Case series study of the clinical profile of H1N1 swine flu influenza.
To study the clinical profile of the H1N1 influenza cases attending government hospitals in South India and to study the impact of H1N1 infection on pregnancy outcome. A total number of 442 H1N1 positive patients (198 inpatients and 244 outpatients) from two government hospitals in Chennai, Madras Medical College & Government General Hospital and Institute of Child Health, Egmore were studied retrospectively during a period of 6 months from August 2009 to January 2010. The rate of reported cases and hospitalization rates was highest among individuals aged 5 to 24 years. H1N1 cases were equally distributed in both the sexes in the adult population In our study 86.92% percent of patients with pandemic H1N1 influenza A met the case definition for influenza like illness (subjective fever plus cough and/or sorethroat). Similar to the western data bronchial asthma, pulmonary tuberculosis were found to risk factors for complications in H1N1 infection. The overall mortality rate was 1.8% and the most common cause of death in patients was due to pneumonia. Ventilator requirement was associated with poor prognosis in H1N1 patients. P value < 0.01. The percentage of persons > 65 years who were affected was far less ie 0.67% which is quite unusual in the case of seasonal flu. H1N1 pnuemonia was found to involve predominantly the lower lobe of lung. (p value < 0.01).The mortality rate among pregnant women with H1N1 infection was 25% and the fetal loss rate was 16.67%. There was an increased risk of H1N1 influenza infection during the third trimester of pregnancy. (p value-0.027). Individuals with comorbid conditions, pregnancy were found to be severely affected. Hence individuals with risk factors need to be protected by vaccination.


Addressing the learning needs of multidisciplinary students at a distance using a virtual learning environment (VLE): A novice teacher reflects.
This paper analyses the experience of one individual in the development and delivery of an innovative, undergraduate leadership development module. The module is accessed by practising health care professionals in Malaysia as part of a top-up Honours Degree and is delivered solely using a virtual learning environment (VLE), in this case Blackboard. The aim of this analysis is to contribute to the current body of knowledge regarding the use of VLE technology to facilitate learning at a distance. Of particular relevance is the paper's focus on: the drivers for e-learning; widening participation and increasing access; the experience of designing and delivering learning of relevance for this contemporary student population and evaluating the VLE experience/module. The development and delivery of this module is one result of a rapidly growing area of education. As a novice teacher in her first year in the higher education sector, this experience was a significant and stimulating challenge for a number of reasons and these are explored in greater depth. This is achieved by means of personal reflection using the phases of module development and delivery as a focus.


High-level expression of enzymatically active mature human gamma-glutamyltransferase in transgenic V79 Chinese hamster cells.
gamma-Glutamyltransferase [GGT; (5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 220.127.116.11] is a glutathione-metabolizing enzyme, whose activity variations in serum and organs are valuable markers of preneoplastic processes, alcohol abuse, and induction by xenobiotics. To elucidate the implication of GGT in various metabolic pathways, we established a stable transgenic V79 cell line, highly producing the human GGT. A full-length cDNA, encoding the human hepatoma HepG2 GGT, was subcloned in an expression vector under the control of the simian virus 40 early promoter and was used to transfect V79 cells. We selected a cell line exhibiting a GGT activity of 2 units per mg of protein, the highest GGT expression level reported to date. As described for the human kidney and liver enzymes, the recombinant GGT purified from this cell line showed a heterodimeric structure. Its two subunits existed as sialylated and differentially glycosylated isoforms, with mean molecular masses of 80 and 29 kDa. However, catalytic features were found to be identical to those of human serum and HepG2 GGTs. The newly engineered cell line thus should be useful for the production of human GGT and as a potential alternative model for pharmacological studies.


Interaction of carbolines and some GABA receptor ligands with the GABA and the benzodiazepine receptors.
The binding of different drugs were investigated on benzodiazepines and GABA receptors using P2 fraction or 0.05% Triton X-100 treated membrane preparation (TX-100 P) obtained from rat's CNS. Bicuculline and picrotoxin have the ability to modulate the specific 3H-flunitrazepam binding to its receptor present in P2 fraction; this modulation decreases for bicuculline and disappears for picrotoxin when a TX-100 P was used. Bicuculline at the opposite of picrotoxin displaces 3H-GABA binding on TX-100 P. The beta-CCE binds to the brain benzodiazepines receptor with a high affinity (IC50 = 8.5 nM on TX-100 P) and does not inhibit the binding of 3H-GABA on TX-100 P. On the contrary, other related carbolines such as harmine, harmaline, harmane and harmalol have a much lower ability to inhibit flunitrazepam binding (IC50 between 28 and 130 microM with TX-100 P) and can also inhibit 3H-GABA binding (IC50 between 75 and 186 microM with TX-100 P). But the inhibition of 3H-GABA binding by those related carbolines can't be reversed by a benzodiazepine like flunitrazepam or a benzodiazepine antagonist like Ro 15-1788.


The CA125 level postoperative change rule and its prognostic significance in patients with resectable pancreatic cancer.
The relationship between postoperative CA125 level changes and early recurrence after curative resection of resectable PDAC is still unclear. The electronic medical records and follow-up data of patients with resectable pancreatic cancer were evaluated. Dynamic CA125 detection was used to identify the rules for postoperative CA125 level change and its prognostic value in patients with resectable pancreatic cancer. The study included a total of 118 patients with resectable pancreatic cancer who underwent curative resection. Early postoperative CA125 levels were significantly higher than those before surgery (P < 0.05). It decreased gradually in the group without early recurrence (P < 0.05) but not in the early recurrence group (P>0.05). There was no correlation between early postoperative CA125 levels and early recurrence (P > 0.05). CA125 levels three months after surgery were associated with an increased risk of early recurrence (P = 0.038, 95% CI (1.001-1.025)). The cutoff CA125 level at 3 months after surgery for predicting early recurrence was 22.035. Patients with CA125 levels < 22.035 three months postoperatively had similar DFS and OS, regardless of whether the value was exceeded in the early postoperative period, but these values were significantly better than those of patients with CA125 levels > 22.035 at 3 months postoperatively (p < 0.05). Patients with different prognoses have different patterns of CA125 level changes. Elevations in CA125 levels > 3 months postoperatively, rather than early postoperative elevation, were associated with a poor prognosis.


Differential time-course and dose-response relationships of TCDD-induced CYP1B1, CYP1A1, and CYP1A2 proteins in rats.
This study examined the relationship between dose- and time-dependent hepatic localization of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and expression of CYP1B1, CYP1A1 and CYP1A2 proteins. A dose-dependent increase in hepatic TCDD in female Sprague-Dawley rats treated with 0.01-30.0 microg TCDD/kg was observed. TCDD induced CYP1A1 protein in rats treated with 0.3 microg TCDD/kg or higher. TCDD induced CYP1A2 and CYP1B1 proteins in rats treated with 1.0 microg TCDD/kg or higher. The in vivo ED50 (microg TCDD/kg) for TCDD-induced CYP1A1, CYP1A2 and CYP1B1 proteins were 0.22, 0.40 and 5.19, respectively. Hepatic accumulation of TCDD reached a maximum at 8 hours post dosing with a t1/2 of approximately 10 days. TCDD-induced CYP1A1/CYP1A2 protein expression was increased time-dependently, reaching a maximum at 3 days after dosing and remaining elevated for 35 days. In contrast, TCDD-induced CYP1B1 protein showed significant expression at 3 days after dosing and decreased to basal concentrations by 35 days. This study demonstrates that TCDD exhibits differential dose-response and time-course relationships on hepatic localization and cytochrome P-450 protein expression.


Outcomes and patterns of failure in solitary plasmacytoma: a multicenter Rare Cancer Network study of 258 patients.
To assess the outcomes and patterns of failure in solitary plasmacytoma (SP). The data from 258 patients with bone (n = 206) or extramedullary (n = 52) SP without evidence of multiple myeloma (MM) were collected. A histopathologic diagnosis was obtained for all patients. Most (n = 214) of the patients received radiotherapy (RT) alone; 34 received chemotherapy and RT, and 8 surgery alone. The median radiation dose was 40 Gy. The median follow-up was 56 months (range 7-245). The median time to MM development was 21 months (range 2-135), with a 5-year probability of 45%. The 5-year overall survival, disease-free survival, and local control rate was 74%, 50%, and 86%, respectively. On multivariate analyses, the favorable factors were younger age and tumor size <4 cm for survival; younger age, extramedullary localization, and RT for disease-free survival; and small tumor and RT for local control. Bone localization was the only predictor of MM development. No dose-response relationship was found for doses >30 Gy, even for larger tumors. Progression to MM remains the main problem. Patients with extramedullary SP had the best outcomes, especially when treated with moderate-dose RT. Chemotherapy and/or novel therapies should be investigated for bone or bulky extramedullary SP.


Clinical Efficacy of Laparoscopic Cholecystectomy via Cystic Plate Approach for Gallstone Patients with Chronic Cholecystitis.
Introduction: Chronic cholecystitis has evolved into one of the digestive system diseases that negatively affect the quality of life of patients. This study was conducted to explore the clinical efficacy of laparoscopic cholecystectomy via cystic plate approach for the treatment of gallstones with chronic cholecystitis. Materials and Methods: Totally 184 gallstone patients with chronic cholecystitis who underwent laparoscopic cholecystectomy in The First People's Hospital of Wuhu from January 2021 to October 2022 were randomly divided into a control group (n = 92) and an observation group (n = 92). In the observation group and control group, the gallbladder was removed using the cystic plate approach and traditional approach, respectively. Surgical indicators and complications of patients were compared. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay. The quality of life of patients was assessed using the SF-36 scale. Results: The recovery time of gastrointestinal function, intraoperative blood loss, and postoperative drainage volume in the observation group were significantly lower than those in the control group (P < .05). At 24 hours after surgery, the serum levels of IL-6, TNF-α, and CRP in the observation group were much lower than those in the control group (P < .05). Three months after surgery, the observation group showed a much higher quality of life score than the control group (P < .05). Conclusion: Laparoscopic cholecystectomy via cystic plate approach can effectively treat chronic gallstones with chronic cholecystitis. It shortened the recovery time of gastrointestinal function, reduced postoperative inflammation, and improved the quality of life.


Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration.
There is inconclusive evidence from observational studies to suggest that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD). To examine the evidence as to whether or not taking antioxidant vitamin or mineral supplements prevents the development of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 12), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), Open Grey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 26 January 2012. We included all randomised controlled trials (RCTs) comparing an antioxidant vitamin and/or mineral supplement (alone or in combination) to control. Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5 and the other author checked the data entry. We pooled data using a fixed-effect model. We included four RCTs in this review; 62,520 people were included in the analyses. The trials were conducted in Australia, Finland and the USA and investigated vitamin E and beta-carotene supplements. Overall the quality of the evidence was high. People who took these supplements were not at decreased (or increased) risk of developing AMD. The pooled risk ratio for any antioxidant supplement in the prevention of any AMD was 0.98 (95% confidence interval 0.89 to 1.08) and for advanced AMD was 1.05 (95% CI 0.80 to 1.39). Similar results were seen when the analyses were restricted to beta-carotene and alpha-tocopherol alone. There is accumulating evidence that taking vitamin E or beta-carotene supplements will not prevent or delay the onset of AMD. There is no evidence with respect to other antioxidant supplements, such as vitamin C, lutein and zeaxanthin, or any of the commonly marketed multivitamin combinations. Although generally regarded as safe, vitamin supplements may have harmful effects and clear evidence of benefit is needed before they can be recommended. People with AMD should see the related Cochrane review 'Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration' written by the same review team.


Role for animal research in the investigation of human mental retardation.
Animal models of the cognitive deficiency states of mental retardation per se are underutilized. A general learning impairment model and a reasoning/insight model, both in rats, were reviewed for parallels to theories of human cognitive deficiency. Predictions were made for the relevance to human mental retardation. Although the parallel development of human mental deficiency research and animal cognition research has precluded substantial benefits at this time, a wider reading of the animal literature by human mental retardation researchers would benefit both animal cognition research and human mental retardation research.


Indices for the brittleness of pharmaceutical tablets: A reassessment.
Brittleness is an important mechanical property. In the classical sense, a material is considered brittle if, during loading, it behaves elastically until failure. Nevertheless, it is also sometimes understood as the fact to be resistant to breakage. In the case of pharmaceutical tablets, three different indices have been defined to measure brittleness: the brittle fracture index (BFI), the brittle/ductile index (BDI) and the tablet brittleness index (TBI). The aim of this work was to reassess the meaning of the different indices that are known to give contradictory results. Using theoretical considerations, numerical modelling and experiments, it was possible to show that the only index that unequivocally measures the brittleness of the tablet understood as elastic until failure is the BFI. If the other two indices can be useful, for example to assess the friability of the tablet in the case of the TBI, they do not make it possible to measure tablet brittleness in the classical sense, i.e. as opposed to ductility.


How do women with secondary breast cancer experience telling their adolescent children about their diagnosis?
This study investigated how women with secondary breast cancer experience telling their adolescent children. Semi-structured interviews were conducted with women who had been diagnosed with secondary breast cancer at least 1 year prior to the interview. Seven women, who had at least one child between 12 and 19 years old living at home at the time of diagnosis, were interviewed. The interviews were analysed using interpretative phenomenological analysis for an in-depth understanding of women's experiences. Women found that it was easier to tell their children of their secondary breast cancer diagnosis compared to their primary cancer. However, they talked about the impact the diagnosis had on their family.


Opuntia ficus-indica (L.) Mill. - anticancer properties and phytochemicals: current trends and future perspectives.
Cancer is a leading cause of mortality worldwide, and conventional cancer therapies such as chemotherapy and radiotherapy often result in undesirable and adverse effects. Natural products have emerged as a promising alternative for cancer treatment, with comparatively fewer side effects reported. Opuntia ficus-indica (L.) Mill., a member of the Cactaceae family, contains a diverse array of phytochemicals, including flavonoids, polyphenols, betalains, and tannins, which have been shown to exhibit potent anticancer properties. Various parts of the Opuntia plant, including the fruits, stems/cladodes, and roots, have demonstrated cytotoxic effects against malignant cell lines in numerous studies. This review comprehensively summarizes the anticancer attributes of the phytochemicals found in Opuntia ficus-indica (L.) Mill., highlighting their potential as natural cancer prevention and treatment agents. Bibliometric metric analysis of PubMed and Scopus-retrieved data using VOSviewer as well as QDA analysis provide further insights and niche to be explored. Most anticancer studies on Opuntia ficus-indica and its purified metabolites are related to colorectal/colon cancer, followed by melanoma and breast cancer. Very little attention has been paid to leukemia, thyroid, endometrial, liver, and prostate cancer, and it could be considered an opportunity for researchers to explore O. ficus-indica and its metabolites against these cancers. The most notable mechanisms expressed and validated in those studies are apoptosis, cell cycle arrest (G0/G1 and G2/M), Bcl-2 modulation, antiproliferative, oxidative stress-mediated mechanisms, and cytochrome c. We have also observed that cladodes and fruits of O. ficus-indica have been more studied than other plant parts, which again opens the opportunity for the researchers to explore. Further, cell line-based studies dominated, and very few studies were related to animal-based experiments. The Zebrafish model is another platform to explore. However, it seems like more in-depth studies are required to ascertain clinical utility of this biosustainable resource O. ficus-indica.


4-(4,4-Difluoro-1,3,5,7-tetra-methyl-3a-aza-4a-azonia-4-borata-s-indacen-8-yl)benzonitrile.
The title compound, C(20)H(18)BF(2)N(3), contains one C(9)BN(2) (Bodipy) framework and one cyano-benzyl group. The Bodipy framework is essentially planar with a maximum deviation of 0.041 (2) Å. The introduction of two methyl groups at positions 1 and 7 of s-indacene in the Bodipy unit results in almost orthogonal configuration between the mean plane of the Bodipy unit and the cyano-benzyl group [dihedral angle = 89.78 (4)°].


Nanoflow LC-MS for High-Performance Chemical Isotope Labeling Quantitative Metabolomics.
Nanoflow liquid chromatography mass spectrometry (nLC-MS) is frequently used in the proteomics field to analyze a small amount of protein and peptide samples. However, this technique is currently not widespread in the metabolomics field. We report a detailed investigation on the development of an nLC-MS system equipped with a trap column for high-performance chemical isotope labeling (CIL) metabolomic profiling with deep coverage and high sensitivity. Experimental conditions were optimized for profiling the amine/phenol submetabolome with (13)C-/(12)C-dansylation labeling. Comparison of analytical results from nLC-MS and microbore LC-MS (mLC-MS) was made in the analysis of metabolite standards and labeled human urine and sweat samples. It is shown that, with a 5-μL loop injection, 7 labeled amino acid standards could be detected with S/N ranging from 7 to 150 by nLC-MS with an injection of 5 nM solution containing a total of 25 fmol labeled analyte. For urine metabolome profiling where the sample amount was not limited, nLC-MS detected 13% more metabolites than mLC-MS under optimal conditions (i.e., 4524 ± 37 peak pairs from 26 nmol injection in triplicate vs 4019 ± 40 peak pairs from 52 nmol injection). This gain was attributed to the increased dynamic range of peak detection in nLC-MS. In the analysis of human sweat where the sample amount could be limited, nLC-MS offered the advantage of providing much higher coverage than mLC-MS. Injecting 5 nmol of dansylated sweat, 3908 ± 62 peak pairs or metabolites were detected by nLC-MS, while only 1064 ± 6 peak pairs were detected by mLC-MS. Because dansyl labeled metabolites can be captured on a reversed phase (RP) trap column for large volume injection and are well separated by RPLC, the CIL platform can be readily implemented in existing nLC-MS instruments such as those widely used in shotgun proteomics.


Chronic disease diagnosis model based on convolutional neural network and ensemble learning method.
Chronic diseases have become one of the main causes of premature death all around the world in recent years. The diagnosis of chronic diseases is time-consuming and costly. Therefore, timely diagnosis and prediction of chronic diseases are very necessary. In this paper, a new method for chronic disease diagnosis is proposed by combining convolutional neural network (CNN) and ensemble learning. This method utilizes random forest (RF) as the base classifier to improve classification performance and diagnostic accuracy, and then combines AdaBoost to successfully replace the Softmax layer of CNN to generate multiple accurate base classifiers while determining their optimal attributes, achieving high-quality classification and prediction of chronic diseases. To verify the effectiveness of the proposed method, real-world Electronic Medical Records dataset (C-EMRs) was used for experimental analysis. The results show that compared with other traditional machine learning methods such as CNN, K-Nearest Neighbor, and RF, the proposed method can effectively improve the accuracy of diagnosis and reduce the occurrence of missed diagnosis and misdiagnosis. This study will provide effective information for the diagnosis of chronic diseases, assist doctors in making clinical decisions, develop targeted intervention measures, and reduce the probability of misdiagnosis.


A revisionist history of adult marrow stem cell biology or 'they forgot about the discard'.
The adult marrow hematopoietic stem cell biology has largely been based on studies of highly purified stem cells. This is unfortunate because during the stem cell purification the great bulk of stem cells are discarded. These cells are actively proliferating. The final purified stem cell is dormant and not representative of the whole stem cell compartment. Thus, a large number of studies on the cellular characteristics, regulators and molecular details of stem cells have been carried on out of non-represented cells. Niche studies have largely pursued using these purified stem cells and these are largely un-interpretable. Other considerations include the distinction between baseline and transplant stem cells and the modulation of stem cell phenotype by extracellular vesicles, to cite a non-inclusive list. Work needs to proceed on characterizing the true stem cell population.


CART-a chemical annotation retrieval toolkit.
Data on bioactivities of drug-like chemicals are rapidly accumulating in public repositories, creating new opportunities for research in computational systems pharmacology. However, integrative analysis of these data sets is difficult due to prevailing ambiguity between chemical names and identifiers and a lack of cross-references between databases. To address this challenge, we have developed CART, a Chemical Annotation Retrieval Toolkit. As a key functionality, it matches an input list of chemical names into a comprehensive reference space to assign unambiguous chemical identifiers. In this unified space, bioactivity annotations can be easily retrieved from databases covering a wide variety of chemical effects on biological systems. Subsequently, CART can determine annotations enriched in the input set of chemicals and display these in tabular format and interactive network visualizations, thereby facilitating integrative analysis of chemical bioactivity data. CART is available as a Galaxy web service (cart.embl.de). Source code and an easy-to-install command line tool can also be obtained from the web site. email@example.com Supplementary data are available at Bioinformatics online.


Ab initio calculation of (2+1) resonance enhanced multiphoton ionization spectra and lifetimes of the (D,3)2Sigma- states of OH and OD.
High-level ab initio potential-energy curves and transition dipole moments for the OH X 2Pi, 2 2Pi, 1 2Sigma-, D 2Sigma-, 3 2Sigma-, A 2Sigma+, B 2Sigma+, 1 2Delta, 1 4Sigma-, and 1 4Pi states are computed. The results are used to estimate the (2+1) resonance enhanced multiphoton ionization spectrum for the (D,3)2Sigma-(upsilon')<--2hnuX 2Piupsilon") transitions, which are compared with experiments by Greenslade et al. [see M. E. Greenslade, M. I. Lester, D. C. Radenovic, J. A. van Roij, and D. H. Parker, J. Chem. Phys. 123, 074309 (2005), preceeding paper]. We use the discrete variable representation-absorbing boundary condition method to incorporate the effect of the dissociative intermediate 1 2Sigma- state. We obtain qualitative agreement with experiment for the line strengths. Radiative and predissociative decay rates of the Rydberg (D,3)2Sigma- states of OH and OD were computed, including spin-orbit coupling effects and the effect of spin-electronic and gyroscopic coupling. We show that the lifetime of the Rydberg 2Sigma- states for rotationally cold molecules is limited mainly by predissociation caused by spin-orbit coupling.


Incorporation of choline, serine, ethanolamine and inositol into phospholipids of isolated rat mast cells.
The incorporation of labelled phospholipid precursors, [Me-14C]-choline, L-[3(-14)C]-serine, [2(-14)C]-ethanolamine and [2(-3)H]-myoinositol into the phospholipids of isolated rat mast cells was studied. The label from the different precursors were found to be essentially associated with compounds with the t.1.c.-motility of the respective phospholipids. Whereas the incorporation of [Me(-14)c]-choline and L-[3(-14)C]-serine showed evidence of saturation the incorporation of [2(-14)C]-ethanolamine was linear with time (2 h) and it was not saturated by increasing the concentration from 0.07 mM to 2.07 mM. The incorporation of [2(-3)H]-myoinositol was stimulated by Ca2+ (1 mM) or Mg2+ (1 mM), while the incorporation of the other precursors was stimulated only in the presence of both Ca2+ and Mg2+ (1 mM). Antimycin A (1muM), an inhibitor of the respiratory chain, significantly ingibited the incorporation of [Me(-14)c]-choline, L-[3(-14)C]-serine and [2(-3)H]-myoinositol but not that of [2(-14)C]-ethanolamine. The experimental system used might be a useful model for studies on the turnover of membrane phospholipids during histamine release.


Aerobic and anaerobic exercise capacities in obstructive sleep apnea and associations with subcutaneous fat distributions.
Obesity is a strong risk factor for the development and progression of sleep apnea. Responses to exercise by patients with obstructive sleep apnea syndrome (OSAS) are clinically relevant to reducing body weight and cardiovascular risk factors. This study aimed to clarify the aerobic and anaerobic exercise capacities and their possible relationships with other findings in patients with OSAS. Forty patients (30 males, 10 females) and 40 controls (30 males, 10 females) were enrolled in this study. Questionnaires (excessive daytime sleepiness, daytime tiredness, morning headache, waking unrefreshed, and imbalance), overnight polysomnography, indirect laryngoscopy, and aerobic and anaerobic exercise tests were performed. Triceps, subscapular, abdomen, and thigh skinfold thicknesses were measured. Subcutaneous abdominal fat (abdomen skinfold) was significantly higher in OSAS patients than in controls. Maximal anaerobic power and anaerobic capacity were not different significantly between the patients and controls. We found that aerobic capacity was significantly lower in OSAS patients than in controls. Aerobic capacity was negatively correlated with upper-body subcutaneous fat (triceps and subscapular skinfolds) but not correlated with subcutaneous abdominal fat in OSAS patients. In multivariate analyses using all patients, the apnea-hypopnea index remained a significant independent predictor of aerobic capacity after controlling for a variety of potential confounders including body mass index. Our data confirm that central obesity (subcutaneous abdominal fat) is prominent in patients with OSAS. Our results suggest that lower aerobic exercise capacity in patients with OSAS might be due to daily physical activity that is restricted by OSA itself. This study also suggests that the degree of subcutaneous abdominal fat cannot be used for predicting aerobic capacity level. We think that upper-body subcutaneous fat might be suitable for determining the physical fitness of patients with OSAS.


Recognition of illness associated with exposure to chemical agents--United States, 2003.
Since September 11, 2001, concern has increased about potential terrorist attacks involving the use of chemical agents. In addition, recent cases involving intentional or inadvertent contamination of food with chemicals have highlighted the need for health-care providers and public health officials to be alert for patients in their communities who have signs and symptoms consistent with chemical exposures. For example, in February 2003, a Michigan supermarket worker was charged with intentionally contaminating 200 lbs. of meat with a nicotine-containing insecticide. Although intentional release of chemical agents might be an overt event (i.e., one whose nature reveals itself), such as release of a nerve agent in a subway or a large explosion of a chemical container, a chemical release might instead be a covert event (i.e., an unrecognized release in which the presence of ill persons might be the first sign of an exposure), such as deliberate contamination of food, water, or a consumer product. To increase the likelihood that health-care providers will recognize a chemical-release-related illness and that public health authorities will implement the appropriate emergency response and public health actions, CDC identified examples of chemical-induced illness and created appropriate guidance for health-care providers and public health personnel. This report summarizes the epidemiologic clues and clinical signs or patterns of illness that might suggest covert release of a chemical agent. CDC is working to develop national surveillance capabilities for detecting chemical-release-related illnesses.


QTL Mapping for Yield and Resistance against Mediterranean Corn Borer in Maize.
Introduction: The Mediterranean corn borer (MCB), Sesamia nonagrioides, is a major pest of maize, Zea mays, in Mediterranean countries, inflicting significant kernel yield losses. For that reason, it necessary to know the genetic mechanisms that regulate the agronomic and resistance traits. A quantitative trait loci (QTL) mapping study for yield, resistance against MCB attack, and other relevant agronomic traits was performed using a recombinant inbred line (RIL) population derived from the cross A637 × A509 that is expected to segregate for yield, and ear, and stalk resistance to MCB. 171 RILs were evaluated in 2014 and 2015 at Pontevedra, Spain, along with the two parental inbreds A637 and A509 using a 13 × 14 single lattice design with two replications. A genetic map with 285 SNP markers was used for QTL analysis. Our objectives were to detect QTL for resistance to MCB and tolerance-related agronomic traits, to gain insights on the genetic relationship between resistance to MCB attack and yield, and to establish the best way for simultaneously improving yield and resistance to MCB. Results: Twelve significant QTL were detected for agronomic and resistance traits. QTL at bins 1.10 and 5.04 were especially interesting because the same allelic variant at these QTL simultaneously improved yield and insect resistance. In contrast, in the region 8.04-8.05, QTL showed opposite effects for yield and resistance. Several QTL for indexes which combine yield and resistance traits were found especially in the region 10.02-10.03. Conclusions: Selecting genotypes with the favorable allele of QTL on chromosome 5 (bin 5.01) will decrease tunnel length without affect yield, silking and plant height and QTL on the region 5.04 could be used to improve stalk resistance and yield simultaneously. An allele of QTL on bin 9.07 will increase ear resistance to MCB attack but it could produce later varieties while favorable allele in region 1.10 could improve ear and stalk resistance and yield without secondary negative effects. The region 8.03-8.05 mainly but also the region 10.02-10.03 and 5.04 may play an important role to elucidate the association between yield, other agronomic traits and MCB resistance.


Ghrelin receptor gene polymorphisms are associated with female metabolic syndrome in Chinese population.
The ghrelin plays an important role in the regulation of food intake and energy homeostasis. Therefore, the ghrelin receptor gene (GHSR) is an excellent candidate for studying metabolic syndrome. This study aimed to investigate whether polymorphisms in ghrelin receptor gene are associated with metabolic syndrome in Chinese population. Subjects consisted of 698 patients aged 41 to 80 years, diagnosed as metabolic syndrome by International Diabetes Federation (IDF) 2005 criteria, and 762 age- and gender-matched controls. Three variants within the GHSR were selected and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Odds ratios were estimated using a case-control study design by controlling confounding factors. The A/A genotype (rs2922126) in the promoter was associated with metabolic syndrome (OR 1.41, 95% CI 1.03-1.94), increased waist circumference (OR 1.75, 95% CI 1.26-2.42), and increased fast blood glucose (OR 1.49, 95% CI 1.07-2.06) in women. The A/A genotype (rs509030) in the intron was associated with lower plasma high density lipoprotein in women (OR 1.37, 95% CI 1.02-1.84). The polymorphisms within GHSR might be a genetic risk factor for metabolic syndrome in women.


Eosinophil Cationic Protein (ECP), a predictive marker of bullous pemphigoid severity and outcome.
Bullous Pemphigoid (BP) is an inflammatory rare autoimmune bullous dermatosis, which outcome cannot be predicted through clinical investigations. Eosinophils are the main immune infiltrated cells in BP. However, the release of Major Basic Protein (MBP), Eosinophil Derived Neurotoxin (EDN), and Eosinophil Cationic Protein (ECP) upon eosinophil activation has still not been evaluated with respect to BP development. MBP, EDN and ECP were measured by ELISA in serum (n = 61) and blister fluid (n = 20) of patients with BP at baseline, and in serum after 2 months of treatment (n = 41). Eosinophil activation in BP patients was illustrated at baseline by significantly higher MBP, EDN and ECP serum concentrations as compared with control subjects (n = 20), but without distinction according to disease severity or outcome. EDN and ECP values were even higher in the blister fluids (P < 0.01 and P < 0.05, respectively), whereas MBP values were lower (P < 0.001). ECP serum concentration decreased after 60 days of treatment in BP patients with ongoing remission but not in patients who later relapsed (P < 0.05). A reduction of at least 12.8 ng/mL in ECP concentrations provided a positive predictive value for remission of 81%, showing that ECP serum variation could be a useful biomarker stratifying BP patients at risk of relapse.


Forceps delivery after two previous Caesarean sections.
Caesarean section is one of the most frequently performed surgical procedures in current obstetric practice. There are several reasons for this upward tendency, including well developed hemotherapy, anesthesia, antibiotic treatment and skilled doctors. Despite such risks as uterine rupture, necessity of blood transfusion or the possibility of the necessity of ending the delivery by means of surgery, it is possible, in justified cases, to attempt spontaneous labor. A decision jointly made by the patient and her doctor, based on careful consideration of benefits and risks, as well as positive attitude on the woman's part may lead to positive outcome of labor. Taking the above factors into account we have decided to present a study of a difficult, operational labor after two Caesarean sections.


Factors associated with postoperative complications and 1-year mortality after surgery for colorectal cancer in octogenarians and nonagenarians.
To identify the factors affecting 30-day postoperative complications and 1-year mortality after surgery for colorectal cancer in octogenarians and nonagenarians. Between 2005 and 2014, a total of 204 consecutive patients aged ≥80 years who underwent major colorectal surgery were included. One hundred patients were male (49%) and 52 patients had American Society of Anesthesiologists (ASA) score ≥3 (25%). Combined surgery was performed in 32 patients (16%). Postoperative complications within 30 days after surgery occurred in 54 patients (26%) and 30-day mortality occurred in five patients (2%). Independent risk factors affecting 30-day postoperative complications were older age (≥90 years, hazard ratio [HR] with 95% confidence interval [CI] =4.95 [1.69-14.47], P=0.004), an ASA score ≥3 (HR with 95% CI =4.19 [1.8-9.74], P=0.001), performance of combined surgery (HR with 95% CI =3.1 [1.13-8.46], P=0.028), lower hemoglobin level (<10 g/dL, HR with 95% CI =7.56 [3.07-18.63], P<0.001), and lower albumin level (<3.4 g/dL, HR with 95% CI =3.72 [1.43-9.69], P=0.007). An ASA score ≥3 (HR with 95% CI =2.72 [1.15-6.46], P=0.023), tumor-node-metastasis (TNM) stage IV (HR with 95% CI =3.47 [1.44-8.39], P=0.006), and occurrence of postoperative complications (HR with 95% CI =4.42 [1.39-14.09], P=0.012) were significant prognostic factors for 1-year mortality. Patient-related factors (older age, higher ASA score, presence of anemia, and lower serum albumin) and procedure-related factors (performance of combined surgical procedure) increased postoperative complications. Avoidance of 30-day postoperative complications may decrease 1-year mortality.


Neurological Soft Signs in Schizophrenia: An Update on the State- versus Trait-Perspective.
Neurological soft signs (NSS) represent minor neurological signs, which indicate non-specific cerebral dysfunction. In schizophrenia, their presence has been documented extensively across all stages of the disease. Until recently, NSS were considered an endophenotype or a trait phenomenon. During the past years, however, researchers report fluctuations of the NSS scores. To further clarify the question whether NSS exhibit state or trait components or both, studies that have investigated NSS longitudinally were reviewed. Studies which have assessed NSS longitudinally in adults suffering from schizophrenia, were searched for. The time frame was January 1966 to June 2017. Studies on teenagers were excluded because of interferences between brain maturation and pathology. Twenty-nine follow-up studies were identified. They included patients during different stages of their illness and mainly used established instruments for NSS assessment. Patients with a first episode or a remitting course predominantly show a decrease of NSS over time, whereas a worsening of NSS can be found in the chronically ill. It was shown that change of NSS total scores over time is predominantly caused by motor system subscales and to a lesser extent by sensory integration scales. With respect to medication, the majority of studies agree on a relationship between medication response and improvement of NSS while the type of antipsychotic does not seem to play a major role. Moreover, where information on side-effects is given, it does not favor a strong relationship with NSS. However, NSS seem to correlate with negative and cognitive symptoms. Studies manifest a conformity regarding the presence of NSS in schizophrenia patients on the one hand. On the other hand, fluctuations of NSS scores have been widely described in subgroups. Taken together results strongly support a state-trait dichotomy of NSS. Thus, the usage of NSS as an endophenotype has to be called into question.


Effects of chitosan and a low-molecular-weight chitosan on Bacillus cereus and application in the preservation of cooked rice.
Shrimp chitosan with 95% deacetylation and low-molecular-weight chitosan (LMWC) isolated from chitosan hydrolysate were investigated for their effects on the growth of Bacillus cereus and for use in the preservation of cooked rice. Four strains of Bacillus cereus were used: standard strain BCRC 10603 and three isolates (nos. 1 through 3) from cooked rice. The antibacterial activity of chitosan against B. cereus was greatly decreased when the reaction pH was changed from 6.0 to 7.0, but LMWC activity was less affected by this pH change. The susceptibility of B. cereus cells to chitosan decreased with increasing of cell age, in accordance with the relative electronegativity of the cell surface. B. cereus spores were more sensitive to LMWC and chitosan than were vegetative cells. Addition of 80 ppm LMWC and chitosan in sterile saline (pH 7.0) greatly reduced the D-value for the tested four strains at 90 degrees C from 30.77 to 46.51 min to 7.47 to 10.17 min and 4.68 to 7.91 min, respectively, and at 100 degrees C from 1.95 to 2.56 min to 0.89 to 0.93 min and 0.72 to 0.80 min, respectively. Addition of 2,000 ppm LMWC to raw rice water before steam cooking effectively inhibited increases in total aerobic bacteria and B. cereus in cooked rice stored at 37 and 18 degrees C.


Pharmacogenetics of dabigatran etexilate interindividual variability.
Dabigatran etexilate is given in fixed doses without coagulation monitoring for the prevention of blood clots in at risk adults. A high inter-individual variability in blood concentrations of the active metabolite of dabigatran has been reported. ABCB1 and CES1 exert an important effect in the metabolism of dabigatran etexilate and allele variants at these two loci are likely to play a pivotal role. To investigate whether screening for polymorphisms within the ABCB1 and the CES1 genes would explain a portion of the inter-individual variability in blood concentrations of the active metabolite of dabigatran. In a cohort of patients who had atrial fibrillation and on anticoagulant prophylaxis with dabigatran etexilate, we investigated whether genotypes at rs4148738 (ABCB1), rs8192935 (CES1), and rs2244613 (CES1) loci would affect plasma dabigatran trough and peak concentrations. Among 92 patients (median age: 72.0years, range: 52-92) analyzed, no clinical variable or genotype was associated with a significant difference in dabigatran peak concentrations. As for trough concentrations, in addition to creatinine clearance, and sex a significant association with the CES1 SNP rs8192935 (p=0.023) was detected. The mean adjusted plasma levels were higher among patients with the CC genotype (86.3ng/dl) than in those carrying the T allele (62.1ng/dl). No significant effect was found for the ABCB1 SNP rs4148738. The CES1 SNP rs8192935 significantly influenced the dabigatran trough concentrations and carriers of the T allele showed significantly lower concentrations than did carriers of the CC genotype.


Comparison of Ultrasonography Features and K-TIRADS for Isthmic and Lobar Papillary Thyroid Carcinomas: A Single-Center Study.
Objective: This study aimed to compare ultrasonography (US) features and the Korean-Thyroid Imaging Reporting and Data System (K-TIRADS) categories for diagnosing isthmic and lobar papillary thyroid carcinomas (PTC). Methods: From January 2009 to December 2012, 163 patients who underwent thyroid surgery and were confirmed with a post-operative histopathological diagnosis of isthmic PTC were retrospectively included. Fifty-nine patients were excluded because their tumor size was <0.5 cm or because of other reasons. The control group comprised of 145 patients who underwent thyroid surgery from January to April 2013 for a classic type of PTC, with the largest diameter being ≥ 0.5 cm and located in the thyroid lobe. A single radiologist retrospectively reviewed the US features and K-TIRADS categories of each nodule using a picture archiving and communication system. Results: Among 104 patients with isthmic PTC, 95 and 9 had primary and secondary cancers, respectively. On the other hand, all 145 patients with lobar PTC had primary cancers. Isthmic PTC showed a lower prevalence of non-parallel orientation than lobar PTC (23.1 and 71%). Nodule orientation was the only US feature statistically different between the two groups (p < 0.0001). However, there was no significant difference in patient age, sex, nodule size, composition, echogenicity, microcalcification, spiculated/microlobulated margin, and K-TIRADS category between the two groups (p > 0.05). Conclusions: K-TIRADS may be useful in the diagnosis of both isthmic and lobar PTC.


Dendritic cells fused with allogeneic hepatocellular carcinoma cell line compared with fused autologous tumor cells as hepatocellular carcinoma vaccines.
To investigate the specific antitumor responses against autologous hepatocellular carcinoma (HCC) cells of dendritic cells (DCs) fused with allogeneic HCC cell line, and evaluated the feasibility of BEL7402 as an alternative strategy to deliver shared HCC antigens to DCs. Previous studies demonstrated fusions of patient-derived DCs and autologous tumor cells could induce T-cell responses against autologous tumors. These fusion cells require patient-derived tumor cells, which are not, however, always available. Here, we report the fusing of autologous DCs with allogeneic HCC cell line to induced cytotoxic T-lymphocyte (CTL) response against autologous HCC cells compare with autologous tumor cells. These DC/ BEL7402 fusion cells co-expressed tumor-associated antigens and DC-derived costimulatory and major histocompatibility complex molecules. Both CD4+ and CD8 T+ cells were activated by the fusion cells as demonstrated by the proliferation of T-cells, the production of cytokines and the simultaneous induction of specific CTL responses. Significantly, CTL induced by dendritic cell/allogeneic BEL7402 fusion cells were able to kill autologous HCC cells by human leukocyte antigen-A2 restricted mechanisms. The results did not show significant difference between DC fusion with autologous hepatocellular carcinoma cells and DC fusion with allogeneic hepatocellular carcinoma cell line. The fusion of allogeneic HCC cell line and autologous DCs may have applications in antitumor immunotherapy through cross-priming against shared tumor antigens and may provide a platform for adoptive immunotherapy.


Phonemic segmentation of narrative speech in human cerebral cortex.
Speech processing requires extracting meaning from acoustic patterns using a set of intermediate representations based on a dynamic segmentation of the speech stream. Using whole brain mapping obtained in fMRI, we investigate the locus of cortical phonemic processing not only for single phonemes but also for short combinations made of diphones and triphones. We find that phonemic processing areas are much larger than previously described: they include not only the classical areas in the dorsal superior temporal gyrus but also a larger region in the lateral temporal cortex where diphone features are best represented. These identified phonemic regions overlap with the lexical retrieval region, but we show that short word retrieval is not sufficient to explain the observed responses to diphones. Behavioral studies have shown that phonemic processing and lexical retrieval are intertwined. Here, we also have identified candidate regions within the speech cortical network where this joint processing occurs.


SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras.
SHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function. Solving the structure of the SHANK3 N-terminal region revealed that the SPN domain is an unexpected Ras-association domain with high affinity for GTP-bound Ras and Rap G-proteins. The role of Rap1 in integrin activation is well established but the mechanisms to antagonize it remain largely unknown. Here, we show that SHANK1 and SHANK3 act as integrin activation inhibitors by sequestering active Rap1 and R-Ras via the SPN domain and thus limiting their bioavailability at the plasma membrane. Consistently, SHANK3 silencing triggers increased plasma membrane Rap1 activity, cell spreading, migration and invasion. Autism-related mutations within the SHANK3 SPN domain (R12C and L68P) disrupt G-protein interaction and fail to counteract integrin activation along the Rap1-RIAM-talin axis in cancer cells and neurons. Altogether, we establish SHANKs as critical regulators of G-protein signalling and integrin-dependent processes.


Overcoming stereotypes: nursing in 2017.
Sex kitten or battleaxe, doctor's handmaiden or angel. Nurses have faced various stereotypes over the years, especially in the mainstream media, and have endured a lack of professional respect as a result.


Analyzing changes in help-seeking from mental and physical health professionals during COVID-19 in Japan.
Japan witnessed the outbreak of coronavirus disease (COVID-19) in March - May 2020. We examined whether the impact of COVID-19 on people seeking help from mental and physical health professionals varied with changes in employment (from full-time employment to unemployment or leave of absence) and psychological predisposition to new-type depression (Interpersonal Sensitivity [IS]/Privileged Self [PS]) associated with the pandemic. An online survey was conducted in June 2020 (after the outbreak of COVID-19) among people who were full-time employees as of April 2019. Data from 1,053 individuals were analyzed. The survey asked about regular visits to health professionals one year prior to the survey (June 2019) and at the time of the survey. Employment status, personality traits, and demographic characteristics were also examined. We found that consultation rates changed little before and after the pandemic. Logistic regression analysis showed that after controlling for age and gender, being unemployed or absent from work after the pandemic and having higher scores for IS/PS were positively associated with regular visits to health professionals. Considering that COVID-19 has been shown to increase the incidence of physical and mental illness, the finding that the rate of consultations remained unchanged implies that consultations were withheld. Joblessness/absence from work and IS/PS had negative effects on physical and mental health, leading to fewer visits.


[Restless legs syndrome. Definition, cause and treatment].
Restless legs syndrome (RLS) is a common disorder affecting more than 2% of adults. RLS is characterized by sensory-motor phenomena predominantly in the legs, but other body parts may be involved. The symptoms are most pronounced during rest and present a characteristic diurnal variation with maximum symptoms in the evening and at night. The disease is often associated with periodic limb movements. RLS is present in an idiopathic and secondary form due to medical and other neurological diseases. Iron and DOPA are involved in the pathogenesis of the disease. The current best-documented treatment is partial dopamine-agonists and gabapentin.


[The new clinical picture of primary hyperparathyroidism. Diagnostic circumstances and current symptomatic characteristics. Results of a multicenter study].
Primary hyperparathyroidism (PHP) is particularly interesting at this time because of the modifications of its traditional symptoms, which have renewed the conditions of its diagnosis. This is the result of a better knowledge and consequently an increased frequency of the simple forms, mild or clearly atypical, usually expressing the initial stages of the disease which are now better detected. The relative part of the classical manifestations of the disease is therefore reduced as well. In order to verify this fact, the authors have initiated a retrospective study of 535 recent cases of PHP, over 12 years, comparing them with 322 older cases, examined and operated upon between 1954 and 1976 by P.L. Chigot. Analysis of the differences that were noted, was the subject of a statistical evaluation. The first result of this investigation is that PHP remains a disease affecting predominantly women, especially between the ages of 40 and 60 years, and beyond that age to a lesser degree. In comparing the data obtained from analyzing the circumstances of discovery of the disease and its symptoms, the most striking modification consisted in a real drop in the frequency of bony lesions. These modifications are much more rare, only exceptionally presenting their classical characteristic X-ray appearance and they only represent a factor of contingency in the clinical picture of PHP. This is probably the result of a much earlier discovery of the disease. The incidence of renal insufficiency is also remarkably low, probably for the same reason. In return, asthenia and urinary lithiasis are now the major symptoms of PHP.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunohistochemical analysis of in vivo patterns of Bcl-X expression.
The in vivo patterns of bcl-X gene expression were assessed in human and mouse tissues using an immunohistochemical approach. Polyclonal antisera were raised against synthetic peptides corresponding to amino acids 46-66 and 61-79 of the human Bcl-X protein and were shown to be specific for detection of human and mouse Bcl-X-L and Bcl-X-S proteins by immunoblotting. Bcl-X immunoreactivity was detected in a wide variety of cell types and was typically present in the cytosol in a punctate pattern suggestive of association with intracellular organelles. Among the cell types with prominent Bcl-X immunostaining were: (a) a variety of neuronal populations in the brain as well as sensory neurons in dorsal root ganglia; (b) cortical (but not medullary) thymocytes and activated lymphocytes and plasma cells in lymph nodes; (c) several types of cells in the bone marrow, including megakaryocytes, red cell precursors, and some types of differentiating myeloid cells; (d) reproductive tissues, including the spermatocytes and spermatids in the testes and germinal epithelium of the ovary; and (e) a variety of epithelial cells including mammary epithelium, the secretory epithelial and basal cells of the prostate, uterine endometrium, gastric and intestinal epithelial cells, renal tubule epithelium, and differentiated keratinocytes in the upper layers of the epidermis but not in the basal cells. In many cases, these patterns of Bcl-X expression were strikingly different from those reported previously for Bcl-2, suggesting that Bcl-X and Bcl-2 regulate cell life and death at different stages of cell differentiation through tissue-specific control of their expression.


Cholestatic jaundice caused by sequential carbimazole and propylthiouracil treatment for thyrotoxicosis.
A 36-year-old Chinese man presented to the Queen Mary Hospital in August 1999 with a 2-week history of jaundice due to propylthiouracil treatment for thyrotoxicosis. He had previously received carbimazole but had developed an urticarial skin rash after 2 weeks of treatment. The patient developed liver failure and fulminant pneumonitis shortly after hospital admission. Despite receiving treatment with broad-spectrum antibiotics and intravenous immunoglobulin, he died 11 days after the onset of the respiratory symptoms. Postmortem examination using electron microscopy showed typical glycogen bodies within the cytoplasm of the hepatocytes, which corresponded to eosinophilic cytoplasmic inclusion bodies visible under light microscopy. Immunohistochemical studies of the inclusion bodies were positive for carcinoembryonic antigen and albumin, and negative for fibrinogen, complement protein C3, immunoglobulins G, M, and A, alpha-fetoprotein, and alpha-1-antitrypsin. This is the first report of a patient who received two sequential antithyroid drugs and developed predominate cholestasis with unique histological features. Extreme caution should be taken when a patient develops allergy to one type of antithyroid drug, because cross-reactivity may develop to the other type.


Expression of the Endothelin-axis in the different histologic subtypes of renal cell carcinoma: a tissue microarray analysis.
Endothelin-1 and its receptors ETAR and ETBR, commonly referred to as the Endothelin-axis, are emerging to play a role in cancer. The Endothelin-axis has been shown to be involved in proliferation, angiogenesis and metastasis in various human tumours. To assess the role of the Endothelin-axis in renal cell carcinoma, we analysed its expression in archival tumour tissue of 183 patients. Representative tumour blocks were selected for constructing a tissue microarray. Paraffin sections were assessed immunohistochemically using monoclonal and polyclonal antibodies for Endothelin-1, ETAR and ETBR. Staining intensities were analysed semiquantitatively and the results were correlated with various histopathologic factors. Overexpression of Endothelin-1, ETAR and ETBR was identified in 12.8%, 84.1% and 93.3% of cases, respectively. No association with pathological tumour stage and histologic grading was found. Papillary renal cell carcinomas expressed highly significantly more Endothelin-1 than clear cell renal cell carcinomas (34.5% vs. 6.7%, p<0.001), while there was no difference between ETAR- and ETBR-expression in these histologic subtypes. However, ETAR tended to be overexpressed in the subgroup of G3-tumours (p=0.044). Studies are underway assessing the role of the Endothelin-axis and its potential use as a molecular target in renal cell carcinoma.


Alterations of amino acids and monoamine metabolism in male Fmr1 knockout mice: a putative animal model of the human fragile X mental retardation syndrome.
The Fragile X syndrome, a common form of mental retardation in humans, is caused by silencing the fragile X mental retardation (FMR1) gene leading to the absence of the encoded fragile X mental retardation protein 1 (FMRP). We describe morphological and behavioral abnormalities for both affected humans and Fmr1 knockout mice, a putative animal model for the human Fragile X syndrome. The aim of the present study was to identify possible neurochemical abnormalities in Fmr1 knockout mice, with particular focus on neurotransmission. Significant region-specific differences of basal neurotransmitter and metabolite levels were found between wildtype and Fmr1 knockout animals, predominantly in juveniles (post-natal days 28 to 31). Adults (postnatal days 209 to 221) showed only few abnormalities as compared with the wildtype. In juvenile knockout mice, aspartate and taurine were especially increased in cortical regions, striatum, hippocampus, cerebellum, and brainstem. In addition, juveniles showed an altered balance between excitatory and inhibitory amino acids in the caudal cortex, hippocampus, and brainstem. We detected very few differences in monoamine turnover in both age stages. The results presented here provide the first evidence that lack of FMRP expression in FMRP knockout mice is accompanied by age-dependent, region-specific alterations in neurotransmission.


[The age aspect of treatment of patient with ulcer of gastroduodenal zone].
The existent methods of treatment patient with ulcer of gastroduodenal zone provide treatment of ills in correspondence with "Standards..." and don't take into account age features of patient. For increase efficiency of treatment patient with gastric ulcer taking into account infection Helicobacter pylori, age features a patient, we conduct the treatment 612 ills using eradication therapy, laser therapy, needlereflexotherapy. We made deduction that eradicates Helicobacter pylori increases time of remission of disease. The needlereflexotherapy conducting with using our methods measures spud of cicatrisation gastric ulcer, especially in cases with the elderly ills. The laser therapy conducting with using our methods especially increases speed of cicatrisation gastric ulcer in cases with the elderly ills, too.


Periodontal inflammation in renal transplant recipients receiving everolimus or tacrolimus - preliminary results.
To compare oral health status between renal transplant recipients (RTRs) receiving tacrolimus (Tac) or everolimus (ERL) as immunosuppressive therapy. This study is a cross-sectional study. Thirty-six RTRs receiving Tac and 22 RTRs receiving ERL were included in the study. Age, gender, time since transplant and pharmacological data were recorded for both groups. Oral health status was assessed through the evaluation of teeth, periodontal parameters as well as saliva flow rate and pH. RTRs receiving ERL were older than those receiving Tac. No differences were found between groups concerning oral hygiene habits, oral symptoms, smoking habits, unstimulated and stimulated saliva flow rate and pH, clinical attachment level or the number of decayed, missing and filled teeth. However, RTRs receiving ERL presented lower visible plaque index and lower values for bleeding on probing when compared to RTRs receiving Tac. In addition, RTRs receiving ERL presented a gingival index varying from normal to moderate inflammation whereas RTRs receiving Tac presented a gingival index varying from mild to severe inflammation. RTRs receiving ERL have lower periodontal inflammation when compared to RTRs receiving Tac.


Derm Access: a new triage system to rapidly identify suspicious skin lesions.
Many screening programs have been implemented for the general population; however, dermatology appointment wait times continue to be long. Changes in scheduling would allow patients with suspicious skin lesions access to more immediate care. The objective was to introduce a method for decreasing dermatology appointment wait times to allow patients with a high-risk skin lesion to be seen in a more efficient manner. A telephone screening method was developed to allow for the most suspicious lesions to be seen within 72 hours if the patient wished to do so; appointment time slots were left open in physician schedules to accommodate these patients; and wait time, procedure, and treatment data were collected and compared against national wait time data. A total of 233 patients were seen during this study. A total of 146 of these patients were diagnosed with a cancerous or precancerous lesion. This was 63% of the total study population. The mean wait time in actual working days was 7.44 for this same period. This program substantially decreased patient anxiety, increased patient satisfaction, increased public relations for the practice, and increased public awareness of skin cancer. The Derm Access strategy can be implemented in any practice to reduce wait times for suspicious skin lesions.


An effective hybrid cuckoo search algorithm with improved shuffled frog leaping algorithm for 0-1 knapsack problems.
An effective hybrid cuckoo search algorithm (CS) with improved shuffled frog-leaping algorithm (ISFLA) is put forward for solving 0-1 knapsack problem. First of all, with the framework of SFLA, an improved frog-leap operator is designed with the effect of the global optimal information on the frog leaping and information exchange between frog individuals combined with genetic mutation with a small probability. Subsequently, in order to improve the convergence speed and enhance the exploitation ability, a novel CS model is proposed with considering the specific advantages of Lévy flights and frog-leap operator. Furthermore, the greedy transform method is used to repair the infeasible solution and optimize the feasible solution. Finally, numerical simulations are carried out on six different types of 0-1 knapsack instances, and the comparative results have shown the effectiveness of the proposed algorithm and its ability to achieve good quality solutions, which outperforms the binary cuckoo search, the binary differential evolution, and the genetic algorithm.


Possible Oxcarbazepine Inductive Effects on Aripiprazole Metabolism: A Case Report.
Oxcarbazepine is a cytochrome P450 (CYP) 3A4 inducer, which is structurally similar to carbamazepine. Although lacking Food and Drug Administration approval, oxcarbazepine is sometimes prescribed to treat aggressive behavior in youth with autism spectrum disorder (ASD). These youths may also be taking second-generation antipsychotics, some of which are substrates of the CYP3A4 metabolic pathway. The combination of these medications may result in decreased serum antipsychotic concentrations, potentially reducing effectiveness. A limited number of reports are available which discuss reduced atypical antipsychotic concentrations secondary to oxcarbazepine CYP3A4 induction. We report a young boy taking oxcarbazepine (1200 mg/d) who presented with an unexpectedly low serum aripiprazole concentration. Utilizing therapeutic drug monitoring, pharmacogenetic testing, and a tool to evaluate drug-drug interactions, we estimate that oxcarbazepine possibly reduced his serum aripiprazole concentration by 68%. Our report is important, as it is the first to describe a drug-drug interaction between oxcarbazepine and aripiprazole. This report should encourage the completion of in vitro and clinical studies and the publication of case reports describing the possible inductive effects of oxcarbazepine on atypical antipsychotics (including cariprazine, lurasidone, quetiapine, aripiprazole, brexpiprazole, iloperidone, and risperidone) mediated by induction of the CYP3A4 metabolic pathway.


Mutation analysis of 272 Spanish families affected by autosomal recessive retinitis pigmentosa using a genotyping microarray.
Retinitis pigmentosa (RP) is a genetically heterogeneous disorder characterized by progressive loss of vision. The aim of this study was to identify the causative mutations in 272 Spanish families using a genotyping microarray. 272 unrelated Spanish families, 107 with autosomal recessive RP (arRP) and 165 with sporadic RP (sRP), were studied using the APEX genotyping microarray. The families were also classified by clinical criteria: 86 juveniles and 186 typical RP families. Haplotype and sequence analysis were performed to identify the second mutated allele. At least one-gene variant was found in 14% and 16% of the juvenile and typical RP groups respectively. Further study identified four new mutations, providing both causative changes in 11% of the families. Retinol Dehydrogenase 12 (RDH12) was the most frequently mutated gene in the juvenile RP group, and Usher Syndrome 2A (USH2A) and Ceramide Kinase-Like (CERKL) were the most frequently mutated genes in the typical RP group. The only variant found in CERKL was p.Arg257Stop, the most frequent mutation. The genotyping microarray combined with segregation and sequence analysis allowed us to identify the causative mutations in 11% of the families. Due to the low number of characterized families, this approach should be used in tandem with other techniques.


Pharmacoeconomics of influenza vaccination for healthy working adults: reviewing the available evidence.
A favourable pharmacoeconomic profile has been well established for influenza vaccination in the elderly. For employers relevant benefits seem to exist for vaccinating healthy working adults to avert absenteeism and related production losses. From a pharmacoeconomic point of view it is relevant to consider whether societal benefits of vaccination for healthy working adults is worthwhile given the costs of vaccination for the community. We searched Medline and Embase using the key words influenza (vaccination) in combination with cost, cost-benefit, cost-effectiveness, efficiency, economic evaluation, health-policy and pharmacoeconomics. From this primary search, we selected 11 studies concerned with the group of healthy working adults. We reviewed these studies according to several criteria: benefit-to-cost (B/C) ratio;vaccine effectiveness, influenza incidence, number of days of work absence due to illness; and relative cost of the vaccine. Three studies on vaccinating healthy working adults found costs exceeding the benefits (B/C-ratio <1). The remaining eight pharmacoeconomic studies found a B/C-ratio of almost two or more. Cost savings are strongly related to the inclusion of indirect benefits related to averted production losses. After exclusion of indirect costs and benefits of production gains/losses, only one of the eight studies remains cost saving. Considering the available pharmacoeconomic evidence, vaccination of healthy working adults in Western countries may be an intervention with favourable cost-effectiveness and cost-saving potentials if indirect benefits of averted production losses are included. Excluding indirect benefits and costs of production losses/gains, cost-saving potentials are limited. Recent international guidelines for pharmacoeconomic research advise the inclusion of production gains and losses in the preferred societal perspective. Hence, on the basis of the available evidence, influenza vaccination of healthy working adults may be recommended from pharmacoeconomic point of view. Pharmacoeconomics do, however, present only one argument for consideration aside from ethical issues, budgetary limits and psychosocial aspects.


Catalytic depolymerization of Kraft lignin to high yield alkylated-phenols over CoMo/SBA-15 catalyst in supercritical ethanol.
Lignin is generally considered to be a renewable and sustainable resource of aromatic chemicals. However, the depolymerization of Kraft lignin (KL) for the production of selective phenolic monomers presents a significant challenge due to its highly recalcitrant nature. Therefore, in this work, we investigated the effect of metal sites and acid active sites on Mo/SBA-15, Co/SBA-15 and CoMo/SBA-15 catalysts in supercritical ethanol for the depolymerization of KL to produce phenolic monomers. Ethanol was used as a hydrogen donor solvent instead of using external hydrogen. Results showed that the bimetallic CoMo/SBA-15 catalyst exhibited significantly higher catalytic activity compared to the monometallic, Co/SBA-15, Mo/SBA-15 or bare SBA-15. The highest phenolic monomers yield of 27.04 wt% was achieved at 290 °C for 4 h over CoMo/SBA-15 catalyst. The inter-unit linkages such as β-O-4', β-β and α-O-4' in lignin were considerably cleaved during the catalytic depolymerization in supercritical ethanol. Meanwhile, higher functionality of carbonyl compounds was present in the non-catalytic bio-oil, while more alkylated phenols were produced over CoMo/SBA-15 catalyst. The major phenolic monomers identified in the catalytic bio-oil were 4-ethylguaiacol (9.15 wt%), 4-methylguaiacol (6.80 wt%), and 4-propylguaiacol (2.85 wt%). These findings suggest that the metal sites and abundant acid active sites of CoMo/SBA-15 had a synergistic effect toward the degradation of different linkages of lignin and production of selective phenolic monomers in bio-oils.


When disaster strikes.
In response to the healthcare issues resulting from Hurricane Katrina, The Nurse Practitioner has compiled information from the Centers for Disease Control and Prevention (CDC) to educate nurse practitioners (NPs) about previously uncommon illnesses presenting in the wake of the disaster, CDC recommendations on immunizations and infection prevention, and guidelines for providing proper wound care. Visit http://www.cdc.gov for full text of these articles.


Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics.
The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates. The heterogeneous solid state catalyst (Fe (III) Y-Zeolite) could effectively catalyze the reaction to obtain the product with high yield and short reaction time. The synthesized compounds (5a-5p) were analyzed by NMR, FTIR and HRMS analysis. Compound 5c was confirmed by single crystal XRD studies. All the compounds were biologically evaluated for their potential inhibitory effect on anticancer (MCF-7, Hep-2) and microbial (MRSA, MTCC 201 and FRCA) activities. Among the compounds 5i exhibited the highest levels of inhibitory activity against both MCF-7, Hep-2 cell lines. Furthermore, the compound 5i (BPP) was evaluated for DNA fragmentation, flow cytometry studies and cytotoxicity against MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. In addition, molecular docking (PDB ID: 1T46) studies were performed to predict the binding affinity of ligand with receptor. Moreover, the synthesized BPP compound was loaded in to the PHB-PCL nanofibrous scaffold to check the cytotoxicity against the MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. The in vitro apoptotic potential of the PHB-PCL-BPP nanofibrous scaffold was assessed against MCF-7, Hep-2 cancerous cells and fibroblast cells at 12, 24 and 48h respectively. The nanofibrous scaffold with BPP can induce apoptosis and also suppress the proliferation of cancerous cells. We anticipate that our results can provide better potential research in nanomaterial based cancer research.


[Response to neoadjuvant chemotherapy in breast cancer as assessed by subtype].
The aim of this study was to investigate the responses to neoadjuvant chemotherapy (NAC) in breast cancer according to subtype. The study included 69 women who received NAC at our hospital between January 2004 and January 2013. Complete response( CR) was achieved in 14 patients( 20.3%) and partial response( PR) was achieved in 37 patients (53.6%).CR and PR rates according to subtype were as follows: 0% and 57.1% for the luminal type, 0% and 66.7% for the luminal-human epidermal growth factor receptor (HER)-2 type, 16% and 56% for the triple negative type, and 58.8% and 41.2% for the HER2 type, respectively. The CR rate was the highest among patients with HER2-type breast cancer. Trastuzumab was additionally administered to 12 patients with HER2-type breast cancer, and the CR rate among these patients was significantly higher after trastuzumab treatment( 75%).Thus, it is important to select a treatment strategy for breast cancer on the basis of the subtype diagnosed.


A recombinant TGF-β1 vaccine ameliorates diabetic nephropathy in OLETF rats.
The aim of this study was to investigate the potential of a recombinant vaccine encoding TGF-β1 in OLETF rats with diabetic nephropathy (DN). OLETF rats were treated with vehicle or TGF-β1 vaccine. LETO rats were used as normal controls. At 42 weeks after immunization with vaccine, samples from blood, urine and kidney were collected for biochemical, histologic, immunohistochemical and molecular analyses. OLETF rats treated with the vaccine reduced blood glucose levels, improved renal pathological changes, and inhibited overexpression of TGF-β1 and p-Smad3, as well as MCP-1, TNF-α and IL-1β. TGF-β1 vaccine attenuated diabetic nephropathy in OLETF rats through reduction of inflammation, improvement of kidney fibrosis and partial correction of glucose metabolism.


China's experiences in the quality control of its 1982 population census.
The author reports on experiences with China's 1982 census, which covered approximately one billion people and 19 census items. It is noted that "the postenumeration sample survey indicates that the quality of the census enumeration is: 0.071% of overcounts and 0.056% of undercounts. The paper presents principles governing quality control in the population census and explains a series of quality control procedures adopted to reduce possible errors originating in census planning, enumeration and data processing."


[Scientific rationality, causality and meta-analyses of clinical trials].
Currently, the challenge is to analyze and synthesize as much information as possible in order to make quick, correct decisions. Systematic reviews and meta-analysis have quickly arisen in the health field because they allow researchers to congregate studies of similar characteristics to generate estimators that describe the risk or benefit of practices related to health problems. To understand and attach the appropriate importance to meta-analyses, it is necessary to consider the rationale of the theoretical framework, the methodological criteria, and the possible causal relationship between exposure and outcome, besides contextualizing the information. This paper briefly explores scientific rationality and its application in causal theory within an epidemiological framework, to set the basis that allows decision-makers and health professionals to evaluate the appropriateness and validity of conclusions derived from this type of analyses.


Relationship Between Plasma Vitamin C and COVID-19 Susceptibility and Severity: A Two-Sample Mendelian Randomization Study.
Considering the antioxidant function of Vitamin C, also called ascorbic acid, it is widely used against viral infections such as coronavirus disease (COVID-19) based on in vitro, observational, and ecological studies. Many confounding factors that can affect Vitamin C levels. Thus, the association described to date may not be causal. To determine the causal relationship between genetically predicted plasma Vitamin C and COVID-19 susceptibility and severity, we performed two-sample Mendelian randomization (MR) based on large samples. The summary-level data for Vitamin C was obtained from a GWAS meta-analysis, which included 52,018 individuals from four studies of European ancestry. Data for COVID-19 HGI results were obtained from the meta-analysis of 35 GWASs with more than 1,000,000 subjects of European ancestry, including 32,494 cases with COVID-19 susceptibility and 1,316,207 controls, 9,986 cases with COVID-19 hospitalization and 1,877,672 controls, and 5,101 cases with COVID-19 severe disease and 1,383,241 controls. Mendelian randomization (MR) analysis was conducted to examine the effect of selected single nucleotide polymorphisms and COVID-19 susceptibility, hospitalization, disease severity. Several sensitivity analyses were performed with inverse-variance weighted (random-effect model), inverse variance weighted (fixed-effect model), weighted median, and maximum likelihood methods for estimating the causal effects. In this MR study, genetic predisposition to the levels of plasma Vitamin C was not associated with COVID-19 susceptibility (OR: 0.99, 95% CI: 0.84-1.17, P = 0.91), hospitalization (OR: 1.10, 95% CI: 0.71-1.71, P = 0.67) and severity (OR: 0.83, 95% CI: 0.43-1.59, P = 0.58). The association was consistent in complementary analyses. No potential heterogeneities and directional pleiotropies were observed for the analysis results. According to our study, no correlation was observed between plasma Vitamin C levels and COVID-19 susceptibility and severity. Further studies in different ethnics are necessary to explore the potential role and mechanisms of circulating serum Vitamin C levels on COVID-19.


Undergraduate nursing students' experiences of practicing caring behaviours with standardised patients.
Undergraduate nursing students' learning opportunities to practice caring behaviours to assure compassionate and competent nursing practice with standardised patients are few. Earlier studies primarily focused on practicing communication skills in relation to mental health or developing psychomotor skills while caring for a patient with a specific diagnosis. The study aim was to describe undergraduate nursing students' experiences of practicing caring behaviours with a standardised patient. A sample of forty-eight undergraduate nursing students in semester four at a school of nursing in southern Sweden, enrolled in a full-time, 5-week, on-campus elective caring behaviour course, were at the first and last week individually video-recorded during two caring behaviour simulations encountering a standardised patient. After observing each of their video-recordings, students completed written reflections focusing on their own compassionate and competent verbal and nonverbal caring behaviour. In total, 96 individual written reflections were analysed using qualitative content analysis to describe the experience. One main theme emerged: The challenge of being mindfully present in patient encounters. Four themes further described the experience: A challenging but realistic learning experience, learning the impact of nonverbal behaviour, recognising the complexity of verbal behaviour, and learning to be with the patient instead of only doing for the patient. When caring is intertwined with visible and realistic nursing practice in simulations using standardised patients it facilitates undergraduate nursing students learning compassionate and competent caring behaviour. The learning experience opened the students' eyes to the impact of practicing caring, recognising that being with is not the same as doing for the patient, and thus, how challenging it is to be mindfully present in patient encounters. Designing caring behaviour simulations with standardised patients is a feasible and efficacious educational learning didactic to facilitate students' learning caring behaviour and enhancing patients' experiences.


Hong Kong's domestic health spending--financial years 1989/90 through 2004/05.
This report presents the latest estimates of Hong Kong's domestic health spending between fiscal years 1989/90 and 2004/05, cross-stratified and categorised by financing source, provider and function on an annual basis. Total expenditure on health was HK$67,807 million in fiscal year 2004/05. In real terms, total expenditure on health showed positive growth averaging 7% per annum throughout the period covered in this report while gross domestic product grew at 4% per annum on average, indicating a growing percentage of health spending relative to gross domestic product, from 3.5% in 1989/90 to 5.2% in 2004/05. This increase was largely driven by the rise in public spending, which rose 9% per annum on average in real terms over the period, compared with 5% for private spending. This represents a growing share of public spending from 40% to 55% of total expenditure on health during the period. While public spending was the dominant source of health financing in 2004/05, private household out-of-pocket expenditure accounted for the second largest share of total health spending (32%). The remaining sources of health finance were employer-provided group medical benefits (8%), privately purchased insurance (5%), and other private sources (1%). Of the $67,807 million total health expenditure in 2004/05, current expenditure comprised $65,429 million (96%) while $2378 million (4%) were capital expenses (ie investment in medical facilities). Services of curative care accounted for the largest share of total health spending (67%) which were made up of ambulatory services (35%), in-patient curative care (28%), day patient hospital services (3%), and home care (1%). The next largest share of total health expenditure was spent on medical goods outside the patient care setting (10%). Analysed by health care provider, hospitals accounted for the largest share (46%) and providers of ambulatory health care the second largest share (30%) of total health spending in 2004/05. We observed a system-wide trend towards service consolidation at institutions (as opposed to free-standing ambulatory clinics, most of which are staffed by solo practitioner). In 2004/05, public expenditure on health amounted to $35,247 million (53.9% of total current expenditure), which was mostly incurred at hospitals (76.5%), whilst private expenditure ($30,182 million) was mostly incurred at providers of ambulatory health care (54.6%). This reflects the mixed health care economy of Hong Kong where public hospitals generally account for about 90% of total bed-days and private doctors (including Western and Chinese medicine practitioners) provide 75% to 80% of out-patient care. While both public and private spending were mostly expended on personal health care services and goods (92.9%), the distributional patterns among functional categories differed. Public expenditure was targeted at in-patient care (54.2%) and substantially less on out-patient care (24.5%), especially low-intensity first-contact care. In comparison, private spending was mostly concentrated on out-patient care (49.6%), whereas medical goods outside the patient care setting (22.6%) and in-patient care (18.8%) comprised the majority of the remaining share. Compared to OECD countries, Hong Kong has devoted a relatively low percentage of gross domestic product to health in the last decade. As a share of total spending, public funding (either general government revenue or social security funds) was also lower than in most comparably developed economies, although commensurate with its public revenue collection base.


[Quantification of acetabular coverage in normal adult].
Quantification of acetabular coverage is important and can be expressed by superimposition of cartilage tracings on the maximum cross-sectional area of the femoral head. A practical Autolisp program on PC AutoCAD has been developed by us to quantify the acetabular coverage through numerical expression of the images of computed tomography. Thirty adults (60 hips) with normal center-edge angle and acetabular index in plain X ray were randomly selected for serial drops. These slices were prepared with a fixed coordination and in continuous sections of 5 mm in thickness. The contours of the cartilage of each section were digitized into a PC computer and processed by AutoCAD programs to quantify and characterize the acetabular coverage of normal and dysplastic adult hips. We found that a total coverage ratio of greater than 80%, an anterior coverage ratio of greater than 75% and a posterior coverage ratio of greater than 80% can be categorized in a normal group. Polar edge distance is a good indicator for the evaluation of preoperative and postoperative coverage conditions. For standardization and evaluation of acetabular coverage, the most suitable parameters are the total coverage ratio, anterior coverage ratio, posterior coverage ratio and polar edge distance. However, medial coverage and lateral coverage ratios are indispensable in cases of dysplastic hip because variations between them are so great that acetabuloplasty may be impossible. This program can also be used to classify precisely the type of dysplastic hip.


Death from axillary haemorrhage during haemodialysis in a patient with a history of microscopic polyangiitis.
An older female with a history of microscopic polyangiitis underwent haemodialysis through an end-to-side anastomosis between the left basilica vein and brachial artery. During the last haemodialysis session, repeated punctures induced haemorrhage that required brachial compression. Twenty min posthaemodialysis, haemorrhage had expanded from the axilla to the left lateral thorax. Autopsy disclosed axillary haematoma. The haemorrhage was not derived from punctured vessels or the left axillary artery. Although neither an alveolar nor a glomerular microscopic polyangiitis lesion was detected, fragility of the axillary small vessels due to microscopic polyangiitis, ageing, atherosclerosis and steroid therapy were underlying factors in the haematoma. Aspirin and heparin may have promoted haemorrhage, while shunt vessel stenosis with disturbed flow may have increased the axillary vessel pressure when the shunt vessels were compressed for haemostasis. This is the first report of a death due to haemorrhage from ruptured axillary vessels related to haemodialysis or microscopic polyangiitis.


Nano-Silica Sol-Gel and Carbon Nanotube Coupling Effect on the Performance of Cement-Based Materials.
Carbon nanotubes (CNTs) have shown promise for improving the mechanical performance of cement composites through crack-bridging and frictional pull-out. The interactive behaviors between CNTs and cement matrix act are crucial in optimizing the reinforcement of CNTs in cement composites. This study investigates the effects of nano-silica (NS) sol-gel on the interactive behaviors of CNTs and the cement matrix through a series of experiments and analyses. UV-visible spectrometer results show that CNTs are well-dispersed in suspension and the addition of NS has a negligible effect on the stability of CNT dispersion. Calorimetry tests and dynamic mechanical analysis demonstrate the nucleation and frictional performance of CNTs in cement matrix, respectively. The paper shows that the physical adsorption of NS on the CNT surface could result in the acceleration of cement hydration. Morphology observation confirms that a denser interface between CNTs and cement hydrates is formed. Finally, the improved interaction between CNTs and cement hydrates leads to a substantial increase in friction between CNTs and the cement matrix under periodic loading. NS may act as an ideal admixture for improving both the interactive behaviors between CNTs and cement matrix and the damping properties of cement composite.


A functional Notch-survivin gene signature in basal breast cancer.
Basal-type, or triple-negative, breast cancer (lacking estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression) is a high-risk disease for which no molecular therapies are currently available. We studied genetic signatures of basal breast cancer potentially suitable for therapeutic intervention. We analyzed protein expression of the Notch-1 intracellular domain and survivin by immunohistochemistry in a series of basal breast cancer patients. A hierarchical clustering and overall survival analysis was carried out on a microarray mRNA database of 232 breast cancer patients. Fifteen published mRNA datasets containing estrogen receptor-negative or estrogen receptor-positive samples were subjected to meta-analysis for co-segregated gene expression. Experiments of plasmid transfection and gene silencing were carried out in estrogen receptor-negative MDA-MB-231 breast cancer cells. The developmental signaling regulator Notch-1 was highly expressed in breast cancer, compared with normal tissue, and was segregated with basal disease. Higher Notch-1 levels correlated with progressively abbreviated overall survival, and with increased expression of survivin, a tumor-associated cell death and mitotic regulator implicated in stem cell viability. Analysis of Pearson's correlation coefficient indicated that Notch-1 and survivin co-segregated in basal breast cancer. Notch-1 stimulation in MDA-MB-231 cells increased survivin expression, whereas silencing Notch reduced survivin levels. A Notch-1-survivin functional gene signature is a hallmark of basal breast cancer, and may contribute to disease pathogenesis. Antagonists of Notch and survivin currently in the clinic may be tested as novel molecular therapy for these recurrence-prone patients.


Increased expression and possible role of chitinase 3-like-1 in a colitis-associated carcinoma model.
To investigate the possible role of chitinase 3-like-1 (CHI3L1) in the progression of colitis-associated carcinoma (CAC). Thirty-four Balb/c mice were randomly assigned to five groups, including the control, CAC control, CAC + caffeine, colitis control and colitis + caffeine. Three animals were sacrificed every two weeks for blinded macroscopic inspection, histological analysis, and total RNA extraction. An immunofluorescent assay was performed using specimens from the colitis control and colitis + caffeine groups to investigate whether the protective effect of caffeine was associated with less oxidative DNA damage. In vitro, HT29 cells pre-stimulated with different concentrations of recombinant CHI3L1 protein and H2O2 were loaded with the DCFH-DA fluorescent probe to determine the effect of CHI3L1 on intracellular reactive oxygen species production. CHI3L1 mRNA was increased during the progression of colon carcinogenesis. Tumors were mostly located in the distal end of the colon where the expression of CHI3L1 was higher than in the proximal colon. Caffeine-treated mice developed fewer tumors and milder inflammation than untreated mice. CHI3L1 protein increased reactive oxygen species in HT29 cells when exposed to H2O2. Caffeine reduces tumor incidence by decreasing oxidative DNA damage. CHI3L1 may contribute to CAC by increasing reactive oxygen species production.


The impact of aging and habitual physical activity on static respiratory work at rest and during exercise.
We investigated the effects of aging on the elastic properties of lung tissue and the chest wall, simultaneously quantifying the contribution of each component to static inspiratory muscle work in resting and exercising adults. We further evaluated the interaction of aging and habitual physical activity on respiratory mechanics. Static lung volumes and elastic properties of the lung and chest wall (pressure-volume relaxation maneuvers) in 29 chronically sedentary and 29 habitually active subjects, grouped by age, were investigated: young (Y, 20-30 years), middle-aged (M, 40-50 years), and older (O, >60 years). Using static pressure-volume data, we computed the elastic work of breathing (joules per liter, J.l(-1)), including inspiratory muscle work, over resting and exercising tidal volume excursions. Elastic work of the lung (Y = 0.79 +/- 0.05; M = 0.47 +/- 0.05; O = 0.43 +/- 0.05 J.l(-1)) and chest wall (Y = -0.49 +/- 0.06; M = -0.12 +/- 0.07; O = 0.04 +/- 0.05 J.l(-1) ) changed significantly with age (P < 0.05). With aging, a parallel displacement of the chest wall pressure-volume curve resulted in a shift from energy being stored primarily during expiration to energy storage during inspiration, and driving expiration, both at rest and during exercise. Although deviating significantly from young adults, this did not significantly elevate static inspiratory muscle work but resulted in a redistribution of the tissues on which this work was performed and the phase of the respiratory cycle in which it occurred. Nevertheless, static inspiratory muscle work remained similar across age groups, at rest and during exercise, and habitual physical activity failed to influence these changes.


Pharmacodynamics and pharmacokinetics of an infusion of Org 9487, a new short-acting steroidal neuromuscular blocking agent.
We have evaluated in 10 anaesthetized patients the time course of action, infusion requirements, reversibility and pharmacokinetics of Org 9487. Org 9487 was administered as a bolus dose of 1.5 mg kg-1, followed by an infusion to maintain a block of 75-85% for 60 min. After recovery from the bolus dose, a mean dose of Org 9487 3.4 (SD 1.0) mg kg-1 h-1 was administered to maintain a mean neuromuscular block of 83 (3)%. During the final 15 min of infusion, the infusion requirements were 2.5 (1.1) mg kg-1 h-1. In the five patients who were allowed to recover spontaneously, a TOF ratio of 0.7 was reached 37.9 (12.4) min after stopping the infusion of Org 9487. In the five patients who received neostigmine, a TOF ratio of 0.7 was reached after 14.5 (6.1) min. Plasma clearance was 8.5 (30%) ml kg-1 min-1. Volume of distribution at steady state was 293 (55%) ml kg-1. Terminal half-life and mean residence time were 71.7 (34%) and 33.4 (31%) min, respectively. The concentration of the 3-OH metabolite remained relatively low. Urinary excretion of Org 9487 and its metabolites was 22% in 24 h. In conclusion, a 1-h infusion of the short-acting drug Org 9487 changed its time course characteristics gradually from that of a short-acting neuromuscular blocking agent to that of a neuromuscular blocker with an intermediate duration of action.