Air pollution and hospital admissions for respiratory and cardiovascular diseases in Hong Kong.
To investigate short term effects of concentrations of pollutants in ambient air on hospital admissions for cardiovascular and respiratory diseases in Hong Kong. Retrospective ecological study. A Poisson regression was performed of concentrations of daily air pollutant on daily counts of emergency hospital admissions in 12 major hospitals. The effects of time trend, season, and other cyclical factors, temperature, and humidity were accounted for. Autocorrelation and overdispersion were corrected. Daily concentrations of nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3), and particulate matter < 10 microns in aerodynamic diameter (PM10) were obtained from seven air monitoring stations in Hong Kong in 1994 and 1995. Relative risks (RR) of respiratory and cardiovascular disease admissions (for an increase of 10 micrograms/m3 in concentration of air pollutant) were calculated. Significant associations were found between hospital admissions for all respiratory diseases, all cardiovascular diseases, chronic obstructive pulmonary diseases, and heart failure and the concentrations of all four pollutants. Admissions for asthma, pneumonia, and influenza were significantly associated with NO2, O3, and PM10. Relative risk (RR) for admissions for respiratory disease for the four pollutants ranged from 1.013 (for SO2) to 1.022 (for O3), and for admissions for cardiovascular disease, from 1.006 (for PM10) to 1.016 (for SO2). Those aged > or = 65 years were at higher risk. Significant positive interactions were detected between NO2, O3, and PM10, and between O3 and winter months. Adverse health effects are evident at current ambient concentrations of air pollutants. Further reduction in air pollution is necessary to protect the health of the community, especially that of the high risk group.


Dietary salt intake and time to relapse in paediatric multiple sclerosis.
Salt intake was reported to be associated with increased clinical and MRI activity in adult patients with relapsing-remitting multiple sclerosis (MS). To determine if salt intake is associated with time to relapse in patients with paediatric-onset MS. Paediatric-onset MS and patients with clinically isolated syndrome (CIS) within 4 years of disease onset were recruited from 15 paediatric MS centres in the USA as part of a case-control study. Patients with available prospective relapse data subsequent to enrolment were included in this project. Dietary sodium intake was assessed by self-report questionnaire using the validated Block Kids Food Screener. Cox proportional-hazards regression models were employed to determine the association of sodium density, excess sodium intake and sodium density tertiles with time to relapse following study enrolment, adjusting for several confounders. 174 relapsing-remitting MS/CIS patients were included in this analysis (mean age of 15.0 years, and 64.9% females). Median duration of follow-up was 1.8 years. In an unadjusted analysis, density of daily sodium intake was not associated with time to relapse, and patients with excess sodium intake had no decrease in time to relapse as compared with patients with non-excess sodium intake. The multivariable analysis demonstrated that patients in the medium and high tertile of sodium density had a HR of 0.69 (95% CI 0.37 to 1.30, p=0.25) and 1.37 (95% CI 0.74 to 2.51, p=0.32) compared with patients in the lowest tertile, respectively. Higher salt intake was not associated with decreased time to relapse in patients with paediatric-onset MS.


The evaluation of nailfold capillaroscopy pattern in patients with fibromyalgia.
This study aims to evaluate nailfold capillaroscopic pattern in patents with fibromyalgia and to assess the relation of capillaroscopic parameters with clinical variables and disease-related measures. This cross-sectional, case-control study included 60 participants (4 males, 56 females; mean age: 44.0±8.2 years; range, 26 to 64 years) between August 2019 and November 2019. All participants were divided into two groups as the primary fibromyalgia group (n=30) who met the 2016 modified American College of Rheumatology Diagnostic Criteria for Fibromyalgia and the control group (n=30) consisting of age- and sex-matched healthy individuals. Nailfold capillaroscopy was performed by a digital microscope under a magnification of 200X. Capillary density, capillary loop diameter, number of dilated, giant and neoangiogenic capillaries, capillary shape, number of avascular areas, micro-aneurysms and micro-hemorrhages were evaluated by an assessor who was blind to the group allocation. In the fibromyalgia group, Widespread Pain Index, Symptom Severity Scale scores, and Fibromyalgia Severity scores were calculated. Health status and presence of benign joint hypermobility syndrome (BJHS) were evaluated using the Fibromyalgia Impact Questionnaire (FIQ) and revised Brighton criteria, respectively. Of the capillaroscopic parameters, the mean capillary loop diameter, number of micro-aneurysms, avascular areas, and neoangiogenic capillaries were significantly higher in the patient group compared to the controls (p<0.001, p=0.016, p=0.038, and p=0.04, respectively). Nailfold capillaroscopic findings did not significantly differ between the patients with (n=16) and without concomitant BJHS (n=14). Of the disease-related measures, only FIQ score showed a weak correlation with the number of dilated capillaries (p=0.324). Patients with fibromyalgia have distinct capillaroscopic patterns than healthy population. Capillaroscopic features, in general, are not related to clinical variables and disease-related measures.


GlideScope Use improves intubation success rates: an observational study using propensity score matching.
Rigid video laryngoscopes are popular alternatives to direct laryngoscopy for intubation, but further large scale prospective studies comparing these devices to direct laryngoscopy in routine anesthesiology practice are needed. We hypothesized that the first pass success rate with one particular video laryngoscope, the GlideScope, would be higher than the success rate with direct laryngoscopy. 3831 total intubation attempts were tracked in an observational study comparing first-pass success rate using a Macintosh or Miller-style laryngoscope with the GlideScope. Propensity scoring was then used to select 626 subjects matched between the two groups based on their morphologic traits. Comparing the GlideScope and direct laryngoscopy groups suggested that intubation would be more difficult in the GlideScope group based on the Mallampati class, cervical range of motion, mouth opening, dentition, weight, and past intubation history. Thus, a propensity score based on these factors was used to balance the groups into two 313 patient cohorts. Direct laryngoscopy was successful in 80.8% on the first-pass intubation attempt, while the GlideScope was successful in 93.6% (p <0.001; risk difference of 0.128 with a 95% CI of 0.0771 - 0.181). A greater first-attempt success rate was found when using the GlideScope versus direct laryngoscopy. In addition, the GlideScope was found to be 99% successful for intubation after initial failure of direct laryngoscopy, helping to reduce the incidence of failed intubation.


Subcutaneous Panniculitis-Like T-Cell Lymphoma (SPTL) in a Child with Spontaneous Resolution.
Subcutaneous panniculitis-like T-cell lymphomas (SPTLs) α/β are rare in childhood. The present report refers to a case of a 7-year-old male child presenting an extensive skin lesion that began when he was 5 years of age. Two biopsies were evaluated using the CD3, CD4, CD8, CD56, βF1, and TIA markers. A dense infiltrate of CD3+, CD4-, CD8+, CD56-, βF1+, and TIA+ pleomorphic lymphocytes was found in the subcutis. The previous biopsy showed cytophagic histiocytic panniculitis with a small focus on CD8+ and βF1+ malignant cells. The lesion regressed spontaneously. This case shows that prognosis may be excellent in SPTL (α/β). On the other hand, it also serves as an alert that a biopsy performed in an area of cytophagic panniculitis may lead to misdiagnosis.


Structural basis for altering the stability of homologous RNAs from a mesophilic and a thermophilic bacterium.
Tertiary RNA structures from thermophilic bacteria generally are more stable than their mesophilic homologs. To understand the structural basis of the increase in stability, we investigated equilibrium folding of the specificity domain (S-domain) of RNase P RNA from a mesophilic (Escherichia coli) and a thermophilic (Thermus thermophilus) bacterium. Equilibrium folding of both S-domains is described by a minimal, three-state folding scheme, U-to-I-to-N. In the I-to-N transition of the thermophilic S-domain, more structure forms and protections are stronger against T1 nuclease and hydroxyl radical reactions. Phylogenetic comparison in the context of the native structure reveals that among 39 nucleotide differences between these S-domains, 12 likely contribute to higher stability. These residues participate in extensive networks of hydrogen bonding, stacking, and metal ion coordination throughout the molecule. The thermophilic S-domain achieves higher stability by mutating strategic base pairs to G-C, decreasing surface accessibility of the native state, and increasing the amount of structure formation in the native folding transition. An E. coli S-domain mutant containing these 12 nt has the same stability and folding cooperativity as the T. thermophilus S-domain. E. coli S-domain mutants containing a subset of 4 or 6 nt have the same stability as the T. thermophilus S-domain but the same folding cooperativity as the E. coli S-domain. These results show that increasing stability can be accomplished by mutations within a local structure, but increasing folding cooperativity needs concerted changes among multiple structural units.


A small-molecule inhibitor of T. gondii motility induces the posttranslational modification of myosin light chain-1 and inhibits myosin motor activity.
Toxoplasma gondii is an obligate intracellular parasite that enters cells by a process of active penetration. Host cell penetration and parasite motility are driven by a myosin motor complex consisting of four known proteins: TgMyoA, an unconventional Class XIV myosin; TgMLC1, a myosin light chain; and two membrane-associated proteins, TgGAP45 and TgGAP50. Little is known about how the activity of the myosin motor complex is regulated. Here, we show that treatment of parasites with a recently identified small-molecule inhibitor of invasion and motility results in a rapid and irreversible change in the electrophoretic mobility of TgMLC1. While the precise nature of the TgMLC1 modification has not yet been established, it was mapped to the peptide Val46-Arg59. To determine if the TgMLC1 modification is responsible for the motility defect observed in parasites after compound treatment, the activity of myosin motor complexes from control and compound-treated parasites was compared in an in vitro motility assay. TgMyoA motor complexes containing the modified TgMLC1 showed significantly decreased motor activity compared to control complexes. This change in motor activity likely accounts for the motility defects seen in the parasites after compound treatment and provides the first evidence, in any species, that the mechanical activity of Class XIV myosins can be modulated by posttranslational modifications to their associated light chains.


Geranylgeranylated SNAREs are dominant inhibitors of membrane fusion.
Exocytosis in yeast requires the assembly of the secretory vesicle soluble N-ethylmaleimide-sensitive factor attachment protein receptor (v-SNARE) Sncp and the plasma membrane t-SNAREs Ssop and Sec9p into a SNARE complex. High-level expression of mutant Snc1 or Sso2 proteins that have a COOH-terminal geranylgeranylation signal instead of a transmembrane domain inhibits exocytosis at a stage after vesicle docking. The mutant SNARE proteins are membrane associated, correctly targeted, assemble into SNARE complexes, and do not interfere with the incorporation of wild-type SNARE proteins into complexes. Mutant SNARE complexes recruit GFP-Sec1p to sites of exocytosis and can be disassembled by the Sec18p ATPase. Heterotrimeric SNARE complexes assembled from both wild-type and mutant SNAREs are present in heterogeneous higher-order complexes containing Sec1p that sediment at greater than 20S. Based on a structural analogy between geranylgeranylated SNAREs and the GPI-HA mutant influenza virus fusion protein, we propose that the mutant SNAREs are fusion proteins unable to catalyze fusion of the distal leaflets of the secretory vesicle and plasma membrane. In support of this model, the inverted cone-shaped lipid lysophosphatidylcholine rescues secretion from SNARE mutant cells.


Discriminative Accuracy of FEV1:FVC Thresholds for COPD-Related Hospitalization and Mortality.
According to numerous current guidelines, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1:FVC) of less than 0.70, yet this fixed threshold is based on expert opinion and remains controversial. To determine the discriminative accuracy of various FEV1:FVC fixed thresholds for predicting COPD-related hospitalization and mortality. The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 4 US general population-based cohorts (Atherosclerosis Risk in Communities Study; Cardiovascular Health Study; Health, Aging, and Body Composition Study; and Multi-Ethnic Study of Atherosclerosis). Participants aged 45 to 102 years were enrolled from 1987 to 2000 and received follow-up longitudinally through 2016. Presence of airflow obstruction, which was defined by a baseline FEV1:FVC less than a range of fixed thresholds (0.75 to 0.65) or less than the lower limit of normal as defined by Global Lung Initiative reference equations (LLN). The primary outcome was a composite of COPD hospitalization and COPD-related mortality, defined by adjudication or administrative criteria. The optimal fixed FEV1:FVC threshold was defined by the best discrimination for these COPD-related events as indexed using the Harrell C statistic from unadjusted Cox proportional hazards models. Differences in C statistics were compared with respect to less than 0.70 and less than LLN thresholds using a nonparametric approach. Among 24 207 adults in the pooled cohort (mean [SD] age at enrollment, 63 [10.5] years; 12 990 [54%] women; 16 794 [69%] non-Hispanic white; 15 181 [63%] ever smokers), complete follow-up was available for 11 077 (77%) at 15 years. During a median follow-up of 15 years, 3925 participants experienced COPD-related events over 340 757 person-years of follow-up (incidence density rate, 11.5 per 1000 person-years), including 3563 COPD-related hospitalizations and 447 COPD-related deaths. With respect to discrimination of COPD-related events, the optimal fixed threshold (0.71; C statistic for optimal fixed threshold, 0.696) was not significantly different from the 0.70 threshold (difference, 0.001 [95% CI, -0.002 to 0.004]) but was more accurate than the LLN threshold (difference, 0.034 [95% CI, 0.028 to 0.041]). The 0.70 threshold provided optimal discrimination in the subgroup analysis of ever smokers and in adjusted models. Defining airflow obstruction as FEV1:FVC less than 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different or was more accurate than other fixed thresholds and the LLN. These results support the use of FEV1:FVC less than 0.70 to identify individuals at risk of clinically significant COPD.


Physical activity promotion in primary care: a Utopian quest?
The health benefits of physical activity (PA) are acknowledged and promoted by the scientific community, especially within primary care. However, there is little evidence that such promotion is provided in any consistent or comprehensive format. Brief interventions (i.e. discussion, negotiation or encouragement) and exercise referral schemes (i.e. patients being formally referred to a PA professional) are the two dominant approaches within primary care. These cost-effective interventions can generate positive changes in health outcomes and PA levels in inactive patients who are at increased risk for non-communicable diseases. Their success relies on the acceptability and efficiency of primary care professionals to deliver PA counselling. To this end, appropriate training and financial support are crucial. Similarly, human resourcing and synergy between the different stakeholders must be addressed. To obtain maximum adherence, specific populations should be targeted and interventions adapted to their needs. Key enablers include motivational interviewing, social support and multi-disciplinary approaches. Leadership and lines of accountability must be clearly delineated to ensure the success of the initiatives promoting PA in primary care. The synergic and multisectoral action of several stakeholders, especially healthcare professionals, will help overcome physical inactivity in a sustainable way.


Sexual abuse and psychotic phenomena: a directed acyclic graph analysis of affective symptoms using English national psychiatric survey data.
Sexual abuse and bullying are associated with poor mental health in adulthood. We previously established a clear relationship between bullying and symptoms of psychosis. Similarly, we would expect sexual abuse to be linked to the emergence of psychotic symptoms, through effects on negative affect. We analysed English data from the Adult Psychiatric Morbidity Surveys, carried out in 2007 (N = 5954) and 2014 (N = 5946), based on representative national samples living in private households. We used probabilistic graphical models represented by directed acyclic graphs (DAGs). We obtained measures of persecutory ideation and auditory hallucinosis from the Psychosis Screening Questionnaire, and identified affective symptoms using the Clinical Interview Schedule. We included cannabis consumption and sex as they may determine the relationship between symptoms. We constrained incoming edges to sexual abuse and bullying to respect temporality. In the DAG analyses, contrary to our expectations, paranoia appeared early in the cascade of relationships, close to the abuse variables, and generally lying upstream of affective symptoms. Paranoia was consistently directly antecedent to hallucinations, but also indirectly so, via non-psychotic symptoms. Hallucinosis was also the endpoint of pathways involving non-psychotic symptoms. Via worry, sexual abuse and bullying appear to drive a range of affective symptoms, and in some people, these may encourage the emergence of hallucinations. The link between adverse experiences and paranoia is much more direct. These findings have implications for managing distressing outcomes. In particular, worry may be a salient target for intervention in psychosis.


The Oms66 (p66) protein is a Borrelia burgdorferi porin.
In this study we report the purification and characterization of a 66-kDa protein, designated Oms66, for outer membrane-spanning 66-kDa protein, that functions as a porin in the outer membrane (OM) of Borrelia burgdorferi. Oms66 was purified by fast-performance liquid chromatography and exhibited an average single-channel conductance of 9.62 +/- 0.37 nS in 1 M KCl, as evidenced by 581 individual insertional events in planar lipid bilayers. Electrophysiological characterization indicated that Oms66 was virtually nonselective between cations and anions and exhibited voltage-dependent closure with multiple substates. The amino acid sequence of tryptic peptides derived from purified Oms66 was identical to the deduced amino acid sequence of p66, a previously described surface-exposed protein of B. burgdorferi. Purified Oms66 was recognized by antiserum specific for p66 and serum from rabbits immune to challenge with virulent B. burgdorferi, indicating that p66 and Oms66 were identical proteins and that Oms66/p66 is an immunogenic protein in infected rabbits. In a methodology that reduces liposomal trapping and nonspecific interactions, native Oms66 was incorporated into liposomes, confirming that Oms66 is an outer membrane-spanning protein. Proteoliposomes containing Oms66 exhibited porin activity nearly identical to that of native, purified Oms66, indicating that reconstituted Oms66 retained native conformation. The use of proteoliposomes reconstituted with Oms66 and other Oms proteins provides an experimental system for determinating the relationship between conformation, protection, and biological function of these molecules.


DNA double-strand breaks cooperate with loss of Ink4 and Arf tumor suppressors to generate glioblastomas with frequent Met amplification.
Glioblastomas (GBM) are highly radioresistant and lethal brain tumors. Ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) are a risk factor for the development of GBM. In this study, we systematically examined the contribution of IR-induced DSBs to GBM development using transgenic mouse models harboring brain-targeted deletions of key tumor suppressors frequently lost in GBM, namely Ink4a, Ink4b, Arf and/or PTEN. Using low linear energy transfer (LET) X-rays to generate simple breaks or high LET HZE particles (Fe ions) to generate complex breaks, we found that DSBs induce high-grade gliomas in these mice which, otherwise, do not develop gliomas spontaneously. Loss of Ink4a and Arf was sufficient to trigger IR-induced glioma development but additional loss of Ink4b significantly increased tumor incidence. We analyzed IR-induced tumors for copy number alterations to identify oncogenic changes that were generated and selected for as a consequence of stochastic DSB events. We found Met amplification to be the most significant oncogenic event in these radiation-induced gliomas. Importantly, Met activation resulted in the expression of Sox2, a GBM cancer stem cell marker, and was obligatory for tumor formation. In sum, these results indicate that radiation-induced DSBs cooperate with loss of Ink4 and Arf tumor suppressors to generate high-grade gliomas that are commonly driven by Met amplification and activation.


Shape of the BMI-mortality association by cause of death, using generalized additive models: NHIS 1986-2006.
Numerous studies have examined the association between body mass index (BMI) and mortality. The precise shape of their association, however, has not been established. We use nonparametric methods to determine the relationship between BMI and mortality. Data from the National Health Interview Survey-Linked Mortality Files 1986-2006 for adults aged 50 to 80 are analyzed using a Poisson approach to survival modeling within the generalized additive model (GAM) framework. The BMI-mortality association is more V shaped than U shaped, with the odds of dying rising steeply from the lowest risk point at BMIs of 23 to 26. The association varies considerably by time since interview and cause of death. For instance, the association has an inverted J shape for respiratory causes but is monotonically increasing for diabetes deaths. Our findings have implications for interpreting results from BMI-mortality studies and suggest caution in translating the findings into public health messages.


Transcription factor AP-2 beta genotype and psychosocial adversity in relation to adolescent depressive symptomatology.
The aim of this study was to investigate possible interactions between the gene coding for activating protein-2 beta (AP-2 beta) and psychosocial factors to predict depressive symptoms in adolescents. Two-hundred 16- and 19-year-old adolescents from the county of Västmanland, Sweden, were asked to complete a questionnaire, interviewed about psychosocial risk factors, and genotyped with regard to the transcription factor AP-2 beta intron 2 polymorphism. AP-2 beta genotype interacted significantly both with type of housing and parental separation to predict depressive symptoms. Individuals who were homozygous for the short AP-2 beta allele displayed higher depression scores when psychosocial adversity was taken into account. Amongst carriers of one or two copies of the long allele, there was no difference in depressive symptoms despite differences in psychosocial environments.


Diversity of alpha-fetoprotein gene expression in mice is generated by a combination of separate enhancer elements.
The 5' flanking region of the mouse alpha-fetoprotein (AFP) gene contains a tissue-specific promoter and three upstream regulatory elements that behave as classical enhancers. At least one of these enhancers is now shown to be required for the tissue-specific expression of the AFP gene when it is introduced into the mouse genome by microinjection of cloned DNA fragments into fertilized eggs. Each enhancer can direct expression in the appropriate tissues, the visceral endoderm of the yolk sac, the fetal liver, and the gastrointestinal tract, but each exerts different influence in these three tissues. These differences may explain the tissue-specific diversity in the levels of expression characteristic of the AFP gene. The postnatal repression of transcription of the AFP gene in both liver and gut, as well as the reinitiation of its transcription during liver regeneration, is mimicked by the introduced gene when it is linked to the enhancer domains together or singly. Thus, the DNA sequence elements responsible for directing the activation of AFP transcription, its repression, and reinduction are contained in a limited segment of DNA within or 5' to the gene (or both) and are operative in the absence of the closely linked albumin gene.


Survey of Borreliae in ticks, canines, and white-tailed deer from Arkansas, U.S.A.
In the Eastern and Upper Midwestern regions of North America, Ixodes scapularis (L.) is the most abundant tick species encountered by humans and the primary vector of B. burgdorferi, whereas in the southeastern region Amblyomma americanum (Say) is the most abundant tick species encountered by humans but cannot transmit B. burgdorferi. Surveys of Borreliae in ticks have been conducted in the southeastern United States and often these surveys identify B. lonestari as the primary Borrelia species, surveys have not included Arkansas ticks, canines, or white-tailed deer and B. lonestari is not considered pathogenic. The objective of this study was to identify Borrelia species within Arkansas by screening ticks (n=2123), canines (n=173), and white-tailed deer (n=228) to determine the identity and locations of Borreliae endemic to Arkansas using PCR amplification of the flagellin (flaB) gene. Field collected ticks from canines and from hunter-killed white-tailed were identified to species and life stage. After which, ticks and their hosts were screened for the presence of Borrelia using PCR to amplify the flaB gene. A subset of the positive samples was confirmed with bidirectional sequencing. In total 53 (21.2%) white-tailed deer, ten (6%) canines, and 583 (27.5%) Ixodid ticks (252 Ixodes scapularis, 161 A. americanum, 88 Rhipicephalus sanguineus, 50 Amblyomma maculatum, 19 Dermacentor variabilis, and 13 unidentified Amblyomma species) produced a Borrelia flaB amplicon. Of the positive ticks, 324 (22.7%) were collected from canines (151 A. americanum, 78 R. sanguineus, 43 I. scapularis, 26 A. maculatum, 18 D. variabilis, and 8 Amblyomma species) and 259 (37.2%) were collected from white-tailed deer (209 I. scapularis, 24 A. maculatum, 10 A. americanum, 10 R. sanguineus, 1 D. variabilis, and 5 Amblyomma species). None of the larvae were PCR positive. A majority of the flaB amplicons were homologous with B. lonestari sequences: 281 of the 296 sequenced ticks, 3 canines, and 27 deer. Only 22 deer, 7 canines, and 15 tick flaB amplicons (12 I. scapularis, 2 A. maculatum, and 1 Amblyomma species) were homologous with B. burgdorferi sequences. Data from this study identified multiple Borreliae genotypes in Arkansas ticks, canines and deer including B. burgdorferi and B. lonestari; however, B. lonestari was significantly more prevalent in the tick population than B. burgdorferi. Results from this study suggest that the majority of tick-borne diseases in Arkansas are not B. burgdorferi.


Summertime acute heat illness in U.S. emergency departments from 2006 through 2010: analysis of a nationally representative sample.
Patients with acute heat illness present primarily to emergency departments (EDs), yet little is known regarding these visits. We aimed to describe acute heat illness visits to U.S. EDs from 2006 through 2010 and identify factors associated with hospital admission or with death in the ED. We extracted ED case-level data from the Nationwide Emergency Department Sample (NEDS) for 2006-2010, defining cases as ED visits from May through September with any heat illness diagnosis (ICD-9-CM 992.0-992.9). We correlated visit rates and temperature anomalies, analyzed demographics and ED disposition, identified risk factors for adverse outcomes, and examined ED case fatality rates (CFR). There were 326,497 (95% CI: 308,372, 344,658) cases, with 287,875 (88.2%) treated and released, 38,392 (11.8%) admitted, and 230 (0.07%) died in the ED. Heat illness diagnoses were first-listed in 68%. 74.7% had heat exhaustion, 5.4% heat stroke. Visit rates were highly correlated with annual temperature anomalies (Pearson correlation coefficient 0.882, p = 0.005). Treat-and-release rates were highest for younger adults (26.2/100,000/year), whereas hospitalization and death-in-the-ED rates were highest for older adults (6.7 and 0.03/100,000/year, respectively); all rates were highest in rural areas. Heat stroke had an ED CFR of 99.4/10,000 (95% CI: 78.7, 120.1) visits and was diagnosed in 77.0% of deaths. Adjusted odds of hospital admission or death in the ED were higher among elders, males, urban and low-income residents, and those with chronic conditions. Heat illness presented to the ED frequently, with highest rates in rural areas. Case definitions should include all diagnoses. Visit rates were correlated with temperature anomalies. Heat stroke had a high ED CFR. Males, elders, and the chronically ill were at greatest risk of admission or death in the ED. Chronic disease burden exponentially increased this risk.


Withdrawal of antithrombotic agents and its impact on ischemic stroke occurrence.
Antithrombotic medications (anticoagulants and antiplatelets) are often withheld in the periprocedural period and after bleeding complications to limit the risk of new or recurrent bleeding. These medications are also stopped by patients for various reasons such as cost, side effects, or unwillingness to take medication. Patient records from the population-based Greater Cincinnati/Northern Kentucky Stroke Study were reviewed to identify cases of ischemic stroke in 2005 and determine the temporal association of strokes with withdrawal of antithrombotic medication. Ischemic strokes and reasons for medication withdrawal were identified by study nurses for subsequent physician review. In 2005, 2197 cases of ischemic stroke among residents of the region were identified through hospital discharge records. Of the 2197 ischemic strokes, 114 (5.2%) occurred within 60 days of an antithrombotic medication withdrawal, 61 (53.5%) of these after stoppage of warfarin and the remainder after stoppage of an antiplatelet medication. Of the strokes after withdrawal, 71 (62.3%) were first-ever and 43 (37.7%) were recurrent; 54 (47.4%) occurred after withdrawal of medication by a physician in the periprocedural period. The withdrawal of antiplatelet and antithrombotic medications in the 60 days preceding an acute ischemic stroke was associated with 5.2% of ischemic strokes in our study population. This finding emphasizes the need for thoughtful decision-making concerning antithrombotic medication use in the periprocedural period and efforts to improve patient compliance.


The Effectiveness of Cervical Spondylosis Therapy with Saunders Traction Device and High-Intensity Laser Therapy: A Randomized Controlled Trial.
BACKGROUND Among all spinal therapies, treatment of the cervical segment is the most difficult. The cervical segment is particularly sensitive to injuries and pain, and it also requires special care due to its great mobility and most delicate construction. The aim of this research was to evaluate analgesic efficacy and improvement of active mobility of the cervical spine after traction therapy with the Saunders device and high-intensity laser therapy (HILT) immediately after therapy, and in short-, medium-, and long-term follow-up in patients with cervical spondylosis. MATERIAL AND METHODS The study included 174 patients (114 women and 60 men) aged 24-67 years. The patients were divided into two randomized groups. In group I (88 subjects) traction therapy with the Saunders device was applied, and in group II (86 subjects) HILT was applied. The measurement of the range of cervical spine movement, a subjective visual scale for pain (Visual Analog Scale [VAS]), and the Neck Disability Index-Polish Version (NDI) questionnaire were used. RESULTS The results obtained by the Saunders and HILT methods were similar immediately after the therapy and after 4 weeks (the medium-term follow-up). However, in long-term follow-up, there was a significant increase in the maintenance of positive therapeutic effects with the HILT method. CONCLUSIONS Both therapeutic methods improved the efficiency and demonstrated analgesic efficacy in patients with cervical spondylosis immediately and in the medium term after the therapy. HILT was more effective than the Saunders method in long-term follow-up.


Hepatoprotective properties of kombucha tea against TBHP-induced oxidative stress via suppression of mitochondria dependent apoptosis.
Kombucha, a fermented tea (KT) is claimed to possess many beneficial properties. Recent studies have suggested that KT prevents paracetamol and carbon tetrachloride-induced hepatotoxicity. We investigated the beneficial role of KT was against tertiary butyl hydroperoxide (TBHP) induced cytotoxicity and cell death in murine hepatocytes. TBHP is a well known reactive oxygen species (ROS) inducer, and it induces oxidative stress in organ pathophysiology. In our experiments, TBHP caused a reduction in cell viability, enhanced the membrane leakage and disturbed the intra-cellular antioxidant machineries while simultaneous treatment of the cells with KT and this ROS inducer maintained membrane integrity and prevented the alterations in the cellular antioxidant status. These findings led us to explore the detailed molecular mechanisms involved in the protective effect of KT. TBHP introduced apoptosis as the primary phenomena of cell death as evidenced by flow cytometric analyses. In addition, ROS generation, changes in the mitochondrial membrane potential, cytochrome c release, activation of caspases (3 and 9) and Apaf-1 were detected confirming involvement of mitochondrial pathway in this pathophysiology. Simultaneous treatment of KT with TBHP, on the other hand, protected the cells against oxidative injury and maintained their normal physiology. In conclusion, KT was found to modulate the oxidative stress induced apoptosis in murine hepatocytes probably due to its antioxidant activity and functioning via mitochondria dependent pathways and could be beneficial against liver diseases, where oxidative stress is known to play a crucial role.


Spinal Muscular Atrophy: More than a Disease of Motor Neurons?
Spinal muscular atrophy (SMA) is the most common genetically inherited neurodegenerative disease resulting in infant mortality. SMA is caused by genetic deletion or mutation in the survival of motor neuron 1 (SMN1) gene, which results in reduced levels of the survival of motor neuron (SMN) protein. SMN protein deficiency preferentially affects α- motor neurons, leading to their degeneration and subsequent atrophy of limb and trunk muscles, progressing to death in severe forms of the disease. More recent studies have shown that SMN protein depletion is detrimental to the functioning of other tissues including skeletal muscle, heart, autonomic and enteric nervous systems, metabolic/endocrine (e.g. pancreas), lymphatic, bone and reproductive system. In this review, we summarize studies discussing SMN protein's function in various cell and tissue types and their involvement in the context of SMA disease etiology. Taken together, these studies indicate that SMA is a multi-organ disease, which suggests that truly effective disease intervention may require body-wide correction of SMN protein levels.


Regulation and dysregulation of fibrosis in skeletal muscle.
In response to skeletal muscle injury, distinct cellular pathways are activated to repair the damaged tissue. Activation and restriction of these pathways must be temporally coordinated in a precise sequence as regeneration progresses if muscle integrity and homeostasis are to be restored. However, if tissue injury persists, as in severe muscular dystrophies, the repair process becomes uncontrolled leading to the substitution of myofibers by a non-functional mass of fibrotic tissue. In this review, we provide an overview of how muscle responds to damage and aging, with special emphasis on the cellular effectors and the regulatory and inflammatory pathways that can shift normal muscle repair to fibrosis development.


MACC1 expression is an indicator of recurrence in early-stage glottic cancer.
Metastasis-associated in colon cancer 1 (MACC1) has been reported to be an independent indicator of poor prognoses in some kinds of cancer due to disease metastasis or recurrence. We investigated the correlation between MACC1 expression and the prognosis of glottic cancer. Paraffin-embedded, early-stage (I or II) glottic cancer specimens (n = 52) were immunohistochemically analyzed to explore MACC1 expression. The clinical records associated with each case were also examined. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method, and between-group RFS differences were assessed using the log-rank test. The multivariate analyses were evaluated using the Cox's proportional-hazard model. Patients were treated with only radiotherapy (RT) (n = 37, including 18 with T1 disease and 19 with T2 disease), or with chemoradiotherapy (CRT) (n = 15, including 1 with T1 disease and 14 with T2 disease). Eleven patients demonstrated local recurrence and two patients experienced cervical lymph node recurrence. Tumor specimens were MACC1-positive in 9 of the 13 (69.2%) patients with local or neck recurrence, and 7 of the 11 (63.6%) patients with local recurrence. The RFS rate of patients who were treated with only RT was significantly lower than that of patients who were treated with CRT (P = 0.0243). The RFS rate was significantly lower in cases with MACC1 expression than in those without MACC1 expression (P = 0.0003). Multivariate analysis revealed that MACC1 expression was an independent risk factor of local recurrence (P = 0.0016). MACC1 is an independent indicator of recurrence related to RFS in early-stage glottic cancer.


Betaine-homocysteine methyltransferase: organ distribution in man, pig and rat and subcellular distribution in the rat.
1. Conflicting reports exist as to the organ distribution of betaine-homocysteine methyltransferase (EC 126.96.36.199). It is important to establish its presence or absence in brain, since its substrate, betaine, has recently become established in the treatment of certain diseases involving this organ. 2. It remains unclear whether the reported success of this treatment results from the use of betaine to methylate homocysteine and produce methionine in situ in neural tissue, or whether the effect is secondary to these same reductions happening in other organs, such as the liver. The former would require the presence of betaine-homocysteine methyltransferase in neural tissue. 3. This study demonstrates the complete absence of any activity for this enzyme in the brain of the three species examined. The enzyme was found to be present in both the liver and kidney of man and pig, but only in the liver of the rat. 4. The only source of betaine in cells is via the oxidation of choline. Since the enzymes involved in this conversion have never been shown to exist anywhere other than the mitochondria, it has been assumed that the methyltransferase is also mitochondrial. In this study, it is demonstrated that the enzyme exists only in the cytoplasm of rat liver cells.


Liquid versus gel handrub formulation: a prospective intervention study.
Hand hygiene is one of the cornerstones of the prevention of health care-associated infection, but health care worker (HCW) compliance with good practices remains low. Alcohol-based handrub is the new standard for hand hygiene action worldwide and usually requires a system change for its successful introduction in routine care. Product acceptability by HCWs is a crucial step in this process. We conducted a prospective intervention study to compare the impact on HCW compliance of a liquid (study phase I) versus a gel (phase II) handrub formulation of the same product during daily patient care. All staff (102 HCWs) of the medical intensive care unit participated. Compliance with hand hygiene was monitored by a single observer. Skin tolerance and product acceptability were assessed using subjective and objective scoring systems, self-report questionnaires, and biometric measurements. Logistic regression was used to estimate the association between predictors and compliance with the handrub formulation as the main explanatory variable and to adjust for potential risk factors. Overall compliance (phases I and II) with hand hygiene practices among nurses, physicians, nursing assistants, and other HCWs was 39.1%, 27.1%, 31.1%, and 13.9%, respectively (p = 0.027). Easy access to handrub improved compliance (35.3% versus 50.6%, p = 0.035). Nurse status, working on morning shifts, use of the gel formulation, and availability of the alcohol-based handrub in the HCW's pocket were independently associated with higher compliance. Immediate accessibility was the strongest predictor. Based on self-assessment, observer assessment, and the measurement of epidermal water content, the gel performed significantly better than the liquid formulation. Facilitated access to an alcohol-based gel formulation leads to improved compliance with hand hygiene and better skin condition in HCWs.


'Well, if the kids can do it, I can do it': older rehabilitation patients' experiences of telerehabilitation.
Although trials continue to emerge supporting the role of telerehabilitation, implementation has been slow. Key users include older people living with disabilities who are frequent users of hospital rehabilitation services but whose voices are rarely heard. It is unclear whether the use of technologies and reduced face-to-face contact is acceptable to these people. We report on a qualitative study of community dwelling participants who had received a home telerehabilitation programme as an alternative to conventional rehabilitation. Thirteen older participants, three spouses and one carer were interviewed. All had participated in an individualized therapy programme, using a combination of face-to-face and video consults with therapists. The programme used 'off-the-shelf' technologies including iPads for videoconferencing and electronic FitBitR devices. Interviews were recorded, transcribed verbatim and analysed using NVivo software. Thematic analysis resulted in five emergent themes: (i) telerehabilitation is convenient; (ii) telerehabilitation promotes motivation and self-awareness; (iii) telerehabilitation fosters positive therapeutic relationships; (iv) mastering technologies used by younger relatives is a valued aspect of telerehabilitation; and (v) Telerehabilitation does not replace traditional face-to-face rehabilitation therapies. Participants found telerehabilitation convenient and motivating, coped well with the technology and developed positive therapeutic relationships. The learning and practice aspects sat well in the context of a rehabilitation programme. The use of commercially available technologies may have contributed to respondents' high levels of acceptability. The perception of telerehabilitation as complementary to in-person care and the expectation of technological support have implications for the implementation and delivery of telerehabilitation services to older people.


Postprandial gastric function in pancreatic insufficiency.
Abnormalities in postprandial gastric function could contribute to the maldigestion of pancreatic insufficiency. To measure simultaneously postprandial gastric secretion and emptying and correlate these measurements with intraluminal duodenal changes, we performed intestinal intubation and duodenal perfusion during feeding of a solid-liquid test meal in 10 healthy controls and 10 patients with documented pancreatic insufficiency before and after replacement therapy. In pancreatic insufficiency, intraduodenal pH was significantly decreased late in the postprandial period while simultaneously measured duodenal acid loads were normal, confirming that reduced bicarbonate output rather than increased acid delivery was responsible for higher duodenal acidity in these patients. Significant (P less than 0.05) reductions in postprandial acid, pepsin, and total secretory outputs were noted in untreated patients only during the first postprandial hour. Absolute gastric emptying rates were lower in patients (P less than 0.05) than in healthy subjects, but fractional rates of emptying were similar. Fasting and postprandial hypergastrinaemia were consistently observed in the patients with pancreatic disease. There are postprandial disturbances of secretory function but no primary gastric motor defect in patients with exocrine pancreatic insufficiency.


Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans.
Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement. To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population. Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion. Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars. Here we report the sequence of the P. infestans genome, which at approximately 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for approximately 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.


The importance of Rho-associated kinase-induced Ca2+ sensitization as a component of electromechanical and pharmacomechanical coupling in rat ureteric smooth muscle.
Ureteric peristalsis, which occurs via alternating contraction and relaxation of ureteric smooth muscle, ensures the unidirectional flow of urine from the kidney to the bladder. Understanding of the molecular mechanisms underlying ureteric excitation-contraction coupling, however, is limited. To address these knowledge deficits, and in particular to test the hypothesis that Ca2+ sensitization via activation of the RhoA/Rho-associated kinase (ROK) pathway plays an important role in ureteric smooth muscle contraction, we carried out a thorough characterization of the electrical activity, Ca2+ signaling, MYPT1 (myosin targeting subunit of myosin light chain phosphatase, MLCP) and myosin regulatory light chain (LC20) phosphorylation, and force responses to membrane depolarization induced by KCl (electromechanical coupling) and carbachol (CCh) (pharmacomechanical coupling). The effects of ROK inhibition on these parameters were investigated. We conclude that the tonic, but not the phasic component of KCl- or CCh-induced ureteric smooth muscle contraction is highly dependent on ROK-catalyzed phosphorylation of MYPT1 at T855, leading to inhibition of MLCP and increased LC20 phosphorylation.


Telomeres in the mouse have large inter-chromosomal variations in the number of T2AG3 repeats.
The ultra-long telomeres that have been observed in mice are not in accordance with the concept that critical telomere shortening is related to aging and immortalization. Here, we have used quantitative fluorescence in situ hybridization to estimate (T2AG3)n lengths of individual telomeres in various mouse strains. Telomere lengths were very heterogeneous, but specific chromosomes of bone marrow cells and skin fibroblasts from individual mice had similar telomere lengths. We estimate that the shortest telomeres are around 10 kb in length, indicating that each mouse cell has a few telomeres with (T2AG3)n lengths within the range of human telomeres. These short telomeres may be critical in limiting the replicative potential of murine cells.


Central trajectories of type II spiral ganglion neurons.
Previous attempts to trace the central pathways of the thin axons from type II spiral ganglion neurons have been hampered by technical difficulties such as fading of the reaction product as distance increases from the injection site (Ryugo et al.: Soc. Neurosci. Abstr. 12:779, '86; Brown: J. Comp. Neurol. 260:591-604, '87). By using small rodents (gerbils and mice), which have short auditory nerves, we have succeeded in filling the entire central axon and terminals of type II neurons after peripheral injections of horseradish peroxidase. The general course of the type II fibers within the auditory nerve and cochlear nucleus is similar to that of type I fibers except that terminals from type II neurons are often found in regions of the cochlear nucleus that have high densities of granule cells.


A survey of filariasis among refugees in south Florida.
Between January 1981 and March 1982, a filariasis survey was conducted among 668 Haitian immigrants and 155 Southeast Asian refugees residing in Florida, U.S.A. Microfilariae were detected only in Haitians, with 6.7% positive for Wuchereria bancrofti and 1.3% positive for Mansonella ozzardi. The majority of individuals with bancroftian filariasis came from five coastal urban areas including Port-au-Prince, Duvalierville, Gonaïves, Leógane and Cap-Haitien. No unequivocal signs of bancroftian filariasis or mansonellosis were seen. Membrane feeding of several species and strains of laboratory-reared mosquitoes on blood from a volunteer microfilaremic with W. bancrofti showed that Aedes aegypti and A. taeniorhynchus, but not Culex quinquefasciatus, were susceptible to infection with the Haitian strain of W. bancrofti. Culicoides furens, a known vector of M. ozzardi in Haiti and present in Florida, was not tested. Further studies are needed to determine the competence of Florida vectors for transmitting W. bancrofti and M. ozzardi to the indigenous human population.


Preparation and characterization of high-surface-area Bi(1-x)/3V(1-x)Mo(x)O4 catalysts.
We report the successful application of a templating approach employing ordered mesoporous carbon to the synthesis of BiVO4, Bi2Mo3O12, and Bi0.85V0.55Mo0.45O4 and the performance of these materials as catalysts for the oxidation of propene to acrolein. Ordered mesoporous carbon templates were used to control the nucleation and growth of the mixed metal oxide crystals, allowing higher final surface areas to be obtained. The resulting materials were characterized by X-ray diffraction, Raman spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and BET surface area analysis. The surface area of the mixed metal oxide catalysts was found to depend on the type of mesoporous silica used to prepare the carbon template and on the conditions under which the carbon template was formed. Through an appropriate choice of template, the surface areas of the mixed metal oxides exceeded 15 m(2)/g. Catalytic testing revealed that materials produced via templating in ordered mesoporous carbon had per-gram activities that were up to 85 times higher than those produced by a conventional hydrothermal synthesis and exhibited stable catalytic activities over 24 h.


Implementing a Palliative Care Nurse Leadership Fellowship Program in Uganda.
Global oncology and palliative care needs are increasing faster than the available capacity to meet these needs. This is particularly marked in sub-Saharan Africa, where healthcare capacity and systems are limited and resources are stretched. Uganda, a country of 35.6 million people in eastern Africa, faces the challenges of a high burden of communicable disease and a rising number of cases of non-communicable disease, including cancer. The vast majority of patients in Uganda are diagnosed with cancer too late for curative treatment to be an option because of factors like poor access to healthcare facilities, a lack of health education, poverty, and delays resulting from seeking local herbal or other traditional remedies. This article describes an innovative model of nurse leadership training in Uganda to improve the delivery of palliative care. The authors believe this model can be applicable to other low- and middle-income countries, where health resources are constrained and care needs are great. .


Gas chromatographic analysis of amino acids in physiological fluids: a critique.
The available methodology for sample purification prior to gas chromatographic analysis of amino acids in physiological fluids and tissue extracts is analysed. It would appear that over the past ten years the method of choice is that of an ion-exchange purification step, and little, if any, progress has been achieved in sample purification procedures. The inherent disadvantages of such a methodology are not only perpetuated but also cast some considerable doubt on the accuracy of the quantitative analysis of amino acids.


Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference.
Diamond Blackfan anaemia (DBA) is a rare, genetically and clinically heterogeneous, inherited red cell aplasia. Classical DBA affects about seven per million live births and presents during the first year of life. However, as mutated genes have been discovered in DBA, non-classical cases with less distinct phenotypes are being described in adults as well as children. In caring for these patients it is often difficult to have a clear understanding of the treatment options and their outcomes because of the lack of complete information on the natural history of the disease. The purpose of this document is to review the criteria for diagnosis, evaluate the available treatment options, including corticosteroid and transfusion therapies and stem cell transplantation, and propose a plan for optimizing patient care. Congenital anomalies, mode of inheritance, cancer predisposition, and pregnancy in DBA are also reviewed. Evidence-based conclusions will be made when possible; however, as in many rare diseases, the data are often anecdotal and the recommendations are based upon the best judgment of experienced clinicians. The recommendations regarding the diagnosis and management described in this report are the result of deliberations and discussions at an international consensus conference.


Open-Ended Evolution and a Mechanism of Novelties in Web Services.
Web services are analogous to living ecosystems in nature, in that they form an artificial ecosystem consisting of many tags and their associated media, such as photographs, movies, and web pages created by human users. In biological ecosystems, we view a tag as a species and a human as a hidden environmental resource. Our study examines the evolution of web services, in particular social tagging systems, with respect to the self-organization of new tags. The evolution of new combinations of tags is analyzed as an open-ended evolution (OEE) index. Tag meaning is computed by types of associated tags, including tags that vary their meanings temporally, which, we argue, are examples of OEE.


Interleukin expression after injury and the effects of interleukin-1 receptor antagonist.
Ligament healing follows a series of complex coordinated events involving various cell types, cytokines, as well as other factors, producing a mechanically inferior tissue more scar-like than native tissue. Macrophages provide an ongoing source of cytokines to modulate inflammatory cell adhesion and migration as well as fibroblast proliferation. Studying interleukins inherent to ligament healing during peak macrophage activation and angiogenesis may elucidate inflammatory mediators involved in subsequent scar formation. Herein, we used a rat healing model assayed after surgical transection of their medial collateral ligaments (MCLs). On days 3 and 7 post-injury, ligaments were collected and used for microarray analysis. Of the 12 significantly modified interleukins, components of the interleukin-1 family were significantly up-regulated. We therefore examined the influence of interleukin-1 receptor antagonist (IL-1Ra) on MCL healing. Transected rat MCLs received PBS or IL-1Ra at the time of surgery. Inhibition of IL-1 activation decreased pro-inflammatory cytokines (IL-1α, IL-1β, IL-12, IL-2, and IFN-γ), myofibroblasts, and proliferating cells, as well as increased anti-inflammatory cytokines (IL-10), endothelial cells/blood vessel lumen, M2 macrophages, and granulation tissue size without compromising the mechanical properties. These results support the concept that IL-1Ra modulates MCL-localized granulation tissue components and cytokine production to create a transient environment that is less inflammatory. Overall, IL-1Ra may have therapeutic potential early in the healing cascade by stimulating the M2 macrophages and altering the granulation tissue components. However, the single dose of IL-1Ra used in this study was insufficient to maintain the more regenerative early response. Due to the transient influence on most of the healing components tested, IL-1Ra may have greater therapeutic potential with sustained delivery.


The distribution of active force generators controls mitotic spindle position.
During unequal cell divisions a mitotic spindle is eccentrically positioned before cell cleavage. To determine the basis of the net force imbalance that causes spindle displacement in one-cell Caenorhabditis elegans embryos, we fragmented centrosomes with an ultraviolet laser. Analysis of the mean and variance of fragment speeds suggests that the force imbalance is due to a larger number of force generators pulling on astral microtubules of the posterior aster relative to the anterior aster. Moreover, activation of heterotrimeric guanine nucleotide- binding protein (Gprotein) alpha subunits is required to generate these astral forces.


Alzheimer disease: mercury as pathogenetic factor and apolipoprotein E as a moderator.
The etiology of most cases of Alzheimer's disease (AD) is as yet unknown. Epidemiological studies suggest that environmental factors may be involved beside genetic risk factors. Some studies have shown higher mercury concentrations in brains of deceased and in blood of living patients with Alzheimer's disease. Experimental studies have found that even smallest amounts of mercury but no other metals in low concentrations were able to cause all nerve cell changes, which are typical for Alzheimer's disease. The most important genetic risk factor for sporadic Alzheimer's disease is the presence of the apolipoprotein Ee4 allele whereas the apolipoprotein Ee2 allele reduces the risk of developing Alzheimer's disease. Some investigators have suggested that apolipoprotein Ee4 has a reduced ability to bind metals like mercury and therefore explain the higher risk for Alzheimer's disease. Therapeutic approaches embrace pharmaceuticals which bind metals in the brain of patients with Alzheimer's disease. In sum, both the findings from epidemiological and demographical studies, the frequency of amalgam application in industrialized countries, clinical studies, experimental studies and the dental state of AD patients in comparison to controls suggest a decisive role for inorganic mercury in the etiology of AD.


Maximum likelihood supertrees.
We analyze a maximum likelihood approach for combining phylogenetic trees into a larger "supertree." This is based on a simple exponential model of phylogenetic error, which ensures that ML supertrees have a simple combinatorial description (as a median tree, minimizing a weighted sum of distances to the input trees). We show that this approach to ML supertree reconstruction is statistically consistent (it converges on the true species supertree as more input trees are combined), in contrast to the widely used MRP method, which we show can be statistically inconsistent under the exponential error model. We also show that this statistical consistency extends to an ML approach for constructing species supertrees from gene trees. In this setting, incomplete lineage sorting (due to coalescence rates of homologous genes being lower than speciation rates) has been shown to lead to gene trees that are frequently different from species trees, and this can confound efforts to reconstruct the species phylogeny correctly.


Various penA mutations together with mtrR, porB and ponA mutations in Neisseria gonorrhoeae isolates with reduced susceptibility to cefixime or ceftriaxone.
To examine mutations within the penA, mtrR, porB, ponA and pilQ genes of Neisseria gonorrhoeae to determine their contribution to cephalosporin resistance. A total of 46 N. gonorrhoeae isolates with reduced susceptibility to cefixime or ceftriaxone (MICs > or = 0.12 mg/L) and two susceptible isolates were selected. The full sequence of penA and partial sequences previously reported as hot mutation sites of the other genes were analysed. Genotyping by N. gonorrhoeae multiantigen sequence typing (NG-MAST) was also performed. A mosaic penicillin-binding protein 2 (PBP 2) was found in a single isolate that exhibited the highest cefixime MIC (0.5 mg/L). The majority of the isolates with reduced susceptibility to cephalosporins contained non-mosaic PBP 2 sequences, of which PBP 2 pattern XIII was most common (28/46). All isolates with reduced susceptibility to cephalosporins also had mtrR and porB mutations. Two susceptible isolates had the PBP 2 pattern XIV and an incomplete MtrR protein, which was a new mutation. Isolates with identical PBP 2 patterns comprised multiple NG-MAST sequence types. Reduced susceptibility of N. gonorrhoeae to ceftriaxone and cefixime was associated with diverse penA mutations, particularly PBP 2 pattern XIII containing an Ala-501-->Val substitution, together with mtrR and porB mutations. The existence of only one strain having the mosaic penA sequence indicated that ceftriaxone and cefixime resistance in Korea is mostly not associated with a mosaic penA sequence. Highly heterogeneous NG-MAST sequence types excluded the clonal expansion of a particular subtype.


Telehealth system: A randomized controlled trial evaluating the impact of an internet-based exercise intervention on quality of life, pain, muscle strength, and fatigue in breast cancer survivors.
The chronicity status of breast cancer survivors suggests a growing need for cancer rehabilitation. Currently, the use of technology is a promising strategy for providing support, as reflected in the emergence of research interest in Web-based interventions in cancer survivorship. A randomized controlled trial was conducted that included a total of 81 participants who had completed adjuvant therapy (except hormone treatment) for stage I to IIIA breast cancer. Participants were randomly assigned to an 8-week Internet-based, tailored exercise program (n = 40) or to a control group (n = 41).The instruments used at baseline, 8 weeks, and 6-month follow-up were the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and its breast cancer module, the Brief Pain Inventory, the handgrip dynamometer, the isometric abdominal test, the back dynamometer, the multiple sit-to-stand test, and the Piper Fatigue Scale. After the intervention, the telerehabilitation group had significantly improved scores for global health status, physical, role, cognitive functioning, and arm symptoms (all P < .01) as well as pain severity (P = .001) and pain interference (P = .045) compared with the control group. Significant improvements also were observed favoring the telerehabilitation group for affected and nonaffected side handgrip (both P = .006), abdominal, back and lower body strength (all P < .01), and total fatigue (P < .001). These findings were maintained after 6 months of follow-up, except for role functioning, pain severity, and nonaffected side handgrip. Analysis was based on an intention-to-treat principle. This program may improve adverse effects and maintain benefits in breast cancer survivors. The results of this study have encouraging implications for cancer care. Cancer 2016;122:3166-74. © 2016 American Cancer Society.


Optimizing Cerebral Autoregulation May Decrease Neonatal Regional Hypoxic-Ischemic Brain Injury.
Therapeutic hypothermia provides incomplete neuroprotection for neonatal hypoxic-ischemic encephalopathy (HIE). We examined whether hemodynamic goals that support autoregulation are associated with decreased brain injury and whether these relationships are affected by birth asphyxia or vary by anatomic region. Neonates cooled for HIE received near-infrared spectroscopy autoregulation monitoring to identify the mean arterial blood pressure with optimized autoregulatory function (MAPOPT). Blood pressure deviation from MAPOPT was correlated with brain injury on MRI after adjusting for the effects of arterial carbon dioxide, vasopressors, seizures, and birth asphyxia severity. Blood pressure deviation from MAPOPT related to neurologic injury in several regions independent of birth asphyxia severity. Greater duration and deviation of blood pressure below MAPOPT were associated with greater injury in the paracentral gyri and white matter. Blood pressure within MAPOPT related to lesser injury in the white matter, putamen and globus pallidus, and brain stem. Finally, blood pressures that exceeded MAPOPT were associated with reduced injury in the paracentral gyri. Blood pressure deviation from optimal autoregulatory vasoreactivity was associated with MRI markers of brain injury that, in many regions, were independent of the initial birth asphyxia. Targeting hemodynamic ranges to optimize autoregulation has potential as an adjunctive therapy to hypothermia for HIE.


Serum Omega-6/Omega-3 Ratio and Risk Markers for Cardiovascular Disease in an Industrial Population of Delhi.
High omega-6/omega-3 ratio intake promotes development of many chronic diseases. Secondary prevention studies though have demonstrated a decline in progression of many such diseases after reducing the intake, specific biochemical indices of cardiovascular disease risk markers have not been evaluated. We have evaluated the circulating levels of omega-6/omega-3 ratio and its effect on cardiovascular risk markers in India. Present study was conducted in industrial setting where employees were randomly selected. Data on their demographic characteristics were collected using pre-tested questionnaire. Fasting blood samples were collected from all the participants. Serum was separated and stored at -80°C till the time of analysis. Lipids were estimated using standard kits. Fatty acids in serum were estimated by Gas chromatography. The identified Omega-3 fatty acid included were 18:3 (Alpha-linolenic acid), 20:5 (Eicosapentenoic acid) & 22:6 (Docosahexenoic acid). Among omega-6 included were 18:2 (linoleic acid), 18:3 (gamma-linolenic acid) & 20:4 (Arachidonic acid). Complete data was available for 176 participants (89% males and 11% females) with mean age of 47.23 ± 6.00 years. The bmi of the participants was 24.88 ± 3.43 Kg/m2 and waist circumference was 91.50 ± 9.56 cm. The median of omega-6/omega-3 ratio in the study population was 36.69 (range: 6.21 - 183.69). The levels of total cholesterol, triglycerides, ldl-cholesterol and cholesterol/hdl ratio and apo B correlated significantly with omega-6/3 ratio. There was no correlation observed with hsCRP and LDL-particle size. A direct relationship of omega-6/omega-3 ratio with dyslipidemia was observed in our study.


What do health care unions do?: A response to Manthous.
In response to Manthous, we discuss the role of unions in health care. The ethical quandary that Manthous perceives in health care worker unions is overstated because patient and worker interests are frequently aligned. The search for a "selfless" union overlooks the importance of adequate compensation for providing excellent care. The collective actions employed by health care workers' unions need not include strikes or slowdowns and can be consistent with patient safety and well-being.


Aspergillus fumigatus enhances human NK cell activity by regulating M1 macrophage polarization.
The progression of disease caused by fungal infection is closely associated with the human immune system. Macrophages and natural killer cells (NK cells) are two important types of innate immune cells that serve an important role in anti‑infection immunity. There has been limited research into the interactions between fungi and macrophages. In the present in vitro study, reverse transcription‑quantitative PCR, ELISA and flow cytometry were performed to reveal that the interaction between macrophages and NK cells, regulated by Aspergillus fumigatus conidia, induced macrophages to polarize into M1 macrophages by secreting large quantities of tumor necrosis factor‑α, interleukin‑18 and Galectin‑9. In addition, when NK cells were co‑cultured with the conidia of A. fumigatus‑stimulated M1 macrophages, they exhibited increased activation levels and secretion of interferon‑γ (IFN‑γ). It was further demonstrated via antibody neutralization and gene silencing experiments that galectin‑9 served an important role in the interaction between macrophages and NK cells regulated by A. fumigatus. In conclusion, it was demonstrated that A. fumigatus induced the polarization of macrophages into M1 macrophages by secreting Galectin‑9, which then promoted NK cell activity and IFN‑γ secretion. The results provided improved understanding of the role of innate immune cells in invasive fungal infections. The present study also provided novel insight into the study of macrophages and NK cells in inflammatory infections caused by A. fumigatus and potential strategies to control the progression of inflammation.


Latent Class Detection and Class Assignment: A Comparison of the MAXEIG Taxometric Procedure and Factor Mixture Modeling Approaches.
Taxometric procedures such as MAXEIG and factor mixture modeling (FMM) are used in latent class clustering, but they have very different sets of strengths and weaknesses. Taxometric procedures, popular in psychiatric and psychopathology applications, do not rely on distributional assumptions. Their sole purpose is to detect the presence of latent classes. The procedures capitalize on the assumption that, due to mean differences between two classes, item covariances within class are smaller than item covariances between the classes. FMM goes beyond class detection and permits the specification of hypothesis-based within-class covariance structures ranging from local independence to multidimensional within-class factor models. In principle, FMM permits the comparison of alternative models using likelihood-based indexes. These advantages come at the price of distributional assumptions. In addition, models are often highly parameterized and susceptible to misspecifications of the within-class covariance structure. Following an illustration with an empirical data set of binary depression items, the MAXEIG procedure and FMM are compared in a simulation study focusing on class detection and the assignment of subjects to the latent classes. FMM generally outperformed MAXEIG in terms of class detection and class assignment. Substantially different class sizes negatively impacted the performance of both approaches, whereas low class separation was much more problematic for MAXEIG than for the FMM.


Pelvic kinematic method for determining vertical jump height.
Sacral marker and pelvis reconstruction methods have been proposed to approximate total body center of mass during relatively low intensity gait and hopping tasks, but not during a maximum effort vertical jumping task. In this study, center of mass displacement was calculated using the pelvic kinematic method and compared with center of mass displacement using the ground-reaction force-impulse method, in experienced athletes (n = 13) performing restricted countermovement vertical jumps. Maximal vertical jumps were performed in a biomechanics laboratory, with data collected using an 8-camera motion analysis system and two force platforms. The pelvis center of mass was reconstructed from retro-reflective markers placed on the pelvis. Jump height was determined from the peak height of the pelvis center of mass minus the standing height. Strong linear relationships were observed between the pelvic kinematic and impulse methods (R² = .86; p < .01). The pelvic kinematic method underestimated jump height versus the impulse method, however, the difference was small (CV = 4.34%). This investigation demonstrates concurrent validity for the pelvic kinematic method to determine vertical jump height.


Globalization, migration health, and educational preparation for transnational medical encounters.
Unprecedented migration, a core dimension of contemporary globalization, challenges population health. In a world of increasing human mobility, many health outcomes are shaped by transnational interactions among care providers and care recipients who meet in settings where nationality/ethnic match is not an option. This review article explores the value of transnational competence (TC) education as preparation for ethnically and socially discordant clinical encounters. The relevance of TC's five core skill domains (analytic, emotional, creative, communicative, and functional) for migration health and the medical-school curriculum is elaborated. A pedagogical approach that prepares for the transnational health-care consultation is presented, with a focus on clinical-clerkship learning experiences. Educational preparation for contemporary medical encounters needs to include a comprehensive set of patient-focused interpersonal skills, be adaptable to a wide variety of service users and global practice sites, and possess utility in addressing both the quality of patient care and socio-political constraints on migration health.


A critical requirement for notch signaling in maintenance of the quiescent skeletal muscle stem cell state.
Notch signaling plays a key role in virtually all tissues and organs in metazoans; however, limited examples are available for the regulatory role of this pathway in adult quiescent stem cells. We performed a temporal and ontological assessment of effectors of the Notch pathway that indicated highest activity in freshly isolated satellite cells and, unexpectedly, a sharp decline before the first mitosis, and subsequently in proliferating, satellite cell-derived myoblasts. Using genetic tools to conditionally abrogate canonical Notch signaling during homeostasis, we demonstrate that satellite cells differentiate spontaneously and contribute to myofibers, thereby resulting in a severe depletion of the stem cell pool. Furthermore, whereas loss of Rbpj function provokes some satellite cells to proliferate before fusing, strikingly, the majority of mutant cells terminally differentiate unusually from the quiescent state, without passing through S-phase. This study establishes Notch signaling pathway as the first regulator of cellular quiescence in adult muscle stem cells.


Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma.
In multiple myeloma, karyotopic 14q32 translocations have been identified at a variable frequency (10-60% in different studies). In the majority of cases, the partner chromosome has not been identified (14q+), and in the remaining cases, a diverse array of chromosomal partners has been implicated, with 11q13 being the most common. We developed a comprehensive Southern blot assay to identify and distinguish different kinds of immunoglobulin heavy chain (IgH) switch recombination events. Illegitimate switch recombination fragments (defined as containing sequences from only one switch region) are potential markers of translocation events into IgH switch regions and were identified in 15 of 21 myeloma cell lines, including seven of eight karyotyped lines that have no detectable 14q32 translocation. From all nine lines or tumor samples analyzed further, cloned illegitimate switch recombination fragments were confirmed to be IgH switch translocation breakpoints. In three of these cases, the translocation breakpoint was shown to be present in the primary tumor. These translocation breakpoints involve six chromosomal loci: 4p16.3 (two lines and the one tumor); 6; 8q24.13; 11q13.3 (in three lines); 16q23.1; and 21q22.1. We suggest that translocations into the IgH locus (i) are frequent (karyotypic 14q32 translocations and/or illegitimate switch recombination fragments are present in primary tumor samples and in 19 of 21 lines that we have analyzed); (ii) occur mainly in switch regions; and (iii) involve a diverse but nonrandom array (i.e., frequently 11q13 or 4p16) of chromosomal partners. This appears to be the most frequent genetic abnormality in multiple myeloma.


Rapid assessment of drug susceptibilities of Mycobacterium tuberculosis by means of luciferase reporter phages.
Effective chemotherapy of tuberculosis requires rapid assessment of drug sensitivity because of the emergence of multidrug-resistant Mycobacterium tuberculosis. Drug susceptibility was assessed by a simple method based on the efficient production of photons by viable mycobacteria infected with specific reporter phages expressing the firefly luciferase gene. Light production was dependent on phage infection, expression of the luciferase gene, and the level of cellular adenosine triphosphate. Signals could be detected within minutes after infection of virulent M. tuberculosis with reporter phages. Culture of conventional strains with antituberculosis drugs, including isoniazid or rifampicin, resulted in extinction of light production. In contrast, light signals after luciferase reporter phage infection of drug-resistant strains continued to be produced. Luciferase reporter phages may help to reduce the time required for establishing antibiotic sensitivity of M. tuberculosis strains from weeks to days and to accelerate screening for new antituberculosis drugs.


Comparison of Immunogenetic Properties of Glial Tumors with Advanced Magnetic Resonance Imaging Findings.
To investigate the immunogenetic properties of glial tumors according to the World Health Organization 2016 glial tumor classification and develop an accurate diagnosis and treatment strategy by comparing preoperative advanced magnetic resonance (aMRI) technique findings of these results. This study was conducted at the Department of Neurosurgery at the Medical Faculty Hospital of Selcuk University between January 1, 2010 and January 4, 2017 and included 50 patients. MR spectroscopy (MRS), MR perfusion (PWI), and MR diffusion (DWI) were performed in 50 patients preoperatively. Patient data were obtained from the hospital's information system. Pathological diagnosis of all patients was taken from the department of pathology at the same medical faculty. Among the patients included in the study, 11 were grade II (22%), 7 were grade III (14%), and 32 were grade IV (64%). All patients were IDH1 stained: 22 were IDH mutant (44%) and 28 were IDH wild-type (56%). A statistically significant difference in the survival time was observed between IDH mutant and wild-type. IDH-mutant tumors were commonly located in the frontal lobe and IDH wild-type tumors in the parietal and temporal lobes. A significant difference in PWI relative cerebral blood volume (rCBV) and DWI apparent diffusion coefficients (ADC) was noted among grade II, III, and IV tumor groups. The PWI rCBV cut-off value for grade IV tumors was 2.05 (90% sensitivity, 78% specificity). No difference in the Cho/Cr ratio among grade II, III, and IV tumor groups was noted. A significant difference was noted between the IDH mutant and wild type in terms of PWI rCBV. The PWI rCBV cut-off value of IDH mutantâ€"wild type was 2.15. No difference in the Cho/Cr, Cho/NAA, and DWI apparent diffusion coefficients (p > 0.05) was noted between the IDH mutant and wild type. PWI rCBV is the most important prognostic value of aMRI used in tumor grading. PWI rCBV values could be significant in distinguishing IDH wild and mutant.


Estimate of the degree of inhomogeneity of the refractive index of dielectric films from spectroscopic ellipsometry.
Dielectric thin films often present microstructures that give rise to a variation of the refractive index with the distance from the substrate. We propose a method of analysis of ellipsometric data for homogeneous and slightly inhomogeneous films that are deposited on transparent substrates. Assuming a linear refractive-index gradient, we are able to determine not only the average index and the thickness but also the degree of inhomogeneity of the films by spectroscopic ellipsometry at variable angles of incidence. We apply this method to titanium dioxide films deposited on glass, which present different degrees of inhomogeneity depending on the preparation conditions.


Recruitment and retention of low-income minority women in a behavioral intervention to reduce smoking, depression, and intimate partner violence during pregnancy.
Researchers have frequently encountered difficulties in the recruitment and retention of minorities resulting in their under-representation in clinical trials. This report describes the successful strategies of recruitment and retention of African Americans and Latinos in a randomized clinical trial to reduce smoking, depression and intimate partner violence during pregnancy. Socio-demographic characteristics and risk profiles of retained vs. non-retained women and lost to follow-up vs. dropped-out women are presented. In addition, subgroups of pregnant women who are less (more) likely to be retained are identified. Pregnant African American women and Latinas who were Washington, DC residents, aged 18 years or more, and of 28 weeks gestational age or less were recruited at six prenatal care clinics. Potentially eligible women were screened for socio-demographic eligibility and the presence of the selected behavioral and psychological risks using an Audio Computer-Assisted Self-Interview. Eligible women who consented to participate completed a baseline telephone evaluation after which they were enrolled in the study and randomly assigned to either the intervention or the usual care group. Of the 1,398 eligible women, 1,191 (85%) agreed to participate in the study. Of the 1,191 women agreeing to participate, 1,070 completed the baseline evaluation and were enrolled in the study and randomized, for a recruitment rate of 90%. Of those enrolled, 1,044 were African American women. A total of 849 women completed the study, for a retention rate of 79%. Five percent dropped out and 12% were lost-to-follow up. Women retained in the study and those not retained were not statistically different with regard to socio-demographic characteristics and the targeted risks. Retention strategies included financial and other incentives, regular updates of contact information which was tracked and monitored by a computerized data management system available to all project staff, and attention to cultural competence with implementation of study procedures by appropriately selected, trained, and supervised staff. Single, less educated, alcohol and drug users, non-working, and non-WIC women represent minority women with expected low retention rates. We conclude that with targeted recruitment and retention strategies, minority women will participate at high rates in behavioral clinical trials. We also found that women who drop out are different from women who are lost to follow-up, and require different strategies to optimize their completion of the study.


Nonfatal clinical presentation of elephant endotheliotropic herpes virus discovered in a group of captive Asian elephants (Elephas maximus).
Several different strains of elephant endotheliotropic herpes virus-1 (EEHV-1) have been identified via polymerase chain reaction (PCR) techniques in both African and Asian elephants. EEHV-1 has been identified in both cutaneous lesions in healthy African elephants and fatal cases of hemorrhagic syndrome in Asian elephants. However, until now, no EEHV-1 strain has been identified or associated with otherwise healthy Asian elephants. This article describes recurrent nonendothelial lesions associated with EEHV-1 infection in a herd of Asian elephants not exhibiting fatal hemorrhagic syndrome. Genotypes of EEHV-1 strains, based on viral DNA polymerase and glycoprotein B, associated with fatal hemorrhagic syndrome, were compared to those identified in nonendothelial lesions. The same EEHV-1 genotypes were identified in fatal cases and mucosal lesions in otherwise healthy Asian elephants in this herd. Further studies of the Asian elephant immune system and virologic studies to determine the triggers of tissue tropism are needed before any conclusion can be reached. Elephant endotheliotropic herpes virus, EEHV, herpetic lesions, tropism.


Low vitamin D status is an independent predictor of increased frailty and all-cause mortality in older men: the Health in Men Study.
Hypovitaminosis D and frailty are common in the older population. We aimed to determine whether 25-hydroxyvitamin D [25(OH)D] concentrations are associated with frailty and mortality. We conducted a prospective cohort study. Participants included 4203 older men aged 70-88 years in Perth, Western Australia. 25(OH)D was measured by immunoassay. Frailty was assessed with the 5-point FRAIL (fatigue, resistance, ambulation, illness, and loss of weight) scale. Mortality was determined from the death registry via the Western Australian Data Linkage System. At baseline, 676 (16.1%) men were frail, as defined by having ≥3 deficits (FRAIL scale ≥ 3). In multivariate cross-sectional analysis, low vitamin D status, defined by the lowest quartile of 25(OH)D values (<52.9 nmol/L), was associated with increased prevalent frailty (odds ratio, 1.96; 95% confidence interval [CI], 1.52 to 2.52) in comparison to the highest quartile of 25(OH)D values (>81.6 nmol/L). After a mean period of 5.3 years, the adjusted odds ratio of being frail at follow-up for men with low vitamin D and having zero deficit at baseline (FRAIL scale = 0) was 1.56 (95% CI, 1.07 to 2.27). Low vitamin D also predicted all-cause mortality over a period of up to 9.2 years (hazard ratio, 1.20; 95% CI, 1.02 to 1.42), independent of baseline frailty and other covariates. Hypovitaminosis D is associated with prevalent and incident frailty in older men. Hypovitaminosis D also predicts all-cause mortality, independent of frailty. The association between vitamin D and mortality is not solely dependent on the occurrence of frailty.


A cluster randomised controlled trial on the efficacy of client-centred occupational therapy in multiple sclerosis: good process, poor outcome.
To assess the efficacy of client-centred occupational therapy (OT) according to a client-centred process framework, as compared to usual care OT, in patients with multiple sclerosis (MS). A multicentre cluster randomised controlled trial with the institution (i.e. hospital or rehabilitation centre) as the unit of randomisation was performed. A total of 269 outpatients with MS, 13 hospitals and rehabilitation centres and 29 occupational therapists participated. Primary outcomes included measures of disability, participation and autonomy. Secondary outcomes included fatigue, generic health-related quality of life, quality and evaluation of therapy, therapy compliance and therapy frequency. Measurements were taken at baseline, four months and at eight months follow-up. Primary outcome measures did not show significant differences between the two interventions. Secondary outcomes revealed significant differences in favour of the usual care OT on fatigue (physical scale and total scale) and health-related quality of life (bodily pain and vitality) at four months. After eight months only significant differences on mental health were found. Process outcomes (i.e. the information scale of therapy quality and the client-centredness of the organisation) were in favour of the client-centred intervention. Because the client-centred intervention resulted in no effects on the primary outcomes and small but negative effects on the secondary functional outcomes, we should seriously reconsider the application of client-centred practice. An increasing number of interventions claim to incorporate client-centred practice. Client-centred practice is associated with improved satisfaction but the effects on functional health-related outcomes have not been fully evaluated. The findings of this study show that the process outcomes of therapy were in favour of the client-centred intervention, but no effects were found on the primary outcomes and negative effects on the secondary functional health outcomes. It is suggested that the implementation of client-centred practice should be adjusted in order to achieve optimal health outcomes.


Subjective and Objective Quality Assessment of 2D and 3D Foveated Video Compression in Virtual Reality.
In Virtual Reality (VR), the requirements of much higher resolution and smooth viewing experiences under rapid and often real-time changes in viewing direction, leads to significant challenges in compression and communication. To reduce the stresses of very high bandwidth consumption, the concept of foveated video compression is being accorded renewed interest. By exploiting the space-variant property of retinal visual acuity, foveation has the potential to substantially reduce video resolution in the visual periphery, with hardly noticeable perceptual quality degradations. Accordingly, foveated image / video quality predictors are also becoming increasingly important, as a practical way to monitor and control future foveated compression algorithms. Towards advancing the development of foveated image / video quality assessment (FIQA / FVQA) algorithms, we have constructed 2D and (stereoscopic) 3D VR databases of foveated / compressed videos, and conducted a human study of perceptual quality on each database. Each database includes 10 reference videos and 180 foveated videos, which were processed by 3 levels of foveation on the reference videos. Foveation was applied by increasing compression with increased eccentricity. In the 2D study, each video was of resolution 7680×3840 and was viewed and quality-rated by 36 subjects, while in the 3D study, each video was of resolution 5376×5376 and rated by 34 subjects. Both studies were conducted on top of a foveated video player having low motion-to-photon latency (~50ms). We evaluated different objective image and video quality assessment algorithms, including both FIQA / FVQA algorithms and non-foveated algorithms, on our so called LIVE-Facebook Technologies Foveation-Compressed Virtual Reality (LIVE-FBT-FCVR) databases. We also present a statistical evaluation of the relative performances of these algorithms. The LIVE-FBT-FCVR databases have been made publicly available and can be accessed at https://live.ece.utexas.edu/research/LIVEFBTFCVR/index.html.


Female elk contacts are neither frequency nor density dependent.
Identifying drivers of contact rates among individuals is critical to understanding disease dynamics and implementing targeted control measures. We studied the interaction patterns of 149 female elk (Cervus canadensis) distributed across five different regions of western Wyoming over three years, defining a contact as an approach within one body length (-2 min). Using hierarchical models that account for correlations within individuals, pairs, and groups, we found that pairwise contact rates within a group declined by a factor of three as group sizes increased 33-fold. Per capita contact rates, however, increased with group size according to a power function, such that female elk contact rates fell in between the predictions of density- or frequency-dependent disease models. We found similar patterns for the duration of contacts. Our results suggest that larger elk groups are likely to play a disproportionate role in the disease dynamics of directly transmitted infections in elk. Supplemental feeding of elk had a limited impact on pairwise interaction rates and durations, but per capita rates were more than two times higher on feeding grounds. Our statistical approach decomposes the variation in contact rate into individual, dyadic, and environmental effects, and provides insight into factors that may be targeted by disease control programs. In particular, female elk contact patterns were driven more by environmental factors such as group size than by either individual or dyad effects.


Efficacy of fexofenadine in isolated rat tracheas.
Histamine is an important chemical mediator in both nasal and bronchial inflammation in patients with allergic rhinitis and asthma. The effect of histamine receptor-1 antagonists on nasal mucosa in vivo is well known, however, the effect on tracheal smooth muscle has rarely been explored. The purpose of this study was to determine the effects of fexofenadine on isolated tracheal smooth muscle in vitro. Six tracheal strips were used for each experiment, and one untreated strip served as a control. We examined the effectiveness of fexofenadine on isolated rat tracheal smooth muscle by testing the effect on: 1) tracheal smooth muscle resting tension; 2) contraction caused by 10E-6 M methacholine as a parasympathetic mimetic; and 3) electrically induced tracheal smooth muscle contractions. The results indicated that addition of methacholine caused the trachea to contract in a dose-dependent manner. The addition of fexofenadine at a dose of 10E-4 M elicited a significant relaxation response compared to 10E-6 M methacholine-induced contraction. There were no detectable changes in the peak tension of electrical field stimulation-induced contractions in the fexofenadine group. High concentrations of fexofenadine had an anti-cholinergic effect. In addition to diminishing histamine-mediated allergic symptoms, fexofenadine may have a potentially therapeutic implication in alleviating asthma-related symptoms due to reducing methacholine-induced contractions of tracheal smooth muscle though these aspects were not studied.


Flow tube studies of the C((3)P) reactions with ethylene and propylene.
Product detection studies of C((3)P) atom reactions with ethylene, C2H4(X(1)Ag) and propylene, C3H6(X(1)A') are carried out in a flow tube reactor at 332 K and 4 Torr (553.3 Pa) under multiple collision conditions. Ground state carbon atoms are generated by 193 nm laser photolysis of carbon suboxide, C3O2 in a buffer of helium. Thermalized reaction products are detected using tunable VUV photoionization and time of flight mass spectrometry. For C((3)P) + ethylene, propargyl (C3H3) is detected as the only molecular product in agreement with previous studies on this reaction. The temporal profiles of the detected ions are used to discriminate C((3)P) reaction products from side reaction products. For C((3)P) + propylene, two reaction channels are identified through the detection of methyl (CH3) and propargyl (C3H3) radicals for the first channel and C4H5 for the second one. Franck-Condon Factor simulations are employed to infer the C4H5-isomer distribution. The measured 1 : 4 ratio for the i-C4H5 isomer relative to the methylpropargyl isomers is similar to the C4H5 isomer distribution observed in low-pressure flames and differs from crossed molecular beams data. The accuracy of these isomer distributions is discussed in view of large uncertainties on the photoionization spectra of the pure C4H5 isomers.


Emerging from obscurity: biological, clinical, and diagnostic aspects of Dientamoeba fragilis.
Ever since its first description in 1918, Dientamoeba fragilis has struggled to gain recognition as a significant pathogen. There is little justification for this neglect, however, since there exists a growing body of case reports from numerous countries around the world that have linked this protozoal parasite to clinical manifestations such as diarrhea, abdominal pain, flatulence, and anorexia. A number of studies have even incriminated D. fragilis as a cause of irritable bowel syndrome, allergic colitis, and diarrhea in human immunodeficiency virus patients. Although D. fragilis is most commonly identified using permanently stained fecal smears, recent advances in culturing techniques are simplifying as well as improving the ability of investigators to detect this organism. However, there are limitations in the use of cultures since they cannot be performed on fecal samples that have been fixed. Significant progress has been made in the biological classification of this organism, which originally was described as an ameba. Analyses of small-subunit rRNA gene sequences have clearly demonstrated its close relationship to Histomonas, and it is now known to be a trichomonad. How the organism is transmitted remains a mystery, although there is some evidence that D. fragilis might be transmitted via the ova of the pinworm, Enterobius vermicularis. Also, it remains to be answered whether the two distinct genotypes of D. fragilis recently identified represent organisms with differing virulence.