Metabolic syndrome across Europe: different clusters of risk factors.
Metabolic syndrome (MetS) remains a controversial entity. Specific clusters of MetS components - rather than MetS per se - are associated with accelerated arterial ageing and with cardiovascular (CV) events. To investigate whether the distribution of clusters of MetS components differed cross-culturally, we studied 34,821 subjects from 12 cohorts from 10 European countries and one cohort from the USA in the MARE (Metabolic syndrome and Arteries REsearch) Consortium. In accordance with the ATP III criteria, MetS was defined as an alteration three or more of the following five components: elevated glucose (G), fasting glucose ≥110 mg/dl; low HDL cholesterol, < 40mg/dl for men or <50 mg/dl for women; high triglycerides (T), ≥150 mg/dl; elevated blood pressure (B), ≥130/≥85 mmHg; abdominal obesity (W), waist circumference >102 cm for men or >88 cm for women. MetS had a 24.3% prevalence (8468 subjects: 23.9% in men vs. 24.6% in women, p < 0.001) with an age-associated increase in its prevalence in all the cohorts. The age-adjusted prevalence of the clusters of MetS components previously associated with greater arterial and CV burden differed across countries (p < 0.0001) and in men and women (p < 0.0001). In details, the cluster TBW was observed in 12% of the subjects with MetS, but was far more common in the cohorts from the UK (32.3%), Sardinia in Italy (19.6%), and Germany (18.5%) and less prevalent in the cohorts from Sweden (1.2%), Spain (2.6%), and the USA (2.5%). The cluster GBW accounted for 12.7% of subjects with MetS with higher occurrence in Southern Europe (Italy, Spain, and Portugal: 31.4, 18.4, and 17.1% respectively) and in Belgium (20.4%), than in Northern Europe (Germany, Sweden, and Lithuania: 7.6, 9.4, and 9.6% respectively). The analysis of the distribution of MetS suggested that what follows under the common definition of MetS is not a unique entity rather a constellation of cluster of MetS components, likely selectively risky for CV disease, whose occurrence differs across countries.


Yeast m6A Methylated mRNAs Are Enriched on Translating Ribosomes during Meiosis, and under Rapamycin Treatment.
Interest in mRNA methylation has exploded in recent years. The sudden interest in a 40 year old discovery was due in part to the finding of FTO's (Fat Mass Obesity) N6-methyl-adenosine (m6A) deaminase activity, thus suggesting a link between obesity-associated diseases and the presence of m6A in mRNA. Another catalyst of the sudden rise in mRNA methylation research was the release of mRNA methylomes for human, mouse and Saccharomyces cerevisiae. However, the molecular function, or functions of this mRNA 'epimark' remain to be discovered. There is supportive evidence that m6A could be a mark for mRNA degradation due to its binding to YTH domain proteins, and consequently being chaperoned to P bodies. Nonetheless, only a subpopulation of the methylome was found binding to YTHDF2 in HeLa cells.The model organism Saccharomyces cerevisiae, has only one YTH domain protein (Pho92, Mrb1), which targets PHO4 transcripts for degradation under phosphate starvation. However, mRNA methylation is only found under meiosis inducing conditions, and PHO4 transcripts are apparently non-methylated. In this paper we set out to investigate if m6A could function alternatively to being a degradation mark in S. cerevisiae; we also sought to test whether it can be induced under non-standard sporulation conditions. We find a positive association between the presence of m6A and message translatability. We also find m6A induction following prolonged rapamycin treatment.


Kinase joins the chaperone club: Androgen-regulated kinome reveals choline kinase alpha as a potential drug target in prostate cancer.
To identify clinically relevant downstream effectors of androgen signaling, the androgen-regulated kinome was defined in prostate cancer (PCa). Within this study, choline kinase α (CHKA) was identified as an androgen receptor chaperone that is both a biomarker of progression and a potential therapeutic target for PCa.


Detecting free-living steps and walking bouts: validating an algorithm for macro gait analysis.
Research suggests wearables and not instrumented walkways are better suited to quantify gait outcomes in clinic and free-living environments, providing a more comprehensive overview of walking due to continuous monitoring. Numerous validation studies in controlled settings exist, but few have examined the validity of wearables and associated algorithms for identifying and quantifying step counts and walking bouts in uncontrolled (free-living) environments. Studies which have examined free-living step and bout count validity found limited agreement due to variations in walking speed, changing terrain or task. Here we present a gait segmentation algorithm to define free-living step count and walking bouts from an open-source, high-resolution, accelerometer-based wearable (AX3, Axivity). Ten healthy participants (20-33 years) wore two portable gait measurement systems; a wearable accelerometer on the lower-back and a wearable body-mounted camera (GoPro HERO) on the chest, for 1 h on two separate occasions (24 h apart) during free-living activities. Step count and walking bouts were derived for both measurement systems and compared. For all participants during a total of almost 20 h of uncontrolled and unscripted free-living activity data, excellent relative (rho ⩾ 0.941) and absolute (ICC(2,1) ⩾ 0.975) agreement with no presence of bias were identified for step count compared to the camera (gold standard reference). Walking bout identification showed excellent relative (rho ⩾ 0.909) and absolute agreement (ICC(2,1) ⩾ 0.941) but demonstrated significant bias. The algorithm employed for identifying and quantifying steps and bouts from a single wearable accelerometer worn on the lower-back has been demonstrated to be valid and could be used for pragmatic gait analysis in prolonged uncontrolled free-living environments.


Molecular analysis of the anaerobic rumen fungus Orpinomyces - insights into an AT-rich genome.
The anaerobic gut fungi occupy a unique niche in the intestinal tract of large herbivorous animals and are thought to act as primary colonizers of plant material during digestion. They are the only known obligately anaerobic fungi but molecular analysis of this group has been hampered by difficulties in their culture and manipulation, and by their extremely high A+T nucleotide content. This study begins to answer some of the fundamental questions about the structure and organization of the anaerobic gut fungal genome. Directed plasmid libraries using genomic DNA digested with highly or moderately rich AT-specific restriction enzymes (VspI and EcoRI) were prepared from a polycentric Orpinomyces isolate. Clones were sequenced from these libraries and the breadth of genomic inserts, both genic and intergenic, was characterized. Genes encoding numerous functions not previously characterized for these fungi were identified, including cytoskeletal, secretory pathway and transporter genes. A peptidase gene with no introns and having sequence similarity to a gene encoding a bacterial peptidase was also identified, extending the range of metabolic enzymes resulting from apparent trans-kingdom transfer from bacteria to fungi, as previously characterized largely for genes encoding plant-degrading enzymes. This paper presents the first thorough analysis of the genic, intergenic and rDNA regions of a variety of genomic segments from an anaerobic gut fungus and provides observations on rules governing intron boundaries, the codon biases observed with different types of genes, and the sequence of only the second anaerobic gut fungal promoter reported. Large numbers of retrotransposon sequences of different types were found and the authors speculate on the possible consequences of any such transposon activity in the genome. The coding sequences identified included several orphan gene sequences, including one with regions strongly suggestive of structural proteins such as collagens and lampirin. This gene was present as a single copy in Orpinomyces, was expressed during vegetative growth and was also detected in genomes from another gut fungal genus, Neocallimastix.


Methodological aspects of economic evaluations conducted in the palliative or end of life care settings: a systematic review protocol.
In light of this growing palliative care and end of life care patient population, as well as new (expensive) drugs and treatments, quality research providing evidence for decision-making is required. However, common research guidance is lacking in this field, especially in respect to the methods applied in economic evaluations. Therefore, the aim of the planned systematic review is to identify and summarise relevant information on methodological challenges, potential solutions and recommendations for conducting economic evaluations of interventions in adult patients, irrespective of their underlying disease and gender in the palliative or end of life care settings, with no restrictions in regards to countries/geographical regions. The results of this systematic review may help to clarify the current methodological questions and form the basis of new, setting specific methods guidelines and support ongoing applied economic evaluations in the field. A systematic review will be conducted using Medline, Embase, Health Technology Assessment Database and NHS Economic Evaluation Database to identify the studies published from 1999 onwards with relevant information on methodological challenges, potential solutions and recommendations for conducting economic evaluations in the palliative or end of life care settings. Articles in English, German, Spanish, French or Dutch language will be considered. Two independent reviewers will conduct the screening of articles; any discrepancies will be resolved by discussion and involvement of a third reviewer. Predesigned data extraction forms will be applied, consequently narratively synthesised and categorised. Studies' methodological quality will be critically appraised. Besides existing economic guidelines and checklists for specific information on the palliative and end of life care sector will be searched. Ethical approval is not required, as this is a planned systematic review of published literature. An article will be disseminated in a related peer-reviewed journal, as well as presented at leading palliative care and health economic conferences. CRD42020148160.


Colloidal joints with designed motion range and tunable joint flexibility.
The miniaturization of machines towards the micron and nanoscale requires the development of joint-like elements that enable and constrain motion. We present a facile method to create colloidal joints, that is, anisotropic colloidal particles functionalized with surface mobile DNA linkers that control the motion range of bonded particles. We demonstrate quantitatively that we can control the flexibility of these colloidal joints by tuning the DNA linker concentration in the bond area. We show that the shape of the colloidal joint controls the range of motion of bonded particles through a maximisation of the bond area. Using spheres, cubes, and dumbbells, we experimentally realize spherical joints, planar sliders, and hinges, respectively. Finally we demonstrate the potential of the colloidal joints for programmable bottom-up self-assembly by creating flexible colloidal molecules and colloidal polymers. The reconfigurability and motion constraint offered by our colloidal joints make them promising building blocks for the development of switchable materials and nanorobots.


microRNA-192 suppresses the expression of the farnesoid X receptor.
Farnesoid X receptor (FXR, NR1H4) plays an important role in the regulation of bile acid homeostasis in liver and intestine and may exert protective effects against certain forms of cancer such as colon carcinoma. However, the role of FXR in cell growth regulation, apoptosis, and carcinogenesis is still controversial. Similar to FXR, microRNA-192 (miR-192) is mainly expressed in the liver and colon and plays an important role in the pathogenesis of colon carcinoma. In this study, we investigated the extent to which FXR is regulated by miR-192. Two in silico-predicted binding sites for miR-192-3p within the NR1H4-3' untranslated region (UTR) were examined in vitro by luciferase reporter assays. Wild-type and mutated forms of the NR1H4-3'UTR were subcloned into a pmirGLO vector and cotransfected into Huh-7 cells with miR-192-3p. To study the effects of miR-192 on the expression of FXR, FXR target genes and cell proliferation, Huh-7 and Caco-2 cells were transfected with miR-192-5p and -3p mimics or antagomirs. In addition, the correlation between FXR and miR-192 expression was studied by linear regression analyses in colonic adenocarcinoma tissue from 27 patients. MiR-192-3p bound specifically to the NR1H4-3'UTR and significantly decreased luciferase activity. Transfection with miR-192 led to significant decreases in NR1H4 mRNA and protein levels as well as the mRNA levels of the FXR-inducible bile acid transporters OSTα-OSTβ and OATP1B3. Significant inverse correlations were detected in colonic adenocarcinoma between NR1H4 mRNA and miR-192-3p expression. In summary, microRNA-192 suppresses the expression of FXR and FXR target genes in vitro and in vivo.


Patient safety perspectives of providers and nurses: the experience of a rural ambulatory care practice using an EHR with E-prescribing.
The purpose of this study was to identify and describe safety improvements and concerns indicated by providers and nurses in a rural community ambulatory care practice using an electronic health record with an e-prescribing feature (EHR with eRx). Two focus groups were conducted; 1 with providers and the other with nurses. Participants responded to questions and discussed their perceptions of safety improvements and concerns with use of an EHR with eRx. Transcripts were analyzed using sequential and continuous analytic methods. Three themes centered on efficiency and patient safety emerged from data analysis: (1) EHR with eRx adoption has led to new improvements and concerns for patient safety, (2) the EHR with eRx has affected efficiency in the clinic, and (3) EHR with eRx adoption has led to workarounds. Concerns remain among providers and nurses regarding the use of EHR with eRx applications, although concerns differed between groups. Therefore, When EHR improvements are planned, it is important to consider the differing needs of the professionals who deliver care.


Development of a language screening instrument for Swedish 4-year-olds.
The Swedish Program for health surveillance of preschool children includes screening of language and communication abilities. One important language screening is carried out at age 4 years as part of a general screening conducted by health nurses at child health centres. The instruments presently in use for this screening mainly focus on expressive phonology. This may result in both over-referral of children with phonological difficulties and under-referral of children with language disorders (LDs), involving difficulties with vocabulary, grammar and/or language comprehension. Previous research has proposed non-word repetition as a clinical marker for LD. It has also been found that higher predictive power is achieved when non-word repetition is combined with the assessment of lexical/semantic skills. Taking these findings into account, the construction of a language screening instrument may yield more adequate referrals to speech-language therapists (SLTs). To construct a new standardized language screening instrument for 4-year-olds and to test its properties. An instrument was developed and revised after piloting. A population of 352 children was screened at the regular 4-year check-up by 11 health nurses. The final sample consisted of 328 children aged 46-53 months (23% multilingual). Children performing below a preliminary cut-off were referred to an SLT (n = 52). Five SLTs carried out an assessment on average within 5 weeks using a gold standard language test battery. Children who screened negatively were followed up with a parent questionnaire at age 5;6. Thirty-one true-positives and 11 false-positives were identified after SLT assessment. A further six children were identified as false-negatives (two through referral to an SLT and four through parent questionnaire at age 5;6). A receiver-operating characteristics curve with a C statistic of .94 was calculated. Based on optimal cut-off, the sensitivity of the screening instrument was found to be .84, and specificity was .96. Multilingual children performed similar to monolingual children; boys performed significantly lower than girls; and children with a family history of language-related problems performed lower than those without. Interrater reliability was high, as was Cronbach's alpha. The screening instrument seems sufficiently valid for its purpose to identify children who need further assessment by an SLT. A follow-up study including SLT assessment for all children to check for false-negatives would be interesting in future, as would studies comparing results from the 4-year screening with those from earlier screens.


Entanglement and Coherence in Quantum State Merging.
Understanding the resource consumption in distributed scenarios is one of the main goals of quantum information theory. A prominent example for such a scenario is the task of quantum state merging, where two parties aim to merge their tripartite quantum state parts. In standard quantum state merging, entanglement is considered to be an expensive resource, while local quantum operations can be performed at no additional cost. However, recent developments show that some local operations could be more expensive than others: it is reasonable to distinguish between local incoherent operations and local operations which can create coherence. This idea leads us to the task of incoherent quantum state merging, where one of the parties has free access to local incoherent operations only. In this case the resources of the process are quantified by pairs of entanglement and coherence. Here, we develop tools for studying this process and apply them to several relevant scenarios. While quantum state merging can lead to a gain of entanglement, our results imply that no merging procedure can gain entanglement and coherence at the same time. We also provide a general lower bound on the entanglement-coherence sum and show that the bound is tight for all pure states. Our results also lead to an incoherent version of Schumacher compression: in this case the compression rate is equal to the von Neumann entropy of the diagonal elements of the corresponding quantum state.


Nonheme oxoiron(IV) complexes of tris(2-pyridylmethyl)amine with cis-monoanionic ligands.
Treatment of [Fe(IV)(O)(TPA)(NCMe)](CF3SO3)2 [TPA, N,N,N-tris(2-pyridylmethyl)amine] with 3 equiv of NR4X (X = CF3CO2, Cl, or Br) in MeCN at -40 degrees C affords a series of metastable [Fe(IV)(O)(TPA)(X)]+ complexes. Some characteristic features of the S = 1 oxoiron(IV) unit are quite insensitive to the ligand substitution in the equatorial plane, namely, the Fe-O distances (1.65-1.66 A), the energy ( approximately 7114.5 eV) and intensity [25(2) units] of the 1s-to-3d transition in the X-ray absorption spectra, and the Mössbauer isomer shifts (0.01-0.06 mm.s(-1)) and quadrupole splittings (0.92-0.95 mm.s(-1)). The coordination of the anionic X ligand, however, is evidenced by red shifts of the characteristic near-IR ligand-field bands (720-800 nm) and spectroscopic observation of the bound anion by (19)F NMR for X = CF3CO2 and by EXAFS analysis for X = Cl (r(Fe-Cl) = 2.29 A) and Br (r(Fe-Br) = 2.43 A). Density functional theory calculations yield Mössbauer parameters and bond lengths in good agreement with the experimental data and produce excited-state energies that follow the trend observed in the ligand-field bands. Despite mitigating the high effective charge of the iron(IV) center, the substitution of the MeCN ligand with monoanionic ligands X- decreases the thermal stability of [Fe(IV)(O)(TPA)]2+ complexes. These anion-substituted complexes model the cis-X-Fe(IV)=O units proposed in the mechanisms of oxygen-activating nonheme iron enzymes.


Participation of leaky ribosome scanning in protein dual targeting by alternative translation initiation in higher plants.
Postendosymbiotic evolution has given rise to proteins that are multiply targeted within the cell. Various mechanisms have been identified to permit the expression of proteins encoding distinct N termini from a single gene. One mechanism involves alternative translation initiation (aTI). We previously showed evidence of aTI activity within the Arabidopsis thaliana organellar DNA polymerase gene POLgamma2. Translation initiates at four distinct sites within this gene, two non-AUG, to produce distinct plastid and mitochondrially targeted forms of the protein. To understand the regulation of aTI in higher plants, we used Polgamma2 as a model to investigate both cis- and trans-acting features of the process. Here, we show that aTI in Polgamma2 and other plant genes involves ribosome scanning dependent on sequence context at the multiple initiation sites to condition specific binding of at least one trans-acting factor essential for site recognition. Multiple active translation initiation sites appear to operate in several plant genes, often to expand protein targeting. In plants, where the mitochondrion and plastid must share a considerable portion of their proteomes and coordinate their functions, leaky ribosome scanning behavior provides adaptive advantage in the evolution of protein dual targeting and translational regulation.


Mechanisms of behavioural maintenance: Long-term effects of theory-based interventions to promote safe water consumption.
Theory-based interventions can enhance people's safe water consumption, but the sustainability of these interventions and the mechanisms of maintenance remain unclear. We investigated these questions based on an extended theory of planned behaviour. Seven hundred and ten (445 analysed) randomly selected households participated in two cluster-randomised controlled trials in Bangladesh. Study 1 promoted switching to neighbours' arsenic-safe wells, and Study 2 promoted switching to arsenic-safe deep wells. Both studies included two intervention phases. Structured interviews were conducted at baseline (T1), and at 1-month (T2), 2-month (T3) and 9-month (T4) follow-ups. In intervention phase 1 (between T1 and T2), commitment-based behaviour change techniques--reminders, implementation intentions and public commitment--were combined with information and compared to an information-only control group. In phase 2 (between T2 and T3), half of each phase 1 intervention group was randomly assigned to receive either commitment-based techniques once more or coping planning with reminders and information. Initial well-switching rates of up to 60% significantly declined by T4: 38.3% of T2 safe water users stopped consuming arsenic-safe water. The decline depended on the intervention. Perceived behavioural control, intentions, commitment strength and coping planning were associated with maintenance. In line with previous studies, the results indicate that commitment and reminders engender long-term behavioural change.


Habitual coffee drinkers display a distinct pattern of brain functional connectivity.
Coffee is the most widely consumed source of caffeine worldwide, partly due to the psychoactive effects of this methylxanthine. Interestingly, the effects of its chronic consumption on the brain's intrinsic functional networks are still largely unknown. This study provides the first extended characterization of the effects of chronic coffee consumption on human brain networks. Subjects were recruited and divided into two groups: habitual coffee drinkers (CD) and non-coffee drinkers (NCD). Resting-state functional magnetic resonance imaging (fMRI) was acquired in these volunteers who were also assessed regarding stress, anxiety, and depression scores. In the neuroimaging evaluation, the CD group showed decreased functional connectivity in the somatosensory and limbic networks during resting state as assessed with independent component analysis. The CD group also showed decreased functional connectivity in a network comprising subcortical and posterior brain regions associated with somatosensory, motor, and emotional processing as assessed with network-based statistics; moreover, CD displayed longer lifetime of a functional network involving subcortical regions, the visual network and the cerebellum. Importantly, all these differences were dependent on the frequency of caffeine consumption, and were reproduced after NCD drank coffee. CD showed higher stress levels than NCD, and although no other group effects were observed in this psychological assessment, increased frequency of caffeine consumption was also associated with increased anxiety in males. In conclusion, higher consumption of coffee and caffeinated products has an impact in brain functional connectivity at rest with implications in emotionality, alertness, and readiness to action.


First detection of infectious haematopoietic necrosis virus in farmed rainbow trout in North Macedonia.
Infectious haematopoietic necrosis virus (IHNV) is the causative agent of infectious haematopoietic necrosis (IHN), a disease of salmonids responsible for great economic losses. The disease occurs in most parts of the world where rainbow trout is reared but has not been previously reported in North Macedonia. In this study, 150 pooled samples in total, each consisting of organ mix of 10 freshly killed rainbow trout Oncorhynchus mykiss, were collected from 50 trout farms by the Food and Veterinary Agency of North Macedonia as part of the annual surveillance plan for IHN and viral haemorrhagic septicaemia (VHS) control. Screening of samples was done by cell culture and real-time RT-PCR (qRT-PCR). All 150 tested samples were VHS virus (VHSV) qRT-PCR negative. Two samples from different trout farms were IHNV qRT-PCR positive. On cell culture, 1 IHNV qRT-PCR positive sample caused cytopathic effect after 2 passages on EPC cells. The virus, isolated from an asymptomatic rainbow trout fry, was identified by qRT-PCR and designated as MAKIHNV1. The phylogenetic reconstruction indicates that the isolated virus belongs to the European E genogroup, more specifically within the E-1 clade, and is similar to the German, Italian and Iranian isolates. This study has revealed for the first time the presence of IHNV in rainbow trout in North Macedonia. However, it is not possible to make interpretations about the source of infection from the phylogenetic analysis, and the origin of MAKIHNV1 remains unclear.


Virus-induced gene silencing as a tool for comparative functional studies in Thalictrum.
Perennial woodland herbs in the genus Thalictrum exhibit high diversity of floral morphology, including four breeding and two pollination systems. Their phylogenetic position, in the early-diverging eudicots, makes them especially suitable for exploring the evolution of floral traits and the fate of gene paralogs that may have shaped the radiation of the eudicots. A current limitation in evolution of plant development studies is the lack of genetic tools for conducting functional assays in key taxa spanning the angiosperm phylogeny. We first show that virus-induced gene silencing (VIGS) of a PHYTOENE DESATURASE ortholog (TdPDS) can be achieved in Thalictrum dioicum with an efficiency of 42% and a survival rate of 97%, using tobacco rattle virus (TRV) vectors. The photobleached leaf phenotype of silenced plants significantly correlates with the down-regulation of endogenous TdPDS (P<0.05), as compared to controls. Floral silencing of PDS was achieved in the faster flowering spring ephemeral T. thalictroides. In its close relative, T. clavatum, silencing of the floral MADS box gene AGAMOUS (AG) resulted in strong homeotic conversions of floral organs. In conclusion, we set forth our optimized protocol for VIGS by vacuum-infiltration of Thalictrum seedlings or dormant tubers as a reference for the research community. The three species reported here span the range of floral morphologies and pollination syndromes present in Thalictrum. The evidence presented on floral silencing of orthologs of the marker gene PDS and the floral homeotic gene AG will enable a comparative approach to the study of the evolution of flower development in this group.


Management of Pneumocystis Jirovecii pneumonia in HIV infected patients: current options, challenges and future directions.
The discovery of the Human Immunodeficiency Virus (HIV) was led by the merge of clustered cases of Pneumocystis jirovecii Pneumonia (PCP) in otherwise healthy people in the early 80's.1,2 In the face of sophisticated treatment now available for HIV infection, life expectancy approaches normal limits. It has dramatically changed the natural course of HIV from a nearly fatal infection to a chronic disease.3-5 However, PCP still remains a relatively common presentation of uncontrolled HIV. Despite the knowledge and advances gained in the prevention and management of PCP infection, it continues to have high morbidity and mortality rates. Trimethoprim-sulfamethoxazole (TMP-SMZ) remains as the recommended first-line treatment. Alternatives include pentamidine, dapsone plus trimethoprim, clindamycin administered with primaquine, and atovaquone. For optimal management, clinicians need to be familiar with the advantages and disadvantages of the available drugs. The parameters used to classify severity of infection are also important, as it is well known that the adjunctive use of steroids in moderate to severe cases have been shown to significantly improve outcome. Evolving management practices, such as the successful institution of early antiretroviral therapy, may further enhance overall survival rates.


On the origin of the hierarchy of color names.
One of the fundamental problems in cognitive science is how humans categorize the visible color spectrum. The empirical evidence of the existence of universal or recurrent patterns in color naming across cultures is paralleled by the observation that color names begin to be used by individual cultures in a relatively fixed order. The origin of this hierarchy is largely unexplained. Here we resort to multiagent simulations, where a population of individuals, subject to a simple perceptual constraint shared by all humans, namely the human Just Noticeable Difference, categorizes and names colors through a purely cultural negotiation in the form of language games. We found that the time needed for a population to reach consensus on a color name depends on the region of the visible color spectrum. If color spectrum regions are ranked according to this criterion, a hierarchy with [red, (magenta)-red], [violet], [green/yellow], [blue], [orange], and [cyan], appearing in this order, is recovered, featuring an excellent quantitative agreement with the empirical observations of the WCS. Our results demonstrate a clear possible route to the emergence of hierarchical color categories, confirming that the theoretical modeling in this area has now attained the required maturity to make significant contributions to the ongoing debates concerning language universals.


Ethical dilemmas in nursing.
Nurses are increasingly realising that they can offer relevant information and participate in decision-making involving ethical issues. However, inter-professional communications are frequently inadequate, and do not permit exchange of opinions. The consequences are often frustrating and upsetting for nurses whose care is affected by others' policies. This paper explores these issues using some clinical examples.


Sexual violence, HSV-2 and HIV are important predictors for infertility in Rwanda.
In order to formulate cost-effective health interventions aimed at preventing infertility it is necessary to identify modifiable risk factors for infertility in sub-Saharan Africa. This case-control study examined potential predictors and their population attributable fraction (PAF%) for various infertility types including lifestyle factors, sexual behaviour and reproductive tract infections (RTIs). Sexually active women aged 21-45 year presenting with infertility problems at the infertility clinic of the Kigali University Teaching Hospital (n = 312), and fertile controls who recently delivered (n = 283) were surveyed together with their male partners. Participants were interviewed about socio-demographic characteristics, sexual behaviours and lifestyle factors, and were tested for HIV and RTIs. Variables significantly associated with tubal infertility were history of sexual violence [adjusted odds ratio (AOR) 2.41; 95% CI 1.36-4.25]; positive HIV (AOR 2.41; 95% CI 1.36-4.25), herpes simplex virus type 2 (HSV-2; AOR 1.67; 95% CI 1.03-2.71) and Chlamydia trachomatis serology (AOR 1.78; 95% CI 0.99-3.21), and current bacterial vaginosis by Amsel criteria (AOR 1.97; 95% CI 1.12-3.47). Among men, male factor infertility was associated with positive HIV (AOR 2.43; 95% CI 1.31-5.23) and HSV-2 serology (AOR 1.71; 95% CI 1.02-2.87) and current urologic abnormalities (AOR 2.38; 95% CI 1.01-5.31). Positive HSV-2 serostatus carried the greatest PAF% (26%) for tubal infertility, followed by positive HIV serostatus (20%) and history of sexual violence (17%). Although temporal relationships are difficult to ascertain, history of sexual violence, HSV-2 infection and HIV infection are important predictors of infertility in Rwanda.


Event-related potentials and event-related oscillations during identity and facial emotional processing in schizophrenia.
Impairments in emotional recognition have been consistently reported in schizophrenic patients. The main aim of the present study was to evaluate time-sequenced responses in ERPs and event-related oscillations during emotional recognition of happiness and fear compared to facial identity recognition in schizophrenic patients (SCH) versus healthy controls (CON). Ten paranoid SCH and ten CON subjects performed three oddball paradigm tasks, evaluating face identity recognition and facial emotional recognition of happiness and fear. Event-related potentials and event-related theta and alpha oscillations were obtained for each task. N170 and P2 components appeared with higher amplitude in SCH than in CON at the occipital locations. An early prefrontally distributed P3a component was observed while doing the identity task with lower amplitude in SCH than in CON. Comparatively, P3b amplitude was lower in SCH than in CON over parietal leads in the identity and happiness tasks. Additionally, theta oscillations showed significantly lower RMS values in SCH between 250 and 500 ms post-stimuli in frontal and central regions. On the other hand, the grand-averaged alpha oscillations demonstrated higher RMS values in the occipital leads in SCH compared to CON and the opposite over the frontal regions. Results are interpreted in the framework of a functional disruption in the distributed neuronal networks involved both in facial identity and emotional recognition in schizophrenics as indexed by the brain oscillatory activity and related ERP components.


Metagenomic binning of a marine sponge microbiome reveals unity in defense but metabolic specialization.
Marine sponges are ancient metazoans that are populated by distinct and highly diverse microbial communities. In order to obtain deeper insights into the functional gene repertoire of the Mediterranean sponge Aplysina aerophoba, we combined Illumina short-read and PacBio long-read sequencing followed by un-targeted metagenomic binning. We identified a total of 37 high-quality bins representing 11 bacterial phyla and two candidate phyla. Statistical comparison of symbiont genomes with selected reference genomes revealed a significant enrichment of genes related to bacterial defense (restriction-modification systems, toxin-antitoxin systems) as well as genes involved in host colonization and extracellular matrix utilization in sponge symbionts. A within-symbionts genome comparison revealed a nutritional specialization of at least two symbiont guilds, where one appears to metabolize carnitine and the other sulfated polysaccharides, both of which are abundant molecules in the sponge extracellular matrix. A third guild of symbionts may be viewed as nutritional generalists that perform largely the same metabolic pathways but lack such extraordinary numbers of the relevant genes. This study characterizes the genomic repertoire of sponge symbionts at an unprecedented resolution and it provides greater insights into the molecular mechanisms underlying microbial-sponge symbiosis.


Association Between Television Viewing and Physical Activity in 10-Year-Old Brazilian Children.
Studies have found an association between television (TV) viewing and physical activity levels. The purpose of this study was to examine the association between TV viewing and physical activity in 10-year-old Brazilian children. The sample consisted of 485 children. Self-reported TV viewing on weekdays and weekends was assessed by questionnaire. An Actigraph GT3X+ accelerometer was used to monitor the range of physical activity intensities (including moderate-to-vigorous physical activity; MVPA), sedentary behavior (SB) and steps/day over 7 days. Daily MVPA was highest among children viewing TV <1 hour/day (69 min) compared with children viewing 1 to 2 hours/day (61 min), 3 to 4 hours/day (55 min) and ≥ 5 hours/day (59 min) on weekdays (P = .0015). Differences in MVPA were not observed across TV categories on weekends. The prevalence of reaching 60 min/day of MVPA and 12,000 steps/day on weekdays was significantly greater in children viewing ≤ 2 hours/day (51.7% and 23.5%, respectively) compared with those viewing > 2 hours/day (38.6%, P = .0058; and 15.1%, P = .0291, respectively). There was no difference in SB across TV viewing categories. Time spent in MVPA and the frequency of meeting MVPA guidelines were significantly higher among children viewing ≤ 2 hours/day of TV on weekdays compared with those viewing more.


Validation of a Modified Child-Turcotte-Pugh Classification System Utilizing Insulin-Like Growth Factor-1 for Patients with Hepatocellular Carcinoma in an HBV Endemic Area.
Recently, a modified insulin-like growth factor-1 (IGF)-Child-Turcotte-Pugh (CTP) classification was proposed to improve the original CTP classification. This study aimed to validate the new IGF-CTP classification system as a prognostic maker for patients with hepatocellular carcinoma (HCC) in a hepatitis B virus endemic area. We conducted a post-hoc analysis of a prospective cohort study. We used Harrell's C-index and U-statistics to compare the prognostic performance of both IGF-CTP and CTP classifications for overall survival. We evaluated the relationship between HCC stage and the four components of the IGF-CTP classification (serum levels of IGF-1, albumin, and total bilirubin and prothrombin time [PT]) using nonparametric trend analysis. We included a total of 393 patients in this study. In all, 55 patients died during the median follow-up of 59.1 months. There was a difference between IGF-CTP class and CTP class in 14% of patients. Overall, the IGF-CTP classification system had a higher prognostic value (C-index = 0.604, 95% confidence interval [CI] = 0.539-0.668) than the CTP system (C-index = 0.558, 95% CI = 0.501-0.614), but the difference was not statistically significant (P = .07 by U-statistics). A lower serum level of IGF-1 was related to a more advanced cancer stage (P < .01). The remaining components of the IGF-CTP classification were not significantly related to tumor stage (P = .11 for total bilirubin; P = .33 for albumin; and P = .39 for PT). The IGF-CTP classification was slightly better than the original CTP classification for predicting survival of patients with HCC in a chronic hepatitis B endemic area. This is most likely due to the fact that serum IGF-1 levels reflect underlying HCC status.


The Neighborhood of the Spike Gene Is a Hotspot for Modular Intertypic Homologous and Nonhomologous Recombination in Coronavirus Genomes.
Coronaviruses (CoVs) have very large RNA viral genomes with a distinct genomic architecture of core and accessory open reading frames (ORFs). It is of utmost importance to understand their patterns and limits of homologous and nonhomologous recombination, because such events may affect the emergence of novel CoV strains, alter their host range, infection rate, tissue tropism pathogenicity, and their ability to escape vaccination programs. Intratypic recombination among closely related CoVs of the same subgenus has often been reported; however, the patterns and limits of genomic exchange between more distantly related CoV lineages (intertypic recombination) need further investigation. Here, we report computational/evolutionary analyses that clearly demonstrate a substantial ability for CoVs of different subgenera to recombine. Furthermore, we show that CoVs can obtain-through nonhomologous recombination-accessory ORFs from core ORFs, exchange accessory ORFs with different CoV genera, with other viruses (i.e., toroviruses, influenza C/D, reoviruses, rotaviruses, astroviruses) and even with hosts. Intriguingly, most of these radical events result from double crossovers surrounding the Spike ORF, thus highlighting both the instability and mobile nature of this genomic region. Although many such events have often occurred during the evolution of various CoVs, the genomic architecture of the relatively young SARS-CoV/SARS-CoV-2 lineage so far appears to be stable.


Biomimicry for Regenerative Built Environments: Mapping Design Strategies for Producing Ecosystem Services.
: Built environment professionals must solve urgent and complex problems related to mitigating and adapting to climate change and biodiversity loss. Cities require redesign and retrofit so they can become complex systems that create rather than diminish ecological and societal health. One way to do this is to strategically design buildings and cities to generate and provide ecosystem services. This is an aspect of biomimicry, where whole ecosystems and their functions are emulated, in order to positively shift the ecological performance of buildings and urban settings. A small number of methodologies and frameworks for ecosystem services design have been proposed, but their use is not wide spread. A key barrier is the lack of translational work between ecology concepts and practical examples of ecosystem services design for a built environment context. In response, this paper presents research underpinning the creation of a qualitative relational diagram in an online interactive format that relates ecosystem services concepts to design strategies, concepts, technologies, and case studies in a format for use by built environment professionals. The paper concludes that buildings and whole cities should be expected to become active contributors to socio-ecological systems because, as the diagram shows, many strategies and technologies to enable this already exist.


The Association Between Reduced Inflammation and Cognitive Gains After Bariatric Surgery.
Bariatric surgery is associated with improved cognitive function, although the mechanisms are unclear. Elevated inflammation is common in obesity and associated with impaired cognition. Inflammation decreases after bariatric surgery, implicating it as a possible mechanism for cognitive improvement. The objective of this study was to examine whether reduced inflammation is a possible mechanism for postoperative cognitive improvement in bariatric surgery patients. Participants were 77 bariatric surgery patients who completed cognitive testing before surgery and 1 year postsurgery. Cognitive domains assessed were attention/executive function, language, and memory. High-sensitivity C-reactive protein (CRP) was assessed at both time points. Patients exhibited preoperative cognitive impairment, although improvements 1 year postsurgery were seen in both attention/executive function (mean [M; standard deviation {SD}]baseline = 53.57 [8.68] versus M (SD)follow-up= 60.32 [8.19]) and memory (M [SD]baseline= 44.96 [7.98] versus M [SD]follow-up= 51.55 [8.25]). CRP was elevated at baseline and fell into the normative range postsurgery (M [SD]baseline= 0.9 [0.7] versus M [SD]follow-up= 0.2 [0.3] mg/dl). Preoperative CRP was not associated with baseline cognitive function (β values = -0.10 to 0.02) and changes in CRP also did not correspond to changes in cognition postsurgery (β values = 0.02-0.11; p values > .05 for all domains). A trend was detected for smaller improvements in memory among participants with elevated baseline CRP (>0.30 mg/dl) versus those with normal levels (group × time: p = .083). Improvements in high-sensitivity CRP were not associated with postoperative cognitive benefits. Future studies are needed to explore other inflammatory markers and potential mechanisms of cognitive improvement after bariatric surgery, including improved glycemic control and neurohormone changes.


Association of Albuminuria and Estimated Glomerular Filtration Rate with Functional Performance Measures in Older Adults with Chronic Kidney Disease.
Chronic kidney disease (CKD) is increasingly common and disproportionately affects older adults. The contribution of kidney disease to the functional impairment noted in the elderly CKD population is unclear. This is a cross-sectional analysis of a hypertensive cohort of people aged ≥75 years from the Systolic Blood Pressure Intervention Trial. We evaluated estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) as predictors of 3 measures of functional status: EuroQol-5 Dimensional (EQ-5D) score, Falls Efficacy Scale (FES) score, and gait speed. Linear regression models were used to evaluate the associations between our independent variables and outcome measures. Our analysis included 2,620 participants, mean age of 79.9 (4.0) years. Unadjusted models showed that lower eGFR level and higher UACR level were associated with lower EQ-5D (p < 0.001 for both) and slower gait speed (p < 0.001 for both) and worse scores on FES (p = 0.032 and p = 0.039). In the fully adjusted models, higher levels of UACR remained significantly associated with lower EQ-5D scores and slower gait speed (p = 0.011 and p = 0.002, respectively). In contrast, level of eGFR was not associated with any functional outcome measures when accounting for covariates. In individuals aged ≥75 years, albuminuria and eGFR were associated with impairments in physical performance and self-reported functional status; however, only the association with albuminuria remained after adjusting for relevant demographics and comorbidities. Evaluation of albuminuria may provide an additional tool for identifying older individuals at risk for functional impairment.


Role of portal insulin delivery in the disappearance of intravenous glucose and assessment of insulin sensitivity.
The contribution of portal insulin delivery to the disappearance of glucose administered intravenously was assessed in the present study. Paired insulin-modified intravenous glucose tolerance tests (IVGTTs) were performed in dogs in which insulin was administered into the portal vein or into a peripheral vein. Peripheral insulin levels were matched in the paired IVGTTs by adjusting the portal insulin dose in proportion to first-pass hepatic insulin extraction. Two sets of IVGTTs were performed. In the first set, hepatic insulin extraction was assumed to be 50% (insulin doses of 0.03 U/kg portal and 0.015 U/kg peripheral; n = 6); in the second set, the assumed extraction rate was reduced to 33% (0.0225 U/kg portal and 0.015 U/kg peripheral; n = 8). In the second set of experiments, a control "zero" dose (no insulin injection) was also performed. For these latter three IVGTTs, the exogenous glucose bolus was labeled with 3-[3H]glucose (25 microCi) to separately assess insulin's effects on the rate of glucose disappearance (Rd) and endogenous glucose production (EGP). For the paired IVGTT based on 33% extraction, the area under the insulin curves after the portal insulin injection was within 2% of that observed with peripheral insulin injection (1,820 +/- 711 vs. 1,791 +/- 661 microU/ml min; P = 0.79). For these conditions, neither the glucose profiles nor the minimal model estimate of insulin sensitivity (S(I)) was significantly influenced by the higher portal insulin delivery (S(I): 3.69 +/- 0.56 vs. 3.35 +/- 0.60 10(-4) min(-1) per microU/ml; portal vs. peripheral; P > 0.05). Analysis of the 3-[3H]glucose tracer dynamics failed to reveal any differences in the portal versus peripheral insulin effect on glucose disappearance or production. We conclude that portal insulin delivery per se does not significantly affect insulin's ability to normalize plasma glucose during acute glucose challenges.


Regulation of cardiovascular development and integrity by the heart of glass-cerebral cavernous malformation protein pathway.
Cerebral cavernous malformations (CCMs) are human vascular malformations caused by mutations in three genes of unknown function: KRIT1, CCM2 and PDCD10. Here we show that the heart of glass (HEG1) receptor, which in zebrafish has been linked to ccm gene function, is selectively expressed in endothelial cells. Heg1(-/-) mice showed defective integrity of the heart, blood vessels and lymphatic vessels. Heg1(-/-); Ccm2(lacZ/+) and Ccm2(lacZ/lacZ) mice had more severe cardiovascular defects and died early in development owing to a failure of nascent endothelial cells to associate into patent vessels. This endothelial cell phenotype was shared by zebrafish embryos deficient in heg, krit1 or ccm2 and reproduced in CCM2-deficient human endothelial cells in vitro. Defects in the hearts of zebrafish lacking heg or ccm2, in the aortas of early mouse embryos lacking CCM2 and in the lymphatic vessels of neonatal mice lacking HEG1 were associated with abnormal endothelial cell junctions like those observed in human CCMs. Biochemical and cellular imaging analyses identified a cell-autonomous pathway in which the HEG1 receptor couples to KRIT1 at these cell junctions. This study identifies HEG1-CCM protein signaling as a crucial regulator of heart and vessel formation and integrity.


Novel Laccaria Species From Juglandaceae Forest in Panama With Notes on Their Ecology.
Since 2013 there have been 22 new species of Laccaria described worldwide. Only three of these represent species from the neotropics. In Panama, Laccaria is abundant in monodominant Oreomunnea mexicana (Juglandaceae) forests based on sporocarps and environmental sequencing of roots. This study uses a combination of morphological and phylogenetic evidence to document up to seven species of Laccaria from these forests, one previously described, three described as new, and three requiring more data before being formally described. Molecular data used for phylogenetic analysis include the nuclear ribosomal ITS and 28S regions, along with TEF1 and RPB2. Laccaria stellata, has previously been reported from O. mexicana cloud forests of Panama. Laccaria dallingii sp. nov., L. nitrophila sp. nov., and L. fortunensis sp. nov. are described as new based on morphology and phylogenetic analysis of multiple collections. A taxon referred to as "PAN sp3" is resolved sister to L. stellata. Phylogenetic analysis also resolved two separate clades of Panamanian Laccaria as sister to L. roseoalbescens, a species previously described from Mexico. These three taxa are not described in this paper as there is too little material from which to make effective morphological descriptions even though their placement in phylogenetic analysis identify them as being unique. Ecologically, all described species except for L. fortunensis were amplified from O. mexicana ectomycorrhizal root tips. L. nitrophila was one of the most recovered species from the roots of O. mexicana in a previous study, and it has been shown to respond positively to long term nitrogen addition. Our results expand the knowledge of Laccaria diversity for Central America and highlight that at least some species of Laccaria are nitrophilic in neotropical Juglandaceae forests as well as in temperate forests.


Spatial clustering of notified tuberculosis in Ethiopia: A nationwide study.
Tuberculosis (TB) remains a major health problem worldwide and in Ethiopia. This study aimed to investigate the spatial distributions of notified TB over the whole territory of Ethiopia and to quantify the role of health care access, environmental, socio-demographic, and behavioural factors associated with the clustering of TB. A spatial analysis was conducted using national TB data reported between June 2016 and June 2017 in Ethiopia. Spatial clustering of TB was explored using Moran's I statistic and the local indicator of spatial autocorrelation (LISA). A multivariate Poisson regression model was developed with a conditional autoregressive (CAR) prior structure and with posterior parameters estimated using Bayesian Markov chain Monte Carlo (MCMC) simulation with Gibbs sampling to investigate the drivers of the clustering. A total of 120,149 TB cases were reported from 745 districts in Ethiopia during the study period; 41,343 (34%) were bacteriologically confirmed new pulmonary TB and 33,997 (28%) were clinically diagnosed, new, smear-negative pulmonary TB patients. The nationwide annual incidence rate of notified TB was 112 per 100,000 population. The highest incidence was observed in three city administrative regions, namely Dire Dewa (348 cases per 100,000 population), Addis Ababa (262 per 100,000 population) and Harari (206 per 100,000 population), and the lowest incidence was observed in Somali region (51 per 100,000 population). High-high spatial clustering of notified TB was detected at Humera, Gog, and Surima district, and low-low clustering was detected in some districts located in the Somali region. Poor health care access (IRR = 0.78; 95%CI: 0.66, 0.90) and good knowledge about TB (IRR = 0.84; 95%CI: 0.73, 0.96) were negatively associated with the incidence of notified TB. Substantial spatial clustering of notified TB was detected at region, zone and district level in Ethiopia. Health care access and knowledge about TB was associated with incidence of TB. This study may provide policy makers target hotspot areas, where national control programs could be implemented more efficiently for the prevention and control of TB, and to address potential under-reporting in poor access areas.


Structural and functional properties of a probabilistic model of neuronal connectivity in a simple locomotor network.
Although, in most animals, brain connectivity varies between individuals, behaviour is often similar across a species. What fundamental structural properties are shared across individual networks that define this behaviour? We describe a probabilistic model of connectivity in the hatchling Xenopus tadpole spinal cord which, when combined with a spiking model, reliably produces rhythmic activity corresponding to swimming. The probabilistic model allows calculation of structural characteristics that reflect common network properties, independent of individual network realisations. We use the structural characteristics to study examples of neuronal dynamics, in the complete network and various sub-networks, and this allows us to explain the basis for key experimental findings, and make predictions for experiments. We also study how structural and functional features differ between detailed anatomical connectomes and those generated by our new, simpler, model (meta-model).


The measurement and monitoring of surgical adverse events.
Surgical adverse events contribute significantly to postoperative morbidity, yet the measurement and monitoring of events is often imprecise and of uncertain validity. Given the trend of decreasing length of hospital stay and the increase in use of innovative surgical techniques--particularly minimally invasive and endoscopic procedures--accurate measurement and monitoring of adverse events is crucial. The aim of this methodological review was to identify a selection of common and potentially avoidable surgical adverse events and to assess whether they could be reliably and validly measured, to review methods for monitoring their occurrence and to identify examples of effective monitoring systems for selected events. This review is a comprehensive attempt to examine the quality of the definition, measurement, reporting and monitoring of selected events that are known to cause significant postoperative morbidity and mortality. METHODS - SELECTION OF SURGICAL ADVERSE EVENTS: Four adverse events were selected on the basis of their frequency of occurrence and likelihood of evidence of measurement and monitoring: (1) surgical wound infection; (2) anastomotic leak; (3) deep vein thrombosis (DVT); (4) surgical mortality. Surgical wound infection and DVT are common events that cause significant postoperative morbidity. Anastomotic leak is a less common event, but risk of fatality is associated with delay in recognition, detection and investigation. Surgical mortality was selected because of the effort known to have been invested in developing systems for monitoring surgical death, both in the UK and internationally. Systems for monitoring surgical wound infection were also included in the review. METHODS - LITERATURE SEARCH: Thirty separate, systematic literature searches of core health and biomedical bibliographic databases (MEDLINE, EMBASE, CINAHL, HealthSTAR and the Cochrane Library) were conducted. The reference lists of retrieved articles were reviewed to locate additional articles. A matrix was developed whereby different literature and study designs were reviewed for each of the surgical adverse events. Each article eligible for inclusion was independently reviewed by two assessors. METHODS - CRITICAL APPRAISAL: Studies were appraised according to predetermined assessment criteria. Definitions and grading scales were assessed for: content, criterion and construct validity; repeatability; reproducibility; and practicality (surgical wound infection and anastomotic leak). Monitoring systems for surgical wound infection and surgical mortality were assessed on the following criteria: (1) coverage of the system; (2) whether or not denominator data were collected; (3) whether standard and agreed definitions were used; (4) inclusion of risk adjustment; (5) issues related to data collection; (6) postdischarge surveillance; (7) output in terms of feedback and wider dissemination. RESULTS - SURGICAL WOUND INFECTION: A total of 41 different definitions and 13 grading scales of surgical wound infection were identified from 82 studies. Definitions of surgical wound infection varied from presence of pus to complex definitions such as those proposed by the Centres for Disease Control in the USA. A small body of literature has been published on the content, criterion and construct validity of different definitions, and comparisons have been made against wound assessment scales and multidimensional indices. There are examples of comprehensive hospital-based monitoring systems of surgical wound infection, mainly under the auspices of nosocomial surveillance. To date, however, there is little evidence of systematic measurement and monitoring of surgical wound infection after hospital discharge. RESULTS - ANASTOMOTIC LEAK: Over 40 definitions of anastomotic leak were extracted from 107 studies of upper gastrointestinal, hepatopancreaticobiliary and lower gastrointestinal surgery. No formal evaluations were found that assessed the validity or reliability of definitions or severity scales of anastomotic leak. One definition was proposed during a national consensus workshop, but no evidence of its use was found in the surgical literature. The lack of a single definition or gold standard hampers comparison of postoperative anastomotic leak rates between studies and institutions. RESULTS - DEEP VEIN THROMBOSIS: Although a critical review of the DVT literature could not be completed within the realms of this review, it was evident that a number of new techniques for the detection and diagnosis of DVT have emerged in the last 20 years. The group recommends a separate review be undertaken of the different diagnostic tests to detect DVT. RESULTS - SURGICAL MORTALITY MONITORING SYSTEMS: The definition of surgical mortality is relatively consistent between monitoring systems, but duration of follow-up of death postdischarge varies considerably. The majority of systems report in-hospital mortality rates; only some have the potential to link deaths to national death registers. Risk assessment is an important factor and there should be a distinction between recording pre-intervention factors and postoperative complications. A variety of risk scoring systems was identified in the review. Factors associated with accurate and complete data collection include the employment of local, dedicated personnel, simple and structured prompts to ensure that clinical input is complete, and accurate and automated data capture and transfer. The use of standardised, valid and reliable definitions is fundamental to the accurate measurement and monitoring of surgical adverse events. This review found inconsistency in the quality of reporting of postoperative adverse events, limiting accurate comparison of rates over time and between institutions. The duration of follow-up for individual events will vary according to their natural history and epidemiology. Although risk-adjusted aggregated rates can act as screening or warning systems for adverse events, attribution of whether events are avoidable or preventable will invariably require further investigation at the level of the individual, unit or department. CONCLUSIONS - RECOMMENDATIONS FOR RESEARCH: (1) A single, standard definition of surgical wound infection is needed so that comparisons over time and between departments and institutions are valid, accurate and useful. Surgeons and other healthcare professionals should consider adopting the 1992 Centers for Disease Control (CDC) definition for superficial incisional, deep incisional and organ/space surgical site infection for hospital monitoring programmes and surgical audits. There is a need for further methodological research into the performance of the CDC definition in the UK setting. (2) There is a need to formally assess the reliability of self-diagnosis of surgical wound infection by patients. (3) There is a need to assess formally the reliability of case ascertainment by infection control staff. (4) Work is needed to create and agree a standard, valid and reliable definition of anastomotic leak which is acceptable to surgeons. (5) A systematic review is needed of the different diagnostic tests for the diagnosis of DVT. (6) The following variables should be considered in any future DVT review: anatomical region (lower limb, upper limb, pelvis); patient presentation (symptomatic, asymptomatic); outcome of diagnostic test (successfully completed, inconclusive, technically inadequate, negative); length of follow-up; cost of test; whether or not serial screening was conducted; and recording of laboratory cut-off values for fibrinogen equivalent units. (7) A critical review is needed of the surgical risk scoring used in monitoring systems. (8) In the absence of automated linkage there is a need to explore the benefits and costs of monitoring in primary care. (9) The growing potential for automated linkage of data from different sources (including primary care, the private sector and death registers) needs to be explored as a means of improving the ascertainment of surgical complications, including death. This linkage needs to be within the terms of data protection, privacy and human rights legislation. (10) A review is needed of the extent of the use and efficiency of routine hospital data versus special collections or voluntary reporting.


Preventing tuberculosis in children receiving anti-TNF treatment.
Anti-tumor necrosis factor (TNF) treatment has been a breakthrough in the management of juvenile idiopathic arthritis (JIA). However, they are associated with a significant risk of tuberculosis. We evaluated JIA patients who received etanercept treatment from an eastern Mediterranean country with moderate tuberculosis frequency. JIA patients under anti-TNF treatment, etanercept, were enrolled to the study. Chest X-rays, Tuberculin Skin Test (TST), clinical histories, family screening, and physical examinations were reviewed retrospectively. If TST was above 10 mm in a patient with one Bacillus Calmette-Guerin, cultures and, if needed, thorax computerized tomography were obtained. These patients received 1-2 months of isoniazid (INH) treatment which was followed by an INH prophylaxis for a period of 9 months while etanercept treatment was started. All were re-evaluated within 3 months intervals. A total of 36 patients under etanercept treatment were enrolled to the study. Mean age of the patients was 14.00 years (range 4-22 years). Median duration of disease was 36.00 months (range 4-216 months). Median duration of etanercept therapy was 11.5 months (3-48 months) at final evaluation. Seven patients had an initial TST score above 10 mm. All received INH treatment as outlined above. They had normal examinations and X-rays during followup. With proper initial evaluation, anti-TNF treatment is safe even in countries where tuberculosis is moderately frequent. An initial 1-2 months of INH treatment followed by chemoprophylaxis for 9 months is suggested for children with a TST of >10 mm.


Patient outcomes from symptomatic intracerebral hemorrhage after stroke thrombolysis.
To assess the impact of symptomatic intracerebral hemorrhage (sICH) on outcome of thrombolysis-treated ischemic stroke patients, as additional to recognized prognosticators. The study cohort included 985 ischemic stroke patients treated with IV thrombolysis at the Helsinki University Central Hospital (1995-2008). In a multivariable model adjusted for baseline stroke severity, age, onset-to-treatment time, baseline glucose, hyperdense cerebral artery sign, and early infarct signs on baseline imaging, and prior modified Rankin Scale (mRS), we calculated risk ratios (RRs) of patients with sICH (separately per Safe Implementation of Thrombolysis in Stroke[SITS]-Monitoring Study, European Cooperative Acute Stroke Study II [ECASS-II], and National Institute of Neurological Disorders and Stroke [NINDS] definitions) for poor 3-month outcome (mRS 3-6) and mortality. Receiver operating characteristic (ROC) curve and integrated discrimination improvement (IDI) evaluated impact of sICH on outcome. Internal cross-validation of the model was done with bootstrap statistics. The frequency of sICH was 2.1% (SITS), 7.0% (ECASS-II), and 9.4% (NINDS). RRs for poor and fatal outcome, respectively, were 1.7 and 4.8 (SITS), 1.6 and 3.8 (ECASS-II), and 1.6 and 3.4 (NINDS). In IDI analyses, sICH improved prediction model for 3-month mRS of 3-6 and 4-6, respectively, by 1.4% and 3.0% (SITS), 4.0% and 5.9% (ECASS-II), and 4.7% and 6.1% (NINDS). In case of 3-month mRS 5-6 and mortality, it was 6.1% and 5.3% (SITS), 11.3% and 9.3% (ECASS-II), and 10.3% and 8.0% (NINDS). ROC analysis revealed similar results. Patients with sICH have increased risk of poor and fatal outcome. Compared with recognized stroke prognosticators, contribution of sICH is smaller. Definition-wise, ECASS-II- and NINDS-based sICH contribute relatively more; ECASS-II has the largest contribution to worst outcomes.


A rapidly-prototyped microfluidic device for size-based nucleic acid fractionation using isotachophoresis.
We present a novel microfluidic device for size-based nucleic acid (NA) fractionation using isotachophoresis (ITP) and an ionic spacer. Our rapid-prototyped laser-cut plastic device has easily modifiable channel dimensions, can process up to 10 μL of sample, and contains an in-line extraction reservoir for minimally-disruptive manual collection of size-fractionated NAs. We designed custom buffering reservoirs using 1 mL pipette tips to provide high buffering capacity and prevent bubbles from entering the microfluidic channels. We demonstrated the utility of the device by implementing a proof-of-concept assay in which NAs were preconcentrated (via ITP) and then segregated by size (using the ionic spacer and sieving matrix) to generate two separate fractions, the first comprised of small (<50 nt) NA, and the second comprised of NAs of all sizes. Through this approach, we demonstrated size-based fractionation of both DNA and RNA samples (a mixture of synthetic ssDNA molecules, and a commercially-available RNA molecular weight standard, respectively). Our results indicate that this simple, rapid (≤10 min), and label-free approach is a promising and cost-effective alternative to the commercially-available size-selection kits currently on the market. We discuss the design and features of the device, as well as challenges which must be met in the future in order to further improve its performance and utility.


Patient demographic and tumor characteristics influencing oncologist follow-up frequency in older breast cancer survivors.
Although recommendations for breast cancer follow-up frequency exist, current follow-up guidelines are standardized, without consideration of individual patient characteristics. Some studies suggest oncologists are using these characteristics to tailor follow-up recommendations, but it is unclear how this is translating into practice. The objective of this study was to examine current patterns of oncologist breast cancer follow-up and determine the association between patient and tumor characteristics and follow-up frequency. The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify stage I-III breast cancer patients diagnosed 2000-2007 (n = 39,241). Oncologist follow-up visits were defined using Medicare specialty provider codes and the linked AMA Masterfile. Multinomial logistic regression determined the association between patient and tumor characteristics and oncologist follow-up visit frequency. Younger age (p < 0.001), positive nodes (p < 0.001), estrogen receptor/progesterone receptor positivity (p < 0.001), and increasing treatment intensity (p < 0.001) were most strongly associated with more frequent follow-up. However, after accounting for these characteristics, significant variation in follow-up frequency was observed. In addition to patient factors, the number and types of oncologists involved in follow-up were associated with follow-up frequency (p < 0.001). Types of oncologists providing follow-up varied, with medical oncologists the sole providers of follow-up for 19-51 % of breast cancer survivors. Overall, 58 % of patients received surgical oncology, and 51 % undergoing radiation received radiation oncology follow-up, usually in combination with medical oncology. Significant variation in breast cancer follow-up frequency exists. Developing follow-up guidelines tailored for patient, tumor, and treatment characteristics while also providing guidance on who should provide follow-up has the potential to increase clinical efficiency.


Comprehensive analysis of alternative splicing in Digitalis purpurea by strand-specific RNA-Seq.
Digitalis purpurea (D. purpurea) is one of the most important medicinal plants and is well known in the treatment of heart failure because of the cardiac glycosides that are its main active compounds. However, in the absence of strand specific sequencing information, the post-transcriptional mechanism of gene regulation in D. purpurea thus far remains unknown. In this study, a strand-specific RNA-Seq library was constructed and sequenced using Illumina HiSeq platforms to characterize the transcriptome of D. purpurea with a focus on alternative splicing (AS) events and the effect of AS on protein domains. De novo RNA-Seq assembly resulted in 48,475 genes. Based on the assembled transcripts, we reported a list of 3,265 AS genes, including 5,408 AS events in D. purpurea. Interestingly, both glycosyltransferases and monooxygenase, which were involved in the biosynthesis of cardiac glycosides, are regulated by AS. A total of 2,422 AS events occurred in coding regions, and 959 AS events were located in the regions of 882 unique protein domains, which could affect protein function. This D. purpurea transcriptome study substantially increased the expressed sequence resource and presented a better understanding of post-transcriptional regulation to further facilitate the medicinal applications of D. purpurea for human health.


Choosing GnRH Antagonist Protocol Shows Improved Oocyte and Embryo Quality, Coherent with the Perifollicular Vascularity (PFV) in Assisted Reproductive Techniques.
The parent oocyte from which the embryo is derived, determines its quality and the perifollicular vascularity (PFV) determines the micro-environment of the developing ovum. The PFV correlates well with the follicular oxygenation, oocyte maturation and embryo viability. PFV is imaged with Power Doppler Ultrasound. To study and compare the association of the PFV of follicles with the quality of the oocytes and embryos in agonist and antagonist protocol, employed in Assisted Reproductive techniques (ART). A prospective observational study was conducted on 75 patients, who were recruited for ART cycles, out of which 25 were given the Agonist protocol and the remaining 50 received the Antagonist protocol. The patients underwent the stimulation protocol. The PFV of preovulatory follicles were studied with Transvaginal Power Doppler and graded. Each oocyte retrieved carried the same label of its parent follicle. Embryos were cultured. The embryologist was blinded. The oocyte and embryo quality were assessed and compared with the PFV of parent follicle. Follicles with grade 1 and 2 PFV were predominantly observed. The yield of oocytes was independent of PFV. The mean yield of good quality embryos in conjunction with the PFV of the parent follicle was found to be highly significant in both the groups. The antagonist group had statistically significant yield of mature oocytes and embryos, compared to the agonist group. Antagonist protocol had favourable outcomes compared with the agonist protocol. The retrieval of oocytes, even the mature ones and the yield of high grade embryos were found higher. As the PFV increased, the yield and overall pregnancy rates were higher. PFV as assessed by Power Doppler is a useful non-invasive biomarker of embryo quality and can be employed in conjunction with other biomarkers in ART to predict successful outcome.


Quantum mechanical calculation of electric fields and vibrational Stark shifts at active site of human aldose reductase.
Recent advance in biophysics has made it possible to directly measure site-specific electric field at internal sites of proteins using molecular probes with C = O or C≡N groups in the context of vibrational Stark effect. These measurements directly probe changes of electric field at specific protein sites due to, e.g., mutation and are very useful in protein design. Computational simulation of the Stark effect based on force fields such as AMBER and OPLS, while providing good insight, shows large errors in comparison to experimental measurement due to inherent difficulties associated with point charge based representation of force fields. In this study, quantum mechanical calculation of protein's internal electrostatic properties and vibrational Stark shifts was carried out by using electrostatically embedded generalized molecular fractionation with conjugate caps method. Quantum calculated change of mutation-induced electric field and vibrational Stark shift is reported at the internal probing site of enzyme human aldose reductase. The quantum result is in much better agreement with experimental data than those predicted by force fields, underscoring the deficiency of traditional point charge models describing intra-protein electrostatic properties.


Beyond the memory mechanism: person-selective and nonselective processes in recognition of personally familiar faces.
Special processes recruited during the recognition of personally familiar people have been assumed to reflect the rich episodic and semantic information that selectively represents each person. However, the processes may also include person nonselective ones, which may require interpretation in terms beyond the memory mechanism. To examine this possibility, we assessed decrease in differential activation during the second presentation of an identical face (repetition suppression) as an index of person selectivity. During fMRI, pictures of personally familiar, famous, and unfamiliar faces were presented to healthy subjects who performed a familiarity judgment. Each face was presented once in the first half of the experiment and again in the second half. The right inferior temporal and left inferior frontal gyri were activated during the recognition of both types of familiar faces initially, and this activation was suppressed with repetition. Among preferentially activated regions for personally familiar over famous faces, robust suppression in differential activation was exhibited in the bilateral medial and anterior temporal structures, left amygdala, and right posterior STS, all of which are known to process episodic and semantic information. On the other hand, suppression was minimal in the posterior cingulate, medial prefrontal, right inferior frontal, and intraparietal regions, some of which were implicated in social cognition and cognitive control. Thus, the recognition of personally familiar people is characterized not only by person-selective representation but also by nonselective processes requiring a research framework beyond the memory mechanism, such as a social adaptive response.


Plasmonic library based on substrate-supported gradiential plasmonic arrays.
We present a versatile approach to produce macroscopic, substrate-supported arrays of plasmonic nanoparticles with well-defined interparticle spacing and a continuous particle size gradient. The arrays thus present a "plasmonic library" of locally noncoupling plasmonic particles of different sizes, which can serve as a platform for future combinatorial screening of size effects. The structures were prepared by substrate assembly of gold-core/poly(N-isopropylacrylamide)-shell particles and subsequent post-modification. Coupling of the localized surface plasmon resonance (LSPR) could be avoided since the polymer shell separates the encapsulated gold cores. To produce a particle array with a broad range of well-defined but laterally distinguishable particle sizes, the substrate was dip-coated in a growth solution, which resulted in an overgrowth of the gold cores controlled by the local exposure time. The kinetics was quantitatively analyzed and found to be diffusion rate controlled, allowing for precise tuning of particle size by adjusting the withdrawal speed. We determined the kinetics of the overgrowth process, investigated the LSPRs along the gradient by UV-vis extinction spectroscopy, and compared the spectroscopic results to the predictions from Mie theory, indicating the absence of local interparticle coupling. We finally discuss potential applications of these substrate-supported plasmonic particle libraries and perspectives toward extending the concept from size to composition variation and screening of plasmonic coupling effects.


Running Mechanics and Metabolic Responses With Water Bottles and Bottle Belt Holders.
To determine whether differential kinematics, kinetics, rates of energy use, and cardiopulmonary responses occur during running with water bottles and bottle belt holders compared with running only. Trained runners (N = 42; age 27.2 [6.4] y) ran on an instrumented treadmill for 4 conditions in a randomized order: control run (CON), handheld full water bottle (FULL; 16.9 fluid oz; 454 g), handheld half-full water bottle (HALF; 8.4 fluid oz; 227 g), and waist-worn bottle belt holder (BELT; hydration belt; 676 g). Gas exchange was measured using a portable gas analyzer. Kinetic and kinematic responses were determined by standard 3-dimensional videographic techniques. Interactions of limb side (right and left) by study condition (CON, FULL, HALF, and BELT) were tested for rates of oxygen use and energy expenditure and kinematic and kinetic parameters. No significant limb-side × condition interactions existed for rates of oxygen use or energy expenditure. A significant interaction occurred with sagittal elbow flexion (P < .001). Transverse pelvic-rotation excursions differed on average 3.8° across conditions. The minimum sagittal hip-flexion moment was higher in the right leg in the HALF and BELT conditions compared with CON (P < .001). Carrying water by hand or on the waist does not significantly change the kinematics of running motion, rates of oxygen use and energy expenditure, or cardiopulmonary measures over short durations. Runners likely make adjustments to joint moments and powers that preserve balance and protect the lower-extremity joints while maintaining rates of oxygen use and energy expenditure.


Distinct modes of ubiquitination of peroxisome-targeting signal type 1 (PTS1) receptor Pex5p regulate PTS1 protein import.
Peroxisome targeting signal type-1 (PTS1) receptor, Pex5p, is a key player in peroxisomal matrix protein import. Pex5p recognizes PTS1 cargoes in the cytosol, targets peroxisomes, translocates across the membrane, unloads the cargoes, and shuttles back to the cytosol. Ubiquitination of Pex5p at a conserved cysteine is required for the exit from peroxisomes. However, any potential ubiquitin ligase (E3) remains unidentified in mammals. Here, we establish an in vitro ubiquitination assay system and demonstrate that RING finger Pex10p functions as an E3 with an E2, UbcH5C. The E3 activity of Pex10p is essential for its peroxisome-restoring activity, being enhanced by another RING peroxin, Pex12p. The Pex10p·Pex12p complex catalyzes monoubiquitination of Pex5p at one of multiple lysine residues in vitro, following the dissociation of Pex5p from Pex14p and the PTS1 cargo. Several lines of evidence with lysine-to-arginine mutants of Pex5p demonstrate that Pex10p RING E3-mediated ubiquitination of Pex5p is required for its efficient export from peroxisomes to the cytosol and peroxisomal matrix protein import. RING peroxins are required for both modes of Pex5p ubiquitination, thus playing a pivotal role in Pex5p shuttling.


Frequency-domain simulations of a negative-index material with embedded gain.
We solve the equations governing light propagation in a negative-index material with embedded nonlinearly saturable gain material using a frequency-domain model. We show that available gain materials can lead to complete loss compensation only if they are located in the regions where the field enhancement is maximal. We study the increased enhancement of the fields in the gain composite as well as in the metal inclusions and show analytically that the effective gain is determined by the average near-field enhancement.


Impact of acute kidney injury in elderly (≥80 years) patients undergoing percutaneous coronary intervention.
This study sought to investigate the prevalence and impact of acute kidney injury (AKI) in elderly patients undergoing percutaneous coronary intervention (PCI). AKI may complicate PCI and has been associated with worse outcomes. Data on AKI following PCI in elderly patients are scarce. A total of 458 elderly (≥80 years) patients undergoing PCI at Charité-University Medicine Berlin between January 2009 and December 2014 were stratified according to the presence/absence of AKI. The primary endpoint was all-cause mortality. The secondary endpoint was rate of major adverse cardiovascular events (MACE), a composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, and rehospitalization for heart failure. Median follow-up was 280 (interquartile range 22-1190) days. Of the 458 patients, 125 (27.3%) developed AKI following PCI. Age >90 years, congestive heart failure, and C-reactive protein at presentation emerged as independent predictors of AKI. All-cause mortality was 20.0% and 8.4% in patients with and without AKI (P = 0.001), and corresponding rates of MACE were 39.2% and 26.4% (P = 0.01), respectively. The occurrence of AKI was associated with an increased risk of all-cause mortality (adjusted HR 2.41, 95%CI 1.12-5.17, P = 0.02) and MACE (adjusted HR 1.75, 95%CI 1.15-2.67, P = 0.01). AKI occurs in a third of elderly (≥80 years) patients undergoing PCI and is associated with increased mortality. These findings underline the unmet clinical need to identify novel strategies for the prevention of AKI in this high-risk patient subset.


Association between depressive symptoms and adherence among adolescents living with HIV in the Republic of Congo: A cross sectional study.
The increasing availability of antiretroviral therapy (ART) worldwide is yet to result in decreasing HIV-related mortality among adolescents (10-19 years old) living with HIV (ALHIV) in part because of poor adherence. the poor adherence might itself be due to high level of depression. We assess the prevalence of depressive symptomatology and it's associated with adherence among ALHIV receiving ART care in Brazzaville and Pointe Noire, Republic of Congo (RoC).Adolescents aged 10 to 19 years, on antiretroviral therapy (ART), followed in the two Ambulatory Treatment Centers (ATC) in Brazzaville and Pointe Noire, RoC were included in this cross-sectional study. From April 19 to July 9, 2018, participants were administered face to face interviews using a standardized questionnaire that included the nine-item Patient Health Questionnaire (PHQ-9). Participants who reported failing to take their ART more than twice in the 7 days preceding the interview were classified as non-adherent. Bivariate and multivariable log-binomial models were used to estimate the prevalence ratio (PR) and 95% confidence interval (95%CI) assessing the strength of association between predictors and presence of depressive symptoms (PHQ-9 score ≥9).Overall, 135 adolescents represented 50% of ALHIV in active care at the 2 clinics were interviewed. Of those, 67 (50%) were male, 81 (60%) were 15 to 19 years old, 124 (95%) had been perinatally infected, and 71 (53%) knew their HIV status. Depressive symptoms were present in 52 (39%) participants and 78 (58%) were adherent. In univariate analyses, the prevalence of depressive symptoms was relative higher among participants who were not adherent compared to those who were (73% vs 33%; PR: 2.20 [95%CI: 1.42-3.41]). In multivariate analysis, after adjustment for report of been sexually active, alcohol drinking, age category (10-14 and 15-19), not in school, loss of both parents, the association between depression and adherence was strengthened (PR: 2.06 [95%CI: 1.23-3.45]).The prevalence of depressive symptoms in adolescents living with HIV is high and was strongly associated with poor adherence even after adjustment of potential confounders. Efforts to scale-up access to screening and management of depression among ALHIV in sub-Saharan is needed for them to realize the full of ART.


Possible Transpacific Contact on the Coast of Ecuador.
The earliest pottery-producing culture on the coast of Ecuador, the Valdivia culture, shows many striking similarities in decoration and vessel shape to pottery of eastern Asia. In Japan, resemblances are closest to the Middle Jomon period. Both early Valdivia and Middle Jomon are dated between 2000 and 3000 B.C. A transpacific contact from Asia to Ecuador during this time is postulated.


The role of distraction in improving the space available for the cord in cervical spondylosis.
This study analyzed the effects of distraction via strut graft insertion on the canal dimensions in spondylotic human cadaver cervical spines. Transverse and anteroposterior diameters and cross-sectional areas were measured by transverse computed tomography imaging before and after distraction without direct decompression. This experiment was designed to address whether distraction across the disc space without direct canal decompression can improve the space available for the cord. Smith-Robinson anterior discectomy and fusion have been shown to improve clinical symptoms of radiculopathy and myelopathy even in the absence of direct decompression. This has been postulated to be the result of gradual resorption of intruding osteophytes. However, the immediate effects of indirect distraction alone have not been previously investigated. Four cadaver spines from elderly donors were harvested intact. The transverse diameter, anteroposterior diameter, and cross-sectional area of the spinal canal were measured before and after discectomy and distraction via insertion of fibular strut graft by digitization of contiguous computed tomography scan slices. The spinal canal dimensions before distraction were found to vary in a sinusoidal pattern around the disc space, with the maximum measurements located at the pedicle and the minimum measurements at the spondylotic ridge above or below the disc space. Distraction via strut graft insertion significantly increased the anteroposterior diameter and cross-sectional area, but had a negligible effect on transverse diameter. Anterior discectomy and distraction with a strut graft can significantly improve the space available for the cord in cervical spondylosis. Osteophyte debridement, which risks iatrogenic injury to the cord, may not always be necessary for improving clinical radiculopathy and myelopathy.


The head-mounted microscope.
Microsurgical equipment has greatly advanced since the inception of the microscope into the operating room. These advancements have allowed for superior surgical precision and better post-operative results. This study focuses on the use of the Leica HM500 head-mounted microscope for the operating phonosurgeon. The head-mounted microscope has an optical zoom from 2× to 9× and provides a working distance from 300 mm to 700 mm. The headpiece, with its articulated eyepieces, adjusts easily to head shape and circumference, and offers a focus function, which is either automatic or manually controlled. We performed five microlaryngoscopic operations utilizing the head-mounted microscope with successful results. By creating a more ergonomically favorable operating posture, a surgeon may be able to obtain greater precision and success in phonomicrosurgery. Phonomicrosurgery requires the precise manipulation of long-handled cantilevered instruments through the narrow bore of a laryngoscope. The head-mounted microscope shortens the working distance compared with a stand microscope, thereby increasing arm stability, which may improve surgical precision. Also, the head-mounted design permits flexibility in head position, enabling operator comfort, and delaying musculoskeletal fatigue. A head-mounted microscope decreases the working distance and provides better ergonomics in laryngoscopic microsurgery. These advances provide the potential to promote precision in phonomicrosurgery.


Community general practitioner.
The attainment of quality in general practice entails explicit recognition of the public-health content of primary care. General practitioners should accept responsibility for auditing the state of the practice health, monitoring and controlling environmental disease, planning local services, auditing the effectiveness of preventive programmes, and evaluating the population effects of medical intervention. This requires specific training in the skills of population medicine, reallocation of scarce resources, and cooperation with existing public-health doctors. Eventual integration of community medicine and general practice is desirable.


Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage.
Caenorhabditis elegans is an alternative in vivo model that is being successfully used to assess the pharmacological and toxic effects of drugs. The exponential growth of nanotechnology requires the use of alternative in vivo models to assess the toxic effects of theses nanomaterials. The use of polymeric nanocapsules has shown promising results for drug delivery. Moreover, these formulations have not been used in cases of intoxication, such as in treatment of paraquat (PQ) poisoning. Thus, the use of drugs with properties improved by nanotechnology is a promising approach to overcome the toxic effects of PQ. This research aimed to evaluate the absorption of rhodamine B-labeled melatonin (Mel)-loaded lipid-core nanocapsules (LNC) by C. elegans, the application of this model in nanotoxicology, and the protection of Mel-LNC against PQ damage. The formulations were prepared by self-assembly and characterized by particle sizing, zeta potential, drug content, and encapsulation efficiency. The results demonstrated that the formulations had narrow size distributions. Rhodamine B-labeled Mel-LNC were orally absorbed and distributed in the worms. The toxicity assessment of LNC showed a lethal dose 50% near the highest dose tested, indicating low toxicity of the nanocapsules. Moreover, pretreatment with Mel-LNC significantly increased the survival rate, reduced the reactive oxygen species, and maintained the development in C. elegans exposed to PQ compared to those worms that were either untreated or pretreated with free Mel. These results demonstrated for the first time the uptake and distribution of Mel-LNC by a nematode, and indicate that while LNC is not toxic, Mel-LNC prevents the effects of PQ poisoning. Thus, C. elegans may be an interesting alternative model to test the nanocapsules toxicity and efficacy.


Perspectives of Medical Specialists on Sharing Decisions in Cancer Care: A Qualitative Study Concerning Chemotherapy Decisions With Patients With Recurrent Glioblastoma.
In cancer care, difficult decisions concerning advanced treatment need to be made, weighing possible life prolongation against harmful side effects. Treatment is frequently started, showing the need to explore how decisions are made. Little is known about the perspectives of physicians on sharing decision making with patients. This qualitative study aimed to describe the perspectives of medical specialists on the decision-making process with patients with glioblastoma concerning starting new treatment. Qualitative interviews were held with medical specialists. One focus group was organized with medical professionals. Their opinions about elements of shared decision making and the applicability in the context of patients with glioblastoma were assessed. The topic list for the focus group was based on the analysis of the interviews. Qualitative analysis of the transcripts was performed by three researchers independently. Medical specialists considered shared decision making to be important; however, they did not adhere to its elements. Stopping treatment was not considered equal to continuing treatment. Exploration of the patients' wishes was done implicitly, and shared responsibility for the decision was not highly recognized. The main barriers to shared decision making were preferences of both patients and specialists for starting or continuing treatment and assumptions of physicians about knowing what patients want. Medical specialists recognized the importance of patient involvement but experienced difficulty in sharing decision making in practice. Elements of shared decision making are partly followed but do not guide decision making. To improve cancer care, education of medical specialists and adjustment to the elements are needed to involve patients.


SynCardia: the total artificial heart.
The SynCardia total artificial heart (TAH) currently provides the most definitive option for patients with biventricular failure who are not candidates for isolated left ventricular (LV) assist device placement. The techniques for implantation are adaptable to almost all patients with advanced heart failure, including those with severe biventricular cardiomyopathy, complex congenital heart disease, failed LV assist devices, failed transplantations, and acquired structural heart defects that have failed or are not amenable to conventional surgical treatment. Over the years, the implantation technique has evolved in order to minimize the surgical invasiveness of the procedure, in anticipation of additional future surgery. Meticulous hemostasis with double layer sutures, use of Gore-Tex sheets around the TAH and the pericardial cavity, and use of tissue expanders to avoid contraction of pericardial cavity around the device are discussed in detail in the following report. Additionally, we will provide our experience with implantation of TAH in various challenging scenarios, such as patients with a small chest cavity, congenital heart defects, and simultaneous use of extracorporeal membrane oxygenation (ECMO).


Smoldering (asymptomatic) multiple myeloma: current diagnostic criteria, new predictors of outcome, and follow-up recommendations.
To provide an overview on smoldering (asymptomatic) multiple myeloma (SMM) including current diagnostic criteria, predictors of progression, pattern of progression, and outcome. A comprehensive review of the literature on risk factors for progression, treatment attempts to delay progression and outcome in patients with SMM. The risk factors for progression of SMM include: plasma cell mass including M-protein size and percentage of bone marrow clonal plasma cells (BMPC), abnormal free light chain ratio, proportion of phenotypically abnormal BMPC, immunoparesis, evolution pattern (evolving v nonevolving), and pattern of magnetic resonance imaging abnormalities. Most patients with SMM progress with anemia and/or skeletal involvement. Immediate therapy with cytotoxic agents, such as melphalan/prednisone has not resulted in improved outcome. Patients should not be treated until progressive disease with end-organ damage occurs. Increasing anemia is the most reliable indicator of progression. These recently recognized predictors of outcome may be helpful for better disease monitoring and for investigation of new treatment approaches. Thus, recommendations for follow-up every to 3 to 6 months depending on the risk of progression are suggested, and clinical trials with new noncytotoxic biologically derived agents to delay progression, particularly in high-risk patients, are ongoing.