A viral long terminal repeat expressed in CD4+CD8+ precursors is downregulated in mature peripheral CD4-CD8+ or CD4+CD8- T cells.
The long terminal repeat from a thymotropic mouse mammary tumor virus variant, DMBA-LV, was used to drive the expression of two reporter genes, murine c-myc and human CD4, in transgenic mice. Expression was observed specifically in thymic immature cells. Expression of c-myc in these cells induced oligoclonal CD4+ CD8+ T-cell thymomas. Expression of human CD4 was restricted to thymic progenitor CD4- CD8- and CD4+ CD8+ T cells and was shut off in mature CD4+ CD8- and CD4- CD8+ T cells, known to be derived from the progenitor double-positive T cells. These results suggest the existence of similar and common factors in CD4+ CD8- and CD4- CD8+ T cells and support a model of differentiation of CD4+ CD8+ T cells through common signal(s) involved in turning off the expression of the CD4 or CD8 gene.


A protocol for the development of core outcome sets for effectiveness trials and clinical audits in renal cell cancer (R-COS).
There is inconsistency in outcomes collected in renal cell cancer (RCC) intervention effectiveness studies and variability in their definitions. This makes critical summaries of the evidence base difficult and sub-optimally informative for clinical practice guidelines and decision-making by patients and healthcare professionals. A solution is to develop a core outcome set (COS), an agreed minimum set of outcomes to be reported in all trials in a clinical area. To develop three COS for (a) localised, (b) locally advanced and (c) metastatic. The methods are the same for each of our three COS and are structured in two phases. Phase 1 identifies potentially relevant outcomes by conducting both a systematic literature review and patient interviews (N ~ 30 patients). Qualitative data will be analysed using framework analysis. In phase 2, all outcomes identified in phase 1 will be entered in a modified eDelphi, whereby patients and healthcare professionals (50 of each) will score each outcome's importance (Likert scale from 1 [not important] to 9 [critically important]). Outcomes scored in the 7-9 range by ≥70% and 1-3 by ≤15% will be regarded as 'consensus in', and the vice versa of this will constitute 'consensus out'. All other combinations will be regarded as equivocal and discussed at consensus meetings (including 10 patients and 10 healthcare professionals) in order to vote on them and ratify the results of the eDelphi. The R-COS will reduce outcome reporting heterogeneity and improve the evidence base for RCC. The study is registered with the COMET initiative: https://www.comet-initiative.org/studies/details/1406.


The Diverse Effects of Complex Chromosome Rearrangements and Chromothripsis in Cancer Development.
In recent years, enormous progress has been made with respect to the identification of somatic mutations that contribute to cancer development. Mutation types range from small substitutions to large structural genomic rearrangements, including complex reshuffling of the genome. Sets of mutations in individual cancer genomes may show specific signatures, which can be provoked by both exogenous and endogenous forces. One of the most remarkable mutation patterns observed in human cancers involve massive rearrangement of just a few chromosomal regions. This phenomenon has been termed chromothripsis and appears widespread in a multitude of cancer types. Chromothripsis provides a way for cancer to rapidly evolve through a one-off massive change in genome structure as opposed to a gradual process of mutation and selection. This chapter focuses on the origin, prevalence and impact of chromothripsis and related complex genomic rearrangements during cancer development.


Association of Acute Myocardial Infarction with ankylosing Spondylitis: A nationwide longitudinal cohort study.
Pertaining to an association between Acute Myocardial Infarction (AMI) and Ankylosing Spondylitis (AS) is sparse. The purpose of this nationwide longitudinal study was to investigate the prevalence of AMI in newly diagnosed AS patients. A total of 12,988 patients were enrolled in the AS group from January 1, 2010 to December 31, 2014 from the Korean National Health Insurance Service (NHIS). The control group consisted of 64,940 subjects according to 1:5 age-sex stratified matching. The AMI incidence rates in AS and control group were compared using the Kaplan-Meier method. The hazard ratio of AMI and the control group was estimated by Cox proportional hazards regression analyses. During a 6 year follow up, 62 patients (0.48%) in the AS group and 157 persons (0.24%) in the control group developed AMI. The hazard ratio of AMI in the AS group was 1.99 (95% confidence interval [95% CI], 1.48-2.67) after adjusting for sex and age. The hazard ratio of AMI in the AS group was 1.81 (95% CI, 1.34-2.43) after adjusting for demographics and comorbid medical disorders. The incidence rate of AMI increases in newly diagnosed AS patients.


Ultrastructural morphometric examinations on the protection provided by prostacyclin against myocardial ischaemia.
Myocardial ischaemia in the dog lasting for three hours is followed by swellings of the mitochondria and dilatation of the sarcoplasmic reticulum. The volume density (Vv) of mitochondria in the peripheral ischaemia zone is 0.2890, that of sarcoplasmic reticulum is 0.0101. Prostacyclin was administered either i.v. or by triggering in conjunction with an intra-aortic balloon pump which led to an increase in the volume density of the mitochondria, mainly as a result of an increase in the volume of average mitochondria. The dilatation of the sarcoplasmic reticulum is reversed. It was not possible to prove in our investigations that prostacyclin provides protection against myocardial ischaemia.


The Relationship Between Rosacea and Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.
Rosacea and inflammatory bowel disease (IBD) are chronic inflammatory disorders of the skin and the gut, which are interfaces between the environment and the human body. Although growing evidence has implicated a possible link between rosacea and IBD, it remains unclear whether IBD increases the risk of rosacea and vice versa. Therefore, we investigated the association between rosacea and IBD in this study. We performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Eight eligible studies were included in this meta-analysis. Overall, the prevalence of rosacea was higher in the IBD group than in the control group, with a pooled odds ratio (OR) of 1.86 (95% confidence interval [CI](1), 1.52-2.26). Both the Crohn's disease and the ulcerative colitis groups had higher prevalences of rosacea than the control group, with ORs of 1.74 (95% CI 1.34-2.28) and 2.00 (95% CI 1.63-2.45), respectively. Compared with those in the control group, the risks of IBD, Crohn's disease, and ulcerative colitis were significantly higher in the rosacea group, with incidence rate ratios of 1.37 (95% CI 1.22-1.53), 1.60 (95% CI 1.33-1.92), and 1.26 (95% CI 1.09-1.45), respectively. Our meta-analysis suggests that IBD is bidirectionally associated with rosacea. Future interdisciplinary studies are needed to better understand the mechanism of interaction between rosacea and IBD .


SWL in lower calyceal calculi: evaluation of the treatment results in children and adults.
To evaluate the treatment parameters of shockwave lithotripsy (SWL) in lower calyceal calculi in adults and children in a comparative manner. Between 2006 and 2011, SWL was performed for lower calyceal calculi in 282 adults (mean age 48.5 years, range 28-64) and 54 children (mean age 48 months, range 5-141). The Wolf Piezolith 3000 lithotriptor has been used for SWL. Success rates, auxiliary procedures, additional interventions, and complications were evaluated in detail in a comparative manner. Mean stone size was 7.7 mm (range 5-25) and 8.1 mm (range 5-23) in children and in adults, respectively. Mean SWL sessions were 1.5 (range 1-5) in children and 2.4 (range 1-6) in adults. Although 66.6% of children were stone-free after the first session, 28% of adult patients were stone-free after the first SWL session, showing a statistically significant difference (P = .0001). After the treatments, although a complete stone-free status was obtained in 85% of children, 31.5% of adults were stone-free at 3-month follow-up after SWL (P = .0001). Although no auxiliary procedures were needed in children, 8.2% of adults required them. Likewise, the percentage of additional procedures were higher in adults than children (20.2%). SWL for lower calyceal calculi has been found to be highly successful in pediatric patients. These results demonstrate that, irrespective of stone size, SWL should be the first treatment alternative in the management of lower calyx stones in children.


Vacuum-assisted closure therapy in the management of patients undergoing vulvectomy.
To investigate whether systematic postoperative VAC therapy could improve vulvectomy healing. We reviewed medical data from 54 women who underwent in the period of March 2006 to December 2009 radical vulvectomy or wide local vulvectomy with defect volume >40cm(3). Patients were divided into two groups according to immediate postoperative care. Patients treated with systematic vacuum-assisted closure (VAC) therapy immediately after surgery were included in the "VAC group" while patients receiving conventional care (CC) were included in the "CC group". The characteristics of the VAC group (n=30) and CC group (n=24) were similar and there were no significant differences in operative data, histological results or oncologic follow-up. The median length of use of VAC was 11 days after surgery (6-38). The length of hospital stay for patients in the VAC group and CC group was 17.8 (±8.7) and 18.4 days (±9.9) (p=0.8) respectively. The lengths of complete healing were 44.4 (±18.4) vs. 60.2 (±28.7) days (p=0.0175) respectively. In our study we proved that using VAC dressing immediately after vulvectomy (at least 6cm×7cm) for 11 days reduces the total length of cicatrization by approximately 16 days.


Resolving bottlenecks for recombinant protein expression in E. coli.
Escherichia coli is widely used as an expression system for production of recombinant proteins of prokaryotic and eukaryotic origin. A large body of knowledge has accumulated throughout the last few decades regarding expression of recombinant proteins in E. coli. However, despite this progress, protein production, primarily of eukaryotic origin, still remains a challenge. The biggest obstacle lies in obtaining large amounts of a given protein in a correctly folded form. Several strategies are being used to increase both yield and solubility. These include expression as fusion proteins, co-expression with molecular chaperones, or with a protein partner(s), and the use of multiple constructs for each protein. In this chapter, we focus on strategies for creating expression vectors, as well as on guidelines for improving recombinant protein solubility.


[Multicystic lung revealing a Sjogren's syndrome].
The Sjogren's syndrome is a chronic inflammatory autoimmune disease that affects primarily the exocrine glands, but can affect other organs particularly the lungs. Cystic lung disease is very significant but exceptionally recounted in the literature. We report the case of a patient, 54 years old, whose disease was discovered incidentally after a routine chest radiograph. The diagnosis of cystic lung revealing a primary Sjogren's syndrome was held before a group of radio-clinical, immunological and histological arguments. Through our observation, the diagnosis of Sjogren's syndrome should be included in the list of diagnoses to raise in a multicystic lung.


Description of Himalayan mosquito pupae III, Ochlerotatus albolateralis and Ochlerotatus deccanus.
The pupae of Ochlerotatus albolateralis and Oc. deccanus are described and illustrated for the first time from specimens collected in the Himalayan Mountains in Nepal, breeding in tree holes and bamboo stumps. Chaetotaxal tables and illustrations show the morphology of their setae. Characters to recognize each species are explained.


Laparoscopic sleeve gastrectomy for morbid obesity.
The epidemic of obesity in the United States is a major public health issue and more than a third of adults are now considered obese (body mass index > or = 30 kg/m(2)). Surgery for morbid obesity, bariatric surgery, is the most durable treatment for this disease and about 140,000 cases are performed annually. Laparoscopic sleeve gastrectomy (LSG) has been advocated as the first of a 2-stage procedure for the high-risk, super-obese patient. More recently, LSG has been studied as a single-stage procedure for weight loss in the morbidly obese. LSG has been shown in initial studies to produce excellent excess weight loss comparable with laparoscopic Roux-en-Y gastric bypass in many series with a very low incidence of major complications and death. We describe our technique for LSG.


Three-dimensional evaluation of the effects of Bionator and Forsus appliances on oropharyngeal airway volume in patients with mandibular retrognathia.
To evaluate whether there is a difference between the effects of Bionator and Forsus appliances on airway volume. Forty patients with mandibular retrognathia were divided into two groups. The Bionator appliance was applied to Group 1, while the Forsus FRD EZ2 appliance was applied to Group 2. Three-dimensional images were captured before and after functional appliance use in both groups. Dolphin 3D software was used for airway measurements. No statistically significant difference was found between the groups in terms of volumetric and area measurements. There was a statistically significant difference between the minimum axial T and O-N border T measurements of the groups. The use of functional appliances may contribute to an increase in oropharyngeal airway dimensions, but there was no difference between the Bionator and Forsus groups in terms of volumetric measurements.


Status and significance of CpG island methylator phenotype in endometrial cancer.
Endometrial cancer is a common gynecologic malignant disease, but patients with advanced disease have a poor prognosis. The CpG island methylator phenotype (CIMP) involves hypermethylation targeted toward the promoters of multiple genes. To investigate the role of epigenetic aberration of tumor-related genes in endometrial cancer. The promoter methylation status of 5 genes was examined in 35 endometrial cancer tissues, 15 matched adjacent normal endometrial tissues (NET) from the same cancer patients, and 22 benign endometria from unaffected patients by methylation-specific PCR. CIMP positivity (CIMP+) was defined as concordant methylation of ≥3 genes. The methylation frequency of promoters for the 5 genes in the cancer tissues ranged from 37% for P16 to 57% for P14. Cancer and benign endometria, but not cancer and adjacent NET, significantly differed in methylation of P14, P16, ER, COX-2 and RASSF1A (p < 0.05). CIMP+ was frequent in cancer and adjacent NET (46 and 47%, respectively; p > 0.05), but absent in benign endometria. Moreover, CIMP+ was significantly correlated with methylation of P16 and COX-2 (r = 0.673 and 0.662, respectively; p < 0.001). CIMP+ is an important and frequent epigenetic event in endometrial cancer or adjacent NET, and may be a biomarker for predicting early carcinogenesis. COX-2 is a good representative gene of CIMP+ in this cancer.


Interaction of wild-type and catalytically inactive mutant forms of tissue-type plasminogen activator with human umbilical vein endothelial cell monolayers.
Several groups have demonstrated that radioiodinated tissue-type plasminogen activator (t-PA) binds to saturable sites on human umbilical vein endothelial cells (HUVECs) in culture (Hajjar, K. A., Hamel, N. M., Harpel, P. C., and Nachman, R. L. (1987) J. Clin. Invest. 80, 1712-1719; Beebe, D. P. (1987) Thromb. Res. 46, 241-254; Barnathan, E. S., Kuo, A., van der Keyl, H., McCrae, K. R., Larsen, G. L., and Cines, D. B. (1988) J. Biol. Chem. 263, 7792-7799). Here we report that most of the specific binding of 125I-t-PA to our HUVEC cultures is accounted for by binding to (i) plasminogen activator inhibitor type 1 (PAI-1), a t-PA inhibitor produced in abundance by HUVECs; and (ii) specific binding sites present on the plastic culture surface. The contribution of the sites on plastic can be eliminated by taking several precautions. Then, most or all of the specifically bound 125I-t-PA is present in a sodium dodecyl sulfate-stable 110-kDa 125I-t-PA.PAI-1 complex. Interestingly, a radioiodinated mutant form of t-PA, S478A, which is catalytically inactive and therefore unable to form the covalent complex with PAI-1, still binds to HUVECs. In fact, this ligand binds to HUVECs in 10-30-fold greater amounts than does wild-type 125I-t-PA (resulting in greater than 1 x 10(7) S478A 125I-t-PA molecules bound/cell at 12 nM ligand concentration). In contrast, diisopropyl fluorophosphate-treated t-PA binds to HUVECs in much smaller amounts than does wild-type t-PA. Several findings suggest that PAI-1 is a major binding site for S478A t-PA. The vast amount of binding observed with S478A t-PA, compared with wild-type t-PA, may be accounted for by an observed large scale release of wild-type 125I-t-PA.PAI-1 complexes from the solid phase (cells or extracellular matrix) into the culture medium. Immunoprecipitation experiments demonstrate that, in contrast to wild-type t-PA, S478A t-PA does not extract [35S]methionine-PAI antigen from metabolically labeled extracellular matrix. It is proposed that t-PA releases PAI-1 from the solid phase when it forms the irreversible covalent complex with the inhibitor, a process that does not occur with the catalytically inactive mutant form of t-PA.


An enzymatic activity in uninfected cells that cleaves the linkage between poliovirion RNA and the 5' terminal protein.
The 5' terminal protein (VPg) on poliovirion RNA can be removed by cell-free extracts from a variety of uninfected cells. This soluble enzymatic activity is found in both nuclear and cytoplasmic extracts of heLa cells and is activated by Mg++. The enzyme activity cleaves the tyrosine-phosphate bond that links the protein to the RNA. In a partially purified form it has insufficient nonspecific protease or nuclease activity to account for its action. The existence of this enzyme implies that poliovirus RNA is translated in cell-free extracts in a form that lacks the 5' terminal protein. The role of this enzyme in the uninfected cell is not known.


[Elective termination of respiratory therapy in amyotrophic lateral sclerosis].
Due to the growing use of artificial respiration in amyotrophic lateral sclerosis (ALS), physicians are increasingly confronted with patients seeking discontinuation of therapy. Yet there are few systematic investigations of the withdrawal of ventilation therapy. In a retrospective investigation of nine German ALS patients, clinical data were recorded from the discontinuation of noninvasive ventilation (n=4) and mechanical ventilation (n=5). In cases of residual spontaneous breathing, intensified symptom control of dyspnea and anxiety was possible with intravenous morphine sulfate at a low dose rate (10 mg/h) but high cumulative dose (185-380 mg). The terminal phase after removing the mask was protracted (22:10 h to 28:00 h). In cases of minimal or absent spontaneous breathing the disconnection was realized in deep sedation, which required a moderate total dose of morphine sulfate (120 mg) but a high dosage rate (up to 300 mg/h). The terminal phase in deep sedation was short (15-80 min). The elective termination of ventilation requires differentiated pharmacologic palliative care. More controlled studies are required in order to establish evidence-based guidelines for the termination of ventilation.


Electrical properties of the myotendon region of frog twitch muscle fibers measured in the frequency domain.
The electrical properties of the end of a muscle fiber were determined using three microelectrodes, one passing sinusoidal current, the other two recording the resulting voltages. An electrical model was constructed from the morphology of the fiber, including the resistance of the extracellular space between cells; the parameters of this model were determined by fitting the model to the observed voltage responses. Our results, analyzed directly or by curve fits, show that the end of muscle fibers contains a large capacitance resulting from the extensive membrane folds at the myotendon junction. Analysis and simulations show that the extra capacitance at the myotendon junction has substantial effects on measurements of linear properties, in particular on estimates of the capacitance of the membranes. There is little qualitative effect on classical measurements of nonlinear charge movement (provided they were made with one set of electrode locations) if the linear components have been subtracted. Quantitative estimates of nonlinear charge movement and ionic currents are significantly affected, however, because these estimates are customarily normalized with respect to the linear capacitance.


Physiological and metabolic traits of Taxol biosynthesis of endophytic fungi inhabiting plants: Plant-microbial crosstalk, and epigenetic regulators.
Attenuating the Taxol productivity of fungi with the subculturing and storage under axenic conditions is the challenge that halts the feasibility of fungi to be an industrial platform for Taxol production. This successive weakening of Taxol productivity by fungi could be attributed to the epigenetic down-regulation and molecular silencing of most of the gene clusters encoding Taxol biosynthetic enzymes. Thus, exploring the epigenetic regulating mechanisms controlling the molecular machinery of Taxol biosynthesis could be an alternative prospective technology to conquer the lower accessibility of Taxol by the potent fungi. The current review focuses on discussing the different molecular approaches, epigenetic regulators, transcriptional factors, metabolic manipulators, microbial communications and microbial cross-talking approaches on restoring and enhancing the Taxol biosynthetic potency of fungi to be industrial platform for Taxol production.


Lactate dehydrogenase isoenzymes of human erythrocyte membranes.
Human erythrocyte membranes and cytosol were fractionated in detergent-containing polyacrylamide gels and stained for lactate dehydrogenase activity. A highly significant difference in the distribution of three isoenzymes of lactate dehydrogenase (LD-1, LD-2 and LD-3) between membranes and cytosol was found, a striking feature being the poor binding of LD-3 to the membrane fraction.


Electrophysiologic evidence of epicardial connections between low right atrium and remote right atrial region or coronary sinus musculature: Relevance for catheter ablation of typical atrial flutter.
The coronary sinus (CS) is surrounded by a myocardial coat with extensive connections to the left and right atria that contributes to the interatrial electrical connection. Whereas epicardial connections between CS musculature and the left atrium have largely been demonstrated, clinically relevant epicardial connections from the CS musculature toward the low right atrium (LRA) and epicardial connections between two regions of the right atrium remain questionable. Five patients underwent electrophysiology (EP) study for typical atrial flutter (AFl) using either conventional multipolar catheters (four patients) or three-dimensional high-density mapping system (one patient). All five patients had a similar sequence of events during the EP studies. After several cavotricuspid isthmus (CTI) radiofrequency (RF) applications, double potentials were recorded along the ablation line while tachycardia persisted. The right atrial activation pattern strongly suggested the presence of a complete endocardial CTI line of the block. Based on the detailed conventional atrial mapping, RF applications at the middle cardiac vein/CS ostium allowed sinus rhythm restoration in four patients. High-density mapping showed an early breakthrough site at the septal side of the ablation line, close to the CS ostium during counterclockwise AFl, in the fifth patient. RF applications at this site resulted in tachycardia termination. Our observations suggested the existence of epicardial fibers connecting the LRA with either the CS musculature or a remote right atrial region. When AFl ablation fails whereas evidence for the local endocardial block is observed, the operators should integrate this finding in the diagnosis and ablation strategy.


Culture of neonatal rodent microglia, astrocytes, and oligodendrocytes from cortex and spinal cord.
The protocol described in this chapter covers the preparation and culture of enriched populations of microglia, astrocytes, and oligodendrocytes from the cortex and spinal cord of neonatal rat and mouse. The procedure is based on the enzymatic digestion of tissue, followed by the culture of a mixed glial cell population which is then utilized as the starting point for the isolation, via differential attachment, of the different cell types.


Sharp estimates for the p-adic Hardy type operators on higher-dimensional product spaces.
In this paper, we introduce the p-adic Hardy type operator and obtain its sharp bound on the p-adic Lebesgue product spaces. Meanwhile, an analogous result is computed for the p-adic Lebesgue product spaces with power weights. In addition, we characterize a sufficient and necessary condition which ensures that the weighted p-adic Hardy type operator is bounded on the p-adic Lebesgue product spaces. Furthermore, the p-adic weighted Hardy-Cesàro operator is also obtained.


Sensitivity and specificity of three diabetes diagnostic criteria in people with non-alcoholic fatty liver disease (NAFLD) and otherwise healthy people: Analysis of NHANES III.
Establishing whether fasting plasma glucose (FPG), postprandial glucose (PPG), and HbA1c have the same diagnostic accuracy in NAFLD versus otherwise healthy people could inform T2DM screening recommendations for those with NAFLD. Cross-sectional analysis of the Third National Health and Nutrition Examination Survey (NHANES III) 1989-1994. T2DM was defined as PPG ≥ 200 mg/dL, FPG ≥ 126 mg/dL, or HbA1c ≥ 6.5 %. We estimated sensitivity and specificity between the six pairwise combinations between the three T2DM definitions in people with and without NAFLD. With Poisson regressions, we investigated if people with NAFLD were more likely to have T2DM with two diagnostic criteria yet not with the third one. There were 3652 people with mean age 55.6 years and 49.4 % were men; 673 (18.4 %) people had NAFLD. Compared to NAFLD-free individuals, those with NAFLD had lower specificity in all pairwise comparisons except when PPG was the reference vs HbA1c [98.28 % (95 % CI: 97.73 %-98.72 %) in people without NAFLD vs 96.15 % (95 % CI: 94.28 %-97.54 %)]. The sensitivity of FPG was slightly superior to PPG and HbA1c in people without NAFLD; for example, 64.62 % (95 % CI: 55.75 %-72.80 %) for FPG vs 56.58 % (95 % CI: 44.71 %-67.92 %) for HbA1c. People with NAFLD were more likely to be diagnosed with FPG and PPG yet not with HbA1c (PR=2.15; p = 0.020). While these T2DM diagnostic criteria may capture different patients both in people with and without NAFLD, in the NAFLD population FPG appears to have the best sensitivity and there were no differences between PPG and HbA1c in terms of specificity.


Cirrhosis Is Associated with Increased Mortality in Patients with Diverticulitis: A Nationwide Cross-Sectional Study.
Diverticulitis in patients with cirrhosis has been associated with higher surgical mortality, but no prior studies evaluate non-surgical treatment results. Our aim was to compare the outcomes of hospitalization for diverticulitis in patients with and without cirrhosis. We utilized the Nationwide Inpatient Sample (2007-2013) for patients with and without cirrhosis hospitalized for diverticulitis. Patients were further stratified by the presence of compensated versus decompensated cirrhosis. Validated ICD-9 codes captured patients and surgical procedures. Multivariate logistic regression models were fit. The primary outcomes of interest were mortality and surgical intervention rates. There were 1,555,469 patients hospitalized for diverticulitis without cirrhosis, and 7523 patients hospitalized for diverticulitis with cirrhosis. On multivariate analysis, patients with cirrhosis had an increased mortality rate (OR 2.28; 95% CI 1.48-3.5). There were no significant differences in surgical interventions. Subgroup multivariate analyses of compensated cirrhosis (n = 6170) and decompensated cirrhosis (n = 1353) revealed that decompensated cirrhosis had an increased mortality rate (OR 4.99; 95% CI 2.48-10.03) when compared to patients without cirrhosis, whereas those with compensated cirrhosis did not (OR 1.67; 95% CI 0.96-2.91). Those with compensated cirrhosis underwent less surgical interventions (OR 0.82; 95% CI 0.67-0.99) compared to those without cirrhosis. Patients with diverticulitis and cirrhosis had increased costs and lengths of hospitalization. Presence of cirrhosis in patients hospitalized for diverticulitis is associated with an increased mortality rate. These are novel findings, and future clinical studies should focus on improving diverticulitis outcomes in this group.


Simultaneous determination of multiclass illegal dyes with different acidic-basic properties in foodstuffs by LC-MS/MS via polarity switching mode.
Simultaneous determination of multiclass illegal dyes possessing different chemical properties is difficult. By using LC-MS/MS via negative/positive ion switching mode, an efficient and fast multi-residual method for simultaneous determination of multiclass 52 illegal dyes with different acidic-basic properties in foodstuffs was developed and validated during one single run, including 23 fat-soluble neutral azo dyes, 8 acidic sulfonated azo dyes, 12 triphenylmethane basic dyes, three basic indole dyes, three xanthene dyes, one quinoline dye, and two anthraquinones dyes. The illegal dyes were extracted with methanol-acetonitrile and further purified with d-SPE procedure to reduce interference. Sample dilution with 100-fold was used for the elimination of matrix effects of the quantitation of LC-MS/MS analysis. Validation data showed the good recoveries in the range of 71.2-111.2%, with relative standard deviations less than 20%, suggesting the developed method is suitable for the identification and quantitation of multiclass illegal dyes at trace levels in foods.


A pilot study of glioblastoma multiforme in elderly patients: treatments, O-6-methylguanine-DNA methyltransferase (MGMT) methylation status and survival.
Elderly Glioblastoma multiforme (GBM) patients have a worse prognosis and receive variable treatments. MGMT gene promoter methylation is linked with improved survival in GBM. We examined treatments administered and survival including in relation to MGMT methylation status in elderly GBM patients. Patients ≥65 years with diagnosed GBM between 1/01/2007 and 30/04/2009 and undergoing either a biopsy, subtotal (STR) or gross total resection (GTR) were included. The collected information included MGMT status [methylated (ME) vs. unmethylated (UN)] and survival data. p<0.05 was considered significant. 59 patients were identified with median age at diagnosis being 72.68 years (65.72-85.04). Treatment included surgery (25 GTR, 8 STR, 26 biopsy), chemoradiation (22) and radiotherapy alone (20). Overall median overall survival (MOS) was 219 days. MOS with chemoradiation was 316 days vs. 143 days without it (p=0.011). 47 patients had definite MGMT status (28 ME, 19 UN). In ME patients, 9/28 received temozolamide compared to 10/19 in UN category. Temozolamide administration in patients with definite MGMT status was based on WHO performance status (p=0.007). MOS in UN group was 308 days vs. 167 days in ME group (p=0.068). In a multivariate Cox model including use of temozolamide, WHO score and methylation status, only temozolamide use was significantly associated with a reduced risk for death (HR 0.443, 95% CI 0.200-0.982, p=0.045). In this small cohort of patients, chemoradiation in suitable elderly GBM patients seemed to afford a survival benefit. MGMT methylation was not associated with an improved survival with temozolamide being the only factor leading to a better survival. Temozolamide use should be considered irrespective of MGMT status in this population with future large prospective studies needed to elucidate this further.


Characterization of cDNAs for calmodulin and calmodulin-like protein in the freshwater mussel Hyriopsis cumingii: differential expression in response to environmental Ca(2+) and calcium binding of recombinant proteins.
Calmodulin and calmodulin-like protein are two crucial calcium regulators in bivalves. However, molecular characteristics and expression patterns of these genes in the freshwater mussel are poorly understood. In this study, two cDNAs encoding novel calmodulin and calmodulin-like protein (HcCaM and HcCaLP) were cloned and characterized from the freshwater pearl mussel Hyriopsis cumingii. The full-length cDNA of HcCaM was 726 bp, including a 118-bp 5'-untranslated region (UTR), a 447-bp open reading frame (ORF), and a 161-bp 3'-UTR. The 1217-bp HcCaLP cDNA comprised of a 51-bp 5'-UTR, a 447-bp ORF, and a 716-bp 3'-UTR. The potential phosphorylation sites of, Arg(80) and Phe(100) in deduced HcCaM were mutated to Thr(80) and Tyr(100) in HcCaLP. Tissue-specific expression analysis revealed that HcCaM mRNA was prominently expressed in the gill, mantle center, and foot. In contrast, HcCaLP mRNA was mainly expressed in the mantle edge. The recombinant HcCaM and HcCaLP proteins expressed in Escherichia coli showed the typical Ca(2+) dependent electrophoretic shift characterization as CaM and differed in the calcium binding affinity. The calcium stimulation test that lasted 5 weeks implied that HcCaM and HcCaLP had differential expression patterns in response to various environmental Ca(2+) concentrations (0.25-1.25 mM). The expression of HcCaM mRNA was up-regulated by low Ca(2+) concentration (0.25 mM), and the highest expression of HcCaLP mRNA occurred under Ca(2+) concentration of 1 mM.


Genome-wide methylation profiling identifies a novel gene signature for patients with synchronous colorectal cancer.
There are no robust tools for the diagnosis of synchronous colorectal cancer (SyCRC). Herein, we developed the first methylation signature to identify and characterise patients with SyCRC. For biomarker discovery, we analysed the genome-wide methylation profiles of 16 SyCRC and 18 solitary colorectal cancer (SoCRC) specimens. We thereafter established a methylation signature risk-scoring model to identify SyCRC in an independent cohort of 38 SyCRC and 42 SoCRC patients. In addition, we evaluated the prognostic value of the identified methylation profile. We identified six differentially methylated CpG probes/sites that distinguished SyCRC from SoCRC. In the validation cohort, we developed a methylation panel that identified patients with SyCRC from not only larger tumour (AUC = 0.91) but also the paired remaining tumour (AUC = 0.93). Moreover, high risk scores of our panel were associated with the development of metachronous CRC among patients with SyCRC (AUC = 0.87) and emerged as an independent predictor for relapse-free survival (hazard ratio = 2.72; 95% CI = 1.12-6.61). Furthermore, the risk stratification model which combined with clinical risk factors was a diagnostic predictor of recurrence (AUC = 0.90). Our novel six-gene methylation panel robustly identifies patients with SyCRC, which has the clinical potential to improve the diagnosis and management of patients with CRC.


Stat3 induces oncogenic Skp2 expression in human cervical carcinoma cells.
Dysregulated Skp2 function promotes cell proliferation, which is consistent with observations of Skp2 over-expression in many types of human cancers, including cervical carcinoma (CC). However, the molecular mechanisms underlying elevated Skp2 expression have not been fully explored. Interleukin-6 (IL-6) induced Stat3 activation is viewed as crucial for multiple tumor growth and metastasis. Here, we demonstrate that Skp2 is a direct transcriptional target of Stat3 in the human cervical carcinoma cells. Our data show that IL-6 administration or transfection of a constitutively activated Stat3 in HeLa cells activates Skp2 mRNA transcription. Using luciferase reporter and ChIP assays, we show that Stat3 binds to the promoter region of Skp2 and promotes its activity through recruiting P300. As a result of the increase of Skp2 expression, endogenous p27 protein levels are markedly decreased. Thus, our results suggest a previously unknown Stat3-Skp2 molecular network controlling cervical carcinoma development.


Reaching out of the shade.
Competition for light determines the success of individual plants in dense vegetation. Much depends on the capacity of plants to detect neighbours quickly and on their ability to respond to these signals. Recent findings indicate that although red:far-red ratios, and thus phytochromes, are of major importance in shade-avoidance responses, they do not act alone. Differences in light intensity also provoke shade-avoidance phenotypes, with blue light playing an important role in dense stands. Moreover, links between shade-avoidance signalling and auxins, gibberellins and ethylene have emerged. Additional breakthroughs are based on transcriptome studies that have unveiled new components in the response to shading. Amongst these, the phytochrome interacting factor 3-like proteins PIL1 and PIL2 underline the importance of circadian gating in shade avoidance.


Banding studies in Canis familiaris. II. Nucleolar organizer regions and NOR association.
Nucleolar organizer regions (NORs) in the female dog karyotype are presented. Eight autosomes Nos. 5, 8, 14, 16, 19, 21, 32, and 37 showed active NORs. We observed a high incidence (50%) of metaphases with NOR association.


Proliferon: the functional unit of rapidly proliferating organs.
Continuously replicating organs are generally composed of several cell population types. These may be divided according to their function into two classes: 1. parenchyma: cells destined to perform a certain metabolic function peculiar to the organ under study, 2. supporting cell populations, consisting of fibroblasts and vascular supply always accompanied by nerve fibers. The kinetics of all the cells are highly coordinated. They all share one progenitor region. It is postulated that in this common progenitor region the two cell population classes are assembled into complex units denominated as proliferons. The proliferon starts its existence as a whole, matures as a whole and disintegrates at the organ periphery. It consists of four basic elements: parenchyma, connective tissue, blood vessels and nerve fibers. This model has been previously called upon to describe the kinetics of the rodent incisor tooth and the intestinal mucosa. It is assumed to be the elementary functional unit of all rapidly proliferating organs such as: skin, hair, endometrium, bone marrow, intestinal mucosa and rodent incisor.


High Tangent Radiation Therapy With Field-in-Field Technique for Breast Cancer.
We evaluated whether the field-in-field (FIF) technique improves the homogeneity of the target in high tangent radiation therapy (HTRT). This study included 30 patients. In total, 3 HTRT plans were created: 1 with conventional opposed fields (Conv-p), 1 with the FIF technique (FIF-p), and 1 with FIF technique using lung-blocked subfields (FIF-LB-p). The maximum dose of the breast and planning target volume (PTV) was significantly lower for FIF-p and FIF-LB-p than Conv-p. Homogeneity index of PTV was also significantly lower for FIF-p and FIF-LB-p than Conv-p. Homogeneity index of the breast or PTV was significantly better for FIF-p than FIF-LB-p. The volumes of the breast or the PTV receiving 95% and 90% of the prescribed dose were also significantly better for FIF-p, indicating the advantages of FIF-p. The FIF technique was useful in HTRT and improved homogeneity in the target.


Epidural stimulation restores muscle synergies by modulating neural drives in participants with sensorimotor complete spinal cord injuries.
Multiple studies have corroborated the restoration of volitional motor control after motor-complete spinal cord injury (SCI) through the use of epidural spinal cord stimulation (eSCS), but rigorous quantitative descriptions of muscle coordination have been lacking. Six participants with chronic, motor and sensory complete SCI underwent a brain motor control assessment (BMCA) consisting of a set of structured motor tasks with and without eSCS. We investigated how muscle activity complexity and muscle synergies changed with and without stimulation. We performed this analysis to better characterize the impact of stimulation on neuromuscular control. We also recorded data from nine healthy participants as controls. Competition exists between the task origin and neural origin hypotheses underlying muscle synergies. The ability to restore motor control with eSCS in participants with motor and sensory complete SCI allows us to test whether changes in muscle synergies reflect a neural basis in the same task. Muscle activity complexity was computed with Higuchi Fractal Dimensional (HFD) analysis, and muscle synergies were estimated using non-negative matrix factorization (NNMF) in six participants with American Spinal Injury Association (ASIA) Impairment Score (AIS) A. We found that the complexity of muscle activity was immediately reduced by eSCS in the SCI participants. We also found that over the follow-up sessions, the muscle synergy structure of the SCI participants became more defined, and the number of synergies decreased over time, indicating improved coordination between muscle groups. Lastly, we found that the muscle synergies were restored with eSCS, supporting the neural hypothesis of muscle synergies. We conclude that eSCS restores muscle movements and muscle synergies that are distinct from those of healthy, able-bodied controls.


The changing characteristics of atrial fibrillation patients treated with warfarin.
It has been suggested that direct oral anticoagulants are being preferentially used in low risk atrial fibrillation (AF) patients. Understanding the changing risk profile of new AF patients treated with warfarin is important for interpreting the quality of warfarin delivery through an anticoagulation clinic. Six anticoagulation clinics participating in the Michigan Anticoagulation Quality Improvement Initiative enrolled 1293 AF patients between 2010 and 2014 as an inception cohort. Abstracted data included demographics, comorbidities, medication use and all INR values. Risk scores including CHADS2, CHA2DS2-VASc, HAS-BLED, SAMe-TT2R2, and Charlson comorbidity index (CCI) were calculated for each patient at the time of warfarin initiation. The quality of anticoagulation was assessed using the Rosendaal time in the therapeutic range (TTR) during the first 6 months of treatment. Between 2010 and 2014, patients initiating warfarin therapy for AF had an increasing mean CHADS2 (2.0 ± 1.1 to 2.2 ± 1.4, p = 0.02) and CCI (4.7 ± 1.8 to 5.1 ± 2.0, p = 0.03), and a trend towards increasing mean CHA2DS2-VASc, HAS-BLED, and SAMe-TT2R2 scores. The actual TTR remained unchanged over the study period (62.6 ± 18.2 to 62.7 ± 17.0, p = 0.98), and the number of INR checks did not change (18.9 ± 5.2 to 18.5 ± 5.1, p = 0.06). Between 2010 and 2014, AF patients newly starting warfarin had mild increases in risk for stroke and death with sustained quality of warfarin therapy.


Complementary anti-cancer pathways triggered by inhibition of sideroflexin 4 in ovarian cancer.
DNA damaging agents are a mainstay of standard chemotherapy for ovarian cancer. Unfortunately, resistance to such DNA damaging agents frequently develops, often due to increased activity of DNA repair pathways. Sideroflexin 4 (SFXN4) is a little-studied inner mitochondrial membrane protein. Here we demonstrate that SFXN4 plays a role in synthesis of iron sulfur clusters (Fe-S) in ovarian cancer cells and ovarian cancer tumor-initiating cells, and that knockdown of SFXN4 inhibits Fe-S biogenesis in ovarian cancer cells. We demonstrate that this has two important consequences that may be useful in anti-cancer therapy. First, inhibition of Fe-S biogenesis triggers the accumulation of excess iron, leading to oxidative stress. Second, because enzymes critical to multiple DNA repair pathways require Fe-S clusters for their function, DNA repair enzymes and DNA repair itself are inhibited by reduction of SFXN4. Through this dual mechanism, SFXN4 inhibition heightens ovarian cancer cell sensitivity to DNA-damaging drugs and DNA repair inhibitors used in ovarian cancer therapy, such as cisplatin and PARP inhibitors. Sensitization is achieved even in drug resistant ovarian cancer cells. Further, knockout of SFXN4 decreases DNA repair and profoundly inhibits tumor growth in a mouse model of ovarian cancer metastasis. Collectively, these results suggest that SFXN4 may represent a new target in ovarian cancer therapy.


A case of invasive thymoma associated with myasthenia gravis, myositis and demyelinating neuropathy.
A 56 year old male presented after 2 months of muscle stiffness, pain and palpable lumps. Biopsy confirmed the presence of myositis. Myasthenia gravis and peripheral neuropathy became clinically apparent within days of commencing corticosteroid therapy. 4 months later, at operation, a locally invasive thymoma was found. This combination of features has not previously been described.


DNA-based bioanalytical microsystems for handheld device applications.
This article reviews and highlights the current development of DNA-based bioanalytical microsystems for point-of-care diagnostics and on-site monitoring of food and water. Recent progresses in the miniaturization of various biological processing steps for the sample preparation, DNA amplification (polymerase chain reaction), and product detection are delineated in detail. Product detection approaches utilizing "portable" detection signals and electrochemistry-based methods are emphasized in this work. The strategies and challenges for the integration of individual processing module on the same chip are discussed.


David S. Miller: Scientist, Mentor, Friend-a tribute and thank you.
David S. Miller was Acting Scientific Director of the Division of Intramural Research at the National Institute of Environmental Health Sciences, National Institutes of Health, and Head of the Intracellular Regulation Group in the Laboratory of Toxicology and Pharmacology before he retired in 2016. David received his Ph.D. in biochemistry from the University of Maine in 1973. David was a Group Leader at the Michigan Cancer Foundation before joining the NIEHS in 1985. His research covered a wide range from renal excretory transport mechanisms to regulation of transporters at the blood-CSF and blood-brain barriers, from fish, amphibians and birds to mammals. David was an outstanding scientist with irresistible enthusiasm for science and an incredible ability to think outside the box while being an exceptional mentor and friend.


Surface cooling rapidly induces coordinated activity in the upper and lower airway muscles of the fetal lamb in utero.
Stimulation of cutaneous thermoreceptors may be an important factor in the initiation of continuous breathing at birth. Maintenance of a patent airway is also important in the continuation of effective ventilation after birth, but whereas in the adult the principal pharyngeal dilator is the genioglossus muscle, in the fetus genioglossus phasic activity is not synchronous with that of the fetal diaphragm. To ascertain whether a cold stimulus that initiates continuous breathing would also induce synchronized inspiratory activity in the upper airway muscles of the fetus, we have cooled fetal lambs in utero and examined the response of the genioglossus and alae nasi muscles in relation to diaphragm activity. Deep regular breathing as recorded by diaphragmatic activity and tracheal pressure started within 1-102 s after cooling commenced and coordinated inspiratory activity was seen in the alae nasi within 2-356 s. Genioglossus activity became synchronized with that of the diaphragm within 11-356 s. Cooling was continued for 4 h but although in one fetus continuous breathing with associated inspiratory activity in the genioglossus and alae nasi muscles lasted throughout the 4-h period, in the others continuous breathing was not sustained and adaptation to the cold stimulus occurred after periods ranging from 27-218 min. The relationship between breathing, upper airway muscle activity, and sleep state passed through one or more different phases, including breathing through high voltage electrocortical activity, before the normal fetal pattern of episodic breathing restricted to the low voltage electrocortical state resumed.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of a Single Dose Dexmedetomidine on Surgical Field Visibility During Middle Ear Microsurgery: A Randomized Study.
To investigate whether a single dose of dexmedetomidine (DEX) improves surgical field visibility. Randomized, prospective, double-blind study. Tertiary teaching hospital. ASA I or II patients undergoing tympanoplasty with ossiculoplasty were randomly assigned to receive either 0.8 μg/kg DEX (Group D) or the same volume of saline (Group N) 10 min before anesthesia induction. The primary outcome was the visibility of the surgical field rated by surgeons by Boezaart score. The secondary outcomes were consumption of anesthesia, hemodynamic profiles, and subsequent recovery. Boezaart scores for surgical visibility were lower in Group D than in Group N (1.3 ± 0.8 versus 1.8 ± 0.9, P = 0.014). Minimum alveolar concentrations of sevoflurane (Group D 1 [0.9/1.1] versus Group N 1 [1/1.2], P = 0.018) and remifentanil consumption (Group D 370 [218/504] μg versus Group N 583 [300/1028] μg, P = 0.002) were less in Group D. Except for a transient increase in blood pressure and a decrease in heart rate during DEX infusion, hemodynamic profiles were more stable in Group D than in Group N. More patients needed morphine rescue and presented with postoperative nausea and vomiting in Group N than in Group D (Group D 1 versus Group N 8, P = 0.029). Recovery time was comparable between the two groups (Group D 19 min versus Group N 18 min, P = 0.569). Use of a single dose of DEX resulted in improved surgical visibility, less consumption of anesthesia, and more favorable hemodynamic profile while not delaying recovery time.


Recent Developments of n-Type Organic Thermoelectric Materials: Influence of Structure Modification on Molecule Arrangement and Solution Processing.
Organic semiconductor (OSCs) thermoelectric materials have been studied widely due to their low thermal conductivity and solution processing characteristics. Currently, the high conductivity (up to 1000 s cm-1 ) has boosted the performance of p-type organic thermoelectric materials substantially. In contrast, the development of n-type organic thermoelectric materials is still limited by their low mobility, inferior air stability, and poor doping efficiency, which is relevant to the molecule structure and dopant dispersion. Herein, the recent development of n-type organic thermoelectric materials was reviewed with an emphasis on molecule structure modification and solution processing. Methods for optimizing conjugate structure were summarized from the effects of conjugated backbone modification and side chains diversification on molecular stacking. The primary n-type dopants were also summarized briefly. Especially, the role of solution aggregation controlling on film preparation and properties was given special attention. Additionally, the emergence of organic diradicals with low lowest unoccupied molecular orbital energy level and no doping was introduced, which shows great potential in n-type organic thermoelectric materials. All these endeavors have led to the development of n-type OSCs materials. This Review is aimed at illustrating the state-of-the-art progress and providing some guideline for the design of organic thermoelectric materials in the future.


Perception of partner sexual history: Effects on safe-sex intentions.
Sexual intercourse is a dyadic activity, and intentions to engage in safe sex vary across partners. Because pregnant and newly parenting adolescents and young adults are at high risk for sexually transmitted infections (STIs), it is important to understand sexual decision-making in this population. This cross-sectional study examined how participants' own risk behavior and their partners' risk behavior influence perceptions of partner risk, and the impact of risk perceptions on condom use intentions and monogamy intentions in 296 pregnant adolescent and young adult couples (MAgeFemale = 18.71 years; MAgeMale = 21.33 years). Participants' behavior and their partners' behavior both related to increased perceptions of partner risk. Male participants' perceptions were more strongly influenced by female partners' behavior than participants' own behavior. Perceiving a partner as having a history of more risk behaviors trended toward a negative relationship with condom use intentions and monogamy intentions. For females, more previous sex partners related negatively to condom use intentions and positively to monogamy intentions. Having a male partner with more previous sex partners related positively to condom use intentions and monogamy intentions. Perceptions of partner risk did not significantly relate to condom use intentions and monogamy intentions, however, trends suggest that risk perception could reflect similarity bias and ongoing risk engagement. Differences in partner perception by gender suggest that females may communicate more openly about risks. Interventions to reduce STI transmission in couples should work to interrupt trajectories of risky behavior and enhance risk communication. (PsycINFO Database Record


[Serum copper levels in early pregnancy complicated by symptoms of spontaneous abortion and infection].
The study evaluates serum levels of copper, chorionic gonadotropin, estradiol, progesterone and prolactin in patients with symptoms of miscarriage and in uncomplicated pregnancies in cases with or without cervical or vaginal infections detected by vaginal or cervical smears, as well as Chlamydia testing. The study included 50 patients with symptoms of threatening miscarriage and 50 patients with uncomplicated pregnancies. Hormone levels were determined by ELISA method and copper was evaluated by acid medium colorimetry. We found that values of serum copper, estradiol, progesterone and prolactin were significantly lower in patients with lower genital tract infection. Decreased levels of serum copper could be used as a method of choice for detecting infection during the first trimester of pregnancy.


Congenital metastatic cervical teratoma: diagnostic and management considerations.
Cervical teratomas in the newborn are uncommon and difficult management problems, as their natural history and prognosis are not well defined. Existing or potential airway obstruction is usually the main concern in acute management of these patients. Total excision is essential to avoid local recurrence in benign lesions, and a small but present risk of malignancy can result in death from metastatic lesions which appear later. A unique case of neonatal malignant cervical teratoma with large congenital metastatic lesions present in liver, lung, and buttocks was successfully managed. Magnetic resonance imaging (MRI) was invaluable, both in delineating these lesions and in planning a four-stage curative resection of all macroscopic disease. Such a case has not been reported previously.


Complete covalent structure of 60-kDa esterase isolated from 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced rabbit liver microsomes.
The 60-kDa esterase was isolated from liver microsomes of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced rabbits and its complete amino acid sequence determined. Automated sequence analysis of intact protein, as well as characterization of the peptides obtained from enzymatic and chemical cleavages, led to the elucidation of the primary structure. The protein is a single polypeptide consisting of 539 residues and molecular weight 59,478. The active site serine is 195, and another diisopropylphospho binding site is at histidyl 441. Carbohydrate chains are attached at aspariginyl residues 61 and 363. Although 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment induces this esterase severalfold, the amino acid sequence of the induced enzyme is identical to that of the enzyme isolated from liver microsomes of untreated rabbits. The sequence of the microsomal esterase is 30% identical with the sequences of human serum cholinesterase and the acetylcholinesterase from Torpedo californica. There is also a close homology between the 60-kDa esterase and the COOH-terminal domain of bovine thyroglobulin.


Schizencephaly: heterogeneous etiologies in a population of 4 million California births.
Schizencephaly is a rare congenital brain defect characterized by gray matter lined clefts of the cerebral mantle, frequently accompanied by other defects of the CNS such as absence of the corpus callosum. This study in a California population of >4 million births from 1985-2001 found a population prevalence of 1.54/100,000. Among 63 cases, there was an association with young parental age in isolated schizencephaly (RR 3.9 mothers; 5.8 fathers), which was also seen in mothers but not fathers of non-isolated cases (RR 3.2). Monozygotic twins may also be at increased risk for schizencephaly (RR 2.1). One third of cases had a non-CNS abnormality, over half of which could be classified as secondary to vascular disruption, including gastroschisis, bowel atresias, and amniotic band disruption sequence. Other apparent rare causes included chromosomal aneuploidy, non-random associations, and unusual syndromes. Our observations suggest that schizencephaly has heterogeneous etiologies many of which are vascular disruptive in origin.


Saturation of ecosystems with toxic metals in Sudbury basin, Ontario, Canada.
Mining and resource recovery activities have not been kind to ecosystems in the Sudbury basin, Ontario. The combination of logging, smelting, fires and erosion resulted in an unusual anthropogenic ecosystem of denuded barren land with lifeless lakes, or a micro-desert. Since the 1970s, however, the concerted efforts made to reduce the emissions and rehabilitate parts of the degraded ecosystem have resulted in improvements in water quality, and recoveries in phytoplankton, zooplankton, zoobenthos and fish communities but have had little impact on toxic metal concentrations in many lakes. We show that most of the catchments in the Sudbury basin have become saturated with Cu and Ni, and some with Zn and Pb. It is estimated that mobilization of metals stored in soils and glacial overburden by surface runoff, groundwater drainage and wind re-working of tailings can sustain the high concentrations of Cu and Ni in many lakes for well over 1000 years. Strategies to immobilize the pollutant metals in the watershed rather than further emission controls may be required for dealing with high levels of toxic metals in surface waters of the saturated ecosystems.


Comparison of the ALPS and PHILOS plating systems in proximal humeral fracture fixation - a retrospective study.
Open reduction and plate osteosynthesis are considered as a successful technique for the treatment of proximal humerus fracture (PHF) despite high complication rates. The objective of our study was to review the clinical outcome and complications of the Anatomic Locking Plate System (ALPS) and compare it to the Proximal Humeral Internal Locking System (PHILOS). Our hypothesis was that ranges of motion (ROM) were superior and complication rates were lower with ALPS. Twenty patients treated with ALPS for PHF were retrospectively compared to 27 patients treated with PHILOS. Union, ROM and complications were clinically and radiologically assessed at 6 weeks, 3, 6, 12 and 18-24 months post-operatively. Mean age was 52 ± 14 in the ALPS group and 58 ± 13 in the PHILOS group. Last follow-ups were conducted at a mean of 20.6 ± 4.8 months. Mean shoulder abduction was superior with ALPS by 14° (p-value = 0.036), 15° (p-value = 0.049), and 15° (p-value = 0.049) at 3, 6, and 12 months respectively. Mean shoulder external rotation was superior with ALPS by 11° (p-value = 0.032), 15° (p-value = 0.010) and 12° (p-value = 0.016) at 6 weeks, 3 and 6 months respectively. At the end of the follow-up, ROM remained better with ALPS, but not significantly. Complication rates over 21 months reached 20% with ALPS and 48% with PHILOS (p-value = 0.045). Implant removal rates reached 10% with ALPS and 37% with PHILOS (p-value = 0.036). Avascular necrosis was the only cause for hardware removal in the ALPS group. The ALPS group showed better clinical outcomes with faster recovery in abduction and external rotation, although no difference in ROM remained after 21 months. Additionally, the complications rate was lower at last follow up. In our experience, the ALPS plating system is an effective management option in some PHF.


Impact of mental health facilities on property values.
Community opposition to the establishment of a small-scale mental health facility is often intense. One frequently voiced fear is that the estabishment of a facility will cause property values in its vicinity to decline. This paper examines empirical evidence of the impact on property values in the neighborhood of 12 mental health centers in Philadelphia. It is concluded that such facilities have an indeterminate effect on property values in their vicinity, contary to popular opinion.


Infection prevention in solid organ transplantation.
As complications from infection are a major cause of morbidity and mortality following transplantation, infection prevention is a cornerstone of any modern solid organ transplantation program. There is no doubt that, among other measures, antimicrobial prophylaxis has decreased the incidence and severity of posttransplant infections, and it is a major contributor to the currently improved survival rates of solid organ transplant recipients. This chapter is not a thorough analysis of all studies examining the prevention of infection following organ transplantation, but a practical guide to widely accepted recommendations regarding the prevention of common infections in the transplant setting, such as bacterial infections, including tuberculosis, cytomegalovirus, hepatitis viruses or invasive fungal infections.


Waterlogging responses of Sporobolus virginicus (L.) Kunth.
Flooding responses in Sporobolus virginicus (L.) Kunth., a perennial C4 grass, propagated from plants collected on the fringes of a mangrove swamp, were examined in a glasshouse study over 42 days. Flooding significantly reduced soil redox potential, induced adventitious root development, shifted resource allocation from below- to above-ground components without affecting total biomass accumulation and significantly decreased below-ground/above-ground biomass ratios. Although soil waterlogging significantly increased alcohol dehydrogenase activity (ADH) after 30 h, significant increase in central air space by 45-50% of the cross-sectional stem area eliminated root hypoxia, and ADH activity decreased to levels equivalent to drained controls after 42 days. In addition, flooded plants exhibited significantly higher carbon dioxide assimilation rates but similar relative growth rates (RGR) to drained controls. The results indicate that S. virginicus responds to water-logging by a combination of metabolic, morphological and anatomical mechanisms, which may account for its widespread distribution in coastal lagoons, estuaries and marshes.


Separation and properties of five glycosaminoglycan sulfatases from rat skin.
Chondroitin sulfates, dermatan sulfate, heparan sulfate, heparin, keratan sulfate, and oligosaccharides derived from these sulfated glycosaminoglycans have been used for the measurement of sulfatase activity of rat skin extracts. Chromatographic fractionation of the extracts followed by specificity studies demonstrated the existence of five different sulfatases, specific for 1) the nonreducing N-acetylglucosamine 6-sulfate end groups of heparin sulfate and keratan sulfate, 2) the nonreducing N-acetylgalactosamine (or galactose) 6-sulfate end groups of chondroitin sulfate (or keratan sulfate), 3) the nonreducing N-acetylgalactosamine 4-sulfate end groups of chondroitin sulfate and dermatan sulfate, 4) certain suitably located glucosamine N-sulfate groups of heparin and heparan sulfate, or 5) certain suitably located iduronate sulfate groups of heparan sulfate and dermatan sulfate. Two arylsulfatases, one of which was identical in its chromatographic behaviors with the third enzyme described above, were also demonstrated in the extracts. These results taken together with those previously obtained from studies on human fibroblast cultures suggest that normal skin fibroblasts contain at least five specific sulfatases and diminished activity of any one may result in a specific storage disease.


Bilateral brain dysfunction during motor activation in type II schizophrenia measured by EEG mapping.
In this final electroencephalographic (EEG) mapping study of our series on motor dysfunction in neuroleptic-treated schizophrenic patients, we studied 10 right-handed patients with marked negative symptomatology [type II; raw score on the SANS (Munich version) 31.4 +/- 5.1]. Simple and multisensorimotor tasks involving both the dominant and nondominant hand were used for cortical activation. All tasks were referred to resting states obtained after specially designed relaxation procedures. In contrast to predominantly type I patients (SANS-MV score 12.3 +/- 4.9) of our previous EEG mapping studies, we found for resting states minor evidence (only) of increased power values in the frequency bands delta and theta. Furthermore, in contrast to signs of "left hemisphere dysfunction" and possible "compensatory right hemisphere overactivation" during motor tasks, which we discussed previously for our type I patients, we found for the type II schizophrenics a bilateral brain dysfunction. This consisted of "nonreactivity" in all frequency bands except alpha, in which, on the contrary, a "hyperreactivity" seemed to be present. In combination with evidence of bilateral hemispheric dysfunction in type II patients reported by other authors using EEG, evoked potentials, regional cerebral blood flow (rCBF) and magnetic resonance imaging (MRI) methods, this suggests that marked bilateral brain dysfunction may be correlated in schizophrenia with a clinical syndrome corresponding rather to the "negative pole" of the positive-negative dimension. In contrast, "left hemisphere dysfunction" and "signs of compensatory overactivation" seem to be linked more to a "positive" symptomatology. Finally, discrepancies of our EEG mapping and rCBF findings during motor activity suggest, speculatively, "uncoupling" between electrical and circulatory parameters in schizophrenia involving both hemispheres in type II, and predominantly the left hemisphere in type I, patients.


Radioiodination and preclinical evaluation of 4-benzyl-1-(3-[125I]-iodobenzylsulfonyl)piperidine as a breast tumor imaging tracer in mouse.
4-Benzyl-1-(3-iodobenzylsulfonyl)piperidine, 4-B-IBSP, has shown high-binding affinity to both sigma (σ) receptors in our previous work. In current study, radiolabeling and preclinical evaluation of 4-benzyl-1-(3-[125I]-iodobenzylsulfonyl)piperidine, 4-B-[125I]IBSP, in human ductal breast carcinoma (T47D) cells and in breast adenocarcinoma-bearing BALB/c mice are described. Radioiodination of this new σ ligand was performed by a palladium-catalyzed stannylation approach followed by oxidative iododestannylation reaction using Iodo-Gen. Competition-binding assays for binding of 4-B-[125I]IBSP to guinea pig brain membranes and to T47D cells were performed with known σ ligands. The selectivity and binding characteristics (B max and K d) were analyzed. In vitro stability and in vivo blood metabolism studies were also evaluated. Moreover, biodistribution studies were performed in normal and into the tumor-bearing mice at interval time points post-injection (p.i.). Both in vitro and in vivo blockade experiments were done in the presence of the σ receptors blocking agents. Radioiodinated ligand was obtained in high yield and high specific activity. The σ inhibition constants (K i, nM) for 4-(3-iodobenzyl)-1-(benzylsulfonyl)piperazine (4-IBBSPz), (+)-pentazocine, haloperidol, DTG, and 4-B-IBSP were 1.37 ± 0.19, 3.90 ± 0.77, 2.69 ± 0.33, 30.62 ± 2.01, and 0.61 ± 0.05, respectively. 4-B-[125I]IBSP bound to σ receptor sites preferably to very high-affinity binding sites on T47D cells. The radioligand showed acceptable in vitro and in vivo stabilities in the blood pool. However, in vivo biodistribution studies in normal Swiss albino mice revealed fast clearance of 4-B-[125I]IBSP from blood and the other normal organs. Biodistribution experiments of 4-B-[125I]IBSP in breast adenocarcinoma tumor-bearing BALB/c mice showed a relatively high tumor uptake at 30 min p.i. (4.13 ± 0.95) that reaches to 1.57 ± 0.24 even after 240 min p.i. A pre-injection of 4-B-IBSP and haloperidol with 4-B-[125I]IBSP resulted in 36-57% decrease in activity in the tumor, liver, and brain at 60 min p.i. The high affinity of 4-B-[125I]IBSP to σ receptor-binding sites, its relatively high uptake, and preferential retention in the tumor as well as an increasing trend observed in the tumor to blood and in the tumor to muscle ratios suggests that an iodine-123 labeled counterpart, 4-B-[123I]IBSP, would be a promising σ radioligand for pursuing further studies to assess its potential for breast tumors imaging with SPECT.


The relative numbers of long-wavelength-sensitive to middle-wavelength-sensitive cones in the human fovea centralis.
The determination of the relative numbers of different cone types in the human retina is fundamental to our understanding of visual sensitivity and color vision; yet direct measurement which provide this basic information have not previously been made for all cone types. Here we present a model which links the detection of a test light of small dimension to the number of cones contributing to detection of the light. We selectively isolated either the long-wavelength-sensitive (L) or the middle-wavelength-sensitive (M) cones, by choosing combinations of wavelengths of adapting backgrounds and tests to favor detection by the cone class of interest. Our model was applied to the detection functions measured for six color normal observers to obtain estimates of the relative numbers of L to M cones. Our estimates ranged between 1.46 and 2.36 for our observers with a mean value near two L cones for every M cone in human fovea centralis.


Preoperative Assessment of Obstructive Sleep Apnea in Bariatric Patients Using Polysomnography or Polygraphy.
Preoperative assessment of obstructive sleep apnea (OSA) in patients scheduled for bariatric surgery can be performed by in-laboratory polysomnography (PSG) or by portable polygraphy (PP) at home. We aimed to evaluate the association between PSG/PP, OSA diagnosis, and implementation of continuous positive airway pressure (CPAP) therapy. All patients who underwent bariatric surgery from 2015 to 2017 were retrospectively reviewed. Patients underwent preoperative PSG or PP, based on prevailing protocols or at the physician's discretion. Logistic regression analyses were performed to determine predictors of CPAP implementation. OSA-related postoperative complications were analyzed in both groups. During the study period, 1464 patients were included. OSA was diagnosed in 79% of 271 patients undergoing PSG, compared to 64% of 1193 patients undergoing PP (p < 0.001), with median apnea-hypopnea index (AHI) of 15.8 and 7.7, respectively. CPAP treatment was initiated in 52% and 27% of patients, respectively, p < 0.001. Predictors (with adjusted odds ratio) in multivariate regression analysis for CPAP implementation were as follows: male gender (5.15), BMI ≥ 50 (3.85), PSG test (2.74), hypertension (2.38), and age ≥ 50 (1.87). OSA-related complications did not differ between groups (p = 0.277). Both PSG and PP are feasible options for preoperative OSA assessment in bariatric patients. When PP is performed, some underdiagnosis may occur as cases of mild OSA may be missed. However, clinically relevant OSA is detected by both diagnostic tools. No difference in OSA-related complications was found. PP is a safe, less invasive option and can be considered as a suitable measure for OSA assessment in this population.


Totally implantable venous access ports via the external jugular vein: safety and effectiveness for young pediatric patients.
Various venous approaches are possible during implanting a totally venous access port. The veins, which are commonly used in pediatric patients are internal and external jugular veins. Comparison of different venous approaches has been discussed in a few reports only. The present study reviews the complication rate, operation time of implanting the port via different veins in children. From January 2003 to December 2005, 94 venous access ports were implanted in 88 consecutive patients in the Pediatric Surgical section of the Taipei Veterans General Hospital. The patients were classified according to the vein used. Group A (n=45), the external jugular vein access group; and group B (n=43), the internal jugular vein access group. The operation time in group A and B were 38.4+/-11.1 and 57.6+/-20.3 min, respectively. The mean operation time of group A was significantly shorter than that of group B (P<0.001). The overall complication rates in group A and B were 8.5%, and 19.1%, respectively. These differences, however, were not significant (P>0.05). The external jugular vein approach has a shorter operation time and a lower complication rate than the internal jugular vein approach. This approach may be a method of choice in selected pediatric patients.


Cardiac troponin T and CK-MB mass release after visually successful percutaneous transluminal coronary angioplasty in stable angina pectoris.
The incidence of cardiac troponin T (Tn-T) and creatine kinase (CK) isoenzyme MB mass release was studied in 23 patients with stable angina pectoris undergoing visually successful percutaneous transluminal coronary angioplasty (PTCA). Serial blood samples were drawn for measurement of serum Tn-T, CK-MB mass, total CK activity, CK-MB activity, and lactate dehydrogenase isoenzyme (LD-1). ST segment monitoring was carried out during PTCA and for the following 24 hours. None of the patients showed electrocardiographic (ECG) evidence of myocardial infarction. However, Tn-T was elevated in three patients (0.23 to 1.32 micrograms/L), and in these three and an additional three patients CK-MB mass was also elevated (7.0 to 27.5 micrograms/L). Total CK activity and LD-1 were only elevated in one of these six patients. None had elevated CK-MB activity. ST segment depression on ECG recording was not predictive of Tn-T or CK-MB mass release. Patients with elevated Tn-T or CK-MB mass did not differ with respect to demographic data, stenosis characteristics, or in the PTCA procedure. We conclude that CK-MB mass uncovers clinically and ambulatory electrocardiographically inapparent severe myocardial ischemia/minor myocardial damage (microembolization) in 26% (6 of 23) of patients after visually successful PTCA; 13% (3 of 23) had elevated Tn-T, indicating minor myocardial damage. The application of these markers in the future could be of considerable value for determining the efficacy of coronary angioplasty and atherectomy, as well as for drug therapy in connection with such procedures.


Wives' evaluation of problems related to laryngectomy.
Previous questionnaire studies of problems after laryngectomy have been directed toward the patients. In this study, 45 wives of laryngectomees were surveyed regarding their prior understanding of laryngeal surgery. The wives were also asked questions pertaining to health and physical care, and financial and social problems encountered after the operation. The survey results indicate a need for improved family counseling both before and after surgery.


Polyglutamine protein in tumor cells sensitizes tumor cells to natural killer cell cytolysis.
Patients with Huntington's diseases display reduced tumor incidence mediated by unclear mechanisms. Besides, the effects of characteristic overexpression of 97 polyglutamine protein (polyQ protein) on tumor surveillance by the host immune system have not been investigated. NK cells are cytotoxic innate lymphocytes that sense and kill stressed and transformed cells through recognition of abnormal molecular patterns. Here, we found that polyQ protein induced the accumulation of misfolded proteins in tumor cells and sensitized these tumor cells to NK cell cytolysis in vitro. Transcriptome analysis showed that polyQ protein overexpression caused an abnormal transcriptome changes in tumor cells, which might predispose these tumor cells to death upon NK cell cytolysis. However, on the other hand, polyQ protein in NK cells compromised NK cell cytolytic activity through forcing the accumulation of misfolded proteins. Furthermore, polyQ overexpression enriched oxidative phosphorylation related gene set in NK cells, which might lead to an exhaustion-like status of NK cells with reduced cytolytic activity. Therefore, our study shows that polyQ protein overexpression in tumors alone, but not in both tumor cells and NK cells, might result in increased tumor rejection by NK cells, revealing a dual role of polyQ protein on tumor surveillance by the immune system.


A binary histologic grading system for ovarian serous carcinoma is an independent prognostic factor: a population-based study of 4317 women diagnosed in Denmark 1978-2006.
To evaluate the prognostic significance of histologic grade on survival of ovarian serous cancer in Denmark during nearly 30 years. Using the nationwide Danish Pathology Data Bank, we evaluated 4317 women with ovarian serous carcinoma in 1978-2006. All pathology reports were scrutinized and tumors classified as either low-grade serous carcinomas (LGSC) or high-grade serous carcinomas (HGSC). Tumors in which the original pathology reports were described as well-differentiated were classified as LGSC, and those that were described as moderately or poorly differentiated were classified as HGSC. We obtained histologic slides from the pathology departments for women with a diagnosis of well-differentiated serous carcinoma during 1997-2006, which were then reviewed by expert gynecologic pathologists. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression analysis with follow-up through June 2009. Women with HGSC had a significantly increased risk of dying (HR=1.9; 95% CI: 1.6-2.3) compared with women with LGSC while adjusting for age and stage. Expert review of 171 women originally classified as well-differentiated in 1997-2006 were interpreted as LGSC in 30% of cases, whereas 12% were interpreted as HGSC and 50% as serous borderline ovarian tumors (SBT). Compared with women with confirmed LGSC, women with SBT at review had a significantly lower risk of dying (HR=0.5; 95% CI: 0.22-0.99), and women with HGSC at review had a non-significantly increased risk of dying (HR=1.6; 95% CI: 0.7-3.4). A binary grading system is a significant predictor of survival for ovarian serous carcinoma.


A standard definition of disease freedom is needed for prostate cancer: undetectable prostate specific antigen compared with the American Society of Therapeutic Radiology and Oncology consensus definition.
Freedom from prostate cancer is defined by undetectable prostate specific antigen (PSA) after surgery and the American Society of Therapeutic Radiology and Oncology (ASTRO) criteria are recommended for irradiation. Whether these definitions of disease freedom are comparable was evaluated in this study. From August 1992 to August 1996 simultaneous irradiation with prostate 125iodine implantation followed by external beam irradiation was performed in 591 consecutive men with stage T1T2NX prostate cancer. All patients had a transperineal implant and none received neoadjuvant hormones. Disease freedom was defined by a PSA cutoff of 0.2 ng./ml. and the ASTRO consensus definition. Median followup was 6 years (range 5 to 8). Of the 591 men in this study 65 had recurrence by ASTRO criteria and 93 had recurrence by a PSA cutoff of 0.2 ng./ml., which was a significant difference (p = 0.001). On multivariate analysis of the factors related to disease-free status the definition of disease freedom, pretreatment PSA and Gleason score were highly significant. Of the 528 men with a minimum 5-year PSA followup the 8-year disease-free survival rate by ASTRO criteria was 99% in those who achieved a PSA nadir of 0.2 ng./ml. and 16% in those with a nadir of 0.3 to 1 ng./ml. Of the 469 disease-free patients by ASTRO criteria with a minimum 5-year followup 455 (97%) achieved a PSA nadir of 0.2 ng./ml. or less. The definition of freedom from prostate cancer significantly affects treatment results. A standard definition is needed and a PSA cutoff of 0.2 ng./ml. is suggested as the standard for all curative treatments for localized prostate cancer.


Nocodazole, a microtubule de-polymerising agent, induces apoptosis of chronic lymphocytic leukaemia cells associated with changes in Bcl-2 phosphorylation and expression.
Microtubule active drugs are used in the treatment of malignancies and their mechanism of action in cycling cells is to produce mitotic arrest followed by apoptosis. In this study, we investigate in detail the specificity and mechanism by which a microtubule de-polymerising agent, nocodazole, induces apoptosis in non-cyclingm, i.e. G(0)/G(1), chronic lymphocytic leukaemia (CLL) B-cells. The majority of cases of CLL are sensitive (IC(50)<or=16 microM) but normal peripheral blood B-cells, which are also in G(0)/G(1), are resistant to the maximum in vitro concentration of this agent. Taxol, a microtubule stabilising drug does not kill CLL cells suggesting a specific effect of nocodazole. The mechanism of apoptosis involves mitochondrial membrane depolarisation, activation of caspases and cleavage of PARP. Nocodazole causes two patterns of change to Bcl-2 expression. In one there is increase in expression of the serine-70 phosphorylated form of Bcl-2 and in the other total Bcl-2 expression is reduced. Collectively the data shows that sensitivity to nocodazole-induced apoptosis is a feature of chronic lymphocytic leukaemia and suggests that newer microtubule active agents be systematically investigated for their effectiveness in this condition.


Composition and Distribution of Aliphatic Hydrocarbon Compounds and Biomarkers in Seafloor Sediments from Offshore of the Leizhou Peninsula (South China).
The offshore of Leizhou Peninsula (LP, China), which contains unique ecosystems such as mangroves, seagrass beds, and coral reefs, is an environmentally sensitive area. For this reason, the levels of aliphatic hydrocarbon including biomarkers (hopanes, steranes) in the offshore seafloor sediments were analyzed in terms of their composition, distribution, and input sources and aimed to evaluate the extent of possible petroleum hydrocarbon contamination in the sediments of coastal areas. The total aliphatic hydrocarbons (TAH) fraction, the content of total n-alkanes (nC14-nC37) (∑n-alkanes), and content of hopane + sterane are in the range of 13.76-99.53, 1.22-8.33, and 0.02-0.23 μg/g dw, respectively. The presence of unresolved complex mixture (UCM) hydrocarbons hump and petrogenic steranes and hopanes in these seafloor sediments suggest that petrogenic sourced hydrocarbon inputs were present. The stations on the peninsula's southwest side had the lowest values of UCM/resolved aliphatic compounds (UCM/R) and UCM/n-alkanes. These findings suggest that seafloor sediments from the southwest offshore of the peninsula were likely contaminated by recently inputted petroleum hydrocarbons. The presence of relatively high ∑n-alkanes content in seafloor sediments from southwest offshore of the LP, combined with relatively low natural n-alkane ratios (NARs), indicates an increased influence of petrogenic hydrocarbons. The elevated levels of recent petrogenic hydrocarbon contamination in the sediments from the LP's southwestern offshore were likely related to petroleum exploitation in the Beibu Gulf's Maichen and Wushi sags.


Changes in the liver protein pattern of female Wistar rats treated with the hypoglycemic agent SDZ PGU 693.
SDZ PGU 693 acts as a hypoglycemic agent by stimulating glucose utilisation in insulin-sensitive peripheral tissues, such as skeletal muscle and fat. In a 28 day toxicity study the compound was found to induce hepatocellular hypertrophy in Wistar rats treated with 300 mg/kg/day. To gain insights into the pathomechanism of these alterations, aliquots of liver samples from control and treated female Wistar rats were separated by two-dimensional protein gel electrophoresis and the digitized images of the protein patterns were searched for protein abundance changes. Significant treatment-related quantitative changes (P < 0.001) were found in 29 liver proteins. Major increases were observed in several microsomal proteins, including NADPH cytochrome P-450 reductase, cytochrome b5 and serine protease inhibitor. The changes in the cytochrome related enzymes, both known co-factors of the P-450 enzyme system, strongly suggest that SDZ PGU 693 induces microsomal proliferation and induction of the P-450 enzyme system. Decreases were observed in a series of mitochondrial proteins, such as F1ATPase-delta subunit and ornithine aminotransferase precursor as well as in several cytosolic proteins such as the liver fatty acid binding protein, arylsulfotransferase and the senescence marker protein-30. The changes in F1ATPase-delta subunit and liver fatty acid binding protein together suggest a down-regulation of the mitochondrial liver fatty acid metabolism, likely reflecting the pharmacological action of the compound. These results show that SDZ PGU 693 produces a complex pattern of gene expression changes which give insights into the molecular mechanisms of both its pharmacological action and a toxic response.


Finite element analysis of left ventricle during cardiac cycles in viscoelasticity.
To investigate the effect of myocardial viscoeslasticity on heart function, this paper presents a finite element model based on a hyper-viscoelastic model for the passive myocardium and Hill's three-element model for the active contraction. The hyper-viscoelastic model considers the myocardium microstructure, while the active model is phenomenologically based on the combination of Hill's equation for the steady tetanized contraction and the specific time-length-force property of the myocardial muscle. To validate the finite element model, the end-diastole strains and the end-systole strain predicted by the model are compared with the experimental values in the literature. It is found that the proposed model not only can estimate well the pumping function of the heart, but also predicts the transverse shear strains. The finite element model is also applied to analyze the influence of viscoelasticity on the residual stresses in the myocardium.


Disrupted actin dynamics trigger an increment in the reactive oxygen species levels in the Arabidopsis root under salt stress.
Changes in actin dynamics represent the primary response of the plant cell to extracellular signaling. Recent studies have now revealed that actin remodeling is involved in abiotic stress tolerance in plants. In our current study, the relationship between the changes in actin dynamics and the reactive oxygen species (ROS) level at the initial stages of salt stress was investigated in the elongation zone of the Arabidopsis root tip. We found that a 200 mM NaCl treatment disrupted the dynamics of the actin filaments within 10 min and increased the ROS levels in the elongation zone cells of the Arabidopsis root tip. We further found that the NADPH oxidase activity inhibitor, diphenyleneiodonium, treatment blocked this ROS increase under salt stress conditions. The roles of actin dynamics and the NADPH oxidases in ROS generation were further analyzed using the actin-specific agents, latrunculin B (Lat-B) and jasplakinolide (Jasp), and mutants of Arabidopsis NADPH oxidase AtrbohC. Lat-B and Jasp promote actin depolymerization and polymerization, respectively, and both were found to enhance the ROS levels following NaCl treatment. However, this response was abolished in the atrbohC mutants. Our present results thus demonstrate that actin dynamics are involved in regulating the ROS level in Arabidopsis root under salt stress conditions. Salt stress disrupts the dynamics of the actin filaments in Arabidopsis in the short term which are involved in regulating the ROS levels that arise under salt stress conditions via the actions of the AtrbohC.


Meta-analysis of dual-energy computed tomography virtual non-calcium imaging to detect bone marrow edema.
This meta-analysis aimed to evaluate the accuracy of dual-energy CT (DECT) virtual non-calcium (VNC) imaging for the detection of bone marrow edema (BME). A systematic literature search up to March 2017 was performed to find relevant original studies. Two reviewers independently selected studies, assessed literature quality, and extracted data. Pooled sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, and other measures of DECT accuracy for detecting BME were calculated using random effects models. Risk of heterogeneity was assessed for the appropriateness of meta-analysis. Fourteen studies involving 2205 regions of vertebrae, hips, knees, and ankles were included. To evaluate the accuracy of BME detection using DECT, calculations were performed to obtain a pooled sensitivity of 0.812 (95% confidence interval [CI], 0.780-0.841) and specificity of 0.951 (95% CI, 0.940-0.960). The AUROC value was 0.9635. The major potential cause of heterogeneity was bone position. No significant publication bias was present. DECT VNC imaging gives very good diagnostic performance for BME detection and will likely be an important and common modality for acute assessment in the future.


Potential antihyperlipidemic polyketones from endophytic Diaporthe sp. JC-J7 in Dendrobium nobile.
Eleven new polyketones named diaporthsins A-K (1-11) were isolated from the fermentation of Diaporthe sp. JC-J7. The chemical structures of compounds (1-11) were elucidated by spectroscopic methods including HRESIMS, 2DNMR, NMR and chemical methods. Compound 11 features an unusual acyclic polyketone-phenolic polyketone hybrid structure that integrates the characteristics of different fungal metabolites (cytosporone and multiplolide). Compound 3 was the only C12-polyketone obtained in this research. These new polyketones showed inhibitory activity on triglycerides (TG) in steatosis hepatocyte L-02 cells. Among them, compound 5 and (4E)-6,7,9-trihydroxydec-4-enoic acid displayed inhibitory activities on TG in steatotic L-02 cells with inhibition ratios of 26% and 21% at concentration of 5 μg mL-1; also, inhibition ratios of 8-O-acetylmultiplolide A and phomopsisporone A at concentration of 5 μg mL-1 were calculated to be about 24% and 16%, respectively, which were equivalent to the antihyperlipidemic activity of lovastatin. The preliminary structure-activity relationship indicated that acetyl at C-8 can increase the antihyperlipidemic activity of multiplolide A and the glycol ester and hydroxyl at C-6 can also increase the corresponding activity of diaporthsin B.


Total arterial myocardial revascularization using composite and sequential grafting with the off-pump technique.
Multiple arterial myocardial revascularizations are increasingly undertaken using off-pump techniques; however, various arterial grafting techniques are utilized. This study aimed to review the outcome of combining arterial composite and sequential grafting with off-pump techniques. We retrospectively reviewed the records of 107 consecutive patients who underwent coronary bypass surgery with off-pump and arterial composite grafting techniques between April 2001 and March 2004. The left internal thoracic artery (LITA) was harvested in all patients, and the right internal thoracic artery (RITA), the radial artery (RA), and the gastroepiploic artery (GEA) were harvested in 69 patients, in 83 patients, and in 53 patients, respectively. Early postoperative angiograms were evaluated in 97 patients. There were 488 distal anastomoses, an average of 4.5 per patient. Forty-four in situ LITAs were used as LITA Y-composite grafts with a free RITA (n = 19), RA (n = 24), or free GEA (n = 1). Forty-three in situ RITAs were used as RITA-RA grafts (n = 42) or a RITA-GEA graft (n = 1). Twenty-one in situ GEAs were used as composite grafts with the RA (n = 17) or a free RITA (n = 4). There were no hospital deaths. The patency of the LITA was 100%, and that of the RA was 97.3%, while patencies of both in situ and free RITA and GEA were 100%. During the follow-up period (mean: 22.1 months), there were 3 late deaths, but none were cardiac related. Total arterial revascularization with composite and sequential grafting is a safe and effective technique in patients undergoing off-pump coronary artery bypass surgery.


Gender differences in treatment adherence among youth with cystic fibrosis: development of a new questionnaire.
Some prior studies have reported that girls with cystic fibrosis (CF) experience higher morbidity and mortality compared to boys. In this study, the authors compared boys' and girls' perceptions of disease-related strains and resources associated with living with CF, and the relationship of these factors to CF treatment feelings and behaviors. All 10-21 year olds with CF at the Minnesota Cystic Fibrosis Center were invited by mail to complete a new self-report survey (Living with CF Questionnaire--LCFQ). Of these 177 youth, 58% (49 boys and 54 girls) returned surveys. Exploratory and confirmatory factor analyses revealed nine factors in the LCFQ. Partial support was found for hypothesized gender differences in these factors. Compared to boys, girls reported significantly more illness-related strains and worries, including emotional strains, greater treatment discouragement, lower self-esteem, and lower adherence to some aspects of the CF treatment regimen (coughing, eating high-fat foods, taking meds/pills). Living with CF appears to have a greater emotional impact on adolescent girls compared to boys. These gender differences may contribute to the poorer pulmonary function observed among girls with cystic fibrosis during the adolescent years.


Application of a simplified mathematical model to estimate the effect of forced aeration on composting in a closed system.
The aeration rate is a key process control parameter in the forced aeration composting process because it greatly affects different physico-chemical parameters such as temperature and moisture content, and indirectly influences the biological degradation rate. In this study, the effect of a constant airflow rate on vertical temperature distribution and organic waste degradation in the composting mass is analyzed using a previously developed mathematical model of the composting process. The model was applied to analyze the effect of two different ambient conditions, namely, hot and cold ambient condition, and four different airflow rates such as 1.5, 3.0, 4.5, and 6.0 m(3) m(-2) h(-1), respectively, on the temperature distribution and organic waste degradation in a given waste mixture. The typical waste mixture had 59% moisture content and 96% volatile solids, however, the proportion could be varied as required. The results suggested that the model could be efficiently used to analyze composting under variable ambient and operating conditions. A lower airflow rate around 1.5-3.0 m(3) m(-2) h(-1) was found to be suitable for cold ambient condition while a higher airflow rate around 4.5-6.0 m(3) m(-2) h(-1) was preferable for hot ambient condition. The engineered way of application of this model is flexible which allows the changes in any input parameters within the realistic range. It can be widely used for conceptual process design, studies on the effect of ambient conditions, optimization studies in existing composting plants, and process control.


Response shift in parent-reported psychopathology in children with chronic physical illness.
Because physical-mental comorbidity in children is relatively common, this study tested for response shift (RS) in children with chronic physical illness using a parent-reported measure of child psychopathology. Data come from Multimorbidity in Children and Youth across Life-course (MY LIFE), a prospective study of n = 263 children aged 2-16 years with physical illness in Canada. Parents provided information on child psychopathology using the Ontario Child Health Study Emotional Behavioral Scales (OCHS-EBS) at baseline and 24 months. Oort's structural equation modeling was used to test for different forms of RS in parent-reported assessments between baseline and 24 months. Model fit was evaluated using root mean square error of approximation (RMSEA), comparative fit index (CFI), and standardized root mean residual (SRMR). There were n = 215 (81.7%) children with complete data and were included in this analysis. Of these, n = 105 (48.8%) were female and the mean (SD) age was 9.4 (4.2) years. A two-factor measurement model provided good fit to the data [RMSEA (90% CI) = 0.05 (0.01, 0.10); CFI = 0.99; SRMR = 0.03]. Non-uniform recalibration RS was detected on the conduct disorder subscale of the OCHS-EBS. This RS effect had negligible impact on the longitudinal change in externalizing and internalizing disorders construct over time. Response shift detected on the conduct disorder subscale of the OCHS-EBS, indicated that parents of children with physical illness may recalibrate their responses on child psychopathology over 24 months. Researchers and health professionals should be aware of RS when using the OCHS-EBS to assess child psychopathology over time.