In vitro fertilization, embryo development, and cell lineage segregation after pre- and/or postnatal exposure of female mice to ambient fine particulate matter.
To evaluate effects of pre- and/or postnatal exposure to ambient fine particulate matter on fertilization, embryo development, and cell lineage segregation in preimplantation blastocysts using the IVF mouse model. Animal model. Academic institution. Six-week-old, superovulated mice. Pre- and postnatal exposure to filtered air (FA-FA), filtered-ambient air (FA-AA), or ambient air (AA-AA) in exposure chambers 24 hours a day for 9 weeks. Gestation length, litter size, sex ratio, ovarian response to superovulation, fertilization rate, embryo development, blastocyst and hatching rates, total cell count, and proportion of cell allocation to inner-cell mass (ICM) and trophectoderm (TE). Gestation length, litter size and birth weight, live-birth index, and sex ratio were similar among exposure groups. Ovarian response was not affected by the exposure protocol. A multivariate effect for pre- and/or postnatal exposure to ambient fine particulate matter on IVF, embryo development, and blastocyst differential staining was found. Cell counts in ICM and ICM/TE ratios in blastocysts produced in the FA-FA protocol were significantly higher than in blastocysts produced in the FA-AA and AA-AA protocols. No difference in total cell count was observed among groups. Our study suggests that exposure to ambient fine particulate matter may negatively affect female reproductive health by disrupting the lineage specification at the blastocyst stage without interfering in early development of the mouse embryo.


Argentine ant trail pheromone disruption is mediated by trail concentration.
Argentine ant trail pheromone disruption, using continuous release of the trail pheromone compound (Z)-9-hexadecanal, reduces the incidence of trails and foraging rates of field populations. However, little is known about the concentrations of pheromone required for successful disruption. We hypothesized that higher pheromone quantities would be necessary to disrupt larger ant populations. To test this, we laid a 30-cm long base trail of (Z)-9-hexadecanal on a glass surface at low and high rates (1 and 100 pg/cm) (Trail 1), and laid a second, shorter trail (Trail 2, 10 cm long, located 1.5 cm upwind) near the middle of Trail 1 at six rates (1, 10, 100, 1,000, 10,000, and 100,000 pg/cm). We then recorded and digitized movements of individual ants following Trail 1, and derived a regression statistic, r (2), as an index of trail integrity, and also recorded arrival success at the other end of the trail (30 cm) near a food supply. Disruption of trails required 100 fold more pheromone upwind, independent of base-trail concentration. This implies that in the field, trail disruption is likely to be less successful against high ant-trail densities (greater concentration of trail pheromone), and more successful against newly formed or weak trails, as could be expected along invasion fronts.


[The state of receptor-dependent signal pathways in the agranulocytes from the peripheral blood of the reconvalescent patients following community-acquired pneumonia under the influence of microwave radiation].
The present article reports the study of the influence of low-intensity microwave radiation on the state of the JAK/STAT-signaling pathways in the mononuclear cells and the intercellular levels of the molecules maintaining the functioning of this pathway. The experiments on the model of intercellular interactions in the whole blood cell culture obtained during the convalescence phase of community-acquired bacterial pneumonia were designed to elucidate the effects of the cell-cell interactions in the culture exposed to electromagnetic radiation with a frequency of 1000 MHz and power flux density 0.1 mcW/cm2 on the intracellular levels of total and phosphorylated species of JAK-kinases, STAT-factors and SOCS-proteins. It is concluded that sensitivity of intracellular signaling systems to the effects of low-intensity microwave radiation manifests itself in the form of increased intracellular concentrations of Janus kinases and SOCS proteins with a simultaneous decrease in the level of STAT factors.


Morphology of immatures of Caonabo pseudoscylax (Bergroth) (Hemiptera: Pentatomidae).
Characters of immatures are potentially useful in identifying taxa, but few immatures of Pentatomidae were described. The objectives here are to describe the egg and five nymphal instars of Caonabo pseudoscylax (Bergroth) under light and scanning electron microscopy. Adults, eggs, and nymphs were collected on Homolepsis glutinosa during 2008, in Criciúma (Santa Catarina, Brazil). The egg of C. pseudoscylax is subcylindrical, chorion reddish brown, slightly translucent, and with granulate surface. Aero-micropylar processes translucent, spongy, and strongly clavate. Nymphs without punctures, spiracles placed near the lateral abdominal margin. The dorsal abdominal gland has rounded ostioles bearing cuticular valve; spout peritreme smooth, directed anteriorly; evaporatorium network-shaped; and microsculpture poorly ornamented. Humeral angles of the pronotum were produced from fourth instar. The almost marginal placement of abdominal spiracles may diagnose the nymphs of C. pseudoscylax from first instar to adulthood.


Imaging for planning of cardiac resynchronization therapy.
Cardiac resynchronization therapy (CRT) is a novel therapy for patients with refractory heart failure (HF). Large clinical trials evaluating CRT have demonstrated significant improvements in cardiac survival, decreases in recurrent HF hospitalization, and improvements in indexes of quality of life. Although numerous mechanisms are involved in CRT's therapeutic effects, correction of both interventricular and intraventricular mechanical dyssynchrony has been postulated as the key mechanism. To date, most large randomized controlled trials evaluating CRT have identified dyssynchronous patients on the basis of prolongation of the QRS complex from the baseline electrocardiogram. Concerns have been raised regarding the use of this measure for patient selection, stemming from a significant 30% to 40% nonresponse rate to CRT. Because of the cost and invasive nature of CRT, optimal patient selection for this therapy has become a priority for HF specialists and electrophysiologists. Cardiac imaging modalities have attempted to fulfill this need to improve patient selection by identifying mechanical dyssynchrony. Although early echocardiographic studies reported promising results, more recent larger scale studies have curtailed this enthusiasm, with a lack of established selection criteria for CRT in the current practice guidelines. This review summarizes the evidence to date and the potential role of imaging modalities in the selection and care of patients with HF referred for CRT.


Development and evaluation of an up-converting phosphor technology-based lateral flow assay for rapid detection of Francisella tularensis.
Francisella tularensis is a potential biowarfare/bioterrorism agent and zoonotic pathogen that causes tularemia; thus, surveillance of F. tularensis and first-level emergency response using point-of-care testing (POCT) are essential. The UPT-LF POCT assay was established to quantitatively detect F. tularensis within 15 min, and the sensitivity of the assay was 10(4) CFU · mL(-1) (100 CFU/test). The linear quantitative range covered five orders of magnitude, and the coefficients of variation were less than 10%. Except Shigella dysenteriae, UPT-LF showed excellent specificity to four strains that are also potential biowarfare/bioterrorism agents and 13 food-borne pathogenic strains. Samples with pH 2-13, high ion strengths (≥ 2 mol · L(-1) solution of KCl and NaCl), high viscosities (≤ 50 mg · mL(-1) PEG20000 or ≥ 20% glycerol), and high concentrations of biomacromolecules (≥ 400 mg · mL(-1) bovine serum albumin or ≥ 80 mg · mL(-1) casein) showed little influence on the assay. For practical utilization, the tolerance limits for seven powders and eight viscera were determined, and operation errors of liquid measurement demonstrated a minor influence on the strip. Ftu-UPT-LF is a candidate POCT method because of its excellent sensitivity, specificity, and stability in complex samples, as well as low operation error.


Identification of the 12-O-tetradecanoylphorbol-13-acetate-responsive enhancer of the MS gene of the Epstein-Barr virus.
We previously located two 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive enhancers, MSTRE-I and MSTRE-II, in the upstream sequence of the MS gene of Epstein-Barr virus (Liu, Q., and Summers, W.C. (1989) J. Virol. 63, 5062-5068). The core sequence of the MSTRE-I enhancer is now determined to be between -718 and -708 of the upstream sequence of the MS gene. The activity of the enhancer is also sensitive to its immediate surrounding sequence on either side. A single copy of a 30-base pair (bp) fragment containing the MSTRE-I sequence was able to confer TPA responsiveness upon the MS promoter even in the absence of an AP-1 binding site. Multiple tandem copies of this 30-bp fragment, regardless of their relative orientations to each other, could function synergistically to enhance the MS promoter activity. At least two copies of the 30-bp fragment were required to bestow TPA induction upon the thymidine kinase gene promoter of herpes simplex virus type 1. The MSTRE-I sequence could also be bound by a Fos-GCN4 chimeric protein but with an affinity much lower than that between the chimeric protein and the AP-1 binding site. This MSTRE-I region has strong homology to one of the TPA-responsive elements (the ZII domain) in the upstream sequence of the EBV BZLF1 gene. In addition, a putative negative regulatory region or silencer was found immediately downstream of the MSTRE-I enhancer. This potential silencer region contains a 14-bp sequence that is homologous to the silencer consensus sequence of the BZLF1 gene. Therefore, the regulation of the MS gene may share the same pathway with the immediate early gene BZLF1.


Aberrant differential expression of EZH2 and H3K27me3 in extranodal NK/T-cell lymphoma, nasal type, is associated with disease progression and prognosis.
Enhancer of zeste homolog 2 (EZH2), an H3K27-specific histone methyltransferase, has been shown to be frequently overexpressed in various human cancers including lymphoma. Here we investigate the expression and functionality of EZH2 and H3K27me3 in extranodal NK/T-cell lymphoma, nasal type (ENKTL). Results of NanoString analysis revealed that EZH2 and related histone H3 families were up-regulated genes in ENKTL tissues. Results of immunohistochemistry demonstrated that EZH2 and trimethylation of Lys-27 in histone (H3K27me3) were highly expressed in 55.2% and 78.0% of patients with ENKTL, respectively. EZH2 overexpression was significantly associated with higher tumor cell proliferation (r = 0.582, P = .000), advanced stage (P = .012), and predicted poorer overall survival (P = .016) in ENKTL. H3K27me3-positive expression was correlated with lower tumor cell proliferation (r = -0.623, P = .036), earlier stage (P = .043), and predicted better overall survival (P = .020). In addition, EZH2 and H3K27me3 showed inverse correlations (r = -0.652, P = .002) in clinical samples by immunohistochemistry. Furthermore, inhibition of EZH2 by 3-deazaneplanocin A significantly suppressed tumor cell growth. Interestingly, pharmacologic suppression of the JAK3/STAT3 pathway effectively reduced EZH2 and enhanced H3K27me3 in NK/T tumor cell lines. Our data suggest that EZH2 and H3K27me3 are important prognostic markers and potential therapeutic targets in ENKTL.


Gene polymorphisms involved in manifestation of leucopenia, digestive intolerance, and pancreatitis in azathioprine-treated patients.
Approximately 10-28 % of patients experience adverse drug reactions related to treatment with thiopurines. The most serious reaction is myelosuppression, typically manifested as leucopenia, which occurs in approximately 2-5 % of patients. Other adverse drug reactions that often accompany thiopurine therapy are pancreatitis, hepatotoxicity, allergic reactions, digestive intolerance, arthralgia, febrile conditions, and rash. The objective of this study was to assess the relationship between variant alleles of thiopurine S-methyltransferase (SNPs 238G > C, 460G > A and 719A > G), inosine triphosphate diphosphatase (SNPs 94C > A and IVS2 + 21A > C), and xanthine dehydrogenase (837C > T) and the occurrence of adverse drug reactions to azathioprine therapy. Genotype was determined for 188 Caucasians diagnosed with inflammatory bowel disease treated with a standard dose of azathioprine (1.4-2.0 mg/kg/day). Allelic variants were determined by PCR-REA and real-time PCR methods. Results were statistically evaluated by use of Fisher's test and by odds ratio calculation. Variant genotype thiopurine S-methyltransferase predisposes to development of leucopenia (P = 0.003, OR = 5, CI 95 %, 1.8058-13.8444). Although not statistically significant, we observed a trend that suggested correlation between the occurrence of digestive intolerance and the variant genotype inosine triphosphate diphosphatase (P = 0.1102; OR 15.63, CI 95 %, 1.162-210.1094), and between the occurrence of pancreatitis and the variant allele xanthine dehydrogenase 837T (P = 0.1124; OR 12,1, CI 95 %, 1.15-126.37). The variant genotype thiopurine S-methyltransferase has been associated with the occurrence of leucopenia. The involvement of polymorphisms in inosine triphosphate diphosphatase and xanthine dehydrogenase genes in the development of digestive intolerance and pancreatitis will require further verification.


Walk Smarter, Not Harder: Effects of Cadence Manipulation on Gait Biomechanics in Patients with Patellofemoral Osteoarthritis.
This study aimed to investigate the effect of walking cadence on knee flexion angular impulse and peak external flexion moment in patients with patellofemoral osteoarthritis (OA). Forty-eight patients with patellofemoral OA underwent repeated quantitative gait analyses on an instrumented treadmill using a randomized crossover design. Walking trials were conducted at a fixed gait speed, under three cadence conditions: (i) preferred cadence, (ii) +10% increased cadence, and (iii) -10% decreased cadence, completed in random order. Using a linear mixed model, we tested the association of cadence conditions with surrogate measures of patellofemoral load (primary outcome measure: knee flexion angular impulse) while controlling for body mass. We then repeated the analyses while sequentially replacing the dependent variable with secondary outcome measures. Walking with increased cadence decreased (adjusted mean difference [95% confidence interval]) the knee flexion angular impulse (-0.85 N·m·s -1 [-1.52 to -0.18], d = 0.20) and peak knee flexion moment (-4.11 N·m [-7.35 to -0.86], d = 0.24), whereas walking with decreased cadence increased the knee flexion angular impulse (1.83 N·m·s -1 [1.15 to 2.49], d = 0.42) and peak knee flexion moment (3.55 N·m [0.30 to 6.78], d = 0.21). Similar decreases and increases were observed for secondary outcome measures. Walking with increased cadence, while maintaining a fixed gait speed, reduces knee flexion angular impulse as well as other surrogate measures of knee loading in patients with patellofemoral OA.


Metabolic control and effect on secondary complications of diabetes mellitus by pancreatic transplantation.
After successful pancreatic transplantation blood glucose can be normalized without exogenous insulin, although oral and intravenous glucose tolerance remains impaired in 10-45% of the patients. There is no significant deterioration of glucose control with time in most patients. Since most recipients of pancreatic grafts have far advanced secondary diabetic lesions and the observation time after grafting is rather short, the effects of pancreatic transplantation on these complications are difficult to interpret. However, the development of diabetic nephropathy can be prevented, skin microcirculation improves significantly, while autonomic and peripheral neuropathy and diabetic retinopathy remain stable or improve slightly in most patients. But these ameliorations may be in part due to elimination of uraemia, since in almost all patients combined pancreas/kidney transplantations were performed. It is concluded that pancreas grafting probably has to be performed much earlier in the course of diabetes, although the improvement in the quality of life is striking even in the end-stage diabetics studied so far.


Endogenous Glucocorticoid Signaling in the Regulation of Bone and Marrow Adiposity: Lessons from Metabolism and Cross Talk in Other Tissues.
The development of adiposity in the bone marrow, known as marrow adipose tissue (MAT), is often associated with musculoskeletal frailty. Glucocorticoids, which are a key component of the biological response to stress, affect both bone and MAT. These molecules signal through receptors such as the glucocorticoid receptor (GR), but the role of the GR in regulation of MAT is not yet clear from previous studies. The purpose of this review is to establish and determine the role of GR-mediated signaling in marrow adiposity by comparing and contrasting what is known against other energy-storing tissues like adipose tissue, liver, and muscle, to provide better insight into the regulation of MAT during times of metabolic stress (e.g., dietary challenges, aging). GR-mediated glucocorticoid signaling is critical for proper storage and utilization of lipids in cells such as adipocytes and hepatocytes and proteolysis in muscle, impacting whole-body composition, energy utilization, and homeostasis through a complex network of tissue cross talk between these systems. Loss of GR signaling in bone promotes increased MAT and decreased bone mass. GR-mediated signaling in the liver, adipose tissue, and muscle is critical for whole-body energy and metabolic homeostasis, and both similarities and differences in GR-mediated GC signaling in MAT as compared with these tissues are readily apparent. It is clear that GC-induced pathways work together through these tissues to affect systemic biology, and understanding the role of bone in these patterns of tissue cross talk may lead to a better understanding of MAT-bone biology that improves treatment strategies for frailty-associated diseases.


Coordination of cell growth and division by the ubiquitin-proteasome system.
The coupling of cellular growth and division is crucial for a cell to make an accurate copy of itself. Regulated protein degradation by the ubiquitin-proteasome system (UPS) plays an important role in the coordination of these two processes. Many ubiquitin ligases, in particular the Skp1-Cullin-F-box (SCF) family and the Anaphase-Promoting Complex (APC), couple growth and division by targeting cell cycle and metabolic regulators for degradation. However, many regulatory proteins are targeted by multiple ubiquitin ligases. As a result, we are only just beginning to understand the complexities of the proteolytic regulatory network that connects cell growth and the cell cycle.


Dietary branched-chain amino acids and odds of obesity among immigrant Filipino women: the Filipino women's diet and health study (FiLWHEL).
The dietary environment promoting adiposity keeps evolving and of interest is the significance of dietary branched-chain amino acids (BCAA). This study assessed the association between dietary BCAA intakes and odds of obesity among immigrant Filipino women in Korea. We included 423 immigrant Filipino women enrolled in the Filipino Women's diet and health study in the Republic of Korea. Dietary BCAA intakes were estimated from 24 hour recalls and adjusted for energy intake using the residual method. General obesity was derived from direct anthropometric measurements (height, weight and waist circumference - WC) and defined as body mass index (BMI) ≥25 kg/m2 and abdominal obesity as WC ≥80 cm. Odds ratios (OR) and 95% confidence intervals (CI) by tertile distribution of energy-adjusted BCAA intakes were estimated using multivariable logistic regression with a two-sided P < 0.05. Median (interquartile range) for BCAA intakes in g/day were; 7.9 (5.8, 10.3) g/day for total BCAA; 2.0 (1.5, 2.6) g/day for isoleucine, 3.5(2.5, 4.6) g/day for leucine and 2.4 (1.8, 3.1) g/day for valine. Mean BMI and WC were 23.6 ± 3.8 kg/m2 and 79.8 ± 9.3 cm, respectively. Also, 30.2% (128) had BMI ≥25 kg/m2 and 42.0% (178) had WC ≥80 cm. ORs (95%CIs) of general obesity across tertile distribution of energy-adjusted total BCAA intakes were 1.00, 0.81 (0.47, 1.37) and 0.62 (0.36, 1.07; P for trend = 0.08). A similar trend was observed across tertile distribution of energy-adjusted isoleucine, leucine and valine intakes. However, there was a statistically significant inverse association between total BCAA intake and odds of general obesity in a subset of non-smokers; 1.00, 0.68 (0.39, 1.20) and 0.55 (0.31, 0.98; P for trend = 0.04). We found a suggestive inverse association between higher dietary BCAA intake and odds of obesity in this sample of immigrant Filipino women, particularly among non-smokers. Prospective cohort studies among the immigrant population will be necessary to verity these findings.


Improving the phytochemical profile and bioactivity of Chinese cabbage sprouts by interspecific transfer of metabolites.
The high demand for healthy food in recent years has led to an increasing need for highly bioactive plant materials. One such plant, Chinese cabbage, possesses flavonoids with antioxidant and antidiabetic properties, but they appear in low quantities. The interspecific transfer of metabolites is a promising technique that could contribute to the increase of the beneficial properties of food. The objective of the study was to determine how an interspecific source-sink phytochemical transfer from donor extracts to the Chinese cabbage affects its phenolic and vitamin C profile and intestinal bioaccessibility, hypoglycemic potential and antioxidant capacity. In addition, sprouts treated with Rosa sp. and Hypericum perforatum extracts showed better antiproliferative effect towards human breast adenocarcinoma cells than untreated sprouts. The results suggest that treatment of plants with donor extracts is a promising approach to improve the nutritional and phytochemical profile and bioactive properties of acceptor plants.


Medical decision making for older patients during multidisciplinary oncology team meetings.
Multidisciplinary team meetings aim to facilitate efficient and accurate communication surrounding the complex process of treatment decision making for older patients with cancer. This process is even more complicated for older (≥70 years) patients as the lack of empirical evidence on treatment regimens in patients with age-related problems such as comorbidity and polypharmacy, necessitates a patient-centred approach.This study investigates the decision making process for older patients with cancer during multidisciplinary team meetings and the extent to which geriatric evaluation and geriatric expertise contribute to this process. Non-participant observations of 171 cases (≥70 years) during 30 multidisciplinary team meetings in five hospitals and systematically analysed using a medical decision making framework. All cases were in patients with colon or rectal cancer. First, not all steps from the medical decision making framework were followed. Second, we found limited use of patient-centred information such as (age-related) patient characteristics and patient preferences during the decision making process. Third, a geriatric perspective was largely missing in multidisciplinary team meetings. This study uncovers gaps in the treatment decision making process for older patients with cancer during multidisciplinary team meetings. In particular individual vulnerabilities and patient wishes are often neglected.


Proceedings of the diffuse intrinsic pontine glioma (DIPG) Toronto Think Tank: advancing basic and translational research and cooperation in DIPG.
Diffuse intrinsic pontine glioma (DIPG) nearly exclusively affects children. The prognosis of DIPGs has remained grim despite more than three decades of clinical research and numerous clinical trials. More than 90% of the children with DIPG will succumb within 2 years of diagnosis. The tumor's incidence is still undefined, but data suggest 100-150 affected children annually in the US. The single proven effective treatment modality in DIPG remains radiation therapy. For the majority of patients however this treatment is only of transient effectiveness. Recent breakthroughs in the understanding of the molecular biology of DIPG have raised new hope and opened new avenues for therapeutic options. The advancement of basic and translational research and cooperation was the objective of the Toronto Think Tank, as new approaches are urgently needed.


Standardized Clinical Annotation of Digital Histopathology Slides at the Point of Diagnosis.
As digital pathology replaces conventional glass slide microscopy as a means of reporting cellular pathology samples, the annotation of digital pathology whole slide images is rapidly becoming part of a pathologist's regular practice. Currently, there is no recognizable organization of these annotations, and as a result, pathologists adopt an arbitrary approach to defining regions of interest, leading to irregularity and inconsistency and limiting the downstream efficient use of this valuable effort. In this study, we propose a Standardized Annotation Reporting Style for digital whole slide images. We formed a list of 167 commonly annotated entities (under 12 specialty subcategories) based on review of Royal College of Pathologists and College of American Pathologists documents, feedback from reporting pathologists in our NHS department, and experience in developing annotation dictionaries for PathLAKE research projects. Each entity was assigned a suitable annotation shape, SNOMED CT (SNOMED International) code, and unique color. Additionally, as an example of how the approach could be expanded to specific tumor types, all lung tumors in the fifth World Health Organization of thoracic tumors 2021 were included. The proposed standardization of annotations increases their utility, making them identifiable at low power and searchable across and between cases. This would aid pathologists reporting and reviewing cases and enable annotations to be used for research. This structured approach could serve as the basis for an industry standard and be easily adopted to ensure maximum functionality and efficiency in the use of annotations made during routine clinical examination of digital slides.


Mullerian cyst of the uterus misdiagnosed as ovarian cyst on pelvic sonography.
Mullerian cyst of the uterus, also known as endosalpingiosis, is rare and often can be misdiagnosed as adnexal cyst on pelvic sonography. A 47-year-old woman was referred for an incidental finding of a right adnexal mass on pelvic sonography, suspected to be an ovarian cyst. During laparoscopy, a pedunculated cystic mass arising from the right anterior uterine wall was seen. The mass was resected laparoscopically and histologic examination showed a benign Mullerian cyst of the uterus. Diagnosis of Mullerian cyst of the uterus can be challenging. However, with increased awareness, preoperative diagnosis of this condition should be possible sonographically.


Synthesis of amine-functionalized magnetic porous organic polymers for effective extraction of phenolic endocrine disrupting chemicals.
Amine-functionalized porous organic polymers (EDA-POP-PC and EDA-POP-BT) were prepared by post-modification of POP-PC and POP-BT with ethylenediamine (EDA) for the first time. The POP-PC and POP-BT were obtained through Friedel-Crafts acylation reaction of potassium tetraphenylborate with p-phthaloyl chloride (PC) and 1,3,5-benzenetricarbonyl trichloride (BT), respectively. The EDA-POPs exhibited superior adsorption capacity for phenolic endocrine disrupting chemicals (EDCs). After magnetically functionalization, the obtained M-EDA-POP-PC was employed as a magnetic adsorbent for enrichment of phenolic EDCs from real samples prior to high performance liquid chromatography-ultraviolet detection. The current strategy showed low detection limits (S/N = 3) of 0.02-0.07, 0.04-0.08 and 0.04-0.10 ng mL-1 for river water, white peach juice and lychee juice, respectively. The method recoveries were 81.7%-115% with relative standard deviations below 8.6%. The proposed strategy showed good practicality for sensitive determination of phenolic EDCs in real samples.


The benefits of ambulatory physiotherapy after total knee replacement. Clinical practice recommendations.
To develop clinical practice guidelines for ambulatory physiotherapy for patients able to leave the surgery department directly for home just after total knee replacement (TKR). We used the SOFMER (French Society of Physical and Rehabilitation Medicine) methodology, which associates a systematic revue of the literature, collection of information regarding current clinical practice and external review by a multidisciplinary expert panel. Main outcomes considered in the recommendations were impairment, disability, medico-economic implications and postoperative complications. The literature review did not allow for recommending systematic prescription of ambulatory physiotherapy for patients able to leave the surgery department directly for home just after TKR. However, this prescription could improve muscle strength and function but not mobility. When patients can return home directly after surgery, we recommend ambulatory physiotherapy as suggested by French clinical practice to increase function. Good methodological trials must be developed to define the criteria for prescribing ambulatory physiotherapy for patients able to return home just after total knee replacement (TKR) and to evaluate the content of the optimal program.


Therapeutic serum lidocaine and metabolite concentrations in patients undergoing electrophysiologic study after discontinuation of intravenous lidocaine infusion.
Serum concentrations of lidocaine and its metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX) were measured in seven patients after discontinuation of intravenous lidocaine necessary for control of spontaneous arrhythmias prior to electrophysiologic study. Standard loading doses of lidocaine were given intravenously followed by 2 mg/min infusions for 79.5 +/- 6.5 hours. Electrophysiologic studies all started more than 5 half-lives or 7.5 hours after discontinuation of intravenous lidocaine. Local anesthesia with subcutaneous lidocaine (mean 162 +/- 96 mg) was administered in six patients. Plasma concentrations of lidocaine and its metabolites were determined at the termination of the infusion, 2 and 4 hours afterwards, at the start of the electrophysiologic study prior to local anesthesia, and at the end of the study. Levels were also determined at 12 and 24 hours after discontinuation of the infusion. Mean plasma concentrations of lidocaine, MEGX, and GX at the start of the study were 1.02, 0.86, and 0.62 micrograms/ml, respectively. These had increased to 2.78, 0.92, and 0.68 by the end of the electrophysiologic study. One patient with coronary artery disease and prior out-of-hospital ventricular fibrillation had a therapeutic lidocaine level and no inducible arrhythmia at the time of the initial study. At a subsequent electrophysiologic study, no lidocaine or metabolites were detected in the serum and ventricular fibrillation was induced. Thus using the reported half-life of 90 minutes and discontinuing lidocaine 5 half-lives prior to electrophysiologic evaluation does not ensure lack of electrophysiologic effects of the parent compound or its metabolites. Lidocaine given for local anesthesia further increases lidocaine and metabolite levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Diketopyrrolopyrrole Derivatives as Photosensitizing Agents against Staphylococcus aureus.
Diketopyrrolopyrrole (DPP) derivatives containing sulfonamide (Sulfonamide-DPP), pyridyl (Dipyridyl-DPP) and N-methylpyridyl (MePyridyl-DPP) substituents were assessed as antibacterial photosensitizers. Non-charged DPPs showed an intense absorption band centered at about 480 nm and green fluorescence emission (ΦF ~ 0.7) in acetonitrile. The absorption of MePyridyl-DPP was bathochromically shifted at 510 nm, with decreased fluorescence emission. Sulfonamide-DPP and Dipyridyl-DPP photosensitized the formation of O2 (1 Δg ) (ΦΔ ~ 0.15-0.17), while the production induced by MePyridyl-DPP was at least 10 times lower. Furthermore, these DPPs produced a photoreduction of NBT similar to that of the control. Photodynamic inactivation induced by DPPs was first investigated at the single-bacterium level of Staphylococcus aureus attached to a surface. After 30 min irradiation, MePyridyl-DPP produced a complete eradication of the bacteria. In bacterial cell suspensions, dicationic DPP induced more than 7 log10 decrease in S. aureus cell survival after 30 min irradiation. Potentiation with iodide anions allowed a complete elimination of bacteria after 15 min therapy. This compound was also effective to eliminate S. aureus cells on biofilms. The results show that MePyridyl-DPP bearing two positive groups provides an amphiphilic character to the structure that improves the interaction with the cell envelop. This effect enhances the photocytotoxic activity of MePyridyl-DPP against bacteria.


Comparison of bacterial removal from dentinal tubules with different irrigant agitation techniques: An in vitro study.
This investigation was conducted to assess the ability of various irrigant agitation devices to eradicate Enterococcus faecalis from the dentinal tubules of extracted teeth. Fifty roots of extracted human teeth were instrumented to size 30 k with a 0.04 taper. The roots were autoclaved and then injected with E. faecalis. The canals were assigned to one of four intervention groups and disinfected using (A) standard needle irrigation, (B) EndoUltra® Ultrasonic Activator, (C) the EndoActivator system, or (D) EDDY sonic activation and to two control groups that were (E) treated with saline and (F) not inoculated with any bacteria. The roots were split in half, dyed with a LIVE/DEAD Back Light Bacterial Viability Kit, and then scanned with a confocal laser scanning microscope (CLSM) to identify live/dead bacteria in the dentinal tubules. CLSM images revealed differences among the groups. Both the EndoUltra® Ultrasonic Activator group and the EDDY group had a combination of dead and live bacteria, while the EndoActivator group had mostly dead bacteria, in contrast to single needle irrigation which had mostly live bacteria. Activation of the irrigating solution resulted in more dead bacteria than standard needle irrigation at the coronal, middle, and apical parts of the roots. Overall, the EndoActivator system was superior to all other techniques in reducing live bacteria within the root canal. Activation of sodium hypochlorite with sonic and ultrasonic systems dramatically reduced live bacteria contamination in the dentinal tubules of infected root canals.


Expression of CD86 in acute myelogenous leukemia is a marker of dendritic/monocytic lineage.
The aim of this study was to determine whether expression of the CD86 costimulatory molecule in acute myeloid leukemia (AML) can identify blast cells committed to the monocytic/dendritic lineage. One hundred ten consecutive AML patients observed at diagnosis were studied by flow cytometry. In selected experiments, in vitro cultures with CD34(+)CD86(+) or CD34(-)CD86(+) blasts were performed in the presence of granulocyte-macrophage colony-stimulating actor (GM-CSF) with or without tumor necrosis factor-alpha (TNF-alpha) or GM-CSF + interleukin-4 (IL-4), respectively, to induce a dendritic differentiation, documented by morphologic and immunophenotypic assays. T-cell alloreactivity to CD86(+) AML cells and leukemic dendritic cells (AML-DC) was tested in mixed leukocyte cultures and anti-leukemic cytotoxic assays. CD86 was expressed in 54% AML, whereas CD80 and CD1a were only occasionally positive. CD86(+) AML samples included M5 and M4, but also 47% M0-M1 FAB types, and were more frequently CD14(+) (p < 0.00001) and CD34(-) (p = 0.00005) than CD86(-)AML. Six different patterns of CD86(+) AML were identified, according to CD34 or CD14 total or partial coexpression. Four samples enriched in CD34(+)CD86(+) AML cells differentiated into AML-DC CD86(+), CD80(+), CD40(+), CD11c(+), HLA-DR(++), CD14(+/-) that also were CD1a(+) or CD83(+), after 6 days of in vitro culture with GM-CSF +/- TNF-alpha. CD34(-)CD86(+) AML cells differentiated into AML-DC after 3 to 5 days (n = 5 experiments), and trisomy 8 was found in two AML and AML-DC samples by fluorescence in situ hybridization analysis. Finally, AML-DC induced more potent allo-T-cell proliferation, cytokine release, and anti-leukemic cytotoxicity than CD86(+) blasts. In AML, CD86 is a marker of monocytic/dendritic lineage. Because CD86(+) blasts may differentiate into DC rapidly, CD86(+)AML patients could be optimal candidates for immunotherapy studies, both in autologous and allogeneic settings.


Peptide-nucleic acid-mediated enriched polymerase chain reaction as a key point for non-invasive prenatal diagnosis of beta-thalassemia.
The presence of fetal DNA in maternal plasma can be exploited to develop new procedures for non-invasive prenatal diagnosis. Tests to detect 7 frequent beta-globin gene mutations in people of Mediterranean origin were applied to the analysis of maternal plasma in couples where parents carried different mutations. A mutant enrichment amplification protocol was optimized by using peptide nucleic acids (PNAs) to clamp maternal wild-type alleles. By this approach, 41 prenatal diagnoses were performed by microelectronic microchip analysis, with total concordance of results obtained on fetal DNA extracted from chorionic villi. Among these, 27/28 were also confirmed by direct sequencing and 4 by pyrosequencing.


[Effect on dose owing to source displacement in coronary endovascular brachytherapy].
To investigate the effect on the dose distribution of source position displacement with the target region margin in catheter-based 192Ir line source endovascular brachytherapy. Dose rate distribution along longitudinal axes was estimated by the formula recommended by AAPM No.60 and No. 43. In the two cases of source displacement (1.1 and 5 mm) doses of target region margin was decreased dramatically (at most 53.9% and 565.8% respectively) were compared to that of no source displacement, and the affected range was 6 mm and 9 mm respectively. Source displacement will lead to the decrease of dose in target region margin.


Toward a clinical subgrouping of hyperactive and nonhyperactive attention deficit disorder. Results of a comprehensive neurological and neuropsychological assessment.
We studied 32 boys with attention deficit disorder (ADD)--21 with hyperactivity, and 11 without hyperactivity. The ADD group with hyperactivity had significantly more neurological and cognitive abnormalities and a higher frequency of prenatal and neonatal abnormalities. It seems that hyperactivity is an important determinant of the degree of neurological and cognitive involvement in children with ADD. It also seems that a cause of "early" brain insult is more likely when hyperactivity is present.


Androgen receptor in human liver: characterization and quantitation in normal and diseased liver.
Liver is responsive to sex hormones. The role of androgens in normal human liver function is not well understood, although androgens have been implicated in several liver diseases. Because the human hepatic androgen receptor has not been adequately characterized, we analyzed cytosolic and nuclear fractions from normal human liver of both sexes for androgen-binding activity using multipoint saturation analysis with the androgenic radioligand methyltrienelone (R1881). Both cytosolic and nuclear fractions of both sexes displayed high affinity R1881 binding (dissociation constants = nanomolar range). The R1881 binding in both fractions is highly specific in that potent androgens compete well, and the antiandrogens hydroxyflutamide and cyproterone acetate show partial competition; other nonandrogenic steroid hormones do not compete. The cytosolic R1881 receptor displays physicochemical characteristics of androgen receptors in other tissues in that it is retained by heparin-Sepharose and by DNA cellulose after activation, and it displays a molybdate-stabilized 8S form on sucrose gradients and a 7.3-nm species on gel filtration chromatography. Receptor activity was also quantitated in specimens of hepatic adenoma, focal nodular hyperplasia and metastatic carcinoma to the liver and in samples of adjacent histologically normal specimens when available. In general, both the diseased and normal portions of the livers from the patients with hepatic adenoma and metastatic carcinoma to the liver, but not focal nodular hyperplasia, demonstrated reduced total androgen-receptor activity as compared with liver from normal individuals.(ABSTRACT TRUNCATED AT 250 WORDS)


The study on transgenic mice.
The structural gene coding for human growth hormone (hGH) was fused to the promoter of the mouse gene for metallothionein-1. These fusion genes were introduced into pronuclei of the fertilized eggs of mice by micro-injection. We have injected MT-hGH genes into 121 mouse eggs which were transferred into the oviducts of eleven pseudo-mothers. Seven out of eleven mothers gave birth. Forty-three litters were born. These litters were grown-up and their tails were cut for isolating the DNA. The DNA of each mouse was examined by dot hybridization and Southern blotting. We found that eighteen mice had incorporated the fusion genes and grew larger than control mice. Synthesis of human growth hormone was induced further by zinc, which normally induces metallothionein gene expression. We also isolated the RNA from the livers of transgenic mice. The RNA was hybridized with hGH gene. It showed that on the transcription level the hGH gene was transcribed into mRNA in the transgenic mice. Using the same method to examine the second and third generation of the transgenic mice, we found that the incorporated gene could be inherited for generations. But the body-weight of transgenic mice appeared to decrease in the progeny. The offspring obtained from different combinations of parents (carrying or not carrying hGH gene) were different.


Support for practitioners switching work environments mid-career.
Patterns of healthcare demand are changing, so services are increasingly being located in communities. Nurses and nurse managers must. therefore, prepare themselves for mid-career transitions into new roles or working environments. This article explains how these transitions can best be made and offers some tips for nurses and nurse managers who are about to make them, or who want to help colleagues make them, successfully.


Dexamethasone-induced alterations in the glycosphingolipids of rat proximal small-intestinal mucosa.
Prior studies have demonstrated that glucocorticoids can influence the structure and function of several different organs, including the small intestine. However, to date, the effects of glucocorticoids on the glycosphingolipids of the rat small intestinal mucosa have not been examined. In the present experiments, male albino rats of the Sherman strain were subcutaneously administered dexamethasone (100 micrograms/100 g body wt. per day) or diluent for 4 days, and the ceramide, acidic and neutral glycosphingolipid compositions of the proximal small intestine of these animals were examined and compared. The results of these studies demonstrate that dexamethasone administration: (1) increased the content and relative percentage of hematoside (GM3) in this tissue; (2) increased the percentage of N-glycoylneuraminic acid of hematoside; (3) decreased the percentage of the long-chain base phytosphingosine of hematoside, glucosyl- and globotriaosylceramide; and (4) did not appear to influence significantly the concentration of the neutral glycosphingolipids or ceramide in this tissue. These data, therefore, indicate that dexamethasone administration induces alterations in the glycosphingolipids, particularly hematoside, of rat small-intestinal mucosa.


Relation between haemolymph proteins and fat body during metamorphosis in Danais chrysippus Linn. II.
Changes in haemolymph protein fractions and histology, of adipose tissue has been observed in the larvae, pupae and newly emerged adults of Danais chrysippus. At time of pupation, proteins get accumulated in the fat body and in turn are utilized in metabolic process occuring during metamorphosis. A clear correlation exists between the adipose tissue and haemolymph proteins. A human-serum-albumine like proteins was not observed in this insect species.


Developing students' teaching through peer observation and feedback.
With the increasing popularity and scale of peer teaching, it is imperative to develop methods that ensure the quality of teaching provided by undergraduate students. We used an established faculty development and quality assurance process in a novel context: peer observation of teaching for undergraduate peer tutors. We have developed a form to record observations and aid the facilitation of feedback. In addition, experienced peer tutors have been trained to observe peer-taught sessions and provide tutors with verbal and written feedback. We have found peer observation of teaching to be a feasible and acceptable process for improving quality of teaching provided by undergraduate medical students. However, feedback regarding the quality of peer observer's feedback may help to develop students' abilities further.


Humoral immune responses against Wilms tumor gene WT1 product in patients with hematopoietic malignancies.
Wilms tumor gene WT1 is expressed at high levels in hematopoietic malignancies, such as leukemias and myelodysplastic syndromes (MDS), and in various kinds of solid tumors, including lung cancer, and it exerts an oncogenic function in these malignancies. IgM and IgG WT1 antibodies were measured by means of dot blot assay in 73 patients with hematopoietic malignancies (16 acute myeloid leukemia [AML], 11 acute lymphoid leukemia [ALL], 13 chronic myeloid leukemia [CML], and 33 MDS) and 43 healthy volunteers. Immunoglobulin IgM, IgG, and IgM+IgG WT1 antibodies were detected in 40 (54.8%), 40 (54.8%), and 24 (32.8%), respectively, of the 73 patients with hematopoietic malignancies, whereas 7 (16.2%), 2 (4.7%), and none of the 43 healthy volunteers had IgM, IgG, or IgM+IgG WT1 antibodies, respectively. Furthermore, immunoglobulin isotype class switching of WT1 antibodies from IgM to IgG occurred in conjunction with disease progression from refractory anemia (RA) to RA with excess of blasts (RAEB), and further to RAEB in transformation (RAEB-t) in MDS patients. These results showed that humoral immune responses against the WT1 protein could be elicited in patients with WT1-expressing hematopoietic malignancies, and they suggested that the helper T-cell responses needed to induce humoral immune responses and immunoglobulin isotype class switching from IgM to IgG were also generated in these patients. Our findings may provide new insight into the rationale for elicitation of cytotoxic T-cell responses against the WT1 protein in cancer immunotherapy using the WT1 vaccine.


Inhibition of foot and mouth disease virus and procapsid synthesis by zinc ions. Brief report.
Zinc ions inhibit virus production and viral RNA synthesis in FMDV infected-BHK 21 cells. The degree of inhibition depends upon the zinc concentration and the time of addition of the drug. A differential inhibition on virus and procapsids synthesis was observed.


Age-related gene expression and DNA methylation changes in rhesus macaque.
Aging is a very complicated biological process that can change gene expressions. The Chinese rhesus macaque (Macaca mulatta lasiota; CR) is closely related to humans. We explored gene expression with increasing age and DNA methylation changes in young and old CRs. Results showed blood transcriptome and DNA methylome significantly changed from young to old CRs. The age-associated differentially expressed genes (DEGs) and differentially methylated regions (DMRs) were associated with age-related biological features, such as immunity, blood coagulation, and biosynthetic process. The measurements of coagulation indicators confirmed old CRs had shorter coagulation time than young CRs, and the activities of coagulation factor II (FII) and factor VIII (FVIII) were enhanced in old CRs. Humans and CRs exhibited the same enhanced blood coagulation with age phenotype. Our study found aging is a critical factor affecting gene expression in CRs, and also provided new insights into the blood coagulation changes in non-human primates.


Insulin-like growth factor-I concentration in Holstein female cattle: variations with age, stage of lactation and growth hormone-releasing factor administration.
Plasma insulin-like growth factor-I (IGF-I) concentrations were monitored in Holstein females through different periods of their growth, lactation and after acute or chronic growth hormone-releasing factor (GRF) administration. Plasma samples were radioimmunoassayed using a human IGF-I antibody after a 24 hr incubation in a HCl(.1N)-glycine(.2M) buffer (pH 2). In a first study, IGF-I concentrations were measured in Holstein females of different ages and(or) stages of lactation (n = 6 per group). The IGF-I concentrations in newborn calves (102.0 +/- 11.3 ng/ml) markedly decreased (P less than .01) in 1 mo old animals (50.2 +/- 7.1 ng/ml), then increased (P less than .01) to 137.0 +/- 5.1 and 137.4 +/- 11.0 ng/ml in 6 and 10 mo old heifers, respectively. In dairy cows, IGF-I concentrations were low 24 hr post-partum (44.7 +/- 7.6 ng/ml) and then increased (P less than .05) to remain stable throughout lactation (91.3 +/- 4.9, 92.8 +/- 12.9, 96.1 +/- 7.6, 90.7 +/- 8.8 ng/ml at 2, 3, 6 and 9 mo of lactation, respectively). There was a further increase (P less than .05) to 113.7 +/- 3.1 ng/ml during the dry period. In a second trial, blood samples were collected from lactating dairy cows every 2 hr for 24 hr following a sc injection of saline (n = 4) or human (h) GRF (1-29)NH2 (10 micrograms/kg BW, n = 4). The IGF-I peak concentration was reached on average 10 hr after the GRF injection and was higher (P less than .01) in treated cows than in control cows (135.4 vs 86.9 +/- 16.2 ng/ml). In the last trial, daily sc injections of 10 micrograms of hGRF(1-29)NH2 per kg BW to dairy cows (252 days of lactation) for 57 days, which increased milk production by 14% (2 kg/day), also increased (P less than .01) IGF-I concentration: 127.1 +/- 5.3 and 118.0 +/- 1.6 vs 90.7 +/- 4.7 and 96.0 +/- 5.0 ng/ml on days 29 and 57 of treatment for treated (n = 9) and control (n = 8) cows, respectively. Thus, the IGF-I concentration in dairy cattle varies with age and stage of lactation, and is increased by GRF administration in lactating dairy cows.


Superior efficacy of clopidogrel plus acetylsalicylic acid compared with extended-release dipyridamole plus acetylsalicylic acid in preventing arterial thrombogenesis in healthy volunteers.
Recent ex vivo platelet aggregometry data indicate that clopidogrel 75 mg/day plus acetylsalicylic acid (ASA) 75 mg/day is a more potent antiplatelet regimen than the marketed combination of dipyridamole+ASA. The present study was designed to assess the antithrombotic effect of both dual antiplatelet regimens using a human ex vivo model of arterial thrombosis. This was a randomized, double-blind, placebo-controlled, crossover study. During two 10-day treatment periods separated by a 14-day washout period, 23 healthy male volunteers received once-daily clopidogrel 75 mg plus acetylsalicylic acid 75 mg, or twice-daily extended-release dipyridamole 200 mg plus acetylsalicylic acid 25 mg. Assessments were made at baseline and on Day 10 of each period. Arterial thrombus formation was induced ex vivo by exposing a collagen-coated surface in a parallel-plate perfusion chamber to native blood for 3 min (arterial wall shear rate 2600 s(-1)). Total platelet and fibrin deposition was determined by immunoenzymatic methods. Compared with baseline values, the mean inhibition of total platelet deposition was 63.9+/-5.9% with clopidogrel plus acetylsalicylic acid, compared with 18.4+/-5.6% for extended-release dipyridamole plus acetylsalicylic acid (67% reduction; 95% CI, 49-79%; p<0.0001). Corresponding figures for fibrin deposition were 64.9+/-4.8% and 18.3+/-9.7%, respectively (58% reduction; 95% CI, 45-67%; p<0.0001). Both treatments were well tolerated. Clopidogrel plus acetylsalicylic acid showed significantly superior antithrombotic efficacy compared with extended-release dipyridamole plus acetylsalicylic acid in preventing arterial thrombogenesis in humans.


Uptake of labelled tallysomycin by solid Ehrlich ascites tumors in mice.
Tumor and normal tissue uptake of 51Cr- or 57Co-labelled bleomycin (BLEO) and tallysomycin (TLM) was compared in female solid Ehrlich ascites tumor mice of Swiss strain. The complexes were administered intraperitoneally: 30-50 micrograms of each complex with an activity of 40-120 microCi. Activity distribution factors (ADF) and tumor/non-tumor ratios for blood, bone, skeletal muscles, kidneys and liver were determined. The ratios were generally higher for complexes labelled with 57Co than for the 51Cr-labelled ones; bleomycin appears equivalent or superior to tallysomycin.


Characterization of polyphenols from plant materials through their silylation and 29Si NMR spectroscopy-line assignment through 29Si, 13C spin-spin couplings.
The lines in (29)Si NMR spectra of silylated polyphenols and some other compounds are difficult to assign owing to the absence of couplings with protons outside the silyl group. The assignment can be derived through small (n)J((29)Si, (13)C) couplings (n > 1). Using a previously described method for measurements of these couplings, the assignment procedure is demonstrated here on three examples of trimethylsilylated phenols: 7-hydroxyflavone, ferulic acid, and quercetin. In some cases the procedure can be used to identify carbon atoms to which the siloxy groups are attached.


The variation in the light responses of carp retinal ganglion cells is independent of response amplitude.
The variation of the response rate of carp retinal ganglion cells to photopic light stimulation was studied. It was found that the standard deviation was independent of the mean of the response rate, even when responses showed compression. This finding is in agreement with a late origin of retinal noise. Implications of the existence of intrinsic constant amplitude retinal noise and of the presence of a mean maintained activity are discussed.


Urbanization data of Samara city, Russia.
A method has been developed for urbanization by using satellite data and socio-economic data. These datasets consists three decade Landsat images and population data. A detailed description using flow chart is given to show how to use this data to produce land use/cove maps. The land use/cove maps were used to know the urban growth in Samara City, Russia.


Assessment of cardiac involvement of hepatitis C virus; tissue Doppler imaging and NTproBNP study.
Hepatitis C disease burden is substantially increasing in Egyptian community, it is estimated that prevalence of Hepatitis C virus (HCV) in Egyptian community reach 22% of total population. Recently there is a global alert of HCV cardiovascular complications. To evaluate LV diastolic functions of HCV patients using tissue Doppler Imaging and NTPBNP. 30 HCV patients of 30 years, sex & BMI matched controls were evaluated by PCR, ECG, Echocardiography "conventional Doppler, pulsed wave tissue Doppler (PW-TD), strain rate imaging" & NTPBNP to assess LV diastolic functions. Mean age was 32.8 years ± 5.1 in HCV group, 29.8 years ± 6.6 in control group. Cardiovascular anomalies and predisposing factors were excluded. HCV group has shown significant increase in QTc interval, significant statistical increase in A wave, deceleration time; (p < 0.05), highly significant decrease in tissue Doppler E a (p < 0.001), highly significant decrease in A a (p < 0.001), highly significant increased E/E a ratio (p value < 0.001), significant decrease in E a/A a ratio and significant increase in SRa (p < 0.05). NTPBNP levels showed highly significant increase with mean value 222 pg/ml ± 283 in HCV group and 32.7 pg/ml ± 21.2 in control group (p value < 0.001). The best cut-off value of NTPBNP to detect diastolic dysfunction in HCV group was 213 pg/ml. No statistical differences in SRe/SRa and E/SRe ratios were observed, however they had significant correlation with NTPBNP level and tissue Doppler parameters. The best cut-off value of E/SRe ratio to detect diastolic dysfunction in HCV group was 0.91, with 75% sensitivity and 100% specificity. This data show the first direct evidence that HCV infection causes diastolic dysfunction without any other predisposing factors, probably due to chronic inflammatory reaction with mild fibrosis in the heart. Previous studies did not follow strict inclusion and exclusion criteria that confirm the independent role of HCV to cause diastolic dysfunction. Tissue Doppler was more sensitive to diagnose diastolic dysfunction than conventional Doppler.


Diverticulum arising from mitral valve.
Diverticula arising from the mitral valve are very rare. They are usually detected by echocardiography as masses arising from the cardiac valves. We present a case of an incidental finding of a diverticulum arising from the mitral valve. This was initially detected by transesophageal echocardiography, and later confirmed by pathologic appearance. The case illustrates the unique findings on echocardiography that would help to differentiate diverticula from other valvular masses.


Adenomatous hyperplasia of the gallbladder.
Adenomatous hyperplasia of the gallbladder is an uncommon condition, particularly in men. A literature search yields minimal information on this entity, thus suggesting the infrequency of its occurrence. Adenomyomatosis is an entity that closely resembles adenomatous hyperplasia but has hypertrophy of the muscular layer and extensive Rokitansky-Aschoff sinuses. We report the finding of adenomatous hyperplasia in a middle-aged male in the setting of symptomatic cholelithiasis.


Delineation of a KDM2B-related neurodevelopmental disorder and its associated DNA methylation signature.
Pathogenic variants in genes involved in the epigenetic machinery are an emerging cause of neurodevelopment disorders (NDDs). Lysine-demethylase 2B (KDM2B) encodes an epigenetic regulator and mouse models suggest an important role during development. We set out to determine whether KDM2B variants are associated with NDD. Through international collaborations, we collected data on individuals with heterozygous KDM2B variants. We applied methylation arrays on peripheral blood DNA samples to determine a KDM2B associated epigenetic signature. We recruited a total of 27 individuals with heterozygous variants in KDM2B. We present evidence, including a shared epigenetic signature, to support a pathogenic classification of 15 KDM2B variants and identify the CxxC domain as a mutational hotspot. Both loss-of-function and CxxC-domain missense variants present with a specific subepisignature. Moreover, the KDM2B episignature was identified in the context of a dual molecular diagnosis in multiple individuals. Our efforts resulted in a cohort of 21 individuals with heterozygous (likely) pathogenic variants. Individuals in this cohort present with developmental delay and/or intellectual disability; autism; attention deficit disorder/attention deficit hyperactivity disorder; congenital organ anomalies mainly of the heart, eyes, and urogenital system; and subtle facial dysmorphism. Pathogenic heterozygous variants in KDM2B are associated with NDD and a specific epigenetic signature detectable in peripheral blood.


Endogenous CO2 may inhibit bacterial growth and induce virulence gene expression in enteropathogenic Escherichia coli.
Analysis of the growth kinetics of enteropathogenic Escherichia coli (EPEC) revealed that growth was directly proportional to the ratio between the exposed surface area and the liquid culture volume (SA/V). It was hypothesized that this bacterial behavior was caused by the accumulation of an endogenous volatile growth inhibitor metabolite whose escape from the medium directly depended on the SA/V. The results of this work support the theory that an inhibitor is produced and indicate that it is CO(2). We also report that concomitant to the accumulation of CO(2), there is secretion of the virulence-related EspB and EspC proteins from EPEC. We therefore postulate that endogenous CO(2) may have an effect on both bacterial growth and virulence.


Expression of Fos immunoreactivity in the rat supraspinal regions following noxious visceral stimulation.
We used immunohistochemical detection of the Fos protein to study the neuronal activation in the brain of methoxyfluorane-anesthetized rats after noxious deep somatic or visceral stimulation. The anesthesia was effective in triggering gene induction in many brain regions. Nevertheless, Fos appeared de novo in several brain nuclei following noxious stimulation in anesthetized animals. This could be of clinical relevance, as it suggests that the gas anesthetic does not suppress noxious stimulus-evoked reactivity in brain neurons. Two types of visceronociceptive stimuli were used to compare the effects of a diffuse visceral inflammation (peritoneal inflammation) with those of a more restricted inflammation (urinary bladder inflammation). In the same supraspinal areas, there were very few immunostained neurons in unstimulated controls, whereas Fos-positive cells were slightly more numerous in anesthetized controls and significantly more numerous after noxious stimulation. The peritoneal inflammation induced more Fos-labeled neurons than the restricted visceral stimulation. Labeled cells were found in these cases mainly in the ventrolateral medulla, parabrachial complex, dorsal raphe nucleus, periaqueductal gray, several hypothalamic and thalamic nuclei, amygdaloid complex, and cortex. Altogether these findings indicated that somatic and visceral inputs generally activate the same neuronal groups. However, a separation between the activation of somatic and visceral pathways was found in some brain nuclei, such as the parabrachial complex, hypothalamic, and thalamic nuclei.


Growth performance and carcass characteristics of Koekoek chickens exposed to temperature variation with supplementary Coriander seed powder.
The aim of the present study was to evaluate the effects of ambient temperature and coriander seeds supplementation on growth performance and carcass characteristics of Koekoek chickens. In the experiment, chickens were exposed to two temperature rooms with a heated room of 32 ± 1.2 °C from 11:00 to16:00 h and a normal room temperature with an average maximum and minimum of 23.8 ± 3 °C and 16.6 ± 1.6 °C, respectively, and a relative humidity between 34.5 ± 4 and 44.8 ± 3%. The chickens were supplemented with 0, 5, and 10 g/kg of coriander seed powder. The results showed that the group of Koekoek chickens placed in a heated room had significantly lower (P < 0.05) feed intake and weight gain and significantly higher (P < 0.05) feed conversion ratio than the groups placed at normal room temperature. Water intake was 1.8% higher in the groups placed in a heated room than those placed at normal room temperature. Supplementation with coriander seed powder enhanced growth performance and carcass traits. The carcass weight and breast percentage were higher (P < 0.05) in the groups that received 10 g/kg coriander seed powder. The growth performance of the Koekoek groups supplemented with 10 g/kg coriander seed powder in a heated room also improved significantly compared to groups in a heated room without supplementation. This suggests that the supplementation of coriander seed improves performance, and has a positive potential effect in alleviating the negative effects of heat stress on growth performance of chickens.


Field evolved resistance to pyrethroids, neonicotinoids and biopesticides in Dysdercus koenigii (Hemiptera: Pyrrhocoridae) from Punjab, Pakistan.
The red cotton bug, Dysdercus koenigii (Fabricius) is an important emerging economic pest of cotton, Gossypium hirsutum Linnaeus in Pakistan. Insecticides are the primary management tactics to suppress populations of this pest. However, resistance to insecticides evolves due to substantial and repeated applications. The resistance to pyrethroids, neonicotinoids and biopesticides have been evaluated in many pests worldwide, nevertheless lack of information in D. koenigii. Therefore, the aforementioned insecticide resistance in five field populations of D. koenigii collected from Multan, Makhdoom Rashid, Jahanian, Lodhran and Vehari districts of Punjab, Pakistan during 2015-2017 was determined by using seed dip method. Based on the present results, D. koenigii has developed moderate to very high resistance to acetamiprid (RR = 33-433) and imidacloprid (RR = 21-173), low to high resistance to emamectin benzoate (RR = 14-52), and very low to high resistance to spinosad (RR = 4.13-54), compared to the susceptible population. However, all field populations of D. koenigii remained susceptible to deltamethrin (RR = 0.62-2.17) and lambda-cyhalothrin (RR = 0.91-1.97). A rotational use of pyrethroids with provision of other integrated pest management tactics is recommended to manage insecticide resistance in D. koenigii.


The Value of Pathological Examination of the Foreskin Following Circumcision.
We determined the clinical impact and value of routine histopathological examination of the foreskin following circumcision. We performed a retrospective study of 225 consecutive adult circumcisions. Indications for circumcision were categorized as benign or malignant based on preoperative clinical evaluation. Histopathological results were similarly classified as benign or malignant. Preoperative clinical impression and postoperative histological diagnosis were compared and reported as concordant (in agreement) or discordant (in disagreement). The cost impact of histopathology examination was analyzed with respect to study findings. Of the 225 patients 209 (92.9%) had clinically benign disease on preoperative evaluation and 16 (7.1%) had foreskin lesions suspicious for malignancy. Mean age was 57.0 years (range 23 to 92). Patients were younger in the benign group than in the malignant group (56.5 vs 62.8 years, p = 0.018). Black patients represented 65.8% of the study population and were similarly distributed between the 2 groups (p = 0.405). There was no statistical difference in patient height, weight, body mass index or comorbidities between the 2 groups. Preoperative clinical impression and postoperative histological diagnosis were concordant in all 209 patients in the benign group. Of the 16 patients suspected to have malignant disease preoperatively 9 (56.2%) had malignancy and 7 (43.8%) had benign disease on histopathological examination. Routine histological examination of a foreskin specimen in the absence of clinical suspicion for malignancy appears to have diminished benefit in the setting of benign preoperative indications. Omitting this traditional practice in patients with benign surgical indications may positively impact health care costs without compromising quality of care.


Resistance to antibacterial therapy in pediatric febrile urinary tract infections-a single-center analysis.
Febrile urinary tract infections (UTIs) are common serious bacterial infections in childhood and require early diagnosis and antibacterial therapy. However, considerable uncertainty exists regarding the optimal antibacterial agent for primary treatment of pediatric UTIs. Additionally, patterns of susceptibility and resistance change over time and microbiological in vitro resistance is not necessarily associated with treatment failure. Here, we analyzed uropathogens, their resistance patterns, and response to antibacterial treatment in children with acute pyelonephritis. We used billing codes (international classification of diseases) to identify all inpatients aged 0-18 years with febrile UTIs in a German university tertiary care center from 2009 until 2018. Microbial results were retrieved from the laboratory information system for all children, and treatment regimen and treatment response were analyzed in a subgroup of children. We identified 907 children with acute pyelonephritis; in 590 cases (65%) an uropathogen was detected. Escherichia coli (60.8%), Enterococcus faecalis (13.2%), Klebsiella pneumoniae (7.0%), Proteus spp. (5.2%), and Pseudomonas aeruginosa (4.2%) were the most common pathogens. 353 of 436 E.coli isolates (81.0%) were susceptible or intermediate to aminopenicillin/β-lactamase-inhibitor (BLI) combinations. We examined 52 cases where E. coli was resistant to initial therapy with aminopenicillin/BLI combinations: Therapy was changed in 35 cases (67%) and left unchanged in 17 cases (33%), and we found no significant differences in C-reactive protein and leucocyte count in blood and urine between both groups after 3 days. We present the spectrum of uropathogens and susceptibility test results in pediatric UTIs in a tertiary care center. Our findings suggest a satisfactory response to first-line therapy with aminopenicillin/BLI combinations.


Invasion of campylobacter-like organisms in the duodenal mucosa in patients with active duodenal ulcer.
The ultrastructure of campylobacter-like organisms found within duodenal biopsy specimens from 7 of 24 patients (28%) with active duodenal ulcer is described. Their curved shape and variable size are similar to what has previously been reported in descriptions of light microscopies. The organisms were found at the edge of active duodenal ulcers exclusively near neutral-mucous producing antral cells, to which they can adhere. The presence of these bacteria within cells and in the intercellular fluid implies that they can penetrate through the cell membrane or through tight intercellular junctions. The occurrence of these bacteria as well as numerous polymorphonuclear leukocytes in the afflicted regions suggests that the bacteria originally described by Warren and Marshall are indeed pathogenic and that their influence on ulcer healing should be included in designing treatment protocols.


Safety and efficacy of a novel continence device in colostomy patients.
This study aimed to assess the safety and efficacy of a novel colostomy continence device. This phase II, 142-day, open-label, nonrandomized, multicenter study enrolled patients who had end colostomies for ≥3 months. Study stages were usual pouching (21 days), wafer transition (14 days), and the device (107 days). During device wear, up to 8 hours per day, patients recorded the following outcomes in daily diaries: skin condition (if the wafer was changed); stoma color, moisture, and physical condition; and gastrointestinal symptoms. Of the 26 patients enrolled, 25 wore at least one device. The device was worn on 96% of study days and a mean of 6.8 hours per day. Adverse events were reported by 1 patient during the usual pouching 21-day period, by 5 patients during the wafer transition 14-day period, and by 15 patients during the device wear 107-day period. Stoma color and moisture were within normal range on all daily assessments. The device did not affect microbiology or vascularity. During device wear, patients had no unusual gastrointestinal symptoms or odor on >99% and 80% of days, respectively. The mean number of leaks per patient-month was 1.2 with usual pouching, 4.2 with the device overall, and 2.1 during the last 3 weeks with the device, suggesting a learning curve. Approximately 65% of patients preferred the device to usual pouching at the end of study. The novel continence device was safe and effective for up to 8 hours per day in colostomy patients.


The physiologic properties and therapeutic potential of coherin.
Coherin, a peptide isolated from the bovine neurohypophysis, has been shown to be an effective therapeutic agent in post-gastric surgery physiologic obstruction and regional ileitis. Of twenty-four patients with post-gastric surgery physiologic obstruction, coherin relieved symptoms in twenty-three, a 96 per cent efficacy rate. The efficacy of coherin with ileitis was based on the fact that ten of twenty-seven patients treated have required coherin on a continuing basis to stay functional. These patients have requested coherin treatment for an average of five years each, and have each on multiple occasions tried to discontinue coherin treatment with prompt return of symptoms and cessation of symptoms when coherin was reinstituted. All of the ileitis patients had previously failed to respond to standard and usual medical treatment.


Influence of Fucoxanthin on Proliferative Activity of Human Melanocyte Culture.
We studied the effect of algae pigment fucoxanthin on proliferative activity of melanocyte culture from human skin. Fucoxanthin in high concentrations can be cytotoxic, which was confirmed by changes in melanocyte morphology and a decrease in their proliferative activity.


Lipocortin 1 immunoreactivity identifies microglia in adult rat brain.
Immunohistochemical localization of two Ca(++)-binding proteins, Lipocortin 1 (LC1) and S100-beta, demonstrates two distinct classes of primitive glia in the floor plate of rat embryos. With proper fixation (formalin-lysine-periodate-acetic acid), dendritic glia in the CNS of adult rats also apparently stain for either LC1 or S100-beta in the ratio of 1:3. In order to further distinguish and identify these two glial classes, we have examined their population density, topography, and responses to localized neuron death. Neurons of the ipsilateral thalamus undergo apoptosis following cortical ablation; the contralateral thalamus serves as control. By eight days post-lesion, the number of LC1 cells in the ipsilateral thalamus has increased > 4-fold, the increase comprising primarily activated phagocytes adjacent to degenerating neurons. The S100-beta glia in the same region are virtual- ly indistinguishable from control; but background staining (apparently representing extra-cellular S100-beta) is increased. Thus, the responses of dendritic LC1 glia resemble these previously described for microglia and are quite different from the astrocytes identified by S100-beta immunoreactivity. Both dendritic and activated forms of LC1 glia stain with the microglial marker, Griffonia simplicifolia iso-lectin B4. However, before the correspondence of LC1 glia and microglia can be confirmed, two anomalies require resolution: (1) the LC1 glia are greater in number and more evenly distributed than microglia marked with other methods; (2) the dendritic LC1 glia apparently are progeny of primitive glia that form the midline raphe of the embryonic floor plate. The participation of LC1 glia in the removal of CNS debris supports the hypothesis that LC1 plays anti-inflammatory and/or immunosuppressive roles in phagocytes.


Distraction osteogenesis--a review.
This review describes the technique of distraction osteogenesis, outlining its application and current developments for the correction of craniofacial anomalies. Also described are some of the difficulties and complications which can arise with speculation on how this may be overcome. Finally, there is an exploration of how this technique might be routinely used to deal with orthognathic, orthodontic and alveolar problems.


Non-Hodgkin's lymphoma of the uterus in a child.
A unique case of a 14-year-old girl with malignant lymphocytic lymphoma of the uterus clinically misdiagnosed as sarcoma botyroides is presented. Total abdominal hysterectomy was performed followed by limited chemotherapy. The patient is asymptomatic and without clinical evidence of tumor 38 months after the onset of symptoms.


Transcriptomic profiling of Melon necrotic spot virus-infected melon plants revealed virus strain and plant cultivar-specific alterations.
Viruses are among the most destructive and difficult to control plant pathogens. Melon (Cucumis melo L.) has become the model species for the agriculturally important Cucurbitaceae family. Approaches that take advantage of recently developed genomic tools in melon have been extremely useful for understanding viral pathogenesis and can contribute to the identification of target genes for breeding new resistant cultivars. In this work, we have used a recently described melon microarray for transcriptome profiling of two melon cultivars infected with two strains of Melon necrotic spot virus (MNSV) that only differ on their 3'-untranslated regions. Melon plant tissues from the cultivars Tendral or Planters Jumbo were locally infected with either MNSV-Mα5 or MNSV-Mα5/3'264 and analysed in a time-course experiment. Principal component and hierarchical clustering analyses identified treatment (healthy vs. infected) and sampling date (3 vs. 5 dpi) as the primary and secondary variables, respectively. Out of 7566 and 7074 genes deregulated by MNSV-Mα5 and MNSV-Mα5/3'264, 1851 and 1356, respectively, were strain-specific. Likewise, MNSV-Mα5/3'264 specifically deregulated 2925 and 1618 genes in Tendral and Planters Jumbo, respectively. The GO categories that were significantly affected were clearly different for the different virus/host combinations. Grouping genes according to their patterns of expression allowed for the identification of two groups that were specifically deregulated by MNSV-Mα5/3'264 with respect to MNSV-Mα5 in Tendral, and one group that was antagonistically regulated in Planters Jumbo vs. Tendral after MNSV-Mα5/3'264 infection. Genes in these three groups belonged to diverse functional classes, and no obvious regulatory commonalities were identified. When data on MNSV-Mα5/Tendral infections were compared to equivalent data on cucumber mosaic virus or watermelon mosaic virus infections, cytokinin-O-glucosyltransferase2 was identified as the only gene that was deregulated by all three viruses, with infection dynamics correlating with the amplitude of transcriptome remodeling. Strain-specific changes, as well as cultivar-specific changes, were identified by profiling the transcriptomes of plants from two melon cultivars infected with two MNSV strains. No obvious regulatory features shared among deregulated genes have been identified, pointing toward regulation through differential functional pathways.


Evaluation of (Z)-2-((1-benzyl-1H-indol-3-yl)methylene)-quinuclidin-3-one analogues as novel, high affinity ligands for CB1 and CB2 cannabinoid receptors.
A small library of N-benzyl indolequinuclidinone (IQD) analogs has been identified as a novel class of cannabinoid ligands. The affinity and selectivity of these IQDs for the two established cannabinoid receptor subtypes, CB1 and CB2, was evaluated. Compounds 8 (R=R(2)=H, R(1)=F) and 13 (R=COOCH3, R(1)=R(2)=H) exhibited high affinity for CB2 receptors with Ki values of 1.33 and 2.50 nM, respectively, and had lower affinities for the CB1 receptor (Ki values of 9.23 and 85.7 nM, respectively). Compound 13 had the highest selectivity of all the compounds examined, and represents a potent cannabinoid ligand with 34-times greater selectivity for CB2R over CB1R. These findings are significant for future drug development, given recent reports demonstrating beneficial use of cannabinoid ligands in a wide variety of human disease states including drug abuse, depression, schizophrenia, inflammation, chronic pain, obesity, osteoporosis and cancer.


Aminoacyl-tRNA synthetase inhibitors as potential antibiotics.
Increasing resistance to antibiotics is a major problem worldwide and provides the stimulus for development of new bacterial inhibitors with preferably different modes of action. In search for new leads, several new bacterial targets are being exploited beside the use of traditional screening methods. Hereto, inhibition of bacterial protein synthesis is a long-standing validated target. Aminoacyl-tRNA synthetases (aaRSs) play an indispensable role in protein synthesis and their structures proved quite conserved in prokaryotes and eukaryotes. However, some divergence has occurred allowing the development of selective aaRS inhibitors. Following an outline on the action mechanism of aaRSs, an overview will be given of already existing aaRS inhibitors, which are largely based on mimics of the aminoacyl-adenylates, the natural reaction intermediates. This is followed by a discussion on more recent developments in the field and the bioavailability problem.


Education and health informatics.
In this contribution, the role of health informatics in the medical curriculum is discussed. Firstly, trends in healthcare are presented that may have an impact on the use of IT in healthcare and consequently on education. Then, the traditional educational system is discussed and it is argued that the educational system should be changed. The problem-based approach is presented as an example of a new approach. The implications for education and training in health informatics are given. Given the lack of knowledge with respect to the basics of health informatics of both health professionals and students, attention has to be paid to learning materials. Both IT-EDUCTRA and NIGHTINGALE are presented as European projects that focus on education and training.


FGF21 and GDF15 are elevated in Barth Syndrome and are correlated to important clinical measures.
Barth Syndrome (BTHS) is a rare X-linked disorder that is caused by defects TAFAZZIN, which leads to an abnormal cardiolipin (CL) profile of the inner mitochondrial membrane and clinical features including cardiomyopathy, neutropenia and skeletal myopathy. The ratio of monolysocardiolipin (MLCL, the remodeling intermediate of cardiolipin) to remodeled CL is always abnormal in Barth Syndrome and 3-methylglutaconic acid is often elevated affected patients, however neither of these biomarkers has been shown to temporally correlate to clinical status. In this study, we measured plasma FGF21 and GDF15 levels in 16 individuals with Barth Syndrome and evaluated whether these biomarkers were correlated to the MLCL/CL ratio in patient bloodspots and clinical laboratory parameters indicative of organ involvement in Barth Syndrome including: neutrophil and monocyte counts, liver function, and cardiac function (NT-proBNP). We found that FGF21 and GDF15 were elevated in all 16 patients and that FGF21 was significantly correlated to AST, ALT GGT, percentage of neutrophils comprising total white blood cells, percent monocytes comprising total white blood cells, and NT-proBNP levels. GDF-15 was significantly positively associated with NT-proBNP. We conclude that clinical measurements of FGF21 and GDF-15 may be relevant in the monitoring multi-organ system involvement in Barth Syndrome.


Application of photon Doppler velocimetry to direct impact Hopkinson pressure bars.
Direct impact Hopkinson pressure bar systems offer many potential advantages over split Hopkinson pressure bars, including access to higher strain rates, higher strains for equivalent striker velocity and system length, lower dispersion, and faster achievement of force equilibrium. Currently, these advantages are gained at the expense of all information about the striker impacted specimen face, preventing the experimental determination of force equilibrium, and requiring approximations to be made on the sample deformation history. In this paper, we discuss an experimental method and complementary data analysis for using photon Doppler velocimetry to measure surface velocities of the striker and output bars in a direct impact bar experiment, allowing similar data to be recorded as in a split bar system. We discuss extracting velocity and force measurements, and the precision of measurements. Results obtained using the technique are compared to equivalent split bar tests, showing improved stress measurements for the lowest and highest strains in fully dense metals, and improvement for all strains in slow and non-equilibrating materials.


Ocular circulatory responses to exhaustive exercise in humans.
It is unclear whether exhaustive dynamic exercise increases ocular blood flow, although we have reported that submaximal exercise increases ocular blood flow. We hypothesized that ocular blood flow decreases at exhaustion, since exhaustion causes hyperventilation, which induces a reduction in PaCO(2). To test this hypothesis, ocular blood flow, blood pressure, and respiratory measurements were made in 12 healthy male subjects during cycle ergometer exercise at 75% of maximal heart rate, until exhaustion. Blood flows in the retinal and choroidal vasculature (RCV), the superior temporal retinal arteriole (STRA), and the superior nasal retinal arteriole (SNRA) were measured with the aid of laser-speckle flowgraphy every 3 min during the exercise. The conductance index (CI) in the ocular vasculature was calculated by dividing the blood flow by the mean arterial pressure (MAP). The mean arterial partial pressure of CO(2) (PaCO(2)) was estimated from tidal volume and end-tidal CO(2) partial pressure. MAP significantly increased from the resting baseline throughout the exercise, while PaCO(2) was significantly decreased at exhaustion and during the recovery period. By 6 min after the onset of exercise, blood flow velocity in the RCV significantly increased by 32 ± 6% (mean ± SD) from the resting baseline value. At exhaustion, blood flow velocity in the RCV did not differ significantly from the resting baseline value, and the STRA blood flow was significantly decreased by 13 ± 4%. The CIs in the RCV, STRA, and SNRA were significantly decreased compared to baseline at exhaustion. These findings suggest that ocular blood flow is increased by submaximal exercise, whereas it is suppressed by the hypocapnia associated with exhaustion.


Direct search for charged higgs bosons in decays of top quarks.
We present a search for charged Higgs bosons in decays of pair-produced top quarks in pp collisions at sqrt[s] = 1.8 TeV recorded by the D0 detector at the Fermilab Tevatron collider. With no evidence for signal, we exclude most regions of the ( M(H+/-),tan(beta)) parameter space where the decay t--> H(+)b has a branching fraction >0.36 and B(H+/--->tau(nu)(tau)) is large.


Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension.
Meaningful translational large animal models for cardiac diseases are indispensable for studying disease mechanisms, development of novel therapeutic strategies, and evaluation of potential drugs. For induction of heart failure, cardiac hypertrophy and fibrosis, a bare metal stent was implanted in the descending aorta of growing pigs (n = 7), inducing pressure stress on the left ventricle (group HYPI). The constant stent size in growing pigs resulted in antegrade partial obstruction of the aortic flow with a gradual increase in afterload. Five pigs with sham intervention served as control. Serial haemodynamic, pressure-volume loop measurements and transthoracic echocardiography (TTE) were performed to detect developing pressure overload of the LV and cardiac MRI with late enhancement for measuring LV and RV mass and ejection fraction. At 5-month follow-up, CT and contrast aortography, and intraluminal echocardiography confirmed aortic isthmus stenosis with a mean trans-stenotic gradient of 64 ± 13.9 mmHg. Invasive haemodynamic measurements revealed a secondary increase in pulmonary artery pressure (44.6 ± 5.1 vs 25.9 ± 6.2 mmHg, HYPI vs control, p < 0.05). TTE and ex vivo analyses confirmed severe concentric LV hypertrophy (mean circumferential wall thickness, 19.4 ± 3.1, n = 7 vs 11.4 ± 1.0 mm, n = 5, HYPI vs controls, p < 0.05). The LV and RV mass increased significantly, paralleled by increased isovolumic relaxation constant (tau). Histological analyses confirmed substantial fibrosis and myocyte hypertrophy in both LV and RV. Expressions of ANP, BNP, and miRNA-29a were up-regulated, while SERCA2a and miRNA-1 were down-regulated. Plasma NGAL levels increased gradually, while the elevation of NT-proBNP was detected only at the 5-month FUP. These data prove that percutaneous artificial aortic stenosis in pigs is useful for inducing clinically relevant progredient heart failure based on myocardial hypertrophy and fibrosis.


More than meets the islet: aligning nutrient and paracrine inputs with hormone secretion in health and disease.
The pancreatic islet is responsive to an array of endocrine, paracrine, and nutritional inputs that adjust hormone secretion to ensure accurate control of glucose homeostasis. Although the mechanisms governing glucose-coupled insulin secretion have received the most attention, there is emerging evidence for a multitude of physiological signaling pathways and paracrine networks that collectively regulate insulin, glucagon, and somatostatin release. Moreover, the modulation of these pathways in conditions of glucotoxicity or lipotoxicity are areas of both growing interest and controversy. In this review, the contributions of external, intrinsic, and paracrine factors in pancreatic β-, α-, and δ-cell secretion across the full spectrum of physiological (i.e., fasting and fed) and pathophysiological (gluco- and lipotoxicity; diabetes) environments will be critically discussed.


Genetic polymorphism: from electrophoresis to DNA sequences.
Recent studies indicate that the amount of protein variation undetected by electrophoresis may be reasonably small. Nevertheless, at the protein level, a typical sexually-reproducing organism may be heterozygous at 20 or more percent of the gene loci. Although the evidence is limited, it appears that at the level of the DNA nucleotide sequence every individual is heterozygous at every locus - if introns as well as exons are taken into account. The evidence available does not support the hypothesis that, at least at the protein level, the variation is adaptively neutral.


Effectiveness of intravenous haemocoagulase on haemorrhage control in bi-maxillary orthognathic surgery-A prospective, randomised, controlled, double-blind study.
Haemocoagulase is a snake venom protein derivative that is known to possess haemostatic activity. It is reported to minimise blood loss in orthopaedic, otorhinolaryngologic, and abdominal surgeries. The use of intravenous haemocoagulase in orthognathic surgery is unknown and not yet reported. The purpose of this trial is to study the efficacy of haemocoagulase in haemorrhage control in orthognathic surgery. Forty-six consecutive patients scheduled to undergo bi-maxillary orthognathic surgery within the time period of the study were recruited and randomized. They received either the study drug or placebo. All patients underwent operation with hypotensive anaesthesia. Intraoperative blood loss, operating time, drop in haemoglobin and haematocrit were the variables analysed in the study. Haemocoagulase caused an 11% (52 ml) reduction in blood loss in the study group (p = 0.01). There was no adverse reaction in any of the patients.


Adhesion of enterotoxigenic (ETEC) and bovine mastitis Escherichia coli strains to rat embryonic fibroblasts: role of amino-terminal domain of fibronectin in bacterial adhesion.
Adherence of human enterotoxigenic and bovine mastitis Escherichia coli to rat embryonic fibroblasts was studied. Adhesion of E. coli strains B34289c (human) and 1407 (bovine) was rapid and reached maximum after 30-40 min. Strain 1410 (bovine), which binds fibronectin but not its 29K amino-terminal fragment, did not adhere to the fibroblasts. Strain B34289c grown at 25 C or below and at 40 C or above lost its binding and adhesive properties simultaneously. Maximum binding and adhesion for this strain was achieved when it was grown at 33 C. Strains grown at this temperature adsorbed to fibronectin-, 29K fragment-, and Octyl Sepharose, with the exception of bovine strain 1410, which did not adsorb to 29K-Sepharose as expected. None of the strains adsorbed to cross-linked Sepharose 4B. 29K-IgG and Fab fragments thereof specifically blocked both binding (max 55%) and adhesion (greater than 95%). Sonicated and trypsin-treated bacteria were no longer able to bind or adhere. The supernatant of sonicated bacteria inhibited both binding and adhesion. Penicillin G at 0.5 micrograms/ml (1/5 minimal inhibitory concentration: MIC) and tetracycline at 0.2 micrograms/ml (1/5 MIC), when included in the growth medium, suppressed the cell surface components responsible for fibronectin binding and fibroblast adhesion. The presence of fibronectin was demonstrated in the fibroblast extracellular matrix by immunofluorescens with 29K-IgG antibodies.


A semi-quantitative analysis of Fos expression by mustard oil.
In the present study, a semi-quantitative analysis of Fos expression by mustard oil was performed. For this purpose, mustard oil was applied to the skin of the right hind foot of Wistar rats at various concentrations: 5%, 10%, 30%, 50%, 80% and 100% in liquid paraffin. The distribution and number of activated Fos-positive cells in the stimulated side (ipsilateral) and contralateral side of the spinal cord were investigated following the application. The ED50 of the response was also determined. The number of Fos-labelled cells gradually increased in a dose dependent manner in both sides of superficial layers (laminae I-II) of the spinal cord with increasing concentration of mustard oil. The increase between the doses was found significant in the ipsilateral superficial layers. The increase was significant in the contralateral superficial layers at concentrations above 50%. Very few Fos-labelled cells were observed around the central canal region in all concentrations. Higher doses of the mustard oil did not increase the number of activated cells in the deeper layers. However, the expression in the deeper layers (laminae III-X) does not show a consistent trend. Also, none of the concentrations used produced labelling in neurons of the deep ventral horn neurons or in motor neurons. Forty percent (40%) of mustard oil gave an approximately 1/2 maximum response i.e. an approximate ED 50. This may be important for studies using intrathecal application of antagonist following the mustard oil activation of skin nerve fibres.


Different HONO Sources for Three Layers at the Urban Area of Beijing.
Gaseous nitrous acid (HONO) is a crucial precursor of the hydroxyl (OH) radical, which is a "detergent" in the atmosphere. Nowadays, HONO formation mechanisms at polluted urban areas are controversial, which restricts the understanding of atmospheric oxidative capacity and radical cycling. Herein, multiday vertical observation of HONO and NOx was simultaneously performed at three heights at the urban area of Beijing for the first time. The vertical distribution of HONO was often unexpected, and it had the highest HONO concentration at 120 m, followed by those at 8 and 240 m. 0D box model simulations suggest that ground and aerosol surfaces might play similar roles in NO2 conversion at 8 m during the whole measurement. NO2 conversion on aerosol surfaces was the most important HONO source aloft during haze days. At daytime, a strong missing HONO source unexpectedly existed in the urban aloft, and it was relevant to solar radiation and consumed OH.


Synthesis and Structure-Activity Relationship Studies of N-monosubstituted Aroylthioureas as Urease Inhibitors.
Thiourea is a classical urease inhibitor which is usually used as a positive control, and many N,N'-disubstituted thioureas have been determined as urease inhibitors. However, due to steric hindrance, N,N'-disubstituted thiourea motif could not bind urease as thiourea. On the contrary, N-monosubstituted thiourea with a tiny thiourea motif could theoretically bind into the active pocket as thiourea. A series of N-monosubstituted aroylthioureas were designed and synthesized for evaluation as urease inhibitors. Urease inhibition was determined by the indophenol method and IC50 values were calculated using computerized linear regression analysis of quantal log dose-probit functions. The kinetic parameters were estimated via surface plasmon resonance (SPR) and by nonlinear regression analysis based on the mixed type inhibition model derived from Michaelis-Menten kinetics. Compounds b2, b11, and b19 reversibly inhibited urease with a mixed mechanism, and showed excellent potency against both cell-free urease and urease in the intact cell, with IC50 values being 90- to 450-fold and 5- to 50-fold lower than the positive control acetohydroxamic acid, respectively. The most potent compound b11 showed an IC50 value of 0.060 ± 0.004μM against cell-free urease, which bound to urea binding site with a very low KD value (0.420±0.003nM) and a very long residence time (6.7 min). Compound b11 was also demonstrated to have very low cytotoxicity to mammalian cells. The results revealed that N-monosubstituted aroylthioureas bound to the active site of urease as expected, and represent a new class of urease inhibitors for the development of potential therapeutics against infections caused by urease-containing pathogens.


Mortuary technicians in Western Australia.
After a long and protracted history of quasi-professional assistance to forensic and clinical pathologists, mortuary technicians are gaining recognition and an improvement in status in an unusual and unique vocation.