Surface-immobilized and self-shaped DNA hydrogels and their application in biosensing.
Hydrogels are of great interest in the field of biosensing for their good biocompatibility, plasticity, and capability of providing 3D scaffolds. Nevertheless, the application of hydrogels has not been linked with broad surface biosensing systems yet. To overcome the limitations, here for the first time, surface-immobilized pure DNA hydrogels were synthesized using a surficial primer-induced strategy and adopted for biosensing applications. The DNA hydrogel 3D scaffold is successfully constructed on a transparent ITO electrode, which facilitates both colourimetric and electrochemical measurements. Results show that the hydrogel is able to wrap enzymes solidly and exhibits favourable stability under different conditions. Owing to the free diffusion of the micromolecular targets throughout the hydrogel, while isolating the enzymes from the macromolecular interferences outside the hydrogel, the direct colourimetric and electrochemical detection of hydrogen peroxide and bilirubin in serum is achieved. The detection limit of hydrogen peroxide in serum is 22 nM by colourimetric analysis and 13 nM by electrochemical measurement. The detection limit of bilirubin is 32 nM, a favourable limit that could be used in jaundice diagnosis. In addition, the enzyme@hydrogel can be easily regenerated and the catalytic activity is retained for a few cycles, thus allowing the recycling of the hydrogel-based biosensing system. The successful integration of DNA hydrogels with surface biosensing systems will greatly expand the applications of hydrogels for diagnostic and environmental monitoring purposes.


Nuclear envelope disassembly in mitotic extract requires functional nuclear pores and a nuclear lamina.
Using sea urchin embryonic and in-vitro-assembled nuclei incubated in sea urchin mitotic extract, I provide evidence for a requirement for functional nuclear pores and a nuclear lamina for nuclear envelope disassembly in vitro. In interphase gastrula nuclei, lamin B interacts with p56, an integral protein of inner nuclear membrane cross-reacting with antibodies to human lamin B receptor. Incubation of gastrula nuclei in mitotic cytosol containing an ATP-generating system rapidly induces hyperphosphorylation of p56 and lamin B. Subsequently, p56-lamin B interactions are weakened and the two proteins segregate into distinct nuclear envelope-derived vesicles upon disassembly of nuclear membranes and of the lamina. Nuclear disassembly is accompanied by chromatin condensation. Blocking nuclear pore function with wheat germ agglutinin or antibodies to nucleoporins prevents p56 and lamin B hyperphosphorylation, nuclear membrane breakdown and lamina solubilization. These events are not rescued by permeabilization of nuclear membranes to molecules of 150, 000 Mr with lysolecithin. In-vitro-assembled nuclei containing nuclear membranes with functional pores but no lamina do not disassemble in mitotic cytosol in spite of p56 hyperphosphorylation. Nuclear import of soluble lamin B and reformation of a lamina in interphase extract restores nuclear disassembly in mitotic cytosol. The data indicate a role for functional nuclear pores in nuclear disassembly in vitro. They show that p56 hyperphosphorylation is not sufficient for nuclear membrane disassembly in mitotic cytosol and argue that the nuclear lamina plays a critical role in nuclear disassembly at mitosis.


Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial.
Alcohol dependence is a common disorder associated with significant morbidity and mortality. Naltrexone, an opioid antagonist, has been shown to be effective for treatment of alcohol dependence. However, adherence to daily oral pharmacotherapy can be problematic, and clinical acceptance and utility of oral naltrexone have been limited. To determine efficacy and tolerability of a long-acting intramuscular formulation of naltrexone for treatment of alcohol-dependent patients. A 6-month, randomized, double-blind, placebo-controlled trial conducted between February 2002 and September 2003 at 24 US public hospitals, private and Veterans Administration clinics, and tertiary care medical centers. Of the 899 individuals screened, 627 who were diagnosed as being actively drinking alcohol-dependent adults were randomized to receive treatment and 624 received at least 1 injection. An intramuscular injection of 380 mg of long-acting naltrexone (n = 205) or 190 mg of long-acting naltrexone (n = 210) or a matching volume of placebo (n = 209) each administered monthly and combined with 12 sessions of low-intensity psychosocial intervention. The event rate of heavy drinking days in the intent-to-treat population. Compared with placebo, 380 mg of long-acting naltrexone resulted in a 25% decrease in the event rate of heavy drinking days (P = .02) [corrected] and 190 mg of naltrexone resulted in a 17% decrease (P = .07). Sex and pretreatment abstinence each showed significant interaction with the medication group on treatment outcome, with men and those with lead-in abstinence both exhibiting greater treatment effects. Discontinuation due to adverse events occurred in 14.1% in the 380-mg and 6.7% in the 190-mg group and 6.7% in the placebo group. Overall, rate and time to treatment discontinuation were similar among treatment groups. Long-acting naltrexone was well tolerated and resulted in reductions in heavy drinking among treatment-seeking alcohol-dependent patients during 6 months of therapy. These data indicate that long-acting naltrexone can be of benefit in the treatment of alcohol dependence.


Specific changes in the synthesis of mitochondrial DNA in chick embryo fibroblasts transformed by Rous sarcoma viruses.
In chick-embryo fibroblasts infected with the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup A (wild type), or with a thermosensitive mutant of this virus, T5, the rates of mitochondrial DNA synthesis differ in cells that exhibit normal and malignant phenotypes. In wild type virus-infected cells grown at 36 or 41 degrees C, morphological transformation is expressed, the rate of 2-deoxy-D-[3H]glucose uptake is stimulated, and mitochondrial DNA synthesis in vivo is stimulated three- to fivefold over that in uninfected cells. In T5-infected cells these changes occur only at the permissive temperature (36 degrees C); a shift to the nonpermissive temperature (41 degrees C) causes the reversal of these effects, and the specific activity of purified mitochondrial DNA is characteristic of that from uninfected cells. In contrast, the specific activities of nuclear DNA purified from cells maximally transformed under the permissive conditions do not differ between wild type-infected and uninfected with the T5 virus. In parallel experiments with isolated mitochondria, the rate of mtDNA synthesis in vitro is again greater in mitochondria isolated from transformed cells. In addition, mitochondrial DNA synthesis in vitro in mitochondria from nontransformed and virus-transformed cells exhibits differential sensitivity to inhibition by mercaptoethanol. Furthermore, the ntDNAP polymerase activity in mitochondrial extracts prepared from cells with transformed phenotypes is about sevenfold higher than in extracts from cells with nontransformed phenotypes.


Superfluid Weight Bounds from Symmetry and Quantum Geometry in Flat Bands.
Flat-band superconductivity has theoretically demonstrated the importance of band topology to correlated phases. In two dimensions, the superfluid weight, which determines the critical temperature through the Berezinksii-Kosterlitz-Thouless criteria, is bounded by the Fubini-Study metric at zero temperature. We show this bound is nonzero within flat bands whose Wannier centers are obstructed from the atoms-even when they have identically zero Berry curvature. Next, we derive general lower bounds for the superfluid weight in terms of momentum space irreps in all 2D space groups, extending the reach of topological quantum chemistry to superconducting states. We find that the bounds can be naturally expressed using the formalism of real space invariants (RSIs) that highlight the separation between electronic and atomic degrees of freedom. Finally, using exact Monte Carlo simulations on a model with perfectly flat bands and strictly local obstructed Wannier functions, we find that an attractive Hubbard interaction results in superconductivity as predicted by the RSI bound beyond mean field. Hence, obstructed bands are distinguished from trivial bands in the presence of interactions by the nonzero lower bound imposed on their superfluid weight.


On the Exploration of Adaptive Mechanisms Providing Reliability in Clustered WSNs for Power Plant Monitoring.
Wireless Sensor Networks (WSNs) are used in almost every sensing and detection environment instead of wired devices in the current world, all the more in power plant monitoring applications. In such a kind of environment, providing reliability is a challenging task, since WSN makes use of low powered sensors. There are many existing works that provide reliable transmission in WSN (predominantly via multipath routing). However, most of the existing works take additional delay, excessive packet loss, and energy consumption, and hence they provide less packet delivery and throughput. Adaptive Priority Routing (APR) is first proposed during the initial design to provide efficiency in next hop selection. APR computes the priority value for selecting the intermediate nodes during the data transmission in order to improve the packet delivery, throughput, and energy efficiency. In addition to this, APR is developed into QAPR protocol to provide reliability which can operate in two modes, D representing distance mode and Q representing quality of service (QoS) mode. The proposed work is simulated in both flat topology and hierarchical topologies and the simulation analysis shows that the reliability is increased significantly in comparison with existing works.


Phosphate removal from wastewater using novel renewable resource-based, cerium/manganese oxide-based nanocomposites.
Nanocomposites containing mixed metal oxides show excellent phosphate removal results and are better compared to individual metal oxides. In this research, cerium/manganese oxide nanocomposites, embedded on the surface of modified cellulose pine wood shaving, were synthesized by a simple technique that is both eco-friendly and economically feasible. No toxic or petroleum chemicals were employed during preparation. Scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), surface area analysis, and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy were performed to study the shape and size of nanocomposites as well as composition of elements present on the surface of the nanocomposites. Adsorption isotherm (Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich) and kinetic studies (pseudo first and second-order, Elovich and Weber-Morris) were carried out to determine the adsorption mechanism for phosphate removal from contaminated water. The maximum adsorption capacity of nanocomposites was found to be 204.09 mg/g, 174.42 mg/g, and 249.33 mg/g for 100 mg, 300 mg, and 500 mg, respectively. The results indicate that the nanocomposites were able to decrease the phosphorus concentration from 10 to 0.01 ppm, below the threshold limit required by EPA guidelines in the USA. We also demonstrated that the media could be regenerated and reused five times without loss of performance.


Point-of-care ultrasonography for the diagnosis of acute cardiogenic pulmonary edema in patients presenting with acute dyspnea: a systematic review and meta-analysis.
Acute dyspnea is a common presenting complaint to the emergency department (ED), and point-of-care (POC) lung ultrasound (US) has shown promise as a diagnostic tool in this setting. The primary objective of this systematic review was to determine the sensitivity and specificity of US using B-lines in diagnosing acute cardiogenic pulmonary edema (ACPE) in patients presenting to the ED with acute dyspnea. A systematic review protocol adhering to Cochrane Handbook guidelines was created to guide the search and analysis, and we searched the following databases: PubMed, EMBASE, Ovid MEDLINE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, and the Cochrane Database of Systematic Reviews. References of reviewed articles were hand-searched, and electronic searches of conference abstracts from major emergency medicine, cardiology, and critical care conferences were conducted. The authors included prospective cohort and prospective case-control studies that recruited patients presenting to hospital with symptomatic, acute dyspnea, or where there was a clinical suspicion of congestive heart failure, and reported the sensitivity and specificity of B-lines in diagnosing ACPE. Studies of asymptomatic individuals or in patients where there was no suspicion of ACPE were excluded. The outcome of interest was a diagnosis of ACPE using US B-lines. A final diagnosis from clinical follow-up was accepted as the reference standard. Two reviewers independently reviewed all citations to assess for inclusion, abstracted data, and assessed included studies for methodologic quality using the QUADAS-2 tool. Contingency tables were used to calculate sensitivity and specificity. Three subgroup analyses were planned a priori to examine the effects of the type of study, patient population, and lung US protocol employed. Seven articles (n = 1,075) were identified that met inclusion criteria (two studies completed in the ED, two in the intensive care unit [ICU], two on inpatient wards, and one in the prehospital setting). The seven studies were rated as average to excellent methodologic quality. The sensitivity of US using B-lines to diagnosis ACPE is 94.1% (95% confidence interval [CI] = 81.3% to 98.3%) and the specificity is 92.4% (95% CI = 84.2% to 96.4%). Preplanned subgroup analyses did not reveal statistically significant changes in the overall summary estimates, nor did exclusion of three potential outlier studies. This study suggests that in patients with a moderate to high pretest probability for ACPE, an US study showing B-lines can be used to strengthen an emergency physician's working diagnosis of ACPE. In patients with a low pretest probability for ACPE, a negative US study can almost exclude the possibility of ACPE. Further studies including large numbers of ED patients presenting with undifferentiated dyspnea are required to gain more valid and reliable estimates of test accuracy in ED patients.


Arterial heparin deposition: role of diffusion, convection, and extravascular space.
Transvascular transport has been studied with atherogenic, tracer, and inert compounds such as low-density lipoprotein, horseradish peroxidase, and albumin, respectively. Few studies used vasoactive compounds, and virtually all studies examined entry from the lumen and not from the perivascular space. We compared several mechanisms that govern arterial heparin deposition after administration to the perivascular and endovascular aspects of the calf carotid artery in vitro and the rabbit iliac artery in vivo. In the absence of transmural hydrostatic pressure gradients, heparin deposition following endovascular administration was unaffected by deendothelialization and was indistinguishable from perivascular delivery. Deposition in the former was enhanced by the addition of a pressure gradient and to a greater extent in denuded arteries, indicating that convection influences transport but is dampened by the endothelium. Neither the endothelium nor the adventitia pose significant resistances to heparin. Deposition in vivo was greater following endovascular hydrogel release than perivascular application from similar devices to native or denuded arteries. The loss of drug to extra-arterial microvessels exceeded the loss of drug to the lumen flow. These findings are essential for describing vascular pharmacokinetics and for implementing local pharmacotherapies.


Predictors of risk for smoking relapse in men and women: a prospective examination.
The current study examined whether prequit trait negative mood and smoking motives have different predictive patterns of smoking relapse in men and women. Thirty-three female (mean age±SEM: 34.9±2.5) and 38 male (mean age±SEM: 37.1±2.3) smokers interested in smoking cessation completed forms on smoking history, negative mood (i.e., depression, anxiety, and anger), stress, and smoking motives. Participants also provided samples for measurement of cotinine and carbon monoxide. Then, they set a quit date and were required to abstain from smoking at least for 24 hours. Participants were followed up for 12 months postcessation to measure their smoking status. Cox proportional hazard models revealed that motivation to reduce craving was a unique predictor of smoking relapse in men, while depressive mood, anxiety, anger, and perceived stress were predictive of time to relapse among women. These findings remained significant after statistically controlling for smoking-related variables, providing preliminary evidence that different factors may be associated with nicotine withdrawal and smoking relapse in men and women.


Online interprofessional simulation for undergraduate health professional students during the COVID-19 pandemic.
This report describes the Obstetric and Neonatal Simulation (ONE-Sim) workshop run in a remote learning format for medical and midwifery students in an interprofessional setting during the COVID-19 pandemic. It explores the observation of students as participants in the online learning of using Personal Protective Equipment and simulation-based learning of perinatal emergency management. This was followed by their mutual interaction and reflections. This paper aims to understand the role of synchronous remote learning through simulation and its impact on interprofessional interactions. We describe the experience of medical and midwifery students with the ONE-Sim workshop, facilitated by medical (obstetric and neonatal) and midwifery educators. Formal thematic analysis will be performed as part of the ongoing study; however, initial direct observation demonstrated that students reacted positively to the online ONE-Sim workshop and engaged well with facilitators and peers. Students mutually interacted amongst themselves, shared their previous experiences, knowledge of roles as medical and midwifery practitioners and how they see themselves in those roles in a perinatal emergency setting. The initial observations demonstrate that interprofessional education delivered in an e-learning format can be useful and meaningful, and may be utilized across a number of specialties.


Bis{2-hydr-oxy-N-[2-(2-pyrid-yl)eth-yl]benzamide}copper(I) tetra-fluoridoborate.
The title complex, [Cu(C(14)H(14)N(2)O(2))(2)]BF(4), is a monomeric copper(I) species with linear two-coordinate geometry around the Cu(I) atom. The asymmetric unit contains two half-cations that sit on crystallographic twofold rotation axes. The selected crystal was non-merohedrally twinned by a twofold rotation about an axis normal to the (100) family of planes. The ratio of the twin components refined to 0.4123 (6). Two 2-hydr-oxy-N-[2-(2-pyrid-yl)eth-yl]benzamide ligands coordinate to each Cu(I) atom via the pyridyl N atom. Intra-molecular hydrogen bonding between the phenol OH groups and the amide O atoms imparts rigidity and planarity to the non-coordinating end of the ligand. The cationic complex is linked to the BF(4) (-) anions via hydrogen bonding between the amide NH groups in the cations and BF(4) (-) anions.


A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response.
Repair of DNA double-strand breaks is critical to genomic stability and the prevention of developmental disorders and cancer. A central pathway for this repair is homologous recombination (HR). Most knowledge of HR is derived from work in prokaryotic and eukaryotic model organisms. We carried out a genome-wide siRNA-based screen in human cells. Among positive regulators of HR we identified networks of DNA-damage-response and pre-mRNA-processing proteins, and among negative regulators we identified a phosphatase network. Three candidate proteins localized to DNA lesions, including RBMX, a heterogeneous nuclear ribonucleoprotein that has a role in alternative splicing. RBMX accumulated at DNA lesions through multiple domains in a poly(ADP-ribose) polymerase 1-dependent manner and promoted HR by facilitating proper BRCA2 expression. Our screen also revealed that off-target depletion of RAD51 is a common source of RNAi false positives, raising a cautionary note for siRNA screens and RNAi-based studies of HR.


Thirteen-week repeated dose toxicity study of wormwood (Artemisia absinthium) extract in rats.
Wormwood, Artemisia absinthium, is a very bitter plant, and its extract has been used as food additives such as seasonings for food and drinks. A 13-week repeated dose toxicity study of wormwood extract was performed in both sexes of Wistar Hannover (GALAS) rats. Rats were divided into 4 groups consisting of 10 males and 10 females each, and were given water containing 0, 0.125, 0.5, or 2% wormwood extract. All rats had survived at the end of the study, and no changes indicating obvious toxicities that are attributable to the treatment of wormwood extract were observed in the body weights, hematological and serum biochemical examinations, organ weights, and histopathological examinations. Based on the results of the present study, the NOAEL (no-observed-adverse-effect-level) of wormwood extract of Wistar Hannover rats was estimated to be 2% (equivalent to 1.27 g/kg/day in males and 2.06 g/kg/day in females) or more.


Coordinate regulation of the messenger ribonucleic acids encoding the alpha- and beta-subunits of human chorionic gonadotropin in HeLa cells and butyrate-resistant variants.
Short term exposure of HeLa S3 cells to sodium butyrate induces accumulation of the mRNAs encoding both the alpha- and beta-subunits of hCG. Both mRNAs accumulate with the same kinetics and reach maximal levels with the same concentration of butyrate, suggesting that the levels of alpha and hCG beta mRNAs are coordinately regulated. In addition, induction of both mRNAs is tightly coupled with a similar increase in secreted levels of hCG subunit protein, further suggesting that regulation of CG biosynthesis in HeLa cells occurs before translation. To determine whether HeLa cells which have overcome the growth inhibitory properties of butyrate show uniformly high levels of alpha and hCG beta mRNAs, we isolated clonal variants by stepwise selection with increasing concentrations of butyrate. Of 69 isolated variants, at least 2 (AO and B2) display different patterns of CG gene expression. In AO cells, alpha-subunit mRNA was not detectable, while in B2 cells, the level of alpha-subunit mRNA was similar to that of wild-type HeLa S3 cells. Conversely, hCG beta mRNA levels in both variant cell lines approximated levels found in butyrate-treated HeLa S3 cultures, suggesting that the mRNAs for alpha and hCG beta are regulated independently. Analysis of genomic DNA by blot hybridization indicated that the alpha-subunit gene was present as a single unrearranged copy in HeLa S3 cells and in both variants, indicating that differences in alpha-subunit gene expression are not associated with major genomic alterations, but probably reflect more subtle changes.


Approved monoclonal antibodies for cancer therapy.
Monoclonal antibodies are a rapidly expanding class of agents for the treatment of cancer. In 1997 rituximab became the first approved monoclonal antibody for the treatment of low grade B cell lymphoma. Since then several monoclonal antibodies have received approval from the United States Food and Drug Administration (US FDA) for the treatment of a variety of solid tumors and hematological malignancies. To review the literature using Medline and summarize the mechanisms of action, indications and outcome of treatment of currently approved monoclonal antibodies used in clinical practice for patients with solid tumors and hematologic malignancies. An overview of the FDA approved monoclonal antibodies is provided. Monoclonal antibodies are currently used as the standard of care as first and second line therapy for a number of hematologic malignancies and solid tumors. Over the next 5 - 10 years additional monoclonal antibodies and monoclonal antibody conjugates will be approved by the US FDA and will dramatically affect the standard of care of many cancers.


HPV vaccination and sexual behavior in a community college sample.
Many US parents are concerned that vaccinating daughters against human papillomavirus (HPV) will communicate implicit approval for sexual activity and be associated with early or risky sexual behavior (Scarinci et al. in J Womens Health 16(8):1224-1233, 2007; Schuler et al. in Sex Transm Infect 87:349-353, 2011). The aims of this study were to understand (a) whether the HPV vaccine was associated with risky sexual behavior among a diverse sample of female adolescents and young adults, and (b) to better understand the chronology of HPV vaccination and sexual behavior. An anonymous web-based survey was used to collect data from 114 female community college students. T test and Chi square analyses were used to compare vaccinated and unvaccinated groups on age at first intercourse and proportion who had ever had sexual intercourse. Linear multiple regression was used to predict frequency of condom use and number of sexual partners in the past year, using vaccination status and demographic factors as predictors. About 38% reported receiving at least one dose of the HPV vaccine. Many of those vaccinated (45%) received the vaccine after having initiated sexual activity. The proportion of women who were sexually experienced did not differ by HPV vaccine status, nor did age at first intercourse, number of partners in the past year, or frequency of condom use. Current findings suggest that HPV vaccination is not associated with riskier sexual activity for the young women in this sample. Adolescents and their parents may benefit from education about the need to receive the HPV vaccine before onset of sexual activity.


Capsanthin-Loaded Micelles: Preparation, Characterization and in vitro Evaluation of Cytotoxicity Using MDA-MB-231 Breast Cancer Cell Line.
Breast cancer is one of the most common cancers and remains a major cause of morbidity and mortality among women worldwide. In developed countries, breast cancer as a multifactorial disease is a major health concern, and its incidence is constantly rising in low and middle-income countries. Numerous studies have demonstrated that phytochemicals such as carotenoids inhibit breast cancer growth and induce apoptosis. We recently enhanced the solubility of capsanthin in water by encapsulating it in diosgenin polyethylene glycol succinate, a novel non-ionic surfactant. Thus, this study aims to evaluate the cytotoxicity of water-soluble capsanthin-loaded micelles in MDA-MB-231 cells in vitro through tetrazolium dye MTT assay. In the current study, capsanthin, a hydrophobic carotenoid, is extracted from sweet red pepper (Capsicum annuum). Capsanthin-loaded diosgenin polyethylene glycol succinate 1000 (cap-DPGS-1000) micelles were prepared from capsanthin extract (cap) and diosgenin polyethylene glycol succinate 1000 (DPGS-1000) using the solid dispersion method. The capsanthin extract and cap-DPGS-1000 micelles were characterized by UV-visible spectroscopy, high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), particle size distribution, polydispersity, and scanning electron microscopy (SEM). The effects of capsanthin extract and cap-DPGS-1000 micelles on a human triple-negative breast cancer cell line (MDA-MB-231) were tested to check the cell viability, proliferation and cytotoxicity of the micelles. The solubility of encapsulated cap-DPGS-1000 micelles in water is greatly enhanced and leads to an increased scope for localized drug delivery, a better delivery option for treating residual cancerous tumours. The encapsulated capsanthin showed a sustained release in simulated intestinal fluid (pH=6.8). Our research proposes a sustained drug delivery system that ensures effective and controlled release to the affected site. The characterization data revealed no change in the structure and functional groups in the encapsulated capsanthin. The IC50 value of the cap-DPGS-1000 micelles against MDA-MB-231 breast cancer cells was (3.10±1.09) μg/mL, which is much lower than of capsanthin extract ((81.1±1.5) μg/mL). Capsanthin extract and capsanthin-loaded micelles are promising drug candidates to induce apoptosis and increase reactive oxygen species (ROS) in cancer cells. The result shows the cytotoxic effect of capsanthin and capsanthin-loaded micelles on MDA-MB-231 cell line for the first time. Capsanthin from sweet red pepper (Capsicum annuum) showed remarkable cytotoxic effect on the triple-negative MDA-MB-231 cell line.


Correlation of the Canadian Pediatric Emergency Triage and Acuity Scale to ED resource utilization.
The aim of this study was to find if there is a correlation between acuity measured by the Canadian Pediatric Emergency Triage and Acuity Scale (Ped-CTAS) and resource utilization in a large tertiary academic emergency department (ED). If correlation exists, it may indicate that resource allocation was done in accordance with needs (the more acute the patient, the more resources needed). This may also be the basis for future consideration regarding resource allocation decisions. All pediatric patients (0-19 years of age) who were seen in the ED during 12 randomly selected days between May 1, 2005, and April 30, 2006, were included in the study. Detailed information regarding number and types of investigations ordered was collected. To look at the aggregate use of resources, we used the unit of cost. Resource utilization was calculated using standardized cost lists, and results were used to explore the correlation between different Ped-CTAS levels and resource utilization. A fixed cost model was used to predict the remainder of costs, other than diagnostic services. Of the 1661 patients presenting during the study period, 1618 (97.4%) were included in the study. The mean laboratory, microbiology, imaging, and total investigational costs increased with increasing acuity. This difference was insignificant between the semiurgent and the nonurgent categories of the Ped-CTAS. The Ped-CTAS level correlates well with resource utilization for patient management in the ED. Further research should focus on measuring nursing and physician time use for each Ped-CTAS level to more accurately document ED resource utilization.


Angiotensin II type 1 receptor antibodies and increased angiotensin II sensitivity in pregnant rats.
Pregnant women who subsequently develop preeclampsia are highly sensitive to infused angiotensin (Ang) II; the sensitivity persists postpartum. Activating autoantibodies against the Ang II type 1 (AT(1)) receptor are present in preeclampsia. In vitro and in vivo data suggest that they could be involved in the disease process. We generated and purified activating antibodies against the AT(1) receptor (AT(1)-AB) by immunizing rabbits against the AFHYESQ epitope of the second extracellular loop, which is the binding epitope of endogenous activating autoantibodies against AT(1) from patients with preeclampsia. We then purified AT(1)-AB using affinity chromatography with the AFHYESQ peptide. We were able to detect AT(1)-AB both by ELISA and a functional bioassay. We then passively transferred AT(1)-AB into pregnant rats, alone or combined with Ang II. AT(1)-AB activated protein kinase C-α and extracellular-related kinase 1/2. Passive transfer of AT(1)-AB alone or Ang II (435 ng/kg per minute) infused alone did not induce a preeclampsia-like syndrome in pregnant rats. However, the combination (AT(1)-AB plus Ang II) induced hypertension, proteinuria, intrauterine growth retardation, and arteriolosclerosis in the uteroplacental unit. We next performed gene-array profiling of the uteroplacental unit and found that hypoxia-inducible factor 1α was upregulated by Ang II plus AT(1)-AB, which we then confirmed by Western blotting in villous explants. Furthermore, endothelin 1 was upregulated in endothelial cells by Ang II plus AT(1)-AB. We show that AT(1)-AB induces Ang II sensitivity. Our mechanistic study supports the existence of an "autoimmune-activating receptor" that could contribute to Ang II sensitivity and possible to preeclampsia.


Preparing for preventive clinical trials: the Predict-HD study.
The optimal design and outcome measures for preventive clinical trials in neurodegenerative diseases are unknown. To examine measures that may be associated with disease in the largest cohort ever recruited of prediagnosed individuals carrying the gene expansion for Huntington disease (HD). The Predict-HD study is a multicenter observational research study in progress at 17 sites in the United States, 4 in Canada, and 3 in Australia. Genetics and HD outpatient clinics. Five hundred five at-risk individuals who had previously undergone elective DNA analyses for the CAG expansion in the HD gene (predictive testing) and did not currently have a clinical diagnosis of HD. Basal ganglia volumes on magnetic resonance images, estimated probability of diagnosis (based on CAG repeat length), performances on 21 standardized cognitive tasks, total scores on 3 scales of psychiatric distress, and motor diagnosis based on the Unified Huntington's Disease Rating Scale. Several variables showed progressive decline as the diagnostic ratings advanced toward manifest disease. Estimated probability of diagnosis was associated with Unified Huntington's Disease Rating Scale prediagnostic stages and varied from 15% in persons with no motor abnormalities to nearly 40% in those with abnormalities suggestive of probable disease. Striatal volumes, cognitive performances, and even psychiatric ratings declined significantly with motor manifestations of disease. The documentation of biological and refined clinical markers suggests several clinical end points for preventive clinical trials. Longitudinal study is critical to further validate possible markers for prediagnosed HD.


Total en bloc resection of primary and metastatic spine tumors.
Primary and metastatic tumors of the spine represent a significant cause of patient morbidity, and present a management challenge to treating providers. From a neurosurgical standpoint, resection surgery may be warranted in cases of spinal instability, progressive disease, neurological compromise, or intractable symptoms. Removal of a tumor "en bloc" offers a more aggressive modality over more conservative resection techniques. En bloc resection entails the removal of the entirety of a tumor without violation of its capsule, and may offer improved rates of local control and overall survival in appropriately selected patients. Conversely, this technique carries a higher complication rate, and requires a unique set of technical skills as compared to more traditional resection. Here, we describe the technical aspects of en bloc resection, as well as specific indications and considerations when employing this operative technique.


Gain analysis of optically-pumped Si nanocrystal waveguide amplifiers on silicon substrate.
The SiO(2)/SiO(x)/SiO(2) strip-loaded waveguide on Si substrate with buried Si nanocrystals (Si-ncs) in SiO(x) layer is demonstrated to show the Si-nc dependent optical gain. The amplified spontaneous emission (ASE) spectrum at 750-850 nm is observed with central wavelength of 805 nm and 3dB spectral linewidth of 140 nm. The optical net modal gain and loss coefficients of 85.7 cm(-1) and 21 cm(-1), respectively, are determined from the waveguide length dependent ASE intensity. By attenuating 785-nm laser diode signal to inject the pumped SiO(2)/SiO(x)/SiO(2) strip-loaded waveguide, a small-signal power gain of 13.5 decibel (dB) is obtained. Increasing the laser diode power shows a significantly reduced power gain with a saturated output power due to the finite density of the optically pumped Si-ncs. The fitting of power-dependent gain with a gain-saturated amplifier model reveals a peak gain of 35 dB and a saturation power of 1.1 nW for the SiO(2)/SiO(x):Si-nc/SiO(2)/Si strip-loaded waveguide. Similar output saturation is also observed with increasing pumping power. With the presence of optical gain in the optically pumped Si-ncs, the intended application will be the monolithic integration of the Si-nc based optical waveguide amplifier with the other on-board photonic integrated circuits for the future optical interconnect communication.


Neonatal injections of methoxychlor decrease adult rat female reproductive behavior.
Methoxychlor (MXC), a commonly used pesticide, has been labeled as an endocrine disruptor. To evaluate the impact of neonatal exposure to MXC on female reproduction, female Sprague-Dawley rats were given subcutaneous injections on postnatal days 1, 3, and 5. The injections contained 1.0mg MXC, 2.0mg MXC, 10 μg 17β-estradiol benzoate (positive control), or sesame oil (vehicle). The injections of MXC had no effect on anogenital distance or day of vaginal opening. Treatment with either 2.0mg MXC or estradiol significantly increased the total number of days with vaginal keratinization. Treatment with MXC had no effect on ability to exhibit a mating response as an adult female, although the high dose MXC (2.0) and the positive control (estradiol) animals demonstrated a decrease in degree of receptivity, a decrease in proceptive behavior and an increase in rejection behavior. These data suggest that higher doses of MXC given directly to pups during the neonatal period can act as an estrogen and alter aspects of the nervous system, impacting adult reproductive characteristics.


Native trees of Mexico: diversity, distribution, uses and conservation.
Mexico is one of the most floristically rich countries in the world. Despite significant contributions made on the understanding of its unique flora, the knowledge on its diversity, geographic distribution and human uses, is still largely fragmented. Unfortunately, deforestation is heavily impacting this country and native tree species are under threat. The loss of trees has a direct impact on vital ecosystem services, affecting the natural capital of Mexico and people's livelihoods. Given the importance of trees in Mexico for many aspects of human well-being, it is critical to have a more complete understanding of their diversity, distribution, traditional uses and conservation status. We aimed to produce the most comprehensive database and catalogue on native trees of Mexico by filling those gaps, to support their in situ and ex situ conservation, promote their sustainable use, and inform reforestation and livelihoods programmes. A database with all the tree species reported for Mexico was prepared by compiling information from herbaria and reviewing the available floras. Species names were reconciled and various specialised sources were used to extract additional species information, i.e. endemic status, threat status, availability in seed collections, reports on plant uses and conservation actions currently in place. With this information, a comprehensive catalogue of native trees from Mexico was redacted. Available georeferenced records were used to map each species distribution and perform spatial analyses to identify gaps of information and priority areas for their conservation and exploration. Mexico has at least 2,885 native tree species, belonging to 612 genera and 128 families. Fabaceae is the most represented family and Quercus the most represented genus. Approximately 44% of tree species are endemic to the country. The southern part of the country showed the highest values of species richness. Six hundred and seventy-four species have at least one documented human use. In terms of conservation assessment, ca. 33% of species have been assessed by either the IUCN Red List (919) or the National protection catalogue "NORMA Oficial Mexicana NOM-059" (29) or both (45). Additionally, 98 species have been included in the CITES listing for protection. In terms of existing conservation efforts, 19% of species have ex situ protection in seed banks, while protected areas overlap with all the identified peaks of species richness, except for those in the states of Veracruz and Chiapas. This work constitutes a key milestone for the knowledge, management, and conservation of the Mexican native trees. The two areas with high density of tree species identified in Veracruz and Chiapas represent two priority areas for tree conservation in Mexico, where integrated in situ and ex situ conservation efforts should be focused.


Working memory deficits in adults with ADHD: is there evidence for subtype differences?
Working memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD). There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, however, remains to be more fully documented. This study assessed differences in working memory functioning between Normal Control (NC) adults (N = 18); patients with ADHD, Combined (ADHD-CT) Type ADHD (N = 17); and ADHD, Inattentive (ADHD-IA) Type (N = 16) using subtests from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-III and the Paced Auditory Serial Addition Task (PASAT). The ADHD groups displayed significant weaknesses in contrast to the NC group on working memory tests requiring rapid processing and active stimulus manipulation. This included the Letter-Number-Sequencing test of the Wechsler scales, PASAT omission errors and the longest sequence of consecutive correct answers on the PASAT. No overall ADHD group subtype differences emerged; however differences between the ADHD groups and the NC group varied depending on the measure and the gender of the participants. Gender differences in performance were evident on some measures of working memory, regardless of group, with males performing better than females. In general, the data support a dimensional interpretation of working memory deficits experienced by the ADHD-CT and ADHD-IA subtypes, rather than an absolute difference between subtypes. Future studies should test the effects of processing speed and load on subtype performance and how those variables interact with gender in adults with ADHD.


Biomechanical aspects of the muscle-bone interaction.
There is growing interest in the interaction between skeletal muscle and bone, particularly at the genetic and molecular levels. However, the genetic and molecular linkages between muscle and bone are achieved only within the context of the essential mechanical coupling of the tissues. This biomechanical and physiological linkage is readily evident as muscles attach to bone and induce exposure to varied mechanical stimuli via functional activity. The responsiveness of bone cells to mechanical stimuli, or their absence, is well established. However, questions remain regarding how muscle forces applied to bone serve to modulate bone homeostasis and adaptation. Similarly, the contributions of varied, but unique, stimuli generated by muscle to bone (such as low-magnitude, high-frequency stimuli) remains to be established. The current article focuses upon the mechanical relationship between muscle and bone. In doing so, we explore the stimuli that muscle imparts upon bone, models that enable investigation of this relationship, and recent data generated by these models.


Mapping the pork value chain in Vietnam: a systematic review.
In Vietnam, pork is the most commonly consumed type of meat, and the demand is expected to rise even further. Nevertheless, food safety is a major concern, as the country bears a high burden of food-borne diseases, including these caused by pork products. Knowledge of the flows of pigs and pork from producers up to the consumers is important; however, up to now, a comprehensive overview is lacking. We addressed this by conducting a systematic review on the pork value chain (PVC) mapping for the country. Four international and three Vietnamese databases were searched for data on the pork value chain in Vietnam, and the results were reported according to the PRISMA guidelines. Data obtained from the retained records showed that 10 main PVC types are present in Vietnam, comprising of five main actors including: producers, middlemen, slaughter men, retailers and consumers. Among the identified chains, the one involving producers, slaughter men, retailers and consumers is the most common one, with up to 75% of pork following this route. In cities or export routes to other countries, middlemen and/or traders are important additional actors in the PVCs. The small scale of PVC linkages is prominent. The presence of middlemen, pig traders and pork traders is contributing to further distribution of pork products in geographical terms. Transactions between actors in the traditional PVCs in Vietnam are characterized by the absence of official contracts; therefore, the linkages in the chains are loose and the origin of pork is not traceable. More industrial forms of PVCs are slowly developing; however, the traditional PVCs are still prevailing in Vietnam. The weak linkages between actors and poor hygienic practices in these chains form a risk to pork safety.


Effectiveness of interventions targeting physical activity, nutrition and healthy weight for university and college students: a systematic review and meta-analysis.
To examine the effectiveness of interventions aimed at improving physical activity, diet, and/or weight-related behaviors amongst university/college students. Five online databases were searched (January 1970 to April 2014). Experimental study designs were eligible for inclusion. Data extraction was performed by one reviewer using a standardized form developed by the researchers and checked by a second reviewer. Data were described in a narrative synthesis and meta-analyses were conducted when appropriate. Study quality was also established. Forty-one studies were included; of these, 34 reported significant improvements in one of the key outcomes. Of the studies examining physical activity 18/29 yielded significant results, with meta-analysis demonstrating significant increases in moderate physical activity in intervention groups compared to control. Of the studies examining nutrition, 12/24 reported significantly improved outcomes; only 4/12 assessing weight loss outcomes found significant weight reduction. This appears to be the first systematic review of physical activity, diet and weight loss interventions targeting university and college students. Tertiary institutions are appropriate settings for implementing and evaluating lifestyle interventions, however more research is needed to improve such strategies.


Breeding implications resulting from classification of patellae luxation in dogs.
Patellar luxation (PL) is one of the major hereditary orthopaedic abnormalities observed in a variety of dog breeds. When the patellae move sideways out of the trochlear groove, this is called PL. The PL score varies between dogs from normal to very severe. Reducing the prevalence of PL by breeding could prevent surgery, thereby improve welfare. Orthopaedic specialists differentiate between normal and loose patellae, where the patellae can be moved to the edge of the trochlear groove, considering scoring loose patellae as normal in the future. Loose patellae are considered acceptable for breeding so far by the breeding organization. The aim of this study was to analyse the genetic background of PL to decide on the importance of loose patellae when breeding for healthy dogs. Data are available from two dog breeds, that is Flat-coated Retrievers (n = 3808) and Kooiker dogs (n = 794), with a total of 4602 dogs. Results show that loose patellae indicate that dogs are genetically more susceptible to develop PL because family members of the dogs with loose patellae showed more severe PL. In addition, the estimated breeding values for dogs with loose patellae indicate that breeding values of dogs with loose patellae were worse than breeding values obtained for dogs with a normal score. Given these results, it is advised to orthopaedic specialists to continue to score loose patellae as a separate class and to dog breeders to minimize the use of dogs in breeding with a genetically higher susceptibility for PL.


Relapsed Waldenstrom's Macroglobulinemia and Therapy-Related Myelodysplastic Syndrome with Complex Cytogenetics: A Treatment Dilemma.
Waldenstrom's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by the infiltration of the bone marrow by clonal lymphoplasmacytic cells that produce monoclonal immunoglobulin M as defined by the World Health Organization Classification of hematological malignancies. Historically, the treatment options for WM were limited to alkylating agents and purine analogs. The introduction of immune therapy, including CD20 targeted therapy, proteasome inhibitors, and immune modulators, has provided benefit to those patients and has now become the standard of care. As WM patients become long-term survivors, treatment's late toxicities have become more apparent. Here, we report a case of a 74-year-old female who presented to the hospital with fatigue and was diagnosed with WM. She was treated with bortezomib, doxorubicin, and bendamustine, followed by rituximab. After a remission period of 15 years, the patient had a relapse of WM, and bone marrow biopsy findings were consistent with intermediate-risk t-MDS with complex cytogenetics, presenting us with a treatment dilemma. We decided to treat WM, and the patient went into VGPR with residual lymphoma cells. Despite having dysplasia and complex cytogenetics, she did not have any cytopenia. Currently, she is under observation anticipating the progression of her MDS, given her intermediate I risk status. This case features the occurrence of t-MDS after therapy with bendamustine, cladribine, and doxorubicin. This highlights the need for closer monitoring and consideration of long-term adverse effects when treating patients with indolent lymphomas, especially WM. Late complications need to be considered, and risk versus benefit analysis needs to be carefully evaluated, especially in younger patients with WM.


Possible Routes to Obtain Enhanced Magnetoresistance in a Driven Quantum Heterostructure with a Quasi-Periodic Spacer.
In this work, we perform a numerical study of magnetoresistance in a one-dimensional quantum heterostructure, where the change in electrical resistance is measured between parallel and antiparallel configurations of magnetic layers. This layered structure also incorporates a non-magnetic spacer, subjected to quasi-periodic potentials, which is centrally clamped between two ferromagnetic layers. The efficiency of the magnetoresistance is further tuned by injecting unpolarized light on top of the two sided magnetic layers. Modulating the characteristic properties of different layers, the value of magnetoresistance can be enhanced significantly. The site energies of the spacer is modified through the well-known Aubry-André and Harper (AAH) potential, and the hopping parameter of magnetic layers is renormalized due to light irradiation. We describe the Hamiltonian of the layered structure within a tight-binding (TB) framework and investigate the transport properties through this nanojunction following Green's function formalism. The Floquet-Bloch (FB) anstaz within the minimal coupling scheme is introduced to incorporate the effect of light irradiation in TB Hamiltonian. Several interesting features of magnetotransport properties are represented considering the interplay between cosine modulated site energies of the central region and the hopping integral of the magnetic regions that are subjected to light irradiation. Finally, the effect of temperature on magnetoresistance is also investigated to make the model more realistic and suitable for device designing. Our analysis is purely a numerical one, and it leads to some fundamental prescriptions of obtaining enhanced magnetoresistance in multilayered systems.


Four meta-analyses across 164 studies on atypical footedness prevalence and its relation to handedness.
Human lateral preferences, such as handedness and footedness, have interested researchers for decades due to their pronounced asymmetries at the population level. While there are good estimates on the prevalence of handedness in the population, there is no large-scale estimation on the prevalence of footedness. Furthermore, the relationship between footedness and handedness still remains elusive. Here, we conducted meta-analyses with four different classification systems for footedness on 145,135 individuals across 164 studies including new data from the ALSPAC cohort. The study aimed to determine a reliable point estimate of footedness, to study the association between footedness and handedness, and to investigate moderating factors influencing footedness. We showed that the prevalence of atypical footedness ranges between 12.10% using the most conservative criterion of left-footedness to 23.7% including all left- and mixed-footers as a single non-right category. As many as 60.1% of left-handers were left-footed whereas only 3.2% of right-handers were left-footed. Males were 4.1% more often non-right-footed compared to females. Individuals with psychiatric and neurodevelopmental disorders exhibited a higher prevalence of non-right-footedness. Furthermore, the presence of mixed-footedness was higher in children compared to adults and left-footedness was increased in athletes compared to the general population. Finally, we showed that footedness is only marginally influenced by cultural and social factors, which play a crucial role in the determination of handedness. Overall, this study provides new and useful reference data for laterality research. Furthermore, the data suggest that footedness is a valuable phenotype for the study of lateral motor biases, its underlying genetics and neurodevelopment.


Population genetics of Leptoglossus clypealis (Hemiptera: Coreidae) in the Western United States.
The leaffooted bug, Leptoglossus clypealis Heidemann, is a seed-feeding economic pest of crops including almonds and pistachios. The historical distribution of L. clypealis has been considered to be West of the Mississippi in the United States. L. clypealis was recently found in sorghum in the Coastal Bend of Texas, representing a new host record and new collection locality. This study investigated the genetic diversity of L. clypealis museum voucher samples from the Western United States (i.e., Texas, California, and Idaho) collected from 1994 to 2019, including the L. clypealis samples from the Coastal Bend. Eleven new sequences were obtained. Sample sequences were compared with public sequences of L. clypealis from the Western United States. The mitochondrial DNA cytochrome oxidase 1 (mtDNA COI) barcode gene region revealed differences among and within the collection regions. Texas, Idaho, and California all had samples with unique genotypes, and the combined dataset had a haplotype diversity of 1.0. The Texas specimens recently collected in the Coastal Bend did not match genotypes from California or Idaho, and it is unlikely they were recently introduced. Overall, L. clypealis from Texas, Idaho, and California have a high level of genetic diversity, and the 3 regions appear to be within the native range of the species.


Corticofugal influences of S1 cortex on ventrobasal thalamic neurons in the awake rat.
Corticofugal influences on the responses of 39 ventrobasal (VB) thalamic neurons to repetitive stimuli were studied in awake rats by focally suppressing the evoked and spontaneous electrocortical activity of the primary (S1) somatosensory cortex with magnesium or lidocaine plus magnesium. Suppression of the S1 cortex reduced the number of spikes discharged by 19 (66%) of 29 VB units in response to each of 25 electrical stimuli delivered to the medial lemniscus; 9 units were unaffected and 1 showed an increased response to 1-10 Hz stimuli. The responses of 6 (38%) of 16 VB units to electrical somatic stimuli were also reduced following S1 cortical suppression; 9 units were unaffected and 1 showed an increased response to 20-40 Hz stimuli. A comparison of the reduced responsiveness of 5 units studied during medial lemniscal and somatic stimulation did not reveal any additional response attenuation attributable to subthalamic corticofugal influences. We conclude that, in the awake rat, somatosensory transmission to VB thalamic neurons is primarily facilitated by S1 corticothalamic neurons.


Restriction of extracellular lipids renders pancreatic cancer dependent on autophagy.
KRAS is the predominant oncogene mutated in pancreatic ductal adenocarcinoma (PDAC), the fourth cause of cancer-related deaths worldwide. Mutant KRAS-driven tumors are metabolically programmed to support their growth and survival, which can be used to identify metabolic vulnerabilities. In the present study, we aimed to understand the role of extracellularly derived fatty acids in KRAS-driven pancreatic cancer. To assess the dependence of PDAC cells on extracellular fatty acids we employed delipidated serum or RNAi-mediated suppression of ACSL3 (to inhibit the activation and cellular retention of extracellular fatty acids) followed by cell proliferation assays, qPCR, apoptosis assays, immunoblots and fluorescence microscopy experiments. To assess autophagy in vivo, we employed the KrasG12D/+;p53flox/flox;Pdx1-CreERT2 (KPC) mice crossed with Acsl3 knockout mice, and to assess the efficacy of the combination therapy of ACSL3 and autophagy inhibition we used xenografted human cancer cell-derived tumors in immunocompromised mice. Here we show that depletion of extracellularly derived lipids either by serum lipid restriction or suppression of ACSL3, triggers autophagy, a process that protects PDAC cells from the reduction of bioenergetic intermediates. Combined extracellular lipid deprivation and autophagy inhibition exhibits anti-proliferative and pro-apoptotic effects against PDAC cell lines in vitro and promotes suppression of xenografted human pancreatic cancer cell-derived tumors in mice. Therefore, we propose lipid deprivation and autophagy blockade as a potential co-targeting strategy for PDAC treatment. Our work unravels a central role of extracellular lipid supply in ensuring fatty acid provision in cancer cells, unmasking a previously unappreciated metabolic vulnerability of PDAC cells.


RNA processing bodies, peroxisomes, Golgi bodies, mitochondria, and endoplasmic reticulum tubule junctions frequently pause at cortical microtubules.
Organelle motility, essential for cellular function, is driven by the cytoskeleton. In plants, actin filaments sustain the long-distance transport of many types of organelles, and microtubules typically fine-tune the motile behavior. In shoot epidermal cells of Arabidopsis thaliana seedlings, we show here that a type of RNA granule, the RNA processing body (P-body), is transported by actin filaments and pauses at cortical microtubules. Interestingly, removal of microtubules does not change the frequency of P-body pausing. Similarly, we show that Golgi bodies, peroxisomes, and mitochondria all pause at microtubules, and again the frequency of pauses is not appreciably changed after microtubules are depolymerized. To understand the basis for pausing, we examined the endoplasmic reticulum (ER), whose overall architecture depends on actin filaments. By the dual observation of ER and microtubules, we find that stable junctions of tubular ER occur mainly at microtubules. Removal of microtubules reduces the number of stable ER tubule junctions, but those remaining are maintained without microtubules. The results indicate that pausing on microtubules is a common attribute of motile organelles but that microtubules are not required for pausing. We suggest that pausing on microtubules facilitates interactions between the ER and otherwise translocating organelles in the cell cortex.


The Stone Age Plague and Its Persistence in Eurasia.
Yersinia pestis, the etiologic agent of plague, is a bacterium associated with wild rodents and their fleas. Historically it was responsible for three pandemics: the Plague of Justinian in the 6th century AD, which persisted until the 8th century [1]; the renowned Black Death of the 14th century [2, 3], with recurrent outbreaks until the 18th century [4]; and the most recent 19th century pandemic, in which Y. pestis spread worldwide [5] and became endemic in several regions [6]. The discovery of molecular signatures of Y. pestis in prehistoric Eurasian individuals and two genomes from Southern Siberia suggest that Y. pestis caused some form of disease in humans prior to the first historically documented pandemic [7]. Here, we present six new European Y. pestis genomes spanning the Late Neolithic to the Bronze Age (LNBA; 4,800 to 3,700 calibrated years before present). This time period is characterized by major transformative cultural and social changes that led to cross-European networks of contact and exchange [8, 9]. We show that all known LNBA strains form a single putatively extinct clade in the Y. pestis phylogeny. Interpreting our data within the context of recent ancient human genomic evidence that suggests an increase in human mobility during the LNBA, we propose a possible scenario for the early spread of Y. pestis: the pathogen may have entered Europe from Central Eurasia following an expansion of people from the steppe, persisted within Europe until the mid-Bronze Age, and moved back toward Central Eurasia in parallel with human populations.


Within-Compound Versus Public Latrine Access and Child Feces Disposal Practices in Low-Income Neighborhoods of Accra, Ghana.
In crowded urban settlements in low-income countries, many households rely on shared sanitation facilities. Shared facilities are not currently considered "improved sanitation" because of concerns about whether hygiene conditions sufficiently protect users from the feces of others. Prevention of fecal exposure at a latrine is only one aspect of sanitary safety. Ensuring consistent use of latrines for feces disposal, especially child feces, is required to reduce fecal contamination in households and communities. Household crowding and shared latrine access are correlated in these settings, rendering latrine use by neighbors sharing communal living areas as critically important for protecting one's own household. This study in Accra, Ghana, found that household access to a within-compound basic latrine was associated with higher latrine use by children of ages 5-12 years and for disposal of feces of children < 5 years, compared with households using public latrines. However, within-compound access was not associated with improved child feces disposal by other caregivers in the compound. Feces was rarely observed in household compounds but was observed more often in compounds with latrines versus compounds relying on public latrines. Escherichia coli and human adenovirus were detected frequently on household surfaces, but concentrations did not differ when compared by latrine access or usage practices. The differences in latrine use for households sharing within-compound versus public latrines in Accra suggest that disaggregated shared sanitation categories may be useful in monitoring global progress in sanitation coverage. However, compound access did not completely ensure that households were protected from feces and microbial contamination.


Terahertz single pixel imaging with an optically controlled dynamic spatial light modulator.
We present a single pixel terahertz (THz) imaging technique using optical photoexcitation of semiconductors to dynamically and spatially control the electromagnetic properties of a semiconductor mask to collectively form a THz spatial light modulator (SLM). By co-propagating a THz and collimated optical laser beam through a high-resistivity silicon wafer, we are able to modify the THz transmission in real-time. By further encoding a spatial pattern on the optical beam with a digital micro-mirror device (DMD), we may write masks for THz radiation. We use masks of varying complexities ranging from 63 to 1023 pixels and are able to acquire images at speeds up to 1/2 Hz. Our results demonstrate the viability of obtaining real-time and high-fidelity THz images using an optically controlled SLM with a single pixel detector.


Structural characterization by confocal laser scanning microscopy and electrochemical study of multi-walled carbon nanotube tyrosinase matrix for phenol detection.
A novel visualization methodology based on the use of immunofluorescence and Confocal Laser Scanning Microscopy (CLSM) was used to quantify and visualize tyrosinase enzyme within a MWCNTs matrix immobilized onto carbon based screen-printed electrodes. CLSM was shown to be an extremely powerful technique which allowed a clear visualization of the distribution of the enzyme within both the MWCNTs and carbon based layers and provided additional and useful morphological data for a better understanding of the interaction between biomolecules and electrode materials. Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) were also employed to fully characterize the system components. The proposed MWCNT/Tyrosinase matrix was applied to the detection of phenol, as an alternative biosensor material. Electrochemical analytical performances of the biosensor were investigated in order to determine the optimal fabrication design along with the enzyme stability. The biosensor based on the developed biomaterial matrix proved promising results in terms of cost, simplicity and analytical performance. A detection limit of 1.35 microM and a sensitivity of 47.4 microA mM(-1) within a linear response range of 2.5 to 75 microM phenol were obtained. The biosensor performed well as a disposable device and could be stored in a refrigerator (-18 degrees C) without loss of activity for up to 2 months.


Prospective assessment of the value of computed tomography for trauma.
The use of computed tomography (CT) has helped revolutionize the process and accuracy of diagnosis of the trauma patient. We have noted a striking increase in the use of CT scanning early in the management of trauma patients at our trauma center and sought to assess our experience. All trauma patients admitted to our trauma center from February 1991 to February 1992 who received any CT scan within the first 12 hours after arrival were enrolled in the study. A positive (+) CT scan was defined as a scan that demonstrated a significant finding consistent with the injury and a negative (-) CT scan was one in which there were either no abnormalities or only incidental findings unrelated to the injury. Each patient was followed daily by one of the authors (A.G.R.). Patient records were reviewed and treating surgeons were interviewed to determine whether the CT scan improved the process of therapy. Morbidity incident to the performance of the CT scans was assessed. 1609 trauma patients underwent 2047 CT scans (1.3 CT scans per patient). Sixteen percent (n = 260) had scans of more than one part of the body. Thirty-eight percent (n = 770) of scans were positive but 29% (n = 225) of these were not helpful to the patient care process. Overall, 29% of scans, either because they were positive or negative, assisted in the clinical care of the patient. Six percent (n = 45) of CT scans were falsely positive. Sixty-five percent of scans were true negatives. Two patients died in the CT suite, 6 died shortly after completion of the scan, and 12 required emergency trips to the operating room from the CT suite. A large number of CT scans are being performed in our trauma patient population. Less than 30% contributed to patient management. Because of morbidity and cost, strict surgeon and radiologist oversight of CT for trauma is essential.


High Genomic Variability in Equine Infectious Anemia Virus Obtained from Naturally Infected Horses in Pantanal, Brazil: An Endemic Region Case.
Equine infectious anemia virus (EIAV) is a persistent lentivirus that causes equine infectious anemia (EIA). In Brazil, EIAV is endemic in the Pantanal region, and euthanasia is not mandatory in this area. All of the complete genomic sequences from field viruses are from North America, Asia, and Europe, and only proviral genomic sequences are available. Sequences from Brazilian EIAV are currently available only for gag and LTR regions. Thus, the present study aimed for the first time to sequence the entire EIAV genomic RNA in naturally infected horses from an endemic area in Brazil. RNA in plasma from naturally infected horses was used for next-generation sequencing (NGS), and gaps were filled using Sanger sequencing methodology. Complete viral genomes of EIAV from two horses were obtained and annotated (Access Number: MN560970 and MN560971). Putative genes were analyzed and compared with previously described genes, showing conservation in gag and pol genes and high variations in LTR and env sequences. Amino acid changes were identified in the p26 protein, one of the most common targets used for diagnosis, and p26 molecular modelling showed surface amino acid alterations in some epitopes. Brazilian genome sequences presented 88.6% nucleotide identity with one another and 75.8 to 77.3% with main field strains, such as EIAV Liaoning, Wyoming, Ireland, and Italy isolates. Furthermore, phylogenetic analysis suggested that this Brazilian strain comprises a separate monophyletic group. These results may help to better characterize EIAV and to overcome the challenges of diagnosing and controlling EIA in endemic regions.


An experimental system to study mechanotransduction in fetal lung cells.
Mechanical forces generated in utero by repetitive breathing-like movements and by fluid distension are critical for normal lung development. A key component of lung development is the differentiation of alveolar type II epithelial cells, the major source of pulmonary surfactant. These cells also participate in fluid homeostasis in the alveolar lumen, host defense, and injury repair. In addition, distal lung parenchyma cells can be directly exposed to exaggerated stretch during mechanical ventilation after birth. However, the precise molecular and cellular mechanisms by which lung cells sense mechanical stimuli to influence lung development and to promote lung injury are not completely understood. Here, we provide a simple and high purity method to isolate type II cells and fibroblasts from rodent fetal lungs. Then, we describe an in vitro system, The Flexcell Strain Unit, to provide mechanical stimulation to fetal cells, simulating mechanical forces in fetal lung development or lung injury. This experimental system provides an excellent tool to investigate molecular and cellular mechanisms in fetal lung cells exposed to stretch. Using this approach, our laboratory has identified several receptors and signaling proteins that participate in mechanotransduction in fetal lung development and lung injury.


Effects of environmental noise exposure on DNA methylation in the brain and metabolic health.
Environmental noise exposure is associated with adverse effects on human health including hearing loss, heart disease, and changes in stress-related hormone levels. Alteration in DNA methylation in response to environmental exposures is a well-known phenomenon and it is implicated in many human diseases. Understanding how environmental noise exposures affect DNA methylation patterns may help to elucidate the link between noise and adverse effects on health. In this pilot study we examined the effects of environmental noise exposure on DNA methylation of genes related to brain function and investigated whether these changes are related with metabolic health. We exposed four groups of male Wistar rats to moderate intensity noise (70-75dB with 20-4000Hz) at night for three days as short-term exposure, and for three weeks as long-term exposure. Noise exposure was limited to 45dB during the daytime. Control groups were exposed to only 45dB, day and night. We measured DNA methylation in the Bdnf, Comt, Crhr1, Mc2r, and Snca genes in tissue from four brain regions of the rats (hippocampus, frontal lobe, medulla oblongata, and inferior colliculus). Further, we measured blood pressure and body weight after long-term noise exposure. We found that environmental noise exposure is associated with gene-specific DNA methylation changes in specific regions of the brain. Changes in DNA methylation are significantly associated with changes in body weight (between Bdnf DNA methylation and Δ body weight: r=0.59, p=0.018; and between LINE-1 ORF DNA methylation and Δ body weight: =-0.80, p=0.0004). We also observed that noise exposure decreased blood pressure (p=0.038 for SBP, p=0.017 for DBP and p 0. 017 for MAP) and decreased body weight (β=-26g, p=0.008). In conclusion, environmental noise exposures can induce changes in DNA methylation in the brain, which may be associated with adverse effects upon metabolic health through modulation of response to stress-related hormones.


Oxidative Stress Induced Dysfunction of Protein Synthesis in 661W Mice Photoreceptor Cells.
Photoreceptor cells are highly susceptible to oxidative-stress-induced damage due to their high metabolic rate. Oxidative stress plays a key role in driving pathological events in several different ocular diseases, which lead to retinal degeneration and ultimately blindness. A growing number of studies have been performed to understand downstream events caused by ROS induced oxidative stress in photoreceptor cells; however, the underlying mechanisms of ROS toxicity are not fully understood. To shed light on ROS induced downstream pathological events, we employed a tandem mass tag (TMT) labelling-based quantitative mass-spectrometric approach to determine proteome changes in 661W photoreceptor cells following oxidative stress induction via the application of different concentrations of H2O2 at different time points. Overall, 5920 proteins were identified and quantified, and 450 differentially expressed proteins (DEPs) were identified, which were altered in a dose and time dependent manner in all treatment groups compared to the control group. These proteins were involved in several biological pathways, including spliceosome and ribosome response, activated glutathione metabolism, decreased ECM-receptor interaction, oxidative phosphorylation, abnormally regulated lysosome, apoptosis, and ribosome biogenesis. Our results highlighted ECM receptor interaction, oxidative phosphorylation and spliceosome pathways as the major targets of oxidative stress that might mediate vascular dysfunction and cellular senescence.


Combined in silico/in vivo analysis of mechanisms providing for root apical meristem self-organization and maintenance.
The root apical meristem (RAM) is the plant stem cell niche which provides for the formation and continuous development of the root. Auxin is the main regulator of RAM functioning, and auxin maxima coincide with the sites of RAM initiation and maintenance. Auxin gradients are formed due to local auxin biosynthesis and polar auxin transport. The PIN family of auxin transporters plays a critical role in polar auxin transport, and two mechanisms of auxin maximum formation in the RAM based on PIN-mediated auxin transport have been proposed to date: the reverse fountain and the reflected flow mechanisms. The two mechanisms are combined here in in silico studies of auxin distribution in intact roots and roots cut into two pieces in the proximal meristem region. In parallel, corresponding experiments were performed in vivo using DR5::GFP Arabidopsis plants. The reverse fountain and the reflected flow mechanism naturally cooperate for RAM patterning and maintenance in intact root. Regeneration of the RAM in decapitated roots is provided by the reflected flow mechanism. In the excised root tips local auxin biosynthesis either alone or in cooperation with the reverse fountain enables RAM maintenance. The efficiency of a dual-mechanism model in guiding biological experiments on RAM regeneration and maintenance is demonstrated. The model also allows estimation of the concentrations of auxin and PINs in root cells during development and under various treatments. The dual-mechanism model proposed here can be a powerful tool for the study of several different aspects of auxin function in root.


Predictors of the Effect of Tolvaptan on the Prognosis of Cirrhosis.
Objective Tolvaptan was first approved for use for cirrhosis in Japan in September 2013. The aim of the study was to examine the effect of tolvaptan, a vasopressin V2 receptor antagonist, on the prognosis of cirrhosis. Methods The effect of tolvaptan was evaluated in 26 patients with cirrhosis treated at our hospital from September 2013 to April 2015. Results The primary disease was hepatitis C in 20 patients, hepatitis B in 2, nonalcoholic steatohepatitis in 2 and others in 2; and 12 had hepatocellular carcinoma. The Child-Pugh score was 9.7±1.6 and the serum albumin level was 2.53±0.44 g/dL. Body weight decreased from 55.5±11.8 kg before administration to 52.1±14.7 kg after 7 days of tolvaptan treatment. After 7 days, patients with weight loss ≥2 kg (n=16, mean decrease of 4.3±2.3 kg) had significantly lower blood urea nitrogen (24.2±14.4 vs. 36.1±11.4 mg/dL) and serum creatinine (1.1±0.5 vs. 1.5±0.7 mg/dL) levels and decreased urine osmolality 4 h after the administration of tolvaptan (236±96 vs. 364±122 mOsm/kg) compared with patients with weight loss <2 kg (n=10, mean increase of +0.7±2.1 kg) (all p<0.05). The prognosis was significantly better in the group with weight loss ≥2 kg. Conclusion The effect of tolvaptan on the renal function is likely to improve the prognosis of patients with cirrhosis if the drug is started at a stage in which the renal function is maintained.


The Diagnostic Accuracy of Transvaginal Ultrasound for Detection of Ureteral Involvement in Deep Infiltrating Endometriosis: A Systematic Review and Meta-Analysis.
The aim of this study is to determine the accuracy of transvaginal ultrasound (TVU) for the diagnosis of ureteral involvement in women with deep infiltrating endometriosis (DIE). The meta-analysis included primary studies comparing the use of TVU for diagnosing endometriotic involvement of the ureter, using laparoscopic surgery and histological diagnosis as the reference standard. Search was performed in several databases (Scopus, Web of Science, and PubMed/MEDLINE). The studies' quality and bias risk were assessed using the Quality Assessment of Diagnostic Accuracy Study-2 (QUADAS-2). Diagnostic performance was estimated by assessing pooled sensitivity and specificity. A total of 496 citations were found. Six articles were ultimately selected for this systematic review and meta-analysis after the inclusion and exclusion criteria were applied. Pooled sensitivity and specificity were 0.81 (95% CI: 0.42-0.96), 1.00 (95% CI: 0.93-1.00). The heterogeneity observed was high for both sensitivity and specificity. Overall risk of bias was low. TVU is a valuable tool for the pre-operative identification of ureteral involvement by DIE.


Treatment of coronavirus disease 2019 in Shandong, China: a cost and affordability analysis.
Coronavirus disease 2019 (COVID-19) is now a global public threat. Given the pandemic of COVID-19, the economic impact of COVID-19 is essential to add value to the policy-making process. We retrospectively conducted a cost and affordability analysis to determine the medical costs of COVID-19 patients in China, and also assess the factors affecting their costs. This analysis was retrospectively conducted in Shandong Provincial Chest Hospital between 24 January and 16 March 2020. The total direct medical expenditures were analyzed by cost factors. We also assessed affordability by comparing the simulated out-of-pocket expenditure of COVID-19 cases relative to the per capita disposable income. Differences between groups were tested by student t test and Mann-Whitney test when appropriate. A multiple logistic regression model was built to determine the risk factors associated with high cost. A total of 70 COVID-19 patients were included in the analysis. The overall mean cost was USD 6827 per treated episode. The highest mean cost was observed in drug acquisition, accounting for 45.1% of the overall cost. Total mean cost was significantly higher in patients with pre-existing diseases compared to those without pre-existing diseases. Pre-existing diseases and the advanced disease severity were strongly associated with higher cost. Around USD 0.49 billion were expected for clinical manage of COVID-19 in China. Among rural households, the proportions of health insurance coverage should be increased to 70% for severe cases, and 80% for critically ill cases to avoid catastrophic health expenditure. Our data demonstrate that clinical management of COVID-19 patients incurs a great financial burden to national health insurance. The cost for drug acquisition is the major contributor to the medical cost, whereas the risk factors for higher cost are pre-existing diseases and severity of COVID-19. Improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.


Strength gains by motor imagery with different ratios of physical to mental practice.
The purpose of this training study was to determine the magnitude of strength gains following a high-intensity resistance training (i.e., improvement of neuromuscular coordination) that can be achieved by imagery of the respective muscle contraction imagined maximal isometric contraction (IMC training). Prior to the experimental intervention, subjects completed a 4-week standardized strength training program. 3 groups with different combinations of real maximum voluntary contraction (MVC) and mental (IMC) strength training (M75, M50, M25; numbers indicate percentages of mental trials) were compared to a MVC-only training group (M0) and a control condition without strength training (CO). Training sessions (altogether 12) consisted of four sets of two maximal 5-s isometric contractions with 10 s rest between sets of either MVC or IMC training. Task-specific effects of IMC training were tested in four strength exercises commonly used in practical settings (bench pressing, leg pressing, triceps extension, and calf raising). Maximum isometric voluntary contraction force (MVC) was measured before and after the experimental training intervention and again 1 week after cessation of the program. IMC groups (M25, M50, M75) showed slightly smaller increases in MVC (3.0% to 4.2%) than M0 (5.1%), but significantly stronger improvements than CO (-0.2%). Compared to further strength gains in M0 after 1 week (9.4% altogether), IMC groups showed no "delayed" improvement, but the attained training effects remained stable. It is concluded that high-intensity strength training sessions can be partly replaced by IMC training sessions without any considerable reduction of strength gains.


Prenatal methadone exposure impairs adolescent cognition and GABAergic neurodevelopment in a novel rat model of maternal methadone treatment.
Methadone maintenance treatment (MMT) is the most common treatment for opioid-dependent pregnant women worldwide. Despite its widespread use, MMT is associated with a variety of adverse neurodevelopmental outcomes in exposed offspring, particularly cognitive impairments. The neurobiological abnormalities underlying these cognitive impairments are, however, poorly understood. This is, in part, due to a lack of animal models that represents the standard of care that methadone is administered in the clinic, with inconsistencies in the timing, doses and durations of treatment. Here we describe the characterisation of a clinically relevant rat model of MMT in which the long-term behavioural and neurobiological effects of prenatal methadone exposure can be assessed in adolescent offspring. Female Sprague-Dawley rats were treated orally with an ascending methadone dosage schedule (5, 10, 15, 20, 25 and 30 mg/kg/day), self-administered in drinking water prior to conception, throughout gestation and lactation. Pregnancy success, maternal gestational weight gain, litter survival and size were not significantly altered in methadone-exposed animals. Methadone-exposed offspring body and brain weights were significantly lower at birth. Novel object recognition tests performed at adolescence revealed methadone-exposed offspring had impaired recognition memory. Furthermore, the rewarded T-maze alternation task demonstrated that methadone-exposed female, but not male, offspring also exhibit working memory and learning deficits. Immunoblots of the adolescent prefrontal cortex and hippocampus showed methadone-exposed offspring displayed reduced levels of mature BDNF, in addition to the GABAergic proteins, GAD67 and parvalbumin, in a sex- and brain region-specific fashion. This rat model closely emulates the clinical scenario in which methadone is administered to opioid-dependent pregnant woman and provides evidence MMT can cause cognitive impairments in adolescent offspring that may be underlined by perturbed neurodevelopment of the GABAergic system.


Delay line length selection in generating fast random numbers with a chaotic laser.
The chaotic light signals generated by an external cavity semiconductor laser have been experimentally demonstrated to extract fast random numbers. However, the photon round-trip time in the external cavity can cause the occurrence of the periodicity in random sequences. To overcome it, the exclusive-or operation on corresponding random bits in samples of the chaotic signal and its time-delay signal from a chaotic laser is required. In this scheme, the proper selection of delay length is a key issue. By doing a large number of experiments and theoretically analyzing the interplay between the Runs test and the threshold value of the autocorrelation function, we find when the corresponding delay time of autocorrelation trace with the correlation coefficient of less than 0.007 is considered as the delay time between the chaotic signal and its time-delay signal, streams of random numbers can be generated with verified randomness.


Degraded stimulus visibility and the effects of perceptual load on distractor interference.
In this study we examined whether effects of perceptual load on the attentional selectivity are modulated by degradation of the visual input. According to the perceptual load theory, increasing task difficulty via degradation of stimulus visibility should not alter the typical effect of perceptual load. In previous studies only the target was degraded, resulting in increased distractor saliency. Here we combined manipulation of perceptual load with a more systematic degradation of visual information. Experiment 1 included five conditions. Three conditions involved low perceptual load + contrast reduction of: (A) only the target; (B) only the distractor; (C) both target and distractor. The other two conditions included non-degraded stimuli with low or high perceptual load. In Experiment 2 visibility degradation was established via manipulation of exposure duration. It included two exposure durations-100 and 150 ms-for each load level (low vs. high). The results of both experiments demonstrated reliable distractor interference of a similar magnitude with both degraded and non-degraded stimuli. This finding suggests that task difficulty, when manipulated via degradation of stimulus visibility, does not play a critical role in determining the efficiency of the attentional selectivity. However, contrary to the predictions of the perceptual load theory, in both experiments distractor interference emerged under the high load condition. In Experiment 2 the high-load interference was of the same magnitude as that of the low load condition. This high-load interference is not due to the presence of a mask (Experiment 3) or a mixed design (Experiment 4). These findings suggest that perceptual load may also play a lesser role in attentional selectivity than that assigned to it by the perceptual load theory.


Temporal trends in bleeding events in acute myocardial infarction: insights from the SWEDEHEART registry.
To describe the time trends of in-hospital and out-of-hospital bleeding parallel to the development of new treatments and ischaemic outcomes over the last 20 years in a nationwide myocardial infarction (MI) population. Patients with acute MI (n = 371 431) enrolled in the SWEDEHEART registry from 1995 until May 2018 were selected and evaluated for in-hospital bleeding and out-of-hospital bleeding events at 1 year. In-hospital bleeding increased from 0.5% to a peak at 2% 2005/2006 and thereafter slightly decreased to a new plateau around 1.3% by the end of the study period. Out-of-hospital bleeding increased in a stepwise fashion from 2.5% to 3.5 % in the middle of the study period and to 4.8% at the end of the study period. The increase in both in-hospital and out-of-hospital bleeding was parallel to increasing use of invasive strategy and adjunctive antithrombotic treatment, dual antiplatelet therapy (DAPT), and potent DAPT, while the decrease in in-hospital bleeding from 2007 to 2010 was parallel to implementation of bleeding avoidance strategies. In-hospital re-infarction decreased from 2.8% to 0.6% and out-of-hospital MI decreased from 12.6% to 7.1%. The composite out-of-hospital MI, cardiovascular death, and stroke decreased in a similar fashion from 18.4% to 9.1%. During the last 20 years, the introduction of invasive and more intense antithrombotic treatment has been associated with an increase in bleeding events but concomitant there has been a substantial greater reduction of ischaemic events including improved survival.


Determining the service lives of organic-vapor respirator cartridges for nitroglycerin under workplace conditions.
Results of a field study that estimated the service lives of several different brands of organic-vapor respirator cartridges for nitroglycerin are presented. Respirator carbon tubes (RCTs) were used to sample in a workplace where gun powder was manufactured and where nitroglycerin levels varied from approximately 0.1-0.7 mg/m3. Tenax adsorbent tubes were used to monitor for nitroglycerin upstream and downstream of RCTs and were subsequently analyzed by a gas-chromatography method. A series of 10 trials failed to find evidence of nitroglycerin breakthrough. Estimates of the minimum service lives of respirator cartridges varied from 7-81 hours for nitroglycerin levels of 1.0 mg/m3, 10 times the current Occupational Safety and Health Administration Permissible Exposure Level. One trial specifically examined the potential of nitroglycerin to prematurely break through a cartridge due to bed migration, and results failed to indicate this as a potential problem. A field validation of the Tenax adsorbent tube method for nitroglycerin monitoring resulted in an accuracy of +/- 77-88% at the 95% confidence level. An unexpected finding was that up to 10% of the ambient nitroglycerin collected was adsorbed to an aerosol. This finding led to the recommendation that the addition of a prefilter to an organic vapor cartridge may be required when using air-purifying respirators to protect workers from some nitroglycerin exposures.


Patterns of caffeine consumption.
A cross sectional survey of 4757 Australians to assess usual daily consumption of caffeine from all sources was conducted. Individual variations in type and strength of coffee drunk were noted. Average caffeine consumption was 240 mg/day, equivalent to approximately five 150 ml cups of medium strength instant coffee. One third of the population had intakes at this level or higher and may be considered to be physically dependent on caffeine. Only 3 per cent of the population were true abstainers from caffeine. Caffeine consumption patterns were similar for men and women of all ages, although younger persons consumed more coffee and less tea than older persons. Tea, coffee and caffeine consumption were all positively associated with tobacco consumption, but only tea consumption was significantly correlated with alcohol intake (negatively).


Brevilin A, a Natural Sesquiterpene Lactone Inhibited the Growth of Triple-Negative Breast Cancer Cells via Akt/mTOR and STAT3 Signaling Pathways.
Triple-negative breast cancer (TNBC) is a a breast cancer subtype characterized by a lack of estrogen receptor, progesterone receptor and human epidermal growth receptor 2 and is associated with poorer prognoses when compared to other breast cancers. Thus, novel anti-cancer agents with high efficacy are urgently needed. Brevilin A (BA), a natural sesquiterpene lactone, has been reported to exhibit anti-cancer effects. However, the effects of BA on TNBC have not yet been demonstrated. In this study, we investigated the anti-TNBC effects and the underlying mechanism of BA, in vitro and in vivo. Two TNBC cell lines and a xenograft mouse model were employed to assess the effects of BA. Cell viability was detected by MTT assay. Cell cycle status and apoptosis were evaluated by flow cytometry. Cell migration was measured by wound-healing assay. Protein expression was measured by Western blotting analysis. The in vivo anti-cancer activity of BA was assessed in orthotopic tumor xenograft mice. BA significantly inhibited the growth of TNBC cells in a dose- and time-dependent manner via induction of cell cycle arrest at G2/M phase arrest and apoptosis. BA also inhibited tumor cell migration. BA significantly downregulated the expression of Akt, mTOR, Stat3 and their phosphorylation, and thus inhibiting the activation of the Akt/mTOR and STAT3 signaling pathways. Furthermore, oral administration of BA at 25 or 50 mg/kg leads to significant inhibition of tumor growth and proliferation in tumor xenograft model mice. BA significantly inhibited the growth and migration of TNBC cells, and induced cell cycle arrest and apoptosis. These inhibitory effects were associated with the suppression of the Akt/mTOR and Stat3 signal pathways. Based on our findings, BA possesses a promising candidate for development as an anti-cancer therapeutic drug against TNBC.


Treatment of Sciatica and Lumbar Radiculopathy with an Intervertebral Foramen Opening Protocol: Pilot Study in a Hospital Emergency and In-patient Setting.
Perform a pilot study of a static nerve root foramen opening protocol for lumbar radiculopathy from disc hernia in an emergency hospital setting to establish if patients could execute the protocol, consistency would occur across outcomes, superior outcomes would occur in the experimental group, and if the protocol would be safe. Patients with sciatica arrived of their own volition at the local emergency hospital department, were admitted for care and were randomized into two groups: 1) control (n = 10): forward bending, walking, and medication; and 2) experimental (n = 10) as control subjects, plus a static lumbar foramen opening protocol using flexion and contralateral lateral flexion (side-lying). Outcomes were back and leg pain (i.e. visual analog scale), disability (i.e. EuroQol5D5L and Oswestry) and straight leg raise. At admission, the baseline outcome variables between groups were not significantly different. All patients had moderate or large disc hernias on MRI and 75% had neurological deficits in electrophysiology. At discharge, patients in the experimental group were significantly better (p ≤ .05) than controls in all outcomes. Statistical analysis of the outcomes produced greater significance, effect sizes and minimal clinically important differences in the experimental group. Patients in the experimental group consumed less medication than control patients (21% versus 79%), including less than half the opioids (tramadol). No adverse responses occurred. Patients could perform the protocol and superior outcomes occurred, with no adverse effects. The data support more detailed study of therapeutic efficacy, days in hospital, costs, conversion to surgery, and medication consumption, including opioids.


FGF21 as a Stress Hormone: The Roles of FGF21 in Stress Adaptation and the Treatment of Metabolic Diseases.
Fibroblast growth factor 21 (FGF21) is an endocrine hormone that is primarily expressed in the liver and exerts beneficial effects on obesity and related metabolic diseases. In addition to its remarkable pharmacologic actions, the physiological roles of FGF21 include the maintenance of energy homeostasis in the body in conditions of metabolic or environmental stress. The expression of FGF21 is induced in multiple organs in response to diverse physiological or pathological stressors, such as starvation, nutrient excess, autophagy deficiency, mitochondrial stress, exercise, and cold exposure. Thus, the FGF21 induction caused by stress plays an important role in adaptive response to these stimuli. Here, we highlight our current understanding of the functional importance of the induction of FGF21 by diverse stressors as a feedback mechanism that prevents excessive stress.