Is there a role for continuation phase cognitive therapy for depressed outpatients?

Two pilot studies evaluated the rate of relapse or recurrence (i.e., major depressive disorder) after cognitive therapy (CT). Two sequential cohorts included outpatients who responded to acute phase CT (A-CT) and who agreed to monthly, treatment-free follow-up. In Study 1, the Kaplan-Meier technique estimated relapse and recurrence rates of 40% at 6 months, 45% at 8 months, 50% at 12 months, 67% at 18 months, and 74% at 24 months. In Study 2, responders to A-CT received 8 months (10 sessions) of continuation phase CT (C-CT). In Study 2, relapse or recurrence was 20% at 6 and 8 months, 27% at 12 months, and 36% at 18 and 24 months after A-CT. An exploratory log-rank test showed that relapse or recurrence-free survival was greater in Study 2 than in Study 1. If replicated, this result suggests that C-CT can reduce depressive relapse or recurrence. Alternative explanations are presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In vivo processing of the precursor of the major exoglucanase by KEX2 endoprotease in the Saccharomyces cerevisiae secretory pathway

We have established the main post-translational modification of the major exoglucanase of Saccharomyces cerevisiae as the enzyme progresses through the secretory pathway. The protein portion of the enzyme accumulated by sec18 cells was about 2 kDa larger than that of the secreted enzyme. This precursor (form A) was stable when maintained in the endoplasmic reticulum but was processed to the mature form (form B) before the block imposed by the sec7 mutation. Sec7 cells, when incubated at 37 degrees C, accumulated form B first, but upon prolonged incubation, form A was preferentially accumulated. When the supply of newly synthesized exoglucanase was prevented by the addition of cycloheximide, the accumulated A was transformed into B in the presence of altered Sec7p that still prevented secretion. Conversion of A into B was prevented in the double mutant sec7 kex2-1, indicating that Kex2p is central to the in vivo processing. Consistent with this, a KEX2 deletion mutant secreted form A exclusively. Conversion of A into B was also prevented in sec7 cells by the presence of dinitrophenol, a poison that depletes ATP levels, indicating that processing is dependent upon intracellular transport which involves ER --> Golgi and/or, at least, one intra-Golgi step(s). It follows that this transport step(s) is independent of functional Sec7p.     

In vitro activity of lumefantrine (benflumetol) against clinical isolates of Plasmodium falciparum in Yaoundé, Cameroon

The in vitro antimalarial activity of the new Chinese synthetic drug, lumefantrine, also known as benflumetol (a fluorene derivative belonging to the aminoalcohol class), was determined by an isotopic microtest against 61 fresh clinical isolates of Plasmodium falciparum and compared with that of other established antimalarial agents. The geometric mean 50% inhibitory concentration of lumefantrine was 11.9 nmol/liter (95% confidence intervals, 10.4 to 13.6 nmol/liter; range, 3.3 to 25.6 nmol/liter). The in vitro activities of lumefantrine against the chloroquine-sensitive and the chloroquine-resistant isolates did not differ (P > 0.05). There was a significant positive correlation of responses between lumefantrine and two other aminoalcohols studied, mefloquine (r = 0.688) and halofantrine (r = 0.677), and between lumefantrine and artesunate (r = 0.420), suggesting a potential for in vitro cross-resistance. Our data suggest high in vitro activity of lumefantrine, comparable to that of mefloquine, and are in agreement with the promising results of preliminary clinical trials.     

Molecular epidemiology of malaria in Yaoundé, Cameroon. III. Analysis of chloroquine resistance and point mutations in the multidrug resistance 1 (pfmdr 1) gene of Plasmodium falciparum

It has been postulated that chloroquine resistance may be associated with a single point mutation at codon 86 of the Plasmodium falciparum multidrug resistance 1 (pfmdr 1) gene. Using a simple and rapid molecular technique involving polymerase chain reaction and restriction fragment length polymorphism, the frequency of the Asn-to-Tyr mutation associated with chloroquine resistance was established among 129 clinical isolates obtained from indigenous patients in Yaoundé, Cameroon. The results showed that 110 of 129 isolates display a mutant codon. The other clinical isolates had either a pure wild-type Asn-86 codon (n = 12) or mixed Asn/Tyr alleles (n = 7). In vitro drug assays were performed to compare the genotype and phenotype in 102 clinical isolates. Of these isolates, 86 displayed pure Tyr-86 mutant codon; 48 (56%) mutant isolates were chloroquine-resistant (50% inhibitory concentration [IC50] > 100 nM), as expected, but 38 (44%) mutant isolates were chloroquine-sensitive (IC50 < 100 nM). Three chloroquine-resistant isolates and seven chloroquine-sensitive parasites carried a wild-type Asn-86 codon. Mixed alleles were found in six isolates (four chloroquine-sensitive and two chloroquine-resistant isolates). Our results did not confirm previous observations on the possible association between chloroquine resistance phenotype and genotype based on the pfmdr 1 gene.     

Analysis of pfmdr1 and drug susceptibility in fresh isolates of Plasmodium falciparum from subsaharan Africa

In this study, we examined the effect of systemic administration of SSG, a soluble highly branched (1-->3)-beta-D-glucan obtained from a fungus Sclerotinia sclerotiorum IFO 9395, on pulmonary immune responses in mice. SSG (10 mg/kg) administered intravenously (i.v.) rapidly leaked into the alveolar space and enhanced several functions of alveolar macrophages (AMs), such as phagocytic activity, lysosomal enzyme activity, active oxygen secretion and cytokine production, on day 1 post-administration. However, kinetic changes of influx of SSG into alveoli and AM activation after SSG treatment were different. The enhanced AM functions decreased to control value on day 2 when SSG still existed at the alveolar space. Additionally, a high dose (500 micrograms/ml) of SSG was needed to activate AMs in vitro. These data imply that the stimulation by SSG alone is not effective on AM activation. SSG administered i.v. also augmented interferon gamma (IFN gamma) mRNA expression in the lung tissue, and the kinetic change of the expression was similar to that of AM activation. Additionally, a synergistic effect of SSG and IFN gamma was observed on AM activation in vitro. It may be possible that IFN gamma produced by pulmonary T cells is one of the important factors for AM activation in vivo by SSG injection. Furthermore, SSG administered i.v. enhanced candidacidal activity and cytolytic activity against pulmonary metastatic Lewis lung carcinoma (3LL) cells of AMs, and inhibited significantly the experimental pulmonary metastasis of 3LL cells. These observations are very useful for the clinical application of SSG as a biological response modifier (BRM).     

Reduced efficiency in the glycosylation of the first sequon of Saccharomyces cerevisiae exoglucanase leads to the synthesis and secretion of a new glycoform of the molecule

In addition to exoglucanases (EXGs) I and II, old cultures of Saccharomyces cerevisiae secreted into the culture medium a new immunologically-related material that exhibited exoglucanase activity. The new exoglucanase (EXGII_1/2) was purified from stationary-phase cultures. It turned out to be a glycoprotein whose protein portion was identical to that of the other two isoenzymes in terms of ionic properties, size, amino acid composition and NH₂-terminal sequence (25 residues). Disruption of the structural gene encoding EXGs I and II resulted in a strain unable to secrete all three isoenzymes. EXGII_1/2 was indistinguishable in terms of molecular weight from the single intermediate detected during the deglycosylation (mediated by endo H) of EXGII by sodium dodecyl sulphate–polyacrylamide gel electrophoresis. Thus, the new isoenzyme contains only one of the two slightly elongated mannan inner cores present in enzyme II. Two intermediates were, however, detected when the deglycosylation of EXGII was monitored by ion-exchange chromatography (high-pressure liquid chromatography). Site-directed mutagenesis indicated that the major intermediate, which eluted at about the same position as enzyme II_1/2, corresponded to protein molecules carrying the oligosaccharide attached to the Asn of the second sequon, whereas the minor one carried the oligosaccharide in the first potential glycosylation site. Several lines of evidence indicate that EXGII_1/2 is a biosynthetic product resulting from an imbalance between the rate of protein synthesis and the glycosylation capabilities of the glycosylation machinery.     

Monolithic integration of a 94 GHz AlGaAs/GaAs 2-DEG mixer onquartz substrate by epitaxial lift-off

In this paper, we report the integration of an AlGaAs/GaAs two-dimensional electron gas (2-DEG) bolometric mixer and a quartz-based microstrip circuit using the epitaxial lift-off (ELO) technique. The 1 μm thick high-mobility 2-DEG device transplanted on quartz showed no sign of degradation resulting from the ELO process. The 2-DEG mixer fabrication procedure demonstrated here is advantageous for its simplicity and uncritical choice of substrate. We obtained a minimum intrinsic conversion loss of 17 dB at 94 GHz at liquid nitrogen temperature. The measured IF bandwidth of the mixer was greater than 3 GHz     

Who needs an immunization in a pediatric subspecialty clinic?

BACKGROUND: The Standards for Pediatric Immunization Practices recommends that subspecialty clinics screen children's immunization status and ensure the receipt of needed immunizations. OBJECTIVES: To determine the proportion of children presenting to a pediatric subspecialty clinic in whom immunization status can be assessed, and which of those assessed are due an immunization (eligible to receive an immunization on the day of clinic visit). DESIGN: Standardized survey of 196 patients or accompanying children presenting to a pediatric cardiology clinic. Need for immunizations was determined by the Advisory Committee on Immunization Practices recommendations. RESULTS: The reason for visit included 58% return (enrolled in the clinic), 25% initial, and 17% accompanying another patient. Usual immunization provider included 51% health department, 42% primary care physician, and 7% military. We could assess the immunization status of 79 (40%) of 196, and 19 (24%) of these 79 were due an immunization. Logistic regression analysis revealed that children enrolled in the clinic were more likely to be due for immunization than those presenting for initial visits (38% vs 8%; adjusted odds ratio, 7.42; 95% confidence interval, 1.43 to 38.55). CONCLUSIONS: We could not assess the immunization status of most children presenting to this pediatric clinic. Patients enrolled in the clinic were at increased risk for being due immunization. Having a primary care physician as a provider of immunizations did not ensure the receipt of immunizations. Pediatric subspecialists should assess the immunization status of their patients and make sure that they receive needed immunizations.     

The effect of the hydrogen presence on combustion-induced rapid phase transition of CO/O2/N2 mixtures

The explosion behavior of CO/O₂/N₂ mixtures was experimentally studied in a tubular closed vessel at different oxygen contents, in the presence and in the absence of hydrogen.