Comparison of choroidal thicknesses in patients with coronary artery disease and patients at risk of coronary artery disease.
The study aimed to compare choroidal thicknesses (CTh) in patients with coronary artery disease (CAD) and patients at risk of coronary artery disease and investigate whether thinning of the choroid can be used as a biomarker for development of coronary artery disease in patients at risk. The study group was composed of 103 eyes of 53 patients with coronary artery disease, and the control group was composed of 62 eyes of 32 patients with diabetes mellitus, hypertension and/or hyperlipidemia without coronary artery disease. CAD was diagnosed in patients with one of the following: myocardial infarction with/without ST segment elevation, clinically proven history of cardiac catheterization testifying greater than 50% obstruction in at least one coronary artery, revascularization operations. The control group consisted of clinically proven patients with normal coronary arteries. The choroidal thickness was measured with enhanced depth imaging optical coherence tomography under the fovea and at six other points, located at 500 micron, 1000 micron and 1500 micron nasal to the fovea and 500 micron, 1000 micron, 1500 micron temporal to the fovea. The subfoveal choroidal thickness was significantly thinner in the coronary artery disease group compared to the control group (244 µm vs. 289 µm; p < 0,001). In all other measured regions (nasal 500, nasal 1000, nasal 1500, temporal 500, temporal 1000, and temporal 1500 micron), CTh was statistically significant thinner in the CAD group. A negative significant linear relationship (low level) between CAD duration and choroidal thickness in the subfoveal, nasal 1000, nasal 1500, temporal 500, temporal 1000 micron regions was detected. Patients with CAD have a decreased choroidal thickness compared to patients at risk of CAD. Detection of CTh thinning in a patient with diseases, such as diabetes, hypertension and/or hypercholesterolemia, which pose a risk for CAD may be a predictor of development of coronary artery disease. Clinical Trials Registration Kocaeli Derince Training and Research Hospital ethics committee-protocol number: 2020-106.


My story: the discovery and mapping to chromosome 21 of the Alzheimer amyloid gene.
When I decided to clone the amyloid gene I did not know that there were some twenty groups around the research world that desperately tried to do the same. If I knew that I would have never started the project. I was so ignorant about the disease that I did not know how to spell the name Alzheimer. I had to look at the papers of other researchers to make sure that I my spelling was correct. After the cloning, I was invited to numerous national and international meetings on AD. These meetings became my University where I majored in AD.


Thymoma in a dog with a part of granular cell proliferation and concurrent lymphoma cells.
A 12-year-old male Shiba dog showed anemia and the swelling of systemic lymph nodes. X-ray and post mortal examinations revealed a anterior mediastinal mass. Histologically, the tumor mass consisted of four different elements; cord-like proliferation of cuboidal epithelial cells, tubular or cystic structures lined with ciliated epithelial cells, proliferation of large round-shaped epithelial cells with PAS-slightly positive granular cytoplasm, and diffuse proliferation of neoplastic lymphocytes. Epithelial cells in cord-like or cystic structures were strongly positive for cytokeratin. Granular or foamy cells were negative for all markers examined and had myelin-like bodies in the cytoplasm by electron microscopy. The neoplastic lymphocytes in the tumor mass were considered being derived from concurrent multicentric lymphoma. Based on these findings, the present case was diagnosed as thymoma with a part of granular cell proliferation and concurrent lymphoma cells.


Isolation and characterization of complementary deoxyribonucleic acid complementary to the highly abundant class of poly(adenylic acid)-containing ribonucleic acid from oocytes of Drosophila melanogaster.
The complementary deoxyribonucleic acid (cDNA) complementary to the highly abundant class of poly(adenylic acid)-containing ribonucleic acid [poly(A+) RNA] from Drosophila melanogaster oocytes has been isolated and characterized. Analysis of the kinetics of hybridization of this cDNA (cDNAHA) to total poly(A+) RNA of oocytes indicates this class contains approximately 86 different sequences. Hybridization kinetics of cDNAHA annealed to poly(A+) RNA from 19-old embryos is essentially the same as that of oocyte poly(A+) RNA. This suggests the highly abundant class of poly(A+) RNA persists in approximately the same frequency through early development. Analysis of the hybridization of cDNAHA to genomic DNA suggests that the highly abundant poly(A+) RNA from oocytes is not enriched for transcripts from repetitive sequences of the genome.


Comparison of disc and MIC reduction methods with polymerase chain reaction for the detection of metallo-β-lactamase in Pseudomonas aeruginosa.
The present study was undertaken to evaluate the screening antibiotic, confirmatory phenotypic test and agent against PCR as gold standard and to detect the prevalent MBL gene. Three hundred and twenty-six Pseudomonas aeruginosa isolates were screened for resistance to Imipenem (IPM), Meropemem (MEM) and Ceftazidime (CAZ) by disc diffusion. Isolates resistant to any of these were considered screen test-positive for MBL and were subjected to Double disc synergy test (DDST) and Disc potentiation test (DPT: Using IPM, MEM and CAZ alone and with EDTA), Minimum inhibitory concentration (MIC) reduction [four-fold or more reduction in MIC of IPM and MEM in presence of chelators: EDTA and 1,10-phenanthroline (EPI/EPM: EDTA-phenanthroline- Imipenem/Meropenem Broth Microdilution method)] and polymerase chain reaction (PCR) for blaIMP and blaVIM . Screen test-positives by MEM and CAZ were 19.3% as against 17.8% by IPM. MEMDDST, DPT and EPM confirmed 100% screen-test positives as against 93.7% by CAZ DDST and DPT-2, 76.2% by CAZ DPT-1, 88.9% by IPM DDST, 85.7% by IPM DPT-1 and 92.1% by EPI. IPMand CAZ DDST together confirmed 100% while IPM and CAZ DPT-2 confirmed 96.8%. All 63 screen-test positives showed the presence of blaVIM . MEM was found to be the best screening and confirmatory agent for MBL detection and blaVIM was found to be the prevalent MBL gene in this part of the country.


Argon attenuates the emergence of secondary injury after traumatic brain injury within a 2-hour incubation period compared to desflurane: an in vitro study.
Despite years of research, treatment of traumatic brain injury (TBI) remains challenging. Considerable data exists that some volatile anesthetics might be neuroprotective. However, several studies have also revealed a rather neurotoxic profile of anesthetics. In this study, we investigated the effects of argon 50%, desflurane 6% and their combination in an in vitro TBI model with incubation times similar to narcotic time slots in a daily clinical routine. Organotypic hippocampal brain slices of 5- to 7-day-old mice were cultivated for 14 days before TBI was performed. Slices were eventually incubated for 2 hours in an atmosphere containing no anesthetic gas, argon 50% or desflurane 6% or both. Trauma intensity was evaluated via fluorescent imagery. Our results show that neither argon 50% nor desflurane 6% nor their combination could significantly reduce the trauma intensity in comparison to the standard atmosphere. However, in comparison to desflurane 6%, argon 50% displayed a rather neuroprotective profile within the first 2 hours after a focal mechanical trauma (P = 0.015). A 2-hour incubation in an atmosphere containing both gases, argon 50% and desflurane 6%, did not result in significant effects in comparison to the argon 50% group or the desflurane 6% group. Our findings demonstrate that within a 2-hour incubation time neither argon nor desflurane could affect propidium iodide-detectable cell death in an in vitro TBI model in comparison to the standard atmosphere, although cell death was less with argon 50% than with desflurane 6%. The results show that within this short time period processes concerning the development of secondary injury are already taking place and may be manipulated by argon.


Controversies surrounding diet and breast cancer.
What we know about prevention of breast cancer is related to lifetime oestrogen exposure and exposures to specific oestrogens at vulnerable periods of life. This can be influenced by diet. The strongest indicator of a diet-related effect to date is the fairly consistent increase in breast cancer among women who are tall or obese (Hunter & Willett, 1993). The other dietary factors summarized in Table 1 are less strongly associated with breast-cancer risk in epidemiological studies. The relationship between fat and breast-cancer risk has been extensively studied but remains somewhat uncertain. Fat, as a contributor to energy intakes and energy imbalance, is probably a factor in the higher breast-cancer rates in Western countries. Beyond its role as an energy source, the evidence for an independent effect of dietary fat on breast-cancer risk is weak. More focused analyses of the role of individual fatty acids, and on lipid-related pesticide exposures, may reveal strong effects which are currently masked by the use of inadequate exposure measures, as well as by measurement error. Currently, there is substantial evidence of a weak relationship with alcohol consumption, even at frequencies of drinking of less than once daily. The evidence of a protective role for antioxidants is weaker for breast cancer than for other cancers. This might by expected in a cancer which is not strongly associated with cigarette smoking. Specific foods are being studied for other potentially-active ingredients which may be involved in hormone metabolism, but conclusive results for soyabean or cruciferous vegetables are not yet available. Studying these relationships will continue to be a challenge for researchers because of the difficulties in measuring dietary exposures, which is complicated by the uncertainty of the relevant time frame for exposure assessment. While substantial attention has been focused on studying diet in relation to incidence, the potential for diet to reduce recurrence of breast cancer is thoroughly under-studied. There is little reason to believe that the factors which influence the incidence of breast cancer, perhaps during childhood and puberty, are the same as those which affect recurrence in adulthood. In this area, the very limited evidence available suggests that study of biologically-active fatty acids is promising.


Differential display RT-PCR analysis of enterovirus-71-infected rhabdomyosarcoma cells reveals mRNA expression responses of multiple human genes with known and novel functions.
In order to better understand cellular responses to viral infection at the transcriptional level, we employed differential display RT-PCR to analyze mRNAs from RD rhabdomyosarcoma cells following infection with a neurovirulent enterovirus 71 (EV71) strain, compared with mRNAs from uninfected cells. Of 250 expressed sequence tags (ESTs) isolated, sequenced, and identified, all were of cellular origin except 1 that was of viral origin. Of these, 156 were individual distinctive clones, comprising 45 mRNAs showing unaltered expression and 111 mRNAs exhibiting upregulation or downregulation. Of the 45 uniformly expressed mRNAs, 14 represented unknown genes. Of the 111 differentially expressed mRNAs, 63 did not match any known genes. Forty-eight of the 111 mRNAs modified by EV71 infection matched known genes, including those encoding components of cell cycle, cytoskeleton, and cell death mediators; protein degradation mediators; mitochondrial-related proteins; components of protein translation and modification; and cellular transport proteins. The altered expression profiles of representative genes were authenticated by semiquantitative RT-PCR and real-time RT-PCR. We also identified a novel alternatively spliced transcript of TRIP7 thyroid receptor interactor protein; the putative human homolog of murine mc7 mRNA predominantly expressed in the brain; and a novel mRNA similar to that encoding vacuolar protein 8 involved in protein targeting. These results underscore the applicability of the mRNA differential display technique for elucidating the expression profiles of known and even novel genes in response to cellular infection with pathogenic viruses.


Associations between geographic residence and US adolescent and young adult cancer stage and survival.
Multiple studies have indicated that place of residence can influence cancer survival; however, few studies have specifically focused on geographic factors and outcomes in adolescents and young adults (AYAs) with cancer. The objective of this study was to evaluate evidence for geographic disparities in cancer diagnosis stage and overall survival in AYAs and to examine whether stage mediated survival associations. National Cancer Database data on AYAs aged 15 to 39 years who were diagnosed with cancer from 2010 to 2014 were obtained. Residence in Metropolitan (metro), urban, or rural counties at the time of diagnosis was defined using Rural-Urban Continuum Codes. Distance between the patient's residence and the reporting hospital was classified as short (≤2.5 miles), intermediate (>12.5 to <50 miles), or long (≥50 miles). Logistic and Cox proportional hazards regression models were used for analyses. The stage and survival analyses included 146,418 and 178,688 AYAs, respectively. The odds of a late versus early stage at diagnosis (stages III and IV vs I and II) were 1.16 (95% CI, 1.05-1.29) times greater for AYAs living in rural versus metro counties and 1.20 (95% CI, 1.16-1.25) times greater for AYAs living at long versus short distances to the reporting hospital. The hazard of death was 1.17 (95% CI, 1.05-1.31) and 1.30 (95% CI, 1.25-1.36) times greater for those living in rural versus metro counties, respectively, and for long versus short distances to the reporting hospital, respectively. Disease stage mediated 54% and 31% of the associations between metro, urban, or rural residence and residential distance categories and survival. Rural residence and living long distances from the reporting hospital were associated with later stage diagnoses and lower survival in AYAs with cancer. Further research is needed to understand mechanisms. Adolescents and young adults (AYAs) with cancer are a vulnerable population because cancer is of low suspicion in this population and may not be diagnosed in a timely manner. The authors evaluated evidence for geographic disparities in cancer stage at diagnosis and survival in the AYA population. The findings indicate that AYAs living in rural versus metropolitan US counties and those living farther from the diagnosis reporting hospital are more likely to be diagnosed at a later cancer stage, when it is generally less treatable, and have lower survival compared with AYAs living in metropolitan counties.


Mechanical Robustness of Graphene on Flexible Transparent Substrates.
This study reports on a facile and widely applicable method of transferring chemical vapor deposited (CVD) graphene uniformly onto optically transparent and mechanically flexible substrates using commercially available, low-cost ultraviolet adhesive (UVA) and hot-press lamination (HPL). We report on the adhesion potential between the graphene and the substrate, and we compare these findings with those of the more commonly used cast polymer handler transfer processes. Graphene transferred with the two proposed methods showed lower surface energy and displayed a higher degree of adhesion (UVA: 4.40 ± 1.09 N/m, HPL: 0.60 ± 0.26 N/m) compared to equivalent CVD-graphene transferred using conventional poly(methyl methacrylate) (PMMA: 0.44 ± 0.06 N/m). The mechanical robustness of the transferred graphene was investigated by measuring the differential resistance as a function of bend angle and repeated bend-relax cycles across a range of bend radii. At a bend angle of 100° and a 2.5 mm bend radius, for both transfer techniques, the normalized resistance of graphene transferred on polyethylene terephthalate (PET) was around 80 times less than that of indium-tin oxide on PET. After 10(4) bend cycles, the resistance of the transferred graphene on PET using UVA and HPL was found to be, on average, around 25.5 and 8.1% higher than that of PMMA-transferred graphene, indicating that UVA- and HPL-transferred graphene are more strongly adhered compared to PMMA-transferred graphene. The robustness, in terms of maintained electrical performance upon mechanical fatigue, of the transferred graphene was around 60 times improved over ITO/PET upon many thousands of repeated bending stress cycles. On the basis of present production methods, the development of the next-generation of highly conformal, diverse form factor electronics, exploiting the emerging family of two-dimensional materials, necessitates the development of simple, low-cost, and mechanically robust transfer processes; the developed UVA and HPL approaches show significant potential and allow for large-area-compatible, near-room temperature transfer of graphene onto a diverse range of polymeric supports.


Nuclear-encoded mitochondrial ribosomal proteins are required to initiate gastrulation.
Mitochondria are essential for energy production and although they have their own genome, many nuclear-encoded mitochondrial ribosomal proteins (MRPs) are required for proper function of the organelle. Although mutations in MRPs have been associated with human diseases, little is known about their role during development. Presented here are the null phenotypes for 21 nuclear-encoded mitochondrial proteins and in-depth characterization of mouse embryos mutant for the Mrp genes Mrpl3, Mrpl22, Mrpl44, Mrps18c and Mrps22 Loss of each MRP results in successful implantation and egg-cylinder formation, followed by severe developmental delay and failure to initiate gastrulation by embryonic day 7.5. The robust and similar single knockout phenotypes are somewhat surprising given there are over 70 MRPs and suggest little functional redundancy. Metabolic analysis reveals that Mrp knockout embryos produce significantly less ATP than controls, indicating compromised mitochondrial function. Histological and immunofluorescence analyses indicate abnormal organelle morphology and stalling at the G2/M checkpoint in Mrp null cells. The nearly identical pre-gastrulation phenotype observed for many different nuclear-encoded mitochondrial protein knockouts hints that distinct energy systems are crucial at specific time points during mammalian development.


A novel antigen defined by monoclonal antibody CR101 is associated with small cell lung carcinoma.
Small cell lung carcinoma (SCLC) represents about 25% of all lung cancers. Human SCLC shows neuroendocrine features such as the production of neural peptide hormones, marker enzymes and neurosecretory granules, and the expression of neural cell adhesion molecules (NCAMs). Although SCLC is sensitive to both chemotherapy and radiation, prognosis remains poor due to the appearance of post-treatment chemo- and radioresistant variants. Monoclonal antibodies (MAbs) have been developed that bind to SCLC tumor antigens. We have used similar technology to define another SCLC marker designated gP94/115. The MAb CR101 binds to a highly glycosylated, cell-surface antigen associated with SCLC. In vitro expression of the antigen appears to be restricted to cell lines of SCLC origin. Enzymatic removal of the sugars resolves the antigen into two proteins of 94 and 115 kD by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Fluorescence-activated cell sorting (FACS) analysis confirms the antibody's specificity. These results indicate that CR101 may recognize a novel protein expressed by SCLC.


Development of intracranial vasculitis in giant cell arteritis during tocilizumab treatment.
Giant cell arteritis (GCA), a systemic large-vessel vasculitis, is a disease that has been treated with glucocorticoids since 1950. Over the years, several disease-modifying anti-rheumatic drugs have been evaluated as steroid-sparing agents with disappointing results. Tocilizumab, an interleukin-6 inhibitor, has in recent years been approved for the treatment of GCA. It remains uncertain whether the drug suppresses disease activity and maintains remission or just alleviates the symptoms and masks the signs of smoldering disease. This case describes the clinical findings at diagnosis and the course of the disease with the subsequent development of intracranial vasculitis in a 70-year-old male treated with tocilizumab. The present case illustrates the need for further studies regarding tocilizumab in the treatment of GCA patients and the need for meticulous evaluation at follow-ups.


Occult breast carcinoma in reduction mammaplasty specimens: 14-year experience.
Reduction mammaplasty is commonly performed for bilateral macromastia, congenital asymmetry, or as a contralateral symmetry procedure in breast reconstruction following mastectomy for cancer. Occult carcinoma has been detected in 0.06 percent to 0.4 percent of breast reduction specimens. The purpose of this study was to examine the incidence of breast cancer in breast reductions performed in one institution over a 14-year period. The authors reviewed their experience with 800 reduction mammaplasties performed between 1988 and 2001. Six cancers were detected (0.8 percent). Of these cancers, three were invasive (0.4 percent) and three were ductal carcinoma in situ (0.4 percent). Stratified by indication for surgery, there was a trend toward higher detection rates in the reconstruction group (1.2 percent) compared with the macromastia (0.7 percent) or congenital asymmetry (0 percent) groups. Mammography was performed preoperatively in these patients and all results were negative for masses or suspicious microcalcification. Pathological diagnosis was guided by gross specimen evaluation in two patients and specimen radiography in one patient. Reduction mammaplasty has a small but definite risk of finding cancer in the resection specimen.


Measurement of atmospheric pollutants associated with oil and natural gas exploration and production activity in Pennsylvania's Allegheny National Forest.
Oil and natural gas exploration and production (E&P) activities generate emissions from diesel engines, compressor stations, condensate tanks, leaks and venting of natural gas, construction of well pads, and well access roads that can negatively impact air quality on both local and regional scales. A mobile, autonomous air quality monitoring laboratory was constructed to collect measurements of ambient concentrations of pollutants associated with oil and natural gas E&P activities. This air-monitoring laboratory was deployed to the Allegheny National Forest (ANF) in northwestern Pennsylvania for a campaign that resulted in the collection of approximately 7 months of data split between three monitoring locations between July 2010 and June 2011. The three monitoring locations were the Kane Experimental Forest (KEF) area in Elk County, which is downwind of the Sackett oilfield; the Bradford Ranger Station (BRS) in McKean County, which is downwind of a large area of historic oil and gas productivity; and the U.S. Forest Service Hearts Content campground (HC) in Warren County, which is in an area relatively unimpacted by oil and gas development and which therefore yielded background pollutant concentrations in the ANF. Concentrations of criteria pollutants ozone and NO2 did not vary significantly from site to site; averages were below National Ambient Air Quality Standards. Concentrations of volatile organic compounds (VOCs) associated with oil and natural gas (ethane, propane, butane, pentane) were highly correlated. Applying the conditional probability function (CPF) to the ethane data yielded most probable directions of the sources that were coincident with known location of existing wells and activity. Differences between the two impacted and one background site were difficult to discern, suggesting the that the monitoring laboratory was a great enough distance downwind of active areas to allow for sufficient dispersion with background air such that the localized plumes were not detected. Implications: Monitoring of pollutants associated with oil and natural gas exploration and production activity at three sites within the Allegheny National Forest (ANF) showed only slight site-to-site differences even with one site far removed from these activities. However, the impact was evident not in detection of localized plumes but in regional elevated ethane concentrations, as ethane can be considered a tracer species for oil and natural gas activity. The data presented serve as baseline conditions for evaluation of impacts from future development of Marcellus or Utica shale gas reserves.


Effects of ibudilast on hippocampal long-term potentiation and passive avoidance responses in rats with transient cerebral ischemia.
The present study evaluated the effects of ibudilast on impaired passive avoidance responses and hippocampal long-term potentiation (LTP) caused by transient cerebral ischemia in rats. The hippocampal nerve cell density was also measured. The latency determined in retention trials of passive avoidance shortened significantly in the 4-vessel occlusion (4VO) group (in which four blood vessels were occluded for 20 min to cause cerebral ischemia). A significant recovery in the latency was observed by administration of ibudilast (10 mg kg (-1)). The population spike amplitude in both the hippocampal CA1 region and perforant path-dentate gyrus synapses was potentiated by tetanus stimulation in the sham-operated group, while in the 4VO group, LTP was significantly inhibited. This inhibition was reversed by administration of ibudilast (10 mg kg (-1)). A marked reduction of cell densities in the CA1 region was observed in the 4VO group compared with the normal group. The nerve cell density in the hippocampal CA1 region was decreased by 20 min of cerebral ischemia. Ibudilast significantly inhibited the reduction of cell densities in a dose-dependent manner. In contrast, the cell density in the dentate gyrus was comparable in the 4VO and normal groups, and no significant changes were observed in the ibudilast groups. These findings suggest that ibudilast might possess neuronally protective properties, i.e. protecting neurons not only from deaths but also from functional damage due to certain cerebral ischemia.


Comparison of HR MAS MR spectroscopic profiles of breast cancer tissue with clinical parameters.
Breast cancer is the most frequent form of cancer in women and improved diagnostic methods are desirable. Malignant cells have altered metabolism and metabolic mapping might become a tool in cancer diagnostics. High-resolution magic angle spinning (HR MAS) MR spectroscopy of tissue biopsies provides detailed information on metabolic composition. The 600 MHz 1H HR MAS spectra were acquired of breast cancer tissue from 85 patients and adjacent non-involved tissue from 18 of these patients. Tissue specimens were investigated by microscopy after MR analysis. The resulting spectra were examined by three different approaches. Relative intensities of glycerophosphocholine (GPC), phosphocholine (PC) and choline were compared for cancerous and non-involved specimens. Eight metabolites, choline, creatine, beta-glucose, GPC, glycine, myo-inositol, PC and taurine, were quantified from the recorded spectra and compared with tumor histological type and size, patient's lymph node status and tissue composition of sample. The spectra were also compared with tumor histological type and size, lymph node status and tissue composition of samples using principal component analysis (PCA). Tumor samples could be distinguished from non-involved samples (82% sensitivity, 100% specificity) based on relative intensities of signals from GPC, PC and choline in 1H HR MAS spectra. Tissue concentrations of metabolites showed few differences between groups of samples, which can be caused by limitations in the quantification procedure. Choline and glycine concentrations were found to be significantly higher in tumors larger than 2 cm compared with smaller tumors. PCA of MAS spectra from patients with invasive ductal carcinomas indicated a possible prediction of spread to axillary lymph nodes. Metabolite estimates and PCA of MAS spectra were influenced by the percentage of tumor cells in the investigated specimens.


Novel application of drug-coated balloons in coronary heart disease: A narrative review.
The incidence of coronary heart disease (CAD) has soared over the years, and coronary intervention has become an increasingly important therapeutic approach. The past decade has witnessed unprecedented developments in therapeutic medical instruments. Given that drug-coated balloons bring many benefits, they are indicated for an increasing number of conditions. In this article, we review the results of current clinical trials about drug-coated balloons and summarize their safety and clinical progression in different coronary artery diseases, laying the groundwork for basic research, and clinical therapeutics of this patient population.


Multiplex zymography captures stage-specific activity profiles of cathepsins K, L, and S in human breast, lung, and cervical cancer.
Cathepsins K, L, and S are cysteine proteases upregulated in cancer and proteolyze extracellular matrix to facilitate metastasis, but difficulty distinguishing specific cathepsin activity in complex tissue extracts confounds scientific studies and employing them for use in clinical diagnoses. Here, we have developed multiplex cathepsin zymography to profile cathepsins K, L, and S activity in 10 μg human breast, lung, and cervical tumors by exploiting unique electrophoretic mobility and renaturation properties. Frozen breast, lung, and cervix cancer tissue lysates and normal organ tissue lysates from the same human patients were obtained (28 breast tissues, 23 lung tissues, and 23 cervix tissues), minced and homogenized prior to loading for cathepsin gelatin zymography to determine enzymatic activity. Cleared bands of cathepsin activity were identified and validated in tumor extracts and detected organ- and stage-specific differences in activity. Cathepsin K was unique compared to cathepsins L and S. It was significantly higher for all cancers even at the earliest stage tested (stage I for lung and cervix (n = 6, p < .05), and stage II for breast; n = 6, p < .0001). Interestingly, cervical and breast tumor cathepsin activity was highest at the earliest stage we tested, stages I and II, respectively, and then were significantly lower at the latest stages tested (III and IV, respectively) (n = 6, p < 0.01 and p < 0.05), but lung cathepsin activity increased from one stage to the next (n = 6, p < .05). Using cathepsin K as a diagnostic biomarker for breast cancer detected with multiplex zymography, yielded 100% sensitivity and specificity for 20 breast tissue samples tested (10 normal; 10 tumor) in part due to the consistent absence of cathepsin K in normal breast tissue across all patients. To summarize, this sensitive assay provides quantitative outputs of cathepsins K, L, and S activities from mere micrograms of tissue and has potential use as a supplement to histological methods of clinical diagnoses of biopsied human tissue.


Expression and Function of Eicosanoid-Producing Cytochrome P450 Enzymes in Solid Tumors.
Oxylipins derived from the oxidation of polyunsaturated fatty acids (PUFAs) act as important paracrine and autocrine signaling molecules. A subclass of oxylipins, the eicosanoids, have a broad range of physiological outcomes in inflammation, the immune response, cardiovascular homeostasis, and cell growth regulation. Consequently, eicosanoids are implicated in the pathophysiology of various diseases, most notably cancer, where eicosanoid mediated signaling is involved in tumor development, progression, and angiogenesis. Cytochrome P450s (CYPs) are a superfamily of heme monooxygenases generally involved in the clearance of xenobiotics while a subset of isozymes oxidize PUFAs to eicosanoids. Several eicosanoid forming CYPs are overexpressed in tumors, elevating eicosanoid levels and suggesting a key function in tumorigenesis and progression of tumors in the lung, breast, prostate, and kidney. This review summarizes the current understanding of CYPs' involvement in solid tumor etiology and progression providing supporting public data for gene expression from The Cancer Genome Atlas.


Biotyping and virulence factors in clinical and environmental isolates of Aeromonas species.
Biochemical characteristics and virulence factors were compared in 147 Aeromonas spp. isolated from patients with diarrhea and in 94 strains isolated from metropolitan water supplies in the same area during the same period. Fermentation of arabinose occurred with 58.5% of the environmental strains and 15% of the clinical isolates; 39.4% of the strains from water and 6.8% of the fecal isolates fermented salicin. The frequency of esculin hydrolysis was the same in both groups. Ninety-one percent of clinical isolates and 70.2% of environmental strains were enterotoxigenic and, except for four clinical isolates, all of these strains also produced hemolysins. Hemagglutination that was inhibited by fucose and mannose but not by galactose was found in 67% of the water isolates and 10.2% of the clinical strains. Although the distribution of several characteristics differs in clinical and environmental strains, many of the strains found in water have properties identical with those of the clinical isolates. We suggest that such strains may be potential enteric pathogens.


Expressive language disturbance in borderline personality disorder in response to emotional autobiographical stimuli.
Clinicians recognize expressive language disturbances in borderline personality disorder (BPD) as a feature attenuating psychiatric history-taking. Neuroimaging studies demonstrate activation of key differentiating neural networks characterizing a traumatic memory system in BPD patients. Yet there are few BPD studies evaluating expressive language disturbances in response to emotionally salient, clinically relevant stimuli and no controlled studies. The aim was to examine expressive language disturbances in response to a clinically relevant emotional stimulus, the Adult Attachment Interview (AAI). Twenty BPD participants and 20 age-, sex-, and education-matched controls were administered the AAI. Verbatim transcripts were analyzed by four computerized measures designed to evaluate various linguistic components of speech (i.e., overall expressive language impairment, lexical complexity, syntactic complexity, and semantic complexity). BPD participants evidenced significantly greater levels of overall expressive language impairment and reduced syntactic and lexical complexity, but not semantic complexity scores. Detailed linguistic profiles demonstrated specific deficits linked to BPD.


Retrieval of aerosol size distribution from angular scattering functions: effects of particle composition and shape.
The retrieval sensitivity in regard to the recovery of aerosol size distributions using particle angular scattering properties is investigated. Previous retrieval methods have all assumed that the scattering characteristics of spheres is adequate to retrieve size distributions. The present results show that particle nonsphericity can have a significant effect upon the retrieval. In particular assumptions based upon Mie spheres may lead to interpretations of spurious multimodal distributions. Furthermore, it is also shown that shape effects cannot be separated from composition effects. The effect on retrieved size distributions is investigated due to (1) variations in the particle index of refraction, (2) truncation of angular scattering intensities due to measurement limitations, (3) the use of two-component shell particles, (4) nonsphericity using the semi-empirical approach, and (5) the replacement of spherically shaped particles by cylindrically shaped fibers.


Alzheimer's Disease Drug Discovery--11th International Conference--Promising New Therapeutic Approaches. 27-28 September 2010, Jersey City, NJ, USA.
The 11th Alzheimer's Disease Drug Discovery International Conference, held in Jersey City, NJ, USA, included topics covering new therapeutic developments in the field of Alzheimer's disease. This conference report highlights selected presentations on the use of patient-specific stem cells, and neuroprotection, regeneration and cognitive enhancement strategies for the prevention or treatment of Alzheimer's disease. Investigational approaches discussed include allopregnanolone for neuron protection and regeneration, PDE5 inhibitors as therapeutics, upregulating the protein Klotho to prevent cognitive decline, targeting memory deficits induced by Aβ42 oligomers, inhibiting striatal-enriched protein tyrosine phosphatase (STEP) for treating neuropsychiatric disorders, and agonism of GABA-A receptors to treat age-related cognitive deficits.


International conference on byssinosis. Mechanisms of disease induction.
From this work and other published data there are at least three distinct compounds that have been shown to be capable of inducing symptoms of byssinosis. There is an aminopolysaccharide-protein complex in cotton plant bracts that acts by causing histamine release in the human lung and also causes necrosis of bronchiolar epithelium. There is endotoxin or endotoxin-like material present in cotton plant bracts that acts by a mechanism other than by causing histamine release. This can induce histologic features of chronic bronchitis over a period of time. There is a polyphenol compound whose action is unlikely to be via complement activation, even though higher titers of antibody to it are present in byssinotic compared with nonbyssinotic subjects. It is postulated that such a compound is held in the lungs by antibody and exerts its effect on the pulmonary vasculature, altering capillary resistance. It also produces pathologic change as might be expected from its ability to precipitate proteins and activate complement.


Combined Therapy for a Rare Case of Type III Dens Invaginatus in a Mandibular Central Incisor with a Periapical Lesion: A Case Report.
Type III dens invaginatus has a complex root canal structure that poses a greater challenge when endodontic treatment is necessary. Type III dens invaginatus rarely affects mandibular central incisors. In this case, we reported a combined therapy of type III dens invaginatus in a mandibular central incisor with a periapical lesion. Cone-beam computed tomographic (CBCT) imaging was used in the diagnosis and management of the unusual anatomy of dens invaginatus. First, the hard tissue of the dens invaginatus was removed using a dental operating microscope. The root canal was then prepared with a nickel-titanium instrument and filled with mineral trioxide aggregate and gutta-percha. Subsequently, a surgical treatment was performed using a dental operating microscope because the patient still had an apical infection after root canal treatment and the periapical lesion was not fully healed. In addition, the patient had requested a quick and thorough treatment for personal reasons. The granulomatous soft tissue was then curetted under local anesthesia followed by a surgical retrograde approach to negotiate and obturate the apical patent portion of the invagination. The bone window was filled with BonaGraft (YHJ Science and Trade, Beijing, China) and covered with a collagen membrane. The use of CBCT imaging and a dental operating microscope was important for ensuring a predictable outcome in this case.


The lived experience of feeling misunderstood.
The purpose of this study was to uncover the structure of the lived experience of feeling misunderstood. Parse's phenomenological-hermeneutic research method was used to answer the research question: What is the structure of the lived experience of feeling misunderstood? Extraction-synthesis revealed four core concepts. The structure is the lived experience of feeling misunderstood is disheartening insignificance surfacing with discordant affiliations, as resignation with resiliency emerges with inventive endeavors. Implications for nursing research and practice are presented.


[Hormone level and metabolism of xenobiotics in rats with various phenotype of resistance to hypoxia].
The blood of rats with initially low (LR) and high (HR) resistance to hypoxia was characterized with respect to the levels of testosterone, corticosterone, insulin and the activity of liver monooxygenase system enzymes. In response to the acute hypoxia model induction, the level of corticosterone in LR rats was significantly greater than that in HP rats (179 and 24%, respectively). The increase in the blood corticosterone level was accompanied by an increase in the activity of enzymes involved in the metabolism of xenobiotics. Animals with the high corticosterone level were also characterized by more intensive metabolism of testosterone and erythromycine. The metabolism of these substrates depends on the activity of isoforms of the cytochrome P-450 3A family. The high corticosterone concentrations in the plasma of LR rats, appearing in response to the acute hypoxia, exhibit a pronounced stimulating action upon the enzyme 11 beta-hydroxysteroiddehydrogenase, which is accompanied by a more pronounced increase in the corticosterone concentration in liver tissues as compared to that in HR animals. The higher content of corticosterone in LR rats leads to an increase in the concentration of cytochrome P-450 and stimulates the enzymatic activity of 3A isoforms in the liver tissues.


Changes in stored and short-term cultures of mouse bone marrow cells.
Changes in cells of mouse bone marrow cultured for 6--24 hr were followed both when fresh, and after storage for 3 to 5 days at a temperature of +2 to +4 degrees C. Considerable alterations were observed in the morphology, activity and transformation of these cells both during the storage period and the subsequent culture. Phagocyte ability was also detected in these cultures.


[Regulation of microRNA-126 on the polarization of human macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide].
Objective: To study the effect of microRNA-126 (miR-126) on the polarization of human monocyte-derived macrophages stimulated by Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS). Methods: Macrophages derived from human myeloid leukemia mononuclear cells were stimulated by Pg-LPS (5 mg/L) and by Pg-LPS (5 mg/L) after 24 h-transfection of miR-126 mimic or negative control RNA for 48 h, respectively. Real-time quantitative-PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blotting were conducted to detect the changes in miR-126, pro-inflammatory factor tumor necrosis factor-α (TNF-α), anti-inflammatory factors interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1) and M1 polarization-related pathways such as nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Results: Compared with non-LPS stimulation group (TNF-α: 1.000±0.020, iNOS: 1.125±0.064, miR-126: 1.004±0.113, IL-10: 1.003±0.053, Arg-1: 1.130±0.061), the mRNA levels of TNF-α (3.105±0.278) and iNOS (4.296±0.003) increased significantly (t=6.53, P=0.003; t=42.63, P<0.001, respectively), while miR-126, IL-10 and Arg-1 expressions (0.451±0.038, 0.545±0.004 and 0.253±0.017) decreased significantly (t=7.95, P=0.001; t=7.36, P=0.002; t=11.94, P<0.001, respectively) after Pg-LPS stimulated by human-derived macrophages for 48 h. The protein expression of iNOS, TNF-α, Arg-1 and IL-10 were consistent at mRNA levels. Meanwhile, the expressions of phospho-NF-κB p65 (p-p65), phospho-extracellular signal-regulated kinase (p-ERK) and phospho-p38 MAPK (p-p38) increased significantly, while the expression of Arg-1 decreased significantly. Compared with the negative controls (scramble RNA) (TNF-α: 1.141±0.197, iNOS: 1.173±0.115, IL-10: 1.032±0.138, Arg-1: 0.933±0.044), the mRNA levels of TNF-α (0.342±0.022) and iNOS (0.588±0.085) expressions significantly decreased (t=5.35, P=0.006; t=5.05, P=0.007), while IL-10 (1.786±0.221) and Arg-1 expressions (2.152±0.229) significantly increased (t=3.71, P=0.021; t=6.21, P=0.003) after Pg-LPS stimulation with miR-126 mimic transfection. The relative protein expressions of iNOS, p-p65, p-ERK and p-p38 significantly decreased (t=13.00, P<0.001; t=6.98, P=0.002; t=10.86, P<0.001; t=8.32, P=0.001), while the protein level of Arg-1 significantly increased (t=12.08, P<0.001). Conclusions: Pg-LPS could promote M1 polarization of macrophages. miR-126 might inhibit the effect of Pg-LPS on the M1 polarization of macrophages through down-regulating NF-κB and MAPK signaling pathways.


Head and Bottle Angles Achieved by Patients During High-Volume Sinonasal Irrigations.
Certain head positions can optimize topical irrigation distribution to specific sinuses. No studies have assessed whether patients attain these positions when irrigating. The purpose of this study was to assess head and bottle angles achieved when patients irrigate based on instructions from an irrigation device or from a Rhinologist. Study approval was obtained from Henry Ford Health System's Institutional Review Board (10604). Forty-two patients with various rhinologic conditions were equally divided into groups based on irrigation instruction type: pictoral instructions from an irrigation device or written/verbal instructions from a Rhinologist. Both groups' instructions directed nose-to-floor head positioning. Simulating home irrigations, patients irrigated 120 mL of saline into each naris using 240 mL squeeze bottles. Frontal and lateral views were captured using video cameras. On frontal view, angles were measured between (1) nasal dorsum (ND) and bottle tip (BT; n = 84) and (2) ND and vertical (V; n = 84). On lateral view, angles were measured between (1) line from nasion-to-pogonion (NTP) and horizontal (H) (n = 73) and (2) NTP and BT (n = 73). On lateral view, average angle between NTP and H was 20.0° (standard deviation [SD] = 13.1, 95% confidence interval [CI] = 17.0-23.0) and between NTP and BT was 59.4° (SD = 15.8, 95% CI = 55.8-63.1). On frontal view, average angle between ND and V was 9.5° (SD = 19.5, 95% CI = 5.3-13.6) and between ND and BT was 24.5° (SD = 12.0, 95% CI = 21.9-27.0). There were no significant angle differences between sides or instruction types. When instructed to irrigate in the nose-to-floor head position, patients achieved a head position uprotated 20° on lateral view and vertex rotated 10° away from the side of irrigation on frontal view.


Chromatographic Separation and NMR An Integrated Approach in Pharmaceutical Development.
Over the past 10 years, major improvements in the performance of LC-NMR have been realized. The addition of postcolumn SPE, advances in probe technology including cryogenic probes and microcoil probes, improved solvent suppression pulse sequences, and shielded magnets with better homogeneity have all contributed to rapid advancements in this technology. Application of LC-NMR to problems in pharmaceutical development has had a major impact on structure elucidation studies. LC-NMR has been successfully applied to determine the structures of degradation products, impurities, mixtures of compounds, and metabolites. Use of stop flow techniques with LC-NMR experiments has been a critical means of identifying unstable compounds and studying conformational kinetics. The integration of SPE as an intermediate step between the LC unit and the NMR spectrometer has vastly improved the power of the hyphenated technique in trace analysis applications. Online postcolumn enrichment of chromatographic peaks by SPE dramatically reduces the NMR acquisition times by allowing repeated injections to be trapped onto the same cartridge or different cartridges. Because protonated solvents can be easily removed with a drying procedure, solvents and buffers may be freely chosen for maximizing chromatographic separation without compromising NMR spectral quality. The compound of interest may then be eluted from an SPE cartridge using deuterated organic solvent, which helps to reduce dynamic range issues. When combined with cryogenically cooled microcapillary probes, the sensitivity of the NMR signal increases about 10-fold over conventional room temperature probes, enabling full structure characterization at the microgram level. Heteronuclear experiments with concentrations previously only possible in a limited number of cases have now become standard experiments. The availability of HSQC and HMBC experiments and microcoil/cryogenic technology opens the possibility of using LC-(SPE) NMR for the structural elucidation of complete unknowns on a microgram scale. To enable significant future downscaling beyond the current capabilities, improved performance of the LC-NMR interface and improved SPE cartridge retention need to be addressed. In addition, the active volume of the NMR flow cell or capillary tube will have to shrink along with the corresponding detection coils in order not to lose filling factor. As the size of the NMR probes become more efficient with respect to mass sensitivity, techniques such as CE or capillary electrochromatography (CEC) may be interfaced more successfully with NMR spectroscopy. Overall, the current state of the art in LC-NMR has demonstrated proven utility in a variety of applications. When combined with SPE and cryotechnology, LC-NMR has become an extremely valuable tool for mass limited samples, enabling structure elucidation without the need for laborious serial isolation and purification procedures.


Curcumolide reduces diabetic retinal vascular leukostasis and leakage partly via inhibition of the p38MAPK/NF-κ B signaling.
Retinal inflammation in a hyperglycemic condition is believed to play a crucial role in the development of diabetic retinopathy, and targeting inflammatory mediators is a promising strategy for the control of diabetic retinopathy. Curcumolide, a novel sesquiterpenoid with a unique 5/6/5 tricyclic skeleton, was isolated from Curcuma wenyujin. In this study, we demonstrate that treatment with curcumolide alleviated retinal inflammatory activities both in vitro and in vivo in a STZ-induced diabetic rat model and in TNF-α-stimulated HUVECs. Curcumolide alleviated retinal vascular permeability and leukostasis and attenuated the overexpression of TNF-α and ICAM-1 in diabetic retinas. Moreover, curcumolide also inhibited inducible p38 MAPK and NF-κB activation and the subsequent induction of proinflammatory mediators. These data suggest potential treatment strategies against diabetic retinopathy, particularly in the early stages of the disease.


Characteristics and course of major depression in older primary care patients.
Identify the morbidity patterns displayed by older primary care patients experiencing depressive symptomatology who do and do not meet criteria for a major depression. Patients ages sixty and older presenting at two ambulatory internal medicine centers were administered the CES-D. Among those scoring > or = 11, 104 completed a comprehensive assessment of their psychiatric symptomatology, medical illness, and functional abilities. The assessment battery was again administered six months later. The point prevalence of major depression in older primary care patients is estimated at 9 percent based on SCID interviews. Patients meeting criteria for this diagnosis compared to those who are symptomatic but not experiencing a major depression described more extensive psychopathology but also significantly more limitations in performing social and functional roles. At six-month follow-up, only 11.5 percent of those initially diagnosed with a major depression were considered fully recovered. Major depression is a prevalent disorder in older primary care patients which affects their ability to perform expected social and physical roles. Mechanisms for delivering efficacious treatments in routine medical practice are of a high priority.


PredCID: prediction of driver frameshift indels in human cancer.
The discrimination of driver from passenger mutations has been a hot topic in the field of cancer biology. Although recent advances have improved the identification of driver mutations in cancer genomic research, there is no computational method specific for the cancer frameshift indels (insertions or/and deletions) yet. In addition, existing pathogenic frameshift indel predictors may suffer from plenty of missing values because of different choices of transcripts during the variant annotation processes. In this study, we proposed a computational model, called PredCID (Predictor for Cancer driver frameshift InDels), for accurately predicting cancer driver frameshift indels. Gene, DNA, transcript and protein level features are combined together and selected for classification with eXtreme Gradient Boosting classifier. Benchmarking results on the cross-validation dataset and independent dataset showed that PredCID achieves better and robust performance compared with existing noncancer-specific methods in distinguishing cancer driver frameshift indels from passengers and is therefore a valuable method for deeper understanding of frameshift indels in human cancer. PredCID is freely available for academic research at http://bioinfo.ahu.edu.cn:8080/PredCID.


EMS patients and walk-in patients presenting with severe sepsis: differences in management and outcome.
Sepsis is a significant problem. The differences between patients with sepsis who walk into the emergency department (ED) and those who are transported via emergency medical services (EMS) have not been clarified. The aim of the study was to determine whether there was a difference in outcome between patients arriving by EMS and those presenting directly to the ED. We prospectively collected and reviewed a cohort of all cases of severe sepsis and septic shock admitted to the medical intensive care unit from the ED from November 2009 to March 2012. Extracted data were basic demographic information (including mode of ED arrival), clinical data, and treatments. We calculated Systemic Inflammatory Response Syndrome criteria, Acute Physiology and Chronic Health Evaluation II scores, and Sequential Organ Failure Assessment (SOFA) scores. The primary outcome was mortality in severely ill patients with sepsis. A total of 378 subjects (78%) presented by EMS and 107 subjects were walk-in patients (22%). Patients transported via EMS were older (P < 0.01), had fewer lactates >4 (P < 0.02), a more altered mental status (P < 0.01), and higher respiratory rates (P < 0.05) than did walk-in patients. Patients transported by EMS had worse disease severity when measured by an Acute Physiology and Chronic Health Evaluation II score (P < 0.01) but not by SOFA score. EMS patients had a shorter time to receiving antibiotics (P = 0.02) and central line placement (P < 0.01) than did walk-in patients. In a logistic model, mortality was associated with increasing age (adjusted odds ratio 1.3; 95% confidence interval [CI] 1.2-1.4), higher first-measured ED lactates (1.2; 95% CI 1.1-1.2), and increased initial SOFA score (adjusted odds ratio 1.2; 95% CI 1.1-1.3) but not EMS arrival or prehospital fluids. Neither arrival by EMS nor fluid administration by EMS is associated with decreased mortality in severe sepsis.


Social-emotional problems of children with mild intellectual disabilities having parents with mental health concerns: A quantitative comparison study.
Children of parents with mental health concerns are at-risk for social-emotional problems. In this study, we assessed whether children with a mild intellectual disability and parents with mental health concerns are particularly at-risk. Strengths and Difficulties Questionnaire (SDQ) reports of children with a mild intellectual disability (N = 55) and their parents with mental health concerns (N = 45) were compared to two comparison groups. The first group included children with average intelligence (N = 13) and their parents with mental health concerns (N = 56), the second group included children with mild intellectual disability (N = 44) and their parents (N = 36). Children with a mild intellectual disability and a parent with mental health concerns show higher total SDQ problem scores and more internalizing and externalizing problems as compared to children in the two other groups. Children having mild intellectual disability and parents with mental health concerns are particularly at risk for developing social-emotional problems.


Case report of a primary effusion lymphoma successfully treated with oral valganciclovir after failing chemotherapy.
Primary effusion lymphoma is a rare non-Hodgkin lymphoma that presents with pleural effusions and lacking of tumour mass. It is universally associated with human herpesvirus 8 (HHV8) and is more frequent among immunosuppressed patients. There is no standard treatment, chemotherapy and anti-HIV therapy have been used with poor results, but there is still no strong evidence supporting the use of valganciclovir. We present the case of a HIV positive man that presented with pleural effusion compatible with primary effusion lymphoma and positivity for HHV8 DNA in blood. Bortezomib-containing treatment protocol was started, but the disease progressed within the chemotherapy. Therefore, treatment with oral valganciclovir was decided and the patient achieved a sustained radiological complete response. HHV8 DNA turned negative 6 months after starting the treatment with valganciclovir.


Complete heart block and asystole following blunt cardiac trauma.
Cardiac contusion is a well-recognized complication of blunt chest trauma. Various conduction system disorders have been reported in association with this condition, the most common being right bundle branch block. Complete heart block (CHB) is seen rarely. Most cases of CHB are transient. We present the case of an 80-year-old woman who developed CHB and asystole following blunt cardiac trauma. Malignant cardiac arrhythmias such as CHB can be associated with blunt cardiac trauma. In most cases, CHB is transient resolving in days to weeks. In rare cases, however, CHB leads to asystole. Close monitoring and prompt intervention is thus required.


The use of emergency contraceptive pills in India: A meta-analysis.
Unplanned pregnancies are a major public health concern. In India, 33% of an estimated 48.1 million pregnancies end in induced abortions. Emergency contraceptive pills (ECPs) can prevent pregnancy after sexual intercourse, have been part of India's family planning program since 2002-2003 and are available as over-the-counter drugs. While there are concerns about the overuse of ECPs, the pattern of use of ECPs in India is unknown. The objective is to determine the proportion of women who have ever used ECPs and repeatedly used ECPs and also to assess the reasons for use and nonuse of EC pills along with factors associated with the use. A systematic review of ECP use in India was conducted by electronically searching three databases-PubMed, Popline, and Google Scholar. All studies were published between 2001 and 2017, and the electronic search was last conducted in July 2018. The proportion of use was calculated using meta-analysis, and the other factors were assessed by narratively synthesizing the findings. Thirty-three articles met the inclusion criteria. The pooled proportion of women who ever used ECPs was 6% (95% confidence interval, 0.03-0.10). The proportion of repeat use ranged from 12% to 69%. Five studies reported reasons for not using ECPs, and the most common reasons were religious/cultural beliefs followed by fear of side effects and inadequate knowledge. Studies to understand sociodemographic and other factors affecting the use of ECPs in India are lacking. There are significant concerns about the quality of the studies. The definition of repeat use of ECPs is inconsistent across papers. Furthermore, judgmental attitudes of health-care providers were apparent in some papers. The review highlights important research and program gaps.


A phylogenetic study of the tribe Antirrhineae: Genome duplications and long-distance dispersals from the Old World to the New World.
Antirrhineae is a large tribe within Plantaginaceae. Mostly concentrated in the Mediterranean Basin, the tribe members are present both in the Old World and the New World. Current Antirrhineae phylogenies have different views on taxonomic relationships, and they lack homogeneity in terms of geographic distribution and ploidy levels. This study aims to investigate the changes in the chromosome numbers along with dispersal routes as definitive characters identifying clades. With the use of multiple DNA regions and taxon sampling enriched with de novo sequences, we provide an extensive phylogeny for Antirrhineae. The reconstructed phylogeny was then used to investigate changes in ploidy levels and dispersal patterns in the tribe using ChromEvol and RASP, respectively. Antirrhineae is a monophyletic group with six highly supported clades. ChromEvol analysis suggests the ancestral haploid chromosome number for the tribe is six, and that the tribe has experienced several duplications and gain events. The Mediterranean Basin was estimated to be the origin for the tribe with four long-distance dispersals from the Old World to the New World, three of which were associated with genome duplications. On an updated Antirrhineae phylogeny, we showed that the three out of four dispersals from the Old World to the New World were coupled with changes in ploidy levels. The observed patterns suggest that increases in ploidy levels may facilitate dispersing into new environments.


Characterization of cadmium uptake, translocation and storage in near-isogenic lines of durum wheat that differ in grain cadmium concentration.
Here we examined several physiological properties of two near-isogenic lines of durum wheat (Triticum turgidum var. durum) that differ in grain cadmium accumulation, to identify the function of a gene locus that confers differential grain Cd concentrations. Time- and concentration-dependent uptake and translocation studies using 109Cd were conducted on nutrient solution-grown seedlings. Root extracts were analysed by inductively coupled plasma emission spectrometry, gel filtration and capillary electrophoresis to determine the interaction between Cd and phytochelatins (PCs) in storage of Cd in roots. The two isolines did not differ in time- or concentration-dependent root Cd uptake, but the low grain-Cd-accumulating isoline showed decreased movement of Cd from roots to shoots. All buffer-soluble Cd extracted from roots of both isolines was in the form of a low-molecular-weight PC-containing complex. The data suggest that PC synthesis is not a limiting factor in the differential storage of Cd in roots, and that movement of Cd through the root and into the transpiration stream may be the cause of differential Cd partitioning in the two isolines.


Ameliorative effects of quercetin on sodium fluoride-induced oxidative stress in rat's kidney.
The in vivo nephroprotective effect of quercetin against sodium fluoride (NaF)-induced damage was studied. Renal injury was induced by daily administration of NaF (600 ppm) through drinking water for 1 week. The levels of reduced glutathione (GSH), lipid peroxidation as well as superoxide dismutase and catalase activity of kidney homogenates were determined. The serum markers of glomerular damage, including creatinine, serum urea, and blood urea nitrogen levels, were also assessed. The study revealed that administration of fluoride resulted in a significant downregulation of antioxidant defenses coupled with an increased serum level of glomerular damage markers. The administration of quercetin prior to fluoride reversed the antioxidant-oxidant balance to control (fluoride-untreated) level. The level of protection obtained for the 20 mg/kg quercetin treatment was equivalent to the positive control, ascorbic acid (10 mg/kg). The therapeutic implication of antioxidants in fluoride-induced nephrotoxicity is discussed. This study showed that NaF intoxication caused renal damage by increasing oxidative stress, and quercetin and vitamin C administration gave protection against fluoride-induced oxidative stress to some degree.


Expanded functions in the apical cell domain to regulate the growth rate of imaginal discs.
The Drosophila expanded (ex) gene encodes a product (Ex) that shares homology with the Protein 4.1 family of proteins, many of which are enriched at specific lateral cell junctions and the apical cellular domain. Ex colocalizes with actin in the apical domain of imaginal disc epithelial cells, where it partially overlaps the distribution of phosphotyrosine (PY)-containing proteins. This suggests that Ex is present in or associated with adherens junctions. Genetic studies show that Ex is necessary for proper regulation of final cell number in adult wings and for the formation of eyes, distal leg, and distal antennal segments. We have generated mitotic clones that lack Ex using the twin spot technique, and demonstrated that the primary function of Ex is to regulate cell proliferation. Overexpressing Ex protein results in a decrease in final cell number in wings, suggesting a direct relationship between Ex function and proliferation rate.


Mitochondrial DNA restriction fragment length polymorphisms in field isolates of the Aspergillus niger aggregate.
The mitochondrial DNAs (mtDNAs) and the ribosomal repeat unit (ribosomal DNA, rDNA) of black Aspergillus isolates collected in various parts of the world were examined. Wide-ranging mtDNA variation was observed in natural populations of the Aspergillus niger aggregate. Most isolates were classifiable as A. niger or Aspergillus tubingensis according to their rDNA and mtDNA patterns. The mtDNA variation was distributed unevenly in the populations studied. The mtDNAs of most of the isolates collected in Australia were of the A. tubingensis type, with an unexpectedly high degree of variation, while the rDNA of these isolates exhibited the same A. tubingensis pattern as that of isolates from other locations. Some other local populations displayed very little polymorphism in their mtDNA and rDNA. Hybridization experiments in which cloned A. niger and Aspergillus nidulans mtDNA fragments were used revealed that the two main mtDNA groups corresponding to A. niger and A. tubingensis are more distantly related than concluded earlier. Six of the 13 Brazilian isolates examined exhibited mtDNA and rDNA types different from those of all the other strains and could not be classified into the above species. Classical taxonomic examination of these strains is in progress.


Reasons for uses of physical restraint and alternatives to them in geriatric nursing: a questionnaire study among nursing staff.
This study is part of a major research project that is concerned with disruptive behaviour among elderly patients and the use of physical restraint in geriatric nursing. The purpose of this study was to describe the use of physical restraint and alternatives as reported by professional nurses. The data were collected by a structured questionnaire. Nursing staff (n = 287) from a geriatric unit of a health centre, a nursing home, and the medical and psychiatric clinics of a university hospital in one city in central Finland, volunteered for the study. The clear majority (85%) of the nurses stated that physical restraint had been used on the ward during the week preceding the questionnaire. Reasons cited most often for restraint use were reduced physical and cognitive capacity of demented patients. The most common alternative was to try to understand the reasons for the elderly patient's disruptive behaviour. A major challenge for future research and for field experiments is to provide new alternatives to the use of physical restraint in geriatric nursing.


Evaluation of purified protein derivates test at tuberculosis dispensary in Hatay, Turkey, applied to Turks and Syrian refugees (2012-2015).
The aim of the study was to evaluate results of purified protein derivates (PPD) test applied at the Tuberculosis Dispensary between 2012-2015 in Hatay, Turkey, where a large number of Syrian refugees have migrated since the Syrian civil war began in 2011. PPD test records from the Electronic Tuberculosis Management System at the Tuberculosis Dispensary from 2012-2015 were analyzed based on nationality, age groups, BCG scar availability, and PPD reaction. The annual risk of tuberculosis infection (ARTI) was calculated based on years for each age group in Turks and Syrian refugees and the trend was evaluated. Student-t, Chi-square, and Mantel-Haenszel tests were used in statistical analyses, p < 0.05 was considered significant. In total, 5,255 PPD tests were made, 15.5% were Syrian refugees. BCG scar was missing in 48.5% of Turks and 87.3% of refugees (p < 0.001). The 0-5 age group represented the lowest rate (Turks 3.2%, refugees 4.3%) and the 19-64 age group represented the highest rate (Turks 51.1%, refugees 54.1%) of positive PPD reaction among individuals without BCG scar. Among individuals without BCG scar, more positive PPD reactions developed in refugees of the 6-18 group than in Turks (Turks 16.9%, refugees 46.4%, p < 0.001). Among individuals with BCG scar, more positive PPD reactions developed among refugees of the 0-5 (Turks 7.8%, refugees 24.0%, p = 0.049) and 19-64 (Turks 36.6%, refugees 58.8%, p = 0.028) age groups. ARTIs between 2012-2015 were 0.2%, 1.0%, 1.3%, and 1.4% among Turks, (except 2012) 2.3%, 0.3%, 2.4% among refugees in the 0-5 age group, 1.1%, 2.0%, 1.7%, and 1.5% among Turks, and 8.5%, 6.6%, 7.3%, and 2.4% among refugees in the 6-18 age group, respectively. Higher positive PPD reactions and ARTIs were found among Syrian refugees, more specifically in the 6-18 age group.


Alpha-Defensin 1: An Emerging Periodontitis Biomarker.
Background: Research on the development of reliable diagnostic targets is being conducted to overcome the high prevalence and difficulty in managing periodontitis. However, despite the development of various periodontitis target markers, their practical application has been limited due to poor diagnostic accuracy. In this study, we present an improved periodontitis diagnostic target and explore its role in periodontitis. Methods: Gingival crevicular fluid (GCF) was collected from healthy individuals and periodontitis patients, and proteomic analysis was performed. The target marker levels for periodontitis were quantified in GCF samples by enzyme-linked immunosorbent assay (ELISA). Mouse bone marrow-derived macrophages (BMMs) were used for the osteoclast formation assay. Results: LC-MS/MS analysis of whole GCF showed that the level of alpha-defensin 1 (DEFA-1) was higher in periodontitis GCF than in healthy GCF. The comparison of periodontitis target proteins galactin-10, ODAM, and azurocidin proposed in other studies found that the difference in DEFA-1 levels was the largest between healthy and periodontitis GCF, and periodontitis was more effectively distinguished. The differentiation of RANKL-induced BMMs into osteoclasts was significantly reduced by recombinant DEFA-1 (rDEFA-1). Conclusions: These results suggest the regulatory role of DEFA-1 in the periodontitis process and the relevance of DEFA-1 as a diagnostic target for periodontitis.


FasT-Fix versus inside-out suture meniscal repair in the goat model.
Recent all-inside meniscal repair devices are available, but in vivo studies with these devices are sparse. The FasT-Fix has inferior meniscal healing compared with the inside-out suture technique in the goat model. Controlled laboratory study. After Institutional Review Board approval, 73 male castrated goats (Capra hircus) underwent a 2-cm meniscal incision and subsequent repair with the FasT-Fix device on one knee and inside-out meniscal repair on the contralateral knee. Both repairs used a vertical mattress suture technique. Access to the menisci was via an open technique with an extra-articular osteotomy of the medial collateral ligament origin on the femur. The animals were then allowed to ambulate unrestricted in a pasture after a 7-day stay in cages. Necropsy was carried out 6 months postoperatively, and the menisci and articular cartilage were studied with gross and microscopic inspection. Nine of the 73 animals were excluded before necropsy. A total of 64 animals underwent necropsy, gross measurement of residual lesions, gross evaluation for chondral damage, histologic evaluation of meniscal repair, histologic evaluation of any adjacent inflammatory reaction to implants, and data analysis. Compared with the inside-out group, the FasT-Fix group had longer residual full-thickness defects (1.2 +/- 2.9 mm vs 0.2 +/- 1.1 mm; P = .011) and longer residual partial-thickness defects (8.4 +/- 6.3 mm vs 3.6 +/- 5.5 mm; P < .001). A total of 148 FasT-Fix devices were placed for 73 knees. Two devices were replaced for improper deployment. The device deployed and attached correctly 146 of 148 times for a success rate of 98.6%. There was no gross chondral damage and no histologic findings of inflammatory reaction to the implants with either technique. The FasT-Fix meniscal repair had inferior meniscal healing results in this animal model. Previous studies using this animal model have paralleled clinical outcomes. Implantation of the FasT-Fix device does not damage adjacent femoral or tibial cartilage. The deployment of the FasT-Fix implant was simple and reproducible. There was no inflammatory reaction to the FasT-Fix implant. The FasT-Fix meniscal repair has inferior meniscal healing results compared with the inside-out meniscal repair technique in the goat model. The clinical significance of this finding is not known. Further clinical study of the FasT-Fix implant is warranted.


Effect of B-HT 920 on cardiotoxic effects of ouabain in guinea pigs.
Effect of B-HT 920, a selective alpha 2 adrenoceptor agonist, was studied on ouabain induced cardiac arrhythmias and cardiac arrest in guinea pigs. Ventricular premature beats, ventricular tachyarrhythmias and cardiac arrest were induced in anaesthetized guinea pigs by slow infusion of ouabain. B-HT 920 accorded significant protection to guinea pigs against ouabain induced arrhythmias. Yohimbine inhibited the antiarrhythmic effect of B-HT 920 significantly. It is concluded that the protective effect of B-HT 920 against ouabain induced cardiac arrhythmias and cardiac arrest is mediated through the stimulation of alpha 2 adrenoceptors.


Selective vagotomy of the canine oesophagus--a model for the treatment of hiatal hernia.
Hiatal herniation caused by contraction of the longitudinal muscle of the oesophagus has been prevented by disconnecting the local vagal nerve supply while preserving the vagal connections to more distant organs. A selective oesophageal vagotomy above the lung hilum may prove an effective adjunct to orthodox hiatal hernia repair in man.


Early avoidance of a heroin-paired taste-cue and subsequent addiction-like behavior in rats.
The ability to predict individual vulnerability to substance abuse would allow for a better understanding of the progression of the disease and development of better methods for prevention and/or early intervention. Here we use drug-induced devaluation of a saccharin cue in an effort to predict later addiction-like behavior in a model akin to that used by Deroche-Gamonet et al. (2004) and seek to link such vulnerability to changes in expression of various mu opioid receptor and D2 receptor-interacting proteins in brain. The results show that the greatest heroin-induced suppression of intake of a saccharin cue is associated with the greatest vulnerability to later addiction-like behavior and to differences in the expression of WLS, β-catenin, and NCS-1 in brain compared to rats that exhibited the least suppression of intake of the heroin-paired cue and/or saline controls. Finally, because the self-administration model employed produced no significant differences in drug intake between groups, overall, the resultant changes in protein expression can be more closely linked to individual differences in motivation for drug.


Left-Ventricular Energetics in Pulmonary Arterial Hypertension-Induced Right-Ventricular Hypertrophic Failure.
Pulmonary arterial hypertension (PAH) alters the geometries of both ventricles of the heart. While the right ventricle (RV) hypertrophies, the left ventricle (LV) atrophies. Multiple lines of clinical and experimental evidence lead us to hypothesize that the impaired stroke volume and systolic pressure of the LV are a direct consequence of the effect of pressure overload in the RV, and that atrophy in the LV plays only a minor role. In this study, we tested this hypothesis by examining the mechanoenergetic response of the atrophied LV to RV hypertrophy in rats treated with monocrotaline. Experiments were performed across multiple-scales: the whole-heart in vivo and ex vivo, and its trabeculae in vitro. Under the in vivo state where the RV was pressure-overloaded, we measured reduced systemic blood pressure and LV ventricular pressure. In contrast, under both ex vivo and in vitro conditions, where the effect of RV pressure overload was circumvented, we found that LV was capable of developing normal systolic pressure and stress. Nevertheless, LV atrophy played a minor role in that LV stroke volume remained lower, thereby contributing to lower LV mechanical work output. Concomitantly lower oxygen consumption and change of enthalpy were observed, and hence LV energy efficiency was unchanged. Our internally consistent findings between working-heart and trabecula experiments explain the rapid improvement of LV systolic function observed in patients with chronic pulmonary hypertension following surgical relief of RV pressure overload.


A novel cypovirus found in a betabaculovirus co-infection context contains a poxvirus immune nuclease (poxin)-related gene.
The cassava hornworm Erinnyis ello ello (Lepidoptera: Sphingidae) is an important pest in Brazil. This insect feeds on host plants of several species, especially Manihot esculenta (cassava) and Hevia brasiliensis (rubber tree). Cassava hornworm outbreaks are quite common in Brazil and can cause great impact over crop production. Granulare and polyhedral-shaped occlusion bodies (OBs) were observed in extracts of dead E. ello larvae from rubber-tree plantations by light and scanning electron microscopy (SEM), suggesting a mixed infection. The polyhedral-shaped OB surface revealed indentations that resemble those found in cypovirus polyhedra. After OB nucleic acid extraction followed by cDNA production and Illumina deep-sequencing analysis, the results confirmed for the presence of a putative novel cypovirus that carries ten segments and also a betabaculovirus (Erinnyis ello granulovirus, ErelGV). Phylogenetic analysis of the predicted segment 1-enconded RdRP showed that the new cypovirus isolate is closely related to a member of species Cypovirus 2, which was isolated from Inachis io (Lepidoptera: Nymphalidae). Therefore, we named this new isolate Erinnyis ello cypovirus 2 (ErelCPV-2). Genome in silico analyses showed that ErelCPV-2 segment 8 (S8) has a predicted amino acid identity of 35.82 % to a hypothetical protein of betabaculoviruses. This putative protein has a cGAMP-specific nuclease domain related to the poxvirus immune nucleases (poxins) from the 2',3'-cGAMP-degrading enzyme family.


Calculation of subsite affinities of human small intestinal glucoamylase-maltase.
Several years ago, Hiromi et al. (1973) Biochim. Biophys. Acta 302, 362-375 proposed a theory for the action patterns of glucoamylases, based on data from steady-state kinetics. The Michaelis-Menten constants (Km) and the turnover number for maltooligosaccharides were used to evaluate the subsite affinities. We have now used this method for evaluating the subsite affinities for glucoamylases(EC 220.127.116.11)-maltase (EC 184.108.40.206) from human intestinal mucosa. For calculation of the subsite affinities, A1 and A2, and the intrinsic rate constant kint, we use a modified algorithm and a computer program for nonlinear least square fitting. Considerable substrate inhibition was shown by maltotriose, minor inhibition by maltotetraose, and no inhibition by maltose and the other maltooligosaccharides. This indicates a more complex kinetic behaviour of the enzyme with respect to maltotriose. Evaluation of the subsites reveals that A2 is the main binding site (18.1 kJ/mol), whereas the other affinities, with the exception of A1, are lower than 2.5 kJ/mol.


TEGDMA and UDMA monomers released from composite dental material polymerized with diode and halogen lamps.
More than 35 substances released from composite fillings have been identified. Among these, basic monomers and the so-called co-monomers are most often reported. The substances released from polymer-based materials demonstrate allergenic, cytotoxic, genotoxic, mutagenic, embryotoxic, teratogenic, and estrogenic properties. The aim of this study was to measure the amounts of triethylene glycol dimethacrylate (TEGDMA) and urethane dimethacrylate (UDMA) monomers released from composite dental fillings to citrate-phosphate buffer with the pH of 4, 6, 8 after 24 h and 6 months from the polymerization. Ten samples for each polymerization method had been made from the composite material (Filtek Supreme XT, 3M ESPE, St. Paul, USA), which underwent polymerization using the following lamps: halogen lamp (Translux CL, Heraeus Kulzer, Hanau, Germany) (sample H) and diode lamp (Elipar Freelight 2, 3M ESPE), with soft start function (group DS) and without that function (group DWS). It has been demonstrated that the type of light-curing units has a significant impact on the amount of TEGDMA and UDMA released. The amount of UDMA and TEGDMA monomers released from composite fillings differed significantly depending on the source of polymerization applied, as well as the pH of the solution and sample storage time. Elution of the monomers from composite material polymerized using halogen lamp was significantly greater as compared to curing with diode lamps.


In vitro and in vivo evaluation of the movement of Kepone in the rat submaxillary gland.
In vitro studies performed on slices of rat submaxillary gland showed that the rates of uptake and efflux of Kepone consisted of both a fast and a slow component. No significant alteration of these rates was observed after aeration with N2, decreased temperature, or incubations with cyanide or 2,4-dinitrophenol. In vivo data on actual concentration of Kepone in saliva and plasma over a 48 hour period showed no evidence of concentration of Kepone by the submaxillary glands. These data suggest that the movement of Kepone from blood into the saliva through the submaxillary glands occurs by means of passive diffusion.


Fine catheter peritoneal cytology for the acute abdomen: a randomized, controlled trial.
A randomized, controlled clinical trial, of sequential design, was undertaken to determine whether fine catheter aspiration cytology of the peritoneal cavity, using the percentage of neutrophils in the sample as the main test marker, reduces errors about urgent laparotomy in patients admitted to a surgical unit with acute abdominal pain. One hundred and forty-four patients with acute abdominal pain were studied. Of these, 26 were excluded because the test was unlikely to be useful and 20 did not consent. Conventional clinical assessment was undertaken and then the subjects were randomly allocated to have a peritoneal cytology test or not. After the test result was made available, the surgeon(s) decided whether to operate or continue conservative treatment. The correct decision was later ascertained by a blinded clinical referee. With the entry of the 98th patient the difference between the groups achieved the 5% significance level. The groups were well-matched in regard to demographic and other variables. The decision about urgent laparotomy was incorrect in only 8.2% of the test patients, compared with 28.6% of the others. It is concluded that fine catheter aspiration cytology of the peritoneal cavity is likely to reduce the numbers of unnecessary or delayed laparotomies when used in most patients admitted with acute abdominal pain.


PB1-F2 gene in influenza a viruses of different hemagglutinin subtype.
The second ORF frame (+1) of PB1 polymerase gene of Influenza A virus (IAV) encodes the PB1-F2 protein. The length of PB1-F2 encoded by the A/Puerto Rico/8/34 (H1N1) (PR8) virus is 87 aa. The analysis of nucleotide sequences of PB1 gene of 626 IAV isolates available in GenBank and Influenza Sequence Database revealed that this gene has mostly the capacity to encode a putative protein of 90 aa. The predicted extra three amino acids in the 90-aa PB1-F2 are to a great extent conservative. Some IAV isolates, particularly human, avian and swine with hemagglutinin (HA) of H1 subtype can potentially encode a C-terminally truncated PB1-F2 of various lengths. The C-terminally truncated PB1-F2 in H1 isolates is lacking the region responsible for mitochondrial targeting and apoptosis. About 50% of avian isolates of H9 subtype possess an ORF for truncated PB1-F2. Eighteen aa, 10 at the N-terminus and 8 at the C terminus are strictly conservative in all 148 human isolates.


Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice.
Physical exercise is considered a fundamental strategy in improving insulin sensitivity and glucose uptake in skeletal muscle. However, the molecular mechanisms underlying this regulation, primarily on skeletal muscle glucose uptake, are not fully understood. Recent evidence has shown that Rho-kinase (ROCK) isoforms play a pivotal role in regulating skeletal muscle glucose uptake and systemic glucose homeostasis. The current study evaluated the effect of physical exercise on ROCK2 signaling in skeletal muscle of insulin-resistant obese animals. Physiological (ITT) and molecular analysis (immunoblotting, and RT-qPCR) were performed. The contents of RhoA and ROCK2 protein were decreased in skeletal muscle of obese mice compared to control mice but were restored to normal levels in response to physical exercise. The exercised animals also showed higher phosphorylation of insulin receptor substrate 1 (IRS1 Serine 632/635) and protein kinase B (Akt) in the skeletal muscle. However, phosphatase and tensin homolog (PTEN) and protein-tyrosine phosphatase-1B (PTP-1B), both inhibitory regulators for insulin action, were increased in obesity but decreased after exercise. The impact of ROCK2 action on muscle insulin signaling is further underscored by the fact that impaired IRS1 and Akt phosphorylation caused by palmitate in C2C12 myotubes was entirely restored by ROCK2 overexpression. These results suggest that the exercise-induced upregulation of RhoA-ROCK2 signaling in skeletal muscle is associated with increased systemic insulin sensitivity in obese mice and further implicate that muscle ROCK2 could be a potential target for treating obesity-linked metabolic disorders.


Requirements for NF-kappaB activation in hemorrhagic shock.
The activation of nuclear factor (NF)-kappaB contributes to the dysfunctional inflammatory response accompanying resuscitation from hemorrhagic shock (HS), in part through induction of pro-inflammatory cytokines including granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-6. In previous studies, we demonstrated that G-CSF and IL-6 up-regulation required both the ischemic and resuscitation phases of HS. In this study, we examined whether or not both phases of HS were required for NF-kappaB activation and the kinetics of its activation. Sprague-Dawley rats were subjected to unresuscitated HS with increasing duration of the ischemic phase [compensated HS, 0% shed blood return (SBR); decompensated HS, 35% SBR; and irreversible HS, 70% SBR) or HS (compensated or decompensated)] followed by resuscitation. NF-kappaB activity did not increase in any of the unresuscitated groups compared with sham controls. In contrast, resuscitation as early as 1 h following HS resulted in increased NF-kappaB activity compared with both the unresuscitated shock group and sham controls; NF-kappaB activation persisted for 8 h. Thus, NF-kappaB activation requires both phases of HS, occurs rapidly following resuscitation, and persists throughout the early stages of dysfunctional inflammation following resuscitation.


Comparative validation study to demonstrate the equivalence of a minor modification to AOAC methods 996.09, Vip for EHEC and 996.10, assurance Eia EHEC with the reference culture method for the detection of Escherichia coli O157:H7 in beef.
The Visual Immunoprecipitate Assay (VIP) method for the detection of enterohemorrhagic Escherichia coli O157:H7 (VIP for EHEC) and Assurance Enzyme Immunoassay (EIA) method for the detection of EHEC (EHEC EIA) are AOAC INTERNATIONAL Official Methods 996.09 and 996.10, respectively. A minor modification to the enrichment medium used in both methods has been developed. This modification, the BioControl modified EHEC medium (BioControl mEHEC) provides a more cost-effective procedure with performance equivalent to that of the cultural method for detection of E. coli O157:H7 in beef.


Hypouricemic Effects of Ganoderma applanatum in Hyperuricemia Mice through OAT1 and GLUT9.
Ganoderma applanatum (G. applanatum) dispels wind to eliminate dampness and exhibited nephron- and liver-protective effects as noted in Chinese herbal classic literature; it might also affect hyperuricemia. Therefore, we examined the hypouricemia effects and mechanisms underlying G. applanatum on chemical-induced hyperuricemia in mice. Ethanol (GAE) and water (GAW) extracts were prepared by extracting G. applanatum in ethanol (GAE), followed by bathing the remains in water to yield GAW. GAE and GAW were administered orally at different doses to hyperuricemia mice, while allopurinol and benzbromarone served as positive controls. Both GAE and GAW showed remarkable hypouricemia activities, rendering a substantial decline in the SUA (serum uric acid) level in hyperuricemia control (P < 0.01). Moreover, the urine uric acid (UUA) levels were enhanced by GAE and GAW. In contrast to the evident renal toxicity of allopurinol, GAE and GAW did not show a distinct renal toxicity. Almost no suppressing effect was observed on the XOD activities. However, compared to the hyperuricemia control, OAT1 was elevated remarkably in mice drugged with GAE and GAW, while GLUT9 was significantly decreased. Similar to benzbromarone, GAE decreased the URAT1 protein levels significantly (P < 0.01), while GAW did not display a similar effect. GAE and GAW downregulated the level of CNT2 proteins in the gastrointestinal tract of hyperuricemia mice. Thus, G. applanatum produced outstanding hypouricemic effects, mediated by renal OAT1, GLUT9, and URAT1 and gastrointestinal CNT2 that might elevate urine uric secretions and decline in the absorption of purine in the gastrointestinal tracts. G. applanatum showed little negative influence on inner organs. By docking screening, four top-ranked compounds were identified that necessitated further investigation. Compounds: potassium oxonate, hypoxanthine, allopurinol, benzbromarone.


A review of the literature on atrial fibrillation: rate reversion or control?
The aim of this paper is to review the current literature describing the aetiology of atrial fibrillation and to examine the evidence for rate reversion and rate control. Atrial fibrillation is the most commonly seen arrhythmia within the clinical setting. Treatment depends on severity of symptoms, which are predominantly palpitations and shortness of breath. The primary complications from atrial fibrillation are thrombo-embolic events (such as a pulmonary embolus or stroke). A comprehensive literature review on atrial fibrillation, rate reversion and rate control was undertaken to examine the incidence of atrial fibrillation, to review research on management of atrial fibrillation and to determine if rate reversion was superior to rate control in the treatment of atrial fibrillation. Many studies have been carried out to determine the best treatment for this condition. The choices are currently pharmacological and electrical cardioversion in conjunction with anticoagulant therapy. Drug therapies are not without their problems, especially toxicity and the need for close clinical monitoring. Transaesophageal echocardiography has been used to establish the presence of left atrial thrombi and aims to reduce the anticoagulation time and reduce the risk of thrombo-embolic events. A randomized comparative study of transaesophageal echocardiography and conventional anticoagulation therapy prior to cardioversion demonstrated statistically significant reduction in haemorrhagic events and a shorter time to cardioversion in those in the transaesophageal echocardiography group compared with the conventional group. For those with persistent atrial fibrillation, surgery is an option with valve repair or replacement carried out in conjunction with a bi-atrial surgical ablation. The management of atrial fibrillation is dependent on many factors and to date there are no proven clinical rationale for rate control or reversion. Atrial fibrillation requires immediate attention in order to avoid thrombo-embolic complications and the use of transaesophageal echocardiography and conventional anticoagulation therapy can significantly reduce these complications.


Energy-Efficient Oil-Water Separation of Biomimetic Copper Membrane with Multiscale Hierarchical Dendritic Structures.
Membrane-based materials with special surface wettability have been applied widely for the treatment of increasing industrial oily waste water, as well as frequent oil spill accidents. However, traditional technologies are energy-intensive and limited, either by fouling or by the inability of a single membrane to separate all types of oil-water mixtures. Herein, a biomimetic monolayer copper membrane (BMCM), composed of multiscale hierarchical dendritic structures, is cleverly designed and successfully fabricated on steel mesh substrate. It not only possesses the ability of energy-efficient oil-water separation but also excellent self-recovery anti-oil-fouling properties (<150 s). The BMCM even keeps high separation efficiency (>93%) after ten-time cycling tests. More importantly, it retains efficient oil-water separation capacity for five different oils. In fact, these advanced features are benefited by the synergistic effect of chemical compositions and physical structures, which is inspired by the typical nonwetting strategy of butterfly wing scales. The findings in this work may inspire a facile but effective strategy for repeatable and antipollution oil-water separation, which is more suitable for various applications under practical conditions, such as wastewater treatment, fuel purification, separation of commercially relevant oily water, and so forth.


Spectroscopic fingerprints of work-function-controlled phthalocyanine charging on metal surfaces.
The electronic character of a π-conjugated molecular overlayer on a metal surface can change from semiconducting to metallic, depending on how molecular orbitals arrange with respect to the electrode's Fermi level. Molecular level alignment is thus a key property that strongly influences the performance of organic-based devices. In this work, we report how the electronic level alignment of copper phthalocyanines on metal surfaces can be tailored by controlling the substrate work function. We even show the way to finely tune it for one fixed phthalocyanine-metal combination without the need to intercalate substrate-functionalizing buffer layers. Instead, the work function is trimmed by appropriate design of the phthalocyanine's supramolecular environment, such that charge transfer into empty molecular levels can be triggered across the metal-organic interface. These intriguing observations are the outcome of a powerful combination of surface-sensitive electron spectroscopies, which further reveal a number of characteristic spectroscopic fingerprints of a lifted LUMO degeneracy associated with the partial phthalocyanine charging.


Effect of surface finishing and storage media on bi-axial flexure strength and microhardness of resin-based composite.
This in vitro study tested the following null hypotheses: (1) surface finishing treatments do not significantly affect the biaxial flexure strength and microhardness of resin-based composites (RBC) and (2) storage media do not significantly affect these physical properties. Discs (81 RBC and 81 UR; 3M/ESPE) were prepared using a circular polyethylene mold (2.4-mm thick x 16.7 mm in diameter) that was polymerized through a Mylar strip and divided into three surface finishing treatment groups: 1 microm aluminum oxide slurry; 15 microm diamond and a Mylar strip. Randomly selected controls for each finishing group were stored at room temperature in individual vials. Test specimens were immersed in water, stored at 37 degrees C for two days and transferred for an additional seven days to one of three aqueous storage media at 37 degrees C: coffee (pH 5.1), cola (pH 2.4) or red wine (pH 3.7). Post immersion (nine days total), the specimens were tested for biaxial flexure strength (BFS) and Vicker's microhardness (VHN). ANOVA and Tukey's HSD test were used for statistical analysis. ANOVA results indicated that surface finishing treatments had a significant effect on the biaxial flexure strength and microhardness of the RBC and the UR specimens. BFS results for RBC specimens were AL>DD>ML (p<0.0001) and VHN results were AL, DD>ML (p<0.0001). Storage in wine medium reduced the VHN of UR specimens significantly. Both alternative hypotheses were accepted. In addition, the Mylar finishing group, because of the resin-rich surface layer, yielded the lowest mean values of BFS and VHN.