Natural history and risk factors associated with early and established HIV type 1 infection among reproductive-age women in Malawi.
Data evaluating the biological events and determinants of early human immunodeficiency virus type 1 (HIV-1) infection are limited in sub-Saharan Africa. We examined plasma viral levels and trends during early and established HIV-1 infection among reproductive-age women who participated in a randomized trial to treat genital tract infection in Malawi. We also assessed the association of injectable hormonal contraceptive use with HIV-1 infection. We studied 3 groups of women who were infected or uninfected with HIV-1: seroconverters, seroprevalent women, and seronegative women. Questionnaires and blood samples were collected at baseline and every 3 months for 1 year. The virus set point in seroconverters and levels and trends of viral load over time were determined. The associations of injectable hormonal contraceptive use with HIV-1 infection and viral load were assessed using conditional logistic regression and mixed-effect models, respectively. In the original clinical trial, 844 women infected with HIV-1 and 842 women not infected with HIV-1 were enrolled. Of 31 women who experienced seroconversion during 12 months, 27 were matched with 54 seroprevalent and 54 seronegative women. The estimated median plasma virus set point was 4.45 log(10) copies/mL (interquartile range, 4.32-5.14 log(10) copies/mL). Injectable hormonal contraceptive use was significantly associated with HIV-1 seroconversion (adjusted odds ratio, 10.42; P = .03) but not with established HIV-1 infection. Among the seroconverters, a statistically significant interaction was found between the linear association of viral load and time of injectable hormonal contraceptive use (regression coefficient, -0.14; P = .02). Knowledge of virus set point and trends of viral load in HIV-1 seroincident and seroprevalent asymptomatic women could assist in antiretroviral treatment management.


Social class and age at diagnosis of Hodgkin's disease: new epidemiologic evidence for the "two-disease hypothesis".
The bimodality in the age-incidence pattern of Hodgkin's disease (HD) suggests that the disease may result from two causal pathways with differing age peaks. Among young adults, HD may develop as a rare consequence of a common infection (probably viral), with risk increasing with age at time of infection. However, among older persons, HD may result from other causes, probably similar to those of the other lymphomas. We evaluated this hypothesis in a population-based, case-control study in eastern Massachusetts involving 326 newly diagnosed cases (patients greater than or equal to 15 years of age) and 650 population controls. These subjects were compared for factors in childhood environment that influence age of exposure to common viruses, including sibship size, parental education, and type of housing. Among young adults (15-39 years of age), risk of HD was associated with small family size, single-family housing, and relatively high maternal education, consistent with the delayed infectious exposure hypothesis. Among middle-aged persons (40-54 years of age), a similar pattern of social class risk factors was present. However, among older persons (greater than or equal to 55 years of age), risk was not associated with social class; if anything, patients were of somewhat lower social class background than controls. These findings are consistent with the "two-disease hypothesis," in that social class risk factors differed between younger and older persons. These findings, coupled with other epidemiologic observations, suggest that the pathogenesis of HD among older persons is independent of that among younger persons.


Conditional cash transfers and women's reproductive choices.
We study potential non-targeted effects of a large-scale national conditional cash transfer program-Peru's Juntos-on the fertility and reproductive decisions of adult beneficiaries. We use an event study design, exploiting time and geographic variation in the rollout of the program, to identify the causal effects of the program. We find that Juntos decreases the number of children that adult beneficiaries have and that these effects persist over time. We explore various mechanisms and find that Juntos does not affect fertility preferences but rather empowers women to avoid unwanted births. We provide evidence that this decrease is most likely due to better access to and more extensive use of modern birth control methods.


Reduced endurance of the cervical flexor muscles in patients with concurrent temporomandibular disorders and neck disability.
Subjects with temporomandibular disorders (TMDs) have been found to have clinical signs and symptoms of cervical dysfunction. Although many studies have investigated the relationship between the cervical spine and TMD, no study has evaluated the endurance capacity of the cervical muscles in patients with TMD. Thus the objective of this study was to determine whether patients with TMD had a reduced endurance of the cervical flexor muscles at any level of muscular contraction when compared with healthy subjects. One hundred and forty-nine participants provided data for this study (49 subjects were healthy, 54 had myogenous TMD, and 46 had mixed TMD). There was a significant difference in holding time at 25% MVC between subjects with mixed TMD when compared to subjects with myogenous TMD and healthy subjects. This implies that subjects with mixed TMD had less endurance capacity at a lower level of contraction (25% MVC) than healthy subjects and subjects with myogenous TMD. No significant associations between neck disability, jaw disability, clinical variables and neck flexor endurance test were found.


Prevalence and molecular characterisation of Cryptosporidium and Giardia species in pre-weaned sheep in Australia.
A total of 477 faecal samples from pre-weaned sheep from 5 different farms in the south west of Western Australia were screened for the presence of Cryptosporidium and Giardia using PCR. There were substantial differences in prevalence between the farms and overall prevalence was 24.5% and 11.1%, respectively for Cryptosporidium and Giardia. At the 18S locus, 66 Cryptosporidium positives were identified, the majority of which were C. bovis (n=52), followed by the cervid genotype (n=10) and C. parvum (n=2). At a second diagnostic locus, using C. parvum and C. hominis-specific qPCR primers, 63 C. parvum positives were identified, some of which were co-infections with C. bovis. The C. parvum/C. hominis qPCR was more sensitive than the nested 18S PCR at detecting C. parvum. This may be due to the low numbers of oocysts present, as quantitation data indicated that all the C. parvum detected were present in low numbers (1-10 oocysts). It may also be that using C. parvum-specific primers is necessary to determine the true prevalence of C. parvum. Amongst Giardia positive isolates, G. duodenalis genotype E (livestock) was the most prevalent (36/53), with G. duodenalis genotype A detected in five positive isolates. There were also 11 mixed A and E infections detected. The findings of the present study indicate that pre-weaned lambs are not an important source of zoonotic Giardia genotypes in Australia but may be an important source of zoonotic Cryptosporidium.


Subjective awareness of tardive dyskinesia and insight in schizophrenia.
Lack of awareness of tardive dyskinesia (TD) and poor insight into mental illness are common in schizophrenia, raising the possibility that these phenomena are manifestations of a common underlying dysfunction. We investigated relationships between low awareness of TD and poor insight into mental illness in 130 patients with schizophrenia and TD. We also examined selected demographic and clinical correlates of these two phenomena. Sixty-six (51%) patients had no or low awareness of TD and 94 (72%) had at least mild impairment of insight into their mental illness. Low awareness of TD was not significantly correlated with greater impairment of insight into mental illness. Regression analyses indicated that the Positive and Negative Syndrome Scale (PANSS) disorganised factor (β=0.72, t=11.88, p<0.01) accounted for 52% of the variance in insight into mental illness (adjusted R(2)=0.55) (F[2, 127]=81.00, p<0.01) and the Extrapyramidal Symptom Rating Scale (ESRS) dyskinesia subscale score (β=0.47, t=6.80, p<0.01), PANSS disorganised factor (β=-0.26, t=-3.73, p<0.01), and ESRS parkinsonism subscale score (β=0.31, t=4.55, p<0.01) together accounted for 37% of the variance in awareness of TD (adjusted R(2)=0.37) (F[3, 126]=26.87, p<0.01). The two phenomena appear to be dissociated, and may be domain-specific.


Metabolic, membrane, and functional responses of human polymorphonuclear leukocytes to platelet-activating factor.
The phospholipid mediator of anaphylaxis, platelet-activating factor (PAF) is chemotactic for polymorphonuclear leukocytes (PMN). We have examined this agent's effects on several other PMN functions. Human PMN were prepared from heparinized venous blood by Ficoll gradient. Metabolic burst was examined by measurement of O2 use and O2.- production in the presence or absence of PAF (10(-6)--10(-9) M). Unless cells were treated with cytochalasin-B (5 micrograms/ml), no significant respiratory burst was demonstrated. However, pretreatment with PAF (10(-7) M) enhanced approximately threefold the O2 utilization found when cells were subsequently stimulated with 10(-7) M FMLP. PAF also stimulated arachidonic acid metabolism in 14C-arachidonic acid-labeled PMN. Thin-layer chromatography analysis of chloroform-methanol extracts showed substances that comigrated with authentic 5-hydroxyeicosatetraenoic acid had a marked increase in radioactivity following PAF stimulation at 10(-7) M. PAF failed to stimulate release of granule enzymes, B-glucuronidase, lysozyme, or myeloperoxidase unless cytochalasin-B were added. PAF from 10(-6) M to 10(-10) M affected PMN surface responses. PMN labeled with the fluorescent dye, chlorotetracycline, showed decreased fluorescence upon addition of PAF, suggesting translocation of membrane-bound cations. Further, the rate of migration of PMN in an electric field was decreased following PAF exposure, a change consistent with reduced cell surface charge. PMN self-aggregation and adherence to endothelial cells were both influenced by PAF (10(-6) M--10(-9) M). Aggregation was markedly stimulated by the compound, and the percent PMN adhering to endothelial cell monolayers increased almost twofold in the presence of 10(-8) M PAF. Thus, PAF promotes a variety of PMN responses: enhances respiratory burst, stimulates arachidonic acid turnover, alters cell membrane cation content and surface charge, and promotes PMN self-aggregation as well as adherence to endothelial cells.


The anomalous kinetics of coupled aspartate aminotransferase and malate dehydrogenase. Evidence for compartmentation of oxaloacetate.
Cytoplasmic aspartate aminotransferase and malate dehydrogenase were purified from pig heart. Kinetic parameters were determined for the separate reaction catalysed by each enzyme and used to predict the course of the coupled reaction: (see article). Although a lag phase should have been easily seen, none was detected. The same coupled reaction was also carried out by using radioactive aspartate in the presence of unlabelled oxaloacetate. The reaction was quenched with HClO4 after 70 ms and the specific radioactivity of the malate produced in this system was found to be essentially the same as that of the original aspartate. These results show that oxaloacetate produced by the aspartate aminotransferase is converted into malate by malate dehydrogenase before it equilibrates with the pool of unlabelled oxaloacetate and are consistent with a proposal that the enzymes are associated in a complex. However, no physical evidence of the existence of a complex could be found. An alternative means of compartmentation of the intermediate as an unstable isomer is considered.


Does Kiitricha (Protista, Ciliophora, Spirotrichea) belong to Euplotida or represent a primordial spirotrichous taxon? With suggestion to establish a new subclass Protohypotrichia.
The genus Kiitricha was long assumed to be the most primordial taxon in the Stichotrichia [hypotrichs sensu lato (s. l.)] based on its morphological features and was considered to be an intermediate between heterotrichs and the traditional hypotrichous assemblage. In order to evaluate the phylogenetic position of Kiitricha within the Hypotrichia, we sequenced the small-subunit rRNA gene and the alpha-tubulin gene for a Qingdao population of Kiitricha marina. Phylogenetic trees were constructed and compared to morphological and morphogenetic data. The results show that (i) Kiitricha is positioned near Phacodinium, both of which always form a sister clade to the assemblage including Stichotrichia, Hypotrichia, Oligotrichia and Choreotrichia, (ii) Kiitricha, which may represent an intermediate between heterotrichs (s. l.) and the Stichotrichia-Hypotrichia complex, is probably an ancestor-like form of the latter group and (iii) in contrast to morphological characters, both molecular and ontogenetic data support the separation of Kiitricha from the hypotrichs (s. l.). Thus, Kiitricha might be placed in the class Spirotrichea at about subclass level, next to Phaconidiidia, Hypotrichia and Stichotrichia, which supports the establishment of a new subclass Protohypotrichia n. subclass within the class Spirotrichea, with characterizations including slightly differentiated somatic ciliature (i.e. cirri on the ventral side generally uniform and non-grouped, no clearly defined marginal cirral rows, ciliature on the dorsal side mixed with cirri and dikinetids, no clearly differentiated dorsal kineties) and a unique but intermediate morphogenetic pattern of cortical structures between Hypotrichia and Stichotrichia.


Some factors which affect the initiation of growth of Cryptococcus neoformans.
Howard, Dexter H. (University of California, Los Angeles). Some factors which affect the initiation of growth of Cryptococcus neoformans. J. Bacteriol. 82:430-435. 1961.-The observation that a strain of Cryptococcus neoformans failed to grow in a medium containing normal human serum led to an investigation of some of the physiological factors controlling initiation of growth by this fungus. The data presented show that the growth of C. neoformans is markedly inhibited in media with initial pH values slightly above neutrality. The growth of four strains of the fungus was completely suppressed in peptone broth at pH values above 8. The growth of two strains was partially inhibited at a pH of 7.3. Two other strains grew well at 7.3, but were partially inhibited at pH 7.5. The growth in media at pH values which partially inhibited multiplication was granular in appearance. Microscopically the granules were composed of clumps of yeast cells. The possibility is suggested that pH may exert a portion of its effect on the growth of C. neoformans by influencing those factors which affect the stability of the cells in suspension. At a temperature of 25 C, growth of the fungus was initiated in media with a pH which suppressed growth at a temperature of 37 C. Under the experimental conditions employed in these studies, proteose peptone no. 3 (Difco) serves as both a carbon and a nitrogen source. However, glucose, which is assimilated by C. neoformans in contrast to lactose, permitted the growth of the fungus at pH values which suppressed growth in the absence of the sugar. Since weakly buffered media, containing filtered, normal human serum, have an alkaline reaction higher than that shown to suppress the growth of C. neoformans, it was concluded that this factor was primarily responsible for the failure of the fungus to reproduce in tissue culture media. However, it is also possible to show that even under optimal pH conditions normal human serum exerts an anticryptococcal effect. This activity of human serum was relatively heat-stable and was expressed only in high concentrations of serum. Serum adsorbed with viable cells of C. neoformans also inhibited the growth of the fungus, but a partially purified globulin fraction of serum was not inhibitory. The data are discussed in relation to the work of other investigators.


Purification and properties of the ribonucleic acid-dependent ribonucleic acid polymerase from Halobacterium cutirubrum.
1. The RNA-dependent RNA polymerase from Halobacterium cutirubrum was purified to electrophoretic homogeneity. 2. It requires a single-stranded molecule of RNA or polyribonucleotide as template. 3. Nearest-neighbour analyses of the products formed on random poly(A,U) or alternating poly(A-U) templates and base analysis of the product of synthesis directed by wheat-germ RNA prove that the template is copied accurately. 4. The enzyme initiates new chains with purine ribonucleoside triphosphates. 5. Sucrose-density-gradient analysis of the product indicates that it has a size distribution similar to that of the template. 6. Preliminary amino acid analysis of the RNA-dependent polymerase shows that it contains much less serine than either of the subunits of H. cutirubrum DNA-dependent RNA polymerase. 7. The RNA-dependent enzyme is unable to substitute for either subunit of the DNA-dependent polymerase, and both the latter are devoid of RNA-dependent activity.


Mothers' sociodemographic factors and use of health professionals for child feeding advice.
This study examined sociodemographic factors associated with mothers seeking child feeding advice from health professionals (HPs). Cross-sectional analysis of survey data from linked randomized controlled trials was conducted. Surveys asked which sources of feeding information mothers used when their child was 6 months and 5 years old. Logistic regression was used to examine associations between sociodemographic characteristics and use of information from HPs. Here, 947 and 405 mothers completed 6-month and 5-year surveys, respectively. At 6 months, multiparous mothers were less likely to seek advice from child and family health nurses (CFHNs) (adjusted odds ratio [AOR]: 0.558, 95% confidence interval [95% CI]: 0.416-0.749) and other HPs (AOR: 0.706, 95% CI: 0.542-0.919), unmarried mothers were less likely to seek advice from other HPs (AOR: 0.582, 95% CI: 0.342-0.990). At 5 years, mothers with household income ≥$80,000 p.a. were less likely to seek advice from CFHNs (AOR: 0.514, 95% CI: 0.302-0.875) and working mothers less likely to seek advice from general practitioners (GPs) (AOR: 0.581, 95% CI: 0.374-0.905). Mothers born in Australia were less likely to seek information from CFHNs (AOR: 0.462, 95% CI: 0.257-0.833) and GPs (AOR: 0.431, 95% CI: 0.274-0.677). There was a greater likelihood that multiparous mothers (AOR: 2.114, 95% CI: 1.272-3.516) and mothers of children whose fathers had not attended university (AOR: 2.081, 95% CI: 1.256-3.449) had never sought advice from CFHNs, and that mothers who had not attended university (AOR: 1.769, 95% CI: 1.025-3.051), multiparous (AOR: 1.831, 95% CI: 1.105-3.035) and employed (AOR: 2.058, 95% CI: 1.135-3.733) mothers had never sought advice from other HPs. Understanding sociodemographic factors associated with seeking child feeding advice from HPs may inform priorities for engaging families in health promotion.


Potential role of branched-chain amino acids in glucose metabolism through the accelerated induction of the glucose-sensing apparatus in the liver.
Branched-chain amino acids (BCAAs) have a potential to improve glucose metabolism in cirrhotic patients; however, the contribution of liver in this process has not been clarified. To estimate the effect of BCAA on glucose metabolism in liver, we evaluated the mRNA expression levels of glucose-sensing apparatus genes in HepG2 cells and in rat liver after oral administration of BCAA. HepG2 cells were cultured in low glucose (100 mg/dl) or high glucose (400 mg/dl) in the absence or presence of BCAA. The mRNA expression levels and protein levels of GLUT2 and liver-type glucokinase (L-GK) were estimated using RT-PCR and immunoblotting. The expression levels of transcriptional factors, including SREBP-1c, ChREBP, PPAR-γm and LXRα, were estimated. The mRNA expression levels of transcriptional factors, glycogen synthase, and genes involved in gluconeogenesis were evaluated in rat liver at 3 h after the administration of BCAA. BCAA accelerated the expression of GLUT2 and L-GK in HepG2 cells in high glucose. Expression levels of ChREBP, SREBP-1c, and LXRα were also increased in this condition. BCAA administration enhanced the mRNA expression levels of L-GK, SREBP-1c, and LXRα and suppressed the expression levels of G-6-Pase in rat liver, without affecting the expression levels of glycogen synthase or serum glucose concentrations. BCAA administration enhanced the bioactivity of the glucose-sensing apparatus, probably via the activation of a transcriptional mechanism, suggesting that these amino acids may improve glucose metabolism through the accelerated utility of glucose and glucose-6-phosphate in the liver.


Development of a preclinical model of ischemic cardiomyopathy in swine.
A number of promising therapies for ischemic cardiomyopathy are emerging, and the role of translational research in testing the efficacy and safety of these agents in relevant clinical models has become important. The goal of this study was to develop a chronic model of ischemic cardiomyopathy in a large animal model. In this study, 40 consecutive pigs were initially enrolled. To induce progressive stenosis, a plastic occluder with a fixed diameter of 1.0 mm fitted with an 18-gauge copper wire was placed around the proximal left anterior descending (LAD) coronary artery. Coronary angiography, hemodynamic measurements, and echocardiography were performed at 2 wk and 1, 2, and 3 mo. Overall mortality was 26% at 3 mo, and up to 80% of the pigs showed total occlusion of LAD at 1 mo. A significant depression of peak LV pressure rate of rise (+dP/dt(max)) was observed in the animals showing total artery occlusion throughout the study. Left ventricular ejection fraction was also impaired, and the left ventricular volumes tended to be larger in the pigs with occlusion. Approximately 10% of scar tissue was found in the LAD occluded pigs, whereas the coronary flow pattern in the rest of the area took the pattern of hibernating myocardium. At the same time, histological and protein analysis established the presence of fibrosis and ongoing apoptosis in the ischemic area. In this model, the timing and incidence of total occlusion and low mortality offer significant advantages over other ischemic cardiomyopathy models in conducting preclinical studies.


Perioperative parathyroid hormone levels in thyroid surgery.
Perioperative hypocalcemia from temporary parathyroid gland dysfunction is common after thyroid surgery. No reliable cutoff values for parathyroid hormone (PTH) and the subsequent possibility of developing hypocalcemia exist. The purpose of this study is to determine a criterion for predicting hypocalcemia based on different PTH levels as cutoff values. Retrospective chart review. A centralized database of intraoperative PTH levels was analyzed. PTH values approximately 10 minutes after excision of the thyroid gland and in the recovery room were obtained; serial ionized calcium levels were also analyzed. PTH values were then compared using chi-square analysis with significance defined as P < .05. A receiver operator characteristic (ROC) curve was also constructed to define sensitivities and specificities of different PTH levels as potential cutoff values. Eighty patients were identified meeting the study criteria between January 1999 and February 2005. Fourteen of the 80 (17.5%) patients became hypocalcemic during the hospital stay; none experienced permanent hypocalcemia. Patients who became hypocalcemic during their hospitalization were more likely to have a PTH level below 15 pg/mL (P < .01). Patients with a PTH level less than 15 pg/mL were more likely to develop hypocalcemia (P < .01). Finally, an ROC curve was constructed, allowing the surgeon to determine acceptable sensitivities and specificities and various PTH cutoff values. Low perioperative PTH levels significantly correlate with the presence of postoperative hypocalcemia but cannot be used to predict it. Using the ROC curve allows different chosen cutoff values to predict hypocalcemia with varying sensitivity and specificity.


Kinetics of plasma Epstein-Barr virus DNA during radiation therapy for nasopharyngeal carcinoma.
We studied the kinetics of circulating EBV DNA in the plasma of nasopharyngeal carcinoma (NPC) patients. Serial weekly sampling of 10 NPC patients revealed a rapid decline in plasma EBV DNA concentration after treatment. In two subjects, an initial rise in the circulating EBV DNA level was observed immediately after treatment initiation. Plasma EBV DNA levels were monitored daily during the first treatment week in a second cohort of five patients, and the results indicated that an initial rise in plasma EBV DNA concentration could be observed in all subjects during the first treatment week. This observation is consistent with the liberation of EBV DNA after therapy-induced cancer cell death. After this initial rise, plasma EBV DNA concentration was found to decay with a median half-life of 3.8 days (interquartile range, 2.4-4.4 days). Kinetic analysis of circulating tumor-derived DNA during treatment may be a powerful tool for evaluating the in vivo response of NPC and other tumors to antineoplastic treatment and may improve our understanding of the biology of plasma nucleic acids.


An essential role for endocytosis of rhodopsin through interaction of visual arrestin with the AP-2 adaptor.
Previously, we have identified a class of retinal degeneration mutants in Drosophila in which the normally transient interaction between arrestin2 (Arr2) and rhodopsin is stabilized and the complexes are rapidly internalized into the cell body by receptor-mediated endocytosis. The accumulation of protein complexes in the cytoplasm eventually results in photoreceptor cell death. We now show that the endocytic adapter protein AP-2 is essential for rhodopsin endocytosis through an Arr2-AP-2beta interaction, and mutations in Arr2 that disrupt its interaction with the beta subunit of AP-2 prevent endocytosis-induced retinal degeneration. We further demonstrate that if the interaction between Arr2 and AP-2 is blocked, this also results in retinal degeneration in an otherwise wild-type background. This indicates that the Arr2-AP-2 interaction is necessary for the pathology observed in a number of Drosophila visual system mutants, and suggests that regular rhodopsin turnover in wild-type photoreceptor cells by Arr2-mediated endocytosis is essential for photoreceptor cell maintenance.


Transurethral needle ablation for benign prostatic hyperplasia: 12-month results of a prospective, multicenter U.S. study.
To report the safety and efficacy of the transurethral needle ablation (TUNA) procedure for the treatment of clinical benign prostatic hyperplasia (BPH). One hundred thirty patients with BPH were enrolled in two identical protocols and treated by the TUNA procedure. Entry criteria included an American Urological Association symptom index (AUA SI) of 13 points or higher and a peak flow rate of 12 mL/s or less. Patients were followed up for 12 months. Efficacy parameters included the AUA SI, AUA problem index, BPH impact index (BPH II), quality of life (QOL) score, and peak flow rate. At each visit, side effects were elicited. Follow-up data are available for 93 patients at 12 months. All patients were given intraurethral lidocaine augmented by oral and/or parenteral sedation. No patient received spinal or general anesthesia. All patients tolerated the procedure well, and there were no deaths. Forty-one percent of patients (n = 53) had a catheter placed immediately after the procedure. At 12 months, the AUA SI had decreased from 23.7 to 11.9 (P < 0.0001) and the BPH II from 7.5 to 2.5 (P < 0.0001), whereas the peak flow rate had increased from 8.7 to 14.6 mL/s (P < 0.0001). Irritative voiding symptoms were noted in 20 patients (16%) at some point during follow-up. Two patients reported erectile dysfunction, and 1 reported retrograde ejaculation. In this prospective study of 130 patients with clinical BPH and lower urinary tract symptoms, TUNA provided substantive and lasting improvement according to AUA SI, BPH II, and QOL scores as well as peak flow rate over 1 year. The TUNA procedure was well tolerated, with few major side effects and complications noted. Longer follow-up is needed to document the maintenance of clinical benefit beyond 12 months.


Assembly, specific binding, and crystallization of a human TCR-alphabeta with an antigenic Tax peptide from human T lymphotropic virus type 1 and the class I MHC molecule HLA-A2.
T lymphocytes use TCR-alphabeta to bind and to recognize complexes of antigenic peptides bound to MHC proteins located at the surface of APCs. We have assembled and crystallized this intercellular complex of TCR/peptide/MHC from soluble human TCR-alphabeta and soluble peptide/HLA-A2 complexes. The soluble TCR-alphabeta binds specifically to its in vivo ligand, the complex of HLA-A2, and a peptide from the Tax protein of human T lymphotropic virus type 1. The soluble TCR also binds in vitro to an altered peptide ligand, which appears to be a partial agonist in T cell assays as determined by its ability to elicit different cytolytic and lymphokine secretion responses. Heterodimerization and the antigenic specificity of the TCR do not require its interchain disulfide bond, transmembrane segments, or glycosylations. Crystals of the TCR/peptide/HLA-A2 complex diffract x-rays, providing the means to study in atomic detail the mechanism of Ag-specific cell-cell recognition between T cells and target cells.


Screen detection and the WHO stepwise approach to the prevalence and risk factors of arterial hypertension in Kinshasa.
The trend of hypertension and other risk factors of cardiovascular disease is changing because of epidemiological, demographic and nutritional transitions in sub-Saharan Africa. The aim of this study is to determine the prevalence and risk factors of arterial hypertension in the Kinshasa region, Democratic Republic of Congo (DRC). Data were collected from random sample cross-sectional surveys of adult black Africans from Kinshasa, with the help of a structured questionnaire, physical examinations and blood samples, using the World Health Organisation (WHO) stepwise approach. Sex, age, place of residence (urban versus rural), psychosocial risk factors (socioeconomic status, stress), overweight status (BMI: 25-29.9 kg/m), general obesity (BMI: >or=30 kg/m), abdominal obesity (waist circumference: >or=94 cm) and diabetes mellitus were considered to be the potential risk factors for screen-detected hypertension. The weighted prevalences of hypertension, diabetes mellitus, overweight status, general obesity and abdominal obesity were 15.2, 140.2, 13.5, 4.8 and 7.5%, respectively. Blood pressure and the proportion of participants with hypertension increased with age and BMI group in the population, for both men and women. Age, rural residence, low socioeconomic status, high socioeconomic status, general obesity and abdominal obesity were the risk factors for hypertension. Women aged 55 years and above had higher levels of blood pressure and hypertension than men. Absolute levels of hypertension, all types of obesity and diabetes mellitus are high risk factors in the army camps and semiurban extension cities; general obesity and abdominal obesity are the risk factors for detectable hypertension. Effective control of general obesity and abdominal obesity and psychosocial strategies that target both semirural and urban areas of the Kinshasa region have the potential to prevent much premature cardiovascular disease.


Impact of Pulmonary Artery Catheter Use on Short- and Long-Term Mortality in Patients with Cardiogenic Shock.
The impact of pulmonary artery catheterization (PAC) on survival in patients with cardiogenic shock (CS) is not well established. This study aimed to assess whether Swan-Ganz catheter monitoring is related to short- and long-term mortality in patients with CS. One hundred and twenty-nine consecutive patients with a first admission for CS were prospectively enrolled in a single-center registry between December 2005 and May 2009, and were subsequently followed up over 5.3 years. PAC was used in 64% of all patients with a mean age of 68 years (65% men). After adjustment for age, gender and the presence of CS upon admission, PAC was associated with lower short-term mortality [hazard ratio (HR) = 0.55, 95% confidence interval (CI) 0.35-0.86, p = 0.008] as well as lower mortality rates in the long-term follow-up (HR = 0.63, 95% CI 0.41-0.97, p = 0.035). In a subgroup analysis, the use of PAC was associated with reduced mortality in patients without acute coronary syndrome (ACS), i.e. 49% in the Swan-Ganz group vs. 82% (p = 0.010), but there was no difference within the ACS group. The use of PAC in patients with CS was associated with lower short- and long-term mortality rates after adjustment for age, gender and the presence of shock upon admission. This benefit was only significant in those patients without ACS.


Clinical and biological data integration for biomarker discovery.
Biomarkers hold promise for increasing success rates of clinical trials. Biomarker discovery requires searching for associations across a spectrum of data. The field of biomedical data integration has made strides in developing management and analysis tools for structured biological data, but best practices are still evolving for the integration of high-throughput data with less structured clinical data. Integrated repositories are needed to support data analysis, storage and access. We describe a data integration strategy that implements a clinical and biological database and a wiki interface. We integrated parameters across clinical trials and associated genetic, gene expression and protein data. We provide examples to illustrate the utility of data integration to explore disease heterogeneity and develop predictive biomarkers.


Primary and Specialist Palliative Care in Neurosurgery: A Narrative Review and Bibliometric Analysis of Glioblastoma and Stroke.
Due to the increased demand for palliative care (PC) in recent years, a model has been proposed to divide PC into primary PC and specialist PC. This article aimed to delineate the indications for primary and specialist PC within 2 common neurosurgical conditions-glioblastoma (GBM) and stroke. A systematic review and bibliometric analysis was conducted to better appreciate the practice trends in PC utilization for GBM and stroke patients using several databases. There were 70 studies on PC for GBM, the majority of which related to patient preference (22 [31%]). During 1999-2022, there was significant growth in publications per year on this topic at a rate of approximately 0.3 publications per year (P < 0.01). There were 44 studies on PC for stroke, the majority of which related to communication strategies (14 [32%]). During 1999-2022, there was no significant growth in stroke publications per year (P = 0.22). Due to the progressively disabling neurological course of GBM, we suggest that a specialty PC team be used in conjunction with the neurosurgical team early in the disease trajectory while patients are still able to communicate their preferences, goals, and values. In contrast, short-term and long-term stages of management of stroke have differing implications for PC needs, with the short-term stage necessitating adept, time-sensitive communication between the patient, family, and care teams. Thus, we propose that primary PC should be included as a core competency in neurosurgery training, among other stroke specialists.


TOXICOLOGY: Just How Bad Is Dioxin?
The verdict is in--again: Dioxin is even worse for human health than previously believed. But, as has been true with earlier pronouncements on dioxin's risks, that judgment is controversial and may be appealed. This latest assessment comes in an eagerly awaited draft report from the U.S. Environmental Protection Agency.


Psychological wellness and health-related stigma: a pilot study of an acceptance-focused cognitive behavioural intervention for people with lung cancer.
People with lung cancer experience health-related stigma that is related to poorer psychosocial and quality of life outcomes. The present Phase 1 study applied mixed methods to test the acceptability of an acceptance-focused cognitive behavioural intervention targeting stigma for this patient group. Fourteen lung cancer patients completed a 6-week Psychological Wellness intervention with pre- and post-test outcome measures of psychological and cancer-specific distress, depression, health-related stigma and quality of life. In-depth interviews applying interpretative phenomenological analysis assessed participants' experiences of the intervention. Moderate to large improvements were observed in psychological (ηp (2) = 0.182) and cancer-specific distress (ηp (2) = 0.056); depression (ηp (2) = 0.621); health-related stigma (ηp (2) = 0.139). In contrast, quality of life declined (ηp (2) = 0.023). The therapeutic relationship; self-management of distress; and relationship support were highly valued aspects of the intervention. Barriers to intervention included avoidance and practical issues. The lung cancer patients who completed the Psychological Wellness intervention reported improvements in psychological outcomes and decreases in stigma in the face of declining quality of life with patients reporting personal benefit from their own perspectives. A randomised controlled trial is warranted to establish the effectiveness of this approach.


Direct effect of prolactin, induced by TRH injection, on ovarian oestradiol secretion in the ewe.
The effect of sustained high plasma levels of prolactin, induced by repeated 2-h i.v. injections of thyrotrophin-releasing hormone (TRH; 20 micrograms), on ovarian oestradiol secretion and plasma levels of LH and FSH was investigated during the preovulatory period in the ewe. Plasma levels of progesterone declined at the same rate after prostaglandin-induced luteal regression in control and TRH-treated ewes. However, TRH treatment resulted in a significant increase in plasma levels of LH and FSH compared to controls from 12 h after luteal regression until 5 to 6 h before the start of the preovulatory surge of LH. In spite of this, and a similar increase in pulse frequency of LH in control and TRH-treated ewes, ovarian oestradiol secretion was significantly suppressed in TRH-treated ewes compared to that in control ewes. The preovulatory surge of LH and FSH, the second FSH peak and subsequent luteal function in terms of plasma levels of progesterone were not significantly different between control and TRH-treated ewes. These results show that TRH treatment, presumably by maintaining elevated plasma levels of prolactin, results in suppression of oestradiol secretion by a direct effect on the ovary in the ewe.


Nitinol stent design - understanding axial buckling.
Nitinol׳s superelastic properties permit self-expanding stents to be crimped without plastic deformation, but its nonlinear properties can contribute towards stent buckling. This study investigates the axial buckling of a prototype tracheobronchial nitinol stent design during crimping, with the objective of eliminating buckling from the design. To capture the stent buckling mechanism a computational model of a radial force test is simulated, where small geometric defects are introduced to remove symmetry and allow buckling to occur. With the buckling mechanism ascertained, a sensitivity study is carried out to examine the effect that the transitional plateau region of the nitinol loading curve has on stent stability. Results of this analysis are then used to redesign the stent and remove buckling. It is found that the transitional plateau region can have a significant effect on the stability of a stent during crimping, and by reducing the amount of transitional material within the stent hinges during loading the stability of a nitinol stent can be increased.


Rational Design of Nanobody80 Loop Peptidomimetics: Towards Biased β2 Adrenergic Receptor Ligands.
G protein-coupled receptors (GPCRs) play an important role in many cellular responses; as such, their mechanism of action is of utmost interest. To gain insight into the active conformation of GPCRs, the X-ray crystal structures of nanobody (Nb)-stabilized β2 -adrenergic receptor (β2 AR) have been reported. Nb80, in particular, is able to bind the intracellular G protein binding site of β2 AR and stabilize the receptor in an active conformation. Within Nb80, the complementarity-determining region 3 (CDR3) is responsible for most of the binding interactions. Hence, we hypothesized that peptidomimetics of the CDR3 loop might be sufficient for binding to the receptor, inhibiting the interaction of β2 AR with intracellular GPCR interacting proteins (e.g., G proteins). Based on previous crystallographic data, a set of peptidomimetics were synthesized that, similar to the Nb80 CDR3 loop, adopt a β-hairpin conformation. Syntheses, conformational analysis, binding and functional in vitro assays, as well as internalization experiments, were performed. We demonstrate that peptidomimetics can structurally mimic the CDR3 loop of a nanobody and its function by inhibiting G protein coupling as measured by partial inhibition of cAMP production.


Oxygen-collagen priority and the early metazoan fossil record.
The thesis is developed that a low oxygen level Precambrian atmosphere presented early-evolving metazoan organisms with physiological connective tissue priorities resulting from the important molecular oxygen requirements in the biosynthesis of collagen hydroxyproline. Shells, cuticles, and carapaces which are not mandatory metazoan prerequisites but which directly or indirectly demand substantial connective tissue collagen are oxygen expensive, low priority features. A marked increase in atmospheric oxygen level near the beginning of the Paleozoic would eliminate oxygen-collagen priorities simultaneously and on a world-wide basis in all metazoan stocks providing evolutionary pressure for enlarged musculatures and associated "hard parts." This could explain the sudden presence in the fossil record of the early Cambrian of advanced and diversified metazoans, the earlier forms of which were essentially unpreservable.


Incorporation of prior phase information strengthens maximum-likelihood structure refinement.
The application of a maximum-likelihood analysis to the problem of structure refinement has led to striking improvements over the traditional least-squares methods. Since the method of maximum likelihood allows for a rational incorporation of other sources of information, we have derived a likelihood function that incorporates experimentally determined phase information. In a number of different test cases, this target function performs better than either a least-squares target or a maximum-likelihood function lacking prior phases. Furthermore, this target gives significantly better results compared with other functions incorporating phase information. When combined with a procedure to mask 'unexplained' density, the phased likelihood target also makes it possible to refine very incomplete models.


N-cadherin and cadherin 11 modulate postnatal bone growth and osteoblast differentiation by distinct mechanisms.
We have previously shown that targeted expression of a dominant-negative truncated form of N-cadherin (Cdh2) delays acquisition of peak bone mass in mice and retards osteoblast differentiation; whereas deletion of cadherin 11 (Cdh11), another osteoblast cadherin, leads to only modest osteopenia. To determine the specific roles of these two cadherins in the adult skeleton, we generated mice with an osteoblast/osteocyte specific Cdh2 ablation (cKO) and double Cdh2(+/-);Cdh11(-/-) germline mutant mice. Age-dependent osteopenia and smaller diaphyses with decreased bone strength characterize cKO bones. By contrast, Cdh2(+/-);Cdh11(-/-) exhibit severely reduced trabecular bone mass, decreased in vivo bone formation rate, smaller diaphyses and impaired bone strength relative to single Cdh11 null mice. The number of bone marrow immature precursors and osteoprogenitor cells is reduced in both cKO and Cdh2(+/-);Cdh11(-/-) mice, suggesting that N-cadherin is involved in maintenance of the stromal cell precursor pool via the osteoblast. Although Cdh11 is dispensable for postnatal skeletal growth, it favors osteogenesis over adipogenesis. Deletion of either cadherin reduces β-catenin abundance and β-catenin-dependent gene expression, whereas N-cadherin loss disrupts cell-cell adhesion more severely than loss of cadherin 11. Thus, Cdh2 and Cdh11 are crucial regulators of postnatal skeletal growth and bone mass maintenance, serving overlapping, yet distinct, functions in the osteogenic lineage.


Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.
Paclitaxel (PAC) is the first-line chemotherapy drug for most breast cancer patients, but clinical studies showed that some breast cancer patients were insensitive to PAC, which led to chemotherapy failure. It was reported that Notch1 signaling participated in drug resistance of breast cancer. Here, we show whether Notch1 expression is related to PAC sensitivity of breast cancer. We employed Notch1 siRNA and Notch1 inhibitor, N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT), to down regulate Notch1 expression in human breast cancer cells MDA-MB-231, and detected the inhibition effect by Western blotting and reverse trans cription-polymerase chain reaction, respectively. After 24 hours exposure to different concentration of PAC (0, 1, 5, 10, 15, 20, and 25 µg/ml), the viability of the control group and experimental group cells was tested by MTT. We also examined the expression of Notch1 in PAC sensitive and nonsensitive breast cancer patients, respectively by immunohistochemistry (IHC). The PAC sensitivity of breast cancer patients were identified by collagen gel droplet embedded culture-drug sensitivity test (CD-DST). Down regulation of Notch1 expression by Notch1siRNA interference or Notch1 inhibitor increased the PAC sensitivity in MDA-MB-231 cells (P < 0.05). Also, the expression of Notch1 in PAC sensitive patients was much lower than that of PAC non-sensitive patients (P < 0.01). Notch1 expression has an effect on PAC sensitivity in breast cancer patients, and the inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.


Incidence of hepatitis C virus infection in the prison setting: The SToP-C study.
People in prison are at high risk of HCV given high injecting drug use prevalence. This study evaluated HCV incidence and associated injecting drug use characteristics in prison. The SToP-C study enrolled people incarcerated in four Australian prisons. Participants were tested for HCV at enrolment and then every 3-6 months (October-2014 to November-2019). Participants eligible for this analysis included those at-risk of HCV primary infection (anti-HCV negative) or re-infection (anti-HCV positive, HCV RNA negative) with follow-up assessment. A total of 1643 eligible participants were included in analyses (82% male; median age 33 years; 30% injected drugs in prison; 1818 person-years of follow-up). Overall HCV incidence was 6.11/100 person-years (95%CI: 5.07-7.35), with higher rate of re-infection (9.34/100 person-years; 95%CI: 7.15-12.19) than primary infection (4.60/100 person-years; 95%CI: 3.56-5.96). In total population (n = 1643), HCV risk was significantly higher among participants injecting drugs in prison [vs. no injecting; adjusted hazard ratio (aHR): 10.55, 95%CI: 5.88-18.92), and those who were released and re-incarcerated during follow-up (vs. remained incarcerated; aHR: 1.60, 95%CI: 1.03-2.49). Among participants who injected recently (during past month, n = 321), HCV risk was reduced among those receiving high-dosage opioid agonist therapy (OAT), i.e. methadone ≥60 mg/day or buprenorphine ≥16 mg/day, (vs. no OAT, aHR: 0.11, 95%CI: 0.02-0.80) and increased among those sharing needles/syringes without consistent use of disinfectant to clean injecting equipment (vs. no sharing, HR: 4.60, 95%CI: 1.35-15.66). This study demonstrated high HCV transmission risk in prison, particularly among people injecting drugs. High-dosage OAT was protective, but improved OAT coverage and needle/syringe programmes to reduce sharing injecting equipment are required.


Exploring the Nature of Interaction and Stability between Water-Soluble Arsenic Pollutants and Metal-Phosphorene Hybrids: A Density Functional Theory Study.
To search for new uptake platforms for the removal of highly toxic and mobile arsenite [or trivalent arsenic, As(OH)3], we theoretically investigate the adsorption properties of intrinsic and metal-doped phosphorene nanoadsorbents. The doping of phosphorene with Ni or Cu atoms remarkably increases the uptake stability of arsenite at water environments compared to intrinsic phosphorene, with a weak competition of H2O molecules by the adsorption sites, where the adatom doping of phosphorene allows obtaining better uptake performance compared to the substitutional doping. The uptake is explained by a strong inner-sphere surface complexation, which is dominated by permanent electrostatic physical effects. Hydroxide anions show strong competitive adsorption compared to H2O and arsenite; thus, the straightforward recovery of the nanoadsorbents could be reached after removal by treatment at high pH solutions. Therefore, metal-doped phosphorene hybrids could serve as superior nanoadsorbents for arsenic separation from water by adsorption in solid phases.


Sperm function tests after vasovasostomy.
To evaluate the sperm function after vasovasostomy. Semen samples from 42 subjects after vasovasostomy (Group A: 1-6 months, Group B: 6-12 months; Group C: 12-18 months after vasectomy reversal) were investigated. Semen from 34 normal fertile men was used as controls. Sperm function tests, including hypoosmotic swelling test (HOST), acridine orange (AO) fluorescence, acrosome reaction (triple-stain), cervical mucus penetration test (CMPT), etc were done. After vasectomy reversal, the percentage of HOST was significantly lower than that of the normal fertile men. In regard to AO, there were no significant differences between the three vasovasostomy groups and between these 3 groups and the controls. With triple-stain, the percentage of normal acrosome reaction was significantly lower in Group A as compared with the controls, but not in Groups B and C. There were no significant differences in the results of CMPT between the vasovasostomy groups and the controls. However, the number of "poor" type was significantly higher in Groups A and C than in the controls; the percentage of "negative" type were higher in Groups A and B than in the controls. After vasovasostomy a lower level of HOST remained for one year and gradually recovered after one year. Six months after vasectomy reversal, the percentage of acrosome reaction could be changed from lower level to normal range. The data of AO indicated that the genetic material (double-stranded DNA) in spermatozoa was not affected by vasovasostomy. To evaluate the result of CMPT after vasectomy reversal, not only the normal results but also the abnormal results ("poor" and "negative" types) should also be considered.


Helicobacter pylori: a role in schizophrenia?
Schizophrenia is a devastating psychiatric disorder that affects approximately one percent of the world's adult population. Despite substantial investigative efforts over the last decades, the exact mechanisms and pathogenesis of this condition are not yet fully understood. Published data support certain infectious agents as potential risk factors for schizophrenia. Since its discovery, Helicobacter pylori has been implicated in a variety of extra-digestive diseases, but its potential role in the pathogenesis of psychiatric disorders has thus far been neglected. It is hypothesized here that infection with H. pylori occurring in early childhood may induce persisting systemic biochemical aberrations, including dopaminergic dysfunction, decreased levels of essential polyunsaturated fatty acids, subtle inflammation, and homocysteine alterations, that may play a crucial role in the development of schizophrenia in genetically predisposed individuals. Evidence in favor of this hypothesis is provided and possible therapeutic implications are discussed.


[The current situation of the private health plans and insurance market in Brazil and trends for the future].
This paper presents an overview of the Brazilian private health plan market over the period 2000-2006. The current situation is analyzed with respect to the profile of private insurance companies, health plans and beneficiaries and some possible trends that were identified in the study are emphasized. The increase of employer group-plans as a work-related benefit and the reduction of individual plans are discussed. Although the market is restricted to only a few companies, there are more people covered by local plans than by plans offering coverage on a national basis. Finally, the paper approaches aspects related to the financial resources, among them the governmental incentive for the health area, and points to the need of further studies for a better understanding of the supplementary healthcare market.


Double vs single internal thoracic artery harvesting in diabetic patients: role in perioperative infection rate.
The aim of this prospective study is to evaluate the role in the onset of surgical site infections of bilateral internal thoracic arteries harvesting in patients with decompensated preoperative glycemia. 81 consecutive patients with uncontrolled diabetes mellitus underwent elective CABG harvesting single or double internal thoracic arteries. Single left ITA was harvested in 41 patients (Group 1, 50.6%), BITAs were harvested in 40 (Group 2, 49.4%). The major clinical end points analyzed in this study were infection rate, type of infection, duration of infection, infection relapse rate and total hospital length of stay. Five patients developed sternal SSI in the perioperative period, 2 in group 1 and 3 in group 2 without significant difference. All sternal SSIs were superficial with no sternal dehiscence. The development of infection from the time of surgery took 18.5 +/- 2.1 and 7.3 +/- 3.0 days for Groups 1 and 2 respectively. The infections were treated with wound irrigation and debridement, and with VAC therapy as well as with antibiotics. The VAC system was removed after a mean of 12.8 +/- 5.1 days, when sterilization was achieved. The overall survival estimate at 1 year was 98.7%. Only BMI was a significant predictor of SSI using multivariate stepwise logistic regression analysis (Odds Ratio: 1.34; 95%Conficdence Interval: 1.02-1.83; p value: 0.04). In the model, the use of BITA was not an independent predictor of SSI. CABG with bilateral pedicled ITAs grafting could be performed safely even in diabetics with poor preoperative glycaemic control.


miR-582-5p is a potential prognostic marker in human non-small cell lung cancer and functions as a tumor suppressor by targeting MAP3K2.
Emerging evidence has shown that microRNAs (miRNAs) play important roles in tumor development and progression. The aim of the present study was to investigate the role of miR-582-5p in non-small cell lung cancer (NSCLC) and to determine the molecular mechanisms underlying its action. Using quantitative RT-PCR, we detected miR-582-5p expression in NSCLC cell lines and primary tumor tissues. The association of miR-582-5p expression with clinicopathological factors and prognosis was statistically analyzed. The effect of miR-582-5p on proliferation was evaluated by CCK-8. Cell migration and invasion were assessed by transwell assay. miR-582-5p target genes were confirmed using luciferase activity, RT-PCR and Western blot assays. We found that miR-582-5p expression was significantly downregulated in NSCLC cell lines and clinical specimens. Low miR-582-5p expression was significantly associated with lymph node metastasis (p = 0.012) and advanced TNM stage (p = 0.004). Kaplan-Meier assay showed that patients with low expression of miR-582-5p had a shorter overall survival than those with high expression of miR-582-5p (p = 0.0033). Functional experiments demonstrated that overexpression of miR-582-5p suppressed the proliferation, migration and invasion of NSCLC cells in vitro. We identified MAP3K2 as a direct target gene of miR-582-5p in NSCLC cells. In addition, ectopic expression of MAP3K2 restored the effects of miR-582-5p on NSCLC cell proliferation, migration and invasion. We showed that miR-582-5p inhibits NSCLC metastasis by targeting MAP3K2 expression and could be used as an independent prognostic biomarker for patients with NSCLC.


Gastric contractions produce phasic changes in perfusion pressure.
This study examined the relationship between motility and perfusion pressure of an ex vivo segment of the canine stomach perfused at constant flow. Changes in luminal pressure were used to quantitate contractile force. Under control conditions, spontaneous contractions increased luminal pressure by 18.8 +/- 1.1 mmHg and gastric perfusion pressure by 14.2 +/- 0.8 mmHg. Changes in luminal and perfusion pressures during contractions were highly correlated (r2 = 0.963, P less than 0.0001, 109 observations in 5 dogs). In separate studies, we assessed the effects of atropine, neostigmine (an acetylcholinesterase inhibitor), and bethanechol (a muscarinic cholinergic agonist). Atropine attenuated the peristaltic-induced changes in perfusion pressure in a concentration-dependent manner (10(-9) to 10(-6)M) with nearly total inhibition at the highest dose. Neostigmine (10(-9) to 10(-6) M) and bethanechol (10(-8) to 10(-5) M) stimulated contractions, resulting in dose-related increases in luminal and perfusion pressures. Our results demonstrate that cholinergic-dependent contractions produce marked, phasic changes in gastric perfusion pressure.


Evolution reversed: the ability to bind iron restored to the N-lobe of the murine inhibitor of carbonic anhydrase by strategic mutagenesis.
The murine inhibitor of carbonic anhydrase (mICA) is a member of the superfamily related to the bilobal iron transport protein transferrin (TF), which binds a ferric ion within a cleft in each lobe. Although the gene encoding ICA in humans is classified as a pseudogene, an apparently functional ICA gene has been annotated in mice, rats, cows, pigs, and dogs. All ICAs lack one (or more) of the amino acid ligands in each lobe essential for high-affinity coordination of iron and the requisite synergistic anion, carbonate. The reason why ICA family members have lost the ability to bind iron is potentially related to acquiring a new function(s), one of which is inhibition of certain carbonic anhydrase (CA) isoforms. A recombinant mutant of the mICA (W124R/S188Y) was created with the goal of restoring the ligands required for both anion (Arg124) and iron (Tyr188) binding in the N-lobe. Absorption and fluorescence spectra definitively show that the mutant binds ferric iron in the N-lobe. Electrospray ionization mass spectrometry confirms the presence of both ferric iron and carbonate. At the putative endosomal pH of 5.6, iron is released by two slow processes indicative of high-affinity coordination. Induction of specific iron binding implies that (1) the structure of mICA resembles those of other TF family members and (2) the N-lobe can adopt a conformation in which the cleft closes when iron binds. Because the conformational change in the N-lobe indicated by metal binding does not impact the inhibitory activity of mICA, inhibition of CA was tentatively assigned to the C-lobe. Proof of this assignment is provided by limited trypsin proteolysis of porcine ICA.


PET/MRI assessment of lung nodules in primary abdominal malignancies: sensitivity and outcome analysis.
To evaluate PET/MR lung nodule detection compared to PET/CT or CT, to determine growth of nodules missed by PET/MR, and to investigate the impact of missed nodules on clinical management in primary abdominal malignancies. This retrospective IRB-approved study included [18F]-FDG PET/MR in 126 patients. All had standard of care chest imaging (SCI) with diagnostic chest CT or PET/CT within 6 weeks of PET/MR that served as standard of reference. Two radiologists assessed lung nodules (size, location, consistency, position, and [18F]-FDG avidity) on SCI and PET/MR. A side-by-side analysis of nodules on SCI and PET/MR was performed. The nodules missed on PET/MR were assessed on follow-up SCI to ascertain their growth (≥ 2 mm); their impact on management was also investigated. A total of 505 nodules (mean 4 mm, range 1-23 mm) were detected by SCI in 89/126 patients (66M:60F, mean age 60 years). PET/MR detected 61 nodules for a sensitivity of 28.1% for patient and 12.1% for nodule, with higher sensitivity for > 7 mm nodules (< 30% and > 70% respectively, p < 0.05). 75/337 (22.3%) of the nodules missed on PET/MR (follow-up mean 736 days) demonstrated growth. In patients positive for nodules at SCI and negative at PET/MR, missed nodules did not influence patients' management. Sensitivity of lung nodule detection on PET/MR is affected by nodule size and is lower than SCI. 22.3% of missed nodules increased on follow-up likely representing metastases. Although this did not impact clinical management in study group with primary abdominal malignancy, largely composed of extra-thoracic advanced stage cancers, with possible different implications in patients without extra-thoracic spread.


Expression and hemocyte-targeting of a Campoletis sonorensis polydnavirus cysteine-rich gene in Heliothis virescens larvae.
The polydnavirus associated with the parasitic wasp Campoletis sonorensis is injected into the lepidopteran insect, Heliothis virescens, during parasitization, after which viral gene products suppress the cellular immune system of the hosts. Four related cysteine-rich polydnavirus gene have been identified in parasitized H. virescens larvae and grouped into a family. In this study, we investigated the expression and hemocyte targeting of the cysteine-rich VHv1.4 protein. Full-length and truncated VHv1.4 proteins were produced in a bacterial expression system, and the purified proteins were used to raise polyclonal antisera. In immunoblots the VHv1.4 protein was detected in parasitized insects as early as 6 h and throughout the entire course of parasitism. The VHv1.4 protein appeared predominantly in the plasma fraction of hemolymph from parasitized larvae, suggesting that this protein is secreted. The VHv1.4 protein expressed from a recombinant baculovirus was secreted in two lepidopteran cell lines and in larvae injected with the recombinant virus. Digestion with endoglycosidases suggests that the VHv1.4 protein is glycosylated at multiple N-glycosylation sites. Immunofluorescence assays showed that the VHv1.4 protein binds to the hemocytes, most notably the granulocytes, in H. virescens larvae. After binding, the VHv1.4 protein was internalized, probably by endocytosis. Specific binding of the VHv1.4 to granulocytes implies an important function in the suppression of host cellular encapsulation response.


Adenosquamous carcinoma of the pancreas: a single-institution experience comparing resection and palliative care.
Adenosquamous carcinoma is a rare malignancy of the exocrine pancreas. Previous literature has reported dismal survival for these patients. We examined our single-institution experience with this tumor to compare survival for sugical resection and palliative therapy. Records were reviewed for patients with adenosquamous pancreatic cancer evaluated during the years 1985 to 2003. Pathology specimens were reviewed. Survival was calculated by Kaplan-Meier method and categorical variables were compared with Chi-square analysis. A p value < 0.05 was considered significant. Twenty-three patients were identified with adenosquamous carcinoma of the pancreas. Twelve patients underwent curative resection and 11 patients had either no surgery or a palliative bypass procedure. For the resection group the mean age was 69 years (7 men). In the nonoperative group the mean age was 65 years (6 men). Operative procedures included standard pancreaticoduodenectomy (PD), 4 patients; pyloruspreserving PD, 3 patients; and distal pancreatectomy, 5 patients. Median length of stay was 13.5 days (7-30 d). Morbidity included delayed gastric emptying (4 patients), leak (2 patients), superficial skin infection, abscess, and GI bleed (1 patient each). There was no operative or inhospital mortality in the resection group. For R0 resection median survival was 14.4 months compared to 8 months for R1 and 4.8 months for patients undergoing palliative therapies. The retrospective review of our single-institution experience with resection and palliative care for adenosquamous cancer of the pancreas has demonstrated a longer survival for patients that can undergo an R0 resection. Although this is a small series we continue to recommend resection for these patients.


Does cerumen have a risk for transmission of hepatitis B?
Chronic hepatitis B virus infection is a significant worldwide health problem. It affects 350 to 400 million people. The patients with chronic hepatitis B virus infection have a significant risk for the development of cirrhosis or hepatocellular carcinoma. Full awareness of the mechanisms of transmission can allows susceptible individuals to refrain from this infection. Cerumen has never been studied as a route for hepatitis B transmission. The aim of the study was evaluate the importance of cerumen in transmission of hepatitis B virus infection. This study was performed on forty patients with confirmed hepatitis B virus infection. Forty cerumen specimens collected from the patients with hepatitis B virus DNA in their sera were prospectively analyzed for the presence of hepatitis B virus DNA by real-time polymerase chain reaction. Eleven of 40 cerumen specimens (27.5%) were positive for hepatitis B virus DNA, with counts ranging from 4.2 x 10 to 4.7 x 10 copies per sample. There was positive correlation between hepatitis B virus DNA concentrations of serum and cerumen. Half of hepatitis B e antigen (HBeAg)-positive patients had detectable hepatitis B virus DNA levels (5.7 x 10 to 4.7 x 10 copies) in cerumen specimens, whereas 12.5% of cerumen specimens from anti-HBe-positive patients had hepatitis B virus DNA levels (4.2 x 10 to 7.0 x 10 copies). Cerumen can be a potential source of transmission. Therefore, this route should be investigated in further studies for horizontal, nosocomial, and occupational transmission of hepatitis B.


[Is the postoperative course following goniotrepanation modified by the age of the patient?].
The authors tried to establish whether the patient's age has any bearing on the postoperative course of goniotrepanation. A total of 150 eyes operated on, which had been regularly followed up for more than 10 years, were classified in three age groups, each comprising 50 eyes. The following parameters were evaluated: indication for the operation, behavior of the postoperative I.O.P., behaviour of the filtering bleb, behavior of the visual functions, and late complications. The comparative investigations produced the following findings: (1) The postoperative mean IOP value is independent of the patient's age; (2) visual functions were adversely affected to a significant degree postoperatively in older patients, and (3) a cystic configuration of the filtering bleb was significantly more common in older individuals. On the basis of these findings the authors recommend covered sclerectomy procedures, even in younger individuals suffering from chronic simple glaucoma, because the prognosis for the functions and the ultimate fate of the eye is reasonably good.


The relation between alcohol intake and physical activity and the fatty acids 14 : 0, 15 : 0 and 17 : 0 in serum phospholipids and adipose tissue used as markers for dairy fat intake.
The relative contents of the fatty acids 14 : 0, 15 : 0 and 17 : 0 in serum and adipose tissue may be used as biological markers of dairy fat intake. However, the determinants of these fatty acids are not fully understood. This study investigates the relationship between these fatty acids and the intake of macronutrients and physical activity in a cross-sectional study of 301 healthy men aged 61-64 years. Dietary intake was assessed using a pre-coded 7 d food record, and physical activity during the previous year was recorded in an interview. Under-reporters of energy intake were identified by the Goldberg cut-off. Fatty acid composition was determined in serum phospholipids (PL) and subcutaneous adipose tissue (AT) from the upper buttock. The relative content of each of 14 : 0, 15 : 0 and 17 : 0 in PL and AT was positively associated with the intake of dairy fat. In addition, all three fatty acids were inversely correlated with alcohol intake, R ranging from -0.28 to -0.53 (P<0.001). The results were not markedly affected when under-reporters (n 88) were excluded from the analyses. In both PL and AT, the relative content of the fatty acids was approximately 5% higher in a group of high physical activity compared with a group of low physical activity, although significant trends were only seen for 14 : 0 in PL and 17 : 0 in AT. The findings suggest that adjustments should be made for alcohol intake when the fatty acids 14 : 0, 15 : 0 and 17 : 0 are applied as markers for dairy fat intake.


Chlamydia trachomatis infection and persistence of human papillomavirus.
Human papillomavirus (HPV) persistence is the major cause of cervical cancer, but most HPV infections will not persist and risk factors for HPV persistence are not well known. Chlamydia (C.) trachomatis infection seems to also be associated with cervical cancer. We investigated whether C. trachomatis infection is a risk factor for HPV persistence. In a cohort of 12,527 women participating in a population-based HPV screening trial in Sweden, 6,418 women completed testing for HPV DNA by general primer PCR and typing by reverse dot blot hybridization. On average 19 months later, 303 women that had been HPV-positive and had normal cytology at enrollment completed a new HPV test. Environmental exposures were assessed by an 87-item questionnaire. Previous sexually transmitted infections were also investigated by serology. At follow-up, 44% of the women were positive for the same type of HPV DNA as at enrollment. Persistence correlated with length of follow-up (p < 0.01) and condom use seemed to protect against HPV persistence (p < 0.05). The most significant risk factor for persistent presence of HPV DNA was self-reported history of previous C. trachomatis infection (relative risk in multivariate model = 2.09; 95% confidence interval = 1.05-4.18). We conclude that persistence of oncogenic HPV infections is more likely among women with a previous C. trachomatis infection.


Transcription Factor Binding in Embryonic Stem Cells Is Constrained by DNA Sequence Repeat Symmetry.
Transcription factor (TF) recognition is dictated by the underlying DNA motif sequence specific for each TF. Here, we reveal that DNA sequence repeat symmetry plays a central role in defining TF-DNA-binding preferences. In particular, we find that different TFs bind similar symmetry patterns in the context of different developmental layers. Most TFs possess dominant preferences for similar DNA repeat symmetry types. However, in some cases, preferences of specific TFs are changed during differentiation, suggesting the importance of information encoded outside of known motif regions. Histone modifications also exhibit strong preferences for similar DNA repeat symmetry patterns unique to each type of modification. Next, using an in vivo reporter assay, we show that gene expression in embryonic stem cells can be positively modulated by the presence of genomic and computationally designed DNA oligonucleotides containing identified nonconsensus-repetitive sequence elements. This supports the hypothesis that certain nonconsensus-repetitive patterns possess a functional ability to regulate gene expression. We also performed a solution NMR experiment to probe the stability of double-stranded DNA via imino proton resonances for several double-stranded DNA sequences characterized by different repetitive patterns. We suggest that such local stability might play a key role in determining TF-DNA binding preferences. Overall, our findings show that despite the enormous sequence complexity of the TF-DNA binding landscape in differentiating embryonic stem cells, this landscape can be quantitatively characterized in simple terms using the notion of DNA sequence repeat symmetry.


Parasitism of the Invasive Brown Marmorated Stink Bug, Halyomorpha halys (Hemiptera: Pentatomidae), by the Native Parasitoid, Trichopoda pennipes (Diptera: Tachinidae).
The invasive brown marmorated stink bug, Halyomorpha halys (Hemiptera: Pentatomidae), has been an important agricultural pest in the Mid-Atlantic United States since its introduction in 1996. Biological control by native species may play an important role in suppressing H. halys populations and reduce reliance on chemical control. We collected H. halys adults in agricultural areas of five Pennsylvania counties over two years to examine the extent and characteristics of adult stink bug parasitism by Trichopoda pennipes (Diptera: Tachinidae), a native parasitoid of hemipterans. The overall parasitism rate (in terms of T. pennipes egg deposition) was 2.38 percent. Rates differed among counties and seasons, but not between years. Instances of supernumerary oviposition were evident, and eggs were more commonly found on the ventral side of the thorax, although no differences in egg deposition were found between males and female hosts. T. pennipes has begun to target H. halys adults in Pennsylvania and has the potential to play a role in regulating this pest. Adult parasitism of H. halys by T. pennipes should continue to be monitored, and landscape management and ecological pest management practices that conserve T. pennipes populations should be supported in agricultural areas where H. halys is found.


Arteriosclerotic changes as background factors in patients with peripheral vestibular disorders.
Symptoms such as vertigo and unsteady gait occur in various diseases and are among the relatively common chief complaints. Even at present, the mechanisms underlying these disorders are unclear. We considered the possibility of peripheral vestibular disorders correlating with lifestyle-related illnesses. Under these circumstances, we assessed correlations of lifestyle-related illness as background factors for peripheral vestibular disorders and associated arteriosclerotic changes. Using carotid ultrasonography, we assessed maximum intima-media thickness (max IMT) and maximum common carotid artery IMT and evaluated biochemical examinations in 85 patients with peripheral vertigo. The patients were divided into two groups: those with benign paroxysmal positional vertigo (BPPV) and those with peripheral vestibular disorders. The frequency of abnormal IMT was significantly higher in those in the BPPV group. Calculating for average age, max IMT was significantly higher in the BPPV group. The correlation coefficient between age and max IMT was 0.343 (p < .001). All other correlation coefficients also reached statistical significance. Our results indicate that cervical ultrasonography is useful for noninvasive examination of arteriosclerotic changes in patients with peripheral vestibular disorders. Our results also indicated that peripheral vestibular disorder patients show progression of arteriosclerotic changes.


The Design of FluxML: A Universal Modeling Language for 13C Metabolic Flux Analysis.
13C metabolic flux analysis (MFA) is the method of choice when a detailed inference of intracellular metabolic fluxes in living organisms under metabolic quasi-steady state conditions is desired. Being continuously developed since two decades, the technology made major contributions to the quantitative characterization of organisms in all fields of biotechnology and health-related research. 13C MFA, however, stands out from other "-omics sciences," in that it requires not only experimental-analytical data, but also mathematical models and a computational toolset to infer the quantities of interest, i.e., the metabolic fluxes. At present, these models cannot be conveniently exchanged between different labs. Here, we present the implementation-independent model description language FluxML for specifying 13C MFA models. The core of FluxML captures the metabolic reaction network together with atom mappings, constraints on the model parameters, and the wealth of data configurations. In particular, we describe the governing design processes that shaped the FluxML language. We demonstrate the utility of FluxML to represent many contemporary experimental-analytical requirements in the field of 13C MFA. The major aim of FluxML is to offer a sound, open, and future-proof language to unambiguously express and conserve all the necessary information for model re-use, exchange, and comparison. Along with FluxML, several powerful computational tools are supplied for easy handling, but also to maintain a maximum of flexibility. Altogether, the FluxML collection is an "all-around carefree package" for 13C MFA modelers. We believe that FluxML improves scientific productivity as well as transparency and therewith contributes to the efficiency and reproducibility of computational modeling efforts in the field of 13C MFA.


Correlated spontaneous emission laser as an entanglement amplifier.
We consider a two-photon correlated emission laser as a source of an entangled radiation with a large number of photons in each mode. The system consists of three-level atomic schemes inside a doubly resonant cavity. We study the dynamics of this system in the presence of cavity losses, concluding that the creation of entangled states with photon numbers up to tens of thousands seems achievable.


Frailty in Pulmonary and Critical Care Medicine.
Conceptualized first in the field of geriatrics, frailty is a syndrome characterized by a generalized vulnerability to stressors resulting from an accumulation of physiologic deficits across multiple interrelated systems. This accumulation of deficits results in poorer functional status and disability. Frailty is a "state of risk" for subsequent disproportionate declines in health status following new exposure to a physiologic stressor. Two predominant models have emerged to operationalize the measurement of frailty. The phenotype model defines frailty as a distinct clinical syndrome that includes conceptual domains such as strength, activity, wasting, and mobility. The cumulative deficit model defines frailty by enumerating the number of age-related things wrong with a person. The biological pathways driving frailty include chronic systemic inflammation, sarcopenia, and neuroendocrine dysregulation, among others. In adults with chronic lung disease, frailty is independently associated with more frequent exacerbations of lung disease, all-cause hospitalization, declines in functional status, and all-cause mortality. In addition, frail adults who become critically ill are more likely develop chronic critical illness or severe disability and have higher in-hospital and long-term mortality rates. The evaluation of frailty appears to provide important prognostic information above and beyond routinely collected measures in adults with chronic lung disease and the critically ill. The study of frailty in these populations, however, requires multipronged efforts aimed at refining clinical assessments, understanding the mechanisms, and developing therapeutic interventions.


Listening Effort: How the Cognitive Consequences of Acoustic Challenge Are Reflected in Brain and Behavior.
Everyday conversation frequently includes challenges to the clarity of the acoustic speech signal, including hearing impairment, background noise, and foreign accents. Although an obvious problem is the increased risk of making word identification errors, extracting meaning from a degraded acoustic signal is also cognitively demanding, which contributes to increased listening effort. The concepts of cognitive demand and listening effort are critical in understanding the challenges listeners face in comprehension, which are not fully predicted by audiometric measures. In this article, the authors review converging behavioral, pupillometric, and neuroimaging evidence that understanding acoustically degraded speech requires additional cognitive support and that this cognitive load can interfere with other operations such as language processing and memory for what has been heard. Behaviorally, acoustic challenge is associated with increased errors in speech understanding, poorer performance on concurrent secondary tasks, more difficulty processing linguistically complex sentences, and reduced memory for verbal material. Measures of pupil dilation support the challenge associated with processing a degraded acoustic signal, indirectly reflecting an increase in neural activity. Finally, functional brain imaging reveals that the neural resources required to understand degraded speech extend beyond traditional perisylvian language networks, most commonly including regions of prefrontal cortex, premotor cortex, and the cingulo-opercular network. Far from being exclusively an auditory problem, acoustic degradation presents listeners with a systems-level challenge that requires the allocation of executive cognitive resources. An important point is that a number of dissociable processes can be engaged to understand degraded speech, including verbal working memory and attention-based performance monitoring. The specific resources required likely differ as a function of the acoustic, linguistic, and cognitive demands of the task, as well as individual differences in listeners' abilities. A greater appreciation of cognitive contributions to processing degraded speech is critical in understanding individual differences in comprehension ability, variability in the efficacy of assistive devices, and guiding rehabilitation approaches to reducing listening effort and facilitating communication.


Crystal structure of the Redβ C-terminal domain in complex with λ Exonuclease reveals an unexpected homology with λ Orf and an interaction with Escherichia coli single stranded DNA binding protein.
Bacteriophage λ encodes a DNA recombination system that includes a 5'-3' exonuclease (λ Exo) and a single strand annealing protein (Redβ). The two proteins form a complex that is thought to mediate loading of Redβ directly onto the single-stranded 3'-overhang generated by λ Exo. Here, we present a 2.3 Å crystal structure of the λ Exo trimer bound to three copies of the Redβ C-terminal domain (CTD). Mutation of residues at the hydrophobic core of the interface disrupts complex formation in vitro and impairs recombination in vivo. The Redβ CTD forms a three-helix bundle with unexpected structural homology to phage λ Orf, a protein that binds to E. coli single-stranded DNA binding protein (SSB) to function as a recombination mediator. Based on this relationship, we found that Redβ binds to full-length SSB, and to a peptide corresponding to its nine C-terminal residues, in an interaction that requires the CTD. These results suggest a dual role of the CTD, first in binding to λ Exo to facilitate loading of Redβ directly onto the initial single-stranded DNA (ssDNA) at a 3'-overhang, and second in binding to SSB to facilitate annealing of the overhang to SSB-coated ssDNA at the replication fork.


Effectiveness of resistance interval training versus aerobic interval training on peak oxygen uptake in patients with myocardial infarction.
Cardiac rehabilitation reduces the risk factors and improves the aerobic exercise capacity of patients after they have experienced cardiac events. This study compared the effects of two types of interval training in patients with myocardial infarction (MI). A single-blinded randomised controlled trial was conducted on 26 patients with MI which included 16 males and 10 females. After screening via non-probability convenience sampling, patients were randomised into two groups using toss and trial method. The control group was given aerobic interval training (AIT), consisting intervals of stationary cycling and walking on the treadmill. The experimental group received both AIT as well as resistance interval training comprising exercises of the upper and lower limbs. After 6 weeks, the outcomes of peak oxygen uptake (VO2) and 6-minute walk test distance (6MWT) were measured against the baseline. Non-parametric tests were applied for statistical analysis. In the group comparison, the experimental group showed significant improvement in peak VO2 and 6MWT (p=0.003 and 0.003 respectively), as well as in the quality of life measures. The combination of resistance interval training plus AIT proved more effective in improving cardiac outcomes and aerobic capacity.


The theoretical limit to plant productivity.
Human population and economic growth are accelerating the demand for plant biomass to provide food, fuel, and fiber. The annual increment of biomass to meet these needs is quantified as net primary production (NPP). Here we show that an underlying assumption in some current models may lead to underestimates of the potential production from managed landscapes, particularly of bioenergy crops that have low nitrogen requirements. Using a simple light-use efficiency model and the theoretical maximum efficiency with which plant canopies convert solar radiation to biomass, we provide an upper-envelope NPP unconstrained by resource limitations. This theoretical maximum NPP approached 200 tC ha(-1) yr(-1) at point locations, roughly 2 orders of magnitude higher than most current managed or natural ecosystems. Recalculating the upper envelope estimate of NPP limited by available water reduced it by half or more in 91% of the land area globally. While the high conversion efficiencies observed in some extant plants indicate great potential to increase crop yields without changes to the basic mechanism of photosynthesis, particularly for crops with low nitrogen requirements, realizing such high yields will require improvements in water use efficiency.


Selectively immobilized cytochrome c as an effective affinity ligand for electron transfer proteins.
Preparations of horse heart cytochrome c have been obtained immobilized on Sepharose derivatives via lysine epsilon-amino groups, carboxyl groups of aspartic and glutamic acid residues, methionine and histidine residues as well as imidazole groups additionally introduced by means of modification of free carboxyl groups by histamine. Dissociation constants have been determined for complexes of adrenodoxin, hepatoredoxin , cytochrome b5 heme-containing tryptic fragment and myoglobin with cytochrome c preparations immobilized via lysine residues (cytochrome c-Sepharose I) or additional imidazole groups (cytochrome c-Sepharose II). The latter adsorbent possesses a 2-3 times higher affinity to adrenodoxin and hepatoredoxin than the former. The parameters of interaction with cytochrome c-Sepharose II constitute for the proteins studied the following sequence: adrenodoxin (the highest affinity) greater than or equal to hepatoredoxin greater than cytochrome b4 heme- containing tryptic fragment greater than myoglobin. The efficiency of cytochrome c-Sepharose II application in the course of adrenodoxin, hepatoredoxin and cytochrome b5 purification, as well as isolation of cytochrome b4 heme-containing tryptic fragment has been shown.


The establishment of the Chiropractic & Osteopathic College of Australasia in Queensland (1996-2002).
INTRODUCTION: For chiropractors and osteopaths after graduation, the learning process continues by way of experience and continuing education (CE). The provision of CE and other vocational services in Queensland between 1996 and 2002 is the subject of this paper. METHODS: The Chiropractic & Osteopathic College of Australasia (COCA) implemented a plan, which involved continuing education, with speakers from a broad variety of health provider areas; and the introduction of the concepts of evidence-based practice. The plan also involved building membership. RESULTS: Membership of COCA in Queensland grew from 3 in June 1996 to 167 in 2002. There were a total of 25 COCA symposia in the same period. Evidence-based health care was introduced and attendees were generally satisfied with the conferences. DISCUSSION: The development of a vocational body (COCA) for chiropractors and osteopaths in Queensland was achieved. Registrants in the field have supported an organisation that concentrates on the vocational aspects of their practice.


Regulation of glyceraldehyde-3-phosphate dehydrogenase by a cytosolic protein.
Stimulation of glyceraldehyde-3-phosphate dehydrogenase (G3PD) activity and accelerated growth occur in cultures of monkey kidney epithelial cells (BSC-1 line) that are exposed to medium with a reduced K concentration (3.2 mM). We recently found that this activation of G3PD was mediated by the appearance of a new cytosolic protein with an apparent molecular weight of 62,000. G3PD and this modifier protein were isolated from BSC-1 cells, and the interaction between them was characterized to define the mechanism(s) of enzyme activation. The enzyme protein was purified from cells grown in control medium (5.4 mM K). The enzyme, in the presence of modifier, exhibited an increase in maximal rate of enzyme reaction and a decrease in the apparent Km for NAD+. Analysis using Dixon plots revealed that the presence of modifier increased the Ki for NADH by two- to threefold. Inhibition by NADH was competitive with respect to NAD+, glyceraldehyde-3-phosphate, and inorganic phosphate. ATP also inhibited enzyme activity in a competitive manner with respect to NAD+; however, the Ki for ATP was similar both in the presence and absence of modifier. These results suggest that one mechanism by which the cytosolic modifier protein stimulates G3PD activity is to decrease product inhibition by NADH.


Control of anxiety through music in a head and neckoutpatient clinic: a randomized clinical trial.
OBJECTIVE Evaluating the effectiveness of a musical intervention in reducing anxiety and vital parameters in people suffering from head and neck cancer. METHOD A randomized controlled clinical trial, performed in a head and neck outpatient clinic with 40 participants, subdivided into two groups (intervention and control).The classicalmusic"Spring" from The Four Seasons by Vivaldi was used as an intervention.The State-Trait Anxiety Inventory (STAI) was used as the data collectioninstrument,along with an inventory of socio-demographic and clinical data. Student'st-test was used to verify intragroup and intergroup statistical significance. RESULTS Participants presented a statistically significant reduction in levels of perceived anxiety (t= 12.68; p<0.001),as well as blood pressure levels (t = 4.56; p<0.001); pulse (t = 6.15; p<0.001) and respiratory rate (t = 5.10; p<0.001). CONCLUSION Music has proven to be an effective non-pharmacological therapeutic resource in managinganxiety in an outpatient setting for people with cancer, as well as in reducing blood pressure, pulse and respiratory rate. Brazilian Registry of Clinical Trials: RBR-7W4YJJ.


Novel adipokine asprosin modulates browning and adipogenesis in white adipose tissue.
Obesity is an increasingly serious epidemic worldwide characterized by an increase in the number and size of adipocytes. Adipose tissue maintains the balance between lipid storage and energy utilization. Therefore, adipose metabolism is of great significance for the prevention, treatment and intervention of obesity. Asprosin, a novel adipokine, is a circulating hormone mainly secreted by white adipose tissue. Previous studies have shown that asprosin plays a role in fasting-induced homeostasis, insulin resistance, and glucose tolerance. However, whether it can regulate the metabolism of adipose tissue itself has not been studied. This study intended to examine the roles and potential mechanisms of asprosin in adipose regulation. We first demonstrated that the expression level of asprosin was significantly downregulated in subcutaneous white adipose tissue (scWAT) of high-fat diet (HFD)-fed or cold-stimulated mice. Overexpression of asprosin in scWAT reduced heat production, decreased expression of the browning marker uncoupling protein 1 (UCP1) and other browning-related genes, along with upregulation of adipogenic gene expression. Mechanistically, we found that Nrf2 was activated upon cold exposure, but this activation was suppressed after asprosin overexpression. In primary cultured adipocytes, adenovirusmediated asprosin overexpression inhibited adipose browning and aggravated lipid deposition, while Nrf2 agonist oltipraz could reverse these changes. Our findings suggest that novel adipokine asprosin negatively regulated browning and elevate lipid deposition in adipose tissue via a Nrf2-mediated mechanism. Asprosin may be a promising target for the prevention and treatment of obesity and other metabolic diseases.


Whole genome analyses of marine fish pathogenic isolate, Mycobacterium sp. 012931.
Mycobacterium is a genus within the order Actinomycetales that comprises of a large number of well-characterized species, several of which includes pathogens known to cause serious disease in human and animal. Here, we report the whole genome sequence of Mycobacterium sp. strain 012931 isolated from the marine fish, yellowtail (Seriola quinqueradiata). Mycobacterium sp. 012931 is a fish pathogen causing serious damage to aquaculture farms in Japan. DNA dot plot analysis showed that Mycobacterium sp. 012931 was more closely related to Mycobacterium marinum when compared across several Mycobacterium species. However, little conservation of the gene order was observed between Mycobacterium sp. 012931 and M. marinum genome. The annotated 5,464 genes of Mycobacterium sp. 012931 was classified into 26 subsystems. The insertion/deletion gene analysis shows Mycobacterium sp. 012931 had 643 unique genes that were not found in the M. marinum strains. In the virulence, disease, and defense subsystem, both insertion and deletion genes of Mycobacterium sp. 012931 were associated with the PPE gene cluster of Mycobacteria. Of seven plcB genes in Mycobacterium sp. 012931, plcB_2 and plcB_3 showed low identities with those of M. marinum strains. Therefore, Mycobacterium sp. 012931 has differences on genetic and virulence from M. marinum and may induce different interaction mechanisms between host and pathogen.


A sup-score test for the cure fraction in mixture models for long-term survivors.
The evaluation of cure fractions in oncology research under the well known cure rate model has attracted considerable attention in the literature, but most of the existing testing procedures have relied on restrictive assumptions. A common assumption has been to restrict the cure fraction to a constant under alternatives to homogeneity, thereby neglecting any information from covariates. This article extends the literature by developing a score-based statistic that incorporates covariate information to detect cure fractions, with the existing testing procedure serving as a special case. A complication of this extension, however, is that the implied hypotheses are not typical and standard regularity conditions to conduct the test may not even hold. Using empirical processes arguments, we construct a sup-score test statistic for cure fractions and establish its limiting null distribution as a functional of mixtures of chi-square processes. In practice, we suggest a simple resampling procedure to approximate this limiting distribution. Our simulation results show that the proposed test can greatly improve efficiency over tests that neglect the heterogeneity of the cure fraction under the alternative. The practical utility of the methodology is illustrated using ovarian cancer survival data with long-term follow-up from the surveillance, epidemiology, and end results registry.


The cell density-dependent expression of stewartan exopolysaccharide in Pantoea stewartii ssp. stewartii is a function of EsaR-mediated repression of the rcsA gene.
The LuxR-type quorum-sensing transcription factor EsaR functions as a repressor of exopolysaccharide (EPS) synthesis in the phytopathogenic bacterium Pantoea stewartii ssp. stewartii. The cell density-dependent expression of EPS is critical for Stewart's wilt disease development. Strains deficient in the synthesis of a diffusible acyl-homoserine lactone inducer remain repressed for EPS synthesis and are consequently avirulent. In contrast, disruption of the esaR gene leads to hypermucoidy and attenuated disease development. Ligand-free EsaR functions as a negative autoregulator of the esaR gene and responds to exogenous acyl-homoserine lactone for derepression. The focus of this study was to define the mechanism by which EsaR governs the expression of the cps locus, which encodes functions required for stewartan EPS synthesis and membrane translocation. Genetic and biochemical studies show that EsaR directly represses the transcription of the rcsA gene. RcsA encodes an essential coactivator for RcsA/RcsB-mediated transcriptional activation of cps genes. In vitro assays identify an EsaR DNA binding site within the rcsA promoter that is reasonably well conserved with the previously described esaR box. We also describe that RcsA positively controls its own expression. Interestingly, promoter proximal genes within the cps cluster are significantly more acyl-homoserine lactone responsive than genes located towards the middle or 3' end of the gene cluster. We will discuss a possible role of EsaR-mediated quorum sensing in the differential expression of the cps operon.