Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.     

Bacterial attachment to oropharyngeal epithelial cells in breastfed newborns

Dopaminergic agents and carbidopa/levodopa have become the preferred treatment for both the restless legs (RL) syndrome and for periodic limb movements in sleep (PLMS). For once-nightly treatments with carbidopa/ levodopa, a problem with morning end-of-dose rebound increases in leg movements has been reported to occur in the about one-fourth of the patients. In our clinical studies a previously unreported but far more significant problem of markedly augmented RL symptoms occurred in the afternoon and the evening prior to taking the next nightly dose. A systematic prospective evaluation of this augmentation in 46 consecutive patients treated with carbidopa/ levodopa for RL syndrome or PLMS disorder found this augmentation to be the major adverse effect of treatment. Augmentation occurred for 31% of PLMS patients and 82% of all RL patients. It was greater for subjects with more severe RL symptoms and for patients on higher doses (> or = 50/200 mg carbidopa/levodopa) but was unrelated to gender, age or baseline severity of PLMS. This augmentation was severe enough to require medication change for 50% of the RL patients and 13% of PLMS patients. Augmentation resolved with cessation of the medication and could be minimized by keeping the dose low.     

Restoration of blood pressure by choline treatment in rats made hypotensive by haemorrhage

1. Intracerebroventricular (i.c.v.) injection of choline (25-150 micrograms) increased blood pressure in rats made acutely hypotensive by haemorrhage. Intraperitoneal administration of choline (60 mg kg-1) also increased blood pressure, but to a lesser extent. Following i.c.v. injection of 25 micrograms or 50 micrograms of choline, heart rate did not change, while 100 micrograms or 150 micrograms i.c.v. choline produced a slight and short lasting bradycardia. Choline (150 micrograms) failed to alter the circulating residual volume of blood in haemorrhaged rats. 2. The pressor response to i.c.v. choline (50 micrograms) in haemorrhaged rats was abolished by pretreatment with mecamylamine (50 micrograms, i.c.v.) but not atropine (10 micrograms, i.c.v.). The pressor response to choline was blocked by pretreatment with hemicholinium-3 (20 micrograms, i.c.v.). 3. The pressor response to i.c.v. choline (150 micrograms) was associated with a several fold increase in plasma levels of vasopressin and adrenaline but not of noradrenaline and plasma renin. 4. The pressor response to i.c.v. choline (150 micrograms) was not altered by bilateral adrenalectomy, but was attenuated by systemic administration of either phentolamine (10 mg kg-1) or the vasopressin antagonist [beta-mercapto-beta,beta-cyclopenta-methylenepropionyl1, O-Me-Tyr2,Arg8]-vasopressin (10 micrograms kg-1). 5. It is concluded that the precursor of acetylcholine, choline, can increase and restore blood pressure in acutely haemorrhaged rats by increasing central cholinergic neurotransmission. Nicotinic receptor activation and an increase in plasma vasopressin and adrenaline level appear to be involved in this effect of choline.     

An Information Security Strategy for Networkable Devices

Networkable Windows-based operating system devices present information security challenges to both vendors and users of such devices. This article highlights some of those threats and offers measures to improve the link between a firm's business strategy, its operational activities, and its information security strategy.     

Chronic hypertrophic gastropathy in a child resembling adult Menetrier''s disease

N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) followed 24 hours later by a 24-hour infusion of 5-FU (2600 mg/M2) for an initial period of 8 weeks. No objective responses were noted. PALA and 5-FU is inactive against gastric adenocarcinoma at the doses and schedule used in this trial.     

Phasic alerting of neglect patients overcomes their spatial deficit in visual awareness

Patients with extensive damage to the right hemisphere of their brain often exhibit unilateral neglect of the left side of space. The spatial attention of these patients is strongly biased towards the right, so their awareness of visual events on the left is impaired. Extensive right-hemisphere lesions also impair tonic alertness (the ability to maintain arousal). This nonspatial deficit in alertness is often considered to be a different problem from spatial neglect, but the two impairments may be linked. If so, then phasically increasing the patients' alertness should temporarily ameliorate their spatial bias in awareness. Here we provide evidence to support this theory. Right-hemisphere-neglect patients judged whether a visual event on the left preceded or followed a comparable event on the right. They became aware of left events half a second later than right events on average. This spatial imbalance in the time course of visual awareness was corrected when a warning sound alerted the patients phasically. Even a warning sound on the right accelerated the perception of left visual events in this way. Nonspatial phasic alerting can thus overcome disabling spatial biases in perceptual awareness after brain injury.     

The Year 2015 Fusion Power Conversations

Assuming significant technical success in the ITER project by the year 2015, it is likely that governments will want to develop a more comprehensive plan for DT tokamak fusion power commercialization. To provide a glimpse into many of the related issues, we construct conversations between the director of the U.S. fusion program and three specialists key to commercial fusion success: an environment and safety regulator, an environmentalist, and an electric generation investor. The insights from these imagined conversations will hopefully be of value as tokamak fusion power proponents plan beyond ITER.     

Evolution of an instinct under long-term divergent selection for geotaxis in domesticated populations of Drosophila melanogaster..

Describes long-term divergent selection for geotaxis in lines of the fruit fly. After 26 yrs (600+ generations) of intermittent selection, the initial experimental procedure showed that the mean geotactic scores remained stable on relaxed selection, a result suggesting that evolutionary changes had occurred in these lines. Because the stability was not due to genetic fixation (homozygosity) of the lines, it is concluded that it was due to either (a) close linkage of genes associated with geotaxis (which would not result in enduring change) or (b) the development of new coadapted gene complexes utilizing genes associated with extreme geotaxis expression (which should result in enduring change). Better evidence for the latter hypothesis was obtained, during the 2nd experimental procedure, from the low- than the high-geotaxis line. The notions of coadaptation and genetic homeostasis are considered, as well as the prospective use of the geotaxis lines to study such concepts experimentally. The geotactic behavior expressed in each line is defined as instinctive: It increases reproductive success and is characteristic of a population. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)