Ambient air emissions of polycyclic aromatic hydrocarbons and female breast cancer incidence in US.
To examine ambient air pollutants, specifically polycyclic aromatic hydrocarbons (PAHs), as a factor in the geographic variation of breast cancer incidence seen in the US, we conducted an ecological study involving counties throughout the US to examine breast cancer incidence in relation to PAH emissions in ambient air. Age-adjusted incidence rates of female breast cancer from the surveillance, epidemiology, and end results (SEER) program of the US National Cancer Institute were collected and analyzed using SEER*Stat 8.3.2. PAH emissions data were obtained from the Environmental Protection Agency. Linear regression analysis was performed using SPSS 23 software for Windows to analyze the association between PAH emissions and breast cancer incidence, adjusting for potential confounders. Age-adjusted incidence rates of female breast cancer were found being significantly higher in more industrialized metropolitan SEER regions over the years of 1973-2013 as compared to less industrialized regions. After adjusting for sex, race, education, socioeconomic status, obesity, and smoking prevalence, PAH emission density was found to be significantly associated with female breast cancer incidence, with the adjusted β of 0.424 (95% CI 0.278, 0.570; p < 0.0001) for emissions from all sources and of 0.552 (95% CI 0.278, 0.826; p < 0.0001) for emissions from traffic source. This study suggests that PAH exposure from ambient air could play a role in the increased breast cancer risk among women living in urban areas of the US. Further research could provide insight into breast cancer etiology and prevention.


Impact of COVID-19 on Cardiovascular Testing in the United States Versus the Rest of the World.
This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-U.S. institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection.


Protective role of +294 T/C (rs2016520) polymorphism of PPARD in Mexican patients with colorectal cancer.
PPARD encodes for peroxisome proliferator-activated receptor delta, which plays a significant role in controlling lipid metabolism, atherosclerosis, inflammation, cancer growth, progression, and apoptosis. Accumulated evidence suggests that the polymorphism rs2016520 in PPARD is associated with lipid metabolism, obesity, metabolic syndrome, and type 2 diabetes mellitus. The aim of this study was to determine whether the single nucleotide polymorphism +294T/C (rs2016520) in PPARD is associated with colorectal cancer (CRC) in the Mexican population. Genomic DNA from 178 CRC patients and 97 healthy blood donors was analyzed. The polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Results demonstrated that patients with the T/C genotype for the +294T/C (rs2016520) polymorphism present a protective role against CRC [odds ratio (OR) = 0.39; 95% confidence interval (CI) = 0.22-0.69; P = 0.0008]. This association was also evident for the T/C genotype in the stratified analysis by tumor-node-metastasis stages I+II (OR = 0.26, P = 0.0332) and III+IV (OR = 0.44, P = 0.0067). However, in the stratified analysis by tumor location, we observed an increased risk of rectal cancer (OR = 7.57, P = 0.0403) vs colon cancer (OR = 4.87, P = 0.234) in patients carrying the C/C genotype and under the dominant and recessive models of inheritance. In conclusion, for the first time, the association between the +294T/C (rs2016520) polymorphism and colorectal cancer has been studied in Mexican patients. Our results reveal that variations in PPARD may play a significant role in genetic susceptibility to colorectal cancer.


Instability in patient and nurse characteristics, unit complexity and patient and system outcomes.
To explore key factors related to nursing unit instability, complexity and patient and system outcomes. The relationship between nurse staffing and quality of patient outcomes is well known. The nursing unit is an important but different aspect that links to complexity and to system and patient outcomes. The relationship between the instability, complexity and outcomes needs further exploration. Descriptive. Data were collected via a nurse survey, unit profile and review of patient records on 62 nursing units (wards) across three states of Australia between 2008-2010. Two units with contrasting levels of patient and nurse instability and negative system and patient outcomes, were profiled in detail from the larger sample. Ward A presented with greater patient stability (low occupancy, high planned admissions, few ICU transfers, fewer changes to patient acuity/work re-sequencing) and greater nurse instability (nurses changing units, fewer full-time staff, more temporary/casual staff) impacting system outcomes negatively (high staff turnover). In contrast, Ward B had greater patient instability, however, more nurse stability (greater experienced and permanent staff, fewer casuals), resulting in high rates for falls, medication errors and other adverse patient outcomes with lower rates for system outcomes (lower intention to leave). Instability in patient and nurse factors can contribute to ward complexity with potentially negative patient outcomes. The findings highlight the variation of many aspects of the system where nurses work and the importance of nursing unit managers and senior nurse executives in managing ward complexity.


Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution.
Metalloproteases have evolved in a vast number of biological systems, being one of the most diverse types of proteases and presenting a wide range of folds and catalytic metal ions. Given the increasing understanding of protein internal dynamics and its role in enzyme function, we are interested in assessing how the structural heterogeneity of metalloproteases translates into their dynamics. Therefore, the dynamical profile of the clan MA type protein thermolysin, derived from an Elastic Network Model of protein structure, was evaluated against those obtained from a set of experimental structures and molecular dynamics simulation trajectories. A close correspondence was obtained between modes derived from the coarse-grained model and the subspace of functionally-relevant motions observed experimentally, the later being shown to be encoded in the internal dynamics of the protein. This prompted the use of dynamics-based comparison methods that employ such coarse-grained models in a representative set of clan members, allowing for its quantitative description in terms of structural and dynamical variability. Although members show structural similarity, they nonetheless present distinct dynamical profiles, with no apparent correlation between structural and dynamical relatedness. However, previously unnoticed dynamical similarity was found between the relevant members Carboxypeptidase Pfu, Leishmanolysin, and Botulinum Neurotoxin Type A, despite sharing no structural similarity. Inspection of the respective alignments shows that dynamical similarity has a functional basis, namely the need for maintaining proper intermolecular interactions with the respective substrates. These results suggest that distinct selective pressure mechanisms act on metalloproteases at structural and dynamical levels through the course of their evolution. This work shows how new insights on metalloprotease function and evolution can be assessed with comparison schemes that incorporate information on protein dynamics. The integration of these newly developed tools, if applied to other protein families, can lead to more accurate and descriptive protein classification systems.


Electromechanical film as a photoacoustic transducer.
An electromechanical film, EMFi, is utilized as a transducer in a photoacoustic (PA) gas sensor. The film is a sensitive acoustic transducer, it is easily formable, and it exhibits a wide frequency response regardless of its large surface area. As a demonstration of its capabilities, the EMFi-based PA detector is used to measure NO(2) with pulsed excitation at 436 and 473 nm. The minimum detectable absorption coefficient is extrapolated to be 5.10(-7) cm(-1). Improvements for EMFi-based PA detector are discussed.


Flexible, transparent electrodes using carbon nanotubes.
We prepare thin single-walled carbon nanotube networks on a transparent and flexible substrate with different densities, using a very simple spray method. We measure the electric impedance at different frequencies Z(f) in the frequency range of 40 Hz to 20 GHz using two different methods: a two-probe method in the range up to 110 MHz and a coaxial (Corbino) method in the range of 10 MHz to 20 GHz. We measure the optical absorption and electrical conductivity in order to optimize the conditions for obtaining optimum performance films with both high electrical conductivity and transparency. We observe a square resistance of 1 to 8.5 kΩ for samples showing 65% to 85% optical transmittance, respectively. For some applications, we need flexibility and not transparency: for this purpose, we deposit a thick film of single-walled carbon nanotubes on a flexible silicone substrate by spray method from an aqueous suspension of carbon nanotubes in a surfactant (sodium dodecyl sulphate), thereby obtaining a flexible conducting electrode showing an electrical resistance as low as 200 Ω/sq. When stretching up to 10% and 20%, the electrical resistance increases slightly, recovering the initial value for small elongations up to 10%. We analyze the stretched and unstretched samples by Raman spectroscopy and observe that the breathing mode on the Raman spectra is highly sensitive to stretching. The high-energy Raman modes do not change, which indicates that no defects are introduced when stretching. Using this method, flexible conducting films that may be transparent are obtained just by employing a very simple spray method and can be deposited on any type or shape of surface.


Grip pressure distributions and associated variability in golf: a two-club comparison.
Teaching and playing professionals offer multiple theories concerning the manner in which forces should be applied to the handle of the club during the golf swing. This study extends recent research concerning grip pressures and forces in golf, with the purpose of exploring the similarities and differences between force profiles for a 7-iron and driver swung by proficient golfers. A secondary purpose was to further analyze the way that golfers use grip forces to manipulate the club. Grip forces were measured on eight low handicap golfers (USGA indexes 0 to 7) swinging their own 7-irons and drivers. In total, lead-hand and trail-hand grip forces were isolated as well as anatomically specific forces within the hands. Force profile variability across multiple swings for each golfer and between golfers characterized consistencies and important differences. Correlations between 7-iron and driver force profiles characterized force 'signatures.' The data highlight large fluctuations in grip forces during the swing. Marked differences between participants were observed, involving force magnitudes and phasing. Dominant forces arose primarily from the lead hand, specifically the last three fingers. Force profiles were highly repeatable across swings for a golfer (standard deviations < 7% of total force) and force profile correlations between 7-iron and driver for a golfer were remarkably high (r2 = 0.86). Notably, within swing force variability was greatest during club acceleration, but dramatically decreased at impact.


Can procedure time for paracentesis be optimized based on bottle selection?
The purpose of our study was to assess if plastic containers could decrease the overall procedure time for paracentesis relative to more commonly used glass containers. In this IRB exempt study, initial pilot data comparing filling time of glass and plastic containers in an ex vivo setting under identical conditions revealed power calculations that n = 37 patients per group would be needed to achieve standard deviation (SD) = 60 s, difference (diff) = 40 s, two-tailed alpha-level 0.05, and power 80%. Total of 43 patients (93 containers) were enrolled and randomized to glass or plastic bottles at enrollment. Timing of bottle filling was assessed using standardized sonographic screen captures. An interim look at statistics at n = 20 patients indicated that original conjectures from pilot data were conservative and smaller sample size was sufficient to stop the study and conduct the analyses. Specifically, SD = 54 s, diff = 49 s, two-tailed alpha-level 0.05, and power 80% required n = 21 patients per group. Plastic containers had a statistically significantly lower average filling time per bottle (162.7 ± 53.3 s) compared to glass (212.2 ± 50.4 s) (p = 0.003). Viscosity was calculated for each specimen and did not affect the statistical significance of the results (p = 0.32). Plastic containers have 50 s time savings of per bottle filling time as compared to glass bottles as theorized based on their faster flow rate. This holds true in both an ex vivo setting and in patients and can have important downstream impacts on patient throughput, provider efficiency and system wide cost savings.


Culturally and linguistically diverse students in health professional programs: an exploration of concerns and needs.
Cultural diversity among students in tertiary institutions in Australia and globally has increased rapidly in the last decade, and is continuing to do so. Focus groups were held at the University of Newcastle, NSW to: (1) examine the specific needs of international students in the Master of Pharmacy, Bachelor of Medicine and Bachelor of Nursing programs in relation to language and cultural considerations and (2) to understand the attitudes of domestic students to the cultural issues faced among their peers. The project explored these issues with the intention to inform curricula changes to accommodate the needs of culturally and linguistically diverse students. The key themes emerging from international students were: difficulties in spoken language, differences in professional roles and expectations, differences in methods of learning, inadequate social interaction outside the classroom and acceptance of differences in cultural and religious practices. The domestic student views reinforced the comments from international students both in regard to social interaction and in regard to participation in class discussions. Although local students were interested in learning from international students about their culture and religious beliefs, there were limited initiatives from both sides. There is a need for tertiary institutions that benefit economically from increasing the numbers of international students to help them to study and live in a new environment. Assistance needs to go beyond learning the English language to helping students understand its use in a professional context (health terminology and slang used by patients), the nuances of the health professional disciplines in a western society, the approach to study and problem-based learning styles and skills to assist with social interaction. The results of the present exploration have led to a series of proposed actions for the University of Newcastle. These recommendations are applicable to any "Western" teaching institution with a large number of international students from developing countries enrolled in their health programs.


Pulmonary and extrapulmonary features in bronchopulmonary dysplasia: a comparison with healthy children.
[Purpose] The aim of this study was to compare functional capacity and peripheral muscle strength in preterm children with bronchopulmonary dysplasia (BPD) with those of age-matched full-term healthy controls. [Subjects and Methods] Eighteen BPD subjects and 20 healthy subjects were enrolled in the study. Pulmonary function testing was performed. Body composition was determined using the skinfold method. An analysis of posture was scored. Muscle strength was evaluated using a dynamometer. Functional capacity was assessed using the six-minute walking test (6MWT). [Results] Pulmonary function testing parameters, 6MWT distance, and quadriceps strength of the children with BPD were significantly lower than those of healthy peers. The scores of posture analysis of the children with BPD were significantly higher than those of healthy subjects. Exercise heart rate was significantly higher in the children with BPD compared to healthy children. The 6MWT distance correlated with height, fat-free mass, exercise dyspnea perception, and hand grip strength in BPD children. [Conclusion] The study showed that preterm children with BPD had disturbed pulmonary and extrapulmonary characteristics. BPD had lower fat free mass, reduced lung function, worsen postural function, a shorter 6MWT distance, and lower quadriceps strength than healthy children. These features may provide insights into the choice of outcome measures for pulmonary rehabilitation for BPD.


Synthesis of mercapto-(+)-methamphetamine haptens and their use for obtaining improved epitope density on (+)-methamphetamine conjugate vaccines.
This study reports the synthesis of the mercapto-hapten (S)-N-(2-(mercaptoethyl)-6-(3-(2-(methylamino)propyl)phenoxy)hexanamide [3, (+)-METH HSMO9] and its use to prepare METH-conjugated vaccines (MCV) from maleimide-activated proteins. MALDI-TOF mass spectrometry analysis of the MCV synthesized using 3 showed there was a high and controllable epitope density on two different carrier proteins. In addition, the MCV produced a substantially greater immunological response in mice than previous METH haptens, and a monoclonal antibody generated from this MCV in mice showed a very high affinity for (+)-METH (K(D) = 6.8 nM). The efficient covalent coupling of (+)-METH HSMO9 to the activated carrier proteins suggests that this approach could be cost-effective for large-scale production of MCV. In addition, the general methods described for the synthesis of (+)-METH HSMO9 (3) and its use to synthesize MCV will be applicable for conjugated vaccines of small molecules and other substances of abuse such as morphine, nicotine, and cocaine.


Gene-expression patterns reveal underlying biological processes in Kawasaki disease.
Kawasaki disease (KD) is an acute self-limited vasculitis and the leading cause of acquired heart disease in children in developed countries. No etiologic agent(s) has been identified, and the processes that mediate formation of coronary artery aneurysms and abatement of fever following treatment with intravenous immunoglobulin (IVIG) remain poorly understood. In an initial survey, we used DNA microarrays to examine patterns of gene expression in peripheral whole blood from 20 children with KD; each was sampled during the acute, subacute, and convalescent phases of the illness. Acute KD was characterized by increased relative abundance of gene transcripts associated with innate immune and proinflammatory responses and decreased abundance of transcripts associated with natural killer cells and CD8+ lymphocytes. There was significant temporal variation in transcript levels during the acute disease phase and stabilization thereafter. We confirmed these temporal patterns in a second cohort of 64 patients, and identified additional inter-individual differences in transcript abundance. Notably, higher levels of transcripts of the gene for carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) were associated with an increased percentage of unsegmented neutrophils, fewer days of illness, higher levels of C-reactive protein, and subsequent non-response to IVIG; this last association was confirmed by quantitative reverse transcription PCR in a third cohort of 33 patients, and was independent of day of illness. Acute KD is characterized by dynamic and variable gene-expression programs that highlight the importance of neutrophil activation state and apoptosis in KD pathogenesis. Our findings also support the feasibility of extracting biomarkers associated with clinical prognosis from gene-expression profiles of individuals with systemic inflammatory illnesses.


Inhibition of the growth of glioblastomas by CGP 41251, an inhibitor of protein kinase C, and by a phorbol ester tumor promoter.
Protein kinase C (PKC) plays a central role in signal transduction pathways that mediate the action of certain growth factors, tumor promoters, and cellular oncogenes. To explore whether PKC might be an appropriate target for the chemotherapy of human brain tumors, cell lines were established from five glioblastomas, one mixed gliosarcoma and glioblastoma, two astrocytomas, and one choroid plexus carcinoma. The staurosporine derivative CGP 41251, an inhibitor of PKC, inhibited cell proliferation in all nine cell lines with an IC50 in the range of 0.4 micrometer. Drug withdrawal and clonogenicity assays showed that CGP 41251 induced an irreversible growth arrest. Three cell lines were examined in detail: two human glioblastoma cell lines, GB-1 and GB-2, and one gliosarcoma cell line, GS-1. All of these three cell lines were highly aneuploid and displayed morphologies and immunohistochemical markers characteristic of the glial lineage. The compound 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter and activator of PKC, also inhibited the growth of these cell lines. CGP 41251 in combination with TPA caused further growth inhibition. Cultures treated with CGP 41251 displayed an increase in the fraction of cells in G2-M, a decrease of cells in S phase, and no consistent effect on G0-G1. Immunohistochemical analyses demonstrated that growth inhibition by CGP 41251 was associated with the formation of giant nuclei with extensive fragmentation and apoptotic bodies. These effects of CGP 41251 were abrogated by withdrawal of serum from the medium or by exposure of these cells to aphidicolin, actinomycin D, cycloheximide, or TPA. In contrast to the effects seen with the glioblastoma cell lines, nontransformed astrocyte lines remained viable in the presence of 0.4 and 0.8 micrometer CGP 41251 and displayed only a slight increase in the fraction of giant nuclei with fragmentation. The antitumor activity of CGP 41251 was demonstrated in vivo against xenografts of the glioblastoma cell lines U87 MG and U373 MG. These findings suggest that CGP 41251 might be a useful agent for the treatment of glioblastomas.


The role of prolactin and progesterone in the regulation of lipogenesis in maternal and foetal rat liver in vivo and in isolated hepatocytes during the last day of gestation.
The administration of progesterone on day 21 of gestation increases the rates of lipogenesis in the liver in vivo and in hepatocytes isolated from rats on day 22 of pregnancy. Bromocriptine administration increases the rates of hepatic lipogenesis in vivo, but has no effect on lipid synthesis in hepatocytes under the same treatment conditions. Concurrently, the administration of progesterone or bromocriptine on day 21 to the mother increases the rates of lipogenesis in the foetal liver in vivo on day 22. The rates of lipid synthesis in foetal isolated hepatocytes are increased by progesterone administration, but remain unchanged by bromocriptine.


Rotational-shearing irnterferometry.
A brief review of lateral- and radial-shearing interferometry is presented together with a thorough discussion of the theory of rotational-shearing interferometry. A rotational-shearing interferometer is described based on the Jamin principle that was built by the authors while at the Institute of Optics at the University of Rochester in Rochester, New York. Graphs and photographs of the interference patterns of the lenses and a lightweight mirror that were tested with this interferometer are presented and discussed. Finally, the effect of the size of the source on the degree of coherence of the interference pattern is considered.


[Role of coagulation in acute pulmonary lesion physiopathology. Parallelism with sepsis].
Acute respiratory distress syndrome and acute lung injury for a part of a devastating syndrome characterized by acute onset, hypoxemia and bilateral infiltrates in the chest x-ray with absence of heart failure signs. Acute lung injury is the response of the lung to a local or systemic aggression, resulting in local inflammation and coagulation disorders, this leading to increased inflammatory pulmonary edema. Acute lung injury/acute respiratory distress syndrome are associated with increased procoagulant and reduced fibrinolytic activities mainly in alveoli and interstitial spaces in the lung. Fibrin deposits, which are the hallmark of early phase acute lung injury, stimulate fibroblast aggregation and collagen secretion, participating to the constitution of pulmonary fibrosis. The only clinical intervention found to have a significant impact on mortality in acute respiratory distress syndrome, despite the significant pro - gress in the understanding of the disease made over the past 10 years, is the use of low tidal volume ventilation. In severe sepsis, only recombinant human activated protein C administration has demonstrated a mortality reduction, together with faster improvement in respiratory dysfunction and shorter duration of mechanical ventilation. Future clinical trials should consider the potential benefit of anticoagulants administrated systemically or locally in the lungs to determine the role of anticoagulants in the treatment of acute pulmonary injury/acute respiratory distress syndrome.


Testing successional hypotheses of stability, heterogeneity, and diversity in pitcher-plant inquiline communities.
Succession is a foundation concept in ecology that describes changes in species composition through time, yet many successional patterns have not been thoroughly investigated. We highlight three hypotheses about succession that are often not clearly stated or tested: (1) individual communities become more stable over time, (2) replicate communities become more similar over time, and (3) diversity peaks at mid-succession. Testing general patterns of succession requires estimates of variation in trajectories within and among replicate communities. We followed replicate aquatic communities found within leaves of purple pitcher plants (Sarracenia purpurea) to test these three hypotheses. We found that stability of individual communities initially decreased, but then increased in older communities. Predation was highest in younger leaves but then declined, while competition was likely strongest in older leaves, as resources declined through time. Higher levels of predation and competition corresponded with periods of higher stability. As predicted, heterogeneity among communities decreased with age, suggesting that communities became more similar over time. Changes in diversity depended on trophic level. The diversity of bacteria slightly declined over time, but the diversity of consumers of bacteria increased linearly and strongly throughout succession. We suggest that studies need to focus on the variety of environmental drivers of succession, which are likely to vary through time and across habitats.


Plasmodium vivax associated severe malaria complications among children in some malaria endemic areas of Ethiopia.
Although, Plasmodium vivax is a rare parasite in most parts of Africa, it has significant public health importance in Ethiopia. In some parts of the country, it is responsible for majority of malaria associated morbidity. Recently severe life threatening malaria syndromes, frequently associated to P. falciparum, has been reported from P. vivax mono-infections. This prompted designing of the current study to assess prevalence of severe malaria complications related to P. vivax malaria in Ethiopia. The study was conducted in two study sites, namely Kersa and Halaba Kulito districts, located in southwest and southern parts of Ethiopia, respectively. Children, aged ≤ 10 years, who visited the two health centers during the study period, were recruited to the study. Clinical and demographic characteristics such as age, sex, temperature, diarrhea, persistent vomiting, confusion, respiratory distress, hepatomegaly, splenomegaly, hemoglobinuria, and epitaxis were assessed for a total of 139 children diagnosed to have P. vivax mono-infection. Parasitological data were collected following standard procedures. Hemoglobin and glucose level were measured using portable hemocue instrument. Median age of children was 4.25 ± 2.95 years. Geometric mean parasite count and mean hemoglobin level were 4254.89 parasite/μl and 11.55 g/dl, respectively. Higher prevalence rate of malaria and severe malaria complications were observed among children enrolled in Halaba district (P < 0.001). However, severe parasitemia was higher (72.4%) among children who visited Serbo health center (Kersa district). Male children had significantly higher risk of malaria infection (OR = 1.9, 95% CI, 1.08 to 3.34), while female had higher risk to anemia (OR = 1.91, 95% CI, 1.08 - 3.34). The observed number of anemic children was 43%, of which most of them were found in age range from 0-3 years. Furthermore, P. vivax malaria was a risk factor for incidence of anemia (P < 0.05) in the two sites. P. vivax associated severe malaria complications observed in this study was lower than those reported from other countries. However, incidence of severe malaria complications in one of the sites, Halaba district, where there is highest treatment failure to first line drug, could have significant impact on national malaria prevention and control activities.


Pupillographic evaluation of relative afferent pupillary defect in glaucoma patients.
To evaluate the association between the magnitude of relative afferent pupillary defect (RAPD) and the laterality of visual fields in glaucoma patients using pupillography. Evaluations were made with an RAPDx (Konan Medical USA, Irvine, California, USA), which is designed to analyse pupil responses to multiple colour stimuli (white, red, green, blue, and yellow) at multiple controlled stimulus intensities. Humphrey automated perimetry (SITA standard 30-2) was performed to determine mean deviations (MDs), which were used to evaluate associations between MD differences (better eye MD-worse eye MD) and RAPDx amplitude and latency measurements in pupil response to multiple colour stimuli. 58 glaucoma patients (35 men, 23 women; mean age: 62.6±12.8 years; range 28-88 years) were enrolled. The MD values were -2.00±3.1 (range -9.64 to 2.33) dB in the better eyes and -8.17±7.1 (range -26.33 to 1.07) dB in the worse eyes. The differences in MD values (better eye MD-worse eye MD) were 6.17±6.1 (range 0.05-26.41) dB. The results of linear regression analysis between the log-scaled RAPD amplitudes and differences in MD values were as follows: white: R(2)=0.45 (p<0.001), red: R(2)=0.18 (p=0.002), green: R(2)=0.30 (p<0.001), blue: R(2)=0.29 (p<0.001), and yellow: R(2)=0.32 (p<0.001). The log-scaled RAPD latencies and the differences in MD values were: white: R(2)=0.17 (p=0.001), red: R(2)=0.03 (p=0.22), green: R(2)=0.01 (p=0.52), blue: R(2)=0.1 (p=0.02), and yellow: R(2)=0.05 (p=0.11). The log-scaled RAPD amplitudes correlated moderately with the differences in MD values, but the log-scaled RAPD latencies showed a weaker correlation. Stimulation with white light produced the strongest correlation with differences in MD values.


Poxvirus tumor necrosis factor receptor (TNFR)-like T2 proteins contain a conserved preligand assembly domain that inhibits cellular TNFR1-induced cell death.
The poxvirus tumor necrosis factor receptor (TNFR) homologue T2 has immunomodulatory properties; secreted myxoma virus T2 (M-T2) protein binds and inhibits rabbit TNF-alpha, while intracellular M-T2 blocks virus-induced lymphocyte apoptosis. Here, we define the antiapoptotic function as inhibition of TNFR-mediated death via a highly conserved viral preligand assembly domain (vPLAD). Jurkat cell lines constitutively expressing M-T2 were generated and shown to be resistant to UV irradiation-, etoposide-, and cycloheximide-induced death. These cells were also resistant to human TNF-alpha, but M-T2 expression did not alter surface expression levels of TNFRs. Previous studies indicated that T2's antiapoptotic function was conferred by the N-terminal region of the protein, and further examination of this region revealed a highly conserved N-terminal vPLAD, which is present in all poxvirus T2-like molecules. In cellular TNFRs and TNF-alpha-related apoptosis-inducing ligand (TRAIL) receptors (TRAILRs), PLAD controls receptor signaling competency prior to ligand binding. Here, we show that M-T2 potently inhibits TNFR1-induced death in a manner requiring the M-T2 vPLAD. Furthermore, we demonstrate that M-T2 physically associates with and colocalizes with human TNFRs but does not prevent human TNF-alpha binding to cellular receptors. Thus, M-T2 vPLAD is a species-nonspecific dominant-negative inhibitor of cellular TNFR1 function. Given that the PLAD is conserved in all known poxvirus T2-like molecules, we predict that it plays an important function in each of these proteins. Moreover, that the vPLAD confers an important antiapoptotic function confirms this domain as a potential target in the development of the next generation of TNF-alpha/TNFR therapeutics.


Effectiveness of α-, γ- and δ-Tocopherol in a CLA-Rich Oil.
Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of octadecadienoic acid with conjugated double bounds. Positive health properties have been attributed to some isomers, such as anticarcinogenic activity, antiartherosclerotic effects and reduction of body fat gain. Hence, oils rich in CLA such as Tonalin(®) oil (TO), normally obtained through alkaline isomerization of safflower oil (SO), an oil rich in linoleic acid (LA), are currently used in functional foods. However, special care must be taken to protect them from oxidation to ensure the quality of the supplemented foods. The objective of this work was to evaluate the oxidation and effectiveness of different tocopherol homologues (α-, γ- and δ-), alone or in combination with synergists (ascorbyl palmitate and lecithin), in TO compared to SO at different conditions, ambient temperature (25 °C) and accelerated conditions in Rancimat (100 °C). The oils, the oils devoid of their antioxidants and the latter containing the antioxidants added were assayed. Results showed great differences between SO and TO in terms of formation of hydroperoxides and polymers and also in the effectiveness of tocopherols to delay oxidation. TO showed higher levels of polymerization and, in general, the effectiveness of tocopherol homologues, alone or in combination with synergists, was also lower in the TO.


Overview of treatments used in transthyretin-related hereditary amyloidosis: a systematic review.
To carry out a systematic review of the literature to analyse the efficacy and safety of treatments available or under investigation for amyloidosis due to mutations in the transthyretin gene (ATTR). A bibliographic search was carried out in the following electronic databases up to September 2017: PubMed, Cochrane Library and EMBASE. The inclusion criteria were: efficacy and/or safety studies conducted in humans, studies that included treatments, including treatments in the research phase, and studies that included 10 or more patients. A total of 21 articles were included; 16 were clinical trials, eight of them (50%) phase III trials, and five were observational studies. Of the total number of studies selected, 11 were on tafamidis, four on diflunisal, two on liver transplantation, two on patisiran and two on other therapeutic alternatives. Of the 11 studies related to the drug, the pivotal trial, the results of its two extension studies and an additional post hoc analysis were selected. In addition, two phase III trials were included in specific populations, two phase II studies, one safety study and two observational studies. Regarding the four included studies related to the drug, one was the pivotal trial that gave the indication to diflunisal, another a safety summary of the pivotal trial, and the other two trials were carried out in specific populations, one in a Japanese population and another phase I trial in cardiac amyloidosis in the USA. As far as other alternatives are concerned, of the six studies included in this section, two were related to liver transplantation, two to patisiran and two to different therapeutic alternatives. Sufficient evidence has not been found that demonstrates superiority among the available oral alternatives, diflunisal or tafamidis, in the treatment of ATTR. Direct comparisons between both drugs and pharmacoeconomic studies would be necessary to select the most efficient treatment.


Identification of Resistance to Multiple Fungicides in Field Populations of Venturia inaequalis.
Venturia inaequalis, the causal agent of apple scab, is controlled primarily by fungicides. Long-term, extensive fungicide use has led to the development of resistance to multiple fungicides. To assess fungicide resistance, isolates of V. inaequalis were collected from Indiana and Michigan orchards. Single-spore derived isolates were evaluated by mycelium growth assays with previously determined discriminatory doses on media containing dodine, kresoxim-methyl, myclobutanil, or thiophanate-methyl. Of 195 isolates tested, 5.2, 0.7, 57.0, and 92.6% of isolates were found to be resistant to dodine, kresoxim-methyl, myclobutanil, and thiophanate-methyl, respectively. This is the first report of kresoxim-methyl field resistance in these states. Isolates resistant or shifted to a single fungicide were often found to have multiple fungicide resistance. Of all isolates tested, 38% were identified as resistant or shifted to two fungicides, and 12% were resistant or shifted to all four fungicides tested. No fitness penalty was found for isolates resistant to multiple fungicides based on a statistical analysis of mycelial growth and conidial production.


A case study of real-time monitoring of solid-state phase transformations in acoustically levitated particles using near infrared and Raman spectroscopy.
The objective of this study was to monitor the amorphous-to-crystalline solid-state phase transformation kinetics of the model drug ibuprofen with spectroscopic methods during acoustic levitation. Chemical and physical information was obtained by real-time near infrared (NIRS) and Raman spectroscopy measurements. The recrystallisation kinetic parameters (overall recrystallisation rate constant β and the time needed to reach 50% of the equilibrated level t(50)), were determined using a multivariate curve resolution approach. The acoustic levitation device coupled with non-invasive spectroscopy enabled monitoring of the recrystallisation process of the difficult-to-handle (adhesive) amorphous sample. The application of multivariate curve resolution enabled isolation of the underlying pure spectra, which corresponded well with the reference spectra of amorphous and crystalline ibuprofen. The recrystallisation kinetic parameters were estimated from the recrystallisation profiles. While the empirical recrystallisation rate constant determined by NIR and Raman spectroscopy were comparable, the lag time for recrystallisation was significantly lower with Raman spectroscopy as compared to NIRS. This observation was explained by the high energy density of the Raman laser beam, which might have led to local heating effects of the sample and thus reduced the recrystallisation onset time. It was concluded that acoustic levitation with NIR and Raman spectroscopy combined with multivariate curve resolution allowed direct determination of the recrystallisation kinetics of amorphous drugs and thus is a promising technique for monitoring solid-state phase transformations of adhesive small-sized samples during the early phase of drug development.


Endocytosis of the type III transforming growth factor-beta (TGF-beta) receptor through the clathrin-independent/lipid raft pathway regulates TGF-beta signaling and receptor down-regulation.
Transforming growth factor-beta (TGF-beta) signals through three highly conserved cell surface receptors, the type III TGF-beta receptor (T beta RIII), the type II TGF-beta receptor (T beta RII), and the type I TGF-beta receptor (T beta RI) to regulate diverse cellular processes including cell proliferation, differentiation, migration, and apoptosis. Although T beta RI and T beta RII undergo ligand-independent endocytosis by both clathrin-mediated endocytosis, resulting in enhanced signaling, and clathrin-independent endocytosis, resulting in receptor degradation, the mechanism and function of T beta RIII endocytosis is poorly understood. T beta RIII is a heparan sulfate proteoglycan with a short cytoplasmic tail that functions as a TGF-beta superfamily co-receptor, contributing to TGF-beta signaling through mechanisms yet to be fully defined. We have reported previously that T beta RIII endocytosis, mediated by a novel interaction with beta arrestin-2, results in decreased TGF-beta signaling. Here we demonstrate that T beta RIII undergoes endocytosis in a ligand and glycosaminoglycan modification-independent and cytoplasmic domain-dependent manner, with the interaction of Thr-841 in the cytoplasmic domain of T beta RIII with beta-arrestin2 enhancing T beta RIII endocytosis. T beta RIII undergoes both clathrin-mediated and clathrin-independent endocytosis. Importantly, inhibition of the clathrin-independent, lipid raft pathway, but not of the clathrin-dependent pathway, results in decreased TGF-beta1 induced Smad2 and p38 phosphorylation, supporting a specific role for clathrin-independent endocytosis of T beta RIII in regulating both Smad-dependent and Smad-independent TGF-beta signaling.


Histologic evaluation of adhesive restorations on dentin caries in rat molar teeth.
The aim of this study was to evaluate the progress of dentin caries under resin composite and glass-ionomer cement restorations in vivo. Sixteen rats were subjected to oral inoculation of the bacterial strain, Streptococcus mutans, and experimental dental caries was induced in the rats' molars. The dental caries induced in rat molars was sealed with resin composite or glass-ionomer cement without removal of the caries; the depth and width of bacterial penetration in the lesion were measured from histopathologically stained sections. Inflammatory cell infiltrations within the pulp were also examined. Both bacterial penetration into dentin and caries spread were significantly reduced by sealing with glass-ionomer cement or resin composite. No significant differences in bacterial penetration and caries spread were seen between the sealing materials. Regarding the pulpal reactions, moderate to severe inflammatory cell infiltration was observed even in the sealed teeth. The caries lesions could not be completely arrested by sealing alone, although their progress was slowed from an active to a chronic status.


Isolation of a Novel Phage with Activity against Streptococcus mutans Biofilms.
Streptococcus mutans is one of the principal agents of caries formation mainly, because of its ability to form biofilms at the tooth surface. Bacteriophages (phages) are promising antimicrobial agents that could be used to prevent or treat caries formation by S. mutans. The aim of this study was to isolate new S. mutans phages and to characterize their antimicrobial properties. A new phage, ɸAPCM01, was isolated from a human saliva sample. Its genome was closely related to the only two other available S. mutans phage genomes, M102 and M102AD. ɸAPCM01 inhibited the growth of S. mutans strain DPC6143 within hours in broth and in artificial saliva at multiplicity of infections as low as 2.5x10-5. In the presence of phage ɸAPCM01 the metabolic activity of a S. mutans biofilm was reduced after 24 h of contact and did not increased again after 48 h, and the live cells in the biofilm decreased by at least 5 log cfu/ml. Despite its narrow host range, this newly isolated S. mutans phage exhibits promising antimicrobial properties.


KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury.
Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage-activated potassium channel of big-conductance (BK) have a pre-conditioning-like effect on survival of cardiomyocytes after ischemia/reperfusion injury. Recently, mitochondrial BK channels (mitoBKs) in cardiomyocytes were implicated as infarct-limiting factors that derive directly from the KCNMA1 gene encoding for canonical BKs usually present at the plasma membrane of cells. However, some studies challenged these cardio-protective roles of mitoBKs. Herein, we present electrophysiological evidence for paxilline- and NS11021-sensitive BK-mediated currents of 190 pS conductance in mitoplasts from wild-type but not BK-/- cardiomyocytes. Transmission electron microscopy of BK-/- ventricular muscles fibres showed normal ultra-structures and matrix dimension, but oxidative phosphorylation capacities at normoxia and upon re-oxygenation after anoxia were significantly attenuated in BK-/- permeabilized cardiomyocytes. In the absence of BK, post-anoxic reactive oxygen species (ROS) production from cardiomyocyte mitochondria was elevated indicating that mitoBK fine-tune the oxidative state at hypoxia and re-oxygenation. Because ROS and the capacity of the myocardium for oxidative metabolism are important determinants of cellular survival, we tested BK-/- hearts for their response in an ex-vivo model of ischemia/reperfusion (I/R) injury. Infarct areas, coronary flow and heart rates were not different between wild-type and BK-/- hearts upon I/R injury in the absence of ischemic pre-conditioning (IP), but differed upon IP. While the area of infarction comprised 28±3% of the area at risk in wild-type, it was increased to 58±5% in BK-/- hearts suggesting that BK mediates the beneficial effects of IP. These findings suggest that cardiac BK channels are important for proper oxidative energy supply of cardiomyocytes at normoxia and upon re-oxygenation after prolonged anoxia and that IP might indeed favor survival of the myocardium upon I/R injury in a BK-dependent mode stemming from both mitochondrial post-anoxic ROS modulation and non-mitochondrial localizations.


Driving following defibrillator implantation: a nationwide register-linked survey study.
Patients are restricted from driving following implantable cardioverter defibrillator (ICD) implantation or shock. We sought to investigate how many patients are aware of, and adhere to, the driving restrictions, and what proportion experience an ICD shock or other cardiac symptoms while driving. We performed a nationwide survey of all living Danish residents 18 years or older who received a first-time ICD between 2013 and 2016 (n = 3913) and linked their responses with nationwide registers. Of 2741 respondents (47% primary prevention, 83% male, median age 67 years), 2513 (92%) held a valid driver's license at ICD implantation, 175 (7%) of whom had a license for professional driving. Many drivers were unaware of driving restrictions: primary prevention 58%; secondary prevention 36%; post-appropriate shock 28%; professional drivers 55%. Almost all (94%) resumed non-professional driving after ICD implantation, more than one-third during the restricted period; 35% resumed professional driving. During a median follow-up of 2.3 years, 5 (0.2%) reported receiving an ICD shock while driving, one of which resulted in a traffic accident. The estimated risk of harm was 0.0002% per person-year. In this nationwide study, many ICD patients were unaware of driving restrictions, and more than one third resumed driving during a driving restriction period. However, the rate of reported ICD shocks while driving was very low.


Optimal cut-off values for the homeostasis model assessment of insulin resistance (HOMA-IR) and pre-diabetes screening: Developments in research and prospects for the future.
Diabetes mellitus (DM) appears to be increasing rapidly, threatening to reduce life expectancy for humans around the globe. The International Diabetes Federation (IDF) has estimated that there will be 642 million people living with the disease by 2040 and half as many again who will be not diagnosed. This means that pre-DM screening is a critical issue. Insulin resistance (IR) has emerged as a major pathophysiological factor in the development and progression of DM since it is evident in susceptible individuals at the early stages of DM, and particularly type 2 DM (T2DM). Therefore, assessment of IR via the homeostasis model assessment of IR (HOMA-IR) is a key index for the primary prevention of DM and is thus found in guidelines for screening of high-risk groups. However, the cut-off values of HOMA-IR differ for different races, ages, genders, diseases, complications, etc. due to the complexity of IR. This hampers the determination of specific cut-off values of HOMA-IR in different places and in different situations. China has not published an official index to gauge IR for primary prevention of T2DM in the diabetic and non-diabetic population except for children and adolescents ages 6-12 years. Hence, this article summarizes developments in research on IR, HOMA-IR, and pre-DM screening in order to provide a reference for optimal cut-off values of HOMA-IR for the diagnosis of DM in the Chinese population.


On the increase in network robustness and decrease in network response ability during the aging process: a systems biology approach via microarray data.
Aging, an extremely complex and system-level process, has attracted much attention in medical research, especially since chronic diseases are quite prevalent in the elderly population. These may be the result of both gene mutations that lead to intrinsic perturbations and environmental changes that may stimulate signaling in the body. Therefore, analysis of network robustness to tolerate intrinsic perturbations and network response ability of gene networks to respond to external stimuli during the aging process may provide insight into the systematic changes caused by aging. We first propose novel methods to estimate network robustness and measure network response ability of gene regulatory networks by using their corresponding microarray data in the aging process. Then, we find that an aging-related gene network is more robust to intrinsic perturbations in the elderly than the young, and therefore is less responsive to external stimuli. Finally, we find that the response abilities of individual genes, especially FOXOs, NF-κB, and p53, are significantly different in the young versus the aged subjects. These observations are consistent with experimental findings in the aged population, e.g., elevated incidence of tumorigenesis and diminished resistance to oxidative stress. The proposed method can also be used for exploring and analyzing the dynamic properties of other biological processes via corresponding microarray data to provide useful information on clinical strategy and drug target selection.


Prediction of environmental concentrations of glucocorticoids: the River Thames, UK, as an example.
Synthetic glucocorticoids (GCs) are consumed in large amounts as anti-inflammatory and immunosuppressive drugs worldwide. Based on what has been learnt from studies of other human pharmaceuticals, they are likely to be present in the aquatic environment. However, to date, information on the environmental concentrations of GCs is very limited. The situation is complicated by the fact that a considerable number of GCs are in everyday use in most developed countries. Hence, obtaining a full picture of GC concentrations in the aquatic environment using the traditional analytical chemistry approach would be time-consuming and expensive. Thus, we took a modelling approach to predict the total environmental concentration of all synthetic GCs (consisting of 28 individual GCs) in the River Thames, as a first step in risk assessment of these drugs. Using reliable data on consumption, the LF2000-WQX model predicts mean concentrations up to 30 ng/L of total GCs in surface water as a best case scenario when the lowest excretion and highest removal rates in sewage treatment works were used, whereas mean concentrations up to 850 ng/L were predicted when the highest excretion and lowest removal rates are considered. We also present the 10th and 90th percentile concentrations (which indicate the likely range of concentrations seen from high flow to low flow conditions in the river) of the highest and lowest consumed GCs, to show the spatial and temporal variations of the concentrations of individual GCs. These data probably provide reliable estimates of the likely range of concentrations of GCs in a typical river impacted by effluent from many sewage treatment plants. Results also identify the hot spots where field studies on fish could be focused. To determine if aquatic organisms face any threat from GCs, laboratory toxicity studies should be conducted using concentrations similar to those reported here.


Gastrin, via activation of PPARα, protects the kidney against hypertensive injury.
Hypertensive nephropathy (HN) is a common cause of end-stage renal disease with renal fibrosis; chronic kidney disease is associated with elevated serum gastrin. However, the relationship between gastrin and renal fibrosis in HN is still unknown. We, now, report that mice with angiotensin II (Ang II)-induced HN had increased renal cholecystokinin receptor B (CCKBR) expression. Knockout of CCKBR in mice aggravated, while long-term subcutaneous infusion of gastrin ameliorated the renal injury and interstitial fibrosis in HN and unilateral ureteral obstruction (UUO). The protective effects of gastrin on renal fibrosis can be independent of its regulation of blood pressure, because in UUO, gastrin decreased renal fibrosis without affecting blood pressure. Gastrin treatment decreased Ang II-induced renal tubule cell apoptosis, reversed Ang II-mediated inhibition of macrophage efferocytosis, and reduced renal inflammation. A screening of the regulatory factors of efferocytosis showed involvement of peroxisome proliferator-activated receptor α (PPAR-α). Knockdown of PPAR-α by shRNA blocked the anti-fibrotic effect of gastrin in vitro in mouse renal proximal tubule cells and macrophages. Immunofluorescence microscopy, Western blotting, luciferase reporter, and Cut&tag-qPCR analyses showed that CCKBR may be a transcription factor of PPAR-α, because gastrin treatment induced CCKBR translocation from cytosol to nucleus, binding to the PPAR-α promoter region, and increasing PPAR-α gene transcription. In conclusion, gastrin protects against HN by normalizing blood pressure, decreasing renal tubule cell apoptosis, and increasing macrophage efferocytosis. Gastrin-mediated CCKBR nuclear translocation may make it act as a transcription factor of PPAR-α, which is a novel signaling pathway. Gastrin may be a new potential drug for HN therapy.


Mining the Methylome Reveals Extensive Diversity in Staphylococcus epidermidis Restriction Modification.
Staphylococcus epidermidis is a significant opportunistic pathogen of humans. Molecular studies in this species have been hampered by the presence of restriction-modification (RM) systems that limit introduction of foreign DNA. Here, we establish the complete genomes and methylomes for seven clinically significant, genetically diverse S. epidermidis isolates and perform the first systematic genomic analyses of the type I RM systems within both S. epidermidis and Staphylococcus aureus Our analyses revealed marked differences in the gene arrangement, chromosomal location, and movement of type I RM systems between the two species. Unlike S. aureus, S. epidermidis type I RM systems demonstrate extensive diversity even within a single genetic lineage. This is contrary to current assumptions and has important implications for approaching the genetic manipulation of S. epidermidis Using Escherichia coli plasmid artificial modification (PAM) to express S. epidermidishsdMS, we readily overcame restriction barriers in S. epidermidis and achieved electroporation efficiencies equivalent to those of modification-deficient mutants. With these functional experiments, we demonstrated how genomic data can be used to predict both the functionality of type I RM systems and the potential for a strain to be electroporation proficient. We outline an efficient approach for the genetic manipulation of S. epidermidis strains from diverse genetic backgrounds, including those that have hitherto been intractable. Additionally, we identified S. epidermidis BPH0736, a naturally restriction-defective, clinically significant, multidrug-resistant ST2 isolate, as an ideal candidate for molecular studies.IMPORTANCEStaphylococcus epidermidis is a major cause of hospital-acquired infections, especially those related to implanted medical devices. Understanding how S. epidermidis causes disease and devising ways to combat these infections have been hindered by an inability to genetically manipulate clinically significant hospital-adapted strains. Here, we provide the first comprehensive analyses of the barriers to the uptake of foreign DNA in S. epidermidis and demonstrate that these are distinct from those described for S. aureus Using these insights, we demonstrate an efficient approach for the genetic manipulation of S. epidermidis to enable the study of clinical isolates for the first time.


Reducing stroke risk in hypertensive patients: Asian Consensus Conference recommendations.
Stroke results in substantial morbidity and mortality globally. Asia-Pacific countries bear a disproportionate share of the burden of stroke, a burden that will grow as their populations' life expectancies rise. Hypertension is the single most important reversible risk factor for stroke, and effective measures to reduce blood pressure contribute significantly to reducing the incidence of stroke. The Asia-Pacific Consensus Conference on Stroke Prevention in Hypertensive Patients assembled leading experts from the region to reach an actionable consensus aimed at reducing stroke-induced morbidity and mortality in Asia through the evidence-based treatment of hypertension. The discussions of the group focused on how best to improve blood pressure control, how to promote lifestyle changes at the population level, and how to reduce the clinical and health system barriers and other challenges facing developing and low-income countries. The experts concluded that physicians must place an increased priority on reducing their patients' risk of stroke and recognise that all hypertensive patients are at greater risk of having a stroke compared with nonhypertensive individuals. They advocated that physicians must educate hypertensive patients about the risk of stroke, promote lifestyle modification to all patients diagnosed with hypertension, and prescribe rigorous antihypertensive treatment to get patients to recommended blood pressure goals.


Relation between transmural deformation and local myofiber direction in canine left ventricle.
To determine the relation between local myofiber anatomy and local deformation in the wall of the left ventricle, both three-dimensional transmural deformation and myofiber orientation were examined in the anterior free wall of seven canine left ventricles. Deformation was measured by imaging columns of implanted radiopaque markers with high-speed, biplane cineradiography (16 mm, 120 frames/sec). Hearts were fixed at end diastole and sectioned parallel to the local epicardial tangent plane to determine the transmural distribution of fiber directions at the site of strain measurement. The principal direction of deformation associated with the greatest shortening was compared with the local fiber direction in the outer (21 +/- 8% of the wall thickness from the epicardium) and inner (65 +/- 9%) halves of the wall. Although the fiber direction varied substantially with depth from the epicardium, the principal direction did not. In the outer half of the wall, fiber direction averaged -8 +/- 24 degrees, while the principal direction averaged -33 +/- 24 degrees from circumferential (counterclockwise angles are positive). In the inner half, fiber direction averaged 69 +/- 10 degrees, while the principal direction averaged -22 +/- 21 degrees. Therefore, while fiber and principal directions were not substantially different in the outer half, the greatest shortening occurred orthogonally to the fiber direction in the inner half. Normal and shear strains measured in a cardiac coordinate system (circumferential, longitudinal, and radial coordinates) were rotated (transformed) to "fiber" coordinates in both halves of the wall. In the outer half, normal strains observed in the fiber (-0.09 +/- 0.04) and cross-fiber (-0.04 +/- 0.04) directions were not significantly different (paired t test, p less than 0.05). In the inner half, more than twice as much strain occurred in the cross-fiber (-0.17 +/- 0.03) than in the fiber direction (-0.06 +/- 0.06). Moreover, the only shear strain that remained substantial after transformation was transverse shear in the plane of the fiber and radial coordinates. These results suggest that both reorientation and cross-sectional shape changes of myofibers or the interstitium may contribute to the large wall thickenings observed during contraction, particularly in the inner half of the ventricular wall.


Quadruple abnormal protein aggregates in brainstem pathology and exogenous metal-rich magnetic nanoparticles (and engineered Ti-rich nanorods). The substantia nigrae is a very early target in young urbanites and the gastrointestinal tract a key brainstem portal.
Fine particulate air pollution (PM2.5) exposures are linked with Alzheimer's and Parkinson's diseases (AD,PD). AD and PD neuropathological hallmarks are documented in children and young adults exposed lifelong to Metropolitan Mexico City air pollution; together with high frontal metal concentrations (especially iron)-rich nanoparticles (NP), matching air pollution combustion- and friction-derived particles. Here, we identify aberrant hyperphosphorylated tau, ɑ synuclein and TDP-43 in the brainstem of 186 Mexico City 27.29 ± 11.8y old residents. Critically, substantia nigrae (SN) pathology seen in mitochondria, endoplasmic reticulum and neuromelanin (NM) is co-associated with the abundant presence of exogenous, Fe-, Al- and Ti-rich NPs.The SN exhibits early and progressive neurovascular unit damage and mitochondria and NM are associated with metal-rich NPs including exogenous engineered Ti-rich nanorods, also identified in neuroenteric neurons. Such reactive, cytotoxic and magnetic NPs may act as catalysts for reactive oxygen species formation, altered cell signaling, and protein misfolding, aggregation and fibril formation. Hence, pervasive, airborne and environmental, metal-rich and magnetic nanoparticles may be a common denominator for quadruple misfolded protein neurodegenerative pathologies affecting urbanites from earliest childhood. The substantia nigrae is a very early target and the gastrointestinal tract (and the neuroenteric system) key brainstem portals. The ultimate neural damage and neuropathology (Alzheimer's, Parkinson's and TDP-43 pathology included) could depend on NP characteristics and the differential access and targets achieved via their portals of entry. Thus where you live, what air pollutants you are exposed to, what you are inhaling and swallowing from the air you breathe,what you eat, how you travel, and your occupational longlife history are key. Control of NP sources becomes critical.


17β-Hydroxysteroid dehydrogenase type 12 is responsible for maturation-inducing steroid synthesis during oocyte maturation in Nile tilapia.
17α, 20β-Dihydroxy-4-pregnen-3-one (DHP) is a maturation-inducing steroid in many teleost fish. Carbonyl reductase-like 20β-hydroxysteroid dehydrogenase (CR/20β-HSD) is a candidate enzyme responsible for DHP production during oocyte maturation in various fish, including Nile tilapia. However, a novel type of 17β-hydroxysteroid dehydrogenase, type 12-like (17β-HSD12L), is responsible for DHP production during oocyte maturation in masu salmon. 17β-HSD12 (presumably orthologous to salmon 17β-HSD12L) has been detected in Nile tilapia; however, its enzymatic activity and specific ability to convert the DHP substrate 17α-hydroxyprogesterone (17OHP) have not been examined. This study aimed to determine whether CR/20β-HSD or 17β-HSD12 is responsible for DHP production during oocyte maturation in the Nile tilapia. Mammalian expression vectors containing tilapia hsd17b12 or CR/20bhsd were transfected into HEK293T cells, followed by incubation with 17OHP. HEK293T cells transfected with hsd17b12 exhibited a strong ability to convert exogenous 17OHP to DHP (73.8% yield). Cells transfected with CR/20bhsd or the control vector converted only 7.4% and 7.5% of 17OHP to DHP, respectively. In addition, based on LC-MS/MS analyses, 17β-HSD12 did not convert any substrates other than 17OHP, including DHP, adrenosterone, androstenedione, estrone, testosterone, 11-ketotestosterone, and estradiol-17β. CR/20β-HSD showed strong 17β-HSD oxidoreductase activity especially with adrenosterone and androstenedione. Tissue-specific hsd17b12 expression analyzed by RT-PCR showed that hsd17b12 mRNA was strongest amplification in full-grown follicles. Finally, full-grown ovarian follicles were incubated with salmon pituitary extract (SPE, 100 µg/mL) or human chorionic gonadotropin (HCG, 100 IU/mL) to induce 20β-HSD activity in vitro, and enzyme activity was assessed by co-incubation with 100 ng/mL 17OHP for 2, 4, 8, and 16 h. Conversion of 17OHP to DHP by ovarian follicles incubated with SPE and HCG peaked at 16 h, subsequent with increased follicular hsd17b12 mRNA levels, which were significantly higher than those in control incubations. However, the levels of CR/20bhsd mRNA remained low and did not differ among time points. The present study strongly suggests that 17β-HSD12, and not CR/20β-HSD, is the 20β-HSD responsible for DHP production by ovarian follicles during oocyte maturation in Nile tilapia.


Development and validation of genic-SSR markers in sesame by RNA-seq.
Sesame (Sesamum indicum L.) is one of the most important oil crops; however, a lack of useful molecular markers hinders current genetic research. We performed transcriptome sequencing of samples from different sesame growth and developmental stages, and mining of genic-SSR markers to identify valuable markers for sesame molecular genetics research. In this study, 75 bp and 100 bp paired-end RNA-seq was used to sequence 24 cDNA libraries, and 42,566 uni-transcripts were assembled from more than 260 million filtered reads. The total length of uni-transcript sequences was 47.99 Mb, and 7,324 SSRs (SSRs ≥15 bp) and 4,440 SSRs (SSRs ≥18 bp) were identified. On average, there was one genic-SSR per 6.55 kb (SSRs ≥15 bp) or 10.81 kb (SSRs ≥18 bp). Among perfect SSRs (≥18 bp), di-nucleotide motifs (48.01%) were the most abundant, followed by tri- (20.96%), hexa- (25.37%), penta- (2.97%), tetra- (2.12%), and mono-nucleotides (0.57%). The top four motif repeats were (AG/CT)n [1,268 (34.51%)], (CA/TG)n [281 (7.65%)], (AT/AT)n [215 (5.85%)], and (GAA/TTC)n [131 (3.57%)]. A total of 2,164 SSR primer pairs were identified in the 4,440 SSR-containing sequences (≥18 bp), and 300 SSR primer pairs were randomly chosen for validation. These SSR markers were amplified and validated in 25 sesame accessions (24 cultivated accessions, one wild species). 276 (92.0%) primer pairs yielded PCR amplification products in 24 cultivars. Thirty two primer pairs (11.59%) exhibited polymorphisms. Moreover, 203 primer pairs (67.67%) yielded PCR amplicons in the wild accession and 167 (60.51%) were polymorphic between species. A UPGMA dendrogram based on genetic similarity coefficients showed that the correlation between genotype and geographical source was low and that the genetic basis of sesame in China is narrow, as previously reported. The 32 polymorphic primer pairs were validated using an F2 mapping population; 18 primer pairs exhibited polymorphisms between the parents, and 14 genic-SSRs could be integrated into 9 main linkage groups. 2,164 genic-SSR markers have been developed in sesame using transcriptome sequencing. 276 of 300 validated primer pairs successfully yielded PCR amplicons in 24 cultivated sesame accessions. These markers increase current SSR marker resources and will greatly benefit genetic diversity, qualitative and quantitative trait mapping and marker-assisted selection studies in sesame.


Evaluation of a device to improve non-coring needle insertion into implanted intravenous ports.
Implanted intravenous ports (IPs) are increasingly used in health care. The experience of having IPs accessed can vary a great deal for patients. Successful IP access depends on the experience and skill of the health professional and wrongly positioned attempts are not only painful for the patient but can also cause damage to the outer casing of the IP. The more skin punctures made over the port, the higher the risk of infection in the subcutaneous tissue. The Portacator is a sterile, single-use product that sits on the skin over the IP insertion site. Its purpose is to enable the successful insertion of a non-coring needle into the centre of the IP. The device's efficacy was investigated using a port test rig and by conducting a clinical evaluation in two hospital units that support patients with IPs who require regular IV therapy infusions for long-term illness. The device provides an easy reference for central non-coring needle insertion, and users were able to insert the needle closer to the port chamber centre when using the device as only two fingers are used to hold it in place, which gave them a less obstructed view of the site. The device improved the rates of first-time IP puncture success with a non-coring needle. Patient satisfaction increased as they were more confident insertion would be successful first time so they would experience less pain. Nurses felt better supported and more confident they could achieve success at their first attempt at IP access using the device.


Complement receptor 2-mediated targeting of complement inhibitors to sites of complement activation.
In a strategy to specifically target complement inhibitors to sites of complement activation and disease, recombinant fusion proteins consisting of a complement inhibitor linked to a C3 binding region of complement receptor (CR) 2 were prepared and characterized. Natural ligands for CR2 are C3 breakdown products deposited at sites of complement activation. Fusion proteins were prepared consisting of a human CR2 fragment linked to either the N terminus or C terminus of soluble forms of the membrane complement inhibitors decay accelerating factor (DAF) or CD59. The targeted complement inhibitors bound to C3-opsonized cells, and all were significantly more effective (up to 20-fold) than corresponding untargeted inhibitors at protecting target cells from complement. CR2 fusion proteins also inhibited CR3-dependent adhesion of U937 cells to C3 opsonized erythrocytes, indicating a second potential anti-inflammatory mechanism of CR2 fusion proteins, since CR3 is involved in endothelial adhesion and diapedesis of leukocytes at inflammatory sites. Finally, the in vivo validity of the targeting strategy was confirmed by the demonstration that CR2-DAF, but not soluble DAF, targets to the kidney in mouse models of lupus nephritis that are associated with renal complement deposition.


Recombinant human megakaryocyte growth and development factor stimulates thrombocytopoiesis in normal nonhuman primates.
Megakaryocyte growth and development factor (MGDF) is a novel cytokine that binds to the c-mpl receptor and stimulates megakaryocyte development in vitro and in vivo. This report describes the ability of recombinant human (r-Hu) MGDF to affect megakaryocytopoiesis in normal nonhuman primates. r-HuMGDF was administered subcutaneously to normal, male rhesus monkeys once per day for 10 consecutive days at dosages of 2.5, 25, or 250 micrograms/kg of body weight. Bone marrow and peripheral blood were assayed for clonogenic activity and peripheral blood counts were monitored. Circulating platelet counts increased significantly (P < .05) for all doses within 6 days of r-HuMGDF administration and reached maximal levels between day 12 and day 14 postcytokine administration. The 2.5, 25.0, and 250.0 micrograms/kg/d doses elicited peak mean platelet counts that were 592%, 670%, and 449% of baseline, respectively. Bone marrow-derived clonogenic data showed significant increases in the concentration of megakaryocyte (MEG)-colony-forming unit (CFU) and granulocyte-erythroid-macrophage-megakaryocyte (GEMM)-CFU, whereas that of granulocyte-macrophage (GM)-CFU and burst-forming unit-erythroid (BFU-e) remained unchanged during the administration of r-HuMGDF. These data show that r-HuMGDF is a potent stimulator of thrombocytopoiesis in the normal nonhuman primate.


Jumping and hopping in elite and amateur orienteering athletes and correlations to sprinting and running.
Jumping and hopping are used to measure lower-body muscle power, stiffness, and stretch-shortening-cycle utilization in sports, with several studies reporting correlations between such measures and sprinting and/or running abilities in athletes. Neither jumping and hopping nor correlations with sprinting and/or running have been examined in orienteering athletes. The authors investigated squat jump (SJ), countermovement jump (CMJ), standing long jump (SLJ), and hopping performed by 8 elite and 8 amateur male foot-orienteering athletes (29 ± 7 y, 183 ± 5 cm, 73 ± 7 kg) and possible correlations to road, path, and forest running and sprinting performance, as well as running economy, velocity at anaerobic threshold, and peak oxygen uptake (VO(2peak)) from treadmill assessments. During SJs and CMJs, elites demonstrated superior relative peak forces, times to peak force, and prestretch augmentation, albeit lower SJ heights and peak powers. Between-groups differences were unclear for CMJ heights, hopping stiffness, and most SLJ parameters. Large pairwise correlations were observed between relative peak and time to peak forces and sprinting velocities; time to peak forces and running velocities; and prestretch augmentation and forest-running velocities. Prestretch augmentation and time to peak forces were moderately correlated to VO(2peak). Correlations between running economy and jumping or hopping were small or trivial. Overall, the elites exhibited superior stretch-shortening-cycle utilization and rapid generation of high relative maximal forces, especially vertically. These functional measures were more closely related to sprinting and/or running abilities, indicating benefits of lower-body training in orienteering.


Genetic Mouse Models as In Vivo Tools for Cholangiocarcinoma Research.
Cholangiocarcinoma (CCA) is a genetically and histologically complex disease with a highly dismal prognosis. A deeper understanding of the underlying cellular and molecular mechanisms of human CCA will increase our current knowledge of the disease and expedite the eventual development of novel therapeutic strategies for this fatal cancer. This endeavor is effectively supported by genetic mouse models, which serve as sophisticated tools to systematically investigate CCA pathobiology and treatment response. These in vivo models feature many of the genetic alterations found in humans, recapitulate multiple hallmarks of cholangiocarcinogenesis (encompassing cell transformation, preneoplastic lesions, established tumors and metastatic disease) and provide an ideal experimental setting to study the interplay between tumor cells and the surrounding stroma. This review is intended to serve as a compendium of CCA mouse models, including traditional transgenic models but also genetically flexible approaches based on either the direct introduction of DNA into liver cells or transplantation of pre-malignant cells, and is meant as a resource for CCA researchers to aid in the selection of the most appropriate in vivo model system.


Volume-outcome relationship in neurotrauma care.
A positive correlation between outcomes and the volume of patients seen by a provider has been supported by numerous studies. Volume-outcome relationships (VORs) have been well documented in the setting of both neurosurgery and trauma care and have shaped regionalization policies to optimize patient outcomes. Several authors have also investigated the correlation between patient volume and cost of care, known as the volume-cost relationship (VCR), with mixed results. The purpose of the present study was to investigate VORs and VCRs in the treatment of common intracranial injuries by testing the hypotheses that outcomes suffer at small-volume centers and costs rise at large-volume centers. The authors performed a cross-sectional cohort study of patients with neurological trauma using the 2006 Nationwide Inpatient Sample, the largest nationally representative all-payer data set. Patients were identified using ICD-9 codes for subdural, subarachnoid, and extradural hemorrhage following injury. Transfers were excluded from the study. In the primary analysis the association between a facility's neurotrauma patient volume and patient survival was tested. Secondary analyses focused on the relationships between patient volume and discharge status as well as between patient volume and cost. Analyses were performed using logistic regression. In-hospital mortality in the overall cohort was 9.9%. In-hospital mortality was 14.9% in the group with the smallest volume of patients, that is, fewer than 6 cases annually. At facilities treating 6-11, 12-23, 24-59, and 60+ patients annually, mortality was 8.0%, 8.3%, 9.5%, and 10.0%, respectively. For these groups there was a significantly reduced risk of in-hospital mortality as compared with the group with fewer than 6 annual patients; the adjusted ORs (and corresponding 95% CIs) were 0.45 (0.29-0.68), 0.56 (0.38-0.81), 0.63 (0.44-0.90), and 0.59 (0.41-0.87), respectively. For these same groups (once again using < 6 cases/year as the reference), there were no statistically significant differences in either estimated actual cost or duration of hospital stay. A VOR exists in the treatment of neurotrauma, and a meaningful threshold for significantly improved mortality is 6 cases per year. Emergency and interfacility transport policies based on this threshold might improve national outcomes. Cost of care does not differ significantly with patient volume.


Association of genetic variants with primary angle closure glaucoma in two different populations.
A recent large genome-wide association study (GWAS) identified multiple variants associated with primary angle-closure glaucoma (PACG). The present study investigated the role of these variants in two cohorts with PACG recruited from Australia and Nepal. Patients with PACG and appropriate controls were recruited from eye clinics in Australia (n = 232 cases and n = 288 controls) and Nepal (n = 106 cases and 204 controls). Single nucleotide polymorphisms (SNPs) rs3753841 (COL11A1), rs1015213 (located between PCMTD1 and ST18), rs11024102 (PLEKHA7), and rs3788317 (TXNRD2) were selected and genotyped on the Sequenom. Analyses were conducted using PLINK and METAL. After adjustment for age and sex, SNP rs3753841 was found to be significantly associated with PACG in the Australian cohort (p = 0.017; OR = 1.34). SNPs rs1015213 (p = 0.014; OR 2.35) and rs11024102 (p = 0.039; OR 1.43) were significantly associated with the disease development in the Nepalese cohort. None of these SNPs survived Bonferroni correction (p = 0.05/4 = 0.013). However, in the combined analysis, of both cohorts, rs3753841 and rs1015213 showed significant association with p-values of 0.009 and 0.004, respectively both surviving Bonferroni correction. SNP rs11024102 showed suggestive association with PACG (p-value 0.035) and no association was found with rs3788317. The present results support the initial GWAS findings, and confirm the SNP's contribution to PACG. This is the first study to investigate these loci in both Australian Caucasian and Nepalese populations.


Cerebral blood flow after surgery for unruptured cerebral aneurysms: effects of surgical manipulation and irrigation fluid.
Cerebral blood flow (CBF) is important in the management of cerebrovascular diseases. Surgical manipulation may compromise the appropriate interpretation of postoperative CBF changes, but the effects are not well understood. To investigate the effect of surgical manipulation on postoperative CBF in a setting of prospective randomized comparison of 2 irrigation fluids during surgery. Twenty patients undergoing the clipping of unruptured cerebral aneurysms through the pterional approach were randomly assigned to use of Artcereb, an artificial cerebrospinal fluid, or physiological saline as irrigation fluid. Postoperative CBF and clinical conditions were evaluated 3 times in the first 7 to 10 postoperative days. Postoperative CBF decreased by 10 to 15% on the first postoperative day in the ipsilateral inferior frontal gyrus, where surgical manipulation may be greatest. CBF reduction was less in regions remote from the surgical site and later in the follow-up periods. Selection of irrigation fluid did not influence postoperative CBF significantly, although postoperative clinical conditions may be better using Artcereb. Postoperative CBF changes due to surgical manipulation should be considered in patients whose hemodynamic conditions are important for appropriate management.


Three types of scientific evidence to inform physical activity policy: results from a comparative scoping review.
This paper presents a typology of available evidence to inform physical activity policy. It aims to refine the distinction between three types of evidence relating to physical activity and to compare these types for the purpose of clarifying potential research gaps. A scoping review explored the extent, range and nature of three types of physical activity-related evidence available in reviews: (I) health outcomes/risk factors, (II) interventions and (III) policy-making. A six-step qualitative, iterative process with expert consultation guided data coding and analysis in EPPI Reviewer 4. 856 Type I reviews, 350 Type II reviews and 40 Type III reviews were identified. Type I reviews heavily focused on obesity issues (18 %). Reviews of a systematic nature were more prominent in the Type II (>50 %). Type III reviews tended to conflate research about policy intervention effectiveness and research about policymaking processes. The majority of reviews came from the United States, United Kingdom, Australia and Canada. Although evidence gaps exist regarding evidence Types I and II, the most prominent gap regards Type III, i.e. research pertaining to physical activity policymaking. The findings presented herein will be used to inform physical activity policy development and future research.


Communications of normal nasal and paranasal cavities in computed tomography of horses.
Heads from 15 male and female horses of various breeds and ages were examined with computed tomography under general anesthesia in dorsal recumbency. The main interest was the evaluation of the entire paranasal sinus system. Special attention was paid to the location, size, and shape of the conchomaxillary, nasomaxillary, frontomaxillary, and sphenopalatinal openings. The frontomaxillary opening was the largest aperture and was found to be age-dependent in size mostly. Orientation and shape of the openings were sagittal or horizontal; the narrowest of them was the slit-like nasomaxillary aperture. The thickness of the vascularized mucous membranes in the nasal cavity was obtained up to 6 mm; the surface was smooth and well defined. The paranasal lining was invisible in computed tomography (CT) images because of its thin layer. CT proved to be a very useful method for documentation of the paranasal openings and for evaluation of the state of the mucous membranes in the nasal and paranasal cavities.


Longevity studies in GenomEUtwin.
Previous twin studies have indicated that approximately 25% of the variation in life span can be attributed to genetic factors and recent studies have also suggested a moderate clustering of extreme longevity within families. Here we discuss various definitions of extreme longevity and some analytical approaches with special attention to the challenges due to censored data. Lexis diagrams are provided for the Danish, Dutch, Finnish, Italian, Norwegian, and Swedish Twin registries hereby outlining possibilities for longevity studies within GenomEUtwin. We extend previous analyses of lifespan for the Danish 1870-1900 twin cohorts to include the new 1901-1910 cohorts, which are consistent with the previous findings. The size of the twin cohorts in GenomEUtwin and the existence of population-based, nationwide health and death registers make epidemiological studies of longevity very powerful. The combined GenomEUtwin sample will also allow detailed age-specific heritability analyses of lifespan. Finally, it will provide a resource for identifying unusual sibships (i.e., dizygotic twin pairs) where both survived to extreme ages, as a basis for discovering genetic variants of importance for extreme survival.


The oligodendroglia cytoskeleton in health and disease.
Oligodendrocytes have a high rate of synthetic activity and produce vast amounts of myelin. The membrane production requires specific sorting and transport processes and structural support. In culture, oligodendrocytes extend flat membranous sheets containing an extensive cytoskeletal network of microtubules (MTs) and microfilaments (MFs). The microtubules participate in the elaboration and stabilization of the myelin-containing cellular processes and have an impact not only on the complex oligodendroglia architecture but also influence their functions. They participate in intracellular sorting processes and the translocation of myelin basic protein (MBP) mRNAs to the forming myelin sheath. The two major groups of neuronal microtubule-associated proteins (MAPs), MAP2 and tau are expressed in oligodendrocytes and might be involved in the regulation of MT stability and organization. Myelin-specific proteins, such as MBP and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), interact with the cytoskeleton. Glial changes occur in a variety of neurodegenerative diseases, and glial fibrillary tangles and glial cytoplasmic inclusions (GCls), containing abnormal microtubular structures which stain positively for stress proteins and microtubule-associated proteins, are found in oligodendrocytes of the affected brains. The role of MTs and their associated proteins in oligodendrocytes during normal development and pathological situations is specifically emphasized in this review.


A comprehensive comparison and analysis of soil screening values derived and used in China and the UK.
China and the UK use different risk-based approaches to derive soil screening or guideline values (SSVs; SGVs) for contaminants. Here we compare the approaches and the derived values for 6 illustrative contaminants. China's SSVs are derived using an approach developed in the US as follows: for carcinogens, acceptable level of risk (ACR) is set at 10-6 and the SSVs calculated as 10-6 divided by the soil exposure and toxicity data; for non-carcinogens, the hazard quotient is 1 and the SSV is calculated as 1 divided by the soil exposure and toxicity data. The UK's SGVs are calculated by the CLEA model, for which the Average Daily Exposure (ADE) from soil sources by a specific exposure route equals the health criteria values (HCVs) for that route, whether for carcinogens or a non-carcinogens. The UK's CLEA model is also used here to derive SSVs with Chinese input parameters. China's SSVs, the UK's SGVs and values for Chinese conditions derived using the UK approach were as follows (mg/kg): As, <1, 35, 20; Cd, 20, 18, 11; Cr (VI), <1, 14, 29; benzene, 1, 1, 2; toluene, 1200, 3005, 3800; ethyl-benzene, 7, 930, 1200. By comparing the differences in toxicity assessment and risk characterization, exposure assessment and parameter types in the methodologies to obtain SSVs in China and the UK, and by combining the CLEA model with Chinese parameterisation, these comparisons highlight that the difference in toxicity assessment and risk characterization methods of carcinogens results in the biggest difference in SSVs between the 2 countries. However, for non-carcinogenic substances, the difference of SSVs calculation method and SSVs is small. The difference in SSVs for carcinogenic substances is also related to the route of exposure. For volatile organic compounds, the presence of indoor respiratory exposure pathways greatly reduces the differences caused by toxicity assessment and risk characterization methods. For non-volatile substances such as heavy metals, the effects of toxicity assessment and risk characterization methods are significant. The SSV of As obtained by the CLEA model with Chinese parameters is closer to the background value of soil in China. In the management of non-volatile contaminated sites such as heavy metals in China, the CLEA model can be used for risk assessment and calculation of site specific SSVs. In the future, China can use the UK method to strengthen its toxicity assessment and risk characterization methods for carcinogenic substances, to reduce the uncertainty in the risk assessment of contaminated sites and improve the scientific management of contaminated sites.


Brownian dynamics of fully confined suspensions of rigid particles without Green's functions.
We introduce a Rigid-Body Fluctuating Immersed Boundary (RB-FIB) method to perform large-scale Brownian dynamics simulations of suspensions of rigid particles in fully confined domains, without any need to explicitly construct Green's functions or mobility operators. In the RB-FIB approach, discretized fluctuating Stokes equations are solved with prescribed boundary conditions in conjunction with a rigid-body immersed boundary method to discretize arbitrarily shaped colloidal particles with no-slip or active-slip prescribed on their surface. We design a specialized Split-Euler-Maruyama temporal integrator that uses a combination of random finite differences to capture the stochastic drift appearing in the overdamped Langevin equation. The RB-FIB method presented in this work only solves mobility problems in each time step using a preconditioned iterative solver and has a computational complexity that scales linearly in the number of particles and fluid grid cells. We demonstrate that the RB-FIB method correctly reproduces the Gibbs-Boltzmann equilibrium distribution and use the method to examine the time correlation functions for two spheres tightly confined in a cuboid. We model a quasi-two-dimensional colloidal crystal confined in a narrow microchannel and hydrodynamically driven across a commensurate periodic substrate potential mimicking the effect of a corrugated wall. We observe partial and full depinning of the colloidal monolayer from the substrate potential above a certain wall speed, consistent with a transition from static to kinetic friction through propagating kink solitons. Unexpectedly, we find that particles nearest to the boundaries of the domain are the first to be displaced, followed by particles in the middle of the domain.


Knowledge and attitudes of Swedish politicians concerning induced abortion.
Induced abortion is more frequent in Sweden than in many other Western countries. We wanted to investigate attitudes and knowledge about induced abortion among politicians responsible for healthcare in three Swedish counties. A study-specific questionnaire was sent to all 375 elected politicians in three counties; 192 (51%) responded. The politicians stated that they were knowledgeable about the Swedish abortion law. More than half did not consider themselves, in their capacity as politicians, sufficiently informed about abortion-related matters. Most politicians (72%) considered induced abortion to be primarily a 'women's rights issue' rather than an ethical one, and 54% considered 12 weeks' gestational age an adequate upper limit for induced abortion. Only about a third of the respondents were correctly informed about the number of induced abortions annually carried out in Sweden. Information and knowledge on induced abortion among Swedish county politicians seem not to be optimal. Changes aimed at reducing the current high abortion rates will probably not be easy to achieve as politicians seem to be reluctant to commit themselves on ethical issues and consider induced abortion mainly a women's rights issue.


The role of circulating serotonin in the development of chronic obstructive pulmonary disease.
Cigarette smoking is a major risk factor in the development of age-related chronic obstructive pulmonary disease (COPD). The serotonin transporter (SERT) gene polymorphism has been reported to be associated with COPD, and the degree of cigarette smoking has been shown to be a significant mediator in this relationship. The interrelation between circulating serotonin (5-hydroxytyptamine, 5-HT), cigarette smoking and COPD is however largely unknown. The current study aimed at investigating the mediation effects of plasma 5-HT on cigarette smoking-induced COPD and the relation between plasma 5-HT levels and age. The association between plasma 5-HT, age and COPD was analyzed in a total of 62 COPD patients (ever-smokers) and 117 control subjects (healthy non-smokers and ever-smokers). Plasma 5-HT levels were measured by enzyme-linked immuno assay (EIA). The elevated plasma 5-HT levels were significantly associated with increased odds for COPD (OR = 1.221, 95% CI = 1.123 to 1.319, p<0.0001). The effect remained significant after being adjusted for age and pack-years smoked (OR = 1.271, 95% CI = 1.134 to 1.408, p = 0.0003). Furthermore, plasma 5-HT was found to mediate the relation between pack-years smoked and COPD. A positive correlation (r = 0.303, p = 0.017) was found between plasma 5-HT levels and age in COPD, but not in the control subjects (r = -0.149, p = 0.108). Our results suggest that cigarette smoke-induced COPD is partially mediated by the plasma levels of 5-HT, and that these become elevated with increased age in COPD. The elevated plasma 5-HT levels in COPD might contribute to the pathogenesis of this disease.


Raised serum activity of phospholipase A2 immunochemically related to group II enzyme in inflammatory bowel disease: its correlation with disease activity of Crohn's disease and ulcerative colitis.
Calcium dependent phospholipase A2 activity in the mixed micelles of 1-palmitoyl-2-oleoyl-phosphatidylglycerol and cholate was measured in sera of 39 patients with Crohn's disease, 40 patients with ulcerative colitis, and 40 healthy controls. The phospholipase A2 activity was significantly raised in those sera of the patients with active Crohn's disease and those with moderate and severe ulcerative colitis. The major phospholipase A2 activity derived from the sera was separated into two peaks by reverse phase high performance liquid chromatography. The phospholipase A2 active fractions were immunochemically characterised using specific antibody directed against human group II phospholipase A2 purified from rheumatoid synovial fluid. The results suggest that raised serum phospholipase A2 activity in patients with Crohn's disease and ulcerative colitis was mainly attributed to the two forms of phospholipase A2 immunochemically related to group II enzyme. In patients with Crohn's disease, serum phospholipase A2 activity decreased in parallel with clinical improvement, and correlated with serum C-reactive protein and erythrocyte sedimentation rate. The results suggest that serum phospholipase A2 activity may serve as an additional indicator of disease activity. Serum phospholipase A2 activity in patients with ulcerative colitis tends to increase in relation with endoscopic severity, and may be a more sensitive laboratory index than serum C-reactive protein and erythrocyte sedimentation rate to evaluate disease activity.