic patients with relatively severe but uncomplicated insulin-dependent diabetes mellitus (IDDM) were studied. In comparison with a homogeneous group of normoglycemic controls, the diabetic group performed significantly worse in global memory, abstract reasoning, and eye-hand coordination tests. The two groups scored similarly in intelligence, concentration and attention, spatial, visual, and psychomotor tests. The neuropsychological deficits did not correlate with the duration or the severity of the disease. Whether these mild neuropsychological deficits are transient or stable or whether they are caused by central nervous system vascular or metabolic dysfunctions or by the emotional influence of the chronic illness on the intellectual and educational development of patients remains unclear. Our findings need to be cautiously interpreted and perhaps could not be extended to diabetic patients with better metabolic control.


Release of Moxifloxacin from Contact Lenses Using an In Vitro Eye Model: Impact of Artificial Tear Fluid Composition and Mechanical Rubbing.
The aim of this study was to evaluate and compare the release of moxifloxacin from a variety of daily disposable (DD) contact lenses (CLs) under various conditions using a novel in vitro eye model. Four commercially available DD conventional hydrogel (CH) CLs (nelfilcon A, omafilcon A, etafilcon A, and ocufilcon B) and three silicone hydrogel (SH) CLs (somofilcon A, narafilcon A, and delefilcon A) were evaluated. These lenses were incubated in moxifloxacin for 24 hours. The release of the drug was measured using a novel in vitro model in three experimental conditions: (1) phosphate buffered saline (PBS); (2) artificial tear solution (ATS) containing a variety of proteins and lipids; and (3) ATS with mechanical rubbing produced by the device. Overall, CH CLs had a higher drug release than SH CLs (P < 0.05) under all conditions. Typically, a higher drug release was observed in PBS than ATS (P < 0.05). For CH, drug release was found to be higher in ATS with rubbing than PBS or ATS (P < 0.05). For most lens types, ATS with rubbing produced higher drug release than ATS alone (P < 0.05). Generally, the release kinetics for all conditions were sustained over the 24-hour testing period, and no burst release was observed (P < 0.05). Moxifloxacin release from a CL into ATS is lower when compared to release into PBS. When mechanical rubbing is introduced, the amount of drugs released is increased. Results suggest that sophisticated in vitro models are necessary to adequately model on-eye drug release from CL materials.


Thermo-enhanced ring-opening polymerization of ε-caprolactone: the synthesis, characterization, and catalytic behavior of aluminum hydroquinolin-8-olates.
A series of highly sensitive aluminum hydroquinolin-8-olates (C1-C8) was synthesized and characterized by 1H/13C NMR spectroscopy. The molecular structures of compounds C1, C3, C4, and C5 were confirmed by single crystal X-ray crystallography and demonstrated the binuclear form. In the presence of BnOH, all the aluminum complexes exhibited moderate to high activities towards the ring-opening polymerization of ε-CL at high temperatures, but quite low activities at ambient temperature. Microstructure analysis of the resultant polycaprolactones showed that the polymers were linear in nature with a BnO- end group. In addition, the mechanism was investigated by monitoring the 1H NMR and 27Al NMR of C1 and these results suggested that the complexes existed as dimeric species at low temperature and partly converted into active mononuclear species at higher temperatures, which was easily coordinated by BnOH to afford the active species for the ring-opening polymerization of ε-caprolactone.


Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications.
An acute myocardial infarction, particularly one that is large and transmural, can produce alterations in the topography of both the infarcted and noninfarcted regions of the ventricle. This remodeling can importantly affect the function of the ventricle and the prognosis for survival. In the early period, infarct expansion has been recognized by echocardiography as a lengthening of the noncontractile region. The noninfarcted region also undergoes an important lengthening that is consistent with a secondary volume-overload hypertrophy and that can be progressive. The extent of ventricular enlargement after infarction is related to the magnitude of the initial damage to the myocardium and, although an increase in cavity size tends to restore stroke volume despite a persistently depressed ejection fraction, ventricular dilation has been associated with a reduction in survival. The process of ventricular enlargement can be influenced by three interdependent factors, that is, infarct size, infarct healing, and ventricular wall stresses. A most effective way to prevent or minimize the increase in ventricular size after infarction and the consequent adverse effect on prognosis is to limit the initial insult. Acute reperfusion therapy has been consistently shown to result in a reduction in ventricular volume. The reestablishment of blood flow to the infarcted region, even beyond the time frame for myocyte salvage, has beneficial effects in attenuating ventricular enlargement. The process of scarification can be interfered with during the acute infarct period by the administration of glucocorticosteroids and nonsteroidal antiinflammatory agents, which result in thinner infarcts and greater degrees of infarct expansion. Modification of distending or deforming forces can importantly influence ventricular enlargement. Even short-term augmentations in afterload have deleterious long-term effects on ventricular topography. Conversely, judicious use of nitroglycerin seems to be associated with an attenuation of infarct expansion and long-term improvement in clinical outcome. Long-term therapy with an angiotensin converting enzyme inhibitor can favorably alter the loading conditions on the left ventricle and reduce progressive ventricular enlargement as demonstrated in both experimental and clinical studies. With the former therapy, this attenuation of ventricular enlargement was associated with a prolongation in survival. The long-term clinical consequences of long-term angiotensin converting enzyme inhibitor therapy after myocardial infarction is currently being evaluated. Although studies directed at attenuating left ventricular remodeling after infarction are in the early stages, it does seem that this will be an important area in which future research might improve long-term outcome after infarction.


Tailored star block copolymer architecture for high performance chemically amplified resists.
Star block copolymers are demonstrated for their application as a high-performance resist material. This new resist material shows advanced progress in sensitivity and solubility contrast and is finally combinatorially optimized to achieve a 66 nm line/space pattern. The tailored molecular architecture of the star block copolymer is synthesized via core-first atom transfer radical polymerization (ATRP) and shows narrow polydispersity indices below 1.2.


Recurrence of hepatitis B and delta hepatitis after orthotopic liver transplantation.
The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%. Graft infection by HBV occurred in 8 of 10 patients infected with HBV only; and in 4 of 5 patients with previous HBV and HDV infection. There was a widely variable time from transplantation to the appearance of HBV markers in liver or serum, ranging from 6-331 days. Hepatitis D antigen (HDAg) appeared in three grafts very rapidly after transplantation at 4, 8, and 37 days respectively. Graft infection by HBV was accompanied by significant liver injury in six allografts in five recipients. In particular, there was a striking morphological appearance in five infected livers in which the hepatocytes became progressively enlarged and distorted as they accumulated huge amounts of hepatitis B surface and core antigens (HBsAg, HBcAg). These features were accompanied by pericellular fibrosis and cholestasis but little associated inflammation. This syndrome carried a poor prognosis. A gradual progression to cirrhosis occurred in one additional liver. Finally, recurrent HBV infection was a principal or a contributing factor in all deaths. The presence of HBcAg and inflammation in he native liver increased the risk of HBV induced tissue damaged in the graft whereas HDV infection in the host liver seemed to reduce the risk of significant HBV induced tissue damage in the allograft. These data suggest that post transplant HBV infection is accompanied by a variety of changes in the liver allograft, some of which are unique to the transplanted liver and may result in impaired allograft function.


Beyond Their HIV Status: the Occurrence of Multiple Health Risk Behavior Among Adolescents from a Rural Setting of Sub-Saharan Africa.
Health risk behaviors during adolescence may cluster into patterns that might be predicted by specific factors, among which HIV may have an important role. In a cross-sectional study conducted between 2017 and 2018, clustering of HRB and its associated factors was investigated in rural Kenya among 588 adolescents (36% perinatally HIV infected; 28% perinatally HIV exposed but uninfected; and 36% HIV unexposed/uninfected). Latent class analysis of 22 behaviors followed by multinomial logistic regression were conducted. Four risk behavior classes were identified. No significant differences were found in behavioral class membership across the three HIV groups (p = 0.366). The risk of membership to the higher risk behavioral classes relative to class 1 (the substance and drug abstinent low risk takers) increased with older adolescent age (p = 0.047), increased among adolescent who experienced mental distress (p < 0.001), and those who felt unsafe in their neighborhood (p < 0.002). Better working memory (p = 0.0037) was found to be protective. The results highlight a need to include screening and interventions for internalizing mental health problems and deficits in executive functioning, as well as steps to involve family members and communities to address psychosocial risk factors in adolescents in Kenya.


Bilateral nasolacrimal duct mucocele, a rare cause of respiratory distress: CT findings in two newborns.
Two newborns presented with severe respiratory distress caused by nasal obstruction. CT showed bilateral soft-tissue masses located under the inferior turbinates at the level of the inferior meatuses. Histologic examination showed the lesions to be compatible with nasolacrimal mucoceles. The embryology and radiographic features of this rare anomaly are discussed.


Immune Modulatory Effects of Vitamin D on Viral Infections.
Viral infections have been a cause of mortality for several centuries and continue to endanger the lives of many, specifically of the younger population. Vitamin D has long been recognized as a crucial element to the skeletal system in the human body. Recent evidence has indicated that vitamin D also plays an essential role in the immune response against viral infections and suggested that vitamin D deficiency increases susceptibility to viral infections as well as the risk of recurrent infections. For instance, low serum vitamin D levels were linked to increased occurrence of high burdens viral diseases such as hepatitis, influenza, Covid-19, and AIDS. As immune cells in infected patients are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D-deficient individuals with an infectious disease may extend beyond the impact on bone and calcium homeostasis. Even though numerous studies have highlighted the effect of vitamin D on the immune cells, vitamin D's antiviral mechanism has not been fully established. This paper reviews the recent mechanisms by which vitamin D regulates the immune system, both innate and adaptive systems, and reflects on the link between serum vitamin D levels and viral infections.


A novel gene of HIV-1, vpu, and its 16-kilodalton product.
A 16-kilodalton protein expressed in cells producing the human immunodeficiency virus (HIV-1) was identified as the gene product of the vpu open reading frame. When expressed in vitro, the 81-amino acid vpu protein reacted with about one-third of the serum samples from AIDS patients that were tested, indicating that the vpu open reading frame is expressed in vivo as well. Introduction of a frame-shift mutation into the vpu open reading frame did not significantly interfere with expression of the major viral proteins in a transient expression system. However, a five- to tenfold reduction in progeny virions was observed after the infection of T lymphocytes with the mutant virus. These data suggest that the vpu gene product is required for efficient virus replication and may have a role in assembly or maturation of progeny virions.


Intact imitation of emotional facial actions in autism spectrum conditions.
It has been proposed that there is a core impairment in autism spectrum conditions (ASC) to the mirror neuron system (MNS): If observed actions cannot be mapped onto the motor commands required for performance, higher order sociocognitive functions that involve understanding another person's perspective, such as theory of mind, may be impaired. However, evidence of MNS impairment in ASC is mixed. The present study used an 'automatic imitation' paradigm to assess MNS functioning in adults with ASC and matched controls, when observing emotional facial actions. Participants performed a pre-specified angry or surprised facial action in response to observed angry or surprised facial actions, and the speed of their action was measured with motion tracking equipment. Both the ASC and control groups demonstrated automatic imitation of the facial actions, such that responding was faster when they acted with the same emotional expression that they had observed. There was no difference between the two groups in the magnitude of the effect. These findings suggest that previous apparent demonstrations of impairments to the MNS in ASC may be driven by a lack of visual attention to the stimuli or motor sequencing impairments, and therefore that there is, in fact, no MNS impairment in ASC. We discuss these findings with reference to the literature on MNS functioning and imitation in ASC, as well as theories of the role of the MNS in sociocognitive functioning in typical development.


Complete Genome Sequence of "Candidatus Sulcia muelleri" ML, an Obligate Nutritional Symbiont of Maize Leafhopper (Dalbulus maidis).
"Candidatus Sulcia muelleri" is a symbiont of sap-feeding insects in the suborder Auchenorrhyncha. The strain "Ca. Sulcia muelleri" ML is associated with the maize leafhopper (Dalbulus maidis), collected in Brazil, which is a disease vector that affects corn production. Here, we report the complete genome sequence of this bacterium.