Replication and integration of a Vibrio cholerae cryptic plasmid linked to the CTX prophage

We identified a 4.7kb cryptic plasmid in all ctxAB+ Vibrio cholerae strains we tested. An isolate of the V. cholerae classical biotype strain 0395 that harbours the cryptic plasmid at high copy number was found. Hybridization analysis demonstrated that sequences highly related or identical to this plasmid exist in all toxigenic strains of V. cholerae but were notably absent in all non-toxigenic environmental isolates that lacked the genes for toxin-co-regulated pili and the filamentous CTX prophage. Accordingly, we have named the cryptic plasmid pTLC for toxin-linked cryptic. The complete nucleotide sequence of pTLC from the high-copy-number isolate was determined. The largest open reading frame in the plasmid is predicted to encode a protein similar to the replication initiation protein (pII) of Escherichia coli F-specific filamentous phages. The nucleotide sequence of pTLC also facilitated the structural characterization of the DNA homologous to pTLC in other strains of V. cholerae. pTLC-related DNA exists in these strains as both low-copy-number, covalently closed circular DNA and tandemly duplicated, chromosomally integrated DNA. Remarkably, the chromosomally integrated form of pTLC is adjacent to the CTX prophage. The strain distribution, chromosomal location and DNA sequence of pTLC suggests that it may be a genetic element that plays some role in the biology of CTXphi, perhaps facilitating either its acquisition or its replication.     

Life events and post-traumatic stress: the development of a new measure for children and adolescents

BACKGROUND: A new interview measure of life events and post-traumatic stress disorder (PTSD) has been developed for children and adolescents aged 9 through 17, for use in both epidemiological and clinical studies. It includes 'high magnitude' events associated with PTSD as well as other 'low magnitude' events. METHOD: The interview is designed as a module of the Child and Adolescent Psychiatric Assessment, an interviewer-based interview conducted with parent and child separately by trained lay interviewers. The module includes: (1) questions about a wide range of events; (2) a screen for key PTSD symptoms (painful recall, avoidance, hypervigilance); and (3) a detailed interview on all PTSD symptoms, including onset, duration, severity and co-morbidity. A test-retest reliability study was conducted with 58 parents and children, who were interviewed twice by different interviewers. RESULTS: Intraclass correlations were 0.72 (child) and 0.83 (parent) for high magnitude events, and 0.62 (child) and 0.58 (parent) for low magnitude events. Kappa coefficients ranged from high for violence and sexual abuse to low for child reports of serious accidents and natural disasters. The reliability of the PTSD screen symptoms was fair to excellent (kappa = 0.40-0.79), and reliability of PTSD symptoms in those who passed the screen was excellent (ICC = 0.94-0.99). Compared with a general population sample (N = 1015), the clinic-referred subjects and their parents were twice as likely to report a traumatic event and, depending on the event, up to 25 times as likely to report symptoms of PTSD. CONCLUSIONS: The results support the reliability and discriminant validity of the measure.     

A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.     

Synthesis and analgesic properties of new 5-thioaryl pyrazole derivatives

A new series 5-thio aryl pyrazole derivatives were proposed aiming analgesic activity. In this work, 8 new compounds of this class were synthesized using usual synthetic methodology, having as key intermediate the 3-methyl-4-nitro-5-chloropyrazole-1-phenyl derivative and subsequent reaction with several nucleophiles sulfides. Pharmacological evaluation of this series showed analgesic activity in the some extent in especially for 5-(4-bromophenyl)-thio-3-methyl-4-nitro-1-phenylpyrazole which was the most potent in this series, presenting an analgesic action comparable to that show by dipyrone.     

Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid-induced colitis in the rat

BACKGROUND: We investigated the effects of benzalkonium chloride (BAC) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. METHODS: TNBS was administered intrarectally before and/or after BAC treatment. In the first study, the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the second study, animals were treated with BAC before, after or before and after TNBS, and were examined 7 days later. The severity of colitis was assessed by macroscopic and histological scoring of the colonic damage and by determination of colonic myeloperoxidase (MPO) activity. Macrophages and CD4+ and CD8+ T cells were examined by immunohistochemistry. RESULTS: When BAC was instilled into the colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological features of the colon were similar to that of controls (TNBS alone). In contrast, MPO activity was significantly reduced in all three groups post-treated with BAC. In the groups examined 7 days after TNBS treatment, rats post-treated with BAC exhibited increased weight gain and significantly reduced macroscopic damage and MPO activity compared to the TNBS control group. Rats pre-treated with BAC exhibited less macroscopic damage of the colon than rats receiving only TNBS, but histological damage, MPO and weight gain were unchanged from TNBS controls. Immunohistochemistry revealed that BAC pre-treatment increased the numbers of macrophages and T cells in the colon. After TNBS treatment, macrophage accumulation was evident in the colon, but T cells were scarce. However, these cells were preserved or enhanced in the colonic mucosa in TNBS-treated rats that had been pre-treated with BAC. CONCLUSIONS: Treatment with BAC, particularly after induction of colitis, produces a significant reduction in the severity of tissue injury and inflammation through mechanisms that are not fully understood.     

Primary focal segmental glomerulosclerosis: clinical course and response to therapy

Primary focal segmental glomerulosclerosis (FSGS) is a lesion associated with a poor prognosis and results in end-stage renal disease after 5 to 10 years. Based on past experience, many nephrologists have considered primary FSGS a lesion that is steroid resistant and therefore are reluctant to offer steroids as treatment. Recent data, however, have demonstrated that patients with primary FSGS have a response to steroid therapy that is considerably better than had been described. Thus, it may be that nephrologists have been more "steroid reluctant" than the lesion is steroid resistant. To better understand this issue we review the clinical course and response to therapy in patients with primary FSGS.     

Interpretation of the impedance spectroscopy of cement paste via computer modelling

The d.c. conductivity, , and low-frequency relative dielectric constant, k, of Portland cement paste were monitored, using impedance spectroscopy, during cooling from room temperature down to -50 °C. Dramatic decreases in the values of and k, as great as two orders of magnitude, occurred at the initial freezing point of the aqueous phase in the macropores and larger capillary pores. This result provides strong experimental support for the dielectric amplification mechanism, proposed in Part II of this series, to explain the high measured low-frequency relative dielectric constant of hydrating Portland cement paste. Only gradual changes in the electrical properties were observed below this sudden drop, as the temperature continued to decrease. The values of and k of frozen cement paste, at a constant temperature of -40 °C, were dominated by properties of calcium-silicate-hydrate (C-S-H) and so increased with the degree of hydration of the paste, indicating a C-S-H gel percolation threshold at a volume fraction of approximately 15%–20%, in good agreement with previous predictions. Good agreement was found between experimental results and digital-image-based model computations of at -40 °C. Freeze-thaw cycling caused a drop in the dielectric constant of paste in the unfrozen state, indicating that measurements of k could be useful for monitoring microstructural changes during freeze-thaw cycling and other processes that gradually damage parts of the cement paste microstructure.     

RILEM and the National Institute of Standards and Technology (NIST) over the past 50 years

There has been a long partnership in the materials science of building materials between the National Institute of Standards and Technology (NIST) in the United States and the International Union of Laboratories and Experts in Construction Materials, Systems and Structures (RILEM). This paper discusses on the technical contributions NIST has made to RILEM, focusing on the articles published in Materials and Structures, whose 50-year anniversary is being celebrated in this issue. Since 1968, NIST has had a name change and a building materials division was formed, merged, and renamed since the 1970s, while RILEM has stayed constant in its name and organization, although its technical committee structure is purposely fluid. Many NIST personnel have contributed to the partnership between RILEM and NIST in more than one material type. This overview briefly covers these areas.     

The genome of Treponema pallidum: new light on the agent of syphilis

Covert brain activity related to task-free, spontaneous (i.e. unrequested), emotional evaluation of human face images was analysed in 27-channel averaged event-related potential (ERP) map series recorded from 18 healthy subjects while observing random sequences of face images without further instructions. After recording, subjects self-rated each face image on a scale from "liked" to "disliked". These ratings were used to dichotomize the face images into the affective evaluation categories of "liked" and "disliked" for each subject and the subjects into the affective attitudes of "philanthropists" and "misanthropists" (depending on their mean rating across images). Event-related map series were averaged for "liked" and "disliked" face images and for "philanthropists" and "misanthropists". The spatial configuration (landscape) of the electric field maps was assessed numerically by the electric gravity center, a conservative estimate of the mean location of all intracerebral, active, electric sources. Differences in electric gravity center location indicate activity of different neuronal populations. The electric gravity center locations of all event-related maps were averaged over the entire stimulus-on time (450 ms). The mean electric gravity center for disliked faces was located (significant across subjects) more to the right and somewhat more posterior than for liked faces. Similar differences were found between the mean electric gravity centers of misanthropists (more right and posterior) and philanthropists. Our neurophysiological findings are in line with neuropsychological findings, revealing visual emotional processing to depend on affective evaluation category and affective attitude, and extending the conclusions to a paradigm without directed task.     

The dental status of asthmatic British school children

Pancreatic cancer is a dismal disease. The 5-year overall survival ranges from 1% to 5%. Surgery is the only curative treatment available for this cancer, but it is indicated only in selected patients with a less than 4 cm tumor. In these patients, survival rate is about 30%. We have considered several aspects: the very difficult early diagnosis, the correct diagnostic flow chart, actual surgical procedures and new trends in biologic and genetic research. It is likely that better results can be achieved by defining an "early pancreatic cancer" and establishing how to detect it. This could be the wrigth one way is to significantly improve the survival of these patients.