A new workflow for the microbiological diagnosis of febrile neutropenia in patients with a central venous catheter.
We aimed to improve the microbial diagnosis of first episodes of febrile neutropenia (FEFNs) since <30% of episodes are microbiologically documented. Consequently patients are usually treated by empirical antibiotic therapy. A prospective study evaluated a new workflow combining: (i) one 40 mL blood culture (BC) sampled from the central venous catheter; (ii) immediate incubation in an automated BC system on the ward; (iii) direct detection of microbial DNA in blood; and (iv) identification and susceptibility testing using rapid methods performed directly on positive BC bottles. Patients were also sampled for the standard workflow with two BC sets incubated in the central laboratory and assessed by classical procedures. One hundred and twenty consecutive FEFNs were included (February 2008-March 2009). The new workflow was as sensitive as the standard workflow, with BC positivity rates of 30% (36/120) and 28% (34/120), respectively (McNemar's χ(2) =0.67, P=0.41). Direct DNA detection was positive in nine episodes (7.5%) that were also positive in BC. The new workflow provided microbiological results significantly earlier than the standard workflow, with a shorter time to BC positivity (median 12 h 31 min, range 7 h 55 min-25 h 37 min versus median 13 h 01 min, range 9 h 31 min-43 h 33 min, P=0.004) and shorter turnaround times for identification and susceptibility testing, with most of the results obtained <24 h after BC sampling. We retrospectively estimated that the new workflow would lead to earlier adequacy of antimicrobial therapy in 30% of documented cases. Our new process improved the microbiological diagnosis in FEFNs. Cost effectiveness needs to be tested.


Grommets (ventilation tubes) for hearing loss associated with otitis media with effusion in children.
Otitis media with effusion (OME), or 'glue ear', is very common in children, especially between the ages of one and three years with a prevalence of 10% to 30% and a cumulative incidence of 80% at the age of four years. OME is defined as middle ear effusion without signs or symptoms of an acute infection. OME may occur as a primary disorder or as a sequel to acute otitis media. The functional effect of OME is a conductive hearing level of about 25 to 30 dB associated with fluid in the middle ear. Both the high incidence and the high rate of spontaneous resolution suggest that the presence of OME is a natural phenomenon, its presence at some stage in childhood being a normal finding. Notwithstanding this, some children with OME may go on to develop chronic otitis media with structural changes (tympanic membrane retraction pockets, erosion of portions of the ossicular chain and cholesteatoma), language delays and behavioural problems. It remains uncertain whether or not any of these findings are direct consequences of OME. The most common medical treatment options include the use of decongestants, mucolytics, steroids, antihistamines and antibiotics. The effectiveness of these therapies has not been established. Surgical treatment options include grommet (ventilation or tympanostomy tube) insertion, adenoidectomy or both. Opinions regarding the risks and benefits of grommet insertion vary greatly. The management of OME therefore remains controversial. To assess the effectiveness of grommet insertion compared with myringotomy or non-surgical treatment in children with OME. The outcomes studied were (i) hearing level, (ii) duration of middle ear effusion, (iii) well-being (quality of life) and (iv) prevention of developmental sequelae possibly attributable to the hearing loss (for example, impairment in impressive and expressive language development (measured using standardised tests), verbal intelligence, and behaviour). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2003), MEDLINE (1966 to 2003), EMBASE (1973 to 2003) and reference lists of all identified studies. The date of the last systematic search was March 2003, and personal non-systematic searches have been performed up to August 2004. Randomised controlled trials (RCTs) evaluating the effect of grommets on hearing, duration of effusion, development of language, cognition, behaviour or quality of life. Only studies using common types of grommets (mean function time of 6 to 12 months) were included. Data from studies were extracted by two reviewers and checked by the other reviewers. Children treated with grommets spent 32% less time (95% confidence interval (CI) 17% to 48%) with effusion during the first year of follow-up. Treatment with grommets improved hearing levels, especially during the first six months. In the randomised controlled trials that studied the effect of grommet insertion alone, the mean hearing levels improved by around 9 dB (95% CI 4 dB to 14 dB) after the first six months, and 6 dB (95% CI 3 dB to 9 dB) after 12 months. In the randomised controlled trials that studied the combined effect of grommets and adenoidectomy, the additional effect of the grommets on hearing levels was improvement by 3 to 4 dB (95% CI 2 dB to 5 dB) at six months and about 1 to 2 dB (95% CI 0 dB to 3 dB) at 12 months. Ears treated with grommets had an additional risk for tympanosclerosis of 0.33 (95% CI 0.21 to 0.45) one to five years later. In otherwise healthy children with long-standing OME and hearing loss, early insertion of grommets had no effect on language development or cognition. One randomised controlled trial in children with OME more than nine months, hearing loss and disruptions to speech, language, learning or behaviour showed a very marginal effect of grommets on comprehensive language. The benefits of grommets in children appear small. The effect of grommets on hearing diminished during the first year. Potentially adverse effects on the tympanic membrane are common after grommet insertion. Therefore an initial period of watchful waiting seems to be an appropriate management strategy for most children with OME. As no evidence is yet available for the subgroups of children with speech or language delays, behavioural and learning problems or children with defined clinical syndromes (generally excluded from the primary studies included in this review), the clinician will need to make decisions regarding treatment for such children based on other evidence and indications of disability related to hearing impairment. This review does not resolve the discrepancy between parental and clinical observation of a beneficial treatment effect and the results in the reviewed RCT showing only a short-term effect on hearing and virtually no effect on development. Is the perceived, often dramatic, effect of grommets only a short-term one? Are some children more sensitive to OME-related hearing loss than others? If so, how do we identify them?Further research should focus upon indications. Studies should use sufficiently large sample sizes to show significant interactions. There is a need to determine the most suitable variables and appropriate "softer" outcomes to be the subject of these interaction tests. Interesting options include measures of speech-in-noise and binaural hearing. The generally modest results in the trials which are included in this review should make it easier to justify randomisation of more severely affected and higher-risk children in appropriately constructed trials. Randomised controlled trials are necessary in these children before more detailed conclusions about the effectiveness of grommets can be drawn.


Cerebrospinal fluid lactate dehydrogenase levels in early stroke and transient ischemic attacks.
We examined the concentrations of lactate dehydrogenase in the cerebrospinal fluid of 25 patients with strokes and 15 patients with transient ischemic attacks less than or equal to 8 hours after the onset of the vascular event and in a control group of 21 patients. We found significantly higher concentrations in the stroke patients (40.9 +/- 14.5 units/l) than in the transient ischemic attack patients (11.8 +/- 2.9 units/l, p less than 0.001) and the controls (11.2 +/- 6.7 units/l, p less than 0.001). Among the stroke patients, we found a significantly higher lactate dehydrogenase concentration in those with cortical strokes (n = 12, 50 +/- 12.3 units/l) than in those with lacunar white matter infarcts (n = 5, 26.4 +/- 6.5 units/l; p less than 0.001) and those with basal ganglia infarcts (n = 8, 36.37 +/- 11.7 units/l; p less than 0.05). Our study offers a supplementary examination for diagnosing cortical or subcortical infarction during the early stage of the event, with the possibility of distinguishing precisely stroke from transient ischemic attack during the first hours after onset of the event.


Procedural sedation in the acute care setting.
Many patients require sedation during diagnostic or therapeutic procedures. Ideally, procedural sedation minimizes the patient's awareness and discomfort while maintaining the patient's safety. Appropriate monitoring by trained personnel is the key to successful procedural sedation. These techniques should be used only by health care professionals skilled in managing complications, including cardiorespiratory compromise. It is important to take a complete history and perform a thorough physical examination, paying special attention to the selection of pharmacologic agents. Common sedative agents include etomidate, ketamine, fentanyl, and midazolam. These have become the agents of choice for procedural sedation because of their ease of use, predictable action, and excellent safety profiles. All patients requiring procedural sedation should be monitored by qualified staff at the bedside until they have recovered to an age-appropriate baseline mental status and function.


Visualizing a Moving Target: A Design Study on Task Parallel Programs in the Presence of Evolving Data and Concerns.
Common pitfalls in visualization projects include lack of data availability and the domain users' needs and focus changing too rapidly for the design process to complete. While it is often prudent to avoid such projects, we argue it can be beneficial to engage them in some cases as the visualization process can help refine data collection, solving a "chicken and egg" problem of having the data and tools to analyze it. We found this to be the case in the domain of task parallel computing where such data and tooling is an open area of research. Despite these hurdles, we conducted a design study. Through a tightly-coupled iterative design process, we built Atria, a multi-view execution graph visualization to support performance analysis. Atria simplifies the initial representation of the execution graph by aggregating nodes as related to their line of code. We deployed Atria on multiple platforms, some requiring design alteration. We describe how we adapted the design study methodology to the "moving target" of both the data and the domain experts' concerns and how this movement kept both the visualization and programming project healthy. We reflect on our process and discuss what factors allow the project to be successful in the presence of changing data and user needs.


Applauding with closed hands: neural signature of action-sentence compatibility effects.
Behavioral studies have provided evidence for an action-sentence compatibility effect (ACE) that suggests a coupling of motor mechanisms and action-sentence comprehension. When both processes are concurrent, the action sentence primes the actual movement, and simultaneously, the action affects comprehension. The aim of the present study was to investigate brain markers of bidirectional impact of language comprehension and motor processes. Participants listened to sentences describing an action that involved an open hand, a closed hand, or no manual action. Each participant was asked to press a button to indicate his/her understanding of the sentence. Each participant was assigned a hand-shape, either closed or open, which had to be used to activate the button. There were two groups (depending on the assigned hand-shape) and three categories (compatible, incompatible and neutral) defined according to the compatibility between the response and the sentence. ACEs were found in both groups. Brain markers of semantic processing exhibited an N400-like component around the Cz electrode position. This component distinguishes between compatible and incompatible, with a greater negative deflection for incompatible. Motor response elicited a motor potential (MP) and a re-afferent potential (RAP), which are both enhanced in the compatible condition. The present findings provide the first ACE cortical measurements of semantic processing and the motor response. N400-like effects suggest that incompatibility with motor processes interferes in sentence comprehension in a semantic fashion. Modulation of motor potentials (MP and RAP) revealed a multimodal semantic facilitation of the motor response. Both results provide neural evidence of an action-sentence bidirectional relationship. Our results suggest that ACE is not an epiphenomenal post-sentence comprehension process. In contrast, motor-language integration occurring during the verb onset supports a genuine and ongoing brain motor-language interaction.


Barriers to healthcare utilization in fatiguing illness: a population-based study in Georgia.
The purpose of this study was to determine the prevalence of barriers to healthcare utilization in persons with fatiguing illness and describe its association with socio-demographics, the number of health conditions, and frequency of healthcare utilization. Furthermore, we sought to identify what types of barriers interfered with healthcare utilization and why they occurred. In a cross-sectional population-based survey, 780 subjects, 112 of them with chronic fatigue syndrome (CFS), completed a healthcare utilization questionnaire. Text analysis was used to create the emerging themes from verbatim responses regarding barriers to healthcare utilization. Multiple logistic regression was performed to examine the association between barriers to healthcare utilization and other factors. Forty percent of subjects reported at least one barrier to healthcare utilization. Of 112 subjects with CFS, 55% reported at least one barrier to healthcare utilization. Fatiguing status, reported duration of fatigue, insurance, and BMI were significant risk factors for barriers to healthcare utilization. After adjusting for socio-demographics, medication use, the number of health problems, and frequency of healthcare utilization, fatiguing status remained significantly associated with barriers to healthcare utilization. Subjects with CFS were nearly 4 times more likely to forego needed healthcare during the preceding year than non-fatigued subjects while those with insufficient fatigue (ISF) were nearly 3 times more likely.Three domains emerged from text analysis on barriers to healthcare utilization: 1) accessibility; 2) knowledge-attitudes-beliefs (KABs); and, 3) healthcare system. CFS and reported duration of fatigue were significantly associated with each of these domains. Persons with CFS reported high levels of healthcare utilization barriers for each domain: accessibility (34%), healthcare system (25%), and KABs (19%). In further examination of barrier domains to healthcare utilization, compared to non-fatigued persons adjusted ORs for CFS having "accessibility", "KAB" and "Healthcare System" barrier domains decreased by 40%, 30%, and 19%, respectively. Barriers to healthcare utilization pose a significant problem in persons with fatiguing illnesses. Study results suggested two-fold implications: a symptom-targeted model focusing on symptoms associated with fatigue; and an interactive model requiring efforts from patients and providers to improve interactions between them by reducing barriers in accessibility, KABs, and healthcare system.


Reduced N-alkyl substituted bis(imino)pyridine cobalt complexes: molecular and electronic structures for compounds varying by three oxidation states.
The stepwise 1-3 electron reduction of the N-alkyl substituted bis(imino)pyridine cobalt dichloride complexes, ((R)APDI)CoCl(2), was studied where (R)APDI = 2,6-(RN=CMe)(2)C(5)H(3)N, R = C(6)H(11) (Cy), CHMe(2) ((i)Pr). One electron reduction with either zinc metal or NaBEt(3)H furnished the bis(imino)pyridine cobalt monochloride compounds, ((R)APDI)CoCl. X-ray diffraction on the ((iPr)APDI)CoCl derivative established a distortion from square planar geometry where the chloride ligand is lifted out of the idealized cobalt-chelate plane. Superconducting Quantum Interference Device (SQUID) magnetometry on both compounds established spin crossover behavior with an S = 1 state being predominant at room temperature. Computational studies, in combination with experimental results, establish that the triplet spin isomer arises from a high spin Co(II) center (S(Co) = 3/2) antiferromagnetically coupled to a bis(imino)pyridine chelate radical anion, [PDI](-) (S(PDI) = 1/2). At lower temperatures, the Co(II) ion undergoes a spin transition to the low spin form (S(Co) = 1/2) and antiferromagnetic coupling gives rise to the observed diamagnetic ground state. Replacing the chloride ligand with a methyl group, namely ((R)APDI)CoCH(3), also yielded distorted compounds, albeit less pronounced, that are diamagnetic at room temperature. Two electron reduction of the ((R)APDI)CoCl(2) derivatives with excess 0.5% sodium amalgam or 2 equiv of NaBEt(3)H furnished the bis(chelate)cobalt complexes, ((R)APDI)(2)Co, while three electron reduction with 3 equiv of sodium naphthalenide yielded the cobalt dinitrogen anions, [Na(solv)(3)][((R)APDI)CoN(2)] (solv = THF, Et(2)O). Both bis(chelate) compounds were crystallographically characterized and determined to have S = 3/2 ground states by SQUID magnetometry and electron paramagnetic resonance (EPR) spectroscopy. Computational studies, in combination with metrical parameters determined from X-ray diffraction, establish a high spin (S(Co) = 3/2) cobalt(II) center with two bis(imino)pyridine chelate radical anions. Antiferromagnetic coupling between the two chelate centered radicals is mediated by a doubly occupied t(2g) cobalt orbital and gives rise to the observed overall quartet ground state.


Vibrational spectroscopy and imaging with non-resonant coherent anti-Stokes Raman scattering: double stimulated Raman scattering scheme.
We introduce a new coherent anti-Stokes Raman scattering (CARS) suppression scheme based on measuring a non-resonant CARS loss signal by three-beam (pump-Stokes-depletion) double stimulated Raman scattering (SRS) processes, which can be potentially of use for super-resolution Raman microscopy. In the converging configuration with employing both pump-depletion and Stokes-depletion SRS processes, we obtained approximately 94% suppression of non-resonant CARS signal, which is about 1.5 times more efficient than that with the parallel configuration with pump-Stokes and pump-depletion SRS processes. Such an enhanced suppression efficiency in the converging configuration results from a simultaneous loss of photons both in the pump and Stokes beams by double SRS processes, leading to an efficient suppression of the pump-Stokes-pump CARS signal. Based on the present method, we further propose two potential applications: (1) non-resonant background-free CARS imaging and (2) label-free super-resolution Raman imaging, and carry out simple numerical simulations to show their feasibility.


The low-resolution structure of human muscle aldolase.
The three-dimensional structure of human muscle aldolase has been solved at 5 A resolution with the use of two isomorphous heavy atom derivatives. The enzyme's four subunits are arranged about three mutually perpendicular intersecting twofold axes to form a compact spherical molecule. The subunit boundaries are clearly defined but a possible domain structure is not apparent in this preliminary electron density map.


Muscle aging and oxidative stress in wild-caught shrews.
Red-toothed shrews (Soricidae, subfamily Soricinae) are an intriguing model system to examine the free-radical theory of aging in wild mammals, given their short (<18months) lifespan and high mass-specific metabolic rates. As muscle performance underlies both foraging ability and predator avoidance, any age-related decline should be detrimental to fitness and survival. Muscle samples of water shrews (Sorex palustris) and sympatrically distributed short-tailed shrews (Blarina brevicauda) were therefore assessed for oxidative stress markers, protective antioxidant enzymes and apoptosis. Activity levels of catalase and glutathione peroxidase increased with age in both species. Similarly, Cu,Zn-superoxide dismutase isoform content was elevated significantly in older animals of both species (increases of 60% in the water shrew, 25% in the short-tailed shrew). Only one oxidative stress marker (lipid peroxidation) was age-elevated; the others were stable or declined (4-hydroxynonenal adducts and dihydroethidium oxidation). Glutathione peroxidase activity was significantly higher in the short-tailed shrew, while catalase activity was 2x higher in water shrews. Oxidative stress indicators were on average higher in short-tailed shrews. Apoptosis occurred in <1% of myocytes examined, and did not increase with age. Within the constraints of the sample size we found evidence of protection against elevated oxidative stress in wild-caught shrews.


Optomotor and neuropsychological performance in old age.
While a delayed initiation of visually guided saccades with increasing age has been documented in a number of studies, little research has been done on the control of antisaccades. The present study investigates aging effects on the control of visually guided saccades (prosaccades) and antisaccades as well as a selection of neuropsychological functions by the cross-sectional comparison of 14, 22, and 16 participants aged 20-35 years, 59-73 years, and 74-88 years, respectively. The geriatric and neurological status of the elder participants (including evidence from computed tomography, electroencephalography, and neurological soft signs) was assessed. In four task blocks of 200 trials each, pro- and antisaccades were elicited under the 200-ms-gap and overlap conditions. Left- and right-sided stimuli were presented in random order at 4 degrees, and the order of the task blocks was varied within each age group. In addition, the Wisconsin card-sorting test (WCST) and working memory, go-nogo discrimination, alertness, and stimulus-response incompatibility tests were administered. Participants aged 59-73 years exhibited widespread reductions of optomotor and neuropsychological performance, with greatest effect sizes of age differences in the optomotor parameters and the WCST measures. A further decay after the age of 73 years was discernible in those optomotor functions reflecting saccade disinhibition (in particular, directional errors during the antisaccade task and premature responses) and the performance in some neuropsychological tests. In line with previously published reports, variance in optomotor performance could be explained by two factors, accounting for a total of 76% of the age variance. Our results suggest that the investigation of saccade control may be a highly sensitive tool for neurodevelopmental aging research.


When does education matter? The protective effect of education for cohorts graduating in bad times.
Using Eurobarometer data, we document large variation across European countries in education gradients in income, self-reported health, life satisfaction, obesity, smoking and drinking. While this variation has been documented previously, the reasons why the effect of education on income, health and health behaviors varies is not well understood. We build on previous literature documenting that cohorts graduating in bad times have lower wages and poorer health for many years after graduation, compared to those graduating in good times. We investigate whether more educated individuals suffer smaller income and health losses as a result of poor labor market conditions upon labor market entry. We confirm that a higher unemployment rate at graduation is associated with lower income, lower life satisfaction, greater obesity, more smoking and drinking later in life. Further, education plays a protective role for these outcomes, especially when unemployment rates are high: the losses associated with poor labor market outcomes are substantially lower for more educated individuals. Variation in unemployment rates upon graduation can potentially explain a large fraction of the variance in gradients across different countries.


Emerging roles of the microbiome in cancer.
Gene-environment interactions underlie cancer susceptibility and progression. Yet, we still have limited knowledge of which environmental factors are important and how they function during tumorigenesis. In this respect, the microbial communities that inhabit our gastrointestinal tract and other body sites have been unappreciated until recently. However, our microbiota are environmental factors that we are exposed to continuously, and human microbiome studies have revealed significant differences in the relative abundance of certain microbes in cancer cases compared with controls. To characterize the function of microbiota in carcinogenesis, mouse models of cancer have been treated with antibiotics. They have also been maintained in a germfree state or have been colonized with specific bacteria in specialized (gnotobiotic) facilities. These studies demonstrate that microbiota can increase or decrease cancer susceptibility and progression by diverse mechanisms such as by modulating inflammation, influencing the genomic stability of host cells and producing metabolites that function as histone deacetylase inhibitors to epigenetically regulate host gene expression. One might consider microbiota as tractable environmental factors because they are highly quantifiable and relatively stable within an individual compared with our exposures to external agents. At the same time, however, diet can modulate the composition of microbial communities within our gut, and this supports the idea that probiotics and prebiotics can be effective chemoprevention strategies. The trajectory of where the current work is headed suggests that microbiota will continue to provide insight into the basic mechanisms of carcinogenesis and that microbiota will also become targets for therapeutic intervention.


Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts.
Human induced pluripotent stem (iPS) cells are currently used as powerful resources in regenerative medicine. During very early developmental stages, DNA methylation decreases to an overall low level at the blastocyst stage, from which embryonic stem cells are derived. Therefore, pluripotent stem cells, such as ES and iPS cells, are considered to have hypo-methylated status compared to differentiated cells. However, epigenetic mechanisms of "stemness" remain unknown in iPS cells derived from extra-embryonic and embryonic cells. We examined genome-wide DNA methylation (24,949 CpG sites covering 1,3862 genes, mostly selected from promoter regions) with six human iPS cell lines derived from human amniotic cells and fetal lung fibroblasts as well as two human ES cell lines, and eight human differentiated cell lines using Illumina's Infinium HumanMethylation27. A considerable fraction (807 sites) exhibited a distinct difference in the methylation level between the iPS/ES cells and differentiated cells, with 87.6% hyper-methylation seen in iPS/ES cells. However, a limited fraction of CpG sites with hypo-methylation was found in promoters of genes encoding transcription factors. Thus, a group of genes becomes active through a decrease of methylation in their promoters. Twenty-three genes including SOX15, SALL4, TDGF1, PPP1R16B and SOX10 as well as POU5F1 were defined as genes with hypo-methylated SS-DMR (Stem cell-Specific Differentially Methylated Region) and highly expression in iPS/ES cells. We show that DNA methylation profile of human amniotic iPS cells as well as fibroblast iPS cells, and defined the SS-DMRs. Knowledge of epigenetic information across iPS cells derived from different cell types can be used as a signature for "stemness" and may allow us to screen for optimum iPS/ES cells and to validate and monitor iPS/ES cell derivatives for human therapeutic applications.


Flagellar microtubule dynamics in Chlamydomonas: cytochalasin D induces periods of microtubule shortening and elongation; and colchicine induces disassembly of the distal, but not proximal, half of the flagellum.
To study the mechanisms responsible for the regulation of flagellar length, we examined the effects of colchicine and Cytochalasin D (CD) on the growth and maintenance of Chlamydomonas flagella on motile wild type cells as well as on pf 18 cells, whose flagella lack the central microtubules and are immobile. CD had no effect on the regeneration of flagella after deflagellation but it induced fully assembled flagella to shorten at an average rate of 0.03 microns-min. Cells remained fully motile in CD and even stubby flagella continued to move, indicating that flagellar shortening did not selectively disrupt machinery necessary for motility. To observe the effects of the drug on individual cells, pf 18 cells were treated with CD and flagella on cells were monitored by direct observation over a 5-hour period. Flagella on control pf 18 cells maintained their initial lengths throughout the experiment but flagella on CD-treated cells exhibited periods of elongation, shortening, and regrowth suggestive of the dynamic behavior of cytoplasmic microtubules observed in vitro and in vitro. Cells behaved individually, with no two cells exhibiting the same flagellar behavior at any given time although both flagella on any single cell behaved identically. The rate of drug-induced flagellar shortening and elongation in pf 18 cells varied from 0.08 to 0.17 microns-min-1, with each event occurring over 10-60-min periods. Addition of colchicine to wild type and pf 18 cells induced flagella to shorten at an average rate of 0.06 microns-min-1 until the flagella reached an average of 73% of their initial length, after which they exhibited no further shortening or elongation. Cells treated with colchicine and CD exhibited nearly complete flagellar resorption, with little variation in flagellar length among cells. The effects of these drugs were reversible and flagella grew to normal stable lengths after drug removal. Taken together, these results show that the distal half to one-third of the Chlamydomonas flagellum is relatively unstable in the presence of colchicine but that the proximal half to two-thirds of the flagellum is stable to this drug. In contrast to colchicine, CD can induce nearly complete flagellar microtubule disassembly as well as flagellar assembly. Flagellar microtubules must, therefore, be inherently unstable, and flagellar length is stabilized by factors that are sensitive, either directly or indirectly, to the effects of CD.


Machine Learning-Based Data Mining Method for Sentiment Analysis of the Sewol Ferry Disaster's Effect on Social Stress.
The Sewol Ferry Disaster which took place in 16th of April, 2014, was a national level disaster in South Korea that caused severe social distress nation-wide. No research at the domestic level thus far has examined the influence of the disaster on social stress through a sentiment analysis of social media data. Data extracted from YouTube, Twitter, and Facebook were used in this study. The population was users who were randomly selected from the aforementioned social media platforms who had posted texts related to the disaster from April 2014 to March 2015. ANOVA was used for statistical comparison between negative, neutral, and positive sentiments under a 95% confidence level. For NLP-based data mining results, bar graph and word cloud analysis as well as analyses of phrases, entities, and queries were implemented. Research results showed a significantly negative sentiment on all social media platforms. This was mainly related to fundamental agents such as ex-president Park and her related political parties and politicians. YouTube, Twitter, and Facebook results showed negative sentiment in phrases (63.5, 69.4, and 58.9%, respectively), entity (81.1, 69.9, and 76.0%, respectively), and query topic (75.0, 85.4, and 75.0%, respectively). All results were statistically significant (p < 0.001). This research provides scientific evidence of the negative psychological impact of the disaster on the Korean population. This study is significant because it is the first research to conduct sentiment analysis of data extracted from the three largest existing social media platforms regarding the issue of the disaster.


Exploring performance of, and attitudes to, Stop- and Mock-Before-You-Block in preventing wrong-side blocks.
We conducted an online survey to assess the career experiences of wrong side blocks, the practice of Stop-Before-You-Block, the recently described method of Mock-Before-You-Block and attitudes to these. Respondents were 208 anaesthetists across nine hospitals (173 consultants or Staff and Associate Specialist doctors'), representing 3623 years of collective anaesthetic practice. There had been a total of 62 wrong side blocks (by 51 anaesthetists and one current trainee). Predisposing factors for this were commonly ascribed to distractions (35 (69%), for example due to rushing or teaching), patient positioning (9 (18%)) or miscommunication (6 (12%)). Two (4%) respondents felt they had performed Stop-Before-You-Block too early; 62 (41%) of all respondents stated they performed Stop-Before-You-Block as early as preparing the skin or on arrival of the patient in the anaesthetic room, and not any later. Twenty (10%) respondents admitted to not performing Stop-Before-You-Block at all or only occasionally (including 5 (2%) who had performed a wrong side block). Mock-Before-You-Block was easily understood (by 169 out of 197 (86%)) and 14 out of 61 (23%) respondents felt it would have prevented the wrong side error in their case. However, free-text comments indicated that many anaesthetists were reluctant to use a method that interrupted their performance of the block. We conclude that considerable work is needed to achieve full compliance with Stop-Before-You-Block at the correct time.


Nanohydroxyapatite/poly(ester urethane) scaffold for bone tissue engineering.
Biodegradable viscoelastic poly(ester urethane)-based scaffolds show great promise for tissue engineering. In this study, the preparation of hydroxyapatite nanoparticles (nHA)/poly(ester urethane) composite scaffolds using a salt-leaching-phase inverse process is reported. The dispersion of nHA microaggregates in the polymer matrix were imaged by microcomputed X-ray tomography, allowing a study of the effect of the nHA mass fraction and process parameters on the inorganic phase dispersion, and ultimately the optimization of the preparation method. How the composite scaffold's geometry and mechanical properties change with the nHA mass fraction and the process parameters were assessed. Increasing the amount of nHA particles in the composite scaffold decreased the porosity, increased the wall thickness and consequently decreased the pore size. The Young's modulus of the poly(ester urethane) scaffold was improved by 50% by addition of 10 wt.% nHA (from 0.95+/-0.5 to 1.26+/-0.4 MPa), while conserving poly(ester urethane) viscoelastic properties and without significant changes in the scaffold macrostructure. Moreover, the process permitted the inclusion of nHA particles not only in the poly(ester urethane) matrix, but also at the surface of the scaffold pores, as shown by scanning electron microscopy. nHA/poly(ester urethane) composite scaffolds have great potential as osteoconductive constructs for bone tissue engineering.


A non-coding plastid DNA phylogeny of Asian Begonia (Begoniaceae): evidence for morphological homoplasy and sectional polyphyly.
Maximum likelihood and Bayesian analyses of non-coding plastid DNA sequence data based on a broad sampling of all major Asian Begonia sections (ndhA intron, ndhF-rpl32 spacer, rpl32-trnL spacer, 3977 aligned characters, 84 species) were used to reconstruct the phylogeny of Asian Begonia and to test the monophyly of major Asian Begonia sections. Ovary and fruit characters which are crucial in current sectional circumscriptions were mapped on the phylogeny to assess their utility in infrageneric classifications. The results indicate that the strong systematic emphasis placed on single, homoplasious characters such as undivided placenta lamellae (section Reichenheimia) and fleshy pericarps (section Sphenanthera), and the recognition of sections primarily based on a suite of plesiomorphic characters including three-locular ovaries with axillary, bilamellate placentae and dry, dehiscent pericarps (section Diploclinium), has resulted in the circumscription of several polyphyletic sections. Moreover, sections Platycentrum and Petermannia were recovered as paraphyletic. Because of the homoplasy of systematically important characters, current classifications have a certain diagnostic, but only poor predictive value. The presented phylogeny provides for the first time a reasonably resolved and supported phylogenetic framework for Asian Begonia which has the power to inform future taxonomic, biogeographic and evolutionary studies.


Early survival prediction in non-small cell lung cancer from PET/CT images using an intra-tumor partitioning method.
To explore prognostic and predictive values of a novel quantitative feature set describing intra-tumor heterogeneity in patients with lung cancer treated with concurrent and sequential chemoradiotherapy. Longitudinal PET-CT images of 30 patients with non-small cell lung cancer were analysed. To describe tumor cell heterogeneity, the tumors were partitioned into one to ten concentric regions depending on their sizes, and, for each region, the change in average intensity between the two scans was calculated for PET and CT images separately to form the proposed feature set. To validate the prognostic value of the proposed method, radiomics analysis was performed and a combination of the proposed novel feature set and the classic radiomic features was evaluated. A feature selection algorithm was utilized to identify the optimal features, and a linear support vector machine was trained for the task of overall survival prediction in terms of area under the receiver operating characteristic curve (AUROC). The proposed novel feature set was found to be prognostic and even outperformed the radiomics approach with a significant difference (AUROCSALoP = 0.90 vs. AUROCradiomic = 0.71) when feature selection was not employed, whereas with feature selection, a combination of the novel feature set and radiomics led to the highest prognostic values. A novel feature set designed for capturing intra-tumor heterogeneity was introduced. Judging by their prognostic power, the proposed features have a promising potential for early survival prediction.


Tumor rejection by local interferon gamma induction in established tumors is associated with blood vessel destruction and necrosis.
It has been shown that injecting a suspension of IFN-γ-secreting tumor cells results in their rejection. This effect has been attributed to IFN-γ preventing tumor stroma formation but not to a direct effect on the cancer cells. However, it is not known, which influence IFN-γ has on tumors with an established stroma. To address this question, the plasmacytoma cell line J558L was transduced with a vector allowing doxycycline-inducible IFN-γ gene expression. After the injection of the tumor cells into mice, IFN-γ was induced at different time points. Tumors did not grow when inducing IFN-γ immediately after tumor cell inoculation, while approximately half of the tumors were rejected when IFN-γ was induced in early established tumors within 2 weeks. Induction of IFN-γ 2-3 weeks after tumor cell inoculation was less efficient (0-17% rejection). IFN-γ induction in established tumors led to a reduction of CD146(+) endothelial cells and massive necrosis. Together, we show that vascularized tumors can be rejected by local IFN-γ expression, but that rejection of established tumors was less efficient over time. This suggests that transplanted tumors became less susceptible to local IFN-γ treatment the better they are established.


Captopril protects against myocardial injury induced by magnesium deficiency.
We have previously reported that antioxidant drug intervention protects against magnesium deficiency-induced myocardial lesions. In the present study, Golden Syrian male hamsters were fed either a magnesium-deficient diet or a magnesium-supplemented diet. Animals from each group received sulfhydryl-containing angiotensin converting enzyme inhibitors: captopril, epi-captopril (a stereoisomer of captopril), and zofenopril* (arginine blend of zofenopril containing a free SH group); another group of animals received the non-sulfhydryl-containing angiotensin converting enzyme inhibitor enalaprilat. The animals were killed after 14 days, and their hearts were isolated for morphological and morphometric analyses. Hematoxylin and eosin-stained sections were examined by a computer image analysis system for a morphometric determination of the severity of myocardial injury. Captopril reduced both the density of lesions, from 0.32 to 0.08 lesions/(mm2) (p less than 0.01), and the area fraction of lesions, from 7.42 x 10(-4) to 2.03 x 10(-4) lesion area/(mm2) (p less than 0.01), as well as the degree of inflammatory infiltration around the blood vessels. Epi-captopril and zofenopril* were virtually equipotent to captopril, but enalaprilat afforded only slight (nonsignificant) protection. These results indicate that a significant component of the protective effect of captopril in this model was attributable to its sulfhydryl moiety, rather than solely due to the inhibition of the angiotensin converting enzyme. These data further support our previous findings of possible free radical participation in cardiomyopathy due to magnesium deficiency.


Red state, blue state, flu state: media self-selection and partisan gaps in Swine flu vaccinations.
This study assesses the relationship between political partisanship and attitudes and behavior with respect to the H1N1 virus (swine flu) crisis of 2009 in general, and the U.S. mass vaccination program in particular. I argue that even seemingly nonpartisan political issues like public health are increasingly characterized by partisan polarization in public attitudes and that such polarization is attributable, at least partly, to the breakdown of the information commons that characterized the U.S. mass media from roughly the 1950s until the early 1990s. In its place has arisen an increasingly fragmented and niche-oriented media marketplace in which individuals are better able to limit their information exposure to attitudes and opinions that reinforce, rather than challenge, their preexisting beliefs. I test my argument against a variety of data sources, including opinion surveys and state-level swine flu vaccination rate data.


Work ability of employees in changing social services and health care organizations in Finland.
In this study, we examined the connection between organizational changes and employees own evaluations of their work ability. In early 2010, we asked employees (n = 2429) working in the Finnish social services and health care industry to identify all the organizational changes that had occurred at their workplaces over the previous two years, and to evaluate their own work ability and whether different statements related to the elements of work ability were true or false at the time of the survey. For our method of analysis, we used logistical regression analysis. In models adjusted for gender, age, marital status, professional education and managerial position, the respondents who had encountered organizational changes were at a higher risk of feeling that their work ability had decreased (OR = 1.49) than the respondents whose workplaces had not been affected by changes. Those respondents who had encountered organizational changes were also at a higher risk of feeling that several elements related to work ability had deteriorated. The risk of having decreased self-evaluated work ability was in turn higher among the respondents who stated they could not understand the changes than among those respondents who understood the changes (OR = 1.99). This was also the case among respondents who felt that their opportunities to be involved in the changes had been poor in comparison to those who felt that they had had good opportunities to be involved in the process (OR = 2.16). Our findings suggest that the organizational changes in social and health care may entail, especially when poorly executed, costs to which little attention has been paid until now. When implementing organizational changes, it is vital to ensure that the employees understand why the changes are being made, and that they are given the opportunity to take part in the implementation of these changes.


Validation and psychometric properties of the Russian version of the Touch Experiences and Attitudes Questionnaire (TEAQ-37 Rus).
It has been demonstrated that nurturing and affiliative touch is essential for human emotional and physical well-being throughout our entire life. Within the last 30 years a system of low-threshold mechanosensitive C fibers innervating the hairy skin was discovered and described; this system is hypothesized to represent the neurobiological substrate for the affective and rewarding properties of touch. This discovery opens new perspectives for multidisciplinary research of the role of affiliative social touch in health and disease, and calls for establishing novel psychometric tools assessing individual differences in the domain of affective touch. The main objective of the study was to construct and validate a Russian version of the Touch Experiences and Attitudes Questionnaire (TEAQ), a self-report measure recently developed to quantify individual experience and attitude to social and affective touch. A pool of 117 items was translated into Russian and all the items were assessed for appropriateness for Russian culture (232 participants). After exploring the factor structure (468 participants), we composed a 37-item questionnaire (TEAQ-37 Rus) characterized by good reliability and a clear 5-factor structure, covering the aspects of attitude to intimate touch, attitude to friendly touch, attitude to self-care, current intimate touch experiences, and childhood touch experiences. Confirmatory factor analysis (551 participants) has demonstrated good consistency and reliability of the 5-factor structure of the TEAQ-37 Rus. Cross-validation research demonstrated moderate positive correlations between predisposition to social touch and emotional intelligence; positive correlations with extraversion and openness facets of the Big Five personality model were also found. As predicted, participants with higher TEAQ-37 Rus scores rated all observed kinds of touch as more pleasant, with a particular preference for slow touch. We anticipate that this questionnaire will be a valuable tool for researchers of social touch, touch perception abnormalities, and the importance of touch experiences for emotional and mental health.


Assessing voluntary muscle activation with the twitch interpolation technique.
The twitch interpolation technique is commonly employed to assess the completeness of skeletal muscle activation during voluntary contractions. Early applications of twitch interpolation suggested that healthy human subjects could fully activate most of the skeletal muscles to which the technique had been applied. More recently, however, highly sensitive twitch interpolation has revealed that even healthy adults routinely fail to fully activate a number of skeletal muscles despite apparently maximal effort. Unfortunately, some disagreement exists as to how the results of twitch interpolation should be employed to quantify voluntary activation. The negative linear relationship between evoked twitch force and voluntary force that has been observed by some researchers implies that voluntary activation can be quantified by scaling a single interpolated twitch to a control twitch evoked in relaxed muscle. Observations of non-linear evoked-voluntary force relationships have lead to the suggestion that the single interpolated twitch ratio can not accurately estimate voluntary activation. Instead, it has been proposed that muscle activation is better determined by extrapolating the relationship between evoked and voluntary force to provide an estimate of true maximum force. However, criticism of the single interpolated twitch ratio typically fails to take into account the reasons for the non-linearity of the evoked-voluntary force relationship. When these reasons are examined, it appears that most are even more challenging to the validity of extrapolation than they are to the linear equation. Furthermore, several factors that contribute to the observed non-linearity can be minimised or even eliminated with appropriate experimental technique. The detection of small activation deficits requires high resolution measurement of force and careful consideration of numerous experimental details such as the site of stimulation, stimulation intensity and the number of interpolated stimuli. Sensitive twitch interpolation techniques have revealed small to moderate deficits in voluntary activation during brief maximal efforts and progressively increasing activation deficits (central fatigue) during exhausting exercise. A small number of recent studies suggest that resistance training may result in improved voluntary activation of the quadriceps femoris and ankle plantarflexor muscles but not the biceps brachii. A significantly larger body of evidence indicates that voluntary activation declines as a consequence of bed-rest, joint injury and joint degeneration. Twitch interpolation has also been employed to study the mechanisms by which caffeine and pseudoephedrine enhance exercise performance.


Partially endothelium-dependent vasodilator effect of adenosine in rat aorta.
The vasodilator effect of adenosine on the contraction induced by phenylephrine, an alpha 1-adrenergic receptor agonist, was investigated in the isolated rat aorta. We found that the effect of adenosine was greater in intact aortas than in endothelium-denuded preparations. Denuding caused a parallel shift of the dose-response curve of adenosine to the right by a factor of five in comparison with intact aorta. This finding indicates that the relaxing effect of adenosine is partially endothelium-dependent in rat aorta. The mechanism of action of adenosine on vascular smooth muscle was also investigated in receptor-mediated and voltage-dependent calcium influx experiments performed with the addition of phenylephrine and high potassium concentrations, respectively. Although adenosine significantly inhibited only the tonic phase of the contraction induced by phenylephrine (10(-5) M), it did so to both the fast and slow phases of the contraction produced by high potassium concentrations (75 mM) with no preferential difference. In comparison to verapamil, a calcium entry blocker, adenosine behaved in a manner similar to that of verapamil in counteracting the constriction induced by either phenylephrine or potassium. We conclude that the vasodilator effect of adenosine is partially endothelium-dependent and that the mechanism of this effect may involve the inhibition of calcium influx and the release of an endothelium-derived relaxing factor.


The effect of a ban on gender-based pricing on risk selection in the German health insurance market.
Starting from December 2012, insurers in the European Union were prohibited from charging gender-discriminatory prices. We examine the effect of this unisex mandate on risk segmentation in the German health insurance market. Although gender used to be a pricing factor in Germany's private health insurance (PHI) sector, it was never used as a pricing factor in the social health insurance (SHI) sector. The unisex mandate makes PHI relatively more attractive for women and less attractive for men. Based on data from the German socio-economic panel, we analyze how the unisex mandate affects the difference between women and men in switching rates between SHI and PHI. We find that the unisex mandate increases the probability of switching from SHI to PHI for women relative to men. On the other hand, the unisex mandate has no effect on the gender difference in switching rates from PHI to SHI. Because women have on average higher health care expenditures than men, our results imply a worsening of the PHI risk pool and an improvement of the SHI risk pool. Our results demonstrate that regulatory measures such as the unisex mandate can affect risk selection between public and private health insurance sectors.


Pharmacotherapy for Atrial Fibrillation in Patients With Chronic Kidney Disease: Insights From ORBIT-AF.
Background Chronic kidney disease ( CKD ) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control. Methods and Results Patients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow-up data were included (N=9019). CKD was defined as an estimated creatinine clearance <60 mL /min. Patient characteristics were compared by CKD status, and Cox proportional hazards modeling was used to examine the association between oral anticoagulant ( OAC ) use and outcomes and antiarrhythmic drug use and outcomes stratified by CKD stages. At enrollment, 3490 (39%) patients had an estimated creatinine clearance <60 mL /min. Patients with CKD were older and had higher CHA 2 DS 2 VAS c and Anticoagulant and Risk Factors in Atrial Fibrillation (ATRIA) scores. A rhythm control strategy was selected less frequently in patients with CKD , while OAC use was lower among Stage IV and V CKD patients. After adjustment, no significant interaction was noted for OAC and CKD on all-cause mortality ( P=0.5442) or cardiovascular death ( P=0.1233), although a trend for increased major bleeding ( P=0.0608) and stroke, systemic embolism or transient ischemic attack ( P=0.0671) was observed. No interaction was noted for antiarrhythmic drug use and CKD status on all-cause mortality ( P=0.9706), or stroke, systemic embolism or transient ischemic attack ( P=0.4218). Conclusions Patients with atrial fibrillation and CKD are less likely to be treated with rhythm control. Patients with advanced CKD are less likely to receive OAC . Finally, outcomes with OAC in patients with advanced CKD may be materially different with higher rates of both bleeding and stroke.


Picture of the Month.
A 2½year-old boy had the onset of pain and swelling of his penis during the past 3 days. The swelling and pain increased significantly within the past 24 hours. The child's penis is shown in the Figure. DENOUEMENT AND DISCUSSION PARAPHIMOSIS Paraphimosis is an urologic emergency that results when the foreskin is retracted away from the glans penis and cannot be reduced to its former position. The opening in the prepuce, when forcibly retracted beyond the coronal sulcus, becomes a constricting ring that cannot be reduced. The constricting ring created causes a tension greater than the lymphatic pressure and results in edema of the prepuce, the penile shaft, and the glans penis distal to the incarcerated foreskin.1,2As lymphatic drainage is impaired and tissue swelling increases, reduction of the foreskin becomes more difficult. Pain occurs as a result of swelling, and, eventually, as a result of vascular compromise. If.


Routing of strongly confined terahertz spoof surface plasmon polaritons on metasurfaces along straight and curved pathways with subwavelength width.
In search of new technologies for optimizing the performance and space requirements of electronic and optical micro-circuits, the concept of spoof surface plasmon polaritons (SSPPs) has come to the fore of research in recent years. Due to the ability of SSPPs to confine and guide the energy of electromagnetic waves in a subwavelength space below the diffraction limit, SSPPs deliver all the tools to implement integrated circuits with a high integration rate. However, in order to guide SSPPs in the terahertz frequency range, it is necessary to carefully design metasurfaces that allow one to manipulate the spatio-temporal and spectral properties of the SSPPs at will. Here, we propose a specifically designed cut-wire metasurface that sustains strongly confined SSPP modes at terahertz frequencies. As we show by numerical simulations and also prove in experimental measurements, the proposed metasurface can tightly guide SSPPs on straight and curved pathways while maintaining their subwavelength field confinement perpendicular to the surface. Furthermore, we investigate the dependence of the spatio-temporal and spectral properties of the SSPP modes on the width of the metasurface lanes that can be composed of one, two or three cut-wires in the transverse direction. Our investigations deliver new insights into downsizing effects of guiding structures for SSPPs.


The diagnosis of childhood tuberculosis in an HIV-endemic setting and the use of induced sputum.
A hospital in the capital city of Uganda. To determine the proportion of positive induced sputum cultures among probable childhood tuberculosis (TB) cases, to describe the laboratory and radiological features of childhood TB in the context of human immunodeficiency virus (HIV), and to determine the prevalence of HIV infection in these patients. Cross-sectional descriptive study. Seven hundred and fifty children with suspected TB were evaluated clinically, by chest radiography and by tuberculin test (Mantoux). Probable cases underwent sputum induction or lymph node biopsy, HIV testing and RNA-PCR tests. The Mantoux test was positive in 55/121 (45%) of the patients; low sensitivity to Mantoux was associated with HIV infection (P = 0.000). Induced sputum yielded 12/101 (12%) positive smears of Mycobacterium tuberculosis and 30/101 (30%) positive cultures. Six of the eight lymph node biopsies were culture-positive, and the histology of seven samples was supportive of TB. Most of the children with probable and confirmed TB presented with similar signs, symptoms and chest radiography patterns, irrespective of HIV status. Elevated ESR had no significant role in the diagnosis of TB in children and even more so in the presence of HIV infection. The HIV infection rate was high among children with TB (49%).


Pediatric end-of-life care for Taiwanese children who died as a result of cancer from 2001 through 2006.
Patterns of aggressive end-of-life (EOL) care have not been extensively explored in a pediatric cancer population, especially outside Western countries. The purpose of this population-based study was to examine trends in aggressive pediatric EOL cancer care in Taiwan. Retrospective cohort study that used administrative data among 1,208 pediatric cancer decedents from 2001 through 2006. Taiwanese pediatric cancer patients who died in 2001 through 2006 received aggressive EOL care. The majority of these patients in their last month of life continued to receive chemotherapy (52.5%), used intensive care (57.0%), underwent intubation (40.9%), underwent mechanical ventilation (48.2%), or spent greater than 14 days (69.5%) in hospital, and they died in an acute care hospital (78.8%). Of these pediatric cancer patients, one in four received cardiopulmonary resuscitation in the month before they died, and only 7.2% received hospice care. Among those who received hospice care, 21.8% started such care within the last 3 days of life. This pattern of aggressive EOL care did not change over the study period except for significantly decreased intubation in the last month of life. Continued chemotherapy and heavy use of life-sustaining treatments in the last month of life coupled with lack of hospice care to support Taiwanese pediatric cancer patients dying at home may lead to multiple unplanned health care encounters, prolonged hospitalization at EOL, and eventual death in an acute care hospital for the majority of these patients. Future research should design interventions that enable Taiwanese pediatric cancer patients to receive EOL care that best meets the individual or the parental needs and preferences.


Ablation of perimitral flutter following catheter ablation of atrial fibrillation: impact on outcomes from a randomized study (PROPOSE).
Patients with previous ablation for atrial fibrillation (AF) may experience recurrence of perimitral flutter (PMFL). These arrhythmias are usually triggered from sources that may also induce AF. This study aims at determining whether ablation of triggers or completing mitral valve isthmus (MVI) block prevents more arrhythmia recurrences. Sixty-five patients with recurrent PMFL after initial ablation of long standing persistent AF were included in this study. Thirty-two patients were randomized to MVI ablation only (Group 1) and 33 were randomized to cardioversion and repeat pulmonary vein (PV) isolation plus ablation of non-PV triggers (Group 2). MVI bidirectional block was achieved in all but 1 patient from Group 1. In Group 2, reconnection of 17 PVs was detected in 14 patients (42%). With isoproterenol challenge, 44 non-PV trigger sites were identified in 28 patients (85%, 1.57 sites per patient). At 18-month follow-up, 27 patients (84%) from Group 1 had recurrent atrial tachyarrhythmias, of whom 15 remained on antiarrhythmic drug (AAD); however, 28 patients from Group 2 (85%, P < 0.0001 vs Group 1) were free from arrhythmia off AAD. The ablation strategy used in Group 2 was associated with a lower risk of recurrence (hazard ratio = 0.10, 95% CI 0.04-0.28, P < 0.001) and an improved arrhythmia-free survival (log rank P < 0.0001). In patients presenting with PMFL after ablation for longstanding persistent AF, MVI block had limited impact on arrhythmia recurrence. On the other hand, elimination of all PV and non-PV triggers achieved higher freedom from atrial arrhythmias at follow-up.


Targeting EZH2 for cancer therapy: progress and perspective.
Enhancer of Zeste Homolog 2 (EZH2) is the core component of the polycomb repressive complex 2 (PRC2), possessing the enzymatic activity in generating di/tri-methylated lysine 27 in histone H3. EZH2 has important roles during early development, and its dysregulation is heavily linked to oncogenesis in various tissue types. Accumulating evidences suggest a remarkable therapeutic potential by targeting EZH2 in cancer cells. The first part reviews current strategies to target EZH2 in cancers, and evaluates the available compounds and agents used to disrupt EZH2 functions. Then we provide insight to the future direction of the research on targeting EZH2 in different cancer types. We comprehensively discuss the current understandings of the 1) structure and biological activity of EZH2, 2) its role during the assembling of PRC2 and recruitment of other protein components, 3) the molecular events directing EZH2 to target genomic regions, and 4) post-translational modification at EZH2 protein. The discussion provides the basis to inspire the development of novel strategies to abolish EZH2-related effects in cancer cells.


Supporting ethical practice in primary care research: strategies for action.
Researchers in primary care share the general ethical obligations of all researchers. However, these obligations may raise different issues in the unique context of primary care. Current professional ethical guidance for primary care research is complex and fragmentary. The newly introduced research governance framework does not specifically address primary care research, and recent changes in legal requirements have significant implications for research. In this paper, ethical issues arising from research in primary care are considered, current standards and resources are described, and strategies for supporting ethical practice are discussed. Four ethical issues are discussed: consent and competence; confidentiality; power relations; and procedural issues. In the final part of the paper, broad strategies to support ethical practice in primary care research are recommended. These include education and resources, greater clarity of relevant standards, financial support, a greater role for primary care networks, and greater public debate.


Antioxidant potential of bitter cumin (Centratherum anthelminticum (L.) Kuntze) seeds in in vitro models.
Bitter cumin (Centratherum anthelminticum (L.) Kuntze), is a medicinally important plant. Earlier, we have reported phenolic compounds, antioxidant, and anti-hyperglycemic, antimicrobial activity of bitter cumin. In this study we have further characterized the antioxidative activity of bitter cumin extracts in various in vitro models. Bitter cumin seeds were extracted with a combination of acetone, methanol and water. The antioxidant activity of bitter cumin extracts were characterized in various in vitro model systems such as DPPH radical, ABTS radical scavenging, reducing power, oxidation of liposomes and oxidative damage to DNA. The phenolic extracts of bitter cumin at microgram concentration showed significant scavenging of DPPH and ABTS radicals, reduced phosphomolybdenum (Mo(VI) to Mo(V)), ferricyanide Fe(III) to Fe(II), inhibited liposomes oxidation and hydroxyl radical induced damage to prokaryotic genomic DNA. The results showed a direct correlation between phenolic acid content and antioxidant activity. Bitter cumin is a good source of natural antioxidants.


Attenuated typhoid vaccine Salmonella typhi Ty21a: fingerprinting and quality control.
Live attenuated vaccines, developed with molecular genetical techniques, require new approaches for their quality control. To develop novel quality control tests that enhanced and extended existing procedures, the attenuated vaccine strain Salmonella typhi Ty21a and its parent strain Ty2 were characterized by pulsed-field gel electrophoresis (PFGE) and direct nucleotide sequence analysis. Mutant and parent strains were distinguished using fingerprints generated by the resolution on PFGE of chromosomal DNA digested with each of the enzymes SfiI, SpeI or XbaI. These fingerprints were stable through multiple in vitro passages of the vaccine strain and were identical from one batch of vaccine to another. It was also possible to distinguish between the mutant and parent strains by direct nucleotide sequence analysis of the galE gene. This analysis identified two base changes in the gene from strain Ty21a: a single base deletion causing a frameshift that would result in a truncated gene product, accounting for the galE phenotype; and a transition that eliminated an AluI restriction site. The consequent change in the AluI fingerprint of the galE gene in strain Ty21a provided a rapid, PCR-based alternative to the use of differential media or biochemical assays for the identification of the vaccine strain.


Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.
Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.


Vascularization of engineered tissues: approaches to promote angio-genesis in biomaterials.
Although there have been extensive research efforts to create functional tissues and organs, most successes in tissue engineering have been limited to avascular or thin tissues. The major hurdle in development of more complex tissues lies in the formation of vascular networks capable of delivering oxygen and nutrients throughout the engineered constructs. Sufficient neovascularization in scaffold materials can be achieved through coordinated application of angiogenic factors with proper cell types in biomaterials. This review present the current research developments in the design of biomaterials and their biochemical and biochemical modifications to produce vascularized tissue constructs.


Racial and ethnic modifiers of the salt-blood pressure response.
The relation between sodium and blood pressure is a centuries-old question. A substantial body of epidemiological and experimental data has accumulated that strongly implicates NaCl as having a causal role in the genesis of arterial hypertension. Prospective studies that have been performed in diverse populations that have manipulated NaCl exposure by diet or infusion have repeatedly documented an NaCl pressor effect. Further, similar studies in biracial populations have also demonstrated a greater prevalence of "salt sensitivity" in blacks compared with whites. The reasons for this observation are not entirely clear; however, intrinsic or hypertension-induced renal abnormalities that limit natriuretic capacity, reduced Na+,K(+)-ATPase pump activity, other membrane ion transport disturbances, differential exposure to psychological stressors, greater insulin resistance, and dietary factors (reduced Ca+ and K+ intake) have all been suggested as possibly playing a role. Salt sensitivity appears to be a widespread phenomenon. However, it is critically important to determine what factors account for racial differences in salt sensitivity. Moreover, the prevalence of salt sensitivity in the general population is unknown. Current definitions of salt sensitivity are varied and unidirectional. In comparison with bidirectional criteria (blood pressure increase with salt loading and blood pressure decrease with salt restriction), they are probably inadequate to identify salt-sensitive individuals who manifest less extreme blood pressure change after dietary sodium or plasma volume manipulations. More sensitive criteria for diagnosing salt sensitivity will facilitate a better understanding of racial and ethnic differences in the prevalence of salt sensitivity.


From suspect to patient: tuberculosis diagnosis and treatment initiation in health facilities in South Africa.
Thirteen primary health care (PHC) facilities in the Stellenbosch District, South Africa. To assess the use of a sputum register to evaluate the tuberculosis (TB) diagnostic process and the initiation of TB treatment in selected PHC facilities in a country with a centralised laboratory system. This prospective study was conducted between April 2004 and March 2005. The names of all individuals submitting sputum samples for TB testing were noted in a newly introduced sputum register. We classified all TB suspects with two positive smears as TB cases and consulted TB treatment registers until 3 months after sputum submission to determine how many had started treatment. A total of 4062 persons aged > or =15 years submitted sputum samples, of whom 2484 were TB suspects. There were 2037 suspects with at least two results, 367 (18%) had at least two positive smears and 64 (17%) of these did not start treatment (initial defaulters). Over the entire diagnostic process, up to 5% of TB cases were missed, and up to 26% did not start treatment and were not reported. By correcting diagnostic weaknesses identified in the sputum register, PHC facilities will be able to detect, treat and cure a higher percentage of TB patients.


Application of the PredictAD software tool to predict progression in patients with mild cognitive impairment.
The PredictAD tool integrates heterogeneous data such as imaging, cerebrospinal fluid biomarkers and results from neuropsychological tests for compact visualization in an interactive user interface. This study investigated whether the software tool could assist physicians in the early diagnosis of Alzheimer's disease. Baseline data from 140 patients with mild cognitive impairment were selected from the Alzheimer's Disease Neuroimaging Study. Three clinical raters classified patients into 6 categories of confidence in the prediction of early Alzheimer's disease, in 4 phases of incremental data presentation using the software tool. A 5th phase was done with all available patient data presented on paper charts. Classifications by the clinical raters were compared to the clinical diagnoses made by the Alzheimer's Disease Neuroimaging Initiative investigators. A statistical significant trend (p < 0.05) towards better classification accuracy (from 62.6 to 70.0%) was found when using the PredictAD tool during the stepwise procedure. When the same data were presented on paper, classification accuracy of the raters dropped significantly from 70.0 to 63.2%. Best classification accuracy was achieved by the clinical raters when using the tool for decision support, suggesting that the tool can add value in diagnostic classification when large amounts of heterogeneous data are presented.


How SARS-CoV-2 (COVID-19) spreads within infected hosts - what we know so far.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19), belongs to the betacoronavirus genus and shares high homology to the severe acute respiratory syndrome coronavirus (SARS-CoV) that emerged in 2003. These are highly transmissible and pathogenic viruses which very likely originated in bats. SARS-CoV-2 uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as SARS-CoV, and spreads primarily through the respiratory tract. Although several trials for vaccine development are currently underway, investigations into the virology of SARS-CoV-2 to understand the fundamental biology of the infectious cycle and the associated immunopathology underlying the clinical manifestations of COVID-19 are crucial for identification and rational design of effective therapies. This review provides an overview of how SARS-CoV-2 infects and spreads within human hosts with specific emphasis on key aspects of its lifecycle, tropism and immunopathological features.


Phlebotominae spatial distribution asssociated with a focus of tegumentary leishmaniasis in Las Lomitas, Formosa, Argentina, 2002.
Las Lomitas, Formosa, Argentina, reported 96 cases of tegumentary leishmaniasis during 2002. The urban transmission was suggested although previous outbreaks were related with floods of the Bermejo river (BR) 50 km from the village. Phlebotomine collections were performed during March 2002 to define the spatial distribution of risk, together with satellite imaginery. The phlebotomine/trap obtained was 1679.5 in the southern BR shore, 1.1 in the periruban-rural environment and 2.3 in the northern Pilcomayo river marshes. Lutzomyia neivai was the prevalent species (91.1%) among the 2393 phlebotomine captured, and it was only found in the BR traps. The other species were L. migonei (7.9%), L. cortelezzii (0.9%), and Brumptomyia guimaraesi (0.1%). The satellite images analysis indicates that the fishing spots at the BR were significantly overflowed during the transmission peak, consistent with fishermen recollections. This spatial restricted flood might concentrate vectors, reservoirs, and humans in high places. Therefore, both the spatial distribution of vectors and the sensor remoting data suggests that in Las Lomitas area the higher transmission risk it is still related with the gallery forest of the BR, despite of the urban residence of the cases. The surveillance and control implications of these results are discussed.


Ambulatory monitoring of bladder pressure in low compliance neurogenic bladder dysfunction.
Upper tract dilatation is an important complication of neurogenic bladder dysfunction. Risk factors include incomplete bladder emptying with large residual volumes of urine and high tonic increases in bladder pressures during artificial filling. However, on natural bladder filling many of these patients do not have high tonic increases in detrusor pressures. We compared conventional urodynamic studies with ambulatory monitoring during natural bladder filling in 66 patients with low compliance neurogenic bladder dysfunction. There were marked differences in the tonic increase in bladder pressure during filling and in compliance during artificial bladder filling compared with ambulatory monitoring. Faster filling rates during artificial filling resulted in greater end filling pressures and lower compliance but the lowest increases in bladder pressure were found during ambulatory monitoring with natural bladder filling. During natural bladder filling significantly more patients had phasic changes in detrusor pressure; a high intensity of phasic activity during ambulatory monitoring correlated with high end filling pressures during artificial bladder filling. Upper tract dilatation was associated with large volumes of residual urine, high resting bladder pressures and low bladder compliance on filling at 100 ml. per minute. However, upper tract dilatation was most strongly associated with high intensity phasic pressure activity during natural bladder filling in combination with high residual urine volumes and high resting bladder pressures. On multivariate statistical analysis the intensity of phasic pressure activity during ambulatory monitoring was the best discriminator between patients with dilated and normal upper tracts. Our study has highlighted important differences in the results obtained by artificial filling cystometry and ambulatory monitoring during natural bladder filling. In particular, high increases in pressure did not occur during natural bladder filling, apparently being replaced by phasic activity. Within this group of patients who had the high risk factor of low bladder compliance measured during artificial bladder filling, a combination of greater residual urine volumes, greater resting pressures and greater phasic activity during natural bladder filling was found in patients with upper tract dilatation.


Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases.
WHO interim guidelines recommend offering extracorporeal membrane oxygenation (ECMO) to eligible patients with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). The number of patients with COVID-19 infection who might develop severe ARDS that is refractory to maximal medical management and require this level of support is currently unknown. Available evidence from similar patient populations suggests that carefully selected patients with severe ARDS who do not benefit from conventional treatment might be successfully supported with venovenous ECMO. The need for ECMO is relatively low and its use is mostly restricted to specialised centres globally. Providing complex therapies such as ECMO during outbreaks of emerging infectious diseases has unique challenges. Careful planning, judicious resource allocation, and training of personnel to provide complex therapeutic interventions while adhering to strict infection control measures are all crucial components of an ECMO action plan. ECMO can be initiated in specialist centres, or patients can receive ECMO during transportation from a centre that is not specialised for this procedure to an expert ECMO centre. Ensuring that systems enable safe and coordinated movement of critically ill patients, staff, and equipment is important to improve ECMO access. ECMO preparedness for the COVID-19 pandemic is important in view of the high transmission rate of the virus and respiratory-related mortality.


A heme-sensing mechanism in the translational regulation of mitochondrial cytochrome c oxidase biogenesis.
Heme plays fundamental roles as cofactor and signaling molecule in multiple pathways devoted to oxygen sensing and utilization in aerobic organisms. For cellular respiration, heme serves as a prosthetic group in electron transfer proteins and redox enzymes. Here we report that in the yeast Saccharomyces cerevisiae, a heme-sensing mechanism translationally controls the biogenesis of cytochrome c oxidase (COX), the terminal mitochondrial respiratory chain enzyme. We show that Mss51, a COX1 mRNA-specific translational activator and Cox1 chaperone, which coordinates Cox1 synthesis in mitoribosomes with its assembly in COX, is a heme-binding protein. Mss51 contains two heme regulatory motifs or Cys-Pro-X domains located in its N terminus. Using a combination of in vitro and in vivo approaches, we have demonstrated that these motifs are important for heme binding and efficient performance of Mss51 functions. We conclude that heme sensing by Mss51 regulates COX biogenesis and aerobic energy production.


Alcohol problems in women admitted to a level I trauma center: a gender-based comparison.
Male patients constitute such a large proportion of trauma patients that most studies of alcohol problems in trauma patients have been carried out with clinical data largely or totally contributed by male patients. It may be incorrect to assume that the nature of alcoholism in women and men is identical, or that the size of the problem among women is small, eliminating the need to specifically study female patients. The purpose of this study was to perform a gender-based comparison of alcohol problems in trauma patients. Admitted injured patients underwent routine screening, including a blood alcohol concentration, serum gamma-glutamyl transpeptidase, and the Short Michigan Alcohol Screening Test. A random sample of screen positive women and men underwent a comprehensive alcohol use and psychosocial assessment, and the results were compared by gender. The screen-positive rate was higher for men, 51% versus 34% (p < 0.01). However, screen-positive women and men had similar problem severity as reflected by mean blood alcohol concentration (162 mg/dL vs. 142 mg/dL, p = 0.16) and Short Michigan Alcohol Screening Test scores (4.6 vs. 5.0, p = 0.32). The Alcohol Use Disorders Identification Test, NIMH-DIS, and Severity of Alcohol Dependence Data form showed that female trauma patients with alcohol problems have the same severity of dependence symptoms as men. However, women were significantly more likely to have liver dysfunction, depression, psychological distress, and recent physical, emotional, or sexual abuse. Alcohol problems are more common in male trauma patients, but women with alcohol problems are just as severely impaired, have at least as many adverse consequences of alcohol use as their male counterparts, and have more evidence of alcohol-related physical and psychological harm.


[Correlation between end-tidal carbon dioxide levels and cardiac output during cardiac surgery with cardiopulmonary bypass.].
End-tidal carbon dioxide (P ET CO2) not only reflects pulmonary ventilation but also carbon dioxide production (metabolism) and pulmonary blood supply (circulation). During constant metabolism and ventilation, P ET CO2 reflects pulmonary blood perfusion, thus cardiac output (CO). This study aimed at evaluating the correlation between P ET CO2 levels and CO during cardiac surgery with cardiopulmonary bypass (CPB). Participated in this study 25 patients submitted to coronary artery bypass grafting (CABG) with CPB. End-tidal CO2 monitoring started after tracheal intubation. Cardiac output was determined by thermodilution with pulmonary artery catheter (Swan-Ganz). Carbon dioxide partial blood pressure (PaCO2) was obtained with arterial blood gases analysis. Studied parameters were evaluated in the following moments: immediately after general anesthesia induction, before cardiopulmonary bypass, at cardiopulmonary bypass completion and at surgery completion. Statistical analysis has not shown correlation between P ET CO2 and CO2, or between P ET CO2-PaCO2 gradient (Ga-eCO2) and CO. There has been correlation between P ET CO2, Ga-eCO2 and CO values variation as compared to baseline values before CPB, with loss of correlation after CPB until surgery completion. In this study, where patients submitted to cardiac surgery with CPB were evaluated, ventilation/perfusion changes throughout the procedure might have been the factors determining decreased correlation between cardiac output and end tidal CO2.


Perceived causes of severe mental disturbance and preferred interventions by the Borana semi-nomadic population in southern Ethiopia: a qualitative study.
Culture affects the way people conceptualize causes of severe mental disturbance which may lead to a variation in the preferred intervention methods. There is a seemingly dichotomous belief regarding what causes severe mental disturbance: people living in western countries tend to focus mainly on biological and psychosocial risk factors; whereas, in non-western countries the focus is mainly on supernatural and religious factors. These belief systems about causation potentially dictate the type of intervention preferred. Studying such belief systems in any society is expected to help in planning and implementation of appropriate mental health services. A qualitative study was conducted among the Borana semi-nomadic population in southern Ethiopia to explore perceived causes of severe mental disturbance and preferred interventions. We selected, using purposive sampling, key informants from three villages and conducted a total of six focus group discussions: three for males and three for females. The views expressed regarding the causes of mental disturbance were heterogeneous encompassing supernatural causes such as possession by evil spirits, curse, bewitchment, 'exposure to wind' and subsequent attack by evil spirit in postnatal women and biopsychosocial causes such as infections (malaria), loss, 'thinking too much', and alcohol and khat abuse. The preferred interventions for severe mental disturbance included mainly indigenous approaches, such as consulting Borana wise men or indigenous healers, prayer, holy water treatment and seeking modern mental health care as a last resort. These findings will be of value for health care planners who wish to expand modern mental health care to this population, indicating the need to increase awareness about the causes of severe mental disturbance and their interventions and collaborate with influential people and indigenous healers to increase acceptability of modern mental health care. It also provides information for further research in the area of mental health in this semi-nomadic population.


Investigating and Improving the Accuracy of US Citizens' Beliefs About the COVID-19 Pandemic: Longitudinal Survey Study.
The COVID-19 infodemic, a surge of information and misinformation, has sparked worry about the public's perception of the coronavirus pandemic. Excessive information and misinformation can lead to belief in false information as well as reduce the accurate interpretation of true information. Such incorrect beliefs about the COVID-19 pandemic might lead to behavior that puts people at risk of both contracting and spreading the virus. The objective of this study was two-fold. First, we attempted to gain insight into public beliefs about the novel coronavirus and COVID-19 in one of the worst hit countries: the United States. Second, we aimed to test whether a short intervention could improve people's belief accuracy by empowering them to consider scientific consensus when evaluating claims related to the pandemic. We conducted a 4-week longitudinal study among US citizens, starting on April 27, 2020, just after daily COVID-19 deaths in the United States had peaked. Each week, we measured participants' belief accuracy related to the coronavirus and COVID-19 by asking them to indicate to what extent they believed a number of true and false statements (split 50/50). Furthermore, each new survey wave included both the original statements and four new statements: two false and two true statements. Half of the participants were exposed to an intervention aimed at increasing belief accuracy. The intervention consisted of a short infographic that set out three steps to verify information by searching for and verifying a scientific consensus. A total of 1202 US citizens, balanced regarding age, gender, and ethnicity to approximate the US general public, completed the baseline (T0) wave survey. Retention rate for the follow-up waves- first follow-up wave (T1), second follow-up wave (T2), and final wave (T3)-was high (≥85%). Mean scores of belief accuracy were high for all waves, with scores reflecting low belief in false statements and high belief in true statements; the belief accuracy scale ranged from -1, indicating completely inaccurate beliefs, to 1, indicating completely accurate beliefs (T0 mean 0.75, T1 mean 0.78, T2 mean 0.77, and T3 mean 0.75). Accurate beliefs were correlated with self-reported behavior aimed at preventing the coronavirus from spreading (eg, social distancing) (r at all waves was between 0.26 and 0.29 and all P values were less than .001) and were associated with trust in scientists (ie, higher trust was associated with more accurate beliefs), political orientation (ie, liberal, Democratic participants held more accurate beliefs than conservative, Republican participants), and the primary news source (ie, participants reporting CNN or Fox News as the main news source held less accurate beliefs than others). The intervention did not significantly improve belief accuracy. The supposed infodemic was not reflected in US citizens' beliefs about the COVID-19 pandemic. Most people were quite able to figure out the facts in these relatively early days of the crisis, calling into question the prevalence of misinformation and the public's susceptibility to misinformation.


Mycobacterium tuberculosis Beijing genotype is associated with HIV infection in Mozambique.
The Beijing genotype is a lineage of Mycobacterium tuberculosis that is distributed worldwide and responsible for large epidemics, associated with multidrug-resistance. However, its distribution in Africa is less understood due to the lack of data. Our aim was to investigate the prevalence and possible transmission of Beijing strains in Mozambique by a multivariate analysis of genotypic, geographic and demographic data. A total of 543 M. tuberculosis isolates from Mozambique were spoligotyped. Of these, 33 were of the Beijing lineage. The genetic relationship between the Beijing isolates were studied by identification of genomic deletions within some Regions of Difference (RD), Restriction Fragment Length Polymorphism (RFLP) and Mycobacterial Interspersed Repetivie Unit - variable number tandem repeat (MIRU-VNTR). Beijing strains from South Africa, representing different sublineages were included as reference strains. The association between Beijing genotype, Human Immunodeficiency Virus (HIV) serology and baseline demographic data was investigated. HIV positive serostatus was significantly (p=0.023) more common in patients with Beijing strains than in patients with non-Beijing strains in a multivariable analysis adjusted for age, sex and province (14 (10.9%) of the 129 HIV positive patients had Beijing strains while 6/141 (4.3%) of HIV negative patients had Beijing strains). The majority of Beijing strains were found in the Southern region of Mozambique, particularly in Maputo City (17%). Only one Beijing strain was drug resistant (multi-drug resistant). By combined use of RD and spoligotyping, three genetic sublineages could be tentatively identified where a distinct group of four isolates had deletion of RD150, a signature of the "sublineage 7" recently emerging in South Africa. The same group was very similar to South African "sublineage 7" by RFLP and MIRU-VNTR, suggesting that this sublineage could have been recently introduced in Mozambique from South Africa, in association with HIV infection.


Chronic in-vivo experience with an endoscopically delivered and retrieved duodenal-jejunal bypass sleeve in a porcine model.
The role of duodenal bypass as an underlying mechanism of action in gastric bypass surgery has received considerable attention. We report the initial feasibility study of a totally endoscopically delivered and retrieved duodenal-jejunal bypass sleeve in a chronic porcine model. The implant consists of a 60-cm fluoropolymer sleeve that is endoscopically deployed via a coaxial catheter system into the jejunum and fixed in the proximal duodenum with a Nitinol anchor. The system creates a proximal biliopancreatic diversion. Six female Yorkshire pigs were endoscopically implanted; all survived. Four animals (group 1) were slated to survive 90 days, two animals (group 2) for 120 days, and three animals (group 3) underwent sham endoscopy and were survived 120 days. Animals were fed standard dry pig chow 0.5 kg three times daily. Data points included daily general health, weekly weight, serum blood tests (complete blood count, amylase, lipase, liver function tests), and monthly evaluation of anchor/sleeve position/patency by fluoroscopy and endoscopy. Following the in-vivo period, the devices were endoscopically removed and the animals were sacrificed. Duodenal and jejunal tissue samples were assessed histologically. All six test animals were implanted and explanted without significant adverse events. In group 1, the first animal had no device-related issues. The second animal had a pivoted anchor requiring repositioning at day 63. That animal had no further difficulties. The third animal had an incidental partial rotation of the anchor noted at the 90 day explantation. The fourth animal was incidentally implanted with a crossover of the anchor struts, which was endoscopically corrected on day 14. However, on day 20 the animal had persistent vomiting, and the device was explanted. Both group 2 animals survived 120 days. One animal had a partially rotated anchor but was asymptomatic. The average weight gain between test and sham groups was 0.23 kg/day and 0.42 kg/day, respectively (p = 0.01). A totally endoscopic and reversible bypass of the duodenum and proximal jejunum has been achieved for 90-120 days. Initial experience suggests patency of the sleeve and acceptable tissue response. Reduced weight gain in the test animals suggests device efficacy. Further investigation is warranted.


Dance PREEMIE, a Dance PaRticipation intervention for Extremely prEterm children with Motor Impairment at prEschool age: an Australian feasibility trial protocol.
Children born extremely preterm (EP: <28 weeks gestation) and/or extremely low birth weight (ELBW: <1000 g) are at increased risk of motor impairment compared with children born at term. Children with motor impairment have lower rates of physical activity (PA) participation compared with their typically developing peers. PA participation is an important outcome for children with motor impairment, however, there is limited evidence available to support interventions that improve PA participation in this population. The aim of this study is to assess the feasibility, including the recruitment and retention, acceptability and fidelity, of a preschool dance participation intervention for children born EP/EBLW with motor impairment called Dance PaRticipation intervention for Extremely prEterm children with Motor Impairment at prEschool age. This feasibility case series trial will recruit EP/ELBW children with motor impairment (n=10) from the Victorian Infant Collaborative Study 2016/2017 cohort, a prospective longitudinal cohort study. Up to 10 community-based dance teachers will be recruited and provided with physiotherapy-led training and support to facilitate the participation of EP/ELBW children in community dance classes. A mixed-methods approach (quantitative and qualitative) will be used to analyse the primary aim, to determine the feasibility of the intervention from the perspectives of families and dance teachers. This study is approved by the Human Research Ethics Committees of The Royal Children's Hospital and The Royal Women's Hospital, Melbourne. Study outcomes will be disseminated through conference presentations, peer-reviewed publications and social media. ACTRN12619001266156.