Microbiological perspectives of co-trimoxazole.
Trimethoprim-sulfamethoxazole in vitro activity was compared with ampicillin, tetracycline, sulfonamide and trimethoprim against isolates of 24 gram-negative and 11 gram-positive species. The incidence of more than 10% of strains with minimal inhibitory concentrations above 32 mg/l was restricted to Escherichia coli, Shigella spp., Klebsiella pneumoniae, Providencia rettgeri, Morganella morganii, methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Occasionally, Streptococcus pneumoniae and Haemophilus influenzae strains with MICs above 32 mg/l were identified. Co-trimoxazole in vitro activity was superior to the comparative drugs for the majority of species. Co-trimoxazole remains an active combination against major pathogens of infections of the upper and lower respiratory, urinary tract and enteric infections with a still low incidence of resistant organisms.


(90)Y microspheres prepared by sol-gel method, promising medical material for radioembolization of liver malignancies.
A new technology for the production of radiopharmaceutical (90)Y microspheres in the form of spherical yttrium oxide grains obtained by sol-gel method has been described. The authors present and discuss the results of investigations performed in the development of new production technology of yttrium microspheres and determination of their physic-chemical properties. The final product has the structure of spherical yttrium oxide grains with a diameter 25-100μm, is stable and free from contaminants. Irradiation of 20mg samples of grains with diameter of 20-50μm in the thermal neutron flux of 1.7×10(14)cm(-2)s(-1) at the core of MARIA research nuclear reactor allowed to obtain microspheres labelled with the (90)Y isotope on the way of the nuclear reaction (89)Y(n, ɤ)(90)Y. Specific activity of irradiated microspheres has been determined by application of absolute triple to double coincidence ratio method (TDCR) and has been evaluated at 190MBq/mg Y. (90)Y microspheres prepared by the proposed technique can be regarded as a promising medical material for radioembolization of liver malignancies.


Quantitative two-dimensional echocardiography in massive pulmonary embolism: emphasis on ventricular interdependence and leftward septal displacement.
In 14 patients requiring aggressive therapy for circulatory failure resulting from massive pulmonary embolism, hemodynamic and two-dimensional echocardiographic data were obtained at bedside (acute phase) and again after circulatory improvement (intermediate phase) and during recovery. The acute stage was characterized by a low cardiac output state despite inotropic support (cardiac index 1.9 +/- 0.6 liters/min per m2) associated with increased right atrial pressure (12.4 +/- 4.2 mm Hg), increased right ventricular end-systolic and end-diastolic area (12.4 +/- 3.4 and 15.4 +/- 4.1 cm2/m2, respectively) and reduced right ventricular fractional area contraction (20.1 +/- 8.6%). Two-dimensional echocardiography also revealed interventricular septal flattening at both end-systole and end-diastole and markedly decreased left ventricular end-diastolic dimensions. Left ventricular fractional area contraction remained normal. Hemodynamic improvement occurred during the intermediate phase as shown by restoration of cardiac index (3.3 +/- 0.6 liters/min per m2), decrease in right atrial pressure (8.3 +/- 4.8 mm Hg), reduction in right ventricular end-systolic area (9.0 +/- 3.6 cm2/m2 at the intermediate stage and 6.1 +/- 1.8 cm2/m2 at recovery) and end-diastolic area (10.5 +/- 3.6 cm2/m2 at the intermediate stage and 8.9 +/- 2.9 cm2/m2 at recovery) and improvement in right ventricular fractional area contraction (31.5 +/- 16.4%). The interventricular septum progressively returned to a more normal configuration at both end-systole and end-diastole, and left ventricular diastolic dimension steadily increased. It is concluded that circulatory failure secondary to massive pulmonary embolism was mediated through a profound decrease in left ventricular preload, resulting from both pulmonary outflow obstruction and reduced left ventricular diastolic compliance.(ABSTRACT TRUNCATED AT 250 WORDS)


The behavioral pathology in Alzheimer's Disease Scale (BEHAVE-AD): factor structure among community-dwelling Alzheimer's disease patients.
The aims of this study were to (a) determine the factor structure of the Behavioral Pathology in Alzheimer's Disease Scale (BEHAVE-AD), and (b) examine the associations of the observed factors to the level of cognitive impairment. Cross-sectional study of geriatric patients evaluated at an outpatient memory disorders clinic. One hundred and fifty-one consecutive patients diagnosed with Alzheimer's disease (AD) according to NINCDS-ADRDA diagnostic criteria. Principal factors analysis with Varimax rotation resulted in a five-factor solution that accounted for 40.0% of the common variance. The factors included agitation/anxiety (agitation, anxiety of upcoming events; other anxiety), psychosis (delusions of theft, suspiciousness/paranoia; visual hallucinations), aggression (verbal aggressiveness; physical threats/violence; fear of being left alone; other delusions), depression (tearfulness; depressed mood) and activity disturbance (wandering; delusion one's house is not one's home). Several factors were associated with level of cognitive impairment as assessed by the Mini-Mental State Examination (MMSE). The results of this study suggest that the BEHAVE-AD measures a wide range of behavioral pathology that can be empirically represented by five independent symptom clusters among outpatient AD patients.


The association between eating disorders and perfectionism in adults: A systematic review and meta-analysis.
Dimensions of perfectionism are associated with the onset and maintenance of eating disorder pathology in both clinical and non-clinical samples. The aim of this study was to conduct a systematic review and meta-analysis of the association between perfectionism and eating disorders in adults. A literature search was conducted using the PsycINFO, Medline, Scopus, Embase, Web of Science and ProQuest databases. Ninety-five studies met the inclusion criteria and included a total sample of 32,840 participants (clinical eating disorder diagnosis N = 2414, non-clinical N = 30,428). Correlation coefficients (r) for the association between eating disorders and perfectionism were pooled. A meta-analysis to determine the association between two dimensions of perfectionism and eating disorder symptoms was conducted. Subgroup analyses were conducted with studies using clinical samples, and studies using the Eating Disorder Examination Questionnaire. The pooled effect size for the association between perfectionistic concerns and eating disorder symptoms was r = 0.33 [0.30, 0.37]; and r = 0.20 [0.14, 0.25] for the association between perfectionistic strivings and eating disorder symptoms. In the clinical subgroup analyses the effect sizes were r = 0.40 [0.22, 0.58]; and r = 0.35 [0.26, 0.44] respectively. Medium to high heterogeneity was identified across all subgroup analyses and a significant level of publication bias was also identified. The findings indicate both perfectionistic strivings and perfectionistic concerns have significant associations with eating disorders, and further support the argument that both dimensions of perfectionism are important factors in the prevention and treatment of eating disorders.


Generating CD8 T cell heterogeneity: attack of the clones.
Pathogen-induced inflammation modulates CD8 T cell effector and memory differentiation. In this issue of Immunity, Plumlee et al. (2013) demonstrate that clonally distinct CD8 T cells have the ability to generate numerous types of effector cell fates based on extrinsic pathogen-induced environmental cues.


Magnetic resonance imaging in the canine double-haemorrhage subarachnoid haemorrhage model.
In this study, we investigated T2 weighted imaging (T2WI) and T2 values of the cortex, thalamus and cerebrospinal fluid (CSF) of the ventricles in the canine double-haemorrhage subarachnoid haemorrhage (DHSAH) model. T2 values in the cortex increased compared to prescan values from 123.07 +/- 18.72 msec on day 2 to 89.43 +/- 1.98 msec on day 7 (p < 0.05). A trend toward a temporal increase in T2 values was observed in the thalamus, but did not reach significance. The T2 values of the ventricular CSF increased by 102.2% on day 2 and 159.6% on day 7 compared to prescan values. These changes reached significance (p < 0.05) on day 7. Additionally, the ventricular size increased over the study period. Our data suggest that we can use this model to investigate acute brain injury and normal pressure hydrocephalus (NPH) after SAH.


Spatio-temporal distribution of chlorophyll-a in relation to physico-chemical parameters in coastal waters of the northwestern Bay of Bengal.
The present study focuses on understanding the long-term distribution of physico-chemical parameters and their influence on the distribution of chlorophyll-a (chl-a) at a coastal site in the northwestern Bay of Bengal. Chl-a showed large variability (0.12 to 10.05 mg m(-3)) on a spatio-temporal scale during the study period. However, the distribution showed a similar pattern with marginal variability from March 2010 to February 2011 and March 2011 to February 2012. The vertical distribution of salinity, pH, total suspended matter (TSM) and chl-a showed systematic temporal variability. However, dissolved oxygen (DO) and nutrients (nitrite + nitrate, phosphate, silicate) did not show any significant spatio-temporal trend. Chl-a showed bimodal distribution on an annual scale, with the first peak appearing during the pre-monsoon period in March due to a seasonal phytoplankton bloom, whereas the second peak occurring during September as a result of nutrient loading from river influx due to monsoonal precipitation. Factor analysis revealed the association of low salinity and high nutrients with chl-a. This infers that the nutrients brought by the influx of river into the study area were fuelling the growth and abundance of phytoplankton. Cluster analysis resulted in two distinct clusters among all physico-chemical datasets, indicating the presence of two distinct areas separated by the 30 m isobath that were strongly influenced by physico-chemical characteristics associated with the seasonal monsoon.


Skeletal blood flow measured with 18F in patients with osteomalacia and hyperparathyroidism.
Blood flow to bone was measured using the 18F clearance method described by Wootton et al. (1976) in osteomalacia (nine cases) and primary hyperparathyroidism (eight cases). Bone blood flow was elevated above normal in the osteomalacia group and was normal in the hyperparathyroid group (range 3.6%-6.8% blood volume/min). It is suggested that bone blood flow is linked with the osteoblastic response of bone, and remains normal in cases of hyperparathyroidism when no clinical signs of bone involvement are present.


An update on the management of acute esophageal variceal bleeding.
The mortality rate in acute variceal haemorrhage remains high (around 15%). Treatment is based on the combined use of vasoactive drugs, endoscopic band ligation, and prophylactic antibiotics. Effective resuscitation (haemostasis, volume management) is essential to prevent complications. Treatment failure is best managed by transjugular intrahepatic portosystemic shunt (TIPS). Balloon tamponade or specifically designed covered oesophageal stents can be used as a bridge to definitive therapy in unstable patients. Early, pre-emptive TIPS should be the first choice in patients at high risk of treatment failure (Child-Pugh B with active bleeding or Child-Pugh C<14). This article reviews the most recent advances in the management of variceal bleeding and discusses the recent recommendations of the Baveno VI consensus conference.


Transganglionic demonstration of central sensory projections from skin and muscle with HRP-lectin conjugates.
Transganglionic transport of horseradish peroxidase (HRP) was greatly improved by conjugating the enzyme with wheat germ agglutinin (WGA) as described by Gonatas et al. [7]. Intense dorsal horn projections from muscle groups and even discrete skin patches were labeled after peripheral injection of the HRP-WGA conjugate. These projections could not be consistently demonstrated when HRP was injected either alone or in combination with DMSO. Conjugation with WGA thus enhances the uptake and/or transport of HRP and constitutes a valuable advance in HRP technique.


Telemedicine at the VA: Examining smartphone connectivity rates to VA video connect and doximity dialer video.
Telemedicine usage has accelerated as a result of the COVID-19 pandemic, raising concerns those without the necessary technology and digital literacy to participate may face increasing health disparities. In this study, we examined the rates at which veterans are able to connect to two common telemedicine applications: VA Video Connect (VVC) and Doximity Dialer Video (DV). Participants were selected from a pool of vascular surgery patients seen from August 2020 to October 2021 at a single Veterans Affairs medical center. Participants had to be >50 years old and not previously participated in a video visit. Eligible veterans were asked their interest participating in video visits and if they owned a smartphone. Those who met the eligibility requirements were tested on their ability to connect to both VVC and DV with minimal assistance. The connectivity rate for both platforms was recorded, and basic demographic and medical history information was collected. One-hundred-four veterans participated in the study, with an average age of 70 ± 7 years. Seventy-four participants (71%) expressed interest in video visits, and 52 (70%) owned a smartphone. Forty-five smartphone owners (87%) successfully connected to DV, whereas 19 (37%) successfully connected to VVC (p < 0.001). VVC connectivity decreased with increasing age-group: 50-59 = 80%, 60-69 = 44%, ≥70 = 18% (p = 0.02). Older veterans demonstrate difficulty connecting to VVC. The VHA is taking important steps to streamline usability of VVC, however continued expansion of support programs is necessary to improve access and reduce healthcare disparities in this population.


Plasma homocysteine level in cardiac syndrome X and its relation with duke treadmill score.
To investigate the plasma homocysteine level and the relationship between plasma homocysteine level and duke treadmill score (DTS) in cardiac syndrome X (CSX) patients. Seventy-nine patients (36 male, 43 female, mean age: 50 +/- 8.8 years) admitted to Gazi University Hospital, Ankara, Turkey with typical effort angina, positive stress test, and angiographically normal coronary arteries between January and September 2006 were included in this prospective and controlled study. Thirty asymptomatic patients (11 male, 19 female, mean age: 47.6 +/- 8.3 years) with 2 cardiovascular risk factors were chosen as a control group. Plasma homocysteine level was measured in both groups and DTS was calculated in the CSX group. Plasma homocysteine was measured with the AxSYM homocysteine immunoassay method in both groups. Plasma homocysteine level was higher in the CSX group compared to the control group (16.5 +/- 4.9 micromol/L, n=79, versus 12.4 +/- 4.1 micromol/L, n=30, p<0.001). The DTS was -2.7 +/- 5.3 in the CSX group. There was a negative correlation between the DTS and homocysteine levels in the CSX group. (r= -0.506, p<0.001). Plasma homocysteine level, which is known to cause endothelial dysfunction and microvascular ischemia were higher in CSX patients. Also, this increase in homocysteine level inversely correlated with the DTS, which represents the magnitude of ischemia.


A polygraphic study of bioelectrical brain maturation in preterm infants.
Bioelectrical brain maturation was studied in 26 low-risk preterm infants by serial polygraphic recordings. A modified method of visual EEG analysis was used, based on Parmelee's coding system, which allowed quantification. It gave the following results: (1) The main characteristics of EEG maturation in preterm infants were a progressive spatio-temporal differentiation, with an increase of rhythmic activities and a decrease of discontinuity. (2) A strong relationship was found between post-menstrual age of the infants and EEG maturity, but there were exceptions to this rule. (3) longer duration of extra-uterine life had a small accelerating influence on EEG maturation. (4) Certain basic types of EEG patterns were closely related to behavioural states, whereas EEG maturity was not state-dependent. (5) The relationship between EEG pattern types and behavioural states becomes more stable with increasing age.


New record of anoplocephalid eggs (Cestoda: Anoplocephalidae) collected from rodent coprolites from archaeological and paleontological sites of Patagonia, Argentina.
Results of paleoparasitological examination of rodent coprolites collected from archaeological and paleontological sites from Patagonia, Argentina, are present. Each coprolite was processed, rehydrated, homogenized, spontaneously sedimented and examined using light microscope. Coprolites and eggs were described, measured and photographed, and were compared with current faeces of Lagidium viscacia. Eggs with morphological features, attributed to an anoplocephalid cestode were found in samples collected from Cueva Huenul 1 (36°56'45″S, 69°47'32″W, Neuquén Province, Holocene) and Los Altares Profile (43º53'35″S, 68º23'21″W, Chubut Province, Late Holocene). These are the first findings of this anoplocephalid from faecal material from patagonic rodents.


Role of xanthine oxidase in small bowel mucosal dysfunction after surgical stress.
The small intestine is highly susceptible to surgical stress even at remote locations. An earlier study using a rat model indicated that oxidative stress plays an important role in this process. The enzyme xanthine oxidase is an important source of free radicals in the small intestine. The role of this enzyme in intestinal damage after surgical stress was examined. Rats pretreated with xanthine oxidase inhibitors were subjected to surgical stress by opening the abdomen and handling the intestine, as done during laparotomy. Enterocytes at various stages of differentiation were isolated and the protection offered by xanthine oxidase inhibitors against damage due to surgical stress was determined and compared with normal controls. Protection against ultrastructural changes to the mucosa, as well as mitochondrial function was examined. Surgical stress affected both the villus as well as crypt cells, causing increased superoxide generation, accompanied by increased activity of xanthine oxidase. Xanthine oxidase inhibitors ameliorated the increased superoxide generation, and protected against mitochondrial damage and ultrastructural changes in the intestine. Surgical stress affects both the villus and crypt cell populations in the small intestine. The enzyme xanthine oxidase maybe an important mediator of surgical stress in the intestine.


Fetal and Neonatal Anesthesia.
Anesthesia for fetal and neonatal surgery requires subspecialized knowledge and expertise. Attention to important anatomic, physiologic, and metabolic differences seen in pregnancy and at birth are essential for the optimal care of these patients. Thorough preoperative evaluations tailored intraoperative strategies and careful postoperative management are critical when devising the anesthetic approach for each of these cases.


Microtechniques for the gas chromatographic determination of barbiturates in small blood samples.
A method for the determination of therapeutic levels of barbituric acids in 25 microliter of whole blood is described. After extraction and controlled concentration of the extract to a volume of 5 microliter, the barbituric acids are N,N'-dimethylated using a microrefluxer. Of the total extract 20-100% is injected into the gas chromatograph. Low blanks, recoveries of 70--80% and peak ratios that are comparable to those in calibration experiments are obtained provided the detailed working instructions are followed strictly. In addition, barbiturates were determined (1 ng in 25 microliter blood) using column-switching devices and nitrogen-sensitive detection.


Carotenoid supplementation and GnRH challenges influence female endocrine physiology, immune function, and egg-yolk characteristics in Japanese quail (Coturnix japonica).
Androgens and carotenoids circulating in plasma affect the physiology and behavior of vertebrates. Much is known about control mechanisms and functions of each of these substances, yet their interactive effects are not well understood. Here we examine possible additive, multiplicative, and interactive effects of testosterone and carotenoids on female endocrine physiology, immunocompetence, and investment in eggs by simultaneously manipulating levels of testosterone [via gonadotropin releasing hormone (GnRH) challenges] and carotenoids (via diet supplementation) in captive female Japanese quail (Coturnix japonica). Females were randomly assigned to one of four treatments: carotenoid supplementation, GnRH challenge, GnRH challenge + carotenoid supplementation, or control. Carotenoid supplementation significantly increased circulating plasma carotenoid levels and acquired immune system performance, but not innate immunity. GnRH challenges elevated circulating testosterone and carotenoid levels, and induced immunosuppression in females. However, females in the GnRH challenge + carotenoid supplementation treatment had higher cell-mediated immune responses than control females and similar responses to those of carotenoid-supplemented females. Hence, availability of carotenoids in female quail seemed to counteract immunosuppressive effects of GnRH challenges. Our results provide further evidence for synergistic effects of carotenoids and testosterone on endocrine physiology and immune function in female birds. Elevated plasma testosterone or carotenoids levels resulted in increased deposition of those compounds to eggs, respectively. Furthermore, because we found that concentrations of testosterone and carotenoids in yolks were correlated within each treatment group, differential deposition of hormones and carotenoids in eggs may not only respond to surrounding social and environmental conditions, but also to other components of the egg.


Transient, unilateral, isolated hypoglossal nerve palsy.
We report a boy with isolated hypoglossal nerve palsy that recovered within twelve weeks. Investigations of the cervix, base of the skull, medulla and hypoglossal nerve by CT-scan and MRI did not show any abnormal findings. There are a few reports concerning isolated unilateral hypoglossal nerve palsy with benign course. Although we could not establish the cause of our patient's disease, an awareness of this condition should save such patients from unnecessary invasive studies.


Short- and long-term desensitization of serotonergic response in Xenopus oocytes injected with brain RNA: roles for inositol 1,4,5-trisphosphate and protein kinase C.
In Xenopus oocytes injected with rat brain RNA, serotonin (5HT) and acetylcholine (ACh) evoke membrane responses through a common biochemical cascade that includes activation of phospholipase C, production of inositol 1,4,5-trisphosphate (Ins1,4,5-P3), release of Ca2+ from intracellular stores, and opening of Ca-dependent Cl- channels. The response is a Cl- current composed of a transient component (5HT1 or ACh1) and a slow, long-lasting component (5HT2 or ACh2). Here we show that only the fast, but not the slow, component of the response is subject to desensitization that follows a previous application of the transmitter. The recovery of 5HT1 from desensitization is biphasic, suggesting the existence of two types of desensitization: short-term desensitization (STD), which lasts for less than 0.5 h; and long-term desensitization (LTD) lasting for up to 4 h. The desensitization between 5HT and ACh is heterologous and long-lasting. We searched for (a) the molecular target and (b) the cause of desensitization. (a) Pre-exposure to 5HT does not reduce the response evoked by intracellular injection of Ca2+ and by Ca2+ influx. Cl- current evoked by intracellular injection of Ins1,4,5-P3 was reduced shortly after application of 5HT, but fully recovered 30 min later. Thus, the Cl- channel is not a target for desensitization. Neither Ins1,4,5-P3 receptor nor the Ca2+ store is a target of LTD but they may be the targets of STD. (b) Ca2+ injection did not inhibit the 5HT response, suggesting that Ca2+ is not a sole cause of STD or LTD.(ABSTRACT TRUNCATED AT 250 WORDS)


Hepatic 7-ethoxyresorufin O-deethylase activity in eel (Anguilla anguilla) from the Thames Estuary and comparisons with other United Kingdom Estuaries.
Hepatic microsomal 7-ethoxyresorufin O-deethylase (EROD) activities (indicative of exposure to polycyclic aromatic hydrocarbons (PAHs) and polychlorobiphenyls (PCBs)) were measured in eel Anguilla anguilla from the Thames Estuary. Fish were collected from up to 13 sites during November 1997, May and August 1998 and October 1999. Throughout this period no clear seasonal variation could be identified at every site along the Thames. However, during the summer months, fish sampled from sites in the middle to the upper estuary (Woolwich, Greenhithe and West Thurrock) reported up to 3-fold higher EROD activities compared to sites either at the upper reaches (Richmond and Brentford) at the same time of the year, or fish sampled in winter, along the entire length of the estuary. A laboratory exposure experiment demonstrated a 3-fold elevation of EROD activity 2 days after injection with beta-naphthoflavone (beta-NF). However, higher levels of activity could be determined in fish sampled from the Weston canal near the Merseyside. The lowest levels of A. anguilla EROD activity were observed in fish sampled from the upper reaches of the River Tamar, Devon, and were comparable to activities determined in fish from the Wear and Humber estuaries. A. anguilla sampled along the Thames, Tyne and Tees estuaries reported between 2.5- and 7-fold higher EROD activities compared to fish collected from the Tamar. These results indicate that a low to moderate induction of A. anguilla CYP1A had occurred (indicative of low to moderate exposure to PAHs and planar PCBs) in fish collected from the Thames, Tyne, Wear, Tees, Humber and Tamar estuaries. However, the highest level of EROD activity was observed in fish from the Weston Canal (Merseyside).


Translation and Psychometric Analysis of the Japanese Version of the Perceived Maternal Parenting Self-Efficacy Scale.
To translate the Perceived Maternal Parenting Self-Efficacy (PMP S-E) scale to Japanese and test its psychometric properties among Japanese mothers of low-birth-weight (LBW) infants. Descriptive psychometric study. NICUs in two regional perinatal care centers in the Kinki region of Japan. Seventy-nine Japanese mothers of LBW infants hospitalized in NICUs. First, we translated the PMP S-E scale into Japanese and assessed its face and content validity. Second, we assessed the internal consistency, test-retest reliability, and criterion-related and construct validity of the Japanese version of the PMP S-E (JPMP S-E) with data from Japanese mothers of LBW infants. The JPMP S-E mean score was 53.0 (SD = 7.1); the total scores ranged from 38 to 68. The intraclass correlation coefficient of test-retest reliability was .75, and Cronbach's alpha coefficient was .90. With regard to criterion-related validity, we found a significant positive correlation between the JPMP S-E and the Maternal Attachment Inventory Japanese version (r = .45, p < .001), but no correlation existed between the JPMP S-E and the General Self-Efficacy Scale (r = .21, p = .06). We evaluated construct validity using confirmatory factor analysis to assess whether the model fit the previously determined structure of the PMP S-E. The model fit was moderate in the confirmatory factor analysis (comparative fit index = .63, goodness-of-fit index = .63, root mean square error of approximation = .15). We found adequate estimates of reliability and moderate indicators of validity for the JPMP S-E, which support the use of the tool for clinical and research purposes.


Exogenous lipoid pneumonia (oil granulomas of the lung).
The authors observed three cases of exogenous lipid pneumonia clinically suspected of lung carcinoma. Histological examination of material after thoracotomy gave the possibility of correct diagnosis. The lesions in lungs were characteristic granulomas around lipid material and with surrounding advanced fibrosis.


Molding the future of advanced practice nursing.
During this time when the walls that divide inpatient, outpatient, primary, tertiary, and community care are coming down, society should expect that the nursing profession will prepare and regulate advanced nursing practice for the good of patient care and society as a whole. To do so, schools with clinical practice graduate programs must create a consistent product; professional credentialing bodies must use consistent criteria to acknowledge advanced practice knowledge and expertise; and state boards of nursing must give legal recognition for advanced practice to these same nurses. Within this environment, advanced practice nurses will be prepared to serve society, even if their skills are applied in a variety of roles.


Peptidylarginine Deiminase Type 2 Predicts Tumor Progression and Poor Prognosis in Patients with Curatively Resected Biliary Tract Cancer.
(1) Background: PADI2 is a post-translational modification (PTM) enzyme that catalyzes citrullination, which then triggers autoimmune disease and cancer. This study aimed to evaluate the prognostic value of peptidylarginine deiminase 2 (PADI2) protein expression in biliary tract cancer (BTC) patients. (2) Methods: Using immunohistochemistry, the PADI2 protein expression in BTC tissues was analyzed. The correlations between PADI2 protein expression and clinicopathologic characteristics were analyzed using Chi-square tests. The Kaplan-Meier procedure was used for comparing survival distributions. We used Cox proportional hazards regression for univariate and multivariate analyses. From 2014 to 2020, 30 resected BTC patients were enrolled in this study. (3) Results: Patients with high PADI2 protein expression were associated with shorter progress-free survival (PFS; p = 0.041), disease-specific survival (DSS; p = 0.025), and overall survival (OS; p = 0.017) than patients with low PADI2 protein expression. (4) Conclusions: The results indicated that PADI2 protein expression was an independent poor prognostic factor for BTC patients regarding PFS, DSS, and OS.


Combination of leukotoriene receptor antagonist with antihistamine has an additive suppressive effect on the up-regulation of H1-receptor mRNA in the nasal mucosa of toluene 2,4-diisocyanate-sensitized rat.
An attempt was made to clarify the additive suppressive effects of pranlukast, a cysteinyl leukotriene-receptor (LTR) antagonist, in combination with chlorpheniramine, an antihistamine, on the up-regulation of histamine H1-receptor (H1R) mRNA in toluene 2,4-diisocyanate (TDI)-sensitized rats. Although pre-treatment with pranlukast partially, but significantly, suppressed TDI-induced up-regulation of H1R mRNA and nasal symptoms, pre-treatment with the combination of pranlukast and chlorpheniramine significantly suppressed them in a manner greater than either drug alone. These findings suggest that the additive therapeutic effect of the combination of LTR antagonist and antihistamine is due to their additive suppression of H1R up-regulation.


Isolation of high spectral quality RNA using run-on gene transcription; application to gene expression profiling of human brain.
1. Gene expression studies of human brain tissues in both health and disease require the use of intact, high spectral quality messenger RNA (mRNA). Short post-mortem tissues, when adequately controlled, provide a valuable primary source of brain mRNA. 2. Typical mRNA isolation methodologies rely on total RNA extraction from whole cells or tissues. Here we report that as an alternative approach, nuclei can be isolated from the same tissues and programmed for run-on gene transcription to generate enriched mRNA fractions. 3. This novel technique represents a significant improvement over previous methods and provides high quality, high yield mRNA samples suitable for downstream applications that include cloning, sequencing and gene expression studies using DNA array technologies.


NF-κB and innate immunity.
Members of the NF-κB transcription factor family play a critical role in the development of innate immunity. Upon recognition of pathogen infections or tissue damage, the NF-κB pathway is strongly activated by cellular pattern recognition receptors, including Toll-like receptors and multiple cytosolic receptors such as RIG-I-like helicases and NOD family proteins. NF-κB is required not only for the expression, but also for subsequent signal transduction of numerous downstream cytokines. NF-κB-responsive genes affect a diverse array of cellular processes including apoptosis and cell survival, and often directly control the course of a pathogen infection. In this review, we will examine signaling pathways leading to NF-κB activation during the innate immune response and mechanisms of pathogen-modulation of these pathways; the specifics of NF-κB-dependent gene programs, and the physiological consequences for the immune system caused by the absence of individual NF-κB subunits.


Targeting NRF2-KEAP1 axis by Omega-3 fatty acids and their derivatives: Emerging opportunities against aging and diseases.
The transcription factor NRF2 and its endogenous inhibitor KEAP1 play a crucial role in the maintenance of cellular redox homeostasis by regulating the gene expression of diverse networks of antioxidant, anti-inflammatory, and detoxification enzymes. Therefore, activation of NRF2 provides cytoprotection against numerous pathologies, including age-related diseases. An age-associated loss of NRF2 function may be a key driving force behind the aging phenotype. Recently, numerous NRF2 inducers have been identified and some of them are promising candidates to restore NRF2 transcriptional activity during aging. Emerging evidence indicates that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and their electrophilic derivatives may trigger a protective response via NRF2 activation, rescuing or maintaining cellular redox homeostasis. In this review, we provide an overview of the NRF2-KEAP1 system and its dysregulation in aging cells. We also summarize current studies on the modulatory role of n-3 PUFAs as potential agents to prevent multiple chronic diseases and restore the age-related impairment of NRF2 function.


Studies on the effect of corticosterone treatment on testicular activity, serum concentration of gonadotrophins, testosterone and alpha 2 u-globulin in rats pre-treated with estrogen.
Adult male rats were treated with estradiol-17 beta (50 micrograms/100 g body wt./day) for 7 days. When the animals were killed 14 days later, the levels of serum gonadotrophins, testosterone and alpha 2u-Globulin as well as the weight of sex organs were reduced, testicular 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity was also suppressed; spermatogenesis was inhibited. Administration of corticosterone (2 mg/day) for 14 days to estrogen-treated rats increased the concentration of gonadotrophins, testosterone and alpha 2u-globulin in the serum. The weight of accessory sex organs and spermatogenesis appeared to be normal while 17 beta-HSD activity increased in estrogen-treated rats after treatment with corticosterone. It is concluded that corticosterone has an effect on testicular function by inducing alpha 2u-globulin and gonadotrophins in estrogen treated rats.


Synthesis and biological evaluation of novel lipid A antagonists.
A mimetic of Lipid A with a beta-N(OMe) glycosidic linkage, four linear C-14 hydrophobic chains and without phosphate groups has been prepared together with its beta-O-linked analogue. Both these molecules were active in inhibiting the inflammatory action of Escherichia coli lipid A on MT2 macrophages in a dose-dependent manner, while they were completely devoid of inflammatory activity.


Intracellular sites of synthesis and processing of lectin in developing pea cotyledons.
The biosynthesis and processing of pea lectin was studied in developing pea cotyledons by a combination of pulse-chase experiments using 14C-aminoacids and subcellular fractionation of the homogenates. Lectin polypeptides were isolated on immunoaffinity gels and fractionated on sodium dodecyl sulfate-polyacrylamide gels followed by fluorography. Whether made in vivo or in an in vitro chain completion system containing polysomes still attached to microsomal membranes, newly synthesized lectin had an Mr of 23,000. In vivo labeling showed that radioactive lectin first associates with the rough endoplasmic reticulum and is then sequestered into the lumen of the endoplasmic reticulum. Pulse-chase experiments showed that it is chased out of the endoplasmic reticulum considerably more slowly than the storage proteins and accumulates in the protein bodies, initially as a polypeptide of Mr = 23,000. This pro-lectin is processed in the protein bodies to its mature form with polypeptides of Mr = 17,000 and 6,000. Pea lectin is synthesized throughout the protein accumulation phase of seed formation with maximum levels of synthesis and of mRNA approximately half-way through this period.


Characteristics of distribution and configuration of intracranial arachnoid membranes.
An understanding of the microsurgical anatomy of the arachnoid membranes and the subarachnoid cisterns is important in minimally invasive neurosurgery. But the topography of the arachnoid membranes has not been completely elucidated. The description of the distribution and the configuration of the intracranial arachnoid membranes is still a subject of controversy. In order to clarify this we examined eight Han Chinese adult human cadavers under an operating microscope. The dissections were performed with microsurgical instruments and techniques without staining of the intracranial structures nor injection of colored material into blood vessels. Twenty seven arachnoid membranes were identified. They were named according to their locations and attachment. They were divided into three groups: basal, convex and trabecular arachnoid membranes. They varied greatly in appearances and configurations. They were single-leaf structured except Liliequist's membrane, the chiasmatic membrane and the cerebellar precentral membrane. They were distributed extensively and unevenly and crisscrossed in the cranial cavity. The more complexly and intricately the blood vessels or the nerves converged or branched within the subarachnoid space, the more luxuriant and complex the arachnoid membranes and trabeculae were. The areas where the arachnoid membranes crowded most thickly in the subarachnoid space included the regions around the bifurcation of the internal carotid artery, the area around the hypothalamus, the interpeduncular cistern, the arachnoidal sheaths of the oculomotor nerve, the quadrigeminal cistern and the cisterna magna. Almost all the cranial nerves were encased by their own arachnoidal sheaths when they crossed the cisterns. The arachnoid membranes and trabeculae must be dissected or incised sharply during the operations. Thorough knowledge of the anatomy of the intracranial arachnoid membranes is valuable to take full advantage of the natural anatomic landmarks and interfaces formed by them during surgery.


Design and synthesis of novel ureido and thioureido conjugated hydrazone derivatives with potent anticancer activity.
Compounds possessing urea/thiourea moiety have a wide range of biological properties including anticancer activity. On the other hand, taking advantage of the low toxicity and structural diversity of hydrazone derivatives, they are presently being considered for designing chemical compounds with hydrazone moiety in the field of cancer treatment. With this in mind, a series of novel ureido/thioureido derivatives possessing a hydrazone moiety bearing nitro and chloro substituents (4a-4i) have been designed, synthesized, characterized and evaluated for their in vitro cytotoxic effect on HT-29 human colon carcinoma and HepG2 hepatocarcinoma cell lines. Two compounds (4c and 4e) having the chloro phenylurea group hybridized with phenyl hydrazone bearing nitro or chloro moieties demonstrated potent anticancer effect with the IC50 values between 2.2 and 4.8 µM at 72 h. The mechanism of action of compound 4c was revealed in hepatocellular carcinoma cells as an inducer of apoptosis in a caspase-independent pathway. Taken together, the current work presented compound 4c as a potential lead compound in developing future hepatocellular carcinoma chemotherapy drugs. The compounds were synthesized and then characterized by physical and spectral data (FT-IR, 1H-NMR, 13C-NMR, Mass). The anticancer activity was assessed using MTT assay, flowcytometry, annexin-V, DAPI staining and Western blot analysis.


Toward fish and seafood traceability: anchovy species determination in fish products by molecular markers and support through a public domain database.
Traceability in the fish food sector plays an increasingly important role for consumer protection and confidence building. This is reflected by the introduction of legislation and rules covering traceability on national and international levels. Although traceability through labeling is well established and supported by respective regulations, monitoring and enforcement of these rules are still hampered by the lack of efficient diagnostic tools. We describe protocols using a direct sequencing method based on 212-274-bp diagnostic sequences derived from species-specific mitochondria DNA cytochrome b, 16S rRNA, and cytochrome oxidase subunit I sequences which can efficiently be applied to unambiguously determine even closely related fish species in processed food products labeled "anchovy". Traceability of anchovy-labeled products is supported by the public online database AnchovyID ( http://anchovyid.jrc.ec.europa.eu), which provided data obtained during our study and tools for analytical purposes.


Shape transformations induced by amphiphiles in erythrocytes.
Shape alterations induced in human erythrocytes by cationic, anionic, zwitterionic and nonionic amphiphiles (C10-C16) at antihaemolytic concentrations (CAH50 and CAHmax) and at a slightly lytic concentration (2-10% haemolysis) were studied. Anionic (sodium alkyl sulphates) and zwitterionic amphiphiles (3-(alkyldimethylammonio)-1-propanesulfonates) proved to be potent echinocytogenic agents. Among the nonionic amphiphiles there were potent stomatocytogenicagents (octaethyleneglycol alkyl ethers, pentaethyleneglycol dodecyl ether), one potent echinocytogenic agent (dodecyl D-maltoside) and one weak echinocytogenic agent (decyl beta-D-glucopyranoside). Shape alterations induced by cationic amphiphiles (alkyltrimethylammonium bromides, cetylpyridinium chloride and dodecylamine hydrochloride) showed a strong time-dependence. These amphiphiles immediately induced strongly crenated erythrocytes which during incubation shifted to less crenated erythrocytes or to stomatocytes. All of the echinocytogenic amphiphiles induced echinocytes immediately, and there were only small alterations of the induced shape during incubation. Among the stomatocytogenic amphiphiles there were some that induced stomatocytes immediately or after a short lag time while others first passed the erythrocytes through echinocytic stages before stomatocytic shapes were attained. Erythrocytes treated with amphiphiles did not recover their normal discoid shape following repeated washing and reincubation for 1 h in amphiphile-free medium. Our study shows that shape alterations induced by amphiphiles in erythrocytes cannot be explained solely by assuming a selective intercalation of differently charged amphiphiles into the monolayers of the lipid bilayer as suggested in the bilayer couple hypothesis (Sheetz, M.P. and Singer, S.J. (1976) J. Cell Biol. 70, 247-251). We suggest that amphiphiles, when intercalated into the lipid bilayer, trigger a rapid formation of intrabilayer non-bilayer phases which protect the bilayer against a collapse and bring about a transbilayer redistribution of intercalated amphiphiles as well as of bilayer lipids.


The occurrence and taxonomic value of PBS X-like defective phages in the genus Bacillus.
72 strains of 24 Bacillus species were induced with mitomycin C. The lysates were examined for the presence of defective phages resembling PBS X in morphology. All strains tested of B. amyloliquefaciens. B, licheniformis, B. pumilus and B. subtilis contained such phages. Five morphological types of defective, PBS X-like phage could be distinguished, differing in their tail lengths and in the number of cross-striations on the tail. The quaternary structure of the tail, the molecular weight of the main tail protein and the antigenic properties of the phages were identical. The killing ranges of the defective phages have been determined and their possible use in taxonomy discussed.


Diurnal and longer term patterns in carbon dioxide and calcite saturation for the River Kennet, south-eastern England.
Continuous pH, dissolved oxygen and temperature information for three sites on the upper portion of the River Kennet, a tributary of the Thames in southern England is presented. A thermodynamic model is developed which links this information to weekly water quality data allowing the estimation of dissolved carbon dioxide and calcite saturation levels within the river on a continuous basis. The results show a dynamic and variable system along the length of the river. Marked diurnal patterns are observed for pH, dissolved oxygen, dissolved carbon dioxide and calcite saturation and the highest fluctuations occur during the summer months. There is also a marked gradient downstream in average pH (7.5-8.0) and dissolved carbon dioxide (30-10 times atmospheric pressure). Dissolved oxygen levels average approximately 100% saturation across all sites, and the diurnal pattern occurring during the summer months declines downstream. The waters are permanently oversaturated with respect to calcite and the diurnal patterns of change are maximal during the summer months. The results are discussed in relation to: (a) the balance between photosynthesis and respiratory processes; (b) the relative interchanges between the sediment/plant interface with the water column; and (c) the rates of degassing of carbon dioxide and oxygen between the river surface and the atmosphere.


A family with Hoyeraal-Hreidarsson syndrome and four variants in two genes of the telomerase core complex.
We describe an African American family with Hoyeraal-Hreidarrson syndrome (HHS) in which 2 TERT mutations (causing P530L and A880T amino acid changes) and two in the DKC1 variants (G486R and A487A) were segregating. Both genes are associated with dyskeratosis congenita and HHS. It was important to determine the importance of these mutations in disease pathogenesis to counsel family members. From genetic analysis of family members, telomere length and X-inactivation studies we concluded that compound heterozygosity for the TERT mutations was the major cause of HHS and the DKC1 G486R variant is a rare African variant unlikely to cause disease.


Sedative, antiepileptic and antipsychotic effects of Spondias mombin L. (Anacardiaceae) in mice and rats.
In this study, we evaluated the effects of air-dried Spondias mombin leaves extracted with aqueous, methanol and ethanol solvents on hexobarbital-induced sleeping time and novelty-induced rearing (NIR) behaviours in mice and rats. We also studied the effect of the extracts on amphetamine- and apomorphine-induced stereotyped and picrotoxin-induced convulsive behaviour in rats. All residues from different extractions were dissolved in normal saline and administered intraperitoneally (i.p.). The methanolic and ethanolic extracts (12.5-100mg/kg i.p.) prolonged the hexobarbital-induced sleeping time and reduced the NIR in both mice and rat in a dose-dependent manner. The aqueous extract prolonged the hexobarbital-induced sleeping time and reduced (NIR) at doses of 50 and 100mg/kg. The inhibitory effect of the extracts on NIR was not reversed by atropine, yohimbine, naltrexone and flumazenil. However, the extracts blocked the facilitating effect of flumazenil. This suggests that NIR inhibitory effects of extracts of Spondia mombin are not mediated via muscarinic, alpha(2) adrenergic, and mu-opioid receptors, whereas, the extracts appear to facilitate GABAergic transmission. In addition the extracts blocked picrotoxin-induced convulsions. Phenolic compound(s) were present in the ethanolic and methanolic extracts, which exhibited anticonvulsant properties in the picrotoxin-induced convulsions model. The extracts decreased the amphetamine/apomorphine-induced stereotyped behaviour, which suggest that these extracts possess antidopaminergic activity. The effect of the extracts on hexobarbitone-induced sleeping time was blocked by flumazenil a GABA(A) antagonist, indicating that the extracts contain GABA(A) agonists. These results suggest that the leaves extracts of Spondias mombin possess sedative and antidopaminergic effects.


Expression of clara cell 10-kDa protein (CC10) in congenital diaphragmatic hernia.
Clara cell 10 kDa protein (CC10) has been thought to be fairly specific to Clara cells and a major secretory protein that is both synthesized and released from Clara cells. In the present study, morphometric analyses of the immunohistochemical expression of CC10 were carried out on the bronchioles of human neonates with congenital diaphragmatic hernia (CDH) and then compared with morphometric analyses from a gestationally and postnatally age-matched control group in order to clarify the immaturity of Clara cells in CDH lungs. No difference was found in CC10 expression between the affected side and the unaffected side of the lungs in the CDH group. However, compared with the lungs of the control group, the CDH group showed a significant decrease in CC10 expression, namely, the ratio of CC10-positive cells per bronchiole, per unit perimeter of bronchiole, and per unit bronchiolar surface area. These results suggest that in the lungs of CDH cases, a possible delay in either functional maturation or the development of CC10 synthesis by the bronchioles may exist, and this retardation of functional maturation of the airway is also considered to play a role in the postnatal respiratory insufficiency observed in CDH patients.


Anticipatory and reflex coactivation of antagonist muscles in catching.
Reflex and anticipatory coactivation of antagonist muscles is demonstrated to occur when human subjects catch a ball. Amplitude and time course of the electromyographic (EMG) responses are strongly modulated by the presence of visual information. It is argued that these responses are centrally preset to stabilize the limb after ball impact.


The outcome of implementation of a dental prophylactics programme among eleven-year-old children from the Lublin region.
The aim of this study was evaluation of effectiveness of a professional carious disease prevention programme implemented in the Lublin region for a group of 11-year-old children at high risk of caries. On the basis of clinical dental examination a group of children at high risk of caries was selected (yearly increase in the number of new active caries foci of 4 and more--mean D value of 5.66), in whom therapeutic and prophylactic procedures comprising the caries prevention programme were performed. In a follow-up examination performed one year after the completion of the programme, much lower yearly increase in the number of new active caries foci was observed (mean D value of 0.61). Improvement of oral hygiene status was also observed in the study group. The caries prevention programme that we applied in the group of 11-year-old children proved to be highly effective.


Rapid, optimized interactomic screening.
We must reliably map the interactomes of cellular macromolecular complexes in order to fully explore and understand biological systems. However, there are no methods to accurately predict how to capture a given macromolecular complex with its physiological binding partners. Here, we present a screening method that comprehensively explores the parameters affecting the stability of interactions in affinity-captured complexes, enabling the discovery of physiological binding partners in unparalleled detail. We have implemented this screen on several macromolecular complexes from a variety of organisms, revealing novel profiles for even well-studied proteins. Our approach is robust, economical and automatable, providing inroads to the rigorous, systematic dissection of cellular interactomes.


Detection of aneuploidy in human oocytes and corresponding first polar bodies by fluorescent in situ hybridization.
The purpose of the study was to investigate the reliability of the fluorescent in situ hybridization (FISH) analysis of the first polar body (IPB) for cytogenetic evaluation of human oocytes as a method of choice in preimplantation diagnosis of chromosomal aneuploidies. Human unfertilized oocytes and their extruded IPB were analyzed using the directly labeled fluorescence alpha-satellite DNA probes to chromosomes X and 18. Paired signals for chromosomes X and 18 were observed in the second meiotic prophase (MII) of unfertilized oocytes and their extruded IPB. In the series of 156 unfertilized oocytes in which the number of X chromosome- and chromosome 18-specific signals were analyzed in both MII and IPB, five nondisjunction events have been detected, with corresponding signals in MII and their IPB: missing signals in MII corresponded to extra signals in their IPB and extra signals in MII corresponded to missing signals in IPB. In one oocyte chromosome 18 nondisjunction was detected, with both chromosome 18 signals in MII and no chromosome 18 signal in IPB. In four oocytes chromatid malsegregations for chromosome X or chromosome 18 were detected: in two oocytes, three of four chromosome 18 signals were present in MII, with only one in IPB, and in the other two oocytes, three of four chromosome signals were present in MII, with only one left in IPB. The data suggest the possibility of detecting chromosomal aneuploidy in oocytes through cytogenetic analysis of their corresponding IPB by FISH as a possible approach for preimplantation diagnosis of major chromosomal trisomies.


The active components derived from Penthorum chinensePursh protect against oxidative-stress-induced vascular injury via autophagy induction.
Oxidative stress-induced damage has been proposed as a major risk factor for cardiovascular disease and is a pathogenic feature of atherosclerosis. Although autophagy was reported to have a protective effect against atherosclerosis, its mechanism for reducing oxidative stress remains un-elucidated. In this study, we have identified 4 novel autophagic compounds from traditional Chinese medicines (TCMs), which activated the AMPK mediated autophagy pathway for the recovery of mitochondrial membrane potential (MMP) to reduce the production of reactive oxygen species (ROS) in Human umbilical vein endothelial cells (HUVECs). In this study, 4 compounds (TA, PG, TB and PG1) identified from Penthorum chinense Pursh (PCP) were demonstrated for the first time to possess binding affinity to HUVECs cell membranes via cell membrane chromatography (CMC) accompanied by UHPLC-TOF-MS analysis, and the 4 identified compounds induce autophagy in HUVECs. Among the 4 autophagic activators identified from PCP, TA (Thonningianin A, Pinocembrin dihydrochalcone-7-O-[3″-O-galloyl-4″,6″-hexahydroxydiphenoyl]-glucoside) is the major chemcial component in PCP, which possesses the most potent autophagy effect via a Ca2+/AMPK-dependent and mTOR-independent pathways. Moreover, TA efficiently reduced the level of ROS in HUVECs induced by H2O2. Additionally, the expression of pro- and cleaved-IL-1β in the aortic artery of ApoE-KO mice were also alleviated at the transcription and post-transcription levels after the administration of TA, which might be correlated to the reduction of oxidative-stress induced inflammasome-related Nod-like receptor protein3 (NLRP3) in the aortic arteries of ApoE-KO mice. This study has pinpointed the novel autophagic role of TA in alleviating the oxidative stress of HUVECs and aortic artery of ApoE-KO mice, and provided insight into the therapeutic application of TA in treatment of atherosclerosis or other cardiovascular diseases.


[The Role of Personal Resources in Coping].
Stress reactions can be a result of occupational and everyday stress, which are perceived individually. The insufficient compensation of stress can lead to various diseases. Personality traits play an important role in this. Stress reactions can lead to health problems and diseases. Therefore it is important to reduce stress. The aim of this study was to examine the role of personality traits in dealing with stress perception and coping. The questionnaire on Differential stress inventory (DSI) differentiated 217 subjects into 5 types of DSI. The survey compared these 5 types along their personality traits via the Freiburg Personality Inventory (FPI-R). The DSI types showed significant differences in the expression of the personality traits. This applies the everyday stress, professional and private interactions with other people and the existential and future fears. People with pronounced physical disorders in the FPI showed physical and/or emotional-cognitive stress manifestation as well as a sense of helplessness. Life satisfaction is negatively related to stressors, for example through everyday life. The survey revealed the importance of personality traits in coping with job strain. Occupational health diagnostics should be integrated in occupational health care and prevention. The occupational physician or the prevention team appear here to be significant, as they see workers falling through the classic family doctor model. In the prevention team, personality traits can be supplemented by psychologists. Personal resources can be imparted or reinforced to prevent physical disorders.


Ligand-dependent conformational changes in thyroid hormone and retinoic acid receptors are potentially enhanced by heterodimerization with retinoic X receptor.
Recently, many lines of evidence have been accumulated indicating that thyroid hormone receptor (TR) and retinoic acid receptor (RAR) undergo a ligand-dependent conformation change. Since most of these results were obtained by either gel-shift assay or circular dichroism spectroscopic studies, it was not clear which part of the receptor bore the major conformational change. Moreover, it is not clear whether the formation of heterodimer between TR or RAR and retinoic X receptor (RXR) has any effects on this structural change. Utilizing partial proteolytic analysis, we demonstrated that thyroid hormone and retinoic acid induce a specific protease-resistant conformation to their cognate receptors. Studies of various deletion mutants reveal that the entire ligand binding domain of these receptors is involved in this change, and suggest that ligand may induce a more compact structure in its binding domain. Evidence from native gel electrophoresis supports this notion. This conformational change occurs in the absence of DNA and occurs independently of other domains in the receptor. Heterodimerization between TR or RAR and the RXR has little effect on receptor conformation in the absence of hormone but does enhance the ligand-dependent structural change. Interestingly, dual hormone treatment, i.e. thyroid hormone and 9-cis RA, intensifies this enhancement. We suggest that the observed protease-resistant conformation may introduce a different configuration to the receptor and therefore may affect the receptor in various ways, but most likely is involved in converting the receptor from a negative regulator to a positive activator.


Infrequency of MDM2 gene amplification in pediatric solid tumors and lack of association with p53 mutations in adult squamous cell carcinomas.
Loss of function of the p53 tumor suppressor gene by point mutation is the most commonly detected genetic alteration in human cancer. There is growing evidence that amplification and overexpression of the MDM2 gene are alternative mechanisms that also lead to functional inactivation of p53. While p53 mutations and MDM2 amplification have been reported to occur in rhabdomyosarcoma and osteogenic sarcoma, the incidence of MDM2 in other pediatric solid tumors is not known. We therefore tested a series of other pediatric solid tumors for MDM2 gene amplification. MDM2 amplification could not be detected in specimens from 40 Wilms' tumors, 15 neuroblastomas, 12 sarcomas, or 4 hepatoblastomas tested. To determine whether MDM2 amplification was an alternative mechanism of p53 inactivation in adult carcinomas that frequently possess p53 mutations, 68 samples of squamous cell carcinomas of the upper aerodigestive tract, 24% of which were previously shown to contain p53 mutations, were also tested for MDM2 amplification. MDM2 amplification did not occur in any of the tumor specimens tested. These findings suggest that MDM2 amplification may only occur in a limited subset of human tumors. Loss of function of p53 may be an essential event in human tumorigenesis. If so, then other mechanisms of p53 inactivation must occur in those tumors that exhibit neither p53 mutation nor MDM2 amplification.


Demography and the emergence of universal patterns in urban systems.
Urban areas exist in a wide variety of population sizes, from small towns to huge megacities. No proposed form for the statistical distribution of city sizes has received more attention than Zipf's law, a Pareto distribution with power law exponent equal to one. However, this distribution is typically violated by empirical evidence for small and large cities. Moreover, no theory presently exists to derive city size distributions from fundamental demographic choices while also explaining consistent variations. Here we develop a comprehensive framework based on demography to show how the structure of migration flows between cities, together with the differential magnitude of their vital rates, determine a variety of city size distributions. This approach provides a powerful mathematical methodology for deriving Zipf's law as well as other size distributions under specific conditions, and to resolve puzzles associated with their deviations in terms of concepts of choice, symmetry, information, and selection.


Identification of nonstationary dynamics in physiological recordings.
We present a novel framework for the analysis of time series from dynamical systems that alternate between different operating modes. The method simultaneously segments and identifies the dynamical modes by using predictive models. In extension to previous approaches, it allows an identification of smooth transition between successive modes. The method can be used for analysis, diagnosis, prediction, and control. In an application to EEG and respiratory data recorded from humans during afternoon naps, the obtained segmentations of the data agree with the sleep stage segmentation of a medical expert to a large extent. However, in contrast to the manual segmentation, our method does not require a priori knowledge about physiology. Moreover, it has a high temporal resolution and reveals previously unclassified details of the transitions. In particular, a parameter is found that is potentially helpful for vigilance monitoring. We expect that the method will generally be useful for the analysis of nonstationary dynamical systems, which are abundant in medicine, chemistry, biology and engineering.


Automatic detection of lesions in lung regions that are segmented using spatial relations.
This article presents a novel approach for the automatic detection of lesions and selection of features on chest radiographs. We have illustrated the importance of accurate segmentation, which is based on spatial relationships between the lung structures, as a preprocessing step in a Computer Aided Diagnosis (CAD) scheme. Then, three suitable combinations of features have been identified using the forward stepwise selection method from the original images and their transformed ones. Experimental results show that our segmentation approach and the suppression of skeletal structures improve the detection accuracy. The selected features can describe efficiently different kinds of chest lesions.


A comparison of two ATPase based schemes for histochemical muscle fibre typing in various mammals.
A comparative study was performed on the fibre populations in tibialis anterior muscles of mouse, rat, guinea pig, rabbit, cat and dog using the two different methods of histochemical staining for myofibrillar ATPase after acid (Brooke and Kaiser 1970) or alkaline preincubations (Guth and Samaha 1970). For all species a complete correspondence existed between type I (Brooke and Kaiser 1970) and beta fibres (Samaha et al. 1970). Gross correspondence (greater than 85%) existed between IIA and IIB (Brooke and Kaiser 1970) and alpha beta and alpha fibres (Samaha et al. 1970) respectively in mouse, guinea pig, rabbit, cat and dog. In the case of mouse and dog, this high degree of correspondence was based on the assumption that mouse tibialis anterior contains no type I and the dog no type IIB fibres. For the rat, a pronounced overlap existed between IIA fibres on the one hand and alpha beta and alpha fibres on the other hand as well as between IIB fibres and alpha beta and alpha fibres. These observations lead to the conclusion that the two classification schemes are not interchangeable for all species and that the two terminologies should be used only in relation with the methods from which they were derived.


The cAMP-dependent protein kinase downregulates glucose-6-phosphatase expression through RORα and SRC-2 coactivator transcriptional activity.
Fasting hormones activate the cAMP/PKA signaling pathway and stimulate expression of hepatic gluconeogenic enzymes including glucose-6-phosphatase (G6Pase). Previously it was shown that steroid receptor coactivator 2 (SRC-2) knock-out mice exhibit fasting hypoglycemia and that SRC-2 coactivates RAR-related orphan receptor alpha (RORα) at the proximal G6Pase promoter. We have investigated the upstream regulation and functional implications of this RORα/SRC-2 complex on G6Pase expression. In HepG2 cells, overexpression of the catalytic PKA subunit (PKA-Cα) reduced the SRC-2 protein level, recruitment to the G6Pase promoter, and its ability to coactivate RORα. Knock-down and transactivation experiments employing G6Pase promoter constructs demonstrated that RORα and SRC-2 are required for PGC-1α to stimulate G6Pase expression. These results suggest that PKA inhibits SRC-2 coactivation of RORα and in turn reduces PGC-1α dependent regulation of G6Pase. This indirect feedback mechanism may underlie the suppression of gluconeogenesis throughout long-term starvation.


HMG20A was identified as a key enhancer driver associated with DNA damage repair in oral squamous cell carcinomas.
Oral squamous cell carcinoma (OSCC) is the main type of oral cancer. Disturbing DNA repair is an invaluable way to improve the effectiveness of tumor treatment. Here, we aimed to explore the key enhancer drivers associated with DNA damage repair in OSCC cells. Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA) and Kaplan-Meier analysis were applied to explore the relationship among DNA repair-related genes expression and clinical phenotypes based on The Cancer Genome Atlas (TCGA) database. HOMER software and Integrative Genomics Viewer were applied to identify and visualize enhancers using GSE120634. Toolkit for Cistrome Data Browser was applied to predict transcription factors. Human Protein Atlas Database was used to analyze the protein levels of transcription factors in OSCC and control tissues. Seventy-two OSCC patients were included in this study. qRT-PCR was used to detect transcription factor expression in OSCC and adjacent control tissues collected in this study. qRT-PCR and ChIP-qPCR were used to verify the binding of transcription factors to enhancers, and regulation of target genes transcription. Transcription factor knockdown and control cells were treated with cisplatin. CCK8 was used to detect cell viability and proliferation. Western blotting was implemented to detect the levels of DNA repair-related proteins. Transwell assay was used to detect cell invasion. DNA repair was positively associated with the OSCC metastatic phenotype. Patients in the cluster with high expression of DNA repair-related genes had a worse prognosis and a higher proportion of advanced stage, low-differentiation, alcohol consumption and smoking compared to the cluster with low DNA repair-related gene expression. Seventeen metastasis-specific enhancer-controlled upregulated DNA repair-related genes, with the top two upregulated genes being ADRM1 26 S proteasome ubiquitin receptor (ADRM1) and solute carrier family 12 member 7 (SLC12A7) were screened. High mobility group 20 A (HMG20A) was the key prognostic enhancer driver regulating metastasis-specific DNA repair-related genes, with higher expression in OSCC tissues than normal control tissues, and higher expression in metastatic OSCC tissues than non-metastatic OSCC tissues. HMG20A bound to the metastasis-specific enhancers of ADRM1 and SLC12A7, thereby promoting ADRM1 and SLC12A7 expression. Knockdown of HMG20A enhanced cisplatin sensitivity of cells, and inhibited OSCC cells from repairing DNA damage caused by cisplatin, as well as proliferation and invasion of OSCC cells. HMG20A was identified as the key prognostic enhancer driver regulating DNA repair in OSCC cells, providing a new therapeutic target for OSCC.


Probability of progenitor renewal (PPR) and production of clonogenic progeny (CFU-GM) by primitive adherent progenitor cells in adult human bone marrow and umbilical cord blood.
Human haemopoietic tissues contain primitive plastic-adherent progenitor cells (P delta cells) that can be detected by measurement of their granulocyte-macrophage colony-forming cell (CFU-GM) progeny. Limiting dilution analysis and Poisson statistics are necessary for determining the frequency of P delta cells because each of them produces several CFU-GM. Limiting dilution also permits measurement of the abilities of individual P delta progenitors to produce CFU-GM. Here we report that the frequencies of P delta progenitors in cord blood and adult marrow are similar (5.6 and 7.8/10(5) mononuclear cells respectively) and individual cord blood P delta progenitors produce fewer CFU-GM than adult P delta progenitors. To test the possibility that the lower production of differentiated progeny by cord blood cells was the result of a higher rate of self-renewal, we devised a two-stage limiting dilution assay relying on the relative production of CFU-GM after two consecutive weeks of incubation. The probability of progenitor renewal (PPR) was derived from the number of wells (progenitors) that produced CFU-GM on both occasions compared with the number that produced CFU-GM on the first occasion only. The total number of CFU-GM produced on the second occasion compared with the number produced on the first occasion provided an index of the overall change in the size of the P delta cell population. The data indicate that P delta cells in cord blood have a higher PPR (0.59) than those in adult marrow (0.36). Also, the relative numbers of CFU-GM produced in the second and first weeks were greater for cord blood (1.2) than for adult marrow (0.36). Therefore P delta cells in cord blood have a greater capacity for self-maintenance and possibly for expansion than P delta cells in adult marrow.


Discovery of an entropically-driven small molecule streptavidin binder from nucleic acid-encoded libraries.
Dehydrocholic acid was identified as a selective streptavidin binder from a PNA-tagged library. Isothermal calorimetry titration measurements showed this interaction to be entropically driven. Peptides tagged with dehydrocholic acid can be captured on a streptavidin resin and released under thermal conditions.


Uptake of small liposomes by non-reticuloendothelial tissues.
The distribution of liposomes within the intravascular space and the extent to which they escape into extravascular space strongly impact on the application of lipid vesicles as a carrier for pharmacologically active agents. The present study investigates how intact small unilamellar vesicles (SUV) may be taken up by different tissues after intravenous injection into mice, using various types of SUV with different entrapped markers, lipid composition, size, doses of liposomal lipids and stability in the blood. Our focus was specifically on sphingomyelin (or distearoyl phosphatidylcholine)/cholesterol (2:1, mol/mol) SUV, which are known to be stable in the blood circulation. Our results indicated that, in addition to the reticuloendothelial tissues, intact SUV were taken up in several other parts of the body, including intestine, skin, carcass and legs. It appears that the accumulation of SUV in the intestine and the skin increases with time post-injection. Furthermore, from the kinetic data, the process of uptake of SUV by the skin and intestine is compatible with a non-saturable pathway, which follows first-order kinetics. This suggests that the cells involved in the uptake of SUV in the intestine and skin are not phagocytic cells, which are normally saturable.


An innovative model for predicting coronary heart disease using triglyceride-glucose index: a machine learning-based cohort study.
Various predictive models have been developed for predicting the incidence of coronary heart disease (CHD), but none of them has had optimal predictive value. Although these models consider diabetes as an important CHD risk factor, they do not consider insulin resistance or triglyceride (TG). The unsatisfactory performance of these prediction models may be attributed to the ignoring of these factors despite their proven effects on CHD. We decided to modify standard CHD predictive models through machine learning to determine whether the triglyceride-glucose index (TyG-index, a logarithmized combination of fasting blood sugar (FBS) and TG that demonstrates insulin resistance) functions better than diabetes as a CHD predictor. Two-thousand participants of a community-based Iranian population, aged 20-74 years, were investigated with a mean follow-up of 9.9 years (range: 7.6-12.2). The association between the TyG-index and CHD was investigated using multivariate Cox proportional hazard models. By selecting common components of previously validated CHD risk scores, we developed machine learning models for predicting CHD. The TyG-index was substituted for diabetes in CHD prediction models. All components of machine learning models were explained in terms of how they affect CHD prediction. CHD-predicting TyG-index cut-off points were calculated. The incidence of CHD was 14.5%. Compared to the lowest quartile of the TyG-index, the fourth quartile had a fully adjusted hazard ratio of 2.32 (confidence interval [CI] 1.16-4.68, p-trend 0.04). A TyG-index > 8.42 had the highest negative predictive value for CHD. The TyG-index-based support vector machine (SVM) performed significantly better than diabetes-based SVM for predicting CHD. The TyG-index was not only more important than diabetes in predicting CHD; it was the most important factor after age in machine learning models. We recommend using the TyG-index in clinical practice and predictive models to identify individuals at risk of developing CHD and to aid in its prevention.


Minimum income for healthy living and frailty in adults over 65 years old in the English Longitudinal Study of Ageing: a population-based cohort study.
To test whether minimum income for healthy living of a person aged 65 years or older (MIHL65) is associated with frailty in older adults. Secondary analysis of the English Longitudinal Study of Ageing, a multiwave prospective cohort study in England, UK. A subset (n=1342) of English Longitudinal Study of Ageing participants, who at wave 1 in 2002 were aged 65 years or older, without any limiting long-standing illnesses, and who had the information required to calculate MIHL65 in 2002, 2004 and 2006 and two measures of frailty in 2008. Frailty defined using Fried's phenotype criteria and Rockwood's Index of deficits. The odds of frailty in 2008 were significantly higher for participants living below MIHL65 in 2002, both on Fried's phenotype criteria (OR 2.56, 95% CI 1.57 to 4.19) and Rockwood's Index (OR 2.83, 95% CI 1.74 to 4.60). These associations remained after adjustment for age and gender for both Fried's phenotype (OR 1.85, 95% CI 1.18 to 2.90) and Rockwood's Index (OR 2.15, 95% CI 1.38 to 3.35). Compared with those whose income during 2002-2006 was always above MIHL65, the odds of frailty in 2008 for those below MIHL65 were two-to-three times higher, with a tendency for the ORs to increase in line with the length of time spent below MIHL65 (ORs (95% CIs) were: Fried's phenotype, below MIHL65 once: 2.02 (1.23 to 3.34); twice: 2.52 (1.37 to 4.62); thrice: 3.53 (1.65 to 7.55). Rockwood's Index: once: 2.34 (1.41 to 3.86); twice: 3.06 (1.64 to 5.71); thrice: 2.56 (1.22 to 5.34)). These associations remained after adjustment for age and gender on Rockwood's Index, but not Fried's phenotype. These results provide some support for the idea that frailty at older ages is associated with not having sufficient income to lead a healthy life.


TIL Transcriptomic States Enable Successful TCR Prediction.
Neoantigen-specific CD4+ and CD8+ T cells in metastatic solid cancers share gene expression profiles.


Synaptic protein and pan-neuronal gene expression and their regulation by Dicer-dependent mechanisms differ between neurons and neuroendocrine cells.
Neurons in sympathetic ganglia and neuroendocrine cells in the adrenal medulla share not only their embryonic origin from sympathoadrenal precursors in the neural crest but also a range of functional features. These include the capacity for noradrenaline biosynthesis, vesicular storage and regulated release. Yet the regulation of neuronal properties in early neuroendocrine differentiation is a matter of debate and the developmental expression of the vesicle fusion machinery, which includes components found in both neurons and neuroendocrine cells, is not resolved. Analysis of synaptic protein and pan-neuronal marker mRNA expression during mouse development uncovers profound differences between sympathetic neurons and adrenal chromaffin cells, which result in qualitatively similar but quantitatively divergent transcript profiles. In sympathetic neurons embryonic upregulation of synaptic protein mRNA follows early and persistent induction of pan-neuronal marker transcripts. In adrenal chromaffin cells pan-neuronal marker expression occurs only transiently and synaptic protein messages remain at distinctly low levels throughout embryogenesis. Embryonic induction of synaptotagmin I (Syt1) in sympathetic ganglia and postnatal upregulation of synaptotagmin VII (Syt7) in adrenal medulla results in a cell type-specific difference in isoform prevalence. Dicer 1 inactivation in catecholaminergic cells reduces high neuronal synaptic protein mRNA levels but not their neuroendocrine low level expression. Pan-neuronal marker mRNAs are induced in chromaffin cells to yield a more neuron-like transcript pattern, while ultrastructure is not altered. Our study demonstrates that remarkably different gene regulatory programs govern the expression of synaptic proteins in the neuronal and neuroendocrine branch of the sympathoadrenal system. They result in overlapping but quantitatively divergent transcript profiles. Dicer 1-dependent regulation is required to establish high neuronal mRNA levels for synaptic proteins and to maintain repression of neurofilament messages in neuroendocrine cells.


Augmented enkephalin-immunoreactivity in adrenaline-producing phaeochromocytomas.
Immunohistochemical studies for methionine- and leucine-enkephalin were performed on 26 phaeochromocytomas to elucidate the patho-physiological roles of enkephalins. Positive reactions were seen in all phaeochromocytomas with varying intensities. The location of methionine- and leucine-enkephalin agreed fairly well with each other. Stronger immunostaining was obtained in phaeochromocytomas secreting both adrenalin and noradrenaline than in those secreting predominantly noradrenaline. Paroxysmal hypertension was frequently observed in patients with adrenalin-secreting phaeochromocytomas, especially those with marked enkephalin positivity. Urinary excretion of metanephrine was significantly correlated with enkephalin positivity. These findings show that all phaeochromocytomas retain the ability to produce enkephalins of the adreno-medullary or extra-medullary chromaffin tissues from which they derive. Augmented enkephalin-immunoreactivity in adrenalin-producing phaeochromocytomas may be interpreted as reflecting a close association of enkephalins with adrenalin under physiological conditions.


Virulence factors and antimicrobial susceptibility of Escherichia coli isolated from calves in Turkey.
Escherichia coli isolates from calves were investigated by multiplex PCR assays for the presence of genes encoding K99, F41, F17-related fimbriae, heat-stabile enterotoxin a (STa), intimin (eae) and Shiga toxins (stx1 and stx2). A total of 120 E. coli isolates, 75 isolated from diarrhoeic or septicemic calves and 45 from clinically healthy calves aged between 1 day and 2 months were tested. Each isolate was obtained from different calves in different herds. Among the isolates from diseased animals, 12 (16%) isolates from 1- to 7-day-old diarrhoeic calves were detected as enterotoxigenic E. coli which possessed K99, F41 and STa in combination; F17-related fimbriae genes were detected in 33 (44%) isolates and they were found in combination with K99 + F41 + STa in two isolates. Of 120 isolates, 16 carried eae, eight stx1 and five stx2 genes alone or in combination. None of the eae- or stx-positive strains was identified as O157:H7. However, results indicate that calves may be carrier of Shiga toxin-producing E. coli which have potential as a human pathogen. Antimicrobial susceptibility of 75 isolates from diseased calves was determined by agar disk diffusion method for 14 antimicrobial agents. In 77.3% of the isolates, multiresistance was detected. Higher resistance rates were detected for cephalothin (72%), tetracycline (69.3%), kanamycin (69.3%), ampicillin (65.3%), nalidixic acid (53.3%), trimethoprim-sulphamethoxazole (52%) and enrofloxacin (41.3%), respectively. No resistance was found for ceftiofur and cefoxitin.


Thyroid hormone levels in late preterm, early term and term infants: a study with healthy neonates revealing reference values and factors affecting thyroid hormones.
Thyroid function tests in neonates have been challenging to interpret because their levels are affected by several neonatal and delivery-related factors. The aim of the study was to evaluate reference values of thyroxine (T4) and thyrotropin (TSH) levels in different gestational age groups and to demonstrate the affect of perinatal factors on thyroid hormones. Medical records of 7616 neonates whose gestational age ranges between 34 and 42 weeks were analyzed retrospectively. Gender, mode of delivery, gestational age, postnatal age and birth weight were noted together with TSH and T4 levels. Gestational age (r=0.14, p<0.001) and birth weight (r=0.12, p<0.001) had positive correlation with T4 levels, whereas they had no effect on TSH levels. Males had higher TSH and lower T4 levels (p=0.001 for both) compared with females. T4 levels of babies born via vaginal delivery were lower than the ones born via cesarean section (p=0.01). Multivariable analysis yielded gestational age as the only factor affecting T4 levels (p<0.001). T4 and TSH levels based on 2.5-97.5 percentile cutoffs according to gestational age were presented. The thyroid hormone ranges given in this study can help pediatricians to interpret the thyroid hormone results with ease.


Tendon transfer in partially anaesthetic hands.
Stereognosis and sensory localisation were studied in hands of patients with partial anaesthesia due to peripheral nerve injury both before and after tendon transfer to impart movement to the anaesthetic part. One patient showed a marked improvement in stereognosis and localisation, but in general little was gained in terms of improved sensation. Function was improved more in the dominant than in the non-dominant hand. Earlier tendon transfer in cases of peripheral nerve injury might decrease cortical exclusion.


The influence of molsidomine on the hemodynamics of patients with chronic heart failure at rest and during exercise.
The effect of molsidomine on hemodynamic properties was studied in 10 patients with chronic congestive heart failure in New York Heart Association functional classes III and IV. Ten patients with the same degree of heart failure served as control subjects. All patients were receiving standard therapy with digitalis and diuretics. Administration of a single dose of 4 mg of molsidomine orally in the initial phase resulted in significant decreases of pulmonary artery pressure, pulmonary capillary pressure, and right atrial pressure at rest and during exercise (p less than 0.01 and p less than 0.01, respectively). After long-term oral treatment with 4 mg of molsidomine three times daily over a period of 3 weeks, single dose administration of 4 mg of molsidomine orally again caused significant decreases of pulmonary artery, pulmonary capillary, and right atrial pressure at rest and during exercise (range p less than 0.01 to p less than 0.02). Cardiac output, heart rate, systemic arterial pressure, pulmonary artery resistance, and systemic arterial resistance were essentially unchanged.


Effects of habitat degradation, microsite, and seed density on the persistence of two native herbs in a subtropical shrubland.
Species in degraded ecosystems may interact differently with their surroundings from those under historic conditions. Understanding factors affecting variation in early life history stages of plants is fundamental to assessing their persistence in intact and degraded habitats, and the value of degraded lands. We evaluated the effect of seed density on the seed dynamics of two herbaceous species (annual, biennial), and considered how seed availability may influence population dynamics in different habitats (degraded, intact Florida scrub) and microsites (bare sand, leaf litter, shrub). We used data on responses to experimental treatments (seed removal, seedling emergence, establishment) and models to evaluate how effects of these factors may change over time since the last disturbance. Probability of any seed removal, emergence, and establishment per unit increased with seed density, although proportion removal for Chamaecrista fasciculata, proportion emergence for Balduina angustifolia, and proportion establishment for both species decreased with density. When animals were given selective access to seeds, invertebrates were primarily responsible for seed removal of both study species. Models with dynamics changing with time-since-disturbance for both species predicted that population growth may decrease slightly if local available seed density increases. Detailed demographic comparisons of populations in intact and degraded conditions can be used to understand the way that environmental conditions (habitat, microsite) combine with seed density effects to influence population dynamics of herb species. Degraded habitat may act as a transitional state in a trajectory toward intact conditions for some species, or as refugia for other native species.


Creeping Fat in Crohn's Disease: Innocuous or innocuum?
In Crohn's disease, the characteristic expansion of mesenteric tissue on sites of intestinal inflammation is known as creeping fat. In a recent issue of Cell, Ha et al. report that translocation of gut bacteria to the mesenteries is associated with the formation of creeping fat.


Sensitive attribute privacy preservation of trajectory data publishing based on l-diversity.
The widely application of positioning technology has made collecting the movement of people feasible for knowledge-based decision. Data in its original form often contain sensitive attributes and publishing such data will leak individuals' privacy. Especially, a privacy threat occurs when an attacker can link a record to a specific individual based on some known partial information. Therefore, maintaining privacy in the published data is a critical problem. To prevent record linkage, attribute linkage, and similarity attacks based on the background knowledge of trajectory data, we propose a data privacy preservation with enhanced l-diversity. First, we determine those critical spatial-temporal sequences which are more likely to cause privacy leakage. Then, we perturb these sequences by adding or deleting some spatial-temporal points while ensuring the published data satisfy our ( L , α , β )-privacy, an enhanced privacy model from l-diversity. Our experiments on both synthetic and real-life datasets suggest that our proposed scheme can achieve better privacy while still ensuring high utility, compared with existing privacy preservation schemes on trajectory.


Visual and somatosensory integration in the anterior ectosylvian cortex of the cat.
We recorded from single neurons in both banks of the posterior two-thirds of the anterior ectosylvian sulcus. All neurons were tested with visual and tactile stimulations. In each bank of the anterior ectosylvian sulcus the majority of neurons were bimodal, i.e. responded to both visual and tactile stimuli (B cells); the remaining population was strictly unimodal, responding either to visual (V cells) or to somatosensory (T cells) stimulation. Bimodal and unimodal neurons were recorded at all explored cortical sites and were consistently intermixed. Unlike bimodal neurons, unimodal neurons showed an asymmetric localization: the V cells were significantly more numerous in the ventral bank while the T neurons were preferentially found in the dorsal bank of the sulcus. We could not detect an orderly somatotopic or visuotopic representation, nor was it possible to find a systematic spatial correspondence between somatic and visual receptive fields. The functional organization of the anterior ectosylvian cortex is discussed in terms of a hierarchical processing of sensory information.


Using the venous angle as a pressure reservoir to retrogradely fill the subclavian lymphatic trunk with contrast agent for lymphatic mapping.
Visualizing the lymphatic system and recording the spatial relations between the subclavian lymphatic trunk (SLT) and the surrounding anatomical structures will improve radiotherapy treatment planning for breast cancer patients with lymphatic involvement. An experimental approach to retrogradely fill the SLT with contrast agent was explored. Six Thiel embalmed specimens were bilaterally dissected in the cervical and clavicular region to optimize the new experimental approach. A conservative dissection with minimum distortion of spatial relations between different anatomical structures was developed. A pressure reservoir was created inside the venous angle to allow retrograde filling of the SLT under the influence of time and pressure. The new methodology proved feasible, showing successful pressure build-up inside the venous reservoir, resulting in filling of the proximal end of the subclavian lymphatic trunk. The pressures needed to significantly fill the subclavian lymphatic trunk proved to be higher than the pressures that the venous walls could withstand. Thiel embalmed specimens proved useful for optimizing the experimental approach, but the embalming products could have negatively affected the vessel strength. The authors suggest that their method will be applied on fresh frozen specimens in future studies, to obtain SLT filling up to the axillary lymphatic plexus. Our findings also pointed out that there is still a lot to be learned about the anatomical variability of the SLT and its termination sites. The detailed description of our experimental approach offers valuable information for future lymphatic mapping studies.


Trisomy 12 in Epstein-Barr virus-transformed lymphoblastoid cell lines of normal individuals and patients with nonhematologic malignancies.
Karyotypes of 36 lymphoblastoid cell lines established by Epstein-Barr virus (EBV) transformation of peripheral blood lymphocytes (PBL) of eight normal individuals and 28 patients with various nonhematologic malignancies were analyzed. In seven lines (19.4%), cells with trisomy 12 were noted, with clonality in two of these lines. In two of 11 metaphases with such trisomy, chromosome 12 was involved in structural rearrangements [t(8;12)(q12;p12) and t(12;12)(q11;q24)]. No cells with trisomy 12 were observed in phytohemagglutinin (PHA)-stimulated PBL cultures of these individuals. In 250 individuals (normal and with nonhematologic malignancies) examined in our laboratory in the last 5 years, extra copies of chromosome 12 in PHA-stimulated PBL cultures were observed in only five of 23,216 cells (0.02%). There were no cases of clonality in these samples. The frequency of an extra chromosome 12 was comparable to that of the other chromosomes except 21 and X, whose frequency of occurrence was 0.08% and 0.09%, respectively. These findings should be considered random events in PHA-stimulated PBL. On the contrary, in lymphoblastoid cell lines established by EBV transformation, trisomy of chromosome 12 was the most frequent numerical abnormality. It was observed in 64.7% of all cases with chromosome gains and therefore could not be considered a random occurrence. The specificity of this phenomenon for EBV transformation is supported by the results of cytogenetic analysis of eight lymphoblastoid cell lines established by an alternative procedure in our laboratory [1]. In 400 cells analyzed not a single cell with trisomy 12 was observed. We suggest that EBV transformation might either randomly induce formation of such cells in immortalized B-cell populations or show potentially blastomogenic cells or proneness to their formation in certain individuals who could be predisposed to develop lymphoproliferative diseases, especially chronic lymphocytic leukemia (CLL) in which trisomy of chromosome 12 is the most common alteration.


Turner Syndrome: An Update.
Turner syndrome is the most common sex chromosome abnormality in women. Infertility and short stature are the most striking findings seen in these patients. Unfortunately, many girls are still being diagnosed too late and therefore early diagnosis and treatment key. Turner syndrome affects many systems of the body; therefore, a comprehensive approach is key for therapeutic intervention.


In-line system containing porous polymer monoliths for protein digestion with immobilized pepsin, peptide preconcentration and nano-liquid chromatography separation coupled to electrospray ionization mass spectroscopy.
The use of two different monoliths located in capillaries for on-line protein digestion, preconcentration of peptides and their separation has been demonstrated. The first monolith was used as support for covalent immobilization of pepsin. This monolith with well-defined porous properties was prepared by in situ copolymerization of 2-vinyl-4,4-dimethylazlactone and ethylene dimethacrylate. The second, poly(lauryl methacrylate-co-ethylene dimethacrylate) monolith with a different porous structure served for the preconcentration of peptides from the digest and their separation in reversed-phase liquid chromatography mode. The top of the separation capillary was used as a preconcentrator, thus enabling the digestion of very dilute solutions of proteins in the bioreactor and increasing the sensitivity of the mass spectrometric detection of the peptides using a time-of-flight mass spectrometer with electrospray ionization. Myoglobin, albumin, and hemoglobin were digested to demonstrate feasibility of the concept of using the two monoliths in-line. Successive protein injections confirmed both the repeatability of the results and the ability to reuse the bioreactor for at least 20 digestions.


Trends and measurement of HIV prevalence in northern Malawi.
Most data on HIV prevalence in Malawi come from antenatal clinic (ANC) surveillance and are, therefore, subject to bias. HIV prevalence and risk factors were measured using population-based data to assess the accuracy of ANC surveillance and changes in prevalence and risk factors for HIV over time. HIV prevalence was measured in 1988-1993 and 1998-2001 in community controls from case-control studies of mycobacterial disease in Karonga District, Malawi. ANC surveillance studies in the district began in 1999. Age and area-standardized HIV prevalence in women aged 15-49 years in the community was 3.9% in 1988-1990, 12.5% in 1991-1993 and 13.9% in 1998-2001. For men, HIV prevalence was 3.7%, 9.2% and 11.4% in the same periods. In 1988-1993, HIV positivity was associated with occupations other than farming, with increased schooling and being born outside Karonga District. In 1998-2001, non-farmers were still at higher risk but the other associations were not seen. The age- and area-adjusted HIV prevalence in the ANC in 1999-2001 was 9.2%. The underestimate can be explained largely by marriage and mobility. Reduced fertility in HIV-positive individuals was demonstrated in both ANC and community populations. A previously recommended parity-based adjustment gave an estimated female HIV prevalence of 15.0%. HIV prevalence has increased and continues to be higher in non-farmers. The increase is particularly marked in those with no education. ANC surveillance underestimated HIV prevalence in the female population in all but the youngest age group. Although there were differences in sociodemographic factors, a parity-based adjustment gave a reasonable estimate of female HIV prevalence.