Functional equivalence, competitive hierarchy and facilitation determine species coexistence in highly invaded grasslands.
Alien and native plant species often differ in functional traits. Trait differences could lead to niche differences that minimize competitive interactions and stabilize coexistence. However, trait differences could also translate into average fitness differences, leading to a competitive hierarchy that prevents coexistence. We tested whether trait differences between alien and native species translated into average fitness or stabilizing niche differences, and whether competition could explain observed coexistence within invaded grassland communities (New Zealand). Trait differences reflected marked competitive hierarchy, suggesting average fitness differences. Species coexistence was determined by a trade-off between species susceptibility to herbivory vs competitive hierarchy and facilitation. Importantly, although aliens and natives differed in their trait values, they did not differ in their competitive response, highlighting the importance of equalizing mechanisms in structuring invaded communities. Only a few alien species with a particular set of traits were able to jeopardize species coexistence when grazing was ceased. Our study explains why some alien species coexist with natives, whereas others have strong impacts on native communities. It highlights that trait differences can underlie several coexistence processes and that the demonstration of trait differences between aliens and natives is only a first step to understanding the role of biotic interactions in structuring invaded communities.


Time-limited environments affect the evolution of egg-body size allometry.
Initial offspring size is a fundamental component of absolute growth rate, where large offspring will reach a given adult body size faster than smaller offspring. Yet, our knowledge regarding the coevolution between offspring and adult size is limited. In time-constrained environments, organisms need to reproduce at a high rate and reach a reproductive size quickly. To rapidly attain a large adult body size, we hypothesize that, in seasonal habitats, large species are bound to having a large initial size, and consequently, the evolution of egg size will be tightly matched to that of body size, compared to less time-limited systems. We tested this hypothesis in killifishes, and found a significantly steeper allometric relationship between egg and body sizes in annual, compared to nonannual species. We also found higher rates of evolution of egg and body size in annual compared to nonannual species. Our results suggest that time-constrained environments impose strong selection on rapidly reaching a species-specific body size, and reproduce at a high rate, which in turn imposes constraints on the evolution of egg sizes. In combination, these distinct selection pressures result in different relationships between egg and body size among species in time-constrained versus permanent habitats.


Whole cell based microcontact imprinted capacitive biosensor for the detection of Escherichia coli.
In this study, a label-free, selective and sensitive microcontact imprinted capacitive biosensor was developed for the detection of Escherichia coli. The recognition of E. coli was successfully performed by this sensor prepared with the combination of microcontact imprinting method and capacitive biosensor technology. After preparation of bacterial stamps, microcontact-E. coli imprinted gold electrodes were generated using an amino acid based recognition element, N-methacryloyl-L-histidine methylester (MAH), 2-Hydroxyethyl methacrylate (HEMA) as monomers and ethyleneglycol dimethacrylate (EGDMA) as crosslinker under UV-polymerization. Real-time E. coli detection experiments were carried out within the range of 1.0×102-1.0×107CFU/mL. The unique combination of these two techniques provides selective detection with a detection limit of 70CFU/mL. The designed capacitive sensor has high selectivity and was able to distinguish E. coli when present together with competing bacterial strains which are known to have similar shape. In addition, the prepared sensor has the ability to detect E. coli with a recovery of 81-97% in e.g. river water.


Recent efforts and available technologies for safety in delivery of blood products.
Over the past few decades, many efforts to improve the safety of blood products have concentrated on the reduction of transfusion-associated infectious diseases, particularly human immunodeficiency virus and hepatitis C. As health care enters a time of significant economic changes and governmental agencies develop guidances to improve patient safety, new efforts are being implemented and new technologies are being developed to ensure safe delivery of blood products. This article outlines the structure of agencies responsible for blood safety in the United States, reviews the fairly recent implementation of a blood product bar-code labeling system (ISBT 128) in the United States, describes safety efforts at the level of the hospital transfusion service, and reviews some of the emerging technologies for safety in blood delivery at the bedside.


Diminishing the impact of the partial volume effect in cardiac SPECT perfusion imaging.
The partial volume effect (PVE) significantly restricts the absolute quantification of regional myocardial uptake and thereby limits the accuracy of absolute measurement of blood flow and coronary flow reserve by SPECT. The template-projection-reconstruction method has been previously developed for PVE compensation. This method assumes the availability of coregistered high-spatial resolution anatomical information as is now becoming available with commercial dual-modality imaging systems such as SPECT/CTs. The objective of this investigation was to determine the extent to which the impact of the PVE on cardiac perfusion SPECT imaging can be diminished if coregistered high-spatial resolution anatomical information is available. For this investigation the authors introduced an additional parameter into the template-projection-reconstruction compensation equation called the voxel filling fraction (F). This parameter specifies the extent to which structure edge voxels in the emission reconstruction are filled by the structure in question as determined by the higher spatial-resolution imaging modality and the fractional presence of the structure at different states of physiological motion as in combining phases of cardiac motion. During correction the removal of spillover to the cardiac region from the surrounding structures is performed first by using reconstructed templates of neighboring structures (liver, blood pool, lungs) to calculate spillover fractions. This is followed by determining recovery coefficients for all voxels within the heart wall from the reconstruction of the template projections of the left and right ventricles (LV and RV). The emission data are subsequently divided by these recovery coefficients taking into account the filling fraction F. The mathematical cardiac torso phantom was used for investigation correction of PVE for a normal LV distribution, a defect in the inferior wall, and a defect in the anterior wall. PVE correction resulted in a dramatic visual reduction in the impact of extracardiac activity, improved the uniformity of the normally perfused heart wall, and enhanced defect visibility without undue noise amplification. No significant artifacts were seen with PVE correction in the presence of mild (one voxel) misregistration. A statistically significant improvement in the accuracy of the count levels within the normal heart wall was also noted. However, residual spillover of counts from within the myocardium creates a bias in regions of decreased wall counts (perfusion defects/abnormal wall motion) when the anatomical imaging modality does not allow definition of templates for defects present in the heart during emission imaging.


Understanding the Host in the Management of Pneumonia. An Official American Thoracic Society Workshop Report.
Pneumonia causes a significant burden of disease worldwide. Although all populations are at risk of pneumonia, those at extremes of age and those with immunosuppressive disorders, underlying respiratory disease, and critical illness are particularly vulnerable. Although clinical practice guidelines addressing the management and treatment of pneumonia exist, few of the supporting studies focus on the crucial contributions of the host in pneumonia pathogenesis and recovery. Such essential considerations include the host risk factors that lead to susceptibility to lung infections; biomarkers reflecting the host response and the means to pursue host-directed pneumonia therapy; systemic effects of pneumonia on the host; and long-term health outcomes after pneumonia. To address these gaps, the Pneumonia Working Group of the Assembly on Pulmonary Infection and Tuberculosis led a workshop held at the American Thoracic Society meeting in May 2018 with overarching objectives to foster attention, stimulate research, and promote funding for short-term and long-term investigations into the host contributions to pneumonia. The workshop involved participants from various disciplines with expertise in lung infection, pneumonia, sepsis, immunocompromised patients, translational biology, data science, genomics, systems biology, and clinical trials. This workshop report summarizes the presentations and discussions and important recommendations for future clinical pneumonia studies. These recommendations include establishing consensus disease and outcome definitions, improved phenotyping, development of clinical study networks, standardized data and biospecimen collection and protocols, and development of innovative trial designs.


REM sleep in naps differentially relates to memory consolidation in typical preschoolers and children with Down syndrome.
Sleep is recognized as a physiological state associated with learning, with studies showing that knowledge acquisition improves with naps. Little work has examined sleep-dependent learning in people with developmental disorders, for whom sleep quality is often impaired. We examined the effect of natural, in-home naps on word learning in typical young children and children with Down syndrome (DS). Despite similar immediate memory retention, naps benefitted memory performance in typical children but hindered performance in children with DS, who retained less when tested after a nap, but were more accurate after a wake interval. These effects of napping persisted 24 h later in both groups, even after an intervening overnight period of sleep. During naps in typical children, memory retention for object-label associations correlated positively with percent of time in rapid eye movement (REM) sleep. However, in children with DS, a population with reduced REM, learning was impaired, but only after the nap. This finding shows that a nap can increase memory loss in a subpopulation, highlighting that naps are not universally beneficial. Further, in healthy preschooler's naps, processes in REM sleep may benefit learning.


Trans,trans-farnesol, an antimicrobial natural compound, improves glass ionomer cement properties.
A series of experiments were conducted to characterize a novel restorative material. We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM). Two groups were accomplished for all assays: GIC+tt-farnesol and GIC (control). Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM. 3) gtfB, gtfC, gtfD, gbpB, vicR, and covR expression; 4) MTT and microscopic morphology. Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength. Chemical assay: Raman spectroscopy. The adding of tt-farnesol to GIC led to larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05). Polysaccharides levels increased over time, similarly over groups (p>0.05). Viable and non-viable S. mutans were seen on the specimens' surface by CLSM but their virulence was not modulated by tt-farnesol. The tt-farnesol increased the HaCaT cell viability without impact on compressive and diametral tensile strength and roughness although the hardness was positively affected (p<0.05). Raman confirmed the presence of tt-farnesol. The incorporation of tt-farnesol into GIC inhibited the growth of cariogenic bacteria but had a little effect on the composition, structure and physiology of the biofilm matrices. Also, the tt-farnesol increased the hardness and the biocompatibility of the GIC, not influencing negatively other physical properties of the restorative material.


Influence of diabetes mellitus on the clinical manifestations and prognosis of infective endocarditis: a report from the International Collaboration on Endocarditis-Merged Database.
The purpose of this investigation was to study the influence of diabetes mellitus (DM) on outcomes of infective endocarditis (IE). Outcomes were compared between 150 diabetic and 905 non-diabetic patients with IE from the International Collaboration on Endocarditis Merged Database. Compared to non-diabetic patients, diabetic patients were older (median age 63 vs 57 y, p<0.001), were more often female (42.0% vs 31.9%, p=0.01), more often had comorbidities (41.5% vs 26.7%, p<0.001), and were more likely to be dialysis dependent (12.7% vs 4.0%, p<0.001). S. aureus was isolated more often (30.7% vs 21.7%, p=0.02), and microorganisms from the viridans Streptococcus group less often (16.7% vs 28.2%, p = 0.001) in the diabetic group. There was no difference with respect to the presence of congestive heart failure, embolism, intra-cardiac abscess, new valvular regurgitation, or valvular vegetation. Diabetic patients underwent surgical intervention less frequently (32.0% vs 44.9%, p = 0.003), and had higher overall in-hospital mortality (30.3% vs 18.6%, p = 0.001). On multivariable analysis, DM was an independent predictor of mortality (odds ratio (OR) = 1.71, 95% confidence interval (CI) 1.08-2.70), especially in male patients, as diabetic males had higher mortality than non-diabetic males (OR 2.18, CI 1.08-4.35). DM is an independent predictor of in-hospital mortality among patients hospitalized with IE.


The THRIVE© Program: Building Oncology Nurse Resilience Through Self-Care Strategies.
To develop an evidence-based program for addressing the concerns of burnout and secondary trauma and building on the concept of resilience in oncology healthcare providers. 164 oncology staff, of which 160 were nurses, at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute in Columbus, Ohio. Oncology nurses and other providers participated in the THRIVE© program, which consists of an eight-hour retreat designed to teach self-care strategies, a six-week private group study interaction on a social media platform, and a two-hour wrap-up session. The Compassion Fatigue Short Scale and the Connor-Davidson Resilience Scale were used to evaluate the program. In self-assessments prior to THRIVE, nurse managers demonstrated the greatest degree of burnout, and bedside/chairside nurses demonstrated the greatest degree of secondary trauma. The greatest improvement in average scores from pre- to postprogram assessment was in increased resilience and decreased burnout. Increased resilience scores were sustained for a six-month period after THRIVE participation. Oncology healthcare providers must identify self-care strategies that build their resilience for long, successful careers.


Active Fabry-Perot cavity for photonic temporal integrator with ultra-long operation time window.
In this paper, a photonic temporal integrator based on an active Fabry-Perot (F-P) cavity is proposed and theoretically investigated. The gain medium in the F-P cavity is a semiconductor optical amplifier (SOA) with high gain coefficient. Key feature of the proposed photonic integrator is that the length of integration time window is widely tunable and could be ideally extended to infinitely long when the injection current is approaching lasing condition. Based on an F-P cavity with practically feasible parameters, a photonic temporal integrator with an integration time window of 160 ns and an operation bandwidth of 180 GHz is achieved. The time-bandwidth product of this photonic temporal integrator is 28,800, which is about two-orders of magnitude higher than any previously reported results. Gain recovery effect has been also considered and analyzed for the impact on performance of the photonic integrator, followed by the simulation results of the impact of gain recovery.


Association of body mass index with arterial stiffness and blood pressure components: a twin study.
Obesity, blood pressure and arterial stiffness are heritable traits interconnected to each other but their possible common genetic and environmental etiologies are unknown. We studied 228 monozygotic and 150 dizygotic twin pairs aged 18-82 years from Italy, Hungary and the United States, of which 45 monozygotic and 38 dizygotic pairs were discordant for body mass index (BMI; intrapair difference (Δ) in BMI ≥ 3 kg/m(2)). Blood pressure components and arterial stiffness were measured by TensioMed Arteriograph. Hypertension was more prevalent among obese than non-obese individuals (55% vs. 29%, p < 0.001). Age-, sex- and country-adjusted heritability estimates were high for hemodynamic measures (45%-58%) and BMI (78%). According to bivariate Cholesky decomposition, phenotypic correlations between BMI and blood pressure components (r = -0.15 to 0.24, p < 0.05) were largely explained by additive genetic factors (65%-77%) with the remaining explained by the unique environment. When controlling for genetic factors within all monozygotic pairs, ΔBMI was significantly correlated with Δbrachial systolic blood pressure (SBP) and diastolic blood pressure (DBP), Δmean arterial pressure, and Δaortic SBP (r = 0.15-0.17, p < 0.05). For the same measures, heavier co-twins of BMI-discordant monozygotic pairs had significantly higher values than their leaner counterparts (p < 0.05). Blood pressure components are moderately correlated with BMI, largely because of shared genetic factors. However, for the association of BMI with brachial SBP and DBP, aortic SBP and mean arterial pressure, acquired, modifiable factors were also found to be important.


Developmental pattern of a serum binding protein for multiplication stimulating activity in the rat.
The concentration of multiplication stimulating activity (MSA), an insulinlike growth factor (IGF), is high in fetal rat serum. We now report that MSA is exclusively associated wth an albumin-size binding protein in fetal rat serum; the growth hormone-dependent, gamma globulin-size binding protein, which predominates in the older animal, is absent from fetal rat serum. When (125)I-MSA was incubated with fetal rat serum and then gel filtered on Sephadex G-200, specific radioactivity eluted in the void volume (peak I) and the albumin region (peak III); by contrast, specific radioactivity eluted mainly in the gamma globulin region (peak II) in adult rat serum. Pools of the Sephadex G-200 fractions were chromatographed on Sephadex G-50, in 1 M acetic acid, to separate the binding protein from IGF activity. Analysis of IGF activity by chick embryo fibroblast bioassay, competitive protein binding assay, and MSA by radioimmunoassay revealed that all the IGF activity and MSA in fetal rat serum resided in peak III. Measurement of MSA binding capacity of the stripped binding protein by Scatchard analysis demonstrated that the majority of binding capacity also was found in peak III in fetal rat serum; most of MSA binding capacity was in peak II in adult rat serum. In fetal rat sera, in addition to the peak III binding protein, which is the major carrier of endogenous MSA, there is a component in peak I capable of specifically binding (125)I-MSA. This component elutes as a single species from a Sepharose-6B column. As MSA associated with peak III gradually declined in early neonatal life, peak II-associated IGF activity measured by chick embryo fibroblast bioassay showed a rise of activity with a peak at 5 d of neonatal life, a nadir at 20 d, with an increase again to attain adult levels. These studies demonstrate that the MSA binding protein in the fetus is different from the growth hormone-dependent binding protein in adult life.


Intron 4 polymorphism of the endothelial nitric oxide synthase gene is associated with the development of lupus nephritis.
The objective was to investigate whether the functional polymorphism of intron 4 in the endothelial nitric oxide synthase (eNOS) gene is associated with susceptibility to systemic lupus erythematosus (SLE) and its clinical features. The 27-bp repeat polymorphism in intron 4 of the eNOS gene was determined by polymerase chain reaction in 88 SLE patients and 95 healthy control subjects. Clinical manifestations were analysed in each patient and correlated with the genotypes. The genotype distribution of the intron 4 of the eNOS did not differ between SLE patients and control subjects (aa, ab, bb genotypes 0, 15, 73 versus 2, 19, 74 controls respectively, chi-squared = 2.21, 2 df, P = 0.331). In the lupus patients according to the intron 4 genotypes of the eNOS, there was no clinically significant difference in age at onset, anti-dsDNA titre, C3, C4 level, SLEDAI, SLICC/ACR Damage Index, or autoantibodies such as RF, anti-Ro, La, RNP, Sm, or phospholipid antibodies. However, renal involvement was higher in patients with ab genotypes than in those with bb genotypes (53% versus 26%), but it did not reach statistical significance (P = 0.062). Logistic regression showed that having the ab genotype was a significant risk factor for the development of lupus nephritis (odds ratio = 3.28, 95%CI: 1.04-10.2, P = 0.04). In conclusion, our data show that the eNOS ab genotypes may be associated with the development of lupus nephritis, suggesting individuals who carry the 'a' allele are more susceptible to lupus nephritis than those with the 'b' allele.


High-energy chemistry of formamide: a unified mechanism of nucleobase formation.
The coincidence of the Late Heavy Bombardment (LHB) period and the emergence of terrestrial life about 4 billion years ago suggest that extraterrestrial impacts could contribute to the synthesis of the building blocks of the first life-giving molecules. We simulated the high-energy synthesis of nucleobases from formamide during the impact of an extraterrestrial body. A high-power laser has been used to induce the dielectric breakdown of the plasma produced by the impact. The results demonstrate that the initial dissociation of the formamide molecule could produce a large amount of highly reactive CN and NH radicals, which could further react with formamide to produce adenine, guanine, cytosine, and uracil. Based on GC-MS, high-resolution FTIR spectroscopic results, as well as theoretical calculations, we present a comprehensive mechanistic model, which accounts for all steps taking place in the studied impact chemistry. Our findings thus demonstrate that extraterrestrial impacts, which were one order of magnitude more abundant during the LHB period than before and after, could not only destroy the existing ancient life forms, but could also contribute to the creation of biogenic molecules.


Familial variant of dermatofibroma with malignancy in the proband.
Multiple fibrous histiocytomas of the dermis (dermatofibromas) were found in six males of one family. A number of the tumors fell within the histologic patterns commonly encountered in dermatofibromas, but some were unusually large and others were cytologically atypical. In addition, the proband died of a malignant fibrous histiocytoma of the lung. We believe that this is a syndrome and a familial variant of a common dermal entity.


Analysis of microbiota alterations in inflammasome-deficient mice.
Inflammasomes have emerged as central regulators of intestinal infection, immunity, and inflammation. Inflammasome activity mediates intestinal epithelial integrity, antimicrobial responses, and initiates inflammation through generation of the cytokines interleukin (IL-)1 and IL-18. Recent studies have identified an additional layer of inflammasome function in the intestine, namely, the control of intestinal microflora composition. Inflammasome-deficient mice show an aberrant microbial community which is dominantly transmissible to healthy mice. This dysbiosis in inflammasome-deficient mice has a profound impact on their physiology and pathophysiology, both locally in the intestine and systemically. Therefore, it is essential to consider the influence of the composition of microbial communities on experiments performed with inflammasome-deficient and other innate molecule-deficient mice, and to conduct experiments to control for potential dominant effects of the microflora on host responses. In this chapter, we provide experimental procedures to monitor inflammasome-mediated modifications of the intestinal microflora composition in mice and to test the resultant functional consequences of these changes in microbial communities and their transmission to cohoused mice.


Thick and diffuse cisternal clot independently predicts vasospasm-related morbidity and poor outcome after aneurysmal subarachnoid hemorrhage.
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant morbidity and mortality. The presence of thick, diffuse subarachnoid blood may portend a worse clinical course and outcome, independently of other known prognostic factors such as age, aneurysm size, and initial clinical grade. In this post hoc analysis, patients with aSAH undergoing surgical clipping (n = 383) or endovascular coiling (n = 189) were pooled from the placebo arms of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS)-2 and CONSCIOUS-3 randomized, double-blind, placebo-controlled phase 3 studies, respectively. Patients without and with thick, diffuse SAH (≥ 4 mm thick and involving ≥ 3 basal cisterns) on admission CT scans were compared. Clot size was centrally adjudicated. All-cause mortality and vasospasm-related morbidity at 6 weeks and Glasgow Outcome Scale-Extended (GOSE) scores at 12 weeks after aSAH were assessed. The effect of the thick and diffuse cisternal aSAH on vasospasm-related morbidity and mortality, and on poor clinical outcome at 12 weeks, was evaluated using logistic regression models. Overall, 294 patients (51.4%) had thick and diffuse aSAH. Compared to patients with less hemorrhage burden, these patients were older (median age 55 vs 50 years) and more often had World Federation of Neurosurgical Societies (WFNS) grade III-V SAH at admission (24.1% vs 16.5%). At 6 weeks, all-cause mortality and vasospasm-related morbidity occurred in 36.1% (95% CI 30.6%-41.8%) of patients with thick, diffuse SAH and in 14.7% (95% CI 10.8%-19.5%) of those without thick, diffuse SAH. Individual event rates were 7.5% versus 2.5% for all-cause death, 19.4% versus 6.8% for new cerebral infarct, 28.2% versus 9.4% for delayed ischemic neurological deficit, and 24.8% versus 10.8% for rescue therapy due to cerebral vasospasm, respectively. Poor clinical outcome (GOSE score ≥ 4) was observed in 32.7% (95% CI 27.3%-38.3%) and 16.2% (95% CI 12.1%-21.1%) of patients with and without thick, diffuse SAH, respectively. In a large, centrally adjudicated population of patients with aSAH, WFNS grade at admission and thick, diffuse SAH independently predicted vasospasm-related morbidity and poor 12-week clinical outcome. Patients with thick, diffuse cisternal SAH may be an important cohort to target in future clinical trials of treatment for vasospasm.


The effect of modifiable risk factors on pancreatic cancer mortality in populations of the Asia-Pacific region.
Pancreatic cancer accounts for about 220,000 deaths each year. Known risk factors are smoking and type 2 diabetes. It remains to be seen whether these risk factors are equally important in Asia and whether other modifiable risk factors have important associations with pancreatic cancer. An individual participant data analysis of 30 cohort studies was carried out, involving 420,310 Asian participants (33% female) and 99,333 from Australia/New Zealand (45% female). Cox proportional hazard models, stratified by study and sex and adjusted for age, were used to quantify risk factors for death from pancreatic cancer. During 3,558,733 person-years of follow-up, there were 324 deaths from pancreatic cancer (54% Asia and 33% female). Mortality rates (per 100,000 person-years) from pancreatic cancer were 10 for men and 8 for women. The following are age-adjusted hazard ratios (95% confidence interval) for death from pancreatic cancer: for current smoking, 1.61 (1.12-2.32); for diabetes, 1.76 (1.15-2.69); for a 2-cm increase in waist circumference, 1.08 (1.02-1.14). All three relationships remained significant (P < 0.05) after adjustment for other risk factors. There was no evidence of heterogeneity in the strength of these associations between either cohorts from Asia and Australia/New Zealand or between the sexes. In men, the combination of cigarette smoking and diabetes more than doubled the likelihood of pancreatic cancer (2.47; 95% confidence interval, 1.17-5.21) in both regions. Smoking, obesity, and diabetes are important and are potentially modifiable risk factors for pancreatic cancer in populations of the Asia-Pacific region. Activities to prevent them can be expected to lead to a major reduction in the number of deaths from this cancer, particularly in Asia with its enormous population.


Maternal dietary choline deficiency alters angiogenesis in fetal mouse hippocampus.
We examined whether maternal dietary choline modulates angiogenesis in fetal brain. Pregnant C57BL/6 mice were fed either a choline-deficient (CD), control (CT), or choline-supplemented diet (CS) from days 12 to 17 (E12-17) of pregnancy and then fetal brains were studied. In CD fetal hippocampus, proliferation of endothelial cells (EC) was decreased by 32% (p < 0.01 vs. CT or CS) while differentiated EC clusters (expressing factor VIII related antigen (RA)) increased by 25% (p < 0.01 vs. CT or CS). These changes were associated with > 25% decrease in the number of blood vessels in CD fetal hippocampus (p < 0.01 vs. CT and CS), with no change in total cross-sectional area of these blood vessels. Expression of genes for the angiogenic signals derived from both endothelial and neuronal progenitor cells (NPC) was increased in CD fetal hippocampus VEGF C (Vegfc), 2.0-fold, p < 0.01 vs. CT and angiopoietin 2 (Angpt2), 2.1-fold, (p < 0.01 vs. CT)). Similar increased expression was observed in NPC isolated from E14 fetal mouse brains and exposed to low (5 microM), CT (70 microM), or high choline (280 microM) media for 72 h (low choline caused a 9.7-fold increase in relative gene expression of Vegfc (p < 0.001 vs. CT and high) and a 3.4-fold increase in expression of Angpt2, (p < 0.05 vs. CT and high). ANGPT2 protein was increased 42.2% (p < 0.01). Cytosine-phosphate-guanine dinucleotide islands in the proximity of the promoter areas of Vegfc and Angpt2 were hypomethylated in low choline NPC compared to CT NPC (p < 0.01). We conclude that maternal dietary choline intake alters angiogenesis in the developing fetal hippocampus.


Is amiodarone a safe antiarrhythmic to use in supraventricular tachyarrhythmias after lung cancer surgery?
Supraventricular arrhythmias after thoracotomy for pulmonary resections are well documented. There has been considerable interest in their incidence, nature, predictability from preoperative assessment and treatment. The purpose of this study is to define prevalence, type, risk factors for post-thoracotomy supraventricular arrhythmias and to assess the efficacy of amiodarone as an antiarrhythmic drug. The records of 250 patients undergoing pulmonary resection for lung cancer during last two years were followed up in this prospective study with particular attention to possible risk factors (gender, age, extent and side of resection, diabetes mellitus, hypertension, tobacco smoking, beta-blocker ingestion). Patients underwent biopsy only were excluded. Once onset of supraventricular arrhythmia was monitored or documented in the electrocardiogram, intravenous infusion of amiodarone was started with a loading dose of 5 mg/kg in 30 minutes and a maintenance dose of 15 mg/kg until remission of it. Forty-three episodes (21.6%) of supraventricular arrhythmias were documented with atrial fibrillation being the most common (88.3%). Rhythm disturbances were most likely to develop on the second postoperative day. Pneumonectomy, lobectomy and age >65 years were the statistically significant factors. The overall postoperative mortality was 3.2% and 2.3% for the patients with postoperative supraventricular arrhythmias. In none of the cases did supraventricular arrhythmia cause cardiac failure leading to death. Sinus rhythm was achieved with amiodarone in 37 out of 43 patients (86%). Electrical cardioversion was necessary for 6 patients who were hemodynamically unstable. The most common amiodarone-related complication was bradycardia (13.5%). Postoperative supraventricular arrhythmias are a common complication in elderly patients undergoing lung resection surgery (especially pneumonectomy or lobectomy). Amiodarone is both safe and effective in establishing sinus rhythm.


Arteriovenous malformation nidus catheterization with hydrophilic wire and flow-directed catheter.
Arteriovenous malformation nidus catheterization with a flow-directed catheter at times can be difficult owing to tortuosity of the intracranial vasculature and distal location of the nidus. Since January 1995, hydrophilic wire has been used in conjunction with the 1.8F flow-directed microcatheter in over 150 vessel embolizations with cyanoacrylate glue for brain and spinal arteriovenous malformations at our institution. This technique has improved our success rate in achieving superselective catheterization of the nidus and has shortened the overall procedure time. To date, only one complication has occurred that was directly related to wire manipulation.


Floppy eyelid syndrome as a subset of lax eyelid conditions: relationships and clinical relevance (an ASOPRS thesis).
To better define the wide spectrum of lax eyelid conditions, especially the subtype referred to as floppy eyelid syndrome, and to clarify its relationship with associated ophthalmic findings. A case-based retrospective review of all patients seen at UNC Department of Ophthalmology with a diagnosis of floppy eyelid syndrome or lax upper eyelid was performed. The period of review was from March 2002 to March 2007. A literature review was also performed using the term "floppy eyelid syndrome" and "lax eyelid syndrome" as the keywords in a PubMed search. Charts and cases were reviewed for the following information: age, sex, presence or absence of obesity, presence or absence of upper eyelid laxity, presence or absence of lower eyelid laxity, symmetry or asymmetry of eyelid laxity, sleeping position preference, diagnosis of obstructive sleep apnea (OSA), history of eye rubbing, diagnosis of keratoconus (KCN), lash ptosis, history of spontaneous eyelid eversion, papillary conjunctivitis, systemic hyperlaxity, diagnosis of meibomianitis, signs of anterior segment inflammation, and smoking or excessive sun exposure history. From our UNC case review, 14 patients involving 17 eyelids were identified. From the literature review, 72 articles were recovered and evaluated to yield a total of 324 reported cases through February 2007. From the combined data (n = 338), the overall minimum prevalence of sleep apnea in patients with lax eyelid condition was 16% compared with an estimated 9% to 24% in the general population. Of patients with lax eyelid syndrome, those identified with OSA had significantly more individuals with obesity (76% vs. 20%) and male gender (89% vs. 61%) than the group without OSA. The prevalence of KCN in patients with lax eyelid syndrome was a minimum of 6.8%, which is considerably higher than the estimated prevalence in the general population of 0.6%. However, KCN appears to show a significant association with the patient's side of sleeping preference. Eyelid laxity can result from a number of involutional, local, and systemic diseases but is frequently of unknown etiology. When it is consistently associated with papillary conjunctivitis and dry eyes it can be referred to as lax eyelid syndrome (LES). A number of specific subsets of LES can be identified. One such subset, occurring primarily though not exclusively in males and associated with obesity, has been defined as the floppy eyelid syndrome (FES). OSA has been associated with FES where it occurs with greater frequency than in the general population, but no greater than seen in obese males without FES, and therefore appears to represent an epiphonomenom only. However, given the demographics of FES, this condition offers some predictive value for OSA and should alert the physician to evaluate the sleep habits of all such patients. Keratoconus also shows some association with FES and with LES. However, data suggest that the causative factors are sleep preference for the involved side and nocturnal eyelid eversion, rather than any underlying physiologic or anatomic relationship.


Studies on the development of antibodies for the highly hydrophobic plasticizers DINCH and DEHT.
Diisononylcyclohexane-1,2-dicarboxylate (DINCH) and di-2-ethylhexyl terephthalate (DEHT), two of the most important substitutes for phthalate plasticizers, are used for a wide range of applications. Consequently, an increasing occurrence in urine and environmental samples is reported. Reliable and fast analytical methods for the quantification of these plasticizers are needed. So far, mainly GC-MS or LC-MS methods are used. We aimed to develop the first antibodies and immunoassays allowing for high-throughput analysis of samples. We designed two DINCH hapten structures and one DEHT hapten structure and employed hapten-protein conjugates for the immunization of rabbits. Sensitive competitive enzyme-linked immunosorbent assays (ELISAs) against each hapten using the produced polyclonal antibodies were established. Yet, binding of DINCH to the respective antibodies was not observed in neither direct nor indirect assay formats, even when using protein conjugates with the heterologous haptens and different carrier proteins in the indirect format. The use of surfactants and solvents in the sample buffer did not result in recognition of the plasticizers. Also, no binding of DEHT in ELISA employing the respective antibodies was detected. We speculate that the production of antibodies against these highly hydrophobic molecules is not possible via our route, however a different hapten design could overcome this obstacle.


Is Viewing Mass Trauma Television Coverage Associated With Trauma Reactions in Adults and Youth? A Meta-Analytic Review.
This study presents the findings of meta-analyses examining the association between viewing mass trauma television coverage and posttraumatic stress (PTS) outcomes as well as acute stress reactions (ASR) among adults and youth. A literature search identified 43 (N = 31,162) studies assessing the association between viewing mass trauma television coverage and PTS and four (N = 9,083) assessing the association with ASR. The overall size of the association between viewing television coverage and PTS, estimated using a random-effect model, was small but statistically significant, r = .17, 95% CI [.13, .22]. The moderator analysis examined eight preselected variables: man-made versus natural trauma, specific incident versus chronic stressor, adult versus youth sample, proximal versus distal event exposure, television only versus combined media form, specific content in coverage versus no specific content, quantification of media contact using numeric measurement versus subjective measurement versus a binary item, and posttraumatic stress symptoms (PTSS) versus posttraumatic stress disorder (PTSD) outcome. The analysis revealed a statistically significant moderation effect for the quantification of media contact (numeric vs. subjective vs. binary) only, which accounted for 19% of the observed heterogeneity. With a summary estimate of r = .26, 95% CI [.06, .44], the analysis of the ASR studies corroborated the PTS findings. The results suggest that clinicians and public health practitioners should discuss mass trauma television viewing with their patients and with the public. Limitations of the extant research are discussed.


Mix-and-match nanobiosensor design: Logical and spatial programming of biosensors using self-assembled DNA nanostructures.
The evergrowing need to understand and engineer biological and biochemical mechanisms has led to the emergence of the field of nanobiosensing. Structural DNA nanotechnology, encompassing methods such as DNA origami and single-stranded tiles, involves the base pairing-driven knitting of DNA into discrete one-, two-, and three-dimensional shapes at nanoscale. Such nanostructures enable a versatile design and fabrication of nanobiosensors. These systems benefit from DNA's programmability, inherent biocompatibility, and the ability to incorporate and organize functional materials such as proteins and metallic nanoparticles. In this review, we present a mix-and-match taxonomy and approach to designing nanobiosensors in which the choices of bioanalyte and transduction mechanism are fully independent of each other. We also highlight opportunities for greater complexity and programmability of these systems that are built using structural DNA nanotechnology. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Diagnostic Tools > Biosensing Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.


Effect of cleaning methods after reduced-pressure air abrasion on bonding to zirconia ceramic.
To evaluate in vitro the influence of different cleaning methods after low-pressure air abrasion on the bond strength of a phosphate monomer-containing luting resin to zirconia ceramic. A total of 112 zirconia ceramic disks were divided into 7 groups (n = 16). In the test groups, disks were air abraded at low pressure (L) 0.05 MPa using 50-μm alumina particles. Prior to bonding, the disks were ultrasonically (U) cleaned either in isopropanol alcohol (AC), hydrofluoric acid (HF), demineralized water (DW), or tap water (TW), or they were used without ultrasonic cleaning. Disks air abraded at a high (H) pressure of 0.25 MPa and cleaned ultrasonically in isopropanol served as positive control; original (O) milled disks used without air abrasion served as the negative control group. Plexiglas tubes filled with composite resin were bonded with the adhesive luting resin Panavia 21 to the ceramic disks. Prior to testing tensile bond strength (TBS), each main group was further subdivided into 2 subgroups (n=8) which were stored in distilled water either at 37°C for 3 days or for 30 days with 7500 thermal cycles. Statistical analyses were conducted with two- and one-way analyses of variance (ANOVA) and Tukey's HSD test. Initial tensile bond strength (TBS) ranged from 32.6 to 42.8 MPa. After 30 days storage in water with thermocycling, TBS ranged from 21.9 to 36.3 MPa. Storage in water and thermocycling significantly decreased the TBS of test groups which were not air abraded (p = 0.05) or which were air abraded but cleaned in tap water (p = 0.002), but not the TBS of the other groups (p > 0.05). Also, the TBS of air-abraded groups were significantly higher than the TBS of the original milled (p < 0.01). Cleaning procedures did not significantly affect TBS either after 3 days or 30 days storage in water and thermocycling (p > 0.05). Air abrasion at 0.05 MPa and ultrasonic cleaning are important factors for improving bonding to zirconia ceramic.


Using a Syndemics Framework to Understand How Substance Use Contributes to Morbidity and Mortality among People Living with HIV in Africa: A Call to Action.
Substance use is increasing throughout Africa, with the prevalence of alcohol, tobacco, cannabis, and other substance use varying regionally. Concurrently, sub-Saharan Africa bears the world's largest HIV burden, with 71% of people living with HIV (PWH) living in Africa. Problematic alcohol, tobacco, and other substance use among PWH is associated with multiple vulnerabilities comprising complex behavioral, physiological, and psychological pathways that include high-risk behaviors (e.g., sexual risk-taking), HIV disease progression, and mental health problems, all of which contribute to nonadherence to antiretroviral therapy. Physiologically, severe substance use disorders are associated with increased levels of biological markers of inflammation; these, in turn, are linked to increased mortality among PWH. The biological mechanisms that underlie the increased risk of substance use among PWH remain unclear. Moreover, the biobehavioral mechanisms by which substance use contributes to adverse health outcomes are understudied in low- and middle-income countries (LMIC). Syndemic approaches to understanding the co-occurrence of substance use and HIV have largely been limited to high-income countries. We propose a syndemic coupling conceptual model to disentangle substance use from vulnerabilities to elucidate underlying disease risk for PWH. This interventionist perspective enables assessment of biobehavioral mechanisms and identifies malleable targets of intervention.


Fear of falling and its association with life-space mobility of older adults: a cross-sectional analysis using data from five international sites.
fear of falling (FOF) is a major health concern among community-dwelling older adults that could restrict mobility. to examine the association of FOF with life-space mobility (i.e. the spatial area a person moves through in daily life) of community-dwelling older adults from five diverse sites. in total, 1,841 older adults (65-74 years) were recruited from Kingston, Canada; Saint-Hyacinthe, Canada; Tirana, Albania; Manizales, Colombia and Natal, Brazil. FOF was assessed using the Fall Efficacy Scale-International (FES-I total score), and the life space was quantified using the Life-Space Assessment (LSA), a scale that runs from 0 (minimum life space) to 120 (maximum life space). the overall average LSA total score was 68.7 (SD: 21.2). Multiple-linear regression analysis demonstrated a significant relationship of FOF with life-space mobility, even after adjusting for functional, clinical and sociodemographic confounders (B = -0.15, 95% confidence interval (CI) -0.26 to -0.04). The FOF × site interaction term was significant with a stronger linear relationship found in the Canadian sites and Tirana compared with the South American sites. After adjusting for all confounders, the association between FOF with LSA remained significant at Kingston (B = -0.32, 95% CI -0.62 to -0.01), Saint-Hyacinthe (B = -0.81, 95% CI -1.31 to -0.32) and Tirana (B = -0.57, 95% CI -0.89 to -0.24). FOF is an important psychological factor that is associated with reduction in life space of older adults in different social and cultural contexts, and the strength of this association is site specific. Addressing FOF among older adults would help improve their mobility in local communities, which in turn would improve social participation and health-related quality of life.


Adenovirus E1A directly targets the E2F/DP-1 complex.
Deregulation of the cell cycle is of paramount importance during adenovirus infection. Adenovirus normally infects quiescent cells and must initiate the cell cycle in order to propagate itself. The pRb family of proteins controls entry into the cell cycle by interacting with and repressing transcriptional activation by the E2F transcription factors. The viral E1A proteins indirectly activate E2F-dependent transcription and cell cycle entry, in part, by interacting with pRb and family members to free the E2Fs. We report here that an E1A 13S isoform can unexpectedly activate E2F-responsive gene expression independently of binding to the pRb family of proteins. We demonstrate that E1A binds to E2F/DP-1 complexes through a direct interaction with DP-1. E1A appears to utilize this binding to recruit itself to E2F-regulated promoters, and this allows the E1A 13S protein, but not the E1A 12S protein, to activate transcription independently of interaction with pRb. Importantly, expression of E1A 13S, but not E1A 12S, led to significant enhancement of E2F4 occupancy of E2F sites of two E2F-regulated promoters. These observations identify a novel mechanism by which adenovirus deregulates the cell cycle and suggest that E1A 13S may selectively activate a subset of E2F-regulated cellular genes during infection.


Promoting physical activity in primary care settings: health visitors' and practice nurses' views and experiences.
This paper reports a study investigating health visitors' and practice nurses' attitudes, beliefs and practice associated with routinely advising patients about physical activity. There is worldwide concern about increasing rates of obesity and decreasing population levels of physical activity, and it has been argued that primary healthcare professionals are ideally placed to promote physical activity within local communities. In recent years, the public health role of primary care-based nurses in the United Kingdom has been considerably expanded to include playing a key role in improving the health of their local practice populations. A systematic literature search revealed that very few studies investigating nurses' views and experiences of this type work have been published. The limited amount of research that has been conducted is generally small-scale and primarily concerned with general medical practitioners' practice and attitudes, and not those of nurses. A questionnaire survey (n = 630) and 20 in-depth interviews were conducted with health visitors and practice nurses in four health regions in Scotland between March and April 2004. The response rate was 63% overall. Ninety per cent (n = 149) of health visitors and 88% (n = 186) of practice nurses said that they were very likely or likely to recommend all apparently healthy adult patients to take moderate exercise. Health visitors were more likely to discuss psychological benefits than practice nurses. However, only 9% (n = 15) of practice nurses and 11% (n = 15) of health visitors correctly described the current recommendations - an accumulation of 30 minutes of moderate physical activity five times a week. Interview data suggested that most nurses gave physical activity advice based on their beliefs about the patient's willingness to change and their impressions of the patient's presenting condition, underlying physical condition and life circumstances. No measure of underlying physical fitness was used. There was a lack of agreement between the questionnaire and interview data associated with levels of physical activity advising. There were high levels of enthusiasm for physical activity promotion amongst health visitors and practice nurses. However, nursing leaders and opinion-makers should challenge practitioners' current beliefs and assumptions about physical activity promotion in the general population.


ω-3 fatty acids in the prevention of cognitive decline in humans.
The brain is a lipid-rich organ where docosahexaenoic acid (DHA) is enriched and where eicosapentaenoic acid (EPA) may have anti-inflammatory effects. The potential role for n-3 (ω-3) fatty acids such as DHA and EPA in the prevention of cognitive decline, including Alzheimer's disease (AD) has attracted major interest for the past 20 y. This review presents our understanding of recent observational, interventional, and experimental studies, with the aim of providing some answers to the following question: Can n-3 FA intake modulate cognitive function during aging? In longitudinal observation studies we mainly observe inverse relations between fish intake or serum concentrations of DHA and cognitive impairment. Intervention studies of EPA and DHA supplementation in healthy old individuals have been negative so far (i.e., after up to 2 years of treatment, no differences in cognitive decline between treated and nontreated participants have been observed). In studies that provided EPA and DHA to adults with mild cognitive impairment or age-related cognitive impairment the data seem to be positive. However, when patients with established AD were supplemented with EPA and DHA it appears no benefit was gained. For studies on healthy individuals, a major concern is that the treatment periods may have been too short. There might also be subgroup effects because of the carriage of apolipoprotein Eε4 alleles or risk factor burden. Experimental studies appear to be consistently positive (i.e., n-3 FA supplementation in rodents over a substantial portion of their lives reduces amyloid-β deposition and hippocampal neuron loss and improves cognitive functioning). We are getting closer to providing evidence-based recommendations on fish and fish oil intake to facilitate memory function during old age. In the meantime it is advised to follow the general CDC dietary recommendations of 2-3 fish meals per week or the equivalent intake of long chain n-3 fatty acids, particularly DHA.


Confirmation of the potential usefulness of two human beta globin pseudogene markers to estimate gene flows to and from sub-Saharan Africans.
Two polymorphic sites, -107 and -100 with respect to the "cap" site of the human beta globin pseudogene, recently discovered in our laboratory, turned out to have an ethnically complementary distribution. The first site is polymorphic in Europeans, North Africans, Indians (Hindu), and Oriental Asians, and monomorphic in sub-Saharan Africans. Conversely, the second site is polymorphic in sub-Saharan African populations and monomorphic in the aforementioned populations. Here we report the gene frequencies of these two polymorphic sites in nine additional populations (Egyptians, Spaniards, Japanese, Chinese, Filipinos, Vietnamese, Africans from Togo and from Benin, and Pygmies), confirming their ethnospecificity and, through the analysis of these two markers in Oromo and Amhara of Ethiopia (two mixed populations), their usefulness in genetic admixture studies. Moreover, we studied another marker polymorphic in sub-Saharan African populations only, a TaqI restriction fragment length polymorphism located in the same region as the present markers, demonstrating the absence of linkage disequilibrium between it and the -100 site, so that we can exclude that the information they provide is redundant.


Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone.
Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume. Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95% CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding. clinicaltrials.gov Identifier: NCT00799617.


A philanthropy tackles growth in health costs at the state level.
Slowing the rate of growth of health spending is as critical a goal at the state level as it is at the national level. Philanthropy can hardly address this issue alone, yet it has an obligation to take on big and seemingly intractable problems. The New York State Health Foundation is committed to stimulating innovative and replicable approaches to bending the cost curve. This article describes how the foundation recently awarded six grants to support efforts related to payment reform, hospital readmissions, medical malpractice reform, palliative care, and the quantification of other cost containment approaches that could be pursued at the state level.


Fibrosis-4 index predicts mortality in HIV/HCV co-infected patients receiving combination antiretroviral therapy in rural China.
End-stage liver disease (ESLD) is among leading causes of death for people living with HIV and HCV. Little is known how liver fibrosis score predicts mortality in HIV/HCV co-infected population under combination antiretroviral therapy (cART). A retrospective cohort study of 691 HIV/HCV co-infected patients receiving cART in Yunnan, China from 2005 to 2016 was carried out to explore the association between Fibrosis-4 index (FIB-4) and all-cause mortality. Cox proportional hazard models were used to estimate the hazard ratios (HRs) for FIB-4 and covariates. After a median follow-up of 4.8 years with a total follow-up time of 3,696 person-years (PY), 131 deaths occurred and the all-cause mortality was 3.5 per 100 PY. The mortality was 2.9 (95% CI: 2.3-3.5)/100 PY for the FIB-4 ≤ 3.25 group and 5.8 (4.2-7.4)/100 PY for the FIB-4 > 3.25 group at baseline. People with FIB-4 changed from mild to advanced group showed HR of 1.81 (95% CI: 1.01-3.25) for death, and with FIB-4 sustaining advanced showed HR of 3.11 (1.75-5.54), both compared to those with FIB-4 remained mild, while lower risk of death was observed among married people (HR = 0.63, 95% CI: 0.41-0.99) compared to unmarried, among those with most recent CD4+ T cell counts between 200 and 350 cells/μL (0.50, 0.30-0.86) and > 350 cells/μL (0.25, 0.15-0.41) compared to CD4 under 200 cells/μL. Advanced and progressive liver fibrosis is a strong predictor of all-cause mortality in HIV/HCV co-infected patients under cART in China.


Implementation of a surgical intensive care unit service is associated with improved outcomes for trauma patients.
Our trauma service recently transitioned from a pulmonary intensive care unit (ICU) service to a surgical ICU (SICU) service. We hypothesized that a newly formed SICU service could provide comparable outcomes to the existing pulmonary ICU service. A specific aim of this study was to compare outcomes of trauma patients admitted to the ICU before and after implementation of a SICU service. We performed a retrospective study of trauma patients admitted to the ICU of our urban, American College of Surgeons- verified, Level 1 trauma center during a 4-year period (2009-2012). Patients managed by the pulmonary ICU service (2009-2010) were compared with patients managed by a SICU service (2011-2012). The primary outcome was mortality, while secondary outcomes included complications (pulmonary, infectious, cardiac, and thromboembolic), hospital and ICU length of stay, ventilator days, and need for reintubation. There were 2,253 trauma patients admitted to the ICU during the study period, 1,124 and 1,129 managed by the pulmonary ICU and SICU services, respectively. When comparing outcomes for SICU and pulmonary ICU patients, there was no difference in mortality (11% vs. 13%, p = 0.41), but patients managed by the SICU service had fewer pulmonary complications (3% vs. 6%, p < 0.001), fewer days on the ventilator (3 vs. 4, p = 0.002), and less often required reintubation after extubation (4% vs. 9%, p < 0.001). Transition from a pulmonary ICU service to a SICU service at our institution was associated with no change in mortality but an improvement in pulmonary complications, ventilator days, and reintubation rates. Trauma centers currently staffed with a pulmonary ICU service should feel comfortable converting to SICU service and should expect comparable or improved outcomes for trauma patients admitted to the ICU. Therapeutic/care management study, level IV.


Fingertip force and electromyography of finger flexor muscles during a prolonged intermittent exercise in elite climbers and sedentary individuals.
The aim of this study was to characterize forearm muscle fatigue identified by the decrease in electromyogram median frequency and/or fingertip force during intermittent exercise. Nine elite climbers (international competitive level, USA 5.14a on sight) and ten non-climbers were instructed to maintain a fingertip force of 80% of their maximal voluntary contraction force on a dynamometer mimicking a rock climbing grip during a 5 s effort/5 s rest cycle for 36 repetitions (i.e. 6 min of exercise). Elite climbers lasted twice as long as non-climbers (climbers: 3 min; non-climbers: 1 min 30 s) before the force could no longer be maintained (i.e. the failure point). After this moment, fingertip force decreased and stabilized until the end of the exercise around 50% maximum voluntary contraction force in non-climbers and 63% in elite climbers. Electromyogram median frequency showed a greater decrease in non-climbers than in elite climbers before the failure point. No change in median frequency was observed after the failure point in elite climbers or in non-climbers. These results confirm that elite climbers are better adapted than non-climbers for performing the intermittent fingertip effort before the failure point. After this point, the better fingertip force of elite climbers suggests different forearm muscle properties, while the electromyography results do not provide any indication about the fatigue process.


Propolis oil extract: quality analysis and evaluation of its antimicrobial activity.
Designing propolis products for external use involves determining the optimal form of propolis for the introduction into dermatological pharmaceuticals and cosmetic preparations. As a potent ingredient, propolis oil extract from raw material harvested in Lithuania was analysed. The rheological characteristics, content of phenolic compounds, major compounds and antimicrobial activity of the propolis oil extract are investigated here for the first time. The propolis oil extract was produced by maceration using different solvents, raw material was collected in Lithuania. Solvent mixture with 96% ethanol increased the rheological stability and extracted amount of phenolic compound. High-performance liquid chromatography identified the potent quality markers for Lithuanian propolis, phenylpropanoid vanillin, coumaric acid and ferulic acid. Antimicrobial activity of propolis oil extract was evaluated in experimental studies in vitro, and the minimal concentration of phenolic compounds that inhibited respective microorganisms was determined. The results demonstrate that phenolic compounds have effective antimicrobial activity in propolis oil extract; thus, it can be compatible with the semisolid preparation.


Making Decisions About Medication Use During Pregnancy: Implications for Communication Strategies.
Objective To explore women's perceptions of the risks and benefits associated with medication use during pregnancy and to better understand how women make decisions related to medication use in pregnancy. Methods We conducted online focus groups with 48 women who used medication during pregnancy or while planning a pregnancy, and 12 in-depth follow-up interviews with a subset of these women. Results We found that women were aware of general risks associated with medication use but were often unable to articulate specific negative outcomes. Women were concerned most about medications' impact on fetal development but were also concerned about how either continuing or discontinuing medication during pregnancy could affect their own health. Women indicated that if the risk of a given medication were unknown, they would not take that medication during pregnancy. Conclusion This formative research found that women face difficult decisions about medication use during pregnancy and need specific information to help them make decisions. Enhanced communication between patients and their providers regarding medication use would help address this need. We suggest that public health practitioners develop messages to (1) encourage, remind, and prompt women to proactively talk with their healthcare providers about the risks of taking, not taking, stopping, or altering the dosage of a medication while trying to become pregnant and/or while pregnant; and (2) encourage all women of childbearing age to ask their healthcare providers about medication use.


CRISPR/Cas9-Constructed Pseudorabies Virus Mutants Reveal the Importance of UL13 in Alphaherpesvirus Escape from Genome Silencing.
Latent and recurrent productive infection of long-living cells, such as neurons, enables alphaherpesviruses to persist in their host populations. Still, the viral factors involved in these events remain largely obscure. Using a complementation assay in compartmented primary peripheral nervous system (PNS) neuronal cultures, we previously reported that productive replication of axonally delivered genomes is facilitated by pseudorabies virus (PRV) tegument proteins. Here, we sought to unravel the role of tegument protein UL13 in this escape from silencing. We first constructed four new PRV mutants in the virulent Becker strain using CRISPR/Cas9-mediated gene replacement: (i) PRV Becker defective for UL13 expression (PRV ΔUL13), (ii) PRV where UL13 is fused to eGFP (PRV UL13-eGFP), and two control viruses (iii and iv) PRV where VP16 is fused with mTurquoise at either the N terminus (PRV mTurq-VP16) or the C terminus (PRV VP16-mTurq). Live-cell imaging of PRV capsids showed efficient retrograde transport after axonal infection with PRV UL13-eGFP, although we did not detect dual-color particles. However, immunofluorescence staining of particles in mid-axons indicated that UL13 might be cotransported with PRV capsids in PNS axons. Superinfecting nerve cell bodies with UV-inactivated PRV ΔUL13 failed to efficiently promote escape from genome silencing compared to UV-PRV wild type and UV-PRV UL13-eGFP superinfection. However, UL13 does not act directly in the escape from genome silencing, as adeno-associated virus (AAV)-mediated UL13 expression in neuronal cell bodies was not sufficient to provoke escape from genome silencing. Based on this, we suggest that UL13 may contribute to initiation of productive infection through phosphorylation of other tegument proteins.IMPORTANCE Alphaherpesviruses have mastered various strategies to persist in an immunocompetent host, including the induction of latency and reactivation in peripheral nervous system (PNS) ganglia. We recently discovered that the molecular mechanism underlying escape from latency by the alphaherpesvirus pseudorabies virus (PRV) relies on a structural viral tegument protein. This study aimed at unravelling the role of tegument protein UL13 in PRV escape from latency. First, we confirmed the use of CRISPR/Cas9-mediated gene replacement as a versatile tool to modify the PRV genome. Next, we used our new set of viral mutants and AAV vectors to conclude the indirect role of UL13 in PRV escape from latency in primary neurons, along with its spatial localization during retrograde capsid transport in axons. Based on these findings, we speculate that UL13 phosphorylates one or more tegument proteins, thereby priming these putative proteins to induce escape from genome silencing.


Sex differences in T cells in hypertension.
Hypertension is a major risk factor for cardiovascular disease, stroke, and end-organ damage. There is a sex difference in blood pressure (BP) that begins in adolescence and continues into adulthood, in which men have a higher prevalence of hypertension compared with women until the sixth decade of life. Less than 50% of hypertensive adults in the United States manage to control their BP to recommended levels using current therapeutic options, and women are more likely than are men to have uncontrolled high BP. This, is despite the facts that more women compared with men are aware that they have hypertension and that women are more likely to seek treatment for the disease. Novel therapeutic targets need to be identified in both sexes to increase the percentage of hypertensive individuals with controlled BP. The purpose of this article was to review the available literature on the role of T cells in BP control in both sexes, and the potential therapeutic application/implications of targeting immune cells in hypertension. A search of PubMed was conducted to determine the impact of sex on T cell-mediated control of BP. The search terms included sex, gender, estrogen, testosterone, inflammation, T cells, T regulatory cells, Th17 cells, hypertension, and blood pressure. Additional data were included from our laboratory examinations of cytokine expression in the kidneys of male and female spontaneously hypertensive rats (SHRs) and differential gene expression in both the renal cortex and mesenteric arterial bed of male and female SHRs. There is a growing scientific literature base regarding the role of T cells in the pathogenesis of hypertension and BP control; however, the majority of these studies have been performed exclusively in males, despite the fact that both men and women develop hypertension. There is increasing evidence that although T cells also mediate BP in females, there are distinct differences in both the T-cell profile and the functional impact of sex differences in T cells on cardiovascular health, although more work is needed to better define the relative impact of different T-cell subtypes on BP in both sexes. The challenge now is to fully understand the molecular mechanisms by which the immune system regulates BP and how the different components of the immune system interact so that specific mechanisms can be targeted therapeutically without compromising natural immune defenses.


Acetylation of histone H3 lysine 56 regulates replication-coupled nucleosome assembly.
Chromatin assembly factor 1 (CAF-1) and Rtt106 participate in the deposition of newly synthesized histones onto replicating DNA to form nucleosomes. This process is critical for the maintenance of genome stability and inheritance of functionally specialized chromatin structures in proliferating cells. However, the molecular functions of the acetylation of newly synthesized histones in this DNA replication-coupled nucleosome assembly pathway remain enigmatic. Here we show that histone H3 acetylated at lysine 56 (H3K56Ac) is incorporated onto replicating DNA and, by increasing the binding affinity of CAF-1 and Rtt106 for histone H3, H3K56Ac enhances the ability of these histone chaperones to assemble DNA into nucleosomes. Genetic analysis indicates that H3K56Ac acts in a nonredundant manner with the acetylation of the N-terminal residues of H3 and H4 in nucleosome assembly. These results reveal a mechanism by which H3K56Ac regulates replication-coupled nucleosome assembly mediated by CAF-1 and Rtt106.


Change in Epworth Sleepiness Scale after surgical treatment of obstructive sleep apnea.
To evaluate the effect of surgical intervention for obstructive sleep apnea (OSA) on patients' level of excessive daytime sleepiness as determined by the Epworth Sleepiness Scale (ESS). The ESS questionnaire is a validated measure of subjective daytime sleepiness. There have been several studies that have shown that continuous positive airway pressure (CPAP) improves excessive daytime sleepiness in OSA patients as measured by the ESS. Retrospective case series. This is a study of patients who had uvulopalatopharyngoplasty (UPPP); UPPP and tonsillectomy; or UPPP, tonsillectomy, and radiofrequency ablation of the base of the tongue for OSA between January 2007 and December 2009. Forty patients were identified who met the criteria of having had an ESS evaluation and polysomnography prior to surgery for OSA. Across all of the patients there was a mean reduction of their ESS by 5.6 ± 4.1; t = 8.82, P < .001. Only three of the patients did not improve in their ESS scores after surgical treatment for OSA. Surgical intervention for OSA significantly improves sleepiness in OSA patients as measured by the ESS. Two meta-analyses of multiple, randomized, controlled studies showed patients with mild to moderate OSA treated with CPAP demonstrated an improvement in the ESS score of 1.2 points (95% confidence interval, 0.05-1.9, P = .001) and 2.94 points for patients with mild to severe OSA treated with CPAP. The results of this study show an improvement in ESS after surgery that is substantially higher than previously reported with CPAP for all categories of OSA.


Computer simulations of the structure of colloidal ferrofluids.
The structure of a ferrofluid under the influence of an external magnetic field is expected to become anisotropic due to the alignment of the dipoles into the direction of the external field, and subsequently to the formation of particle chains due to the attractive head to tail orientations of the ferrofluid particles. Knowledge about the structure of a colloidal ferrofluid can be inferred from scattering data via the measurement of structure factors. We have used molecular-dynamics simulations to investigate the structure of both monodispersed and polydispersed ferrofluids. The results for the isotropic structure factor for monodispersed samples are similar to previous data by Camp and Patey that were obtained using an alternative Monte Carlo simulation technique, but in a different parameter region. Here we look in addition at bidispersed samples and compute the anisotropic structure factor by projecting the q vector onto the XY and XZ planes separately, when the magnetic field was applied along the z axis. We observe that the XY-plane structure factor as well as the pair distribution functions are quite different from those obtained for the XZ plane. Further, the two-dimensional structure factor patterns are investigated for both monodispersed and bidispersed samples under different conditions. In addition, we look at the scaling exponents of structure factors. Our results should be of value to interpret scattering data on ferrofluids obtained under the influence of an external field.


Perioperative Antibiotic Prophylaxis to Prevent Surgical Site Infections in Solid Organ Transplantation.
Antibiotic prophylaxis in the perioperative period is the standard of care for nearly all surgical procedures and routinely prescribed during solid organ transplantation (SOT). The primary goal of perioperative antibiotic prophylaxis is to minimize postoperative surgical site infections (SSIs). SSIs are a significant issue in SOT. Depending on the organ transplanted, SSIs occur in 3% to 53% of patients, with the highest rates observed in small bowel/multivisceral, liver, and pancreas transplant recipients. SOT recipients are also at increased risk of developing SSIs with antimicrobial-resistant organisms. In this article, we describe the epidemiology and risk factors for SSIs in SOT and examine the available literature to guide the use of different regimens for perioperative antibiotic prophylaxis for each organ. We have further addressed specific situations that are unique to each organ transplant type, such as the use of extracorporeal membrane oxygenation in thoracic organ transplantation, as well as an approach to perioperative antibiotic prophylaxis in the setting of recipient and/or donor infection before transplantation. We provide potential approaches to the selection, dosing, and duration of perioperative antibiotic prophylaxis for each of these clinical situations.


Illustrating novel techniques for analyzing single-case experiments: Effects of pre-session mindfulness practice.
In this article we describe and illustrate various visual and nonparametric techniques that can be used to evaluate the effectiveness of interventions in single-case experiments. Using an alternating treatments design across 2 cases, we tested whether practicing mindfulness would help a novice therapist stay focused and respond to a client more empathically and genuinely. Specifically, after taking a brief workshop on mindfulness, one male and one female doctoral trainee were asked, immediately before beginning each of 10 sessions, either to engage in a guided mindfulness practice for three minutes or a control activity of their choice. Five experimental and 5 control sessions were randomly scheduled for each therapist. The clients were unaware of the purpose of the study and the nature of the experimental manipulation. After each session, we administered measures of client-rated empathy, client- and therapist-rated real relationship, and therapist-rated level of hindering self-awareness. The graphed data were examined separately for each measure. Results showed that the client in Dyad 1 perceived the therapist as more empathic following mindfulness sessions, and the therapist reported less hindering self-awareness and rated the real relationship more favorably, with moderate to strong experimental effects. By contrast, Dyad 2 showed moderate to strong experimental effects for mindfulness practice on ratings of the real relationship, but not on empathy or hindering self-awareness. A cross-case comparison illustrates how replicated single-case experimental research with self-report data can advance our understanding of individual differences in response to psychotherapeutic interventions. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


HIV & immune reconstitution inflammatory syndrome (IRIS).
Antiretroviral therapy (ART) initiation in HIV-infected patients leads to recovery of CD4+T cell numbers and restoration of protective immune responses against a wide variety of pathogens, resulting in reduction in the frequency of opportunistic infections and prolonged survival. However, in a subset of patients, dysregulated immune response after initiation of ART leads to the phenomenon of immune reconstitution inflammatory syndrome (IRIS). The hallmark of the syndrome is paradoxical worsening of an existing infection or disease process or appearance of a new infection/disease process soon after initiation of therapy. The overall incidence of IRIS is unknown, but is dependent on the population studied and the burden of underlying opportunistic infections. The immunopathogenesis of the syndrome is unclear and appears to be result of unbalanced reconstitution of effector and regulatory T-cells, leading to exuberant inflammatory response in patients receiving ART. Biomarkers, including interferon-γ (INF-γ), tumour necrosis factor-α (TNF-α), C-reactive protein (CRP) and inter leukin (IL)-2, 6 and 7, are subject of intense investigation at present. The commonest forms of IRIS are associated with mycobacterial infections, fungi and herpes viruses. Majority of patients with IRIS have a self-limiting disease course. ART is usually continued and treatment for the associated condition optimized. The overall mortality associated with IRIS is low; however, patients with central nervous system involvement with raised intracranial pressures in cryptococcal and tubercular meningitis, and respiratory failure due to acute respiratory distress syndrome (ARDS) have poor prognosis and require aggressive management including corticosteroids. Paradigm shifts in management of HIV with earlier initiation of ART is expected to decrease the burden of IRIS in developed countries; however, with enhanced rollout of ART in recent years and the enormous burden of opportunistic infections in developing countries like India, IRIS is likely to remain an area of major concern.


Acoustic generation of underwater cavities-Comparing modeled and measured acoustic signals generated by seismic air gun arrays.
Underwater vapor cavities can be generated by acoustic stimulation. When the acoustic signals from several air guns are reflected from the sea surface, the pressure drop at some locations is sufficient for cavity growth and subsequent collapse. In this paper the generation of multiple water vapor cavities and their collapses are numerically modeled and the results are validated by comparing with field data from a seismic air gun array test. In a first modeling attempt where cavity interaction is neglected, a correspondence between measured and modeled data is found. Then, this correspondence is improved by assuming that the acoustic signal generated by the other cavities changes the hydrostatic pressure surrounding each cavity. This modeling can be used to estimate the amount and strength of high frequency signals generated by typical marine air gun arrays, given that a calibration step is performed prior to the modeling.


An integrated field-effect microdevice for monitoring membrane transport in Xenopus laevis oocytes via lateral proton diffusion.
An integrated microdevice for measuring proton-dependent membrane activity at the surface of Xenopus laevis oocytes is presented. By establishing a stable contact between the oocyte vitelline membrane and an ion-sensitive field-effect (ISFET) sensor inside a microperfusion channel, changes in surface pH that are hypothesized to result from facilitated proton lateral diffusion along the membrane were detected. The solute diffusion barrier created between the sensor and the active membrane area allowed detection of surface proton concentration free from interference of solutes in bulk solution. The proposed sensor mechanism was verified by heterologously expressing membrane transport proteins and recording changes in surface pH during application of the specific substrates. Experiments conducted on two families of phosphate-sodium cotransporters (SLC20 & SLC34) demonstrated that it is possible to detect phosphate transport for both electrogenic and electroneutral isoforms and distinguish between transport of different phosphate species. Furthermore, the transport activity of the proton/amino acid cotransporter PAT1 assayed using conventional whole cell electrophysiology correlated well with changes in surface pH, confirming the ability of the system to detect activity proportional to expression level.


Detecting DNA synthesis of neointimal formation after catheter balloon injury in GK and in Wistar rats: using 5-ethynyl-2'-deoxyuridine.
Neointimal formation plays an important role in the pathogenesis of coronary restenosis after percutaneous coronary intervention (PCI), especially in patients with diabetes mellitus. Recently, some studies have shown that 5-ethynyl-2'-deoxyuridine (EdU) incorporation can serve as a novel alternative to the 5-bromo-2'-deoxyuridine (BrdU) antibody detection method for detection of DNA synthesis in regenerating avian cochlea, chick embryo and the adult nervous system. However, few studies have been performed to assess the suitability of EdU for detecting DNA synthesis in vascular neointima. The carotid artery balloon injury model was established in Goto-Kakizaki (GK) and Wistar rats. A Cell-LightTM EdU Kit was used to detect EdU-labeled cell nuclei of common carotid arteries at day 7 after catheter balloon injury. Different methods of injecting EdU were tested. The protein levels of proliferating cell nuclear antigen (PCNA) and p-Akt (Ser473), as well as the mRNA levels of PCNA were evaluated by Western blotting and quantitative real-time PCR (qRT-PCR), respectively. Immunohistochemical staining was also employed to visualize PCNA-positive cells. At day 7 after catheter balloon injury, far more EdU-positive and PCNA-positive cells were observed in GK rats. When comparing groups that received different EdU doses, it was found that the percentage of EdU-positive cells at a dose of 100 mg/kg body weight was than at doses of 25 mg/kg and 50 mg/kg. The number of positive cells was significantly higher in the repeated injection group compared to the single injection group. Further, after balloon injury DNA synthesis in GK rats was more notable than in Wistar rats. Neointimal formation in GK rats was more obvious than in Wistar rats. The protein levels of PCNA and p-Akt (Ser473) and the mRNA levels of PCNA were increased in injured rats as compared to uninjured rats, and were significantly higher in GK rats than in Wistar rats. By intraperitoneal injections of EdU at a dose of 100 mg/kg three times, EdU incorporation can detect carotid arterial DNA synthesis caused by neointimal formation in GK rats and Wistar rats at day 7 after balloon injury by the EdU click reaction quickly and effectively. Moreover, more obvious DNA synthesis in the vascular neointima could be observed in GK rats than in Wistar rats.


A new method for predetermining the diffraction quality of protein crystals: using SOAP as a selection tool.
A microscope for quantitative analysis of the birefringence properties of samples is introduced. The microscope is used to measure variations in the slow optical axis position (SOAP) across hen egg-white lysozyme, glucose isomerase and fibronectin crystals. By comparing these variations with indicators of diffraction quality, it is shown that the optical properties of a protein crystal provide a non-invasive method of determining crystal diffraction quality before any X-ray data collection is attempted.


Hierarchical micro/nanoporous ion-exchangeable sponge.
Inspired by the versatile properties of a sponge, we propose an ion-exchangeable sponge composed of hierarchical micropores and nanopores for water treatment. Sodium ions in brackish water (10-300 mM) absorbed in the sponge were exchanged for hydrogen ions in a short incubation time and the desalted water was released by squeezing the sponge with a single hand grip. This simple desalination process was attributed to the multi-scale porous structures in the sponge. A number of nanoporous thin films were formed like bubbles surrounded by the closed backbone of the microporous sponge. The hierarchical micro/nanopores maximized the contact area of the ion-exchanging surface with the saline solution so that scaled-up desalination was achieved. Furthermore, the growth of wheat shoots in the desalted water was demonstrated in vivo after using this micro/nanofluidic based water-treatment with the sponges. Wheat shoots grown in NaHCO3/Na2CO3 solutions treated by the sponges were 110 to 226.45% longer than those grown in the original salty water. This implies that the ion-exchangeable sponge could serve as an appropriate technology for the treatment of ground water affected by acid rain and weathered alkaline rocks.


Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4.
Middle East respiratory syndrome (MERS) represents an important respiratory disease accompanied by lethal outcome in one-third of human patients. Recent data indicate that dromedaries represent an important source of infection, although information regarding viral cell tropism and pathogenesis is sparse. In the current study, tissues of eight dromedaries receiving inoculation of MERS-Coronavirus (MERS-CoV) after recombinant Modified-Vaccinia-Virus-Ankara (MVA-S)-vaccination (n = 4), MVA-vaccination (mock vaccination, n = 2) and PBS application (mock vaccination, n = 2), respectively, were investigated. Tissues were analyzed by histology, immunohistochemistry, immunofluorescence, and scanning electron microscopy. MERS-CoV infection in mock-vaccinated dromedaries revealed high numbers of MERS-CoV-nucleocapsid positive cells, T cells, and macrophages within nasal turbinates and trachea at day four post infection. Double immunolabeling demonstrated cytokeratin (CK) 18 expressing epithelial cells to be the prevailing target cell of MERS-CoV, while CK5/6 and CK14 expressing cells did not co-localize with virus. In addition, virus was occasionally detected in macrophages. The acute disease was further accompanied by ciliary loss along with a lack of dipeptidyl peptidase 4 (DPP4), known to mediate virus entry. DPP4 was mainly expressed by human lymphocytes and dromedary monocytes, but overall the expression level was lower in dromedaries. The present study underlines significant species-specific manifestations of MERS and highlights ciliary loss as an important finding in dromedaries. The obtained results promote a better understanding of coronavirus infections, which pose major health challenges.


American Dental Association Principles of Ethics and Code of Professional Conduct. With official advisory opinions revised to July 1988. Council on Ethics, Bylaws, and Judicial Affairs.
The ethical statements which have historically been subscribed to by the dental profession have had the benefit of the patient as their primary goal. Recognition of this goal, and of the education and training of a dentist, has resulted in society affording to the profession the privilege and obligation of self-government. The Association calls upon members of the profession to be caring and fair in their contact with patients. Although the structure of society may change, the overriding obligation of the dentist will always remain the duty to provide quality care in a competent and timely manner. All members must protect and preserve the high standards of oral health care provided to the public by the profession. They must strive to improve the care delivered--through education, training, research and, most of all, adherence to a stringent code of ethics, structured to meet the needs of the patient.


Influence of disease-modifying therapy on radiographic outcome in inflammatory polyarthritis at five years: results from a large observational inception study.
To determine the effect of early treatment with disease-modifying antirheumatic drugs (DMARDs) in reducing radiographic progression over a 5-year period in patients with new-onset inflammatory polyarthritis. Three hundred thirty-five consecutive patients with paired radiographs obtained 1 year and 5 years after enrollment in a population-based arthritis register were studied. Logistic regression was used to model differences in baseline factors associated with the start of DMARDs. The time from symptom onset to first use of DMARDs was stratified to represent 4 groups: no DMARD use, <6 months, 6-12 months, and >12 months. Radiographs of the hands and feet were scored using the Larsen method. Progression in the Larsen score was evaluated as a 5-year score adjusted for the first film score. Negative binomial regression was used to compare Larsen score progression for each of the 3 treatment groups with that for patients not receiving DMARDs. Results were then adjusted for severity, based on propensity modeling. Patients who received treatment had more radiographic progression than did patients who were untreated. Coefficients (95% confidence intervals), expressed as a multiple of the Larsen score in DMARD-treated patients compared with untreated patients, were as follows: 1.6 (1.1-2.3) for <6 months, 2.4 (1.5-3.6) for 6-12 months, and 2.0 (1.4-2.8) for >12 months. As expected, patients receiving treatment had more severe disease at baseline. Using the propensity score as a method of adjusting for disease severity, the influence of treatment on outcome became attenuated as follows: 1.1 (0.8-1.7) for <6 months, 1.6 (1.0-2.6) for 6-12 months, and 1.5 (1.0-2.2) for >12 months. This effect was also seen in the crude Larsen score at year 5. In this observational study, DMARD treatment was a marker not only of worse disease at presentation but also of the radiographic state and radiographic progression at 5 years. After adjustments were made for baseline disease severity, earlier therapy was shown to have a beneficial effect on outcome.


Excretory nitrogen metabolism and defence against ammonia toxicity in air-breathing fishes.
With the development of air-breathing capabilities, some fishes can emerge from water, make excursions onto land or even burrow into mud during droughts. Air-breathing fishes have modified gill morphology and morphometry and accessory breathing organs, which would tend to reduce branchial ammonia excretion. As ammonia is toxic, air-breathing fishes, especially amphibious ones, are equipped with various strategies to ameliorate ammonia toxicity during emersion or ammonia exposure. These strategies can be categorized into (1) enhancement of ammonia excretion and reduction of ammonia entry, (2) conversion of ammonia to a less toxic product for accumulation and subsequent excretion, (3) reduction of ammonia production and avoidance of ammonia accumulation and (4) tolerance of ammonia at cellular and tissue levels. Active ammonia excretion, operating in conjunction with lowering of ambient pH and reduction in branchial and cutaneous NH₃ permeability, is theoretically the most effective strategy to maintain low internal ammonia concentrations. NH₃ volatilization involves the alkalization of certain epithelial surfaces and requires mechanisms to prevent NH₃ back flux. Urea synthesis is an energy-intensive process and hence uncommon among air-breathing teleosts. Aestivating African lungfishes detoxify ammonia to urea and the accumulated urea is excreted following arousal. Reduction in ammonia production is achieved in some air-breathing fishes through suppression of amino acid catabolism and proteolysis, or through partial amino acid catabolism leading to alanine formation. Others can slow down ammonia accumulation through increased glutamine synthesis in the liver and muscle. Yet, some others develop high tolerance of ammonia at cellular and tissue levels, including tissues in the brain. In summary, the responses of air-breathing fishes to ameliorate ammonia toxicity are many and varied, determined by the behaviour of the species and the nature of the environment in which it lives.


Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects.
Taurine has beneficial effects on lipid metabolism in experimental animals fed with high-cholesterol or high fat diets. Whether taurine benefits lipid metabolism in humans has rarely been investigated. The aim of this study was to evaluate the effects of taurine on serum lipids in overweight or obese young adults. Thirty college students (age: 20.3+/-1.7 years) with a body mass index (BMI) >/=25.0 kg/m(2), and with no evidence of diabetes mellitus were selected and assigned to either the taurine group (n=15) or the placebo group (n=15) by double-blind randomization. Taurine 3 g/day or placebo was taken orally for 7 weeks. Triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and plasma glucose were measured before and after supplementation. The atherogenic index (AI) was calculated as (TC-HDL-C)/HDL-C. There were no differences in any baseline parameter between the two groups. Taurine supplementation decreased TG and AI significantly. Body weight also reduced significantly in the taurine group. These results suggest that taurine produces a beneficial effect on lipid metabolism and may have an important role in cardiovascular disease prevention in overweight or obese subjects.


Improved charge injection of edge aligned MoS2/MoO2 hybrid nanosheets for highly robust and efficient electrocatalysis of H2 production.
Molybdenum disulfide (MoS2) can be an efficient electro-catalyst for the hydrogen evolution reaction (HER) as an alternative to precious metals, but significant efforts are still needed to further improve its efficiency. Among various approaches, the formation of edge aligned MoS2 on an electrically conductive support is highly promising for cost-effective H2 production. Nevertheless, catalysis is highly impeded by the poor charge transport between the electrode materials and also between the multilayers of MoS2. This research presents a strategy to improve the HER catalysis by binding layers of metallic molybdenum dioxide (MoO2) and MoS2 to form hybrid MoS2/MoO2 nanosheets (attached and cross-linked to each other). Taking advantage of the hybrid structure and the mechanical strength of the carbon cloth, a catalyst with outstanding catalytic performance in the HER is demonstrated. This work shows not only a strategy to efficiently improve the electrochemical process, but also the preparation of a highly efficient catalyst for constant and robust H2 production.