Observing the resistive switching of MgZnO thin film via conducting atomic force microscopy.
Conducting atomic force microscopy (C-AFM) is used to observe the formation and removal of conducting filaments of Mg0.6Zn0.4O thin film at a nanoscale in order to study the mechanisms of resistive switching. C-AFM probe with Pt coating is used as a movable top electrode for measuring local I-V and for C-AFM imaging. Writing and reading of micro-bits on the resistive switching thin film are demonstrated. The local I-V behavior is similar to the macroscopic behavior of the resistive switching thin film. However, the probability for successful in situ detection of resistive switching of formation in the current experiment is only one quarter, much less than that with a macroscopic top electrode. Experimental results are explained using the filament model which illustrates the switching mechanism of the thin film. The current work would be useful for the improvement of resistive switching thin films and their applications.


Wiring a medical school and teaching hospital for telemedicine.
The planning and installation of a telemedicine system for communication within a teaching hospital and its academic and hospital units with a capacity for accommodation of up to 400 video-stations is described. The system is intended for improving the communication between patients and health professionals, and between the health professionals themselves. It also provides the basis for improving pre-graduate teaching, especially problem-based learning, and all aspects of postgraduate teaching.


Analysis of microRNA knockouts in mice.
MicroRNAs (miRNAs) are small noncoding RNAs that act as potent regulators of gene expression. The discovery of miRNAs with specific temporal and spatial expression patterns revealed a hidden layer of post-transcriptional gene regulation. Furthermore, differential expression of miRNAs during disease progression identified miRNAs as relevant candidate genes in human pathologies. Currently the exact roles of miRNAs in human development and disease progression remain largely unknown. There have been recent efforts to study the loss of these genes in vivo and this review will discuss published miRNA knockout mouse models, highlighting their potential mechanisms of action in vivo.


[Magnetic resonance imaging for lumbar disk pathology. incidence of false negatives].
Magnetic resonance imaging (MRI) has had an impressive impact on evaluation of degenerative diseases of the spine. Nevertheless, false negatives can occur on images involving lumbar discs. Degenerative disc diseases documented on discrography and/or pathology examination of the discs can go unrecognized. Likewise sensitivity for the detection of protruding discal hernias is not totally satisfactory (20% false negatives). Finally, a magnetic resonance image visualizing displacement of the disc is not specific (10 to 15% false positives); images showing protrusion or hernia can be seen in 30% of asymptomatic patients. Although MRI gives slightly more information than other imaging techniques, false images do exist. Moreover, the usefulness of MRI to demonstrate disc disease in case of a negative CT-scan remains to be demonstrated.


Ibrutinib in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Systematic Review.
Primary Central Nervous System Lymphoma (PCNSL) is a rare variant of Non-Hodgkin Lymphoma (NHL) representing 1-2% of all NHL cases. PCNSL is defined as a lymphoma that occurs in the brain, spinal cord, leptomeninges, or eyes. Efforts to treat PCNSL by traditional chemotherapy and radiotherapy have generally been unsuccessful as a significant proportion of patients have frequent relapses or are refractory to treatment. The prognosis of patients with Refractory or Relapsed (R/R) PCNSL is abysmal. The optimal treatment for R/R PCNSL is poorly defined as there are only a limited number of studies in this setting. Several studies have recently shown that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has promising results in the treatment of R/R PCNSL. However, these are preliminary studies with a limited sample size. In this systematic review, we explored and critically appraised the evidence about the efficacy of the novel agent ibrutinib in treating R/R PCNSL.


Tunable Intrinsic Phonon Mode versus Anomalous Thermal Transport in Two-Dimensional Strongly Anharmonic Group IB Chalcogenides A2IBSe1/2Te1/2 (AIB = Cu, Ag, or Au).
Group IB chalcogenides, as promising thermoelectric materials, have ultralow thermal transport. Here, we propose a peculiar intrinsic B2 phonon mode that includes the in-plane rotational and stretching vibrations of metal atoms in two-dimensional A2IBSe1/2Te1/2 (AIB = Cu, Ag, or Au). The B2 mode is sensitive to the metal-atom mass, temperature, and strain for effectively tuning the lattice thermal conductivity. The in-plane stretching vibration leads to an unexpected increase in the lattice thermal conductivity from Cu to Ag and to Au systems, in contrast to Keyes' theory. The s(I) phase can be stabilized by the temperature-hardened B2 mode to reduce the lattice thermal conductivity, following the ∼T-0.59 instead of the traditional ∼T-1 trend. The s(II)-to-s(I) phase transition is driven by the strain-softened B2 mode to greatly enhance thermal transport via weakening the anharmonicity. Our work establishes the relationship of tunable intrinsic phonon mode versus thermal transport in two-dimensional group IB chalcogenides.


Daily peritoneal ultrafiltration predicts patient and technique survival in anuric peritoneal dialysis patients.
Maintenance dialysis therapy is the only way to remove excess fluid in patients with anuric end-stage renal disease. The optimal ultrafiltration (UF) volume in patients on peritoneal dialysis (PD) remains controversial. We retrospectively analysed a cohort of 86 prevalent anuric PD patients followed up for a median of 25.3 months (range, 6 to 54 months). Clinical and PD parameters were recorded yearly. Kaplan-Meier analysis and Cox proportional hazards models were used to identify risk factors of mortality and technique failure in patients with a UF >/=1 L/24 h or <1 L/24 h. When compared to those with a UF <1 L/24 h, patients with a UF >/=1 L/24 h had significantly higher haemoglobin levels (101.9 +/- 20.5 vs 89.3 +/- 20.2 g/L, P < 0.05) and tended to be younger (55.0 +/- 12.5 vs 60.6 +/- 16.1 years, P = 0.10). Also, while Kt/V and CCr were stable over time, UF decreased significantly over the study period (baseline, 1205.5 +/- 327.3 ml/24 h vs after 3 years, 870.6 +/- 439.8 ml/24 h; P < 0.001). Using Kaplan-Meier analysis, patients with baseline UF <1 L/24 h had significantly worse outcome (survival, 27.2 +/- 3.9 vs 42.4 +/- 1.9 months; P < 0.001). In multivariate Cox regression analysis, age, time-dependent UF volume and serum albumin were independent predictors of mortality, while UF independently predicted technique failure. The present study demonstrates a strong predictive value of daily peritoneal UF for both technique and patient survival in prevalent anuric PD patients. Identifying markers of satisfactory fluid status, as well as optimizing therapy to meet UF goals, remains an important clinical target.


Laryngeal adduction asymmetries in normal speaking subjects.
To investigate the prevalence of asymmetries at vocal fold adduction, 109 vocally healthy subjects between 22 and 80 years of age were examined. All subjects were examined with a rigid endoscope and video recorded. The recordings were analysed off line by two laryngologists. Seventy percent of the subjects displayed some kind of asymmetry. There was no difference between the sexes. Side differences in antero-posterior position of the corniculate or cuneiform tubercles were the most frequent asymmetries, occurring in 66% of the total material and in 92% of the asymmetrical cases. Asymmetries appeared more common and more marked in older subjects and possibly more frequent in singers than in non-singers. Laryngeal adduction asymmetries are probably of little importance for voice function.


Combined treatment of olanzapine and mirtazapine in anorexia nervosa associated with major depression.
Several studies have shown that olanzapine is effective in weight restoration and maintenance for patients with anorexia nervosa (AN). However, major depression is a very common comorbid psychiatric disorder associated with AN. Additional antidepressant therapy may be required for treating anorexic patients with major depression. The authors present a case of AN associated with major depression, who responded well to the combination treatment of olanzapine and mirtazapine. A 27-year-old Taiwanese woman was admitted because of severe weight loss, poor nutrition, amenorrhea, major depression, and starvation complications including hematological dyscrasis, electrolytes and endocrine imbalance, and sinus bradycardia. In additional to nutritional and medical treatments, the patient was given olanzapine 10 mg/day and mirtazapine 30 mg/day. She took the combined medications for six months. Meanwhile she received cognitive behavior therapy and family therapy. With these treatments, the patient's depression was in remission, her body weight was increased from 24 to 38 kg, and her body mass index was increased from 9.8 to 15.5. Our case suggests that the combined treatment of olanzapine and mirtazapine can be used in the treatment of AN associated with major depression.


Characterization of CRF56_cpx, a new circulating B/CRF02/G recombinant form identified in MSM in France.
Several B/CRF02_AG Unique Recombinant Forms (URFs) have previously been identified in France. Here we show that one of them (URF5_B/02/G) is emerging in MSM, a high-risk population where HIV incidence and number of superinfections are increasing. We describe this new Circulating Recombinant Form, CRF56_cpx, estimate the time to its most recent common ancestor, investigate its origins and show that it probably shares common ancestors with strains from the East Mediterranean.


Adipogenic function of mouse tetranectin and identification of its functional domain.
Tetranectin (TN), a plasminogen (Plg) binding protein, enhances the Plg activator (PA)-catalyzed activation of Plg to plasmin (Pln). Previously, TN was identified as an adipogenic serum protein, which promotes adipocyte differentiation. In the present study, we investigated the adipogenic function of mouse TN using recombinant proteins (rmTNs) in full-length and domain-truncated forms. Adipocyte differentiation in TN-depleted-FBS-media was significantly enhanced by rmTNs supplementation. The adipogenic effect of rmTNs was found to be dependent on the presence of a Plg binding domain, indicating the domain is essential for the adipogenic function of mTN. In addition, these results suggested the involvement of Plg activation, however Plg, PA and Pln appeared to have no direct effect on adipocyte differentiation. This study demonstrates the adipogenic function of mTN, which is dependent on the Plg binding domain as its functional domain.


Iohexol in coronary angiography. A double blind investigation.
Iohexol 350 mg I/ml (Omnipaque) was compared with the routine contrast medium meglumine, Na-Ca-metrizoate 370 mg I/ml (Isopaque Coronar) in coronary angiography in 30 patients. A randomized, double blind, crossover design was employed. Angiographic image quality, ECG, heart rate, aortic blood pressure and adverse reactions were recorded. Excellent image quality was obtained with both media. Except for one single event of hypotension, only few and minor changes in the parameters measured were recorded. No distinct difference between the two media was found. Iohexol seems to be suitable for selective coronary angiography.


The role of the external examiner in the assessment of clinical practice.
In the first part of this paper we give a brief overview of the development of the different types of clinical assessment used in the UK. Some general problems related to the assessment of clinical practice are outlined. The second part of the paper focuses on the role of the external examiner in the clinical assessment of students. We outline some of the major problems we encountered as internal and external examiners on the same university-based course in which 'I-day' practical assessments were undertaken. We emphasize the particular problems of externally assessing the clinical practice component of the course in this manner and conclude that the continuous assessment model, while not without its own problems, is potentially a more effective approach to student assessment.


Hand-assisted laparoscopic vs. open subtotal colectomy for severe ulcerative colitis.
This study aimed to assess the feasibility and safety of undergoing emergency subtotal colectomy with hand-assisted laparoscopic surgery in patients with severe ulcerative colitis. We reviewed the medical records of 60 patients who underwent emergency subtotal colectomy with hand-assisted laparoscopic technique (30 cases) or open technique (30 cases) for severe ulcerative colitis. No intraoperative complications occurred in either group. One patient in the laparoscopic group required conversion to open surgery. The median operative time was significantly longer in the laparoscopic group (242 vs. 191 minutes; P < 0.001). The rate of early postoperative complications in the laparoscopic group was significantly less than that in the open group (37 percent vs. 63 percent; P = 0.041). In the open group, four patients required relaparotomy because of peritoneal abscess or strangulation ileus, whereas no patient required relaparotomy in the laparoscopic group (P = 0.040). In the laparoscopic group, the median duration of postoperative food prohibition was significantly shorter (4.8 vs. 5.9 days; P = 0.007), and the median length of hospital stay was significantly shorter (23.0 vs. 33.0 days; P = 0.001). Although the operative time was elongated in the laparoscopic group, intraoperative safety and postoperative recovery were satisfactory. For severe ulcerative colitis, hand-assisted laparoscopic surgery can be an alternative to conventional open surgery.


Creating an ontology driven rules base for an expert system for medical diagnosis.
Expert systems of the 1980s have failed on the difficulties of maintaining large rule bases. The current work proposes a method to achieve and maintain rule bases grounded on ontologies (like NCIT). The process described here for an expert system on plasma cell disorder encompasses extraction of a sub-ontology and automatic and comprehensive generation of production rules. The creation of rules is not based directly on classes, but on individuals (instances). Instances can be considered as prototypes of diseases formally defined by "destrictions" in the ontology. Thus, it is possible to use this process to make diagnoses of diseases. The perspectives of this work are considered: the process described with an ontology formalized in OWL1 can be extended by using an ontology in OWL2 and allow reasoning about numerical data in addition to symbolic data.


Effects of (+)-Catechin on the Composition, Phenolic Content and Antioxidant Activity of Full-Fat Cheese during Ripening and Recovery of (+)-Catechin after Simulated In Vitro Digestion.
(+)-Catechin, the representative catechin in green tea, was incorporated into a full-fat cheese (at 125-500 ppm) followed by ripening for 90 days at 8 °C and digesting for six hours. Determination of pH, proximate composition, total phenolic content (TPC) and antioxidant activity (AA) after manufacture and ripening demonstrated that the addition of (+)-catechin significantly (p ≤ 0.05) decreased the pH of both whey and curd during cheese manufacturing and ripening with no significant (p > 0.05) effect on the moisture, protein and fat contents. (+)-Catechin increased TPC, as well as AA, though the increase was not proportional with increasing the concentration of added (+)-catechin. About 57%-69% of (+)-catechin was retained in the cheese curd, whereas about 19%-39% (depending on the concentration) was recovered from the cheese digesta. Transmission electron micrographs showed that the ripened control cheese had a homogeneous pattern of milk fat globules with regular spacing entrapped in a homogenous structure of casein proteins, whereas the addition of (+)-catechin disrupted this homogenous structure. The apparent interaction between (+)-catechin and cheese fat globules was confirmed by Fourier transform infrared spectroscopy. These associations should be taken into account when incorporating antioxidants, such as (+)-catechin, to create functional dairy products, such as cheese.


Whole‑genome identification and systematic analysis of lncRNA‑mRNA co‑expression profiles in patients with cutaneous basal cell carcinoma.
Cutaneous basal cell carcinoma (BCC) is a common subtype of malignant skin tumor with low invasiveness. Early diagnosis and treatment of BCC and the identification of specific biomarkers are particularly urgent. Long non‑coding RNAs (lncRNAs) have been shown to be associated with the development of various tumors, including BCC. The present study conducted a comparative analysis of the differential expression of lncRNAs and mRNAs through whole‑genome technology. Microarray analyses were used to identify differentially expressed (DE) lncRNAs and DE mRNAs. Reverse transcription‑quantitative (RT‑q) PCR confirmed the differential expression of 10 lncRNAs in BCC. Subsequently, a lncRNA‑mRNA co‑expression network was constructed using the top 10 DE lncRNAs. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the possible biological effects of the identified mRNAs and to speculate on the possible biological effects of the lncRNAs. A total of 1,838 DE lncRNAs and 2,010 DE mRNAs were identified and 10 of the DE lncRNAs were confirmed by RT‑qPCR. A lncRNA‑mRNA co‑expression network comprising 166 specific co‑expressed lncRNAs and mRNAs was constructed using the top 10 DE lncRNAs. According to the results of the GO and KEGG analyses, lncRNA XR_428612.1 may serve an important role in mitochondrial dysfunction and the progression of BCC by modulating TICAM1, USMG5, COX7A2, FBXO10, ATP5E and TIMM8B. The present study provided whole‑genome identification and a systematic analysis of lncRNA‑mRNA co‑expression profiles in BCC.


Construction of a shuttle vector and transformation of Xylella fastidiosa with plasmid DNA.
We have isolated, cloned, and sequenced a 5823-bp cryptic plasmid from a strain of Xylella fastidiosa. This plasmid encodes five open reading frames (ORF) greater than 400 nucleotides each. ORF 2 encodes a protein with 37% amino acid identity to the replication initiator protein of plasmid pECB2 from Pseudomonas alcaligenes. This RepA protein from X. fastidiosa contains both a leucine zipper and helix turn helix motif characteristic of proteins involved in DNA replication. The sequence 5' of ORF 2 has all of the features characteristic of plasmid origins of replication as well as regulatory elements required for transcription of ORF 2. Open reading frame 2, along with the upstream origin of replication, was cloned as an EcoRI fragment into pUC19 to create a shuttle vector. This construct was introduced into Xylella fastidiosa by electroporation, with selection for carbenicillin resistance. Transformation was verified by both PCR and Southern hybridization experiments. Frequency of transformation was low, but increased ten-fold when the plasmid was grown in X. fastidiosa rather than Escherichia coli prior to transformation. This work represents the first step towards the development of a system for genetic analysis of this important plant pathogen of citrus, grapevines, and other horticultural crops.


Willingness to pay for protection from storm surge damages under climate change in Halifax Regional Municipality.
Climate change poses risks to coastal cities due to sea-level rise and changes in storm surge. Using the contingent valuation method and payment card format, this paper seeks to estimate residents of Halifax Regional Municipality's willingness to pay (WTP) for protection from flooding impacts from storm surge. The contribution of this study is the application of this method in a previously unstudied region, to understand individuals' perception of risk and WTP to avoid damage, in order to inform policy aimed at protecting against damage due to sea-level rise and storm surge. WTP is estimated without and with the expectation of future climate change, and also for public vs. private goods. Data is analyzed and compared using OLS, Heckman two-step and Tobit Interval regression models. Results suggest that on average, WTP is roughly $12 per month per household over a ten-year period without the expectation of climate change, and roughly $13 per month per household assuming climate change will have negative impacts in the region. Individuals are most often willing to pay to protect against damages to public infrastructure, as well as power outages. Income and education do not play a major role in individuals WTP. Vulnerability to flooding and level of concern related to risky events have a statistically significant impact on WTP in all models, and gender and age have an impact on WTP in some models.


Estimation of the stereoscopic threshold utilizing perceived depth.
Recent reports in the literature indicate that a random-dot style of stereoscopic test is the most accurate method of assessing stereoscopic threshold [Cooper, J., Feldman, J. and Medlin, D. (1979) J. Am. optom. Ass. 50, 821-825]. While this is undoubtedly true for those who can respond to the test, it is less so for very young, infirm or other patients who do not or cannot have the requisite attention span. This experiment finds that the amount of perceived depth seen on a test like the Titmus fly correlates very accurately with the measured stereoscopic threshold and can therefore be used as a measure of the threshold without having to employ the entire testing procedure of the random dot tests. The regression equation derived from the data is presented, as well as a table that allows a practitioner to estimate the stereoscopic threshold from the amount of perceived depth on a common stereo test: the Titmus fly.


Vein graft aneurysms following popliteal aneurysm repair are more common than we think.
True infrainguinal vein graft aneurysms are reported infrequently in the literature. We sought to identify the true incidence of these graft aneurysms after popliteal aneurysm repair and identify factors which may increase the risk of such aneurysms developing. Using a prospectively compiled database, we identified patients who underwent a popliteal aneurysm repair between January 1996 and January 2011 at a single district general hospital. Patients were routinely followed up in a graft surveillance programme. Out of 45 patients requiring repair of a popliteal aneurysm over a 15-year period, four (8.8%) patients developed aneurysmal graft disease. Of the patients who developed graft aneurysms, all had aneurysmal disease at other sites compared with 18 (45.0%) patients who did not develop graft aneurysms. Patients with graft aneurysms had a mean of 1.60 aneurysms elsewhere compared to 0.58 in patients with non-aneurysmal grafts (P = 0.005). True vein graft aneurysms occur in a significant number of patients following popliteal aneurysm repair. Our data would suggest this to be more likely in patients who have aneurysms elsewhere and therefore a predisposition to aneurysmal disease. It may be appropriate for patients with aneurysms at other sites to undergo more prolonged post-operative graft surveillance.


Recording Patient Data in Burn Unit Logbooks in Rwanda: Who and What Are We Missing?
Systematic data collection in high-income countries has demonstrated a decreasing burn morbidity and mortality, whereas lack of data from low- and middle-income countries hinders a global overview of burn epidemiology. In low- and middle-income countries, dedicated burn registries are few. Instead, burn data are often recorded in logbooks or as one variable in trauma registries, where incomplete or inconsistently recorded information is a known challenge. The University Teaching Hospital of Kigali hosts the only dedicated burn unit in Rwanda and has collected data on patients admitted for acute burn care in logbooks since 2005. This study aimed to assess the data registered between January 2005 and December 2019, to evaluate the extent of missing data, and to identify possible factors associated with "missingness." All data were analyzed using descriptive statistics, Fisher's exact test, and Wilcoxon Rank Sum test. In this study, 1093 acute burn patients were included and 64.2% of them had incomplete data. Data completeness improved significantly over time. The most commonly missing variables were whether the patient was referred from another facility and information regarding whether any surgical intervention was performed. Missing data on burn mechanism, burn degree, and surgical treatment were associated with in-hospital mortality. In conclusion, missing data is frequent for acute burn patients in Rwanda, although improvements have been seen over time. As Rwanda and other low- and middle-income countries strive to improve burn care, ensuring data completeness will be essential for the ability to accurately assess the quality of care, and hence improve it.


Esthesioneuroblastoma metastatic to the thoracic intradural and extradural space.
Ethesioneuroblastoma (ENB) is a rare tumor of the olfactory epithelium that has been shown to metastasize mostly to the cervical lymphatics, with only infrequent spread to other locations. We report a rare case of ENB characterized by recurrence and distant metastasis to the T7-T8 intradural and extradural space. To report a rare case of recurrent ENB metastatic to the thoracic intradural and extradural space. Case report with a review of the literature. A 64-year-old man with recurrent ENB presented with chronic pain in the neck, shoulder, and back. His neurologic exam was normal. Computed tomography of the chest showed no pulmonary metastasis and a high-attenuation spinal canal mass at T8 was noted on magnetic resonance imaging. A laminectomy at T7-T8 was performed for resection of a large epidural mass. A tumor was seen penetrating through the dura, and a midline durotomy was performed for resection of a large intradural mass. Frozen section and permanent stains were consistent with metastatic ENB. The postoperative period was uneventful, and included pain management and physical therapy, followed by chemotherapy and radiation. The patient remains free of spinal recurrence 2 years after surgery. Metastasis of ENB to the spinal column is rare, and of those instances, 80% are localized to the cauda equina. Recurrent ENB metastatic to the thoracic intradural and extradural space is extremely rare, and was successfully treated with surgical resection.


Metal-Organic Framework Adsorbent for Practical Capture of Trace Carbon Dioxide.
Control of indoor CO2 concentration to a safe level is important to human health. Metal-organic-framework-based adsorbents show superior adsorption performance at moderate CO2 concentration compared to other solid adsorbents but suffer from low capacities and high regeneration temperature at indoor CO2 concentrations and poor humidity stability. Herein, we report epn-grafted Mg2(dobpdc) (epn = 1-ethylpropane-1,3-diamine) showing a CO2 capacity of 12.2 wt % at an acceptable concentration of 1000 ppm and a practically low desorption temperature of 70 °C, which surpasses the performance of conventional solid adsorbents under the given conditions. After poly(dimethylsiloxane) coating, this material reveals a significant adsorption amount (∼10 wt %) in humid conditions (up to 98% relative humidity) with structural durability.


Gene Region Association Analysis of Longitudinal Quantitative Traits Based on a Function-On-Function Regression Model.
In the process of growth and development in life, gene expressions that control quantitative traits will turn on or off with time. Studies of longitudinal traits are of great significance in revealing the genetic mechanism of biological development. With the development of ultra-high-density sequencing technology, the associated analysis has tremendous challenges to statistical methods. In this paper, a longitudinal functional data association test (LFDAT) method is proposed based on the function-on-function regression model. LFDAT can simultaneously treat phenotypic traits and marker information as continuum variables and analyze the association of longitudinal quantitative traits and gene regions. Simulation studies showed that: 1) LFDAT performs well for both linkage equilibrium simulation and linkage disequilibrium simulation, 2) LFDAT has better performance for gene regions (include common variants, low-frequency variants, rare variants and mixture), and 3) LFDAT can accurately identify gene switching in the growth and development stage. The longitudinal data of the Oryza sativa projected shoot area is analyzed by LFDAT. It showed that there is the advantage of quick calculations. Further, an association analysis was conducted between longitudinal traits and gene regions by integrating the micro effects of multiple related variants and using the information of the entire gene region. LFDAT provides a feasible method for studying the formation and expression of longitudinal traits.


Endothelin action on pituitary lactotrophs: one receptor, many GTP-binding proteins.
The endothelins are a family of hormones that have a biphasic action on pituitary lactotrophs. The initial effect is stimulatory, followed later by inhibition that persists long after the agonist has been removed. Recent research has uncovered several G protein pathways that mediate these effects.


Role of cell surface GM3 ganglioside and sialic acid in the antitumor activity of a GM3-based vaccine in the murine B16 melanoma model.
To examine the role of GM3 monosialoganglioside and sialic acid in the antitumor activity of a vaccine based on GM3, hydrophobically conjugated with the outer-membrane-protein complex from Neisseria meningitidis (GM3/VSSP). In order to evaluate the relationship between antitumor activity and the presence of GM3 on the surface of tumor cells, we used two murine tumor cell lines with different ganglioside expression. Syngeneic mice were immunized with four i.m. doses of GM3/VSSP (120 micro g) at 14-day intervals and challenged subcutaneously with tumor cells. B16 melanoma cells showed GM3 on cell surface and GM3-dependent in vitro growth. As expected, preimmunization with the vaccine significantly inhibited tumor formation and prolonged survival in mice challenged with B16 cells. In contrast, no antitumor effect was observed in mice challenged with GM3-negative F3II mammary carcinoma cells. The reactivity of sera from immunized mice against B16 cells was confirmed by flow cytometry and immunoperoxidase staining. Depletion of sialic acid residues from the cell surface completely abolished antibody response against melanoma cells. These results indicate that the antitumor activity of GM3/VSSP is associated with GM3 expression on tumor cell surface and demonstrate a major role of sialic acid in the humoral response of vaccinated mice.


Assessing knowledge of genomic concepts among Canadian nursing students and faculty.
Objectives Contemporary nurses require genomic literacy to engage in genomics-informed health care. Little is known about the genomic literacy of undergraduate nursing students and faculty in many countries. Concept inventories can be used to assess levels of knowledge and inform curriculum development. Methods The 31-item Genomic Nursing Concept Inventory (GNCI) was administered to undergraduate nursing students (n=207) and faculty (n=13) in a school of nursing with two sites in western Canada. Results Scores on the GNCI were low and comparable to those of US students and faculty. Six student characteristics were associated with total score on the GNCI. Conclusions Both students and faculty need to increase their knowledge of genomics. Mandates from national nursing organizations and international collaboration are needed to develop and implement foundational genomics content for undergraduate curricula to enable graduates to engage in genomics-informed health care.


Expression of prolactin and its receptor in human breast carcinoma.
The growth regulatory effects of PRL on the human breast are mediated by its receptor (PRLr), a member of the cytokine receptor family. Recent reverse transcriptase-PCR studies by our laboratory and others have shown PRL expression within breast tissues at the RNA level. To confirm the role of this growth factor-receptor complex in normal and malignant breast tissues, the expression of PRL and PRLr was examined in parallel with the estrogen receptor (ER) and progesterone receptor (PR). Sixty-nine cases of primary invasive breast carcinoma were examined for PRL and PRLr expression by in situ hybridization and immunohistochemical technique, respectively. These data revealed widespread expression of PRL and its receptor in the breast cancers studied (>95%) and in the normal breast tissues (>93%), with no association between the expression of PRL-PRLr and ER or PR. These findings stand in contrast to prior RIA-based studies that detected the PRLr in only 20-60% of breast carcinomas, most commonly in ER-PR-positive cells. These results confirm prior data indicating the presence of an autocrine/paracrine loop for the PRL-PRLr complex within human breast tissues. Given the widespread expression of PRL-PRLr in breast cancer, pharmacological interventions aimed at the inhibition of function of this growth regulatory receptor complex may be of considerable utility in the therapy of this disease.


Cholesterol determinations from skin puncture and venous blood have similar imprecisions.
Comparison of cholesterol values from venous blood and skin puncture blood is difficult, because biological differences between both materials may be concealed or increased by the preanalytical imprecision of skin puncture. In 12 adults, we studied the variance of cholesterol and urea determination in 8 blood samples obtained by the puncture of 8 fingers and compared the results with the 8-fold determination of a venous sample drawn simultaneously. Our results show that the additional imprecision of skin puncture is low, and that the differences are not statistically significant. The mean values for cholesterol were 3.9% lower in skin puncture plasma than in venous plasma, whereas the mean values for urea were very similar.


Wide variation in sexually transmitted infection testing and counselling at Aboriginal primary health care centres in Australia: analysis of longitudinal continuous quality improvement data.
Chlamydia, gonorrhoea and syphilis are readily treatable sexually transmitted infections (STIs) which continue to occur at high rates in Australia, particularly among Aboriginal Australians. This study aimed to: explore the extent of variation in delivery of recommended STI screening investigations and counselling within Aboriginal primary health care (PHC) centres; identify the factors associated with variation in screening practices; and determine if provision of STI testing and counselling increased with participation in continuous quality improvement (CQI). Preventive health audits (n = 16,086) were conducted at 137 Aboriginal PHC centres participating in the Audit and Best Practice for Chronic Disease Program, 2005-2014. STI testing and counselling data were analysed to determine levels of variation in chlamydia, syphilis and gonorrhoea testing and sexual health discussions. Multilevel logistic regression was used to determine factors associated with higher levels of STI-related service delivery and to quantify variation attributable to health centre and client characteristics. Significant variation in STI testing and counselling exists among Aboriginal PHC centres with health centre factors accounting for 43% of variation between health centres and jurisdictions. Health centre factors independently associated with higher levels of STI testing and counselling included provision of an adult health check (odds ratio (OR) 3.40; 95% Confidence Interval (CI) 3.07-3.77) and having conducted 1-2 cycles of CQI (OR 1.34; 95% CI 1.16-1.55). Client factors associated with higher levels of STI testing and counselling were being female (OR 1.45; 95% CI 1.33-1.57), Aboriginal (OR 1.46; 95% CI 1.15-1.84) and aged 20-24 years (OR 3.84; 95% CI 3.07-4.80). For females, having a Pap smear test was also associated with STI testing and counselling (OR 4.39; 95% CI 3.84-5.03). There was no clear association between CQI experience beyond two CQI cycles and higher levels of documented delivery of STI testing and counselling services. A number of Aboriginal PHC centres are achieving high rates of STI testing and counselling, while a significant number are not. STI-related service delivery could be substantially improved through focussed efforts to support health centres with relatively lower documented evidence of adherence to best practice guidelines.


Ganglioglioma of the cerebellum: case report.
The authors report a rare case of a cerebellar ganglioglioma. A review of 12 previously reported cases and our case suggest that surgical removal of this neoplasm carries a good prognosis.


The influence of cardiac preload and positive end-expiratory pressure on the pre-ejection period.
The pre-ejection period (PEP) has recently been described as a potential parameter for monitoring cardiac preload. This study further investigated the influence of changes in intravascular volume status and the application of positive end-expiratory pressure (PEEP) on the pre-ejection period. In ten pigs, ECG, arterial pressure and stroke volume derived from an aortic flowprobe were registered. Global end-diastolic volume (GEDV) was measured by transcardiopulmonary thermodilution. Total blood volume (TBV) and intrathoracic blood volume (ITBV) were measured by the dye-dilution technique. Measurements were performed during normovolaemic conditions, after volume loading with haemodilution blood (20 ml kg(-1)) and following haemorrhage (30 ml kg(-1)) without PEEP and with PEEP (15 cm H(2)O) applied. Volume loading increased GEDV, ITBV, TBV and SV, whereas PEP remained constant. However, the changes were not significant (P > 0.05). Subsequent haemorrhage significantly decreased GEDV (from 436 to 308 ml), ITBV (from 729 to 452 ml), TBV (from 2,131 to 1,488 ml) (all P-values <0.05), and SV (from 20.7 ml to 14.3 ml, P < 0.001). However, PEP did not change significantly (from 73 to 82 ms, P > 0.05). No correlation between the changes in PEP and changes in any other variable was observed. It is concluded that PEP is not sensitive to the changes in intravascular volume status.


Studies on liver tumor promotion in the rat by orotic acid: dose and minimum exposure time required for dietary orotic acid to promote hepatocarcinogenesis.
Our earlier studies indicated that orotic acid, a precursor for pyrimidine nucleotide biosynthesis, exerts a promoting effect on rat hepatocarcinogenesis. The present study was designed to determine the optimum conditions of exposure to orotic acid required for promotion of hepatocarcinogenesis in the initiated rats. The first series of experiments was designed to determine the optimum dose of orotic acid needed to exert its liver tumor promoting effect. Accordingly male Fischer rats were given diethylnitrosamine (200 mg/kg, i.p.) or 0.9% NaCl. One week later carcinogen-injected rats were divided into six groups and fed either basal diet or the same diet containing 0.1, 0.5, 1, 2 or 4% orotic acid. Rats given 0.9% NaCl were fed 4% orotic acid. Two-thirds partial hepatectomy was performed on all animals 10 weeks after starting on their respective diets, and all groups were killed 3 weeks thereafter. Analysis of gamma-glutamyltransferase-positive foci and nodules revealed that 0.5-1% orotic acid in the diet is sufficient to exert a significant promoting effect on the selective growth of initiated hepatocytes, while higher concentrations of orotic acid were only marginally more effective. No gamma-glutamyltransferase-positive foci were observed in animals given 4% orotic acid diet following saline injection. Using 1% orotic acid as the promoting regimen, in the next series, the minimum exposure time required for dietary orotic acid to promote liver carcinogenesis was determined. Male Fischer 344 rats were given i.p. either 1,2-dimethylhydrazine dihydrochloride (100 mg/kg) or 0.9% NaCl 18 h after 2/3 partial hepatectomy. After 1 week of recovery one group of rats was continued on a semisynthetic basal diet, while others were transferred to the same basal diet containing 1% orotic acid. Rats that were on the 1% orotic acid diet were progressively transferred to the basal diet after 5, 10, 20, 29 and 40 weeks of exposure. All rats were sacrificed 54 weeks after the beginning of the experiment. The results indicate that 100% of the initiated rats developed hepatic nodules whether or not they were exposed to an orotic acid-containing diet. However, the incidence of hepatocellular carcinoma was greatly increased in animals exposed to the orotic acid diet, with 42% incidence in initiated rats given orotic acid diet for 10 weeks and up to 75% in those exposed to this diet for 40 weeks. Further, promotion by orotic acid exhibited a high metastatic potential with 33-60% metastasis to the lungs.(ABSTRACT TRUNCATED AT 400 WORDS)


Bay846, a new irreversible small molecule inhibitor of EGFR and Her2, is highly effective against malignant brain tumor models.
The epidermal growth factor receptor (EGFR) pathway is aberrantly activated in tumors and plays a key role in promoting tumor growth. Small molecule inhibitors which bind reversibly to EGFR have demonstrated limited clinical activity. Thus, there is a continued need to develop novel EGFR inhibitors with improved anti-tumor activity. Bay846 is a newly developed small molecule inhibitor that binds irreversibly to the tyrosine kinase domains of EGFR and Her2. The in vitro and in vivo efficacy of Bay846 was tested using a panel of nine human malignant brain tumor (glioma) models. Lapatinib, a reversible inhibitor of EGFR and Her2, was included for comparison. Six glioma cell lines were sensitive to Bay846 treatment. Bay846 strongly suppressed tumor cell growth in vitro by inducing cell lysis/death rather than cell cycle arrest. Consistent with this, Bay846 had potent anti-tumor activity which led to regressions in tumor size. The active, phosphorylated form of EGFR was reduced by Bay846 treatment in vitro and in tumors. Importantly, the efficacy of Bay846 was significantly greater than lapatinib in all assays. Bay846-sensitivity was associated with expression of a wild-type PTEN in conjunction with high levels of an oncogenic EGFR variant (A289V or EGFRvIII). These studies demonstrate that targeting the EGFR pathway with the irreversible inhibitor Bay846 has great potential to increase the efficacy of this cancer therapy.


Model protocells from single-chain lipids.
Significant progress has been made in the construction of laboratory models of protocells. Most frequently the developed vesicle systems utilize single-chain lipids rather than the double-chain lipids typically found in biological membranes. Although single-chain lipids yield less robust vesicles, their dynamic characteristics are highly exploitable for protocellular functions. Herein the advantages of using single-chain lipids in the construction of protocells are discussed.


Preventive Physical Training Partially Preserves Heart Function and Improves Cardiac Antioxidant Responses in Rats After Myocardial Infarction Preventive Physical Training and Myocardial Infarction in Rats.
In acute myocardial infarction (AMI), reactive oxygen species may cause irreversible damage to the heart tissue. Physical training is capable of enhancing antioxidant capacity, acting as a cardioprotective factor. We assessed the preventive effects of physical training on the antioxidant and functional responses of the heart of Wistar Kyoto rats after AMI. Wistar Kyoto rats (n = 12) were allocated to sedentary (SED) or trained (EXE-aerobic training on a treadmill) groups. Echocardiographic exams were performed 48 hr before and 48 hr after the induction of AMI. Superoxide dismutase (SOD) and catalase (CAT) activities, and total glutathione (GSH) were measured in vitro in the heart tissue. After AMI, the EXE group showed higher left ventricular shortening fraction (29%; p = .004), higher cardiac output (37%; p = .032) and reduced myocardial infarction size (16%; p = .007) than SED. The EXE group showed a higher nonenzymatic antioxidant capacity (GSH, 23%; p = .004), but the SOD and CAT activities were higher in SED (23% SOD; p = .021 and 20% CAT; p = .016). In addition, the SOD activity was positively correlated with myocardial infarction size and inversely correlated with cardiac output. Physical training partially preserved cardiac function and increased intracellular antioxidant response in cardiac tissue of animals after AMI.


Copper deficiency increases hepatic apolipoprotein A-I synthesis and secretion but does not alter hepatic total cellular apolipoprotein A-I mRNA abundance in rats.
This study was designed to determine whether an increase in hepatic apolipoprotein A-I (apo A-I) synthesis and mRNA abundance is responsible for the enlarged plasma apo A-I pool observed in copper-deficient rats. Weanling male Sprague-Dawley rats were divided into two dietary treatments: copper-adequate (102.2 mumol Cu/kg diet) and copper-deficient (9.0 mumol Cu/kg diet). Copper deficiency resulted in a significant increase (124%) in intravascular apo A-I pool size after 6 wk of treatment. Following intraportal injection of a flooding dose of [3H]phenylalanine, in vivo hepatic apo A-I synthesis and secretion were significantly greater in the copper-deficient animals as detected by [3H]phenylalanine incorporation into immunoprecipitable apo A-I isolated from liver homogenates and plasma using anti-rat apo A-I antibodies. Pulse-chase experiments using freshly isolated hepatocytes demonstrated that a significant increase (148%) in apo A-I secretion by hepatocytes derived from copper-deficient rats may have resulted from increased hepatic synthesis rather than altered intracellular degradation of apo A-I. Hepatic total cellular apo A-I mRNA abundance was not altered by copper deficiency when expressed per microgram of RNA. Thus, the enhanced hepatic apo A-I synthesis, observed in copper-deficient cells, may have resulted from alterations in post-transcriptional and translational processes.


Force Platform-Based Intervention Program for Individuals Suffering with Neurodegenerative Diseases like Parkinson.
The term "neurodegenerative disease" refers to a set of illnesses that primarily affect brain's neurons. Substantia nigra (a midbrain dopaminergic nucleus) with lack of hormone called dopamine causes Parkinson's disease (PD), a neurological disorder. PD leads to tremor, stiffness, impaired posture and balance, and loss of automatic movements. Patient with Parkinson's often develops a parkinsonian gait that includes a tendency to lean forward, small quick steps as if hurrying forward, and reduced swinging of the arms. They also may have trouble initiating or continuing movement. Gait analysis is often used to diagnose neurodegenerative illnesses and determine their stage. In this study, we attempt to investigate postural balance, and of gait signals for Parkinson's patients, also, we incorporate interim rehabilitation technique. We included 25 PD patients who had 2.5 to 3 IV score of Hoehn and Yahr scale. A ten-minute walk test has been performed to observe primary and secondary results of dual task interference on gait velocities, and gait time motion vector for right and left legs was observed. Two experimental ground conditions include three conditions of trunk alignment, that is, erect on a regular basis (RE), trunk dorsiflexion 30° (TF1), and trunk dorsiflexion 50° (TF2) were analysed. We identified the walking speed of PD patients was decreased, and trunk dorsiflexion variables influence the gait pattern of Parkinson's disease patients, where higher 95% CI for TF1 condition was reported. The regular erect trunk showed swing time reduction (0.7%) in PD, so the higher unified PD rating scale (UPDRS) values have significant difference in swing phase time in Parkinson's patients. The average Hoehn and Yahr scale (H&Y scale) was 4.3 ± 2.5 reported in the study participants. In a 10-week follow-up evaluation, the stance duration was shown to be substantial, as was the slower speed gait in the baseline condition. Excessive flexion was discovered in our investigation at the lower limb joints, particularly the knee and ankle. Patients with Parkinson's disease had similar maximum dorsiflexion and minimum plantarflexion values in stance. The trunk fraction conditions were found significant in patients after rehabilitation training. The best response to rehabilitation treatment was seen when the trunk was rotated. When steps and posture distribution analysis performed, we found that the trunk flexure 1 (p < 0.05), and trunk flexure 2 (p < 0.01) were shown significant values. When GRF threshold characteristics are employed, mean accuracy improves by 52%. Regardless of gait posture, the step regular trunk flexure had significantly higher posture than the corresponding level steps, with a considerable rise in the 50 in trunk dorsiflexion 2 gait relative to the step "L." This study shows that there was some significant improvement observed in the gait parameters among patients with PD's which shows positive impact of the intervention. Furthermore, rehabilitation programmes can aid and improve poor gait features in patients with Parkinson's disease, especially those who are in the early stages of the condition. This gait and balance research provides a rationale for intervention treatments, and their use in clinical practise enhances evidence of therapeutic efficacy. However, prolonged follow-up is needed to determine whether the advantages will remain all across disease's course, and future studies may recommend a specific rehabilitation technique based on gait analysis results.


An uncertainty principle in demography and the unisex issue.
"The purpose of this article is to show that if many characteristics affect the mortality of individuals, there are intrinsic limits to the ability of demographers to answer two elementary questions:" whether the force of mortality in the last year was more or less severe in one country relative to that in a second, and whether an individual's chance of survival would have been greater in one or the other of the two countries. The author notes that the conclusions are applicable to all demographic crude rates. "The possibility of encountering Simpson's paradox suggests that since sex is only one of many possible stratifying variables that appear to affect mortality, the use of mortality tables distinguished by sex and by no other variables is, in the absence of information about the importance of other variables, demographically arbitrary."


Optimal fluxes, reaction replaceability, and response to enzymopathies in the human red blood cell.
Characterizing the capabilities, key dependencies, and response to perturbations of genome-scale metabolic networks is a basic problem with important applications. A key question concerns the identification of the potentially most harmful reaction knockouts. The integration of combinatorial methods with sampling techniques to explore the space of viable flux states may provide crucial insights on this issue. We assess the replaceability of every metabolic conversion in the human red blood cell by enumerating the alternative paths from substrate to product, obtaining a complete map of he potential damage of single enzymopathies. Sampling the space of optimal steady state fluxes in the healthy and in the mutated cell reveals both correlations and complementarity between topologic and dynamical aspects.


Observation on the host parasitoid interaction between Periplaneta americana, the American cockroach and Tetrastichus hagenowii, an oothecal parasitoid.
Investigations were carried out on the host parasitoid interaction between Periplaneta americana, the American cockroach and Tetrastichus hagenowii, an oothecal parasitoid. This gregarious female parasitoid infected and or oviposited in only one host and caused 100% mortality of the infected host. However, increase in parasitoid density decreased the progeny production and influenced the sex ratio. The progenies produced were male biased. When host preference was tested by offering oothecae of different species of cockroaches. T. hagenowii showed a predilection towards the oothecae of P. americana, suggesting its host specificity.


Glucocorticoid-dependent and -independent mechanisms involved in lipopolysaccharide tolerance.
Injection of bacterial lipopolysaccharide (LPS) into animals results in a transient increase in serum tumor necrosis factor (TNF). Maximal increases in TNF were detected by 1 h and 3-4 h serum TNF was no longer apparent. These animals were LPS tolerant and a repetitive LPS stimulus did not result in an additional peak in TNF. Regulation of TNF expression in LPS-tolerant animals was at the transcriptional level as TNF mRNA was not apparent in spleen or peritoneal macrophages following a second LPS stimulus. Adrenalectomized (adrex) mice, in contrast, did not become LPS tolerant and sera from these animals demonstrated an additional peak in TNF 1 h following a second LPS stimulus. Concomitant with the secondary rise in serum TNF in adrex mice was an increase in splenic TNF mRNA. The ability of adrex mice to become LPS tolerant was restored by exogenous glucocorticoids. LPS tolerance was also investigated in the galactosamine LPS model which like the adrex model is characterized by a thousandfold increase in the sensitivity of these animals to the lethal effects of LPS. Consistent with the absence of LPS tolerance in adrex mice, galactosamine-sensitized mice were also responsive to a second LPS stimulus and did not become LPS tolerant. While LPS-treated adrex mice had no significant increases in serum corticosterone, corticosterone levels in LPS-treated galactosamine-sensitized mice were comparable to LPS-stimulated normals suggesting that LPS tolerance involves both glucocorticoid-dependent and -independent components. Finally, prophylactic administration of a monoclonal antibody against murine TNF protected normal and galactosamine-sensitized mice from a lethal dose of LPS and yet had no protective effect in adrex animals.


Essential requirement for sphingosine kinase activity in eNOS-dependent NO release and vasorelaxation.
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that acts both as an extracellular ligand for endothelial differentiation gene receptor family and as an intracellular second messenger. Cellular levels of S1P are low and tightly regulated by sphingosine kinase (SPK). Recent studies have suggested that eNOS pathway may function as a downstream target for the biological effects of receptor-mediated S1P. Here we have studied the possible interplay between intracellular SIP generation and the eNOS activation pathway. S1P causes an endothelium-dependent vasorelaxation in rat aorta that is PTX sensitive, inhibited by L-NAME that involves eNOS phosphorylation, and mainly dependent on hsp90. When rat aorta rings were incubated with the SPK inhibitor DL-threo-dihydrosphingosine (DTD), there was a concentration-dependent reduction of Ach-induced vasorelaxation, implying a consistent contribution of sphingolipid pathway through intracellular sphingosine release and phosphorylation. Co-immunoprecipitation experiments consistently showed increased association of hsp90 with eNOS after exposure of cells to S1P as well to BK or calcium ionophore A-23187. Interestingly, as opposite to A-23187, BK and S1P effect were significantly inhibited by pretreatment with the SPK inhibitor DTD. In conclusion, our data demonstrate that an interplay exists among eNOS, hsp90, and intracellularly generated S1P where eNOS coupling to hsp90 is a major determinant for NO release as confirmed by our functional and molecular studies.


Interactions Between Anti-Angiogenic Therapy and Immunotherapy in Glioblastoma.
Glioblastoma is the most aggressive brain tumor with a median survival ranging from 6.2 to 16.7 months. The complex interactions between the tumor and the cells of tumor microenvironment leads to tumor evolution which ultimately results in treatment failure. Immunotherapy has shown great potential in the treatment of solid tumors but has been less effective in treating glioblastoma. Failure of immunotherapy in glioblastoma has been attributed to low T-cell infiltration in glioblastoma and dysfunction of the T-cells that are present in the glioblastoma microenvironment. Recent advances in single-cell sequencing have increased our understanding of the transcriptional changes in the tumor microenvironment pre and post-treatment. Another treatment modality targeting the tumor microenvironment that has failed in glioblastoma has been anti-angiogenic therapy such as the VEGF neutralizing antibody bevacizumab, which did not improve survival in randomized clinical trials. Interestingly, the immunosuppressed microenvironment and abnormal vasculature of glioblastoma interact in ways that suggest the potential for synergy between these two therapeutic modalities that have failed individually. Abnormal tumor vasculature has been associated with immune evasion and the creation of an immunosuppressive microenvironment, suggesting that inhibiting pro-angiogenic factors like VEGF can increase infiltration of effector immune cells into the tumor microenvironment. Remodeling of the tumor vasculature by inhibiting VEGFR2 has also been shown to improve the efficacy of PDL1 cancer immunotherapy in mouse models of different cancers. In this review, we discuss the recent developments in our understanding of the glioblastoma tumor microenvironment specially the tumor vasculature and its interactions with the immune cells, and opportunities to target these interactions therapeutically. Combining anti-angiogenic and immunotherapy in glioblastoma has the potential to unlock these therapeutic modalities and impact the survival of patients with this devastating cancer.


Expression of apoptosis signal-regulating kinase 1 is associated with tight junction protein claudin-6 in cervical carcinoma.
In our previous work, apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase (MAPK) kinase family has been proved to be associated with the pro-apoptosis effect of tight junction protein claudin-6 in breast cancer. However, its expression in cervical carcinoma has not been reported. The ASK1 and claudin-6 expression in cervical carcinoma tissues and adjacent non-neoplastic tissues was examined by immunohistochemistry. The mRNA and protein expression of ASK1 and claudin-6 in cervical cancer carcinoma cells was detected by reverse transcription (RT)-PCR and western blot. The expression level of ASK1 was down-regulated in cervical carcinoma tissues compared with the adjacent non-neoplastic tissues and positively correlated with the level of claudin-6 in cervical carcinoma cells and tissues. Our present study reveals that ASK1 protein expression altered between human cervical carcinoma and adjacent non-neoplastic tissues. The expression of ASK1 is correlated with the level of claudin-6 in cervical carcinoma cells and tissues.


[Polycythemia vera].
Polycythemia vera (PV) is a chronic myeloproliferative disorder due to a haematopoietic stem cell's clonal proliferation. PV is also characterized by independency or hyper sensibility of haematopoietic progenitors to several cytokine as erythropoietin. This acquired disorder is often associated with thrombocytosis, leukocytosis and splenomegaly. Generally, diagnosis remains easy, based on basic clinical and biological abnormalities. Sometimes, positive diagnosis required more sophisticated tests as assay of endogenous erythroid colony, erythropoietin blood level and bone marrow biopsy. Usually natural history of disease remains long with a good quality of life. In some cases complications occur: mainly thrombosis and late myeloid metaplasia with myelofibrosis and acute leukemia. Therapeutic approachs remain complex and difficult to optimize based up on age and disease severity. Treatment searchs for reducing hyper viscosity complications and for avoiding therapeutic induced leukemia.


Group-structured genetic models in analyses of the population and behavioral ecology of poikilothermic vertebrates.
Estimates of gene correlations among individuals within and among populations are frequently derived from statistical analyses of genetic data (e.g., F statistics). These measures can be important tools in molecular ecology and conservation, and offer important insights into population breeding structure. Using recently derived theory developed for group-structured populations, we show that fixation indices, when combined with basic population ecological and demographic data can be used to investigate population mating systems and to predict dispersal rates, trajectories and asymptotic levels of fixation indices, and effective population size. Four case studies of poikilothermic vertebrates are used to demonstrate the broad utility of evolutionary and ecological inferences afforded by group-structured models.


Lung retrieval from non-heart-beating donors: first experience with an innovative preservation strategy in a pig lung transplantation model.
Lung transplantation is limited by the scarcity of donor organs. Lung retrieval from non-heart-beating donors (NHBD) might extend the donor pool and has been reported recently. However, no studies in NHBD exist using the novel approach of retrograde preservation with Perfadex solution. Heparinized asystolic pigs (n = 5, 30-35 kg) were ventilated for 90 min. The lungs were retrogradely preserved with Perfadex solution and stored inflated at 4 degrees C for 3 h. Left lung transplantation in the recipient was followed by exclusion of the right lung. Results were compared to sham-operated animals. Oxygenation, hemodynamics and dynamic compliance were monitored for 4 h. Infiltration of polymorphonuclear cells (PMNs) and stereological quantification of alveolar edema was performed. Statistical analysis comprised Kruskal-Wallis and Mann-Whitney tests and ANOVA analysis with repeated measures. No mortality was observed. During preservation, continuous elimination of blood clots via the pulmonary artery venting site was observed. Oxygenation and compliance were similar between groups, but sham controls showed significantly lower pulmonary vascular resistance. Stereological quantification revealed higher volume fractions of intra-alveolar edema in NHBD grafts, while PMN infiltration was comparable to sham controls. Use of NHBD lungs results in excellent outcome after 90 min of warm ischemia followed by retrograde preservation with Perfadex solution. This novel approach can optimize lung preservation by eliminating clots from the pulmonary circulation and might clinically be considered in brain-dead organ donors who become hemodynamically unstable prior to organ harvest. Further trials with longer warm and cold ischemic periods are necessary to further elucidate this promising approach to donor pool expansion.


The role of CD24 in multiple myeloma tumorigenicity and effects of the microenvironment on its expression.
Multiple myeloma (MM) is an incurable neoplasm characterized by infiltration of malignant plasma cells (PCs). Recently, the tumor microenvironment has become of great interest in MM as it known to be involved in progression and metastasis of the disease. CD24, is an adhesion molecule expressed during B cell maturation, is down regulated through the cells differentiation into PCs. Though the role of CD24 in solid cancers is well defined, its role in MM remains unknown. We aimed to understand the involvement of CD24 in MM by up-regulating its expression on MM cell lines by co-culturing the cells with bone marrow stromal cell (BMSCs). We then studied the differences between CD24+ and CD24- MM cells and found that CD24+ MM cells presented a less tumorigenic phenotype by impaired capability to migrate and to create colonies as compared with CD24- MM cells. Furthermore, there were significantly more apoptotic cells in the CD24+ fraction. Additionally, the CD24+ cells also upregulated CXCR4 expression. The decrease tumorigenicity correlated with a "more normal" PC immunophenotype in patients with MM and correlated with CD45 expression and a stronger expression of CXCR4. In summary, we found the expression of CD24 on PCs to correlate with attenuated tumorigenicity.


In vitro activity of rezafungin against common and rare Candida species and Saccharomyces cerevisiae.
Rezafungin is a novel echinocandin with excellent activity against common Candida species; however, limited data are available regarding rare Candida species. We determined the in vitro susceptibility of 689 clinical isolates of 5 common and 19 rare Candida species, as well as Saccharomyces cerevisiae. The activity of rezafungin was compared with that of anidulafungin, caspofungin, micafungin, amphotericin B and fluconazole, using CLSI broth microdilution methodology (Fourth Edition: M27). Rezafungin MIC90 values were 0.06 mg/L for Candida albicans (n=125), Candida tropicalis (n=51), Candida dubliniensis (n=22), Candida inconspicua (n=41), Candida sojae (n=10), Candida lipolytica (n=10) and Candida pulcherrima (n=10), 0.12 mg/L for Candida glabrata (n=81), Candida krusei (n=53), Candida kefyr (n=52) and Candida fabianii (n=15), 0.25 mg/L for Candida lusitaniae (n=46) and Candida auris (n=19), 0.5 mg/L for Candida metapsilosis (n=15) and S. cerevisiae (n=21), 1 mg/L for Candida orthopsilosis (n=15) and Candida guilliermondii (n=27) and 2 mg/L for Candida parapsilosis sensu stricto (n=59). Caspofungin MIC90 values were 0.25-2 mg/L for all species, while micafungin and anidulafungin MIC90 values were similar to those of rezafungin. Fluconazole resistance was found in C. albicans (5.6%) and C. glabrata (4.9%); rezafungin was effective against these isolates as well. Amphotericin B MIC values did not exceed 2 mg/L. Rezafungin showed excellent in vitro activity against both WT and azole-resistant Candida species, as well as against S. cerevisiae. Rezafungin had similar activity to other echinocandins (excluding caspofungin) against common Candida species and, notably, against clinically relevant uncommon Candida species.


Carcinogenicity and chronic rodent toxicity of the selective progesterone receptor modulator ulipristal acetate.
Carcinogenic properties of ulipristal acetate (UPA), a selective progesterone receptor modulator developed for the treatment of benign gynecological conditions such as uterine fibroids, were assessed in a 26-week carcinogenicity study in transgenic TgRasH2 mice and a 104-week study in Sprague Dawley rats. Dose levels used in the mouse study were 15, 45, or 130 mg/kg/day and for the ratstudy the doses used were 1, 3, or 10 mg/kg/day. Vehicle and water controls were part of both studies and a positive control, N-Nitroso-N-methylurea intraperitoneally, was included in the transgenic mouse assay. Survival at all dose levels was similar to vehicle controls in both sexes of both species and there was no evidence of any UPA-induced carcinogenicity in either species. Rats receiving UPA had decreased incidences of fibroadenomas and adenocarcinomas in the mammary gland in all treated groups. UPA exposure [AUC(0-24h)] at the highest dose in rats was 67 times human therapeutic exposure at 10 mg/day. In mice, no tumor of any type increased at UPA exposures up to 313 times of therapeutic exposure. UPA-related findings in mice were limited to organ weight changes in the liver, pituitary, thyroid/parathyroid glands, and epididymis as well as minimal panlobular hepatocellular hypertrophy in male and female mice receiving 130 mg/kg/day. Rats had UPA-related non-neoplastic findings in the reproductive system (mammary gland, ovary, uterus, vagina, seminal vesicle, prostate), endocrine system (adrenal, pituitary), thymus, muscle, liver, pancreas and lungs most of which are considered to be due to exaggerated pharmacological action of the compound.


Nanoparticle formulation increases Syzygium cumini antioxidant activity in Candida albicans-infected diabetic rats.
Syzygium cumini (L.) Skeels (Myrtaceae) is a medicinal plant widely used in folk medicine for the treatment of diabetes mellitus (DM). However, studies on the use of this plant and of nanoparticle formulations against DM-related fungal infections are scarce. To evaluate the effect of the treatments with aqueous seed extract of S. cumini (ASc) and ASc-loaded polymeric nanoparticles (NPASc) on biochemical parameters in Candida albicans-infected diabetic rats. Male Wistar rats were divided into eight groups: Control, DM, C. albicans, C. albicans + ASc, C. albicans + NPASc, DM + C. albicans, DM + C. albicans + ASc and DM + C. albicans + NPASc. Rats were daily treated with ASc or NPASc (100 mg/kg) for 21 days. Biochemical parameters in serum and urine, advanced oxidation protein product (AOPP) and TBARS levels in the serum, kidney, liver and pancreas and N-acetyl-β-d-glucosaminidase (NAG) activities in kidney and urine were evaluated. Biochemical and oxidative stress parameters increased in rats with DM and/or candidiasis. NPASc was more effective than ASc in decreasing glucose (56%), cholesterol (33%) and creatinine (51%) levels; serum (16%) and pancreatic (46%) AOPP and renal (48%) TBARS levels when compared with DM + C. albicans group. In C. albicans group, both treatments decreased NAG activity but did not decrease creatinine levels. These data suggest that the use of nanotechnology is able to improve plant extract properties such as antioxidant activity that may be useful in diabetes-related complications.


Sufficience serum vitamin D before 20 weeks of pregnancy reduces the risk of gestational diabetes mellitus.
Our aim was to evaluate the relationship between serum vitamin D levels before 20 weeks of pregnancy and the risk of gestational diabetes mellitus. This study is a retrospective study. We analyzed the relationship between serum 25 (OH) D level before 20 weeks of pregnancy (first antenatal examination) and the risk of gestational diabetes mellitus. Age, parity and pre-pregnancy body mass index were used as confounding factors. 8468 pregnant women were enrolled in this study between January 2018 and March 2020 at the Obstetrics and Gynecology Hospital of Fudan University. Adjusted smoothing splinespline plots, subgroup analysis and multivariate logistic regression analysis was conducted to estimate the relative risk between 25(OH)D and gestational diabetes mellitus. After fully adjusting the confounding factors, serum vitamin D is a protective factor in gestational diabetes mellitus (OR = 0.90). Compared with vitamin D deficiency, vitamin D insufficiency (OR = 0.78), sufficience (OR = 0.82) are a protective factor for gestational diabetes mellitus. Sufficience vitamin D before 20 weeks of pregnancy is a protective factor for gestational diabetes mellitus. Vitamin D > 20 ng/mL can reduce the risk of GDM, which is not much different from the effect of > 30 ng/mL. The protective effect of vitamin D is more significant in obese pregnant women.


Effects of color on children's naming of pictures.
Two experiments assessed possible effects of memory for the typical colors of objects on children's naming of pictures. Children, 5 to 10 yr. old (N = 54 per experiment), named pictures of familiar objects in uncolored, typically colored (red for apple), and atypically colored (blue for apple) versions. Presentation of the three types of pictures was mixed in Exp. 1 and blocked in Exp. 2. With mixed presentation, reaction times for naming were unaffected by typical colors but slowed by atypical colors. With blocked presentation, naming was speeded by typical colors, but only for younger children, and was unaffected by atypical colors. Implications are discussed for understanding the processes by which objects are identified and named and the development of knowledge regarding the color of objects.


Whole-body autoradiography in rats after intravenous administration of L-alanyl-L-[U-14C]glutamine.
The uptake and distribution in rats of the radiolabelled dipeptide L-alanyl-L-[U-14C]glutamine were investigated by whole-body autoradiography. Rats were killed 5, 30 and 180 min following bolus injection of the peptide via the tail vein and, as a comparison, 180 min after injection of [U-14C]glutamine; 30-microns sections of the animals were autoradiographed against an X-ray film. Tissue specimens from the remainder of the carcass were completely combusted and the 14CO2 formed was analyzed by liquid scintillation counting. Visceral organs especially exocrine glands and the mucosa of the alimentary tract showed an initially high labelling (5 min), whereas skeletal muscle and brain exhibited maximum radioactivity 30 min after peptide bolus. Muscle and intestine (19 and 10% of the dose injected, respectively) showed the highest 14C incorporation of all tissues investigated. The broad conformity in 14C distribution observed after peptide and glutamine bolus strongly indicates similar utilization of free and peptide-bound glutamine.


Semistabilized Diazatrienyl Anions from Pyridine Imines and Acetylenes: An Access to (Z)-Stilbene/Imidazopyridine Ensembles, Benzyl Imidazopyridines, and Beyond.
Semistabilized diazatrienyl anions are generated by the reaction of 2-pyridylarylimines with arylacetylenes in superbase systems MOtBu (M = Li, Na, K)/DMSO at ambient temperature for 15 min. The initial intermediate N-centered propargyl-1,3-diaza-1,3,5-trienyl anions undergo intermolecular cyclization to benzyl imidazopyridine anions (formally [3 + 2] cycloaddition), further intercepting a second molecule of the starting pyridylimines or a proton of medium to afford (Z)-stilbene/imidazopyridine ensembles and benzyl imidazopyridines. The charge distribution in all intermediate anions and their synthetic evolution are consistent with quantum-chemical analysis (B2PLYPD/6-311+G**//B3LYP/6-31+G*).


Hospice transfer for patients at the end of life: part 1.
This is the first of two articles about improving end of life care for terminally ill patients in a district general hospital. The article describes a hospice transfer service developed by joint working between staff at a medical assessment unit and a hospice to improve end of life care for patients who otherwise might die in the medical assessment unit. It discusses the care received by patients in both settings, and the practicalities of offering patients the option of rapid transfer to the hospice for end of life care, where the emphasis of care is on palliation not acute intervention. The second article explores the ethical, legal and practical considerations involved in developing the service.


Chemotactic Host-Finding Strategies of Plant Endoparasites and Endophytes.
Plants interact with microorganisms in the environment during all stages of their development and in most of their organs. These interactions can be either beneficial or detrimental for the plant and may be transient or long-term. In extreme cases, microorganisms become endoparastic or endophytic and permanently reside within a plant, while the host plant undergoes developmental reprogramming and produces new tissues or organs as a response to the invasion. Events at the cellular and molecular level following infection have been extensively described, however the mechanisms of how these microorganisms locate their plant hosts via chemotaxis remain largely unknown. In this review, we summarize recent findings concerning the signalling molecules that regulate chemotaxis of endoparasitic/endophytic bacteria, fungi, and nematodes. In particular, we will focus on the molecules secreted by plants that are most likely to act as guidance cues for microorganisms. These compounds are found in a wide range of plant species and show a variety of secondary effects. Interestingly, these compounds show different attraction potencies depending on the species of the invading organism, suggesting that cues perceived in the soil may be more complex than anticipated. However, what the cognate receptors are for these attractants, as well as the mechanism of how these attractants influence these organisms, remain important outstanding questions. Host-targeting marks the first step of plant-microorganism interactions, therefore understanding the signalling molecules involved in this step plays a key role in understanding these interactions as a whole.


Improvement in bone properties by using risedronate adsorbed hydroxyapatite novel nanoparticle based formulation in a rat model of osteoporosis.
A superior drug formulation capable of achieving efficient osteogenesis is in imperative demand for the treatment of osteoporosis. In the present study we investigated the potential of using novel risedronate-hydroxyapatite (HA) nanoparticle based formulation in an animal model of established osteoporosis. Nanoparticles of HA loaded with risedronate (NHLR) of various sizes (80-130 nm) were generated for bone targeted drug delivery. Three months after ovariectomy, 36 ovariectomized (OVX) rats were divided into 6 equal groups and treated with various doses of NHLR (500, 350 and 250 microg/kg intravenous single dose) and sodium risedronate (500 microg/kg, intravenous single dose). Untreated OVX and sham OVX served as controls. One month after drug administration, the left tibia and femur were tested for bone mechanical properties and histology, respectively. In the right femur, bone density was measured by method based on Archimedes principle and bone porosity analyses were performed using X-ray imaging. NHLR (250 microg/kg) showed a significant increase in bone density and reduced bone porosity when compared with OVX control. Moreover, NHLR (250 microg/kg) significantly increased bone mechanical properties and bone quality when compared with OVX control. The results strongly suggest that the NHLR, which is a novel nanoparticle based formulation, has a therapeutic advantage over risedronate sodium monotherapy for the treatment of osteoporosis in a rat model of postmenopausal osteoporosis.


Expression of Arabidopsis LINEs from two promoters.
Most Arabidopsis long interspersed elements (LINEs, called ATLNs) have two open reading frames, orf1 and orf2. In the 5' untranslated regions (UTRs) located upstream of orf1, the most proximal segments of tens of base pairs long are not homologous even in two ATLN members with almost identical sequences. In this study, we first show that RT-PCR products from ATLN39, a member of ATLN, can be detected only in total RNA from the hypomethylation mutant ddm1 or from suspension-cultured cells treated with a DNA methylation inhibitor 5-azacytidine, indicating that the expression of ATLN39 is negatively regulated by DNA methylation. We then show that orf1 fused in frame with the luciferase (luc) gene is expressed in suspension-cultured cells of A. thaliana when the 5' UTR is present in the region upstream of orf1. Analysis of deletion in the 5' UTR revealed that the 5' UTR has two promoters, designated here as P1 and P2. Analysis of transcripts by 5' RACE showed that their 5' ends were located at sites immediately upstream of the P1 region or at sites downstream of the P2 region. This observation and the fact that the P1 region contains no TATA sequence indicate that P1 is an internal promoter that initiates transcription from sites upstream of the promoter. A sequence containing GGCGA with a CpG methylatable site is conserved in the P1 regions in members closely related to ATLN39. The P2 region, however, contains the TATA sequence as well as another sequence with a CpG site. The TATA sequence is conserved in members closely related to ATLN39 but not in the other ATLN members, suggesting that P2 is the promoter uniquely present in the ATLN39-related members. Transcripts from promoter P1 can be used as templates to give new copies proficient in retroposition, but those from promoter P2 cannot because of the lack of the proximal half region of the 5' UTR sequence. Transcripts from promoter P2, as well as those from promoter P1 can, however, be used for the production of a sufficient amount of proteins for retroposition. Only a short sequence of the non-homologous region is present at the 5' ends of transcripts from promoter P1, thus suggesting that the non-homologous regions seen in the most proximal regions in ATLN elements are not generated in transcription.


Crystal-deficient alveolar soft-part sarcoma with cutaneous involvement: a case report.
Alveolar soft-part sarcoma (ASPS) is a rare distinctive sarcoma, in most cases involving deep soft tissues of the extremities. It is associated with a specific unbalanced translocation, der(17)t(X;17)(p11;q25) that results in the formation of an ASPL-TFE3 fusion gene. Microscopically, it is typified by an alveolar growth of large cells containing typical periodic acid-Schiff-positive rod-shaped crystals, often serving as a diagnostic clue. Other distinctive features include nuclear immunoreactivity for transcription factor 3 (TFE3) protein and a typical ultrastructural finding of large crystals with a rectangular or rhomboid shape. The authors present an unusual case of ASPS with cutaneous involvement, which did not exhibit typical large crystals; there were striking round granules. Molecular genetic study revealed fusion transcript ASPL-TFE3, type 2. To the best of our knowledge, cutaneous involvement of a crystal-deficient ASPS has not been reported.


Cell origin and identity in limb regeneration and development.
The occurrence of limb regeneration in adult urodele amphibians raises fundamental questions about the relationship between development and regeneration. The use of monoclonal antibodies as cell markers has provided clear evidence that blastemal cells, the progenitor cells of the regenerate, are not the same as limb bud cells in the embryo. For one of these antibodies the distinction has been traced to the relationship between limb regeneration and the nerve supply. Innervation of the limb bud during development appears to establish nerve-dependent growth control for regeneration. The cell markers have also contributed to the problem of how the blastemal cells arise after amputation, although several important questions remain to be answered.


Quantitative characterization of glycan-receptor binding of H9N2 influenza A virus hemagglutinin.
Avian influenza subtypes such as H5, H7 and H9 are yet to adapt to the human host so as to establish airborne transmission between humans. However, lab-generated reassorted viruses possessing hemagglutinin (HA) and neuraminidase (NA) genes from an avian H9 isolate and other genes from a human-adapted (H3 or H1) subtype acquired two amino acid changes in HA and a single amino acid change in NA that confer respiratory droplet transmission in ferrets. We previously demonstrated for human-adapted H1, H2 and H3 subtypes that quantitative binding affinity of their HA to α2→6 sialylated glycan receptors correlates with respiratory droplet transmissibility of the virus in ferrets. Such a relationship remains to be established for H9 HA. In this study, we performed a quantitative biochemical characterization of glycan receptor binding properties of wild-type and mutant forms of representative H9 HAs that were previously used in context of reassorted viruses in ferret transmission studies. We demonstrate here that distinct molecular interactions in the glycan receptor-binding site of different H9 HAs affect the glycan-binding specificity and affinity. Further we show that α2→6 glycan receptor-binding affinity of a mutant H9 HA carrying Thr-189→Ala amino acid change correlates with the respiratory droplet transmission in ferrets conferred by this change. Our findings contribute to a framework for monitoring the evolution of H9 HA by understanding effects of molecular changes in HA on glycan receptor-binding properties.


Comparison of Early Clinical Results of Transcatheter versus Surgical Aortic Valve Replacement in Symptomatic High Risk Severe Aortic Stenosis Patients.
Transcatheter aortic valve implantation (TAVI) has been an alternative to conventional aortic valve replacement (AVR) in old and high risk patients. The goal of this study is to compare the early outcomes of conventional AVR vs. TAVI in high risk severe AS patients. From January 2008 to July 2012, 44 high risk severe aortic stenosis patients underwent conventional AVR, and 15 patients underwent TAVI. We compared echocardiographic data, periprocedural complication, and survival. The mean follow-up duration was 14.5±10 months (AVR), and 6.8±3.5 months (TAVI), respectively. AVR group was younger (78.2±2.4 years vs. 82.2±3.0 years, p<0.001) and had lower operative risk (Euroscore: 9.4±2.7 vs. 11.0±2.0, p=0.044) than TAVI group. There was no significant difference in early mortality (11.4% vs. 13.3%, p=0.839), and 1 year survival (87.4%±5.3% vs. 83.1%±1.1%, p=0.805). There was no significant difference in postoperative functional class. There was no significant difference in periprocedural complication except vascular complication (0% [AVR] vs. 13.3% [TAVI], p=0.014). TAVI group had more moderate and severe paravalvular leakage. In this study, both groups had similar periprocedural morbidity, and mortality. However, TAVI group had more greater than moderate paravalvular leakage, which can influence long-term outcome. Since more patients are treated with TAVI even in moderate risk, careful selection of the patients and appropriate guideline need to be established.


Risk factors for breast cancer in Pakistani women aged less than 45 years.
There has been an increase in the incidence of breast cancer in previously low-risk Asian countries. It is important to identify the risk factors for Asian women, as little information currently exists for this population. The objective of the study was to determine risk factors for breast cancer among Pakistani women. 498 cases younger than 45 years were interviewed from 1 July 1997 to 31 December 1998 at two major cancer hospitals. Age-matched population-based controls were selected from two cities and two villages to represent urban and rural areas. For the variables under study, cases and controls were compared by t-test. Conditional multiple logistic regression models were applied to the data set. Women with BMI >or= 30, with a family history of breast cancer and who were parous were at increased risk. Among parous women risk factors included BMI >or= 30, being in a consanguineous marriage, later age at menarche, later age at first full-term pregnancy, high parity and a history of abortion. The risk factors identified for Pakistani women below 45 years were similar to those observed in other studies. However, obesity in pre-menopausal women and late menarche were not protective and consanguinity was identified as a risk.


Investigations on the Maillard Reaction in Sesame ( Sesamum indicum L.) Seeds Induced by Roasting.
This study investigated the formation of Maillard reaction products in sesame seeds under different roasting conditions. Sesame seeds were roasted at 150, 180, 200, and 220 °C for 10 min, and thermal process contaminants including 5-hydroxymethylfurfural, acrylamide, furan, and dicarbonyl compounds (1-deoxyglucosone, 3-deoxyglucosone, methylglyoxal, and diacetyl) together with glycation markers namely N-ε-fructosyllysine, N-ε-carboxymethyllysine, and N-ε-carboxyethyllysine, were monitored. Roasting induced the formation of 5-hydroxymethylfurfural, acrylamide, and dicarbonyl compounds, except furan, significantly ( p < 0.05). 5-Hydroxymethylfurfural and acrylamide content of roasted sesame seeds were found to vary as 3-40 mg/kg and 135-633 μg/kg, respectively. Dicarbonyl compounds were in the following order: methylglyoxal > 3-deoxyglucosone > 1-deoxyglucosone > diacetyl. On the other hand, N-ε-fructosyllysine concentration decreased while the roasting temperature increased; however, N-ε-carboxymethyllysine and N-ε-carboxyethyllysine formation was induced under those conditions. This is the first study reporting the formation of thermal process contaminants and glycation markers in sesame seeds through Maillard reaction during roasting.


Calculation of actual population momentum.
The author proposes a formula for the calculation of population momentum, defined as "the value of a population that suddenly becomes static at a certain time and at an age-specific rate; it is the ratio between the ultimate size and the current size of a population. Obviously, the greater the population momentum, the stronger the momentum for growth." The method is tested using 1982 data for China.


Developing a process for a metadata standard for environmental public health tracking.
The National Environmental Public Health Tracking Network provides an opportunity for public health practitioners to access more data than previously possible. The availability of metadata about the Tracking Network would enable users to search for and discover data for public health action and decision-making. Specifically, the metadata will be used to establish keyword search terms for data mining and will also provide a description of the content of data sets to point out their uses and limitations.


A Highly Convergent Total Synthesis of Norhalichondrin B.
A new synthetic strategy for the total synthesis of norhalichondrin B featuring a highly convergent approach and our recently disclosed reverse approach for the synthesis of cyclic ether structural motifs is disclosed. Resulting in the shortest route to norhalichondrin B disclosed thus far, the reported total synthesis was achieved through the synthesis of two almost equally complex fragments whose coupling and short elaboration sequence featured an essential epimerization of the C16 stereocenter occurring concurrently with a simple acid-induced deprotection, a tactic based on a prior study along the synthetic route. This unprecedented strategy within the halichondrin family of natural products could find practical application to the synthesis of other more or less complex natural or designed halichondrin analogues.


Normal range of motion of the joints of the upper extremity in male subjects, with special reference to side.
We measured, with a universal full-circle manual goniometer, the active and passive arcs of motion of the shoulder, elbow, forearm, and wrist in 1000 healthy male subjects who were right-hand dominant and who ranged in age from eighteen to twenty-two years. The ranges of motion on the right side were significantly smaller than those on the left. We concluded that the contralateral, normal side may not always be a reliable control in the evaluation of restriction of motion of a joint.


Tests of the power PC theory of causal induction with negative contingencies.
The power PC theory of causal induction (Cheng, 1997) proposes that causal estimates are based on the power p of a potential cause, where p is the contingency between the cause and effect normalized by the base rate of the effect. Previous tests of this theory have concentrated on generative causes that have positive contingencies with their associated outcomes. Here we empirically test this theory in two experiments using preventive causes that have negative contingencies for their outcomes. Contrary to the power PC theory, the results show that causal judgments vary with contingency across conditions of constant power p. This pattern is consistent, however, with several alternative accounts of causal judgment.


Chondrolysis: detection by bone scintigraphy.
Premature closure of the physis of the greater trochanter has been reported to be a predictive sign of chondrolysis in hips with slipped capital femoral epiphysis (SCFE). In the present series, the physis of the greater trochanter showed decreased activity on bone scintigraphy in 16 patients with SCFE and concurrent or developing chondrolysis. In five of these patients, the scintigraphic pattern (decreased activity of the physis of the greater trochanter) preceded radiographic changes of chondrolysis. In 13 patients with SCFE without chondrolysis, the physis of the greater trochanter appeared normal on scintigrams and open on radiographs. Use of scintigraphy in patients with SCFE permitted earlier recognition of chondrolysis, increasing the potential of altering the course of the disease.


Purification and Partial Characterization of a Glucan Containing Indole-3-acetic Acid.
The "bound auxin" of Zea mays, first described by Berger and Avery (Amer. J. Bot. 1944; 31: 199-203) has been purified and partially characterized. It is an indole-3-acetic acid-containing, high molecular weight, lipophilic cellulosicglucan. The indole-3-acetic acid is in ester linkage as evidenced by indoleacetamide formation upon ammonolysis. The glucan is of variable chain length and comprises, in general, 35 to 50 per cent of the dry weight of the compound. The glucosidic residues are beta 1 --> 4 linked and are hydrolyzed by cellulase. Mild acid hydrolysis produces cellobiose and cellotriose. Other components, as yet unidentified, of the compound are described.


Designing Superlubricious Hydrogels from Spontaneous Peroxidation Gradients.
Hydrogels are hydrated three-dimensional networks of hydrophilic polymers that are commonly used in the biomedical industry due to their mechanical and structural tunability, biocompatibility, and similar water content to biological tissues. The surface structure of hydrogels polymerized through free-radical polymerization can be modified by controlling environmental oxygen concentrations, leading to the formation of a polymer concentration gradient. In this work, 17.5 wt % polyacrylamide hydrogels are polymerized in low (0.01 mol % O2) and high (20 mol % O2) oxygen environments, and their mechanical and tribological properties are characterized through microindentation, nanoindentation, and tribological sliding experiments. Without significantly reducing the elastic modulus of the hydrogel (E* ≈ 200 kPa), we demonstrate an order of magnitude reduction in friction coefficient (from μ = 0.021 ± 0.006 to μ = 0.002 ± 0.001) by adjusting polymerization conditions (e.g., oxygen concentration). A quantitative analytical model based on polyacrylamide chemistry and kinetics was developed to estimate the thickness and structure of the monomer conversion gradient, termed the "surface gel layer". We find that polymerizing hydrogels at high oxygen concentrations leads to the formation of a preswollen surface gel layer that is approximately five times thicker (t ≈ 50 μm) and four times less concentrated (≈ 6% monomer conversion) at the surface prior to swelling compared to low oxygen environments (t ≈ 10 μm, ≈ 20% monomer conversion). Our model could be readily modified to predict the preswollen concentration profile of the polyacrylamide gel surface layer for any reaction conditions─monomer and initiator concentration, oxygen concentration, reaction time, and reaction media depth─or used to select conditions that correspond to a certain desired surface gel layer profile.


Haptic-Assisted Interactive Molecular Docking Incorporating Receptor Flexibility.
Haptic-assisted interactive docking tools immerse the user in an environment where intuition and knowledge can be used to help guide the docking process. Here we present such a tool where the user "holds" a rigid ligand via a haptic device through which they feel interaction forces with a flexible receptor biomolecule. To ensure forces transmitted through the haptic device are smooth and stable, they must be updated at a rate greater than 500 Hz. Due to this time constraint, the majority of haptic docking tools do not attempt to model the conformational changes that would occur when molecules interact during binding. Our haptic-assisted docking tool, "Haptimol FlexiDock", models a receptor's conformational response to forces of interaction with a ligand while maintaining the required haptic refresh rate. In order to model receptor flexibility we use the method of linear response for which we determine the variance-covariance matrix of atomic fluctuations from the trajectory of an explicit-solvent molecular dynamics simulation of the ligand-free receptor molecule. The key to satisfying the time constraint is an eigenvector decomposition of the variance-covariance matrix which enables a good approximation to the conformational response of the receptor to be calculated rapidly. This exploits a feature of protein dynamics whereby most fluctuation occurs within a relatively small subspace. The method is demonstrated on glutamine binding protein in interaction with glutamine and maltose binding protein in interaction with maltose. For both proteins the movement that occurs when the ligand is docked near to its binding site matches the experimentally determined movement well. It is thought that this tool will be particularly useful for structure-based drug design.


Organophosphorus pesticide residues in raw milk and infant formulas from Spanish northwest.
Residue levels of seven organophosphorus pesticides (OPPs), widely used as dairy cattle ectoparasiticides or in crops used for animal feed, were determined in raw milk and infant formulas. A total of 312 samples were collected (70 from infant formulas and 242 from raw milk) biweekly during a 24-month period. Pesticides were extracted by means of a solid phase system into acetone. An extract aliquot of acetone was injected into a gas chromatograph (GC) with a nitrogen-phosphorus detector. Recoveries of pesticides spiked in milk samples were 62.2 - 97.2 %. The frequency of total samples containing detectable levels of OPP residues was 6.73 % in total milk and 8.67 % in raw milk. The highest percentage incidence measured was for dichlorvos (5.78 %), followed by coumaphos (2.06 %), and parathion methyl (0.83 %). The range of positive results was calculated to be between 0.005 and 0.220 mg kg(- 1). No residue was detected in the final product (infant formulas), so any risk to consumer health, especially to children's health, would be limited.