Implementation of a liver health check in people with type 2 diabetes.
As morbidity and mortality related to potentially preventable liver diseases are on the rise globally, early detection of liver fibrosis offers a window of opportunity to prevent disease progression. Early detection of non-alcoholic fatty liver disease allows for initiation and reinforcement of guidance on bodyweight management, risk stratification for advanced liver fibrosis, and treatment optimisation of diabetes and other metabolic complications. Identification of alcohol-related liver disease provides the opportunity to support patients with detoxification and abstinence programmes. In all patient groups, identification of cirrhosis ensures that patients are enrolled in surveillance programmes for hepatocellular carcinoma and portal hypertension. When considering early detection strategies, success can be achieved from applying ad-hoc screening for liver fibrosis in established frameworks of care. Patients with type 2 diabetes are an important group to consider case findings of advanced liver fibrosis and cirrhosis, as up to 19% have advanced fibrosis (which is ten times higher than the general population) and almost 70% have non-alcoholic fatty liver disease. Additionally, patients with type 2 diabetes with alcohol use disorders have the highest proportion of liver-related morbidity of people with type 2 diabetes generally. Patients with type 2 diabetes receive an annual diabetes review as part of their routine clinical care, in which the health of many organs are considered. Yet, liver health is seldom included in this review. This Viewpoint argues that augmenting the existing risk stratification strategy with an additional liver health check provides the opportunity to detect advanced liver fibrosis, thereby opening a window for early interventions to prevent end-stage liver disease and its complications, including hepatocellular carcinoma.


Circular Stapled Technique Versus Modified Collard Technique for Cervical Esophagogastric Anastomosis After Esophagectomy: A Randomized Controlled Trial.
This study was performed to investigate the efficacy of the modified Collard (MC) technique for reducing anastomotic stricture after esophagectomy compared with the circular stapled (CS) technique. The currently available techniques of anastomosis after esophagectomy are associated with a significant risk of anasto-motic complications. However, the optimal anastomotic technique after esophagectomy has not yet been established. We randomly allocated patients to either the CS group or the MC group. The primary endpoint was the incidence of anastomotic stricture. The secondary endpoints included the incidence of postoperative complications (including anastomotic leakage) and quality of life (QoL). All anastomoses were performed after indocyanine green evaluation for objective homogeni-zation of blood flow to the gastric conduit between the 2 techniques. Among 100 randomized patients (CS group, n = 50; MC group, n = 50), anastomotic strictures were observed in 18 (42%) patients in the CS group and in no patients in the MC group. There were no significant between-group differences in anastomotic leakage (CS group, 7% vs MC group, 8%; P = 0.94). Quality of life domains of dysphagia and choking when swallowing at 3 months after surgery were significantly better in the MC group than in the CS group. The MC technique reduces the incidence of anastomotic stricture and improves postoperative quality of life. Furthermore, the incidence of anastomotic leakage is comparable between the 2 techniques based on accurate comparison under objective homogenization of the gastric conduit condition.


The Hunchback temporal transcription factor establishes, but is not required to maintain, early-born neuronal identity.
Drosophila and mammalian neural progenitors typically generate a diverse family of neurons in a stereotyped order. Neuronal diversity can be generated by the sequential expression of temporal transcription factors. In Drosophila, neural progenitors (neuroblasts) sequentially express the temporal transcription factors Hunchback (Hb), Kruppel, Pdm, and Castor. Hb is necessary and sufficient to specify early-born neuronal identity in multiple lineages, and is maintained in the post-mitotic neurons produced during each neuroblast expression window. Surprisingly, nothing is currently known about whether Hb acts in neuroblasts or post-mitotic neurons (or both) to specify first-born neuronal identity. Here we selectively remove Hb from post-mitotic neurons, and assay the well-characterized NB7-1 and NB1-1 lineages for defects in neuronal identity and function. We find that loss of Hb from embryonic and larval post-mitotic neurons does not affect neuronal identity. Furthermore, removing Hb from post-mitotic neurons throughout the entire CNS has no effect on larval locomotor velocity, a sensitive assay for motor neuron and pre-motor neuron function. We conclude that Hb functions in progenitors (neuroblasts/GMCs) to establish heritable neuronal identity that is maintained by a Hb-independent mechanism. We suggest that Hb acts in neuroblasts to establish an epigenetic state that is permanently maintained in early-born neurons.


[Isolation and characterization of microorganisms with mannanase activity].
Twenty-three strains of soil microorganisms synthetizing extracellular mannanase were isolated on the medium containing baker's yeast mannan as the sole carbon source. Ten most active strains were identified with respect to their genera. These microorganisms proved capable to hydrolyze mannans, whose mannopyranose units were bound by alpha-1,2-and alpha-1,6-bonds. In addition, 5 of these strains were able to hydrolyze mannans whose mannose residues were bound by alpha-1,3-bond, and 2 strains could synthetize mannanase active towards yeast beta-mannane with 1,3 and 1,4 bonds. The strains tested showed a very low, if any, lytic activity towards yeast Saccharomyces and Candida. This gives evidence that mannanase is an enzyme unable to perform independently lysis of the yeast cell wall.


A Mutation in PGM2 Causing Inefficient Galactose Metabolism in the Probiotic Yeast Saccharomyces boulardii.
The probiotic yeast Saccharomyces boulardii has been extensively studied for the prevention and treatment of diarrheal diseases, and it is now commercially available in some countries. S. boulardii displays notable phenotypic characteristics, such as a high optimal growth temperature, high tolerance against acidic conditions, and the inability to form ascospores, which differentiate S. boulardii from Saccharomyces cerevisiae The majority of prior studies stated that S. boulardii exhibits sluggish or halted galactose utilization. Nonetheless, the molecular mechanisms underlying inefficient galactose uptake have yet to be elucidated. When the galactose utilization of a widely used S. boulardii strain, ATCC MYA-796, was examined under various culture conditions, the S. boulardii strain could consume galactose, but at a much lower rate than that of S. cerevisiae While all GAL genes were present in the S. boulardii genome, according to analysis of genomic sequencing data in a previous study, a point mutation (G1278A) in PGM2, which codes for phosphoglucomutase, was identified in the genome of the S. boulardii strain. As the point mutation resulted in the truncation of the Pgm2 protein, which is known to play a pivotal role in galactose utilization, we hypothesized that the truncated Pgm2 might be associated with inefficient galactose metabolism. Indeed, complementation of S. cerevisiaePGM2 in S. boulardii restored galactose utilization. After reverting the point mutation to a full-length PGM2 in S. boulardii by Cas9-based genome editing, the growth rates of wild-type (with a truncated PGM2 gene) and mutant (with a full-length PGM2) strains with glucose or galactose as the carbon source were examined. As expected, the mutant (with a full-length PGM2) was able to ferment galactose faster than the wild-type strain. Interestingly, the mutant showed a lower growth rate than that of the wild-type strain on glucose at 37°C. Also, the wild-type strain was enriched in the mixed culture of wild-type and mutant strains on glucose at 37°C, suggesting that the truncated PGM2 might offer better growth on glucose at a higher temperature in return for inefficient galactose utilization. Our results suggest that the point mutation in PGM2 might be involved in multiple phenotypes with different effects.IMPORTANCESaccharomyces boulardii is a probiotic yeast strain capable of preventing and treating diarrheal diseases. However, the genetics and metabolism of this yeast are largely unexplored. In particular, molecular mechanisms underlying the inefficient galactose metabolism of S. boulardii remain unknown. Our study reports that a point mutation in PGM2, which codes for phosphoglucomutase, is responsible for inferior galactose utilization by S. boulardii After correction of the mutated PGM2 via genome editing, the resulting strain was able to use galactose faster than a parental strain. While the PGM2 mutation made the yeast use galactose slowly, investigation of the genomic sequencing data of other S. boulardii strains revealed that the PGM2 mutation is evolutionarily conserved. Interestingly, the PGM2 mutation was beneficial for growth at a higher temperature on glucose. We speculate that the PGM2 mutation was enriched due to selection of S. boulardii in the natural habitat (sugar-rich fruits in tropical areas).


Pollen Diet Composition Impacts Early Nesting Success in Queen Bumble Bees Bombus impatiens Cresson(Hymenoptera: Apidae).
Bumble bees are generalist pollinators that typically collect floral rewards from a wide array of flowering plant species. Among the greatest threats to wild bumble bee populations worldwide, many of which are declining, is a loss of floral resource abundance and diversity in the landscapes they inhabit. We examined how composition of pollen diet impacts early nesting success in laboratory-reared queens of the bumble bee Bombus impatiens. Specifically, we provided queens and their young nests with one of three pollen diets, each of which was dominated by a single pollen type, and explored how this diet treatment influenced the length of time until queens initiated nests, total counts of brood in the nest at the end of the experiment (8 wk later), and the size and weight of adult offspring produced. We found that the amount of later-stage brood (pupae and/or adults) produced by recently-initiated nests was strongly impacted by pollen diet. For example, on average 66% fewer later-stage brood were found in nests provided with the Cistus pollen Linnaeus (Cistaceae), relative to the predominantly Asteraceae pollen. This finding suggests that particular pollen diet compositions may delay larval growth, which delays colony development and may ultimately be detrimental for young nests. This study sheds light on how one of the leading stressors for bumble bees (nutritional stress) may negatively impact populations through its influence on brood production during the nest-founding stage of the colony cycle.


Cloning of a growth arrest-specific and transforming growth factor beta-regulated gene, TI 1, from an epithelial cell line.
By cDNA cloning and differential screening, five genes that are regulated by transforming growth factor beta (TGF beta) in mink lung epithelial cells were identified. A novel membrane protein gene, TI 1, was identified which was downregulated by TGF beta and serum in quiescent cells. In actively growing cells, the TI 1 gene is rapidly and transiently induced by TGF beta, and it is overexpressed in the presence of protein synthesis inhibitors. It appears to be related to a family of transmembrane glycoproteins that are expressed on lymphocytes and tumor cells. The four other genes were all induced by TGF beta and correspond to the genes of collagen alpha type I, fibronectin, plasminogen activator inhibitor 1, and the monocyte chemotactic cell-activating factor (JE gene) previously shown to be TGF beta regulated.


Multi-disciplinary perceptions of patient group directions as a replacement for the pro re nata prescribing of antipsychotic medications in acute mental health settings.
Patient group directions have been used in the NHS for 10 years. Despite high levels of reported use, few studies have examined staff perceptions or evaluated them in practice. In mental health services, pro re nata prescriptions continue to contribute to high doses and polypharmacy of antipsychotics. Replacing pro re nata with patient group directions might improve the quality and safety of care associated with this practice. This study aimed to explore the acceptability of patient group directions in acute mental health services. Qualitative methods were used. Data were analysed using thematic content analysis. Twenty-six members of the multi-disciplinary team (doctors, nurses and pharmacists) participated in either focus groups or individual interviews in 2009. A broad range of benefits were suggested, including improved safety and access to treatments, and the professional development of nurses. However, concerns also emerged about the need for a culture shift in thinking, and the danger of multiple systems for the supply of medicines. Despite the widespread use of patient group directions in clinical settings in the last 10 years, limited research has examined their development and potential. Patient group directions can potentially give a rigorous means of supplying or administering medicines. However, their development requires careful consideration.


Pilot Trial of a Social Cognitive Theory-Based Physical Activity Intervention Delivered by Nonsupervised Technology in Persons With Multiple Sclerosis.
Physical inactivity is prevalent in people with multiple sclerosis (MS) and this highlights the importance of developing behavioral interventions for increasing physical activity (PA) in MS. This pilot trial examined the efficacy of a 6-week, behavioral intervention based on social cognitive theory (SCT) delivered by newsletters and phone calls for increasing PA in persons with MS who were physically inactive and had middle levels of self-efficacy. The sample included 68 persons with relapsing-remitting MS who were randomly assigned into intervention and control groups. The intervention group received SCT-based information by newsletters and phone calls, whereas the controls received information regarding topics such as stress management over 6 weeks. Participants completed self-report of PA and social cognitive variables. The intervention group had a significant increase in self-reported PA (d = 0.56, P = .02) over the 6 weeks, but the controls had a nonsignificant change (d = -0.13, P = .45). Goal setting was changed in the intervention group (d = 0.68, P ≤ .01) and identified as a significant mediator of change in self-reported PA. This study provides initial evidence for the benefit of a theory-based behavioral intervention for increasing PA in MS.


Chronic stimulation of mammalian muscle: changes in enzymes of six metabolic pathways.
Twenty-one enzymes of different metabolic systems were measured in the rabbit fast-twitch tibialis anterior (TA) muscle after electrical stimulation (10 Hz, 24 h/day) for 1 day to 10 wk. Nine analytical methods are either new, (3-oxoacid CoA-transferase, branched-chain-amino-acid aminotransferase, carnitine acetyltransferase, thiolase), improved (glutamate dehydrogenase, glycogen synthase, adenylic acid deaminase), or specially adapted (hexokinase, phosphoglucomutase). The activities (based on protein) of 12 mitochondrial or partly mitochondrial enzymes were lower in control TA than in control (slow) soleus (30-84% of soleus level). After 2 wk, 11 of these had surpassed the control soleus level. Maximal increases (3- to 14-fold) occurred after 2-5 wk, and thereafter six of the enzymes declined, whereas the other five maintained or increased their levels. Five glycolytic and two high-energy phosphate transfer enzymes, originally much higher in control TA than in control soleus, decreased gradually to levels at 8-10 wk only 27-123% higher than in soleus. Noncollagen protein concentration dropped 46%, explained largely by a sixfold increase in extracellular (chloride) space and a modest increase in collagen. The data constitute strong evidence for coordinate regulation of (mainly cytosolic) enzymes of glycolysis, glycogenolysis, gluconeogenesis, and high-energy phosphate transfer. Changes in the (mainly mitochondrial) enzymes of oxidative metabolism were more divergent, partly because of a hitherto undescribed secondary phase in the metabolic response. This phase may reflect a lower energy consumption in muscles adapted to continuous activity.


Immunology and male infertility.
This article has attempted to review evidence that suggests that immune factors may be operative in a small but significant number of infertile men. Although our current understanding of the possible processes by which autosensitization to previously sequestered reproductive antigens occurs is incomplete, there are laboratory assays presently available that give an indication, but do not prove, that immune factors may be contributing to the infertile state. Continued research is needed to develop new assays and more purified sperm antigens, which might enhance our knowledge of the underlying immunoreproductive changes. Until these are available, the following procedures should be considered when investigating a patient with infertility of suspected immune origin. The patient's history should be taken, and a physical examination should be performed. A complete blood count, urinalysis, and complete semen analysis and culture should be taken. Next, in vivo cervical tests (Sims-Huhner) are performed, followed by sperm antibody assessment (serum, semen) and perhaps in vitro cervical mucus sperm assays (especially the crossed hostility test). After the tests have been completed, the following possibe treatments exist: 1. Treatment of underlying infections 2. Correction of obstructions 3. Corticosteroid (or testosterone?) therapy 4. Washed sperm insemination 5. First portion of fresh ejaculate insemination 6. Artificial insemination with homologous donor 7. Adoption.


Regulation of hepatocyte nuclear factor 4 alpha-mediated transcription.
Hepatocyte nuclear factor 4alpha (HNF4alpha, NR2A1) is required for development of the liver and for controlling the expression of many genes specifically expressed in the liver and associated with a number of critical metabolic pathways. Among the genes regulated by HNF4alpha are the xenobiotic-metabolizing cytochromes P450, UDP-glucuronosyltransferases and sulfotransferases thus making this transcription factor critical in the control of drug metabolism. HNF4alpha, a member of the nuclear receptor superfamily, binds as a homodimer to direct repeat elements upstream of target genes. However, in contrast to many other nuclear receptors, there is no convincing evidence that HNF4alpha is activated by exogenous ligands, at least in the classic mechanism used by other steroid and metabolic nuclear receptors. X-ray crystallographic studies revealed that HNF4alpha has a fatty acid embedded in its putative ligand binding site that may not be easily released or displaced by exogenous ligands. HNF4alpha, as a general rule, controls constitutive expression of many hepatic genes but under certain circumstances can be subjected to regulation by differential co-activator recruitment, by phosphorylation and by interaction with other nuclear receptors. The ability of HNF4alpha to be regulated offers hope that it could be a drug target.


The evolution of reproductive isolation in the ectomycorrhizal Hebeloma crustuliniforme aggregate (Basidiomycetes) in northwestern Europe: a phylogenetic approach.
To reconstruct the evolution of reproductive isolation in the ectomycorrhizal Hebeloma crustuliniforme aggregate (Basidiomycetes), phylogenetic relationships were determined between strains that belong to a clade consisting of nine intercompatibility groups (ICGs, biological species). Four of these nine ICGs are partially compatible and belong to the H. crustuliniforme aggregate. Different levels of partial compatibility have been found between these four ICGs. Between ICGs 3 and 4, 15% of the combinations were compatible. One strain was compatible with all isolates of both ICGs 3 and 4 and also with one isolate of ICG 2. Both a nuclear phylogeny, based on ribosomal IGS sequence data, and a mitochondrial phylogeny, based on a group-I intron located in the large subunit ribosomal RNA gene (LrRNA), were reconstructed. The level of incompatibility was compared with the phylogenetic history of individuals belonging to this clade. Different relationships were found between the level of compatibility and the relative age of the most recent common ancestor (MRCA) for different ICGs. On the one hand, the evolution of incompatibility between ICGs 2 and 3/4 is most consistent with the class of "divergence- first" models because a positive correlation was found between the relative age of the MRCA and the level of incompatibility for ICG 2 versus 3/4. On the other hand, the lack of such a correlation for ICGs 3 and 4 shows that (partial) incompatibility between these ICGs has arisen without strong divergence. The ecological (and to a lesser extent geographical) differences found between ICGs 3 and 4 suggest that selection for incompatibility, associated with host tree preference, has been important in the evolution of incompatibility between these two ICGs. The incongruence between the nuclear and mitochondrial trees for ICG 1 could be explained by a hybrid origin of this ICG, with different donors of the mitochondrial and nuclear sequences.


Prevalence of sleep bruxism in children: a systematic review.
Prevalence of sleep bruxism (SB) in children is subject to discussions in the literature. This study is a systematic literature review aiming to critically assess the prevalence of SB in children. Survey using the following research databases: MEDLINE, Cochrane, EMBASE, PubMed, Lilacs and BBO, from January 2000 to February 2013, focusing on studies specifically assessing the prevalence of SB in children. After applying the inclusion criteria, four studies were retrieved. Among the selected articles, the prevalence rates of SB ranged from 5.9% to 49.6%, and these variations showed possible associations with the diagnostic criteria used for SB. There is a small number of studies with the primary objective of assessing SB in children. Additionally, there was a wide variation in the prevalence of SB in children. Thus, further, evidence-based studies with standardized and validated diagnostic criteria are necessary to assess the prevalence of SB in children more accurately.


New trends in modelling of breakthrough curves to remove pollutants using adsorption on advanced monoliths geometries.
This work proposes a rigorous mathematical model capable of reproducing the adsorption process in dynamic regime on advanced monoliths geometries. For this, four bed geometries with axisymmetric distribution of channels and similar solid mass were proposed. In each geometry a different distribution of channels was suggested, maintaining constant the bed dimensions of 15 cm high and 5 cm radius. The mathematical modeling includes mass and momentum transfer phenomena, and it was solved with the COMSOL Multiphysics software using mass transfer parameters published in the literature. The overall performance of the column was evaluated in terms of breakthrough (CA/CA0 = 0.1) and saturation times (CA/CA0 = 0.9). The mass and velocity distributions obtained from the proposed model show good physical consistency with what is expected in real systems. In addition, the model proved to be easy to solve given the short convergence times required (2-4 h). Modifications were made to the bed geometry to achieve a better use of the adsorbent material which reached up to 80%. The proposed bed geometries allow obtaining different mixing distributions, in such a way that inside the bed a thinning of the boundary layer is caused, thus reducing diffusive effects at the adsorbent solid-fluid interface, given dissipation rates of about 323 × 10-11 m2/s3. The bed geometry composed of intersecting rings deployed the best performance in terms of usage of the material adsorbent, and acceptable hydrodynamical behavior inside the channels (maximum fluid velocity = 35.4 × 10-5 m/s and drop pressure = 0.19 Pa). Based on these results, it was found that it is possible to reduce diffusional effects and delimit the mass transfer zone inside the monoliths, thus increasing the efficiency of adsorbent fixed beds.


Aerosols Generated during Endodontic Treatment: A Special Concern during the Coronavirus Disease 2019 Pandemic.
The aims of this study were to investigate aerosolized microorganisms generated during endodontic emergencies and nonsurgical root canal therapy (NSRCT), to assess the spread of airborne microbes, and to verify the spatial distribution of airborne microbial spread. A total of 45 endodontic procedures were sampled, including full pulpotomy (n = 15), pulpectomy (n = 15), and NSRCT (n = 15). Samples were collected during room resting and after treatment. The passive air sampling technique using settle plates was applied. Agar plates were set at different locations in the operatory. The colony-forming unit (CFU) was counted in brain-heart infusion blood agar plates. A set of agar plates containing selective chromogenic culture media was used for the isolation and presumptive identification of target microorganisms. Fungi were investigated using Sabouraud dextrose agar. Pulpotomy generated the lowest mean CFU count (P < .05). There was no difference between the mean CFU counts found in pulpectomy and NSRCT (P > .05). A higher mean CFU count was found close to the patient's mouth (0.5 m) than at a 2-m distance in pulpectomy and NSRCT (P < .05). There was no difference between the mean CFU count found in front of the patient's mouth versus diagonal in pulpectomy and NSRCT (P > .05). Staphylococcus aureus (22/45, 48.8%) was the most frequent bacteria species. Longer treatment times were associated with higher CFU counts. Our findings indicated that pulpotomy generates less aerosolized microorganisms than pulpectomy and NSRCT. The proximity to the patient's mouth and the treatment duration were implicated in the level of contamination.


[Mycrob-1000: an alternative for the rapid determination of urine culture in the primary health level].
The use of equipment Mycrob-1000 in detecting urinary infections in 4 hours in a primary health care center is evaluated. Two hundred fifty eight urine samples obtained from spontaneous miction were processed; the reference method was counting of colony-forming units per urine millimeter inoculated in Petri plaque in CLED medium. The coincidence rate between both methods was 92,31, with sensitivity and specificity rates of 79,00% and 96,95% respectively. The level of sensitivity was affected by factors not directly dependent on the equipment. High values of specificity and of coincidence achieved by this equipment in relation to the reference method facilitates its use in urine culture, making possible to differentiate negative urine samples in 4 or 5 hours and to focus work and resources on positive samples.


Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G.
The human APOBEC3G (apolipoprotein B messenger-RNA-editing enzyme, catalytic polypeptide-like 3G) protein is a single-strand DNA deaminase that inhibits the replication of human immunodeficiency virus-1 (HIV-1), other retroviruses and retrotransposons. APOBEC3G anti-viral activity is circumvented by most retroelements, such as through degradation by HIV-1 Vif. APOBEC3G is a member of a family of polynucleotide cytosine deaminases, several of which also target distinct physiological substrates. For instance, APOBEC1 edits APOB mRNA and AID deaminates antibody gene DNA. Although structures of other family members exist, none of these proteins has elicited polynucleotide cytosine deaminase or anti-viral activity. Here we report a solution structure of the human APOBEC3G catalytic domain. Five alpha-helices, including two that form the zinc-coordinating active site, are arranged over a hydrophobic platform consisting of five beta-strands. NMR DNA titration experiments, computational modelling, phylogenetic conservation and Escherichia coli-based activity assays combine to suggest a DNA-binding model in which a brim of positively charged residues positions the target cytosine for catalysis. The structure of the APOBEC3G catalytic domain will help us to understand functions of other family members and interactions that occur with pathogenic proteins such as HIV-1 Vif.


Effect of 3 years of biannual mass drug administration with albendazole on lymphatic filariasis and soil-transmitted helminth infections: a community-based study in Republic of the Congo.
The standard treatment strategy of mass drug administration with ivermectin plus albendazole for lymphatic filariasis cannot be applied in central Africa, because of the risk of serious adverse events in people with high Loa loa microfilaraemia. Thus, alternative strategies are needed. We investigated one such alternative strategy for mass drug administration for elimination of lymphatic filariasis and soil-transmitted helminth infections in Republic of the Congo. In 2012, we started a 3 year community trial of biannual mass administration of albendazole in a village in Republic of the Congo. All volunteering inhabitants aged 2 years or older were offered albendazole (400 mg) every 6 months. Infection with Wuchereria bancrofti was diagnosed with a rapid card immunochromatographic test for antigenaemia. People with antigenaemia were tested for microfilaraemia by night blood smears. Individuals were also tested for soil-transmitted helminth infections (ie, hookworm, Ascaris lumbricoides, Trichuris trichiura) with the Kato-Katz method. Assessment surveys were done at 12, 24, and 36 months. The main outcome measure was change in infection rates from baseline to year 3. Therapeutic coverage was more than 80% in all six rounds of mass administration of albendazole. Between 2012 and 2015, W bancrofti antigenaemia and microfilaraemia rates in the community fell significantly, from 17·3% (95% CI 14·7-20·0) to 4·7% (3·3-6·6; p<0·0001) and from 5·3% (3·9-7·1) to 0·3% (0·1-1·2; p<0·0001), respectively. The geometric mean microfilaria count in microfilaraemic people fell from 199·4 (120·4-330·5) per mL in 2012 to 39·1 (95% CIs not computed) per mL in 2015 (p=0·0095). Hookworm infection was undetectable after 1 year. Between 2012 and 2015, the number of A lumbricoides eggs expelled per g of faeces fell from 9844·6 (8209·0-11 480·0) to 724·4 (340·7-1114·2; p<0·0001), and of T trichiura eggs from 1107·4 (878·5-1336·3) to 366·0 (255·7-476·2; p<0·0001). Our findings strongly support WHO's provisional strategy of biannual mass administration of albendazole to eliminate lymphatic filariasis in areas where loiasis is co-endemic and ivermectin cannot be safely mass administered. Bill & Melinda Gates Foundation.


Contact capitation for specialists.
Though still a relatively young concept, contact capitation has been successfully implemented in provider networks around the country. As a payment methodology, it holds the potential of offering broad physician panels, reduced medical management hassles, greater physician control of clinical decision-making and financial stability for practitioners. Contact capitation allows specialists to regain their voice in clinical decisions and offers them greater financial stability in risk sharing arrangements.


The role of the CD28/B7 interaction in the regulation of NK cell responses during infection with Toxoplasma gondii.
We examined the role of the CD28/B7 interaction in regulation of NK cell activity. Cells transfected with B7 enhanced IL-12-induced production of IFN-gamma by IL-2-activated, CD28+ NK cells, but not by resting CD28- NK cells. The ability of B7 transfectants to enhance NK cell production of IFN-gamma was dependent on the intracellular adhesion molecule-1/LFA-1 interaction and could be inhibited by TGF-beta, but not IL-10. Since IL-12-induced production of IFN-gamma by NK cells is associated with resistance to certain infections, we examined whether the CD28/B7 interaction regulated NK cell responses during infection. Infection of SCID mice with Toxoplasma gondii resulted in the appearance of a population of CD28+ NK cells, NK cell production of IFN-gamma, and increased NK cell cytolytic activity. Administration of CTLA4-Ig to SCID mice infected with T. gondii inhibited these latter two effects and resulted in a significant increase in parasite burden. The stimulus for CD28 expression by NK cells in SCID mice infected with T. gondii appeared to be independent of IL-2. However, mRNA for IL-15, a cytokine with properties similar to those of IL-2, was detected in tissues of SCID mice infected with T. gondii. In vitro experiments demonstrated that IL-15 could stimulate resting NK cells to express functionally active CD28 as well as enhance the production of IFN-gamma by SCID splenocytes stimulated with T. gondii. Together our data demonstrate that the interaction of CD28+ NK cells with B7 regulates NK cell production of IFN-gamma associated with resistance to infection and that IL-15 may be involved in these events.


Decomposition decreases molecular diversity and ecosystem similarity of soil organic matter.
Soil organic matter (SOM) is comprised of a diverse array of reactive carbon molecules, including hydrophilic and hydrophobic compounds, that impact rates of SOM formation and persistence. Despite clear importance to ecosystem science, little is known about broad-scale controls on SOM diversity and variability in soil. Here, we show that microbial decomposition drives significant variability in the molecular richness and diversity of SOM between soil horizons and across a continental-scale gradient in climate and ecosystem type (arid shrubs, coniferous, deciduous, and mixed forests, grasslands, and tundra sedges). The molecular dissimilarity of SOM was strongly influenced by ecosystem type (hydrophilic compounds: 17%, P < 0.001; hydrophobic compounds: 10% P < 0.001) and soil horizon (hydrophilic compounds: 17%, P < 0.001; hydrophobic compounds: 21%, P < 0.001), as assessed using metabolomic analysis of hydrophilic and hydrophobic metabolites. While the proportion of shared molecular features was significantly higher in the litter layer than subsoil C horizons across ecosystems (12 times and 4 times higher for hydrophilic and hydrophobic compounds, respectively), the proportion of site-specific molecular features nearly doubled from the litter layer to the subsoil horizon, suggesting greater differentiation of compounds after microbial decomposition within each ecosystem. Together, these results suggest that microbial decomposition of plant litter leads to a decrease in SOM α-molecular diversity, yet an increase in β-molecular diversity across ecosystems. The degree of microbial degradation, determined by the position in the soil profile, exerts a greater control on SOM molecular diversity than environmental factors, such as soil texture, moisture, and ecosystem type.


Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli--implications for urinary tract infection.
During the course of urinary tract infection (UTI) nitric oxide (NO) is generated as part of the host response. This study investigates the significance of the NO-detoxifying enzyme flavohemoglobin (Hmp) in protection of uropathogenic Escherichia coli (UPEC) against nitrosative stress. An hmp (J96Deltahmp) knockout mutant of UPEC strain J96 was constructed using single-gene deletion. The viability of J96Deltahmp was significantly reduced (P<0.001) compared to the wild-type strain after exposure to the NO-donor DETA/NO. The NO consumption in J96Deltahmp was significantly (P<0.001) impaired compared to J96wt. Screening UPEC isolates from patients with UTI revealed increased hmp expression in all patients. In a competition-based mouse model of UTI, the hmp mutant strain was significantly (P<0.05) out-competed by the wild-type strain. This study demonstrates, for the first time, that Hmp contributes to the protection of UPEC against NO-mediated toxicity in vitro. In addition, hmp gene expression occurs in UPEC isolates from the infected human urinary tract and UPEC that were hmp-deficient had a reduced ability to colonize the mouse urinary tract. Taken together the results suggest that NO detoxification by Hmp may be a fitness advantage factor in UPEC, and a potentially interesting target for development of novel treatment concepts for UTI.


Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways.
In a recently published paper, Harvey and Wessely put forward a 'biopsychosocial' explanatory model for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is proposed to be applicable to (chronic) fatigue even when apparent medical causes are present. Here, we review the model proposed by Harvey and Wessely, which is the rationale for behaviourally oriented interventions, such as cognitive behaviour therapy (CBT) and graded exercise therapy (GET), and compare this model with a biological model, in which inflammatory, immune, oxidative and nitrosative (IO&NS) pathways are key elements. Although human and animal studies have established that the pathophysiology of ME/CFS includes IO&NS pathways, these abnormalities are not included in the model proposed by Harvey and Wessely. Activation of IO&NS pathways is known to induce fatigue and somatic (F&S) symptoms and can be induced or maintained by viral and bacterial infections, physical and psychosocial stressors, or organic disorders such as (auto)immune disorders. Studies have shown that ME/CFS and major depression are both clinical manifestations of shared IO&NS pathways, and that both disorders can be discriminated by specific symptoms and unshared or differentiating pathways. Interventions with CBT/GET are potentially harmful for many patients with ME/CFS, since the underlying pathophysiological abnormalities may be intensified by physical stressors. In contrast to Harvey and Wessely's (bio)psychosocial model for ME/CFS a bio(psychosocial) model based upon IO&NS abnormalities is likely more appropriate to this complex disorder. In clinical practice, we suggest physicians should also explore the IO&NS pathophysiology by applying laboratory tests that examine the pathways involved.


Red emitting, cucurbituril-capped, pH-responsive conjugated oligomer-based nanoparticles for drug delivery and cellular imaging.
Here we report the synthesis of nanoparticles based on a conjugated oligomer which is synthesized through Heck-coupling of divinylfluorene and dibromobenzothiodiazole monomers. These water dispersible nanoparticles emit in the region of red tailing to the near-infrared region of the spectrum with high fluorescent quantum yield and brightness. The nanoparticles were found to be stable in water for a prolonged time without forming any aggregates and could carry camptothecin, an anticancer drug with high loading efficiency. MTT cell viability studies performed with breast cancer cell lines showed that half-maximal inhibitory concentration (IC50) values of nanoparticles for MCF7 and MDA-MB-231 were 44.7 μM and 24.8 μM, respectively. In order to further decrease the cytotoxicity and increase the stability of nanoparticles, amine groups were disguised by capping with cucurbit[7]uril (CB7). Drug release studies showed that drugs were released at low pH (at 5.0) faster than physiological pH (7.4) confirming the pH-responsive nature of the nanoparticles. On the other hand, CB7-capped drug-loaded nanoparticles regulated the release rate by providing slower release at pH 7.4 than the nanoparticles in the absence of CB7s. IC50 values for camptothecin in the presence of nanoparticles with or without CB7 were significantly reduced in MCF7 and MDA-MB-231 cells.


Verifying expressed transcript variants by detecting and assembling stretches of consecutive exons.
We herein describe an integrated system for the high-throughput analysis of splicing events and the identification of transcript variants. The system resolves individual splicing events and elucidates transcript variants via a pipeline that combines aspects such as bioinformatic analysis, high-throughput transcript variant amplification, and high-resolution capillary electrophoresis. For the 14 369 human genes known to have transcript variants, minimal primer sets were designed to amplify all transcript variants and examine all splicing events; these have been archived in the ASprimerDB database, which is newly described herein. A high-throughput thermocycler, dubbed GenTank, was developed to simultaneously perform thousands of PCR amplifications. Following the resolution of the various amplicons by capillary gel electrophoresis, two new computer programs, AmpliconViewer and VariantAssembler, may be used to analyze the splicing events, assemble the consecutive exons embodied by the PCR amplicons, and distinguish expressed versus putative transcript variants. This novel system not only facilitates the validation of putative transcript variants and the detection of novel transcript variants, it also semi-quantitatively measures the transcript variant expression levels of each gene. To demonstrate the system's capability, we used it to resolve transcript variants yielded by single and multiple splicing events, and to decipher the exon connectivity of long transcripts.


Cataracts in patients heterozygous for galactokinase deficiency.
The role of heterozygous galactokinase deficiency in the development of presenile cataracts is presently undetermined. Erythrocyte galactokinase activity was measured from 95 normal Caucasian subjects and from 39 Caucasian patients who had developed idiopathic bilateral cataracts between ages 20 and 55. The diagnosis of heterozygous galactokinase deficiency was based on the following criteria: galactokinase activity more than 2.0 SD below the control population mean; when available, familial evidence for heterozygous galactokinase activity was used as additional evidence. Three of 39 patients (1/13) with cataracts were found to be carriers of the galactokinase deficiency allele (P less than 0.001). Two heterozygotes had high dietary galactose intake suggesting a possible relationship between a high galactose diet and cataract formation. Dietary information was unavailable for the third heterozygote. We conclude that there is a high prevalence of heterozygous galactokinase deficiency existing in patients less than 55 yr of age with cataracts, and recommend that adults at risk restrict their consumption of dairy products.


Microarray platform for profiling enzyme activities in complex proteomes.
Activity-based protein profiling (ABPP) is a chemical method that utilizes active-site-directed probes to determine the functional state of enzymes in complex proteomes. Probe-labeled enzymes are typically detected by in-gel fluorescence scanning, a robust technique that nonetheless exhibits some key deficiencies, including limited sensitivity and resolution, as well as ambiguity regarding the molecular identity of the enzymes under investigation. Here, we report a microarray platform for ABPP that addresses these limitations. In this platform, proteomes are treated with ABPP probes in solution, after which labeled enzymes are captured and visualized on glass slides displaying an array of anti-enzyme antibodies. We show that ABPP microarrays exhibit superior sensitivity and resolution compared to gel-based methods, permitting the parallel analysis of several enzyme activities in proteomes, including cancer-associated proteases such as urokinase, matrix metalloproteinase-9, and prostate-specific antigen.


Assistive Completion of Agrammatic Aphasic Sentences: Amalgamation of NLP and Neurolinguistics-based Synthetic Dataset.
Damage to the inferior frontal gyrus (Broca's area) can cause agrammatic aphasia wherein patients, although able to comprehend, lack the ability to form complete sentences. This inability leads to communication gaps which cause difficulties in their daily lives. The usage of assistive devices can help in mitigating these issues and enable the patients to communicate effectively. However, due to lack of large scale studies of linguistic deficits in aphasia, research on such assistive technology is relatively limited. In this work, we present two contributions that aim to re-initiate research and development in this field. Firstly, we propose a model that uses linguistic features from small scale studies on aphasia patients and generates large scale datasets of synthetic aphasic utterances from grammatically correct datasets. We show that the mean length of utterance, the noun/verb ratio, and the simple/complex sentence ratio of our synthetic datasets correspond to the reported features of aphasic speech. Further, we demonstrate how the synthetic datasets may be utilized to develop assistive devices for aphasia patients. The pre-trained T5 transformer is fine-tuned using the generated dataset to suggest 5 corrected sentences given an aphasic utterance as input. We evaluate the efficacy of the T5 model using the BLEU and cosine semantic similarity scores. Affirming results with BLEU score of 0.827/1.00 and semantic similarity of 0.904/1.00 were obtained. These results provide a strong foundation for the concept that a synthetic dataset based on small scale studies on aphasia can be used to develop effective assistive technology.Clinical relevance- We demonstrate the utilization of Natural Language Processing (NLP) for developing assistive technology for Aphasia patients. While disorders like Broca's aphasia offer a small sample size of patients and data, synthetic linguistic models like ours offer extensive scope for developing assistive technology and rehabilitation monitoring.


The phosphate group of 3-phosphoglycerate accounts for conformational changes occurring on binding to 3-phosphoglycerate kinase. Enzyme inhibition and thiol reactivity studies.
Steady-state kinetic study of the inhibition of 3-phosphoglycerate kinase reaction by the substrate analogues D-glycerol 3-phosphate, 2-phosphoglycolate, tartronate and malonate revealed competition with respect to 3-phosphoglycerate. D-Glycerate had no detectable inhibitory effect. The data indicate that (a) the phosphate of 3-phosphoglycerate plays an essential role in the formation of its complex with the enzyme and, taking into account the relatively strong binding of 3-phosphoglycerate, (b) the two charged groups of the substrate might cause a synergic interaction with the protein. The carboxyl-lacking D-glycerol 3-phosphate is a non-competitive inhibitor with respect to MgATP, while all the investigated carboxyl-containing inhibitors compete for MgATP binding. The inhibitory analogues of 3-phosphoglycerate reduce the reactivity of both the two fast-reacting and the five slow-reacting thiol groups of the enzyme molecule. In the case of the fast-reacting thiols the effect is specifically associated with the presence of a ligand's phosphate group. Similarly mainly the phosphate-containing nucleotides and analogues slow down significantly the reaction rate of the fast-reacting thiols, while adenosine is less effective and the competitive inhibitor adenine has no effect at all. MgADP has an especially dramatic effect as compared to MgATP, in line with the known X-ray structural data. The fast-reacting thiols are of particular interest, since their reactivity is possibly controlled by ligand-induced conformational changes. This is shown by the similar ligand protection against alkylation irrespective of the reagent's electrostatic charge (iodoacetamide or iodoacetate) and also by the similar substrate-binding properties of carboxamidomethylated and the unmodified enzyme.


Preventing anxiety in the children of anxious parents - feasibility of a brief, online, group intervention for parents of one- to three-year-olds.
The evidence suggests an increased risk of developing anxiety problems in children of anxious parents. The current study explored the feasibility and acceptability of an intervention with anxious parents of young children, to inform the possibility of further trials. Participants were recruited through primary and secondary care psychological services and social media. Participants who had a current or recent anxiety disorder and a child aged 12-47 months were included. Assessments of parental and child outcomes occurred at baseline, after the intervention (week-2) and follow-up (week-8). The intervention was delivered in a small group format, in two sessions, one week apart, using videoconferencing. Out of 32 participants, 30 (94%) attended the full intervention. All found the intervention acceptable and reported it as useful and relevant. There was a reduction in parental depression (MD = 2.63, 95%CI 1.01-4.26), anxiety (MD = 3.93, 95%CI 2.49-5.37) and stress (MD = 4.60, 95% CI 3.02-6.18) and increases in parenting confidence. The online group intervention was feasible and acceptable. There were moderate to large effects on parental mental health and no adverse effects on children (decline on outcome measures). This indicates that intervening early in parenting with anxious parents is possible and warrants further investigation to establish prevention efficacy with a larger, controlled trial.


Proton nuclear magnetic resonance of intact Friend leukemia cells: phosphorylcholine increase during differentiation.
Proton nuclear magnetic resonance of intact Friend leukemia cells was used to analyze their erythroid-like differentiation. The technique, which requires only 10(3) to 10(9) cells and approximately 2 minutes for acquisition of each spectrum, demonstrated the occurrence of many signal changes during differentiation. With cell extracts, 64 signals were assigned to 12 amino acids and 19 other intermediary metabolites, and a dramatic signal change was attributed to a fourfold increase in cytoplasmic phosphorylcholines.


Disasters and Depressive Symptoms in Children: A Review.
Disasters are destructive, potentially traumatic events that affect millions of youth each year. The purpose of this paper was to review the literature on depressive symptoms among youth after disasters. Specifically, we examined the prevalence of depression, risk factors associated with depressive symptoms, and theories utilized in this research area. We searched MEDLINE, PsycInfo, and PubMed electronic databases for English language articles published up to May 1, 2013. Reference lists from included studies were reviewed to capture additional studies. Only quantitative, peer reviewed studies, conducted with youth under the age of 18 years, that examined postdisaster depressive symptoms were included. Seventy-two studies met inclusion criteria. Prevalence of depressive symptoms, disaster type, correlates of depressive symptoms, and theories of depressive symptoms were reviewed. Only 27 studies (38%) reported on prevalence rates among youth in their sample. Prevalence rates of depression among youth postdisaster ranged from 2% to 69%. Potential risk factors were identified (e.g., female gender, exposure stressors, posttraumatic stress symptoms). Theories were examined in less than one-third of studies (k = 21). Given the variability in prevalence rates, difficulty identifying a single profile of youth at risk for developing depressive symptoms, and lack of a unifying theory emerging from the studies, recommendations for future research are discussed. Use of established batteries of assessments could enable comparisons across studies. Merging existing theories from children's postdisaster and depression literatures could aid in the identification of risk factors and causal pathways.


Chronic pain following abdominal free flap breast reconstruction: a prospective pilot analysis.
Chronic pain after breast reconstruction is an ill-defined process which can generate significant patient morbidity and disability. The purpose of this study was to examine chronic, persistent pain in a prospective study of free flap breast reconstruction patients, in an effort to identify possible points of intervention and counseling. We performed a prospective study evaluating function, quality of life, and satisfaction in patients undergoing abdominally based autologous reconstruction between 2006 and 2010. Using the short form 36, we examined the presence of chronic body pain (>4 months) as well as overall mental and physical health. Patients with debilitating pain were compared to those without in a post hoc analysis. Overall, 399 women underwent reconstruction during the study period, with 149 enrolling and having long-term follow-up in this portion of the prospective study. Twenty-six (17%) of 149 patients experienced chronic body pain that was moderately debilitating after autologous reconstruction, making it one of the most common complications experienced in this cohort. No differences were noted in demographics, medical history, procedure type, history of axillary surgery, radiation treatment, surgical outcomes, or follow-up time between the cohorts. However, patients with chronic pain were found to have higher preoperative pain scores (P < 0.0001) and lower physical, mental, and overall health scores across time points. All scores significantly worsened with time in comparison to the cohort without pain, who, in contrast showed score improvement across all areas. Although pain issues trended toward being noted in postoperative visits more frequently in the chronic pain cohort (37% vs 19%, P = 0.051), only 1 (4.2%) patient was referred for pain service consultation. Additionally, satisfaction with reconstruction was significantly lower in patients who demonstrated chronic pain (P = 0.03). Factors contributing to chronic pain continue to be elusive and understudied. Our data demonstrate the importance of screening for chronic pain, as we determined that preoperative pain is linked to increased, moderately debilitating postoperative chronic pain. Persistent chronic pain, in turn, is associated with significant morbidity, disability, and dissatisfaction. Such patients with pain issues may benefit from additional preoperative counseling and early involvement of the pain service.


Evolution of Pseudomonas aeruginosa virulence as a result of phage predation.
The rapid increase in the emergence of antibiotic-resistant bacteria has attracted attention to bacteriophages for treating and preventing bacterial infections. Bacteriophages can drive the diversification of Pseudomonas aeruginosa, giving rise to phage-resistant variants with different phenotypes from their ancestral hosts. In this study, we sought to investigate the effect of phage resistance on cytotoxicity of host populations toward cultured mammalian cells. The library of phage-resistant P. aeruginosa PAO1 variants used was developed previously via experimental evolution of an isogenic host population using phages PP7 and E79. Our results presented herein indicate that the phage-resistant variants developed in a heterogeneous phage environment exhibit a greater ability to impede metabolic action of cultured human keratinocytes and have a greater tendency to cause membrane damage even though they cannot invade the cells in large numbers. They also show a heightened resistance to phagocytosis by model murine macrophages. Furthermore, all isolates produced higher levels of at least one of the secreted virulence factors, namely, total proteases, elastase, phospholipase C, and hemolysins. Reverse transcription-quantitative PCR (RT-qPCR) revealed upregulation in the transcription of a number of genes associated with virulence of P. aeruginosa for the phage-resistant variants. The results of this study indicate a significant change in the in vitro virulence of P. aeruginosa following phage predation and highlight the need for caution in the selection and design of phages and phage cocktails for therapeutic use.


Effects of dynamic bedroom lighting on measures of sleep and circadian rest-activity rhythm in inpatients with major depressive disorder.
Bright light therapy is an effective treatment option for seasonal and non-seasonal affective disorders. However up to now, no study has investigated effects of dynamic bedroom lighting in hospitalized patients with major depression. A bedroom lighting system, which automatically delivered artificial dawn and dusk and blue-depleted nighttime lighting (DD-N lighting) was installed in a psychiatric ward. Patients with moderate to severe depression were randomly assigned to stay in bedrooms with the new lighting or standard lighting system. Patients wore wrist actimeters during the first two treatment weeks. Additionally, hospitalization duration and daily psychotropic medication were retrieved from patients' medical charts. Data from thirty patients, recorded over a period of two weeks, were analyzed. Patients under DD-N lighting generally woke up earlier (+ 20 min), slept longer (week 1: + 11 min; week 2: + 27 min) and showed higher sleep efficiency (+ 2.4%) and shorter periods of nighttime awakenings (- 15 min). In the second treatment week, patients started sleep and the most active 10-h period earlier (- 33 min and - 64 min, respectively). This pilot study gives first evidence that depressed patients' sleep and circadian rest/activity system may benefit from bedroom lighting when starting inpatient treatment.


Demonstration of Chlamydophila pneumoniae, Mycoplasma pneumoniae, Cytomegalovirus, and Epstein-Barr virus in atherosclerotic coronary arteries, nonrheumatic calcific aortic and rheumatic stenotic mitral valves by polymerase chain reaction.
The aim of this study was to investigate whether bacterial and viral infectious agents can be demonstrated in atherosclerotic lesions of patients with coronary artery disease (CAD) as well as in stenotic aortic and mitral valves from patients undergoing heart valve replacement. In this cross-sectional study, the presence of Chlamydophila pneumoniae, Mycoplasma pneumoniae, Cytomegalovirus (CMV), and Epstein-Barr virus (EBV) was investigated by polymerase chain reaction in atherosclerotic and non-atherosclerotic vascular samples taken from patients undergoing coronary artery bypass surgery due to CAD, and from patients undergoing aortic (AVR) and/or mitral valve replacement (MVR) secondary to valvular stenosis. For statistical analyses ANOVA, Chi-square test or Fisher's exact test were used. The presence of C. pneumoniae, M. pneumoniae, and CMV in atherosclerotic versus non-atherosclerotic samples was as follows: 30% vs. 16.7% (p=0.222), 6.7% vs. 3.3% (p=0.554), and 10% vs. 0% (p=0.076), respectively. In valve group, same pathogens were present in AVR and MVR patients as follows: 24.2% vs. 21.4% (p=0.773), 9.1% vs. 7.1% (p=0.758), and 21.2% vs. 11.9% (p=0.275). EBV DNA was not detected in any of vascular specimens, but in one (3%) patient with AVR (p=0.256). Our results suggest that C. pneumoniae, M. pneumoniae, and CMV are present with similar frequency both in atherosclerotic and non-atherosclerotic vessels. We conclude that although non-atherosclerotic, vascular samples of CAD patients are invaded by infectious agents as like as atherosclerotic vessels. We further conclude that C. pneumoniae, M. pneumoniae, and CMV are present in stenotic aortic and mitral valves and atherosclerotic tissues with similar frequency indicating that atherosclerosis and valvular stenosis might share a common etiology related to infection.


Osteomyelitis in tropical pyomyositis: a case report.
We report a case of acute tropical pyomyositis in a German girl living in Tanzania. The course of the disease was complicated by osteomyelitis affecting the humerus, which is unusual in tropical pyomyositis. Diagnosis of the osteomyelitis was difficult because a scintigram showed depressed bone activity during the isotope influx and bloodpool phase. The bone phase was abnormal with irregular hypo- and hyperfixation of tracer.


Molecular characterization of Hymenolepis nana based on nuclear rDNA ITS2 gene marker.
Hymenolepis nana is a zoonotic tapeworm with widespread distribution. The goal of the present study was to identify the parasite in the specimens collected from NorthWestern regions of Iran using PCR-sequencing method. A total of 1521 stool samples were collected from the study individuals. Initially, the identification of hymenolepis nana was confirmed by parasitological method including direct wet-mount and formalin-ethyl acetate concentration methods. Afterward, PCR-sequencing analysis of ribosomal ITS2 fragment was targeted to investigate the molecular identification of the parasite. Overall, 0.65% (10/1521) of the isolates were contaminated with H. nana in formalin-ethyl acetate concentration. All ten isolates were succefully amplified by PCR and further sequenced. The determined sequences were deposited in GenBank under the accession numbers MH337810 -MH337819. Our results clarified the presence of H. nana among the patients in the study areas. In addition, the molecular technique could be accessible when the human eggs are the only sources available to identify and diagnose the parasite.


The heartbreak of depression: 'Psycho-cardiac' coupling in myocardial infarction.
Ample evidence identifies strong links between major depressive disorder (MDD) and both risk of ischemic or coronary heart disease (CHD) and resultant morbidity and mortality. The molecular mechanistic bases of these linkages are poorly defined. Systemic factors linked to MDD, including vascular dysfunction, atherosclerosis, obesity and diabetes, together with associated behavioral changes, all elevate CHD risk. Nonetheless, experimental evidence indicates the myocardium is also directly modified in depression, independently of these factors, impairing infarct tolerance and cardioprotection. It may be that MDD effectively breaks the heart's intrinsic defense mechanisms. Four extrinsic processes are implicated in this psycho-cardiac coupling, presenting potential targets for therapeutic intervention if causally involved: sympathetic over-activity vs. vagal under-activity, together with hypothalamic-pituitary-adrenal (HPA) axis and immuno-inflammatory dysfunctions. However, direct evidence of their involvement remains limited, and whether targeting these upstream mediators is effective (or practical) in limiting the cardiac consequences of MDD is unknown. Detailing myocardial phenotype in MDD can also inform approaches to cardioprotection, yet cardiac molecular changes are similarly ill defined. Studies support myocardial sensitization to ischemic insult in models of MDD, including worsened oxidative and nitrosative damage, apoptosis (with altered Bcl-2 family expression) and infarction. Moreover, depression may de-sensitize hearts to protective conditioning stimuli. The mechanistic underpinnings of these changes await delineation. Such information not only advances our fundamental understanding of psychological determinants of health, but also better informs management of the cardiac consequences of MDD and implementing cardioprotection in this cohort.


Impairment of spermatogonial development and spermiation after testosterone-induced gonadotropin suppression in adult monkeys (Macaca fascicularis).
Human male hormonal contraceptive regimens do not consistently induce azoospermia, and the basis of this variable response is unclear. This study used nine adult macaque monkeys (Macaca fascicularis) given testosterone (T) implants for 20 weeks to study changes in germ cell populations in relation to sperm output. Germ cell numbers were determined using the optical disector stereological method. Four animals achieved consistent azoospermia (azoo group), whereas five animals did not (nonazoo group). T-induced gonadotropin suppression in all animals decreased A pale (Ap) spermatogonia to 45% of baseline within 2 weeks, leading to decreased B spermatogonia (32--38%) and later germ cells (20--30%) after 14 and 20 weeks. Though the reduction in later germ cell types could be primarily attributed to the loss of spermatogonia, the data suggested that some cells were lost during the spermatocyte and spermatid phase of development. B spermatogonial number was more markedly suppressed in azoospermic animals, compared with the nonazoo group, as was the conversion ratio between Ap and B spermatogonia. Abnormal retention of elongated spermatids (failed spermiation) was also prominent in some animals after long-term T administration. We conclude that: 1) the variable suppression of sperm output is attributed to the degree of inhibition of germ cell development from type B spermatogonia onwards, and this is related to the degree of FSH suppression; and 2) inhibition of Ap and B spermatogonial development and of spermiation are the major defects caused by long-term T administration to monkeys.


Surgically induced urologic models in swine.
The porcine urological system is similar anatomically and physiologically to that of humans. Swine have a true multirenculate, multipapillate kidney with a calyceal system like that of humans. The gross anatomic and histologic characteristics of the porcine and the human kidney are more similar than most other commonly used laboratory animals. The physiologic functions of the urinary system including urodynamic parameters are also similar to humans. Swine have been used extensively as models of urologic conditions in humans, most commonly in obstructive urologic syndromes. A large number of investigative procedures can be performed in one experiment both in acute and chronic models. Recently, a new technique of surgically induced antenatal lower urinary tract obstruction in swine has been developed.


Longitudinal study assessing the return of chloroquine susceptibility of Plasmodium falciparum in isolates from travellers returning from West and Central Africa, 2000-2011.
Chloroquine (CQ) was the main malaria therapy worldwide from the 1940s until the 1990s. Following the emergence of CQ-resistant Plasmodium falciparum, most African countries discontinued the use of CQ, and now promote artemisinin-based combination therapy as the first-line treatment. This change was generally initiated during the last decade in West and Central Africa. The aim of this study is to describe the changes in CQ susceptibility in this African region, using travellers returning from this region as a sentinel system. The study was conducted by the Malaria National Reference Centre, France. The database collated the pfcrtK76T molecular marker for CQ susceptibility and the in vitro response to CQ of parasites from travellers' isolates returning from Senegal, Mali, Ivory Coast or Cameroon. As a proxy of drug pressure, data regarding CQ intake in febrile children were collated for the study period. Logistic regression models were used to detect trends in the proportions of CQ resistant isolates. A total of 2874 parasite isolates were genotyped between 2000-2011. The prevalence of the pfcrt76T mutant genotype significantly decreased for Senegal (from 78% to 47%), Ivory Coast (from 63% to 37%), Cameroon (from 90% to 59%) and remained stable for Mali. The geometric mean of the 50% inhibitory concentration (IC50) of CQ in vitro susceptibility and the proportion of resistant isolates (defining resistance as an IC50 value > 100 nM) significantly decreased for Senegal (from 86 nM (59%) to 39 nM (25%)), Mali (from 84 nM (50%) to 51 nM (31%)), Ivory Coast (from 75 nM (59%) to 29 nM (16%)) and Cameroon (from 181 nM (75%) to 51 nM (37%)). Both analyses (molecular and in vitro susceptibility) were performed for the 2004-2011 period, after the four countries had officially discontinued CQ and showed an accelerated decline of the resistant isolates for the four countries. Meanwhile, CQ use among children significantly deceased in this region (fixed effects slope = -0.3, p < 10-3). An increase in CQ susceptibility following official withdrawal of the drug was observed in travellers returning from West and Central African countries. The same trends were observed for molecular and in vitro analysis between 2004-2011 and they correlated to the decrease of the drug pressure.


Circulation of copper in the biotic compartments of a freshwater dammed reservoir.
This study concerns a chronic copper release in an aquatic ecosystem: Mirgenbach reservoir; which is characterized by high salinity, conductivity and hardness, a eutrophic state and a high temperature. To study the bioavailability of copper in the biotic compartments, the sampling covered the entire food chain (phyto- and zooplankton, macroalgae, aquatic plants, crustaceans, mollusks, and fish). Of the organisms present, the filter feeder Dreissena polymorpha, the detritivorous Bithynia tentaculata and Orconectes limosus were most contaminated by copper. The level of copper found in fish was the lowest. Body copper concentrations recorded in the present study show large variability between species even in some that are closely related. In most cases, however, the metal handling strategy, feeding habits, morphology and ecology can, at least partially, explain the metal content recorded. Pollution factors have been used to assess the state of contamination of the food chain. This study showed finally that the copper in the lake is bioavailable and bioaccumulated by organisms up to high levels and some effects of long-term toxicity of copper on benthic community and planktonic biomass were pointed out.


The Genus Cladophora Kützing (Ulvophyceae) as a Globally Distributed Ecological Engineer.
The green algal genus Cladophora forms conspicuous nearshore populations in marine and freshwaters worldwide, commonly dominating peri-phyton communities. As the result of human activities, including the nutrient pollution of nearshore waters, Cladophora-dominated periphyton can form nuisance blooms. On the other hand, Cladophora has ecological functions that are beneficial, but less well appreciated. For example, Cladophora has previously been characterized as an ecological engineer because its complex structure fosters functional and taxonomic diversity of benthic microfauna. Here, we review classic and recent literature concerning taxonomy, cell biology, morphology, reproductive biology, and ecology of the genus Cladophora, to examine how this alga functions to modify habitats and influence littoral biogeochemistry. We review the evidence that Cladophora supports large, diverse populations of microalgal and bacterial epiphytes that influence the cycling of carbon and other key elements, and that the high production of cellulose and hydrocarbons by Cladophora-dominated periphyton has the potential for diverse technological applications, including wastewater remediation coupled to renewable biofuel production. We postulate that well-known aspects of Cladophora morphology, hydrodynamically stable and perennial holdfasts, distinctively branched architecture, unusually large cell and sporangial size and robust cell wall construction, are major factors contributing to the multiple roles of this organism as an ecological engineer.


In-hospital mortality associated with the misdiagnosis or unidentified site of infection at admission.
Rapid detection, early resuscitation, and appropriate antibiotic use are crucial for sepsis care. Accurate identification of the site of infection may facilitate a timely provision of appropriate care. We aimed to investigate the relationship between misdiagnosis of the site of infection at initial examination and in-hospital mortality. This was a secondary-multicenter prospective cohort study involving 37 emergency departments. Consecutive adult patients with infection from December 2017 to February 2018 were included. Misdiagnosis of the site of infection was defined as a discrepancy between the suspected site of infection at initial examination and that at final diagnosis, including those infections remaining unidentified during hospital admission, whereas correct diagnosis was defined as site concordance. In-hospital mortality was compared between those misdiagnosed and those correctly diagnosed. Of 974 patients included in the analysis, 11.6% were misdiagnosed. Patients diagnosed with lung, intra-abdominal, urinary, soft tissue, and CNS infection at the initial examination, 4.2%, 3.8%, 13.6%, 10.9%, and 58.3% respectively, turned out to have an infection at a different site. In-hospital mortality occurred in 15%. In both generalized estimating equation (GEE) and propensity score-matched models, misdiagnosed patients exhibited higher mortality despite adjustment for patient background, site infection, and severity. The adjusted odds ratios (misdiagnosis vs. correct diagnosis) for in-hospital mortality were 2.66 (95% CI, 1.45-4.89) in the GEE model and 3.03 (95% CI, 1.24-7.38) in the propensity score-matched model. The difference in the absolute risk in the GEE model was 0.11 (0.04-0.18). Among patients with infection, misdiagnosed site of infection is associated with a > 10% increase in in-hospital mortality.


Preferential occult injury of corpus callosum in multiple sclerosis measured by diffusion tensor imaging.
To investigate the feasibility of diffusion tensor imaging (DTI) assessment of microscopic fiber tract injury in the corpus callosum (CC) and other normal-appearing white matter (NAWM) in patients with early multiple sclerosis (MS). DTI was performed in 12 healthy volunteers and 15 patients who have relatively short disease duration (mean = 2.7 years). Both fractional anisotropy (FA) and mean diffusivity (MD) were obtained in different regions of normal-appearing CC (NACC) and NAWM in frontal and occipital regions. The data showed significantly lower FA (P < 0.001) and higher MD (P < 0.04) for NACC regions, but not for frontal and occipital NAWM regions, in patients than in those in healthy volunteers after Bonferroni adjustment. The increase of MD in the entire NACC regions was correlated with the total cerebral lesion volume (r = 0.75, P = 0.001) in patients. The water diffusion changes indicate that in the early phase of disease there is a preferential occult injury of CC, which is likely due to the Wallerian degeneration from distant lesions.


The use of the functional independence measure in elderly.
To analyze in scientific publications how the Functional Independence Measure (FIM) has been employed to evaluate the elderly. Integrative review of periodical publications between 2011 and 2015, available online in full-text in Portuguese, English and Spanish. 129 articles were found; after the application of the criteria, they resulted in 21. The studies were categorized into two groups: A) follow or compare scores in FIM (cohort studies, case-control, clinical trials), focusing on rehabilitation, evaluation of programs and changes in the functional level after procedures/interventions; and B) measure/associate the functionality of the elderly (cross-sectional studies), focused on evaluation protocols in elderly health and associations to the caregiver burden, hospital stay, balance, satisfaction with life, cognition and clinical/socio-demographic aspects. The FIM was used in several scenarios of healthcare for the elderly, particularly in rehabilitation and outpatient clinics or health centers.


[Legionnaire's disease with predominant liver involvement].
Like other pneumonias due to atypical agents, pneumonia due to Legionela Pneumophila has no characteristic clinical facts, although fever and non-productive cough are almost constant and diarrhea with changes in mental status are common. Hyponatremia and moderate transient hypertransaminasemia are common too. Severe systemic affectation after hematogenous dissemination similar to those described with typical bacterial pneumonias is a prominent difference with other atypical agents, with high mortality rates in the absence of appropriate treatment. Etiological diagnosis is very difficult and it is normally achieved late in the course of the infection. Because of diagnostic difficulties and potential mortality in predisposed patients, empirical antibiotherapy has been extensively recommended. We present a patient affected by critical community-acquired pneumonia due to Legionela Pneumophila serogroup 1 with liver alteration as the main manifestation and good response to empirical antibiotherapy with claritromycine and rifampin. We recommended the empirical use of such therapy in those pneumonias without microbiological diagnosis and torpid evolution.


Microsaccades differentially modulate neural activity in the striate and extrastriate visual cortex.
Saccadic eye movements in primates continually shift the location at which a given stimulus strikes the retina. Even during periods of steady fixation, microsaccades frequently jerk the center of gaze by small but resolvable distances, yet perception remains stable and continuous, uninterrupted by sudden jumps or shifts. The effect of such fixational eye movements on the activity of single neurons was examined in several regions of the visual cortex in macaque monkeys. We found that the firing of many neurons in striate and extrastriate cortex is profoundly influenced by saccades much smaller than the neurons' receptive fields. In striate cortex (V1) many cells showed a transient decrease in their firing shortly following a saccade. In sharp contrast, cells in the extrastriate areas V2 and V4 showed strong excitatory responses that closely coincided in time with the striate depression. No appreciable activity change was observed in the inferotemporal cortex (IT) following saccades. This activity pattern is consistent with the notion that topographic extrastriate areas receive extraretinal input associated with saccadic events. Such signals may be necessary for the stable perception of objects and scenes during eye movements, mediating the mapping between central object representations and the constantly changing retinotopic input.


Measurement of CT lung density in patients with chronic asthma.
Evidence for the presence of emphysema in patients with asthma is controversial. We have previously shown that decreased lung density, measured by computed tomographic (CT) scanning, preoperatively, correlates with morphometric measurements of microscopic emphysema in subsequently resected lungs. The aim of this study was to compare CT lung density, in 17 patients with chronic asthma (forced expiratory volume in one second (FEV1) 1.98 (SD 0.77) L), 17 patients with chronic bronchitis and emphysema (FEV1 0.97 (0.56) L) and seven normal subjects (FEV1 3.5 (034) L). All subjects underwent CT scanning of the lungs and respiratory function testing within 2 days of each other. In five of the asthmatic patients a CT scan was performed on two occasions before and after treatment with nebulized bronchodilator. In a different group of five asthmatics these measurements were performed at the end of and 6 weeks after an exacerbation. The mean value of the lowest fifth percentile of the CT lung density in the patients with chronic obstructive pulmonary disease (COPD) was -942 (SD 36) Hounsfield units (HU), in the 17 asthmatic patients was -912 (34) HU, and in normal subjects was -880 (13). Despite a significant increase in peak expiratory flow rate from 266 (SD 102) to 406 (83) L x s(-1) (p<0.02) following nebulized beta2-agonist in five patients with chronic asthma, there was no significant change in CT lung density (p>0.05) Our study indicates that at least some patients with chronic, stable asthma develop a reduction in computed tomography lung density, similar to that in patients with emphysema.


Innovation During Orientation: How Does Rhetoric Drive New Graduate Nurse Performance?
Modern health care demands knowledge, swift action, and critical thinking from nurses. New and experienced registered nurses are better able to provide excellent care when they are supported by documents that drive consistent nursing action. The process of developing these documents is critically important. Technical writers can improve the adoption of carefully designed forms that help newly licensed registered nurses develop a foundation in critical thinking as they move through orientation.


In Vitro biocompatibility evaluation of a root canal filling material that expands on water sorption.
CPoint is a polymeric endodontic point that takes advantage of water-induced, non-isotropic radial expansion to adapt to canal irregularities. This study evaluated the effects of CPoint on the viability and mineralization potential of odontoblast-like cells. The biocompatibility of CPoint and commercially available gutta-percha points was evaluated by using a rat odontoblast-like cell line (MDPC-23). Cell viability was evaluated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and confocal laser scanning microscopy. The mineralization potential of MDPC-23 cells, in the presence of the root-filling materials, was evaluated by examining the changes in osteogenic gene marker expression (quantitative real-time polymerase chain reaction), alkaline phosphatase activity, alizarin red S assay, and transmission electron microscopy. CPoint showed higher initial cytotoxicity compared with gutta-percha and Teflon (P < .05), which became nonsignificant after 4 immersion cycles. Significant differences were also found between eluents from CPoint and gutta-percha at 1:1 concentration (P < .05) but not at 1:10 or 1:100 concentration. Both materials induced minimal apoptosis-induced alteration in plasma membrane permeability, as evidenced by flow cytometry and confocal laser scanning microscopy. Compared with the Teflon negative control, CPoint and gutta-percha groups showed up-regulation of most osteogenic gene markers except for dentin sialophosphoprotein, which was down-regulated. Alkaline phosphatase activity and alizarin red assay for CPoint and gutta-percha were both significantly higher than for Teflon but not significantly different from each other (P > .05). Transmission electron microscopy showed discrete nodular electron-dense mineralization foci in all 3 groups. The in vitro biocompatibility of CPoint is comparable to gutta-percha with minimal adverse effects on osteogenesis after elution of potentially toxic components.


Inducible HSP70 is critical in preventing the aggregation and enhancing the processing of PMP22.
Chaperones, also called heat shock proteins (HSPs), transiently interact with proteins to aid their folding, trafficking, and degradation, thereby directly influencing the transport of newly synthesized molecules. Induction of chaperones provides a potential therapeutic approach for protein misfolding disorders, such as peripheral myelin protein 22 (PMP22)-associated peripheral neuropathies. Cytosolic aggregates of PMP22, linked with a demyelinating Schwann cell phenotype, result in suppression of proteasome activity and activation of proteostatic mechanisms, including the heat shock pathway. Although the beneficial effects of chaperones in preventing the aggregation and improving the trafficking of PMP22 have been repeatedly observed, the requirement for HSP70 in events remains elusive. In this study, we show that activation of the chaperone pathway in fibroblasts from PMP22 duplication-associated Charcot-Marie-Tooth disease type 1A patient with an FDA-approved small molecule increases HSP70 expression and attenuates proteasome dysfunction. Using cells from an HSP70.1/3(-/-) (inducible HSP70) mouse model, we demonstrate that under proteotoxic stress, this chaperone is critical in preventing the aggregation of PMP22, and this effect is aided by macroautophagy. When examined at steady-state, HSP70 appears to play a minor role in the trafficking of wild-type-PMP22, while it is crucial for preventing the buildup of the aggregation-prone Trembler-J-PMP22. HSP70 aids the processing of Trembler-J-PMP22 through the Golgi and its delivery to lysosomes via Rab7-positive vesicles. Together, these results demonstrate a key role for inducible HSP70 in aiding the processing and hindering the accumulation of misfolded PMP22, which in turn alleviates proteotoxicity within the cells.


Chronic food restriction and the circadian rhythms of pituitary-adrenal hormones, growth hormone and thyroid-stimulating hormone.
Adult male Sprague-Dawley rats were subjected to food restriction so that they ate 65% of food ingested by control rats. While control rats had free access to food over the 24-hour period, food-restricted rats were provided with food daily at 10 a.m. The experimental period lasted for 34 days. On day 35, rats from both experimental groups were killed at 08.00, 11.00, 14.00, 24.00 and 02.00 h. Food restriction modified the circadian rhythms of ACTH and corticosterone. In addition, total circulating corticosterone throughout the day was higher in food-restricted than in control rats. In contrast, food restriction resulted in depressed secretion of thyroid-stimulating hormone and growth hormone. The results indicate that time of food availability entrained circadian corticosterone rhythm but not thyroid-stimulating hormone and growth hormone rhythms.


[Respiratory care in infants following cardiac surgery (author's transl)].
Report on results in postoperative intensive care of 73 infants. 37 underwent corrective surgery on extracorporeal circulation (mortality 24,3%), 36 were operated on without ECC (mortality 16.7%). All infants had been intubated by the nasotracheal route, 39 were treated with CPPV (mean duration 32.5 h), 23 with IPPV (mean duration 28 h). Almost 50% were treated with +7 cm H2O CPAP (mean duration 32 h). Advantages and potential hazards of CPPV and CPAP are discussed.


A point-source outbreak of campylobacteriosis associated with consumption of raw milk.
After a one-day field trip to a Minnesota farm, 22 (45%) of 49 third-grade students and three (14%) of 21 adult chaperones developed campylobacteriosis. Campylobacter jejuni was isolated from specimens of 13 children and one asymptomatic adult. Illness was associated with the consumption of raw milk during a picnic lunch (odds ratio = 41.0, P less than .0001) and participation in hand milking of cows (odds ratio = 37.5, less than .0001). Two additional findings implicated consumption of raw milk as the vehicle for transmission. First, the odds ratio for illness among those who drank raw milk and did not milk cows was 11.8 (P less than .01), whereas the odds ratio for illness among those who milked cows but did not drink raw milk was only 1.2 (P greater than .02). Second, there was a dose-response relation between the occurrence of illness and the quantity of raw milk consumed (P less than .0001). Neither the median incubation period nor duration of illness was related to the amount of milk consumed. All persons with a stool culture positive for C. jejuni excreted the organism for at least two weeks, but less than six weeks. No secondary cases of illness were documented.


Intravenous amiodarone in treatment of recent-onset atrial fibrillation: results of a randomized, controlled study.
This study was designed to determine the efficacy of intravenous amiodarone in the management of recent-onset atrial fibrillation. The optimal approach for acute atrial fibrillation has not been established. Amiodarone is a unique antiarrhythmic agent with activity in both supraventricular and ventricular tachyarrhythmias, but its value for the restoration of sinus rhythm in patients with recent-onset atrial fibrillation has not been demonstrated. Sample size was calculated to detect a 25% increase in reversion rate with amiodarone with a statistical power of 80%. One hundred consecutive patients with recent-onset (<1 week) atrial fibrillation and not taking antiarrhythmic agents were randomized to receive either intravenous amiodarone, 5 mg/kg body weight in 30 min followed by 1,200 mg over 24 h, or an identical amount of saline. Both groups received intravenous digoxin, 0.5 mg initially, followed by 0.25 mg at 2 h and 0.25 mg every 6 h thereafter, to complete 24 h while the ventricular rate was >100 beats/min. Amiodarone and digoxin blood levels were determined. Both groups were homogeneous regarding underlying heart disease, time from onset to treatment, initial ventricular rate and left atrial size. By the end of the 24-h treatment period, 34 patients (68%, 95% confidence interval [CI] 53% to 80%) in the amiodarone group and 30 (60%, 95% CI 45% to 74%) in the control group had returned to sinus rhythm (p = 0.532). Mean times (+/-SD) of conversion were 328 +/- 335 and 332 +/- 359 min, respectively (p =0.957). Among patients who did not convert to sinus rhythm, treatment with amiodarone was associated with a slower ventricular rate (82 +/- 15 beats/min in the amiodarone group vs. 91 +/- 23 beats/min in the control group, p = 0.022). After restoration of sinus rhythm, atrial fibrillation recurred during a 15-day follow-up period in 4 (12%) of 34 patients (95% CI 3% to 27%) in the amiodarone group and in 3 (10%) of 30 (95% CI 2% to 26%) in the control group (p = 0.861). Intravenous amiodarone, at the doses used in this study, produces a modest but not significant benefit in converting acute atrial fibrillation to sinus rhythm.


Surgeon perception is not a good predictor of peri-operative outcomes in robot-assisted radical prostatectomy.
Surgeons have always used their cognitive intuition for the execution of skilled tasks and real-time perception of intra-operative outcomes. We attempted to measure the overall accuracy of intra-operative surgeon perception on the functional outcome of early continence after robot-assisted radical prostatectomy (RARP). A single experienced surgeon (D.I.L.) used a scoring sheet to prospectively capture his subjective opinion of how well a particular portion of the RARP procedure was completed. Surgeon perception of factors affecting post-operative continence such as quality of bladder neck preservation, nerve sparing, urethral length, anastomosis, striated sphincter thickness, quality of Rocco repair and bladder neck plication suture (total 7 variables) were graded as "poor", "average" or "good". Urinary continence was graded as either total continence [0 pads per day (PPD) or social continence (security pad or one PPD)]. A total of 273 (39 patients × 7 variables) responses were recorded: 58.6% were rated as "good", 32.2% as "average" and 8.4% as "poor". A log-rank test for all perception variables showed no significant differences in subsequent achievement of continence (either 0 or 1 PPD) (P > 0.05) at both the 1- and 3-month time points. In the case of some perception variables, patients with "bad" scores gained continence a median of 3 weeks sooner than patients with "good" scores. Surgeon perception of intra-operative performance during RARP is a poor predictive indicator of subsequent functional outcome in terms of urinary continence. Inter-surgeon variability of perception may vary and needs further investigation.


[Continuity of care in primary care; a bygone ideal or new perspective?]
Relational continuity of care has traditionally been an important core value of primary care. Research shows that relational continuity of care contributes to better patient health. However, due to social changes and an altered organization of our health system, it has become more difficult to put this core value into practice. General practitioners, for example, increasingly work part-time and general practices have become larger-scaled. Within practices, there is also an increase of delegation and specialization, leading to fragmentation of healthcare. A weekly rota involving at least three clinical consultation days for each doctor, the establishment of small general practice teams within a larger organisation, and a reduction in the size of a standard practice can facilitate relational continuity of care. In addition, it is necessary for GPs to concentrate on the core activity of their profession: direct personal care.


The E3 ubiquitin ligase TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2.
Limb girdle muscular dystrophy 2H is caused by mutations in the gene encoding the E3 ubiquitin ligase, TRIM32. Previously, we generated and characterized a Trim32 knockout mouse (T32KO) that displays both neurogenic and myopathic features. The myopathy in these mice is attributable to impaired muscle growth, associated with satellite cell senescence and premature sarcopenia. This satellite cell senescence is due to accumulation of the SUMO ligase PIASy, a substrate of TRIM32. The goal of this investigation was to identify additional substrates of TRIM32 using 2D fluorescence difference gel electrophoresis (2D-DIGE) in order to further explore its role in skeletal muscle. Because TRIM32 is an E3 ubiquitin ligase, we reasoned that TRIM32's substrates would accumulate in its absence. 2D-DIGE identified 19 proteins that accumulate in muscles from the T32KO mouse. We focused on two of these proteins, NDRG2 and TRIM72, due to their putative roles in myoblast proliferation and myogenesis. Follow-up analysis confirmed that both proteins were ubiquitinated by TRIM32 in vitro; however, only NDRG2 accumulated in skeletal muscle and myoblasts in the absence of TRIM32. NDRG2 overexpression in myoblasts led to reduced cell proliferation and delayed cell cycle withdrawal during differentiation. Thus, we identified NDRG2 as a novel target for TRIM32; these findings further corroborate the hypothesis that TRIM32 is involved in control of myogenic cells proliferation and differentiation.


Serum Adenosine Deaminase Level is High But Not Related with Disease Activity Parameters in Patients with Rheumatoid Arthritis.
Serum adenosine deaminase (ADA) has been previously proposed to predict disease activity in patients with rheumatoid arthritis (RA). The aim of this study was to investigate the level of serum ADA, and the relationship between ADA and disease activity markers, in a group of patients with RA. A hundred and 10 patients with a diagnosis of RA were recruited from outpatient clinic of Rheumatology Unit. Demographic properties comprising age, gender, disease duration and drugs were recorded. Disease activity based on disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) and DAS28- C reactive protein (CRP,) ESR, CRP levels, as well as pain by visual analog scale and rheumatoid factor (RF) were recorded. Serum ADA levels (IU/L) were determined in all RA patients and in 55 age and sex similar healthy control subjects. Ninety-six female and 14 male RA patients with a mean age of 54.32±11.51, and with a mean disease duration of 11.5±9.13 years were included to the study. The control group comprised of 48 female and 7 male healthy subjects. 35.5% of the patients were on methotrexate (MTX) and 64.5% of patients were on combined DMARDs or combined MTX and anti-TNF therapies. The mean serum ADA level was statistically higher in RA patients than in control subjects (27.01±10.6 IU/L vs 21.8 ±9.9 IU/L). The mean values of ESR (23.2±14.8 mm/h), CRP (1.71±1.11mg/dL), pain by VAS (37.2±27.1), DAS28-ESR (2.72±0.77), DAS28 CRP (1.37±0.5) were not correlated with ADA levels (p>0.05). Our results have shown that serum ADA levels are higher in RA patients than in controls but were not related with any of the disease activity markers. We conclude that ADA in the serum may not be a reliable biochemical marker to predict disease activity in patients with RA.


In Silico and In Vitro Anti-Helicobacter Pylori Effects of Combinations of Phytochemicals and Antibiotics.
Helicobacter pylori infection is a WHO class 1 carcinogenic factor of gastric adenocarcinoma. In the past decades, many studies have demonstrated the increasing trend of antibiotic resistance and pointed out the necessity of new effective treatment. This study was aimed at identifying phytochemicals that can inhibit H. pylori and possibly serve as adjuvant treatments. Here, in silico molecular docking and drug-like properties analyses were performed to identify potential inhibitors of urease, shikimate kinase and aspartate-semialdehyde dehydrogenase. These three enzymes are targets of the treatment of H. pylori. Susceptibility and synergistic testing were performed on the selected phytochemicals and the positive control antibiotic, amoxicillin. The in-silico study revealed that oroxindin, rosmarinic acid and verbascoside are inhibitors of urease, shikimate kinase and aspartate-semialdehyde dehydrogenase, respectively, in which, oroxindin has the highest potency against H. pylori, indicated by a minimum inhibitory concentration (MIC) value of 50 μg/mL. A combination of oroxindin and amoxicillin demonstrated additive effects against H. pylori, as indicated by a fractional inhibitory concentration (FIC) value of 0.75. This study identified phytochemicals that deserve further investigation for the development of adjuvant therapeutic agents to current antibiotics against H. pylori.


Discovery of Novel Cell Surface Markers for Purification of Embryonic Dopamine Progenitors for Transplantation in Parkinson's Disease Animal Models.
Despite the progress in safety and efficacy of cell replacement therapy with pluripotent stem cells (PSCs), the presence of residual undifferentiated stem cells or proliferating neural progenitor cells with rostral identity remains a major challenge. Here we report the generation of a LIM homeobox transcription factor 1 alpha (LMX1A) knock-in GFP reporter human embryonic stem cell (hESC) line that marks the early dopaminergic progenitors during neural differentiation to find reliable membrane protein markers for isolation of midbrain dopaminergic neurons. Purified GFP positive cells in vitro exhibited expression of mRNA and proteins that characterized and matched the midbrain dopaminergic identity. Further quantitative proteomics analysis of enriched LMX1A+ cells identified several membrane-associated proteins including a polysialylated embryonic form of neural cell adhesion molecule (PSA-NCAM) and contactin 2 (CNTN2), enabling prospective isolation of LMX1A+ progenitor cells. Transplantation of human-PSC-derived purified CNTN2+ progenitors enhanced dopamine release from transplanted cells in the host brain and alleviated Parkinson's disease-related phenotypes in animal models. This study establishes an efficient approach for purification of large numbers of human-PSC-derived dopaminergic progenitors for therapeutic applications.