Family with Sequence Similarity 83 Member H Promotes the Viability and Metastasis of Cervical Cancer Cells and Indicates a Poor Prognosis.
Family with sequence similarity 83 member H (FAM83H) plays key roles in tumorigenesis. However, the specific roles of FAM83H in cervical cancer (CC) have not been well studied. The RNA-seq data of 306 CC tissues and three normal samples downloaded from The Cancer Genome Atlas were used to analyze the expression of FAM83H. The Kaplan-Meier method was used to draw survival curves. Associations between FAM83H expression and clinicopathological factors were analyzed by chi-square test. Cox proportional hazards model was used to analyze prognostic factors. Loss-of-function assays were conducted to discover the biological functions of FAM83H in cell proliferation, colony formation, invasion, and migration. Real-time Quantitative Reverse Transcription PCR (qRT-PCR) and Western blotting were used to measure the expression levels of FAM83H in CC cell lines. Our results demonstrated that FAM83H is overexpressed in CC tissues and that high FAM83H expression is associated with worse overall survival (OS). High FAM83H expression in CC was associated with clinical stage, pathologic tumor, and pathologic node. Univariate analysis suggested that FAM83H expression was significantly related to the OS of CC patients. Although multivariate analysis showed that FAM83H expression was not an independent prognostic factor for the OS of CC patients, the effects of FAM83H on CC cell growth and motility was significant. Loss-of-function experiments demonstrated that knockdown of FAM83H inhibited proliferation, colony formation, migration, and invasion of CC cells by inactivating PI3K/AKT pathway. FAM83H might play a crucial role in CC progression and could act as a novel therapeutic target in CC.


Growth arrest-specific gene 6 and Axl signaling enhances gastric cancer cell survival via Akt pathway.
Activation of tyrosine kinases is an important factor during cancer development. Axl, one of the receptor tyrosine kinases, binds to the specific ligand growth arrest-specific gene 6 (Gas6), which encodes a vitamin K-dependent gamma-carboxyglutamyl protein. Although many receptor tyrosine kinases and their ligands are involved in gastric carcinogenesis, whether Gas6-Axl signaling is involved in gastric carcinogenesis has not been elucidated. The aim of this study was to investigate the expression of Gas6 and Axl in gastric cancer and also their roles during gastric carcinogenesis. mRNA and protein of Gas6 and Axl were highly expressed in a substantial proportion of human gastric cancer tissue and cell lines, and Gas6 expression was significantly associated with lymph node metastasis. With recombinant Gas6 and a decoy-receptor of Axl in vitro, we demonstrated that Gas6-Axl signaling pathway enhanced cellular survival and invasion and suppressed apoptosis via Akt pathway. Our results suggests that Gas6-Axl signaling plays a role during gastric carcinogenesis, and that targeting Gas6-Axl signaling could be a novel therapeutic for gastric cancer.


Characterization by EPR spectroscopy of cytochrome b-562 isolated from the cytochrome b-c1 complex of Rhodopseudomonas sphaeroides R-26.
The EPR spectra of cytochrome b-562 isolated from the cytochrome b-c1 complex of Rhodopseudomonas sphaeroides were measured at liquid helium temperature. The purified cytochrome b-562 gives a high spin signal at g = 6.0. Anaerobic titration of this signal confirmed the presence of two redox components with Em = 40 and -110 mV at pH 7.5. These values are consistent with the published ones, Em = 55 and -100 mV at pH 7.0, that were optically estimated for the same type of preparation (Iba et al. (1985) FEBS Lett. 183, 151-154). The power saturation behavior of the g = 6.0 signal at different redox potentials indicated a direct spin-spin interaction between these two redox centers.


Differences Between Cancer-Specific Survival of Patients With Anaplastic and Primary Squamous Cell Thyroid Carcinoma and Factors Influencing Prognosis: A SEER Database Analysis.
Anaplastic thyroid carcinoma (ATC) and primary squamous cell carcinoma of the thyroid (PSCCTh) have similar histological findings and are currently treated using the same approaches; however, the characteristics and prognosis of these cancers are poorly researched. The objective of this study was to determine the differences in characteristics between ATC and PSCCTh and establish prognostic models. All variables of patients with ATC and PSCCTh, diagnosed from 2004-2015, were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) database. Percentage differences for categorical data were compared using the Chi-square test. Kaplan-Meier curves, log-rank test, and Cox-regression for survival analysis, and C-index value was used to evaluate the performance of the prognostic models. After application of the inclusion and exclusion criteria, a total of 1164 ATC and 124 PSCCTh patients, diagnosed from 2004 to 2015, were included in the study. There were no differences in sex, ethnicity, age, marital status, or percentage of proximal metastases between the two cancers; however, radiotherapy, chemotherapy, incidence of surgical treatment, and presence of multiple primary tumors were higher in patients with ATC than those with PSCCTh. Further cancer-specific survival (CSS) of patients with PSCCTh was better than that of patients with ATC. Prognostic factors were not identical for the two cancers. Multivariate Cox model analysis indicated that age, sex, radiotherapy, chemotherapy, surgery, multiple primary tumors, marital status, and distant metastasis status are independent prognostic factors for CSS in patients with ATC, while for patients with PSCCTh, the corresponding factors are age, radiotherapy, multiple primary tumors, and surgery. The C-index values of the two models were both > 0.8, indicating that the models exhibited good discriminative ability. Prognostic factors influencing CSS were not identical in patients with ATC and PSCCTh. These findings indicate that different clinical treatment and management plans are required for patients with these two types of thyroid cancer.


Shrinkage Clustering: a fast and size-constrained clustering algorithm for biomedical applications.
Many common clustering algorithms require a two-step process that limits their efficiency. The algorithms need to be performed repetitively and need to be implemented together with a model selection criterion. These two steps are needed in order to determine both the number of clusters present in the data and the corresponding cluster memberships. As biomedical datasets increase in size and prevalence, there is a growing need for new methods that are more convenient to implement and are more computationally efficient. In addition, it is often essential to obtain clusters of sufficient sample size to make the clustering result meaningful and interpretable for subsequent analysis. We introduce Shrinkage Clustering, a novel clustering algorithm based on matrix factorization that simultaneously finds the optimal number of clusters while partitioning the data. We report its performances across multiple simulated and actual datasets, and demonstrate its strength in accuracy and speed applied to subtyping cancer and brain tissues. In addition, the algorithm offers a straightforward solution to clustering with cluster size constraints. Given its ease of implementation, computing efficiency and extensible structure, Shrinkage Clustering can be applied broadly to solve biomedical clustering tasks especially when dealing with large datasets.


Abundance and diversity of bacterial nitrifiers and denitrifiers and their functional genes in tannery wastewater treatment plants revealed by high-throughput sequencing.
Biological nitrification/denitrification is frequently used to remove nitrogen from tannery wastewater containing high concentrations of ammonia. However, information is limited about the bacterial nitrifiers and denitrifiers and their functional genes in tannery wastewater treatment plants (WWTPs) due to the low-throughput of the previously used methods. In this study, 454 pyrosequencing and Illumina high-throughput sequencing, combined with molecular methods, were used to comprehensively characterize structures and functions of nitrification and denitrification bacterial communities in aerobic and anaerobic sludge of two full-scale tannery WWTPs. Pyrosequencing of 16S rRNA genes showed that Proteobacteria and Synergistetes dominated in the aerobic and anaerobic sludge, respectively. Ammonia-oxidizing bacteria (AOB) amoA gene cloning revealed that Nitrosomonas europaea dominated the ammonia-oxidizing community in the WWTPs. Metagenomic analysis showed that the denitrifiers mainly included the genera of Thauera, Paracoccus, Hyphomicrobium, Comamonas and Azoarcus, which may greatly contribute to the nitrogen removal in the two WWTPs. It is interesting that AOB and ammonia-oxidizing archaea had low abundance although both WWTPs demonstrated high ammonium removal efficiency. Good correlation between the qPCR and metagenomic analysis is observed for the quantification of functional genes amoA, nirK, nirS and nosZ, indicating that the metagenomic approach may be a promising method used to comprehensively investigate the abundance of functional genes of nitrifiers and denitrifiers in the environment.


Cryptotanshinone induces ROS-mediated apoptosis in human gastric cancer cells.
Cryptotanshinone (CT), isolated from the plant Salvia miltiorrhiza Bunge, has been reported to have potential anticancer effects on human prostate and breast cancer cells. However, the mechanisms of action of CT on gastric cancer (GC) cells are not well understood. Here we investigated the antitumor effects of CT on GC cells and its possible molecular mechanism. We found CT suppressed viability of twelve GC cell lines in a dose-dependent manner. CT induced cell cycle arrest at the G2/M phase and mitochondrial apoptosis accompanying the accumulation of reactive oxygen species (ROS). Pretreatment with ROS inhibitor N-acetyl-L-cysteine (NAC) blocked CT-induced apoptosis. CT increased p-JNK and p-p38, and decreased p-ERK and p-STAT3 protein expression, these effects were prevented by NAC. Furthermore, a xenograft assay showed that CT significantly inhibited MKN-45 cell-induced tumor growth in vivo by increasing expression of pro-apoptotic proteins (p-JNK, p-38 and cleaved-caspase-3) and reducing expression of anti-apoptotic proteins (p-ERK and p-STAT3) without adverse effects on nude mice weight. In conclusion, CT induced apoptosis and cell cycle arrest in GC cells via ROS-mediated MAPK and AKT signaling pathways, and this CT may be a useful compound for the developing anticancer agents for GC.


NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation.
NMDA receptors (NMDAR) are important in the development and maintenance of central sensitization. Our objective was to investigate the role of spinal neurons and NMDAR in the maintenance of chronic visceral pain. Neonatal rats were injected with acidic saline adjusted to pH 4.0 in the gastrocnemius muscle every other day for 12 days. In adult rats, NR1 and NR2B subunits were examined in the lumbo-sacral (LS) spinal cord. A baseline, visceromotor response (VMR) to graded colorectal distension (CRD) was recorded before and after administration of the NMDA antagonist, CGS-19755. Extracellular recordings were performed from CRD-sensitive LS spinal neurons and pelvic nerve afferents (PNA) before and after CGS-19755. Rats that received pH 4.0 saline injections demonstrated a significant increase in the expression NR2B subunits and VMR response to CRD>20 mmHg. CGS-19755 (i.v. or i.t.) had no effect in naïve rats, but significantly decreased the response to CRD in pH 4.0 saline injected rats. CGS-19755 had no effect on the spontaneous firing of SL-A, but decreased that of SL-S. Similarly, CGS-19755 attenuates the responses of SL-S neurons to CRD, but had no effect on SL-A neurons or on the response characteristics of PNA fibers. Neonatal noxious somatic stimulation results in chronic visceral hyperalgesia and sensitizes a specific subpopulation of CRD-sensitive spinal neurons. The sensitization of these SL-S spinal neurons is attenuated by the NMDAR antagonist. The results of this study suggest that spinal NMDARs play an important role in the development of hyperalgesia early in life.


Evaluation of coagulation parameters: Coronavirus disease 2019 (COVID-19) between survivors and nonsurvivors.
This study aims to investigate and compare the coagulation parameters of coronavirus disease 2019 (COVID-19) patients with mortal and nonmortal conditions. In this study, 511 patients diagnosed with COVID-19 were included. Information about 31 deceased and 480 recovered COVID-19 patients was obtained from the hospital information management system and analyzed retrospectively. Whether there was a correlation between coagulation parameters between the mortal and nonmortal patients was analyzed. Descriptive analyses on general characteristics of the study population were performed. Visual (probability plots and histograms) and analytical methods (Kolmogorov-Smirnov and Shapiro-Wilk test) were used to test the normal distribution. Analyses were performed using the SPSS statistical software package. Out of 511 patients, 219 (42.9%) were females and 292 (57.1%) were males. There was no statistically significant difference between males and females in terms of mortality (p=0.521). In total, the median age was 67 (22). The median age was 74 (13) in the nonsurvivor group and 67 (22) in the survivor group, and the difference was statistically significant (p=0.007). The D-dimer, prothrombin time, international normalized ratio, neutrophil, and lymphocyte median age values with p-values, in the recovered and deceased patient groups were: 1070 (2129), 1990 (7513) μg FEU/L, p=0.005; 12.6 (2.10), 13.3 (2.1), p=0.014; 1.17 (0.21), 1.22 (0.19), p=0.028; 5.51 (6.15), 8.54 (7.05), p=0.001; and 0.99 (0.96), 0.64 (0.84), p=0.037, respectively, with statistically significant differences. As a result of this study, D-dimer, prothrombin time, and international normalized ratio increase were found to be associated with mortality. These parameters need to be closely monitored during the patient follow-up.


Contextual factors associated with running demands in elite Australian football: a scoping review.
To identify and summarise the contextual factors associated with running demands in elite male Australian football (AF) gameplay that have been reported in the literature. Scoping review. A contextual factor in sporting gameplay is a variable associated with the interpretation of results, yet is not the primary objective of gameplay. Systematic literature searches were performed in four databases to identify what contextual factors associated with running demands in elite male AF have been reported: Scopus, SPORTDiscus, Ovid Medline and CINAHL, for terms constructed around Australian football AND running demands AND contextual factors. The present scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and narrative synthesis was conducted. A total of 36 unique articles were identified by the systematic literature search, which included 20 unique contextual factors. The most studied contextual factors were position (n = 13), time in game (n = 9), phases of play (n = 8), rotations (n = 7) and player rank (n = 6). Multiple contextual factors, such as playing position, aerobic fitness, rotations, time within a game, stoppages, and season phase appear to correlate with running demands in elite male AF. Many identified contextual factors have very limited published evidence and thus additional studies would help draw stronger conclusions.


Hemorheological changes caused by intermittent Pringle (Baron) maneuver in beagle canine model.
In liver resection operations the Pringle (Baron) maneuver can be used for temporary ischemia by clamping the hepatoduodenal ligament intermittently. In this beagle canine model we investigated whether hemorheological parameters may alter in systemic, portal and hepatic venous blood and in arterial samples during-after Pringle maneuvers. In Pringle Group unilateral femoral artery and external jugular vein were cannulated. From median laparotomy the hepatoduodenal ligament was exposed. The portal venous system was catheterized via a mesenteric vein and through the inferior caval vein a catheter was led to the hepatic veins. After stabilization, a 15-minute Pringle maneuver was carried out three times with 5-minute interpolated reperfusion periods. In Control Group Pringle maneuvers were not made. Before and after Pringle maneuvers parallel blood samples were taken from the cannulated vessels for determining hematological parameters and erythrocyte aggregation. Following Pringle maneuvers erythrocyte deformability, blood and plasma viscosity were also tested. The results showed that besides systemic hemorheological effects of the intermittent Pringle maneuver local leukocyte count, hematocrit and erythrocyte aggregation index altered mainly in portal venous blood, depending on the repeating number of the maneuvers. Thus, investigations of hemorheological parameters might be useful to determine the optimal duration of the Pringle maneuver.


Theoretical analysis of continuous pitch evolution and reversed phase sequence in antiferroelectric liquid crystals.
Recent studies reported continuous shortening of the pitch from more than four layers to less than four layers in the helicoidally modulated tilted Sm C(alpha)* phase. In a different system, the reversed phase sequence was found: the ferroelectric tilted Sm C* phase appeared below the four-layer Sm CFI2* phase upon cooling. In this contribution we quantitatively explain the behavior within the discrete phenomenological model and we found that both behaviors are the consequence of the same reason: the quadrupolar interlayer interactions.


Expression of major photosynthetic and salt-resistance genes in invasive reed lineages grown under elevated CO2 and temperature.
It is important to investigate the molecular causes of the variation in ecologically important traits to fully understand phenotypic responses to climate change. In the Mississippi River Delta, two distinct, sympatric invasive lineages of common reed (Phragmites australis) are known to differ in several ecophysiological characteristics and are expected to become more salt resistant due to increasing atmospheric CO2 and temperature. We investigated whether different patterns of gene expression can explain their ecophysiological differences and increased vigor under future climatic conditions. We compared the transcript abundance of photosynthetic genes of the Calvin cycle (Rubisco small subunit, RbcS; Phosphoglycerate kinase, PGK; Phosphoribulokinase, PRK), genes related with salt transport (Na(+)/H(+) antiporter, PhaNHA) and oxidative stress response genes (Manganese Superoxide dismutase, MnSOD; Glutathione peroxidase, GPX), and the total aboveground biomass production between two genotypes representing the two lineages. The two genotypes (Delta-type, Mediterranean lineage, and EU-type, Eurasian lineage) were grown under an ambient and a future climate scenario with simultaneously elevated CO2 and temperature, and under two different soil salinities (0‰ or 20‰). We found neither differences in the aboveground biomass production nor the transcript abundances of the two genotypes, but soil salinity significantly affected all the investigated parameters, often interacting with the climatic conditions. At 20‰ salinity, most genes were higher expressed in the future than in the ambient climatic conditions. Higher transcription of the genes suggests higher abundance of the protein they code for, and consequently increased photosynthate production, improved stress responses, and salt exclusion. Therefore, the higher expression of these genes most likely contributed to the significantly ameliorated salinity impact on the aboveground biomass production of both P. australis genotypes under elevated temperature and CO2. Although transcript abundances did not explain differences between the lineages, they correlated with the increased vigor of both lineages under anticipated future climatic conditions.


Association between body mass index and pain following transobturator sling.
We aimed to prospectively evaluate the association between body mass index (BMI) and development of postoperative-onset pain in women undergoing transobturator midurethral sling procedures. We conducted a prospective, observational cohort study of women undergoing inside-to-out transobturator midurethral sling. At preoperative visit, height, weight, self-reported activity level and baseline pain were documented. At postoperative visits, patients indicated pain location and severity, procedure success, and satisfaction. We used log binomial regression to calculate risk ratios, controlling for potential confounders. For the 129 women included, median age was 50.0 years and BMI was 27.2 kg/m2. Adjusting for age and activity level, overweight and obese women had significantly increased risk of postoperative-onset pain compared to normal BMI women. Overweight women were at 1.70 (95%CI 1.05-2.75) times the risk compared to leaner counterparts, whereas obese women were at 1.76 times the risk (95%CI 1.04-2.89). Neither success nor satisfaction was associated with BMI. Impact statement Over three million midurethral slings have been placed worldwide for the treatment or prevention of stress urinary incontinence. The procedure has been studied in lean, overweight and obese populations, and found to have similar efficacy regardless of BMI. Similarly, the risks of midurethral sling have been well-documented, including the risk of pain after transobturator sling. Little attention has been given to whether this risk of postoperative pain varies based on patient BMI. Our previous work suggesting that leaner patients might be at increased risk of postoperative pain following transobturator sling was limited by the shortcomings of a retrospective study design. In this prospective study, we were able to adjust for age and activity level, finding that higher BMI women were at increased risk of postoperative pain, while reporting similar levels of satisfaction with the procedure. Future research is needed to find what differences in anatomy or physiology can explain this finding. From a clinical standpoint, thorough counselling of all patients but particularly those with elevated BMI, is required so that appropriate expectations regarding recovery can be set preoperatively.


Production, bioactivities and bioavailability of bioactive peptides derived from walnut origin by-products: a review.
Walnut-origin by-products obtained from walnut oil extraction industry are high in proteins with various physiological functions and pharmacological properties and an extensive potential for usage in producing bioactive peptides. This review presents the current research status of bioactive peptides derived from walnut by-products, including preparation, separation, purification, identification, bioactivities, and bioavailability. A plethora of walnut peptides with multiple biological activities, including antioxidative, antihypertensive, neuroprotective, antidiabetic, anticancer, and antihyperuricemia activities, were obtained from walnut-origin by-products by enzymatic hydrolysis, fermentation, and synthesis. Different bioactive peptides show various structural characteristics and amino acid composition due to their diverse mechanism of action. Furthermore, walnut protein and its hydrolysate present a high bioavailability in human gastrointestinal digestive system. Improving the bioavailability of walnut peptides is needful in the development of walnut industry. However, future research still needs to exploit energy conservation, high efficiency, environmentally friendly and low-cost production method of walnut bioactive peptide. The molecular mechanisms of different bioactive walnut peptides still need to be explored at the cell and gene levels. Additionally, the digestion, absorption, and metabolism processes of walnut peptides are also the focus of future research.


Effects of human plasma proteins on maturation of monocyte-derived dendritic cells.
Dendritic cells (DC) are a promising tool for vaccine therapy due to their unique properties as antigen presenting cells and their ability to prime naïve T cells. Increasing evidence suggests that maturation stage of DC critically influences the fate of the immune response. Generation of monocyte-derived DC for clinically applicable immunotherapy requires the use of well-defined components and stringent culture conditions. An alternative strategy is to use human autologous serum. However, its constituents are not stable and reflect the inflammatory condition of the donor. In order to investigate whether DC properties are influenced by proteins present in the plasma, we matured human monocyte-derived DC with four main plasma components: fibrinogen, fibronectin, plasminogen or C-reactive protein. These purified proteins were added at various concentrations on day 6 after the initial differentiation induced by IL-4 and GM-CSF. The maturation was assessed by phenotyping of maturation-associated marker (CD83) and co-stimulatory molecule CD86 as well as IL-12 production. Functional properties of DC were assessed by endocytic activity and mixed leukocyte culture. Our results indicate that fibrinogen had DC-maturation effect comparable to poly-I:C, TNF-alpha and PGE(2) as a positive control, but it failed to induce IL-12 production. The other plasma proteins had no effect on DC maturation. CRP at high concentration had rather inhibitory effect on DC induced lymphocyte function. We conclude that none of the tested plasma components and acute phase proteins sufficiently induce fully competent mature DC. This finding is important for the preparation of human DC-based vaccines supplemented by autologous sera.


Differences in testing, stigma, and perceived consequences of stigmatization among heterosexual men and women living with HIV in Bengaluru, India.
Approximately 2.4 million people in India are living with HIV. Gender inequality affects HIV prevention, detection, and management. The purpose of this paper was to describe gender differences in the experience of living with HIV in Bengaluru, India. A subsample of n = 313 (159 men and 154 women) from a larger cohort was used for these analyses. Participants were recruited through AIDS service organizations. They completed an interviewer-administered survey assessing HIV testing experience, types of stigma, and perceived consequences of stigmatization. The majority of men (67%) reported getting HIV tested because of illness, while women were more likely to be tested after learning their spouse's HIV-positive status (42%). More men (59%) than women (45%, p<0.05) were tested in private care settings. Men reported significantly higher mean levels of internalized stigma (men: M=0.71, SD = 0.63; women: M=0.46, SD = 0.55; p<0.001), whereas the women reported significantly higher scores for enacted stigma (men: M=1.30, SD = 1.69; women: M=2.10, SD = 2.17; p<0.001). These differences remained significant after controlling for potential socio-demographic covariates. Following their diagnosis, more women reported moving out of their homes (men: 16%; women: 26%; p<0.05). More men (89%) than women (66%; p<0.001) reported to have modified their sexual behavior after being diagnosed. These findings suggest that the experience of living with HIV and HIV stigma varies by gender in this population. Suggestions for a gender-based approach to HIV prevention and stigma reduction are provided.


[Protection of the Croatian population from accidental radioactive contamination of the food chain].
The paper indicates the importance of investigating radionuclide translocation in the human food chain, and the contribution of selected food components in total exposure of the population after accidental radioactive contamination. Data on radioactive contamination and risk assessment of the Croatian population after the Chernobyl nuclear accident are given and possibilities of decontamination of food chain components are discussed. Literature data on radionuclide removal from the human food chain are compared to the results of own investigations. Emphasis is placed on biologically most important radionuclides, 131I, 90Sr, 137Cs, and the most effective means of protection are sought. The preventive measures following a nuclear accident should be based on the cost-benefit principle i.e. the damage from applying radiation protection measures should not exceed the benefit from possible dose reduction.


Night shift work and breast cancer risk: a meta-analysis of observational epidemiological studies.
Previous observational epidemiological studies have reported inconsistently the association between night shift work (NSW) and the risk of breast cancer (BC). This study aimed to investigate those associations by using a meta-analysis of observational epidemiological studies. We searched PubMed and EMBASE using keywords related to this topic from inception till November 2020. The pooled effect sizes such as odds ratio (OR), hazard ratio (HR) or relative risk (RR) with 95% confidence interval (CI) were calculated using a random-effects model. In the meta-analysis of a total of 32 observational studies including 13 case-control studies, 4 nested case-control studies and 15 cohort studies, NSW significantly increased the risk of BC (OR/RR/HR, 1.11; 95% CI, 1.04-1.20; I2 = 72.4%). In the subgroup meta-analysis by type of study, NSW was also associated with the increased risk of BC in case-control studies (OR, 1.34; 95% CI, 1.17-1.53; I2 = 63.8%). However, no significant association was found in both nested case-control studies (OR, 1.14; 95% CI, 0.89-1.46; I2 = 65.8%) and cohort studies (RR/HR, 0.98; 95% CI, 0.93-1.03; I2 = 25.3%). Besides, there was no significant association between NSW for over 20 years and the risk of BC (OR/RR/HR, 1.03; 95% CI, 0.95-1.11; I2 = 36.6%, n = 14). Given that cohort studies provide higher evidence than case-control studies, there is no association between NSW and the risk of BC.


Analytical expressions for the fourth virial coefficient of a hard-sphere mixture.
A method of numerical calculation of the fourth virial coefficients of the mixture of additive hard spheres is proposed. The results are compared with an exact analytical formula for the fourth partial virial coefficient B4[1] (i.e., three spheres of diameters sigma1 and one sphere of diameter sigma2) and a semiempirical expression for B4[2] (i.e., two spheres of each kind). It is shown that the first formula is nonanalytic and the implication to the equations of state for hard-sphere mixtures is discussed.


Does global positioning system-based navigation dependency make your sense of direction poor? A psychological assessment and eye-tracking study.
Global positioning system (GPS)-based navigation apps are very useful in our lives. However, whether and how the usage of these apps affects spatial cognition and the sense of direction is still unclear. A total of 108 individuals were recruited and completed the GPS dependence, internet gaming behavior, and impulsivity test using scales. The eye-tracking-based general mental rotation (MR) task and target finding (TF; require individuals to find a target specified in a 3D street map in a rotated version of top 2D view map) task were used to assess their spatial cognition and the sense of direction. The correlation was used to relate GPS navigation usage, spatial cognition ability, and impulsivity. Subgroup analyses stratifying by gaming hours of individuals (< 2 h or ≥ 2 h) or maps (countryside or city) in TF task were performed. The moderating and mediating effect analyses were conducted to verify these relationships. The GPS dependency score was nominal positively correlated with fixations in the TF task in the entire cohort (r = 0.202, unadjusted p = 0.036); it was significant in city (r = 0.254, p = 0.008) and gaming time of < 2 h (r = 0.459, p = 0.001) subgroups. The high-score (upper 30%) group of GPS dependency had more fixations on the original target building in the training area and indicative building in the test area than the low-score (lower 30%) group. GPS dependency was not associated with the correct rate and reaction time in the TF task or any of the indicators in the MR task (p > 0.05). The GPS dependency mediated the indirect effect of impulsivity on the fixations on TF. The internet gaming time moderated the association between GPS dependency and fixations on TF. The dependency on GPS-based navigation apps was associated with impaired spatial cognition but may not significantly affect the sense of direction.


Host Genetics of Response to Porcine Reproductive and Respiratory Syndrome in Sows: Reproductive Performance.
Porcine Reproductive and Respiratory Syndrome (PRRS) is historically the most economically important swine disease worldwide that severely affects the reproductive performance of sows. However, little is still known about the genetic basis of reproductive performance in purebred herds during a PRRS outbreak through the comparison of maternal and terminal breeds. Thus, the objective of this work was to explore the host genetics of response to PRRS in purebred sows from two breeds. Reproductive data included 2546 Duroc and 2522 Landrace litters from 894 and 813 purebred sows, respectively, which had high-density genotype data available (29,799 single nucleotide polymorphisms; SNPs). The data were split into pre-PRRS, PRRS, and post-PRRS phases based on standardized farrow-year-week estimates. Heritability estimates for reproductive traits were low to moderate (≤0.20) for Duroc and Landrace across PRRS phases. On the other hand, genetic correlations of reproductive traits between PRRS phases were overall moderate to high for both breeds. Several associations between MARC0034894, a candidate SNP for response to PRRS, with reproductive performance were identified (P-value < 0.05). Genomic analyses detected few QTL for reproductive performance across all phases, most explaining a small percentage of the additive genetic variance (≤8.2%, averaging 2.1%), indicating that these traits are highly polygenic. None of the identified QTL within a breed and trait overlapped between PRRS phases. Overall, our results indicate that Duroc sows are phenotypically more resilient to PRRS than Landrace sows, with a similar return to PRRS-free performance between breeds for most reproductive traits. Genomic prediction results indicate that genomic selection for improved reproductive performance under a PRRS outbreak is possible, especially in Landrace sows, by training markers using data from PRRS-challenged sows. On the other hand, the high genetic correlations with reproductive traits between PRRS phases suggest that selection for improved reproductive performance in a clean environment could improve performance during PRRS, but with limited efficiency due to their low heritability estimates. Thus, we hypothesize that an indicator trait that could be indirectly selected to increase the response to selection for these traits would be desirable and would also improve the reproductive performance of sows during a PRRS outbreak.


Fluorination Enhances the Osteogenic Capacity of Porcine Hydroxyapatite.
In a previous study, we successfully prepared fluorinated porcine hydroxyapatite (FPHA) by immersing porcine hydroxyapatite (PHA) in an aqueous solution of 0.25 M sodium fluoride (NaF) under thermal treatment, and the resulting FPHA showed better physicochemical and biological properties than PHA. The purpose of this study was to further investigate how fluorine incorporation influenced the biocompatibility and osteogenic capacity of PHA. The concentrations of Ca, P, F, and Mg ions in PHA and FPHA extracts were detected by inductively coupled plasma optical emission spectrometry. Rat bone marrow stromal cells (rBMSCs) were treated with PHA and FPHA extracts, and the effects of these extracts on cell proliferation and osteoblastic differentiation were evaluated via Cell Counting Kit-8 assay, alkaline phosphatase assay, and real time-quantitative polymerase chain reaction. For the in vivo assessment, PHA and FPHA were implanted into subcutaneous pockets (n = 6) and rat calvarial defects (diameter = 5 mm, n = 14) for 12 weeks to determine their biocompatibility and osteogenic capacity by using micro-computed tomography (CT) and histological analysis. FPHA extracts, which release higher concentrations of F and Mg ions, better promoted the osteoblastic differentiation of rBMSCs in vitro. The result of biocompatibility evaluation confirmed that the host response and chronic inflammation cells infiltration degree around PHA and FPHA granules were similar. Micro-CT and histological analysis showed newer mineralized bone formation in rats with FPHA-treated defects than in rats with PHA-treated defects. The results of in vitro and in vivo tests consistently indicate that fluorine incorporation effectively enhanced the osteogenic capacity of PHA.


OsCNGC13 promotes seed-setting rate by facilitating pollen tube growth in stylar tissues.
Seed-setting rate is a critical determinant of grain yield in rice (Oryza sativa L.). Rapid and healthy pollen tube growth in the style is required for high seed-setting rate. The molecular mechanisms governing this process remain largely unknown. In this study, we isolate a dominant low seed-setting rate rice mutant, sss1-D. Cellular examination results show that pollen tube growth is blocked in about half of the mutant styles. Molecular cloning and functional assays reveals that SSS1-D encodes OsCNGC13, a member of the cyclic nucleotide-gated channel family. OsCNGC13 is preferentially expressed in the pistils and its expression is dramatically reduced in the heterozygous plant, suggesting a haploinsufficiency nature for the dominant mutant phenotype. We show that OsCNGC13 is permeable to Ca2+. Consistent with this, accumulation of cytoplasmic calcium concentration ([Ca2+]cyt) is defective in the sss1-D mutant style after pollination. Further, the sss1-D mutant has altered extracellular matrix (ECM) components and delayed cell death in the style transmission tract (STT). Based on these results, we propose that OsCNGC13 acts as a novel maternal sporophytic factor required for stylar [Ca2+]cyt accumulation, ECM components modification and STT cell death, thus facilitating the penetration of pollen tube in the style for successful double fertilization and seed-setting in rice.


The new watchdogs' vision of science: A roundtable with Ivan Oransky ( Retraction Watch) and Brandon Stell ( PubPeer).
On March 3rd, 2016, the authors of this note hosted a conference entitled 'Destabilized Science' at the University of California, Los Angeles, to which we invited two representatives of core actors within the new science watchdog pack: Ivan Oransky, co-founder in 2010 of Retraction Watch, and Brandon Stell, co-founder in 2012 of PubPeer. After the formal conference, we organized a roundtable to discuss these invitees' experience and their vision of contemporary science. Mario Biagioli (University of California, Davis), Michael Chwe (UCLA) and Aaron Panofsky (UCLA) participated to the conversation. An edited transcript of the discussion and a short podcast version are being published on Transmissions ( ssstransmissions.org ) the new blog associated with Social Studies of Science.


Infections Caused by Resistant Gram-Negative Bacteria: Epidemiology and Management.
Infections caused by resistant gram-negative bacteria are becoming increasingly prevalent and now constitute a serious threat to public health worldwide because they are difficult to treat and are associated with high morbidity and mortality rates. In the United States, there has been a steady increase since 2000 in rates of extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii, particularly among hospitalized patients with intraabdominal infections, urinary tract infections, ventilator-associated pneumonia, and bacteremia. Colonization with resistant gram-negative bacteria is common among residents in long-term care facilities (particularly those residents with an indwelling device), and these facilities are considered important originating sources of such strains for hospitals. Antibiotic resistance is associated with a substantial clinical and economic burden, including increased mortality, greater hospital and antibiotic costs, and longer stays in hospitals and intensive care units. Control of resistant gram-negative infections requires a comprehensive approach, including strategies for risk factor identification, detection and identification of resistant organisms, and implementation of infection-control and prevention strategies. In treating resistant gram-negative infections, a review of surveillance data and hospital-specific antibiograms, including resistance patterns within local institutions, and consideration of patient characteristics are helpful in guiding the choice of empiric therapy. Although only a few agents are available with activity against resistant gram-negative organisms, two recently released β-lactam/β-lactamase inhibitor combinations - ceftolozane/tazobactam and ceftazidime/avibactam - have promising activity against these organisms. In this article, we review the epidemiology, risk factors, and antibiotic resistance mechanisms of gram-negative organisms. In addition, an overview of treatment options for patients with these infections is provided.


High-resolution contrast-enhanced optical coherence tomography in mice retinae.
Optical coherence tomography (OCT) is a noninvasive interferometric imaging modality providing anatomical information at depths of millimeters and a resolution of micrometers. Conventional OCT images limit our knowledge to anatomical structures alone, without any contrast enhancement. Therefore, here we have, for the first time, optimized an OCT-based contrast-enhanced imaging system for imaging single cells and blood vessels in vivo inside the living mouse retina at subnanomolar sensitivity. We used bioconjugated gold nanorods (GNRs) as exogenous OCT contrast agents. Specifically, we used anti-mouse CD45 coated GNRs to label mouse leukocytes and mPEG-coated GNRs to determine sensitivity of GNR detection in vivo inside mice retinae. We corroborated OCT observations with hyperspectral dark-field microscopy of formalin-fixed histological sections. Our results show that mouse leukocytes that otherwise do not produce OCT contrast can be labeled with GNRs leading to significant OCT intensity equivalent to a 0.5 nM GNR solution. Furthermore, GNRs injected intravenously can be detected inside retinal blood vessels at a sensitivity of ∼0.5 nM, and GNR-labeled cells injected intravenously can be detected inside retinal capillaries by enhanced OCT contrast. We envision the unprecedented resolution and sensitivity of functionalized GNRs coupled with OCT to be adopted for longitudinal studies of retinal disorders.


Malignant peripheral nerve sheath tumors of the head and neck: Demographics, clinicopathologic features, management, and treatment outcomes.
To determine the epidemiology and prognostic indicators in patients with malignant peripheral nerve sheath tumors (MPNST) of the head and neck. The surveillance, epidemiology, and end results registry was reviewed for patients with head and neck MPNST from 1973 to 2011. Study variables included age, sex, race, tumor size, stage at presentation, and treatment modality. There were 374 cases of head and neck MPNST identified. Mean age at diagnosis was 50.7 y ears; 60.2% of patients were male and 82.6% were white. After diagnosis, 38.8% of patients underwent surgery and radiation therapy and 48.1% underwent surgery alone. Kaplan-Meier analysis demonstrated overall (OS) and disease-specific survival (DSS) of 51% and 67% at 5 years. Multivariate Cox regression analysis showed that age (p=0.030), stage (p=0.002), surgery (p=0.037), and size (p<0.001) were predictors of OS, while stage (p<0.001) and size (p<0.001) were predictors of DSS. For stage I/II cancers, surgery (p=0.011) and size (p=0.010) were predictors of OS, and size (p=0.001) predicted DSS. For stage III/IV cancers, both radiotherapy (p=0.024, p=0.009) and size (p=0.001, p=0.001) predicted OS and DSS. For tumors ⩽5 cm, stage (p=0.031) predicted DSS. For tumors >5 cm, male gender (p=0.005), stage (p=0.001), surgery (p=0.003), and radiotherapy (p=0.050) were determinants of OS, and male gender (p=0.022), stage (p<0.001), and radiotherapy (p=0.002) were determinants of DSS. Surgical resection confers survival benefit in patients with early stage MPNST, while radiotherapy improves survival in cases with metastatic disease. Surgery and radiotherapy are prognostically important in patients with tumors >5 cm.


Bacterial expression of catalytically active fragments of the multifunctional enzyme enniatin synthetase.
Enniatin synthetase catalyzes the biosynthesis of N-methylated cyclohexadepsipeptides. The 347 kDa enzyme is encoded by the esyn1 gene of Fusarium scirpi and contains two domains (EA and EB) homologous to each other and to regions of other microbial peptide synthetases. Parts of the esyn1 gene were subcloned in frame to a small lacZ gene portion of Escherichia coli expression vectors. Overproduced recombinant proteins showed a high tendency towards inclusion body formation and could be only partially dissolved in 8 M urea or 6 M guanidine hydrochloride. After renaturation, a 121 kDa recombinant protein representing the N-terminal conserved domain EA of enniatin synthetase was shown to activate D-hydroxyisolvaleric acid via adenylation. Similarly, a 158 kDa recombinant protein comprising the C-terminal conserved domain EB catalyzed the activation of the substrate amino acid (e.g. L-valine). Moreover, this protein could be photolabeled with S-[methyl-14C]adenosyl-L-methionine, (AdoMet) indicating the presence of the methyltransferase. Both functions, L-valine activation and AdoMet binding, could be assigned to a 108 kDa recombinant protein encompassing the A and the M segment of domain EB. The fact that a 65 kDa recombinant protein representing the M portion could be photolabeled, indicated the localization of the methyltransferase in this region. Three deletion mutants of the 65 kDa protein were shown to be inactive with respect to UV-induced AdoMet labeling.


Determination of erythrocyte deformability and its correlation to cellular ATP release using microbore tubing with diameters that approximate resistance vessels in vivo.
A novel method is described for measuring the deformability of red blood cells (RBCs) in tubing whose diameters approximate forces encountered in vivo. Here, RBCs from rabbits are loaded into a 50 cm section of 75 microm id microbore tubing and connected to a syringe pump. This section of tubing is then connected to a 15 cm section of 25 microm id tubing. As buffer is pumped through the flow system, the RBCs are evacuated from both sections of tubing. However, the inability of the RBCs to move freely through the 25 mirom id section of tubing results in a buildup of cells at the inlet of this portion of tubing. The continued force output by the syringe pump results in a deformation of the RBCs until all of the cells are eventually evacuated from the flow system. It was found that a measurement of the time required to reach half of the maximum pressure (1/2 P(max)) may be used as an indicator of the RBC deformability. For a given sample, a simple buffer results in less time to reach 1/2 P(max) (6.9 +/- 0.2 s) than deformable RBCs (21.6 +/- 0.8 s). To verify that the increased amount of time to reach 1/2 P(max) is indeed due to the RBCs, various hematocrits of an RBC sample were investigated and, as expected, it was found that a 12% RBC hematocrit had a higher 1/2 P(max) value (26.0 s +/- 2.2 s) when compared to a 7% hematocrit (19.1 +/- 0.3 s). In addition, RBCs chemically stiffened with glutaraldehyde were shown to be 25% less deformable than normal RBCs. Finally, a study was performed to examine the relationship between RBC deformability and ATP release and it was found that ATP release increased as a function of RBC deformability. This method greatly simplifies deformability measurements, employing only a syringe pump and microbore tubing, and may lead to a more complete understanding of the physiological significance of erythrocyte deformability.


Phylogeography, colouration, and cryptic speciation across the Indo-Pacific in the sea urchin genus Echinothrix.
The sea urchins Echinothrix calamaris and Echinothrix diadema have sympatric distributions throughout the Indo-Pacific. Diverse colour variation is reported in both species. To reconstruct the phylogeny of the genus and assess gene flow across the Indo-Pacific we sequenced mitochondrial 16S rDNA, ATPase-6, and ATPase-8, and nuclear 28S rDNA and the Calpain-7 intron. Our analyses revealed that E. diadema formed a single trans-Indo-Pacific clade, but E. calamaris contained three discrete clades. One clade was endemic to the Red Sea and the Gulf of Oman. A second clade occurred from Malaysia in the West to Moorea in the East. A third clade of E. calamaris was distributed across the entire Indo-Pacific biogeographic region. A fossil calibrated phylogeny revealed that the ancestor of E. diadema diverged from the ancestor of E. calamaris ~ 16.8 million years ago (Ma), and that the ancestor of the trans-Indo-Pacific clade and Red Sea and Gulf of Oman clade split from the western and central Pacific clade ~ 9.8 Ma. Time since divergence and genetic distances suggested species level differentiation among clades of E. calamaris. Colour variation was extensive in E. calamaris, but not clade or locality specific. There was little colour polymorphism in E. diadema.


The effects of desflurane and sevoflurane on the intraocular pressure associated with endotracheal intubation in pediatric ophthalmic surgery.
For ophthalmic surgery anesthesia, it is vital that intraocular pressure (IOP) is controlled. Most anesthetic drugs affect IOP dose-dependently, and inhalational anesthetics dose-dependently decrease IOP. In this study, we compared the effects of desflurane and sevoflurane on IOP and hemodynamics in pediatric ophthalmic surgery. Thirty eight pediatric patients from the age of 6 to 15 years, who were scheduled for strabismus surgery and entropion surgery, were randomized to be administered desflurane (group D, n = 19) or sevoflurane (group S, n = 19). IOPs and hemodynamic parameters were measured before induction of anesthesia (B), after induction but immediately before intubation (AI), 1 min after intubation (T1), 3 min after intubation (T3), and 5 min after intubation (T5). The mean arterial pressure (MAP) at T1 and heart rates (HRs) at T1 and T3 were significantly higher in group D than those in group S. There was no significant difference between the groups in IOP, cardiac index (CI) and stroke index (SI). There was a significant difference within the group in IOP, SI, MAP and HR. There was no significant difference within the group in CI. There was no significant difference between the groups in IOP and hemodynamic parameters. The two anesthetic agents maintained IOP and hemodynamic parameters in the normal range during anesthetic induction.


The effect of heparin on the cell cycle in human B-lymphoblasts: An in vitro study.
Heparin has been shown to be a strong inhibitor of the proliferation of several cell types. In this in vitro study, we investigated whether different heparin concentrations can affect the cell cycle of lymphoblasts in newly diagnosed acute lymphoblastic leukemia (ALL) patients. Lymphoblasts were incubated in different heparin concentrations (0, 10, 20 U/ml), and the percentages of lymphoblasts in each phase of the cell cycle were simultaneously measured by flow cytometry at 0, 1, and 2 hours (h). The percentages of lymphoblasts at the G2/M and S phases were significantly increased in 20 U/ml heparin concentration at 1 h compared to 0 U/ml (without heparin) concentration. We demonstrated that heparin increases the percentages of lymphoblasts in the S and G2/M phases in a concentration- and time-dependent manner. It was shown that heparin expands the proliferation of lymphoblasts by increasing the transition to G2/M and S phases and the S-phase fraction ratio. Heparin thus appears promising for its contribution to new treatment fields such as by providing a synergistic effect with chemotherapeutic drugs.


Polarity of Hydrated Phosphatidylcholine Headgroups.
The headgroup (H) stratum (sometimes called the polar region) of membrane bilayers is a relevant yet poorly understood solvation phase for small molecules and macromolecules interacting with the membranes. Solvation of compounds in bilayer strata is characterized experimentally by wide- and small-angle X-ray scattering, neutron diffraction, and various NMR techniques. The quantification is tedious and only available for a limited set of small molecules. Our recently published model of liposome partitioning of small molecules shows that solvation of compounds in the H-stratum of fluid phosphatidylcholine (PC) bilayers correlates well with their solvation in hydrated diacetyl phosphatidylcholine (DAcPC), and solvation in the core (C) depends in a similar way on that in n-hexadecane. These two correlations became a basis for a model describing the location of compounds in the H- and C-strata and at the connecting interface as a nonlinear function of the fragment solvation characteristics of the compounds. In this study, refractivity of hydrated DAcPC phases with varying water contents was measured and polarity was determined using the steady-state fluorescence of indole and Nile Red. The results were compared with the published data obtained by other techniques for PC bilayers in liposomes or on solid supports. The demonstrated qualitative agreement, as well as the polarity and refractivity dependencies on the DAcPC concentration, supports the suitability of hydrated DAcPC as the H-stratum surrogate. Interestingly, depending on hydrations typical for the H-strata of fluid PC bilayers, the dielectric constant could decrease significantly from 31.0 to 7.3 for 16 and 8 water molecules per headgroup, respectively. Although additional experiments are needed for confirmation, this observation could help set proper dielectric constant magnitudes in continuum-based computational models of accumulation and crossing of the PC bilayers with varying hydration levels thanks to the temperature or the structure of fatty acid chains.


Lipid metabolism in patients with chronic renal failure in the predialytic phase.
CRF is accompanied by characteristic alterations of lipoprotein metabolism with a retarded catabolism of triglyceride-rich lipoproteins as a prominent feature. Further investigation of the lipoprotein profile of CRF could provide information on the fundamental pathophysiological processes responsible for these disturbances and their possible clinical significance.


Computerized tomographic scan-guided drainage of intra-abdominal abscesses. Preoperative and postoperative modalities in colon and rectal surgery.
Computerized tomographic (CT) scan-guided percutaneous drainage of intra-abdominal abscesses has changed the colon and rectal surgeon's approach to preoperative and postoperative intra-abdominal infections. This study is an effort to prove the efficacy of CT scan-guided percutaneous drainage. A retrospective study was performed on 133 patients who underwent CT scan drainage of intra-abdominal abscesses over a 6.3-year period. 67 patients had underlying lower gastrointestinal disease. Twenty-three of these patients (34 percent) had spontaneous abscesses and underwent drainage as a preoperative or final modality, whereas 44 patients (66 percent) were drained postoperatively. In 78 percent of patients, surgery was successfully avoided or delayed. Ten patients had acute diverticulitis associated with a large pelvic abscess. Eight patients underwent successful CT scan-guided percutaneous drainage, yielding an 80 percent success rate. Morbidity from the CT scan-guided percutaneous drainage procedure in spontaneous and postoperative groups was 0 percent and 9 percent, respectively. Mortality was 9 percent and 11 percent, respectively, and associated with an elevated Acute Physiology and Chronic Health Evaluation II (APACHE II) score. CT scan-guided percutaneous drainage of intra-abdominal abscesses is an important adjunct to colon and rectal surgery because roughly 80 percent of spontaneous and postoperative abscesses were successfully managed.


Neutral endopeptidase inhibitor potentiates the tachykinin-induced increase in ciliary beat frequency in rabbit trachea.
We used cultured rabbit tracheal epithelium to determine the effect of mammalian-derived tachykinin on airway ciliary activity and its modulation by neutral endopeptidase EC 184.108.40.206 (NEP). Neurokinin A (NKA) caused dose-dependent increases in ciliary beat frequency (CBF), as measured by a photoelectric method, with the maximal increase from the baseline 15.7 +/- 1.7% (mean +/- SEM, p less than 0.01), whereas substance P (SP) had no effect. The NKA-induced increase in CBF was not inhibited by phentolamine, propranolol, or atropine, but it was abolished by the tachykinin antagonist [D-Pro2, D-Trp7,9]SP. Pretreatment of tissue with thiorphan (10(-5) M), a NEP inhibitor, had little effect on CBF responses to NKA; however, it significantly potentiated the responses to SP (14.9 +/- 3.0%, p less than 0.01). Other peptidase inhibitors, including captopril, bestatin, and leupeptin, did not alter the tachykinin-induced CBF response, suggesting that angiotensin converting enzyme, aminopeptidases, and serine proteinases do not modulate ciliary activity in response to tachykinins. These results suggest that NKA increases CBF by acting directly on tachykinin receptors and that NEP may play a role in modulating the tachykinin-induced stimulatory effects on CBF.


RECOGNIZING AND TESTING HOMOLOGY OF COURTSHIP DISPLAYS IN STORKS (AVES: CICONIIFORMES: CICONIIDAE).
Ethological studies in the 1940s and 1950s, most notably those of Lorenz and Tinbergen, emphasized a historical perspective. By the 1970s, the notion that behavioral traits are too plastic to retain historical information became prevalent, and evolutionary approaches in behavioral studies were largely abandoned. However, several recent studies have demonstrated that behavioral characters are remarkably consistent with phylogenies obtained from other data and not particularly prone to homoplasy. In this study, I coded descriptions of courtship display behaviors in stork species (Aves: Ciconiiformes: Ciconiidae) as a matrix of discrete characters. I mapped each behavioral character onto a phylogeny based on DNA-DNA hybridization distances to test the homology of individual characters. Generally, displays occurring early in courtship were congruent with phylogenetic relationships and showed little homoplasy, while displays occurring late in courtship were more homoplastic. I also performed a phylogenetic analysis of the behavioral data matrix using maximum parsimony. The strict consensus of the 24 most-parsimonious trees was congruent with the DNA-DNA hybridization tree in all nodes having greater than 70% bootstrap support.


Reductionism in the comments and autobiographical accounts of prominent psychologists.
Many of the researchers in the field of psychological science use strategies and methods in which human actions and experiences are reduced to behavioral contingencies, statistical regularities, neurophysiological states and processes, and computational functions and models. However, many psychologists talk readily and easily about how their research might assist human agents to solve problems, cope, make decisions, self-regulate, and more generally "make a difference" and "take control." The authors considered informally selected comments by several eminent psychologists, and more formally, 73 autobiographical accounts of prominent psychologists to see what could be learned about the attitudes of these psychologists toward reductionism in their own work and in the field of psychology in general. In interpreting these comments and accounts, the authors posit a gap between many psychologists' contemplation of their work and their actual research practices. The authors also suggest that such a gap may be related to psychologists' educational experiences and their scholarly and professional socialization, as well as to their subdisciplinary attachments and contexts.


Beating the rival but losing the game: How the source of alternative offers alters behavior and outcomes in negotiation.
Decades of negotiations research has emphasized the importance of having alternatives. Negotiators with high-value outside offers tend to have greater power and claim higher values in the focal negotiation. We extend this line of work by proposing that the source of alternatives-that is, who negotiators receive an alternative offer from-can significantly shape their negotiation behavior and outcomes. Specifically, we examine how negotiators' behavior changes when they face a counterpart who has an offer from their rival. Four studies demonstrate that this situation enhances negotiators' motivation to outperform their counterpart's alternative by reaching an agreement with the counterpart. This in turn leads the focal negotiator to make less aspirational first offers and eventually claim less value in final agreements. Our findings highlight the importance of considering the existing relationships among actors directly and indirectly involved in a negotiation, reveal a novel motive that can guide negotiators' behavior and outcomes, and uncover a previously unexplored negotiation strategy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


A computational procedure for assessing the significance of RNA secondary structure.
In our recent series of papers, we have used the structures of statistical significance from Monte Carlo simulations to improve the predictions of secondary structure of RNA and to analyze the possible role of locally significant structures in the life cycle of human immunodeficiency virus. Because of intensive computational requirements for Monte Carlo simulation, it becomes impractical even using a supercomputer to assess the significance of a structure with a window size greater than 200 along an RNA sequence of 1000 bases or more. In this paper, we have developed a new procedure that drastically reduces the time needed to assess the significance of structures. In fact, the efficiency of this new method allows us to assess structures on the VAX as well as the CRAY.


Coexpression of neurotrophins and their receptors in neurons of the central nervous system.
Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are neuronal survival molecules which utilize the Trk family of tyrosine kinase receptors. Using double-label in situ hybridization, we demonstrate that mRNAs for BDNF and its high-affinity receptor TrkB are coexpressed in hippocampal and cortical neurons. Also, a large number of neurons in these areas coexpress NGF and BDNF mRNAs. Epileptic seizures lead to increased levels of both BDNF/TrkB and NGF/BDNF mRNAs in double-labeled cells. Our results show that individual neurons of the central nervous system can coexpress neurotrophins and their receptors and produce two neurotrophic factors. These factors could support neuronal survival after brain insults, not only via retrograde transport but also through autocrine mechanisms.


Unlocking Reversible Silicon Redox for High-Performing Chlorine Batteries.
Chlorine (Cl)-based batteries such as Li/Cl2 batteries are recognized as promising candidates for energy storage with low cost and high performance. However, the current use of Li metal anodes in Cl-based batteries has raised serious concerns regarding safety, cost, and production complexity. More importantly, the well-documented parasitic reactions between Li metal and Cl-based electrolytes require a large excess of Li metal, which inevitably sacrifices the electrochemical performance of the full cell. Therefore, it is crucial but challenging to establish new anode chemistry, particularly with electrochemical reversibility, for Cl-based batteries. Here we show, for the first time, reversible Si redox in Cl-based batteries through efficient electrolyte dilution and anode/electrolyte interface passivation using 1,2-dichloroethane and cyclized polyacrylonitrile as key mediators. Our Si anode chemistry enables significantly increased cycling stability and shelf lives compared with conventional Li metal anodes. It also avoids the use of a large excess of anode materials, thus enabling the first rechargeable Cl2 full battery with remarkable energy and power densities of 809 Wh kg-1 and 4,277 W kg-1 , respectively. The Si anode chemistry affords fast kinetics with remarkable rate capability and low-temperature electrochemical performance, indicating its great potential in practical applications.


Development of non-radioisotopic immunoassay systems for measuring flounder IGF-I.
A time-resolved fluoroimmunoassay system (TR-FIA) for measuring flounder insulin-like growth factor-I (IGF-I) was developed using biotinylated flounder IGF-I, anti-fish IGF-I antiserum and europium-avidin conjugate. The detection limit per well was <5 pg/well corresponding to <0.5 ng/ml in a basic procedure for sample of 10 microl/well and to <0.08 ng/ml in a procedure modified for high volume samples (up to 70 microl/well). Specificity of the assay was validated using various IGF-Is and insulins. All IGFs except seabream IGF-I showed very low or no crossreactivity. Binding inhibition curves for flounder and seabream IGF-Is were completely identical to each other. Intra- and interassay variations ranged from coefficients of variations of 3.9% to 7.2%. Recovery tests using barfin flounder plasma varied from 82.7 to 101.6% in the added range from 20 to 160 ng/ml. This assay system was applied for measuring total plasma IGF-I in barfin flounder injected porcine growth hormone (GH). A group injected with GH at the dose of 0.05 IU/gBW showed a significant increase of total plasma IGF-I compared with those of albumin-injected (control) and initial groups. In addition, I was able to substitute time-resolved fluorometric detection in this assay system with enzymatic fluorometric detection (FIA). Binding inhibition curve for flounder IGF-I in this substituted assay system showed equal performance with that of the TR-FIA system. Correlation of IGF-I levels between TR-FIA and FIA was high (r(2)=0.957) in plasma samples from barfin flounders in various physiological conditions. Thus, the present study shows precision and efficiency of two non-radioisotopic immunoassay systems for measuring flounder IGF-I.


CD8+CD4- lymphocyte lines can harbor the AIDS virus in vitro.
A detailed definition of AIDS virus-specific T lymphocytes will require the generation and characterization of HIV-1-specific, cloned T cell populations. In our studies, we show that CD8+CD4- lymphocyte lines, derived from PBL of rhesus monkeys infected with simian immunodeficiency virus of macaques and humans infected with HIV-1, can harbor AIDS viruses. CD8+CD4- lymphocyte lines derived from infected individuals are shown to express AIDS virus-encoded proteins and generate reverse transcriptase activity. Infection of these CD8+CD4- lymphocytes is confirmed at the single cell level by the techniques of immunoelectronmicroscopy and two-color immunohistochemistry. This observation suggests that it may prove problematic to generate cloned, functional T lymphocyte populations from AIDS virus-infected individuals and raises the possibility that CD8+CD4- cells may serve as reservoirs for the AIDS viruses.


Hot-spot p53 mutants interact specifically with two cellular proteins during progression of the cell cycle.
Inactivation of both alleles of the p53 gene is commonly found in human cancers. In contrast to mutations of the retinoblastoma gene, certain altered forms of p53 gain growth-promoting functions. To explore the mechanisms underlying this gain of function, we have identified two nuclear proteins, with molecular masses of 42 and 38 kDa, respectively, that are specifically associated with p53 mutated within the simian virus 40 T-antigen-binding domain, "hot spots" found in many human tumors. These mutants transactivate the multiple-drug resistance gene promoter and cause cells to grow to higher density. Both the mutated p53 complex with p42 and p38 increase when cells enter S phase of the cell cycle but decrease in G1 and M phases, suggesting that they may have a role in promoting cell growth.


[Responses of soil microbial communities in mulberry rhizophere to intercropping and nitrogen application.]
In this study, the effects of intercropping with alfalfa and nitrogen application on the functional diversity of soil microbial community in mulberry rhizosphere were examined by Biolog-EcoplateTM technique, and principal component and canonical analyses. Compared to monoculture with no nitrogen (N) addition, monoculture with N application and intercropping with alfalfa remarkably reduced soil pH and significantly increased the contents of soil organic matter, soil available N, soil water content, and activities of peroxidase and urease. Monoculture with N application and intercropping with alfalfa (with or without N application) increased the AWCD values, diversity index, and the carbon source utilization ratios of soil microbes. Higher increments of these parameters were detected in the treatment of intercropping plus N application. The results of principal component analysis showed that N application and intercropping changed the capacity of the rhizosphere microbial community for utilizing carbon sources. The utilization of carbon sources highly related to the principal components by the rhizosphere microbial communities was similar in the treatments of monoculture with N application and intercropping without N application. The utilization of itaconic acid and D-glucamaminic acid in the latter was more than 4% and was significantly higher than that in the former. The results from redundancy analysis showed that the soil microbial diversity in mulberry rhizosphere of the treatment of monoculture without N application was positively correlated with polyphenol oxidase activity and negatively correlated with soil water content, whereas that of monoculture with N application and intercropping without N application was significantly positively correlated with soil pH and soil water content and negatively correlated with soil N avalaibility. The diversity of the microbes in the rhizosphere soil of mulberries under the treatment of intercropping with N application showed positive correlation with soil N availability and was significantly negatively correlated with soil pH.


Radiography of cutaneous urinary diversions.
Imaging of cutaneous urinary diversions (CUDs) requires the use of special radiographic procedures. This article describes the techniques for radiographic examination of the two major types of CUDs: urinary conduits and continent urinary reservoirs. Diagrams and radiographs depict the structure and function of these urinary diversions. A Quick Procedural Reference guide is included to allow easy introduction of the examination protocols into a radiology department's procedure manual.


Angiopoietin-2 blockade suppresses growth of liver metastases from pancreatic neuroendocrine tumors by promoting T cell recruitment.
Improving the management of metastasis in pancreatic neuroendocrine tumors (PanNETs) is critical, as nearly half of patients with PanNETs present with liver metastases, and this accounts for the majority of patient mortality. We identified angiopoietin-2 (ANGPT2) as one of the most upregulated angiogenic factors in RNA-Seq data from human PanNET liver metastases and found that higher ANGPT2 expression correlated with poor survival rates. Immunohistochemical staining revealed that ANGPT2 was localized to the endothelial cells of blood vessels in PanNET liver metastases. We observed an association between the upregulation of endothelial ANGPT2 and liver metastatic progression in both patients and transgenic mouse models of PanNETs. In human and mouse PanNET liver metastases, ANGPT2 upregulation coincided with poor T cell infiltration, indicative of an immunosuppressive tumor microenvironment. Notably, both pharmacologic inhibition and genetic deletion of ANGPT2 in PanNET mouse models slowed the growth of PanNET liver metastases. Furthermore, pharmacologic inhibition of ANGPT2 promoted T cell infiltration and activation in liver metastases, improving the survival of mice with metastatic PanNETs. These changes were accompanied by reduced plasma leakage and improved vascular integrity in metastases. Together, these findings suggest that ANGPT2 blockade may be an effective strategy for promoting T cell infiltration and immunostimulatory reprogramming to reduce the growth of liver metastases in PanNETs.


Synthesis and biological evaluation of 13α-estrone derivatives as potential antiproliferative agents.
13α-Estrone derivatives containing various substituents on C-3 and C-17 were synthesized, and evaluated by means of MTT assays for in vitro antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF-7, A2780 and A431). Compounds with N-benzyltriazolylmethoxy moieties on C-3 proved to be more potent than their 3-hydroxy or 3-ether counterparts. Some triazoles exerted substantial cytostatic effects against particular tumor cell lines, with submicromolar IC50 values.


Fuse to defuse: a self-limiting ribonuclease-ring nuclease fusion for type III CRISPR defence.
Type III CRISPR systems synthesise cyclic oligoadenylate (cOA) second messengers in response to viral infection of bacteria and archaea, potentiating an immune response by binding and activating ancillary effector nucleases such as Csx1. As these effectors are not specific for invading nucleic acids, a prolonged activation can result in cell dormancy or death. Some archaeal species encode a specialised ring nuclease enzyme (Crn1) to degrade cyclic tetra-adenylate (cA4) and deactivate the ancillary nucleases. Some archaeal viruses and bacteriophage encode a potent ring nuclease anti-CRISPR, AcrIII-1, to rapidly degrade cA4 and neutralise immunity. Homologues of this enzyme (named Crn2) exist in type III CRISPR systems but are uncharacterised. Here we describe an unusual fusion between cA4-activated CRISPR ribonuclease (Csx1) and a cA4-degrading ring nuclease (Crn2) from Marinitoga piezophila. The protein has two binding sites that compete for the cA4 ligand, a canonical cA4-activated ribonuclease activity in the Csx1 domain and a potent cA4 ring nuclease activity in the C-terminal Crn2 domain. The cA4 binding affinities and activities of the two constituent enzymes in the fusion protein may have evolved to ensure a robust but time-limited cOA-activated ribonuclease activity that is finely tuned to cA4 levels as a second messenger of infection.


[A new method for examining the vitreous body: the E1 Bayadi-Kajiura lens].
Vitreous examination is an important component of diagnosing and managing vitreoretinal disease, but the relative transparency of vitreous makes its examination difficult. Study of the vitreous is facilitated by the use of a biomicroscope to create an optical section and appropriate lenses to neutralize or modify the dioptric power of the eye. This article describes the vitreous examination using the preset El Bayadi-Kajiura lens, stretching the advantages and accuracy of this method. This lens is a +58,6 diopter preset lens producing an inverted real image between the slit lamp and the preset lens. This precorneal positive-diopter lens increase the refractive power of the eye, thus permitting biomicroscopic viewing of an ariel image, similar to the principle of indirect ophthalmoscopy. The major advantage compared to the Goldmann lens is the better visualisation of complex posterior vitreoretinal relationships, allowed by larger image, large illumination-observation angle and lower level of distortion and glare. The Goldmann lens permits a comprehensive intraocular examination, whereas with the EBK lens, observation and documentation of vitroretinal structures are limited to within 50 degrees of the fovea. Thus, the Goldmann lens is essential to evaluate more peripheral vitreous pathology. The Goldmann lens is more accurate in evaluating the presence of cells in the vitreous, which could be due to greater magnification. In a comprehensive examination of the vitreous, the Goldmann and EBK lenses are complementary. The latter is optimal for viewing complex posterior vitreous pathology; the former is necessary for viewing the peripheral vitreous. Photographic documentation of vitreoretinal relationship is better with the EBK than with the Goldmann lens.(ABSTRACT TRUNCATED AT 250 WORDS)


Leucocyte migration inhibition and leucocyte adherence inhibition studies, using ferritin as 'antigen', in patients with malignant lymphoma.
Isoelectric focusing of ferritin prepared from three spleens involved by Hodgkin's disease demonstrated only minor differences from normal spleen ferritin. The leucocyte migration inhibition (LMI) and leucocyte adherence inhibition (LAI) assays were used to assess sensitization to Hodgkin's disease spleen ferritin and its component acidic and basic isoferritins in patients with malignant lymphoma compared to patients with other malignancies and control subjects. A difference in response to ferritin was demonstrated in both tests with patients with malignant lymphoma compared to controls, and in LMI test compared to patients with other malignancies. There were also significant differences in responses in, patients with malignant lymphoma compared to controls, against acidic and basic isoferritins in both tests, in lymphoma patients versus patients with other malignancies against acidic isoferritins in both tests, lymphoma versus other malignancy against basic isoferritins in the LMI test only. However, no significant differences, within each group, between responses with acidic and with basic isoferritins were demonstrated, and there was no correlation between individual patients' responses in the two tests.


Prognostic value of arginase-II expression and regulatory T-cell infiltration in head and neck squamous cell carcinoma.
Tumor-infiltrating lymphocytes are present in a variety of tumors and play a central role in antitumor immune responses. Nevertheless, most cancers progress probably because tumors are only weakly immunogenic and develop multiple immunosuppressive mechanisms. In the present study, on head and neck squamous cell carcinoma, we found high intraepithelial infiltration of regulatory FOXP3(+) T cells, and relatively high levels of BDCA2(+) and FOXP3(+) cells in stromal (peripheral) regions of the tumors. Tumor-infiltrating (intraepithelial) FOXP3(+) T cells were significantly more frequent in patients with oropharynx and oral cavity squamous cell carcinoma and in patients without lymph node metastasis. Furthermore, arginase-II (ARG2) was expressed by 60%, inducible nitric oxide synthetase by 9%, cyclooxygenase-2 by 43%, and B-cell lymphoma 2 (BCL2) by 26% of tumors. Interestingly, the absence of ARG2 expression, enhanced stromal infiltration of CD11c(+) myeloid dendritic cells, and high numbers of FOXP3(+) T cells were each significantly associated with prolonged overall survival, and the latter two parameters were also confirmed by multivariate analysis. For disease-free survival, multivariate analysis revealed significant negative correlations with BCL2 and ARG2 expression by tumor cells. These findings shed new light on mechanisms of cancer progression, and provide rationales for therapeutic inhibition of immunosuppressive mechanisms in head and neck squamous cell carcinoma.


Detection of IUPAC and IUPAC-like chemical names.
Chemical compounds like small signal molecules or other biological active chemical substances are an important entity class in life science publications and patents. Several representations and nomenclatures for chemicals like SMILES, InChI, IUPAC or trivial names exist. Only SMILES and InChI names allow a direct structure search, but in biomedical texts trivial names and Iupac like names are used more frequent. While trivial names can be found with a dictionary-based approach and in such a way mapped to their corresponding structures, it is not possible to enumerate all IUPAC names. In this work, we present a new machine learning approach based on conditional random fields (CRF) to find mentions of IUPAC and IUPAC-like names in scientific text as well as its evaluation and the conversion rate with available name-to-structure tools. We present an IUPAC name recognizer with an F(1) measure of 85.6% on a MEDLINE corpus. The evaluation of different CRF orders and offset conjunction orders demonstrates the importance of these parameters. An evaluation of hand-selected patent sections containing large enumerations and terms with mixed nomenclature shows a good performance on these cases (F(1) measure 81.5%). Remaining recognition problems are to detect correct borders of the typically long terms, especially when occurring in parentheses or enumerations. We demonstrate the scalability of our implementation by providing results from a full MEDLINE run. We plan to publish the corpora, annotation guideline as well as the conditional random field model as a UIMA component.


The development of proliferating ductular structures in liver disease. An immunohistochemical study.
Proliferation of bile ductules or ductular hepatocytes occurs in a variety of liver diseases. The origin of these ductular structures and the mechanism of their proliferation are controversial. Using cytokeratin as marker for ductular structures, liver diseases in which ductular proliferation was a consistent and prominent feature were studied. Paraffin-embedded sections of livers (five cases each) with acute or chronic obstruction of extrahepatic bile ducts, primary biliary cirrhosis (stage II), drug-induced cholestatic liver disease, liver allograft rejection, vicinity of metastatic carcinoma, and massive hepatic necrosis were studied by immunohistochemical methods using three kinds of antiserum against cytokeratin polypeptides of different molecular weights. Bile ductules in diseases involving bile ducts and ductular hepatocytes in massive hepatic necrosis were closely associated with hepatocytes at the limiting plate or with injured hepatocytes. These findings suggest that hepatocytes play an important role in the proliferation of ductular structures or may represent their origin.


Robot-assisted thoracoscopic surgery with simple laparoscopy for diaphragm eventration.
Robot-assisted thoracoscopic surgery has been applied for general thoracic operations. Its advantages include not only those of minimally invasive surgery but also those of magnified three-dimensional vision and angulation of the robotic arm. However, there are no direct tactile sensation and force feedback, which can cause unwanted organ damage. We therefore used laparoscopy simultaneously to avoid a blind intraperitoneal area during robotic surgery for diaphragmatic eventration via transthoracic approach and describe the technique herein.


Primary hyperparathyroidism due to an intrathyroidal parathyroid adenoma associated with chronic lymphocytic thyroiditis.
This is a case of a 44-year-old woman with an anterior neck mass and hypothyroidism who presented with an incidental finding of an elevated serum calcium level and was found to have primary hyperparathyroidism and osteoporosis. During surgical exploration no parathyroid adenoma was found, although a nodule was palpated within the right thyroid lobe. Examination of the excised right thyroid lobe revealed an intrathyroidal parathyroid adenoma and chronic lymphocytic thyroiditis. After surgery, she did not develop severe hypocalcaemia and this was attributed to preoperative treatment with pamidronate. In the months following surgery, parathyroid hormone remained undetectable.


Detection of Adult Beetles Inside the Stored Wheat Mass Based on Their Acoustic Emissions.
The efficacy of bioacoustics in detecting the presence of adult beetles inside the grain mass was evaluated in the laboratory. A piezoelectric sensor and a portable acoustic emission amplifier connected with a computer were used. Adults of the most common beetle pests of stored wheat have been detected in varying population densities (0.1, 0.5, 1, and 2 adults per kilogram of wheat). The verification of the presence of the insect individuals was achieved through automated signal parameterization and classification. We tried out two different ways to detect impulses: 1) by applying a Hilbert transform on the audio recording and 2) by subtracting a noise estimation of the recording from the spectral content of the recording, thus allowing the frequency content of possible impulses to emerge. Prediction for infestation was rated falsely negative in 60-74%, 48-60%, 0-28%, and 0-4% of the cases when actual population density was 0.1, 0.5, 1, and 2 adults per kilogram, respectively, irrespective of pest species. No significant differences were recorded in positive predictions among different species in almost all cases. The system was very accurate (72-100%) in detecting 1 or 2 insects per kilogram of hard wheat grain, which is the standard threshold for classifying a grain mass "clean" or "infested." Our findings are discussed on the basis of enhancing the use of bioacoustics in stored-product IPM framework.


Presidential perspectives 2001: nursing issues in the 21st century.
It has been said of 20th century nursing that "despite the changes, new technology, the growth as well as the setbacks, at the close of the century, the essence of nursing [had] not changed" (Schorr, 1999). What is the essence of nursing? I believe that it is best summed up in one word-service. This was the moral vision held by Florence Nightingale over a century ago: that nurses and nursing would demonstrate an unparalleled commitment to serving humanity. This great tradition of humanitarian service undergirds our profession today as we face the complexities, the challenges, and the opportunities of nursing in the 21st century. It is now up to us to go forward and create the future we want for ourselves, for our colleagues, for our profession, and for our patients.


Impact of Ultraviolet Radiation on the Aging Properties of SBS-Modified Asphalt Binders.
Styrene Butadiene Styrene (SBS) polymer-modified asphalt binders have become widely used in asphalt pavement because of their advantages in high- and low-temperature performance and fatigue resistance. Asphalt pavement is inevitably exposed to sunlight and ultraviolet (UV) radiation during its construction and service life. However, consideration of the aging effect of UV radiation is still limited in current pavement design and evaluation systems. In order to evaluate the impact of UV radiation on the aging properties of SBS-modified asphalt binders, UV aging tests were performed on Rolling Thin Film Oven Test (RTFOT)-aged samples with different UV radiation intensities and aging times. Sixteen different groups of tests were conducted to compare the rheological properties and functional group characteristics of SBS-modified asphalt binders. Dynamic Shear Rheometer (DSR), Bending Beam Rheometer (BBR), FTIR, and SEM tests were conducted to evaluate the aging mechanisms in various UV aging conditions. The results found that UV radiation seriously destroys the network structure formed by the cross-linking effect in SBS-modified asphalt binders, which aggravates the degradation of SBS and results in a great change of rheological properties after UV aging. The nature of SBS-modified asphalt binder aging resulted from the degradation of SBS and the changes of asphalt binder base composition, which lead to the transformation of colloidal structure and the deterioration of asphalt binder performance. The tests also found that continuous UV radiation can increase shrinkage stress in the asphalt binder surface and leads to surface cracking of the asphalt binder.


Estimating lead time and sensitivity in a screening program without estimating the incidence in the screened group.
Early indicators of the effectiveness of a screening test for chronic diseases such as breast cancer are the length of time the diagnosis is advanced by screening, the lead time, and the sensitivity of the screening test. This paper describes a model for simultaneously estimating the mean lead time and the sensitivity when only the number of cancers detected at the successive screenings and the number of cancers occurring in the time interval between the screening examinations are known. This model is particularly useful in assessing the effect of screening when the underlying cancer incidence in the screened group is unknown. The model is fitted to the data of 235 screen-detected breast cancer cases and 146 interval cancers diagnosed across 6 screening rounds of the program in Nijmegen. The maximum likelihood estimate for the mean lead time ranges from 1.3 years in the under age 50 group to 2.2 years in the age 50-65 group, both estimates having large confidence intervals. The corresponding sensitivity estimates are 0.92 and 1.00.


Analysis of tRNA halves (tsRNAs) in serum from cattle challenged with bovine viral diarrhea virus.
Acute infections of bovine viral diarrhea virus (BVDV) lead to a range of clinical presentations. Laboratory tests for detection depend on collection of samples during a short viremia. Acutely infected animals remain largely undiagnosed. Transfer RNA halves (tsRNAs) are hypothesized to function like microRNAs to regulate gene expression during an immune response. The objective of this study was to identify tsRNAs in cattle that had been challenged with a non-cytopathic field strain of BVDV. Colostrum-deprived neonatal Holstein calves were either challenged with BVDV (n=5) or mock challenged (n=4). Sera was collected prior to challenge and days 4, 9, and 16 post challenge. RNA was extracted and read counts of small non-coding RNAs were assessed using next-generation sequencing. A total of 87,838,207 reads identified 41 different tsRNAs. Two 5' tsRNAs, tsRNAProAGG and tsRNAValAAC, differed across time. Two 5' tsRNAs, tsRNAGlyCCC and tsRNAGlyGCC, differed between treatment groups across time. Four days post challenge, 5' tsRNAGlyCCC and tsRNAGlyGCC were significantly lower in the challenged group than the control group. Further studies are needed to identify the importance and function of 5' tsRNAGlyCCC and tsRNAGlyGCC in serum samples of cattle challenged with BVDV.


Neosporosis-associated bovine abortion in Pennsylvania.
Neospora caninum was found in fetal tissues of 34 of 688 cases of bovine abortion submitted to the Pennsylvania Animal Diagnostic Laboratory System during the period from May 1994 to November 1996. The aborted fetuses ranged in gestational age from 3 to 8 months. Microscopic lesions consisted primarily of encephalitis and myocarditis. A labeled (strept) avidin-biotin staining procedure using anti-N. caninum polyclonal rabbit serum revealed N. caninum organisms within the fetal brain (27 of 27), heart (10 of 13), placenta (5 of 6), kidney (2 of 2), liver (1 of 4) and skeletal muscle (1 of 1).


Sirtuin-7 knockdown inhibits the growth of endometrial cancer cells by inducing apoptosis via the NF-κB signaling pathway.
Sirtuin-7 is an evolutionarily conserved NAD-dependent deacetylase, which serves an important role in carcinogenesis. However, the potential mechanism of sirtuin-7 in endometrial cancer has not yet been investigated. The purpose of the present study was to investigate whether sirtuin-7 exhibits inhibitory effects on endometrial cancer cells. The potential mechanisms mediated by sirtuin-7 in endometrial cancer cells were also investigated. The expression levels of sirtuin-7 in endometrial cancer cells were compared with normal endometrial cells using western blotting. The results demonstrated that sirtuin-7 is overexpressed in endometrial cancer cells compared with normal endometrial cells. The downregulation of sirtuin-7 inhibited the growth and invasiveness of endometrial cancer cells. The knockdown of sirtuin-7 was observed to increase the sensitivity of the endometrial cancer cells to cisplatin treatment in vitro. An investigation into the potential molecular mechanism demonstrated that sirtuin-7 knockdown promoted the apoptosis of endometrial cancer cells by regulating the nuclear factor (NF)-κB signaling pathway. The knockdown of sirtuin-7 inhibited NF-κB expression and resulted in a decrease in the expression of NF-κB target proteins that are anti-apoptotic: Bcl-xl, Bcl-2 and Mcl-1. Sirtuin-7 knockdown also resulted in an increase of the NF-κB target proteins that are pro-apoptotic: Caspase-3, Bad and Bax. In conclusion, the present study demonstrated that sirtuin-7 knockdown was able to markedly inhibit the growth of endometrial cancer cells, suggesting that sirtuin-7 may be a potential therapeutic target for endometrial cancer therapy.


Have the tsunami and nuclear accident following the Great East Japan Earthquake affected the local distribution of hospital physicians?
The Great East Japan Earthquake occurred on 11 March 2011 near the northeast coast of the main island, 'Honshu', of Japan. It wreaked enormous damage in two main ways: a giant tsunami and an accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP). This disaster may have affected the distribution of physicians in the region. Here, we evaluate the effect of the disaster on the distribution of hospital physicians in the three most severely affected prefectures (Iwate, Miyagi, and Fukushima). We obtained individual information about physicians from the Physician Census in 2010 (pre-disaster) and 2012 (post-disaster). We examined geographical distributions of physicians in two ways: (1) municipality-based analysis for demographic evaluation; and (2) hospital-based analysis for geographic evaluation. In each analysis, we calculated the rate of change in physician distributions between pre- and post-disaster years at various distances from the tsunami-affected coast, and from the restricted area due to the FDNPP accident. The change in all, hospital, and clinic physicians were 0.2%, 0.7%, and -0.7%, respectively. In the municipality-based analysis, after taking account of the decreased population, physician numbers only decreased within the restricted area. In the hospital-based analysis, hospital physician numbers did not decrease at any distance from the tsunami-affected coast. In contrast, there was a 3.3% and 2.3% decrease in hospital physicians 0-25 km and 25-50 km from the restricted area surrounding the FDNPP, respectively. Additionally, decreases were larger and increases were smaller in areas close to the FDNPP than in areas further away. Our results suggest that the tsunami did not affect the distribution of physicians in the affected regions. However, the FDNPP accident changed physician distribution in areas close to the power plant.


Cut-off values of the Japanese Orthopaedic Association score corresponding to Constant scores for evaluating outcomes in rotator cuff tear.
To clarify the cut-off value of the Japanese Orthopaedic Association (JOA) score corresponding to rotator cuff tear outcome as evaluated by the Constant score. The subjects were 230 patients with rotator cuff tear. The Constant and JOA scores on the first examination in our hospital were evaluated. After investigation of the correlation between the Constant and JOA scores, the cut-off JOA score was calculated, corresponding to excellent, good and fair outcomes as evaluated by the Constant score. The Constant and JOA scores on the first examination were 49.64 ± 12.84 and 72.52 ± 12.84, respectively, with a strong correlation ( r = 0.87, p < 0.01). Receiver operating characteristic analysis revealed that the cut-off JOA score was 87.0 for excellent outcome (area under the curve, AUC: 0.93; sensitivity: 100%; specificity: 88.6%; p < 0.01), 84.0 for good outcome (AUC: 0.94; sensitivity: 100%; specificity: 83.4%; p < 0.01) and 78.0 for fair outcome (AUC: 0.88; sensitivity: 100%; specificity: 71.3%; p < 0.01). In patients with rotator cuff tear, good outcome as judged by a Constant score of ≥80 corresponds to a JOA score cut-off of 84.0. Judgement of the treatment outcomes and evaluation of the surgical method may be more accurate when using clear cut-off values for the scoring system employed, such as those determined in our study.


Suicide Attempt by a Corrosive Agent Causing Unusual Outcomes and Complications.
We commonly encounter patients in the emergency department who present after a suicide attempt. The methods can vary and present unique challenges depending on the nature of the attempt. We present an unsuccessful attempt via chemical ingestion that led to severe complications involving the ingestion of drain cleaner with both highly corrosive and caustic properties. The management and presentation are discussed in great detail to further investigate the best treatment plan for both acute and chronic complications.


Mutant non-coding RNA resource in mouse embryonic stem cells.
Gene trapping is a high-throughput approach that has been used to introduce insertional mutations into the genome of mouse embryonic stem (ES) cells. It is performed with generic gene trap vectors that simultaneously mutate and report the expression of the endogenous gene at the site of insertion and provide a DNA sequence tag for the rapid identification of the disrupted gene. Large-scale international efforts assembled a gene trap library of 566,554 ES cell lines with single gene trap integrations distributed throughout the genome. Here, we re-investigated this unique library and identified mutations in 2202 non-coding RNA (ncRNA) genes, in addition to mutations in 12,078 distinct protein-coding genes. Moreover, we found certain types of gene trap vectors preferentially integrating into genes expressing specific long non-coding RNA (lncRNA) biotypes. Together with all other gene-trapped ES cell lines, lncRNA gene-trapped ES cell lines are readily available for functional in vitro and in vivo studies.