Resource abundance and the critical transition to cooperation.

Cooperation is abundant in nature, occurring at all levels of biological complexity. Yet cooperation is continually threatened by subversion from noncooperating cheaters. Previous studies have shown that cooperation can nevertheless be maintained when the benefits that cooperation provides to relatives outweigh the associated costs. These fitness costs and benefits are not fixed properties, but can be affected by the environment in which populations reside. Here, we describe how one environmental factor, resource abundance, decisively affects the evolution of cooperative public goods production in two independent evolving systems. In the Avida digital evolution platform, populations evolved in environments with different levels of a required resource, whereas populations of Vibrio cholerae evolved in the presence of different nutrient concentrations. In both systems, cooperators and cheaters co-existed stably in resource-rich environments, whereas cheaters dominated in resource-poor environments. These two outcomes were separated by a sharp transition that occurred at a critical level of resource. These results offer new insights into how the environment affects the evolution of cooperation and highlight the challenges that populations of cooperators face when they experience environmental change.

Evaluation of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Identification of Mycobacterium species, Nocardia species, and Other Aerobic Actinomycetes.

The value of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for the identification of bacteria and yeasts is well documented in the literature. Its utility for the identification of mycobacteria and Nocardia spp. has also been reported in a limited scope. In this work, we report the specificity of MALDI-TOF MS for the identification of 162 Mycobacterium species and subspecies, 53 Nocardia species, and 13 genera (totaling 43 species) of other aerobic actinomycetes using both the MALDI-TOF MS manufacturer's supplied database(s) and a custom database generated in our laboratory. The performance of a simplified processing and extraction procedure was also evaluated, and, similar to the results in an earlier literature report, our viability studies confirmed the ability of this process to inactivate Mycobacterium tuberculosis prior to analysis. Following library construction and the specificity study, the performance of MALDI-TOF MS was directly compared with that of 16S rRNA gene sequencing for the evaluation of 297 mycobacteria isolates, 148 Nocardia species isolates, and 61 other aerobic actinomycetes isolates under routine clinical laboratory working conditions over a 6-month period. MALDI-TOF MS is a valuable tool for the identification of these groups of organisms. Limitations in the databases and in the ability of MALDI-TOF MS to rapidly identify slowly growing mycobacteria are discussed.

Mobile applications for handheld devices to screen and randomize acute stroke patients in clinical trials.

The availability of internet connectivity and mobile application software used by low-power handheld devices makes smart phones of unique value in time-sensitive clinical trials. Trial-specific applications can be downloaded by investigators from various mobile software distribution platforms or web applications delivered over HTTP. The Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH) II investigators in collaboration with MentorMate released the ATACH-II Patient Recruitment mobile application available on iPhone, Android, and Blackberry in 2011. The mobile application provides tools for pre-screening, assessment of eligibility, and randomization of patients. Since the release of ATACH-II mobile application, the CLEAR-IVH (Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage) trial investigators have also adopted such a mobile application. The video-conferencing capabilities of the most recent mobile devices open up additional opportunities to involve central coordinating centers in the recruitment process in real time.

Heterogeneous glyoxal oxidation: a potential source of secondary organic aerosol.

Laboratory studies are described that suggest reactive uptake of glyoxal on particulate containing HNO(3) could contribute to the formation of secondary organic aerosol (SOA) in the upper troposphere (UT). Using a Knudsen cell flow reactor, glyoxal is observed to react on supercooled H(2)O/HNO(3) surfaces to form condensed-phase glyoxylic acid. This product was verified by derivatization and GC-MS analysis. The reactive uptake coefficient, γ, of glyoxal varies only slightly with the pressure of nitric acid, from γ = 0.5 to 3.0 × 10(-3) for nitric acid pressures between 10(-8) and 10(-6) Torr. The data do not show any dependence on temperature (181-201 K) or pressure of glyoxal (10(-7) to 10(-5) Torr). Using the determined reactive uptake kinetics in a simple model shows that glyoxal uptake to supercooled H(2)O/HNO(3) may account for 4-53% of the total organic mass fraction of aerosol in the UT.

Dietary fat and breast cancer risk revisited: a meta-analysis of the published literature.

Animal experiments and human ecological studies suggest that dietary fat intake is associated with a risk of breast cancer, but individual-based studies have given contradictory results. We have carried out a meta-analysis of this association to include all papers published up to July 2003. Case-control and cohort studies that examined the association of dietary fat, or fat-containing foods, with risk of breast cancer were identified. A total of 45 risk estimates for total fat intake were obtained. Descriptive data from each study were extracted with an estimate of relative risk and its associated 95% confidence interval (CI), and were analysed using the random effects model of DerSimonian and Laird. The summary relative risk, comparing the highest and lowest levels of intake of total fat, was 1.13 (95% CI: 1.03-1.25). Cohort studies (N=14) had a summary relative risk of 1.11 (95% CI: 0.99-1.25) and case-control studies (N=31) had a relative risk of 1.14 (95% CI 0.99-1.32). Significant summary relative risks were also found for saturated fat (RR, 1.19; 95% CI: 1.06-1.35) and meat intake (RR, 1.17; 95% CI 1.06-1.29). Combined estimates of risk for total and saturated fat intake, and for meat intake, all indicate an association between higher intakes and an increased risk of breast cancer. Case-control and cohort studies gave similar results.

Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults.

PURPOSE: Hyperinsulinemia is a common feature of many obesity syndromes. We investigated whether suppression of insulin secretion, without dietary or exercise intervention, could promote weight loss and alter food intake and preference in obese adults. METHODS: Suppression of insulin secretion was achieved using octreotide-LAR 40 mg IM q28d for 24 weeks in 44 severely obese adults (89% female, 39% minority). Oral glucose tolerance testing was performed before and after treatment, indices of beta-cell activity (CIRgp), insulin sensitivity (CISI), and clearance (CP/I AUC) were computed, and leptin levels, 3-day food records and carbohydrate-craving measurements were obtained. DEXA evaluations were performed pre- and post-therapy in an evaluable subgroup. RESULTS: For the entire cohort, significant insulin suppression was achieved with simultaneous improvements in insulin sensitivity, weight loss, and body mass index (BMI). Leptin, fat mass, total caloric intake, and carbohydrate craving significantly decreased. When grouped by BMI response, high responders (HR; DeltaBMI<-3 kg/m(2)) and low responders (LR; DeltaBMI between -3 and -0.5) exhibited higher suppression of CIRgp and IAUC than nonresponders (NR; DeltaBMI-0.5). CISI improved and significant declines in leptin and fat mass occurred only in HR and LR. Conversely, both leptin and fat mass increased in NR. Carbohydrate intake was markedly suppressed in HR only, while carbohydrate-craving scores decreased in HR and LR. For the entire cohort, DeltaBMI correlated with DeltaCISI, Deltafat mass, and Deltaleptin. DeltaFat mass also correlated with DeltaIAUC and DeltaCISI. CONCLUSIONS: In a subcohort of obese adults, suppression of insulin secretion was associated with loss of body weight and fat mass and with concomitant modulation of caloric intake and macronutrient preference.

A pilot study exploring mood state and dyspnea in mechanically ventilated patients.

OBJECTIVE: The objective of this study was to explore preweaning mood state and dyspnea in mechanically ventilated patients. METHODS: Before ventilatory weaning, 21 critically ill patients completed the short profile of mood states (higher scores equal greater disturbance), and a 10 cm dyspnea visual analogue scale (none to extremely severe). Weaning outcome at 24 hours was recorded. RESULTS: The mean +/- SD total mood disturbance (possible range, 0 to 16) and subscale scores (possible range, 0 to 4) were as follows: total, 6.10 +/- 4.06; tension, 1.07 +/- 0.64; depression, 1.16 +/- 0. 93; anger, 1.05 +/- 0.82; vigor, 1.04 +/- 0.84; fatigue, 1.96 +/- 0. 90; and confusion, 1.27 +/- 0.91. Mean dyspnea was 3.22 +/- 2.26 cm. Dyspnea intensity correlated negatively with vigor (r = -0.38, P <. 10). Lower preweaning vigor tended to differentiate successful from unsuccessful weaning (Mann-Whitney U = 22.0; P =.07). CONCLUSION: Patients who weaned successfully experienced greater mood disturbance. Moderate mood disturbance may be a necessary stimulus for successful weaning.

Sweet's syndrome as an initial manifestation of pediatric human immunodeficiency virus infection.

We report a 3-month-old infant in whom Sweet's syndrome was a presenting manifestation of pediatric human immunodeficiency virus infection. Although rare in children, Sweet's syndrome may be associated with certain infections and malignancies. The diagnosis of Sweet's syndrome in a child should always prompt a thorough evaluation to assess for an associated systemic disease.

Effect of ascorbic acid dose taken with a meal on nitrosoproline excretion in subjects ingesting nitrate and proline.

We determined the dose of ascorbic acid (ASC) given to subjects with a standard 400-calorie meal that inhibited N-nitrosoproline (NPRO) formation when we gave 400 mg of nitrate one hour before and 500 mg of L-proline with the standard meal. Volunteers consumed their normal US diets but restricted their intakes of nitrate, proline, NPRO, and ASC. NPRO and N-nitrososarcosine (NSAR) were determined in the 18-hour urines by methylation followed by gas chromatography-thermal energy analysis. Mean NPRO yields were 10.7, 41.9, 33.2, 22.3, and 23.1 nmol for groups of 9-25 subjects taking proline alone, proline + nitrate, and proline + nitrate + 120, 240, and 480 mg of ASC, respectively. There was a significant trend to lower NPRO yields as the ASC dose was raised. These results correspond to inhibitions by ASC of 28%, 62%, and 60%, respectively. Pairwise comparison showed that each group taking ASC formed significantly less NPRO than the group given only proline + nitrate. Mean NSAR yields were 9.0 nmol when proline alone was taken and 16.9-24.0 nmol when proline + nitrate + ASC was taken, with no trend to increase as the ASC dose was raised. However, NPRO and NSAR yields in individual urines were correlated with each other. We concluded that 120 mg of ASC taken with each meal (360 mg/day) would significantly reduce in vivo nitrosamine formation, similar to tests by Leaf and co-workers (Carcinogenesis 8, 791-795, 1987) in which the reactants were taken between meals. The inhibitory dose of ASC may be < 120 mg/meal when doses of nitrate and proline are not taken.

Immunization with recombinant varicella-zoster virus expressing herpes simplex virus type 2 glycoprotein D reduces the severity of genital herpes in guinea pigs.

Varicella-zoster virus (VZV) is an attractive candidate for a live-virus vector for the delivery of foreign antigens. The Oka vaccine strain of VZV is safe and effective in humans, and recombinant Oka VZV (ROka) can be generated by transfecting cells with a set of overlapping cosmid DNAs. By this method, the herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) gene was inserted into an intergenic site in the unique short region of the Oka VZV genome. Expression of gD2 in cells infected with the recombinant Oka strain VZV (ROka-gD2) was confirmed by antibody staining of fixed cells and by immunoblot analysis. Immune electron microscopy demonstrated the presence of gD2 in the envelope of ROka-gD2 virions. The ability of ROka-gD2 to protect guinea pigs against HSV-2 challenge was assessed by inoculating animals with three doses of uninfected human fibroblasts, fibroblasts infected with ROka VZV, or fibroblasts infected with ROka-gD2. Neutralizing antibodies specific for HSV-2 developed in animals immunized with ROka-gD2. Forty days after the third inoculation, animals were challenged intravaginally with HSV-2. Inoculation of guinea pigs with ROka-gD2 significantly reduced the severity of primary HSV-2 infection (P < 0.001). These experiments demonstrate that the Oka strain of VZV can be used as a live virus vector to protect animals from disease with a heterologous virus.

Dosing time with ascorbic acid and nitrate, gum and tobacco chewing, fasting, and other factors affecting N-nitrosoproline formation in healthy subjects taking proline with a standard meal.

The N-nitrosoproline (NPRO) test measures the potential for intragastric formation of carcinogenic nitrosamines in humans. Nitrate and L-proline are administered to volunteers. Noncarcinogenic NPRO is produced by an acid-catalyzed reaction of proline (a model for ingested amines) with nitrate-derived nitrite in the stomach. It is then absorbed and excreted in the urine, which is analyzed for NPRO. We studied the effect of certain dietary and other factors on the levels of urinary NPRO. For (generally) 5 days, healthy adult subjects (mostly men) followed a diet low in preformed NPRO, nitrate, proline, and (on days 4 and 5) ascorbic acid. The tests were conducted on days 4 and 5. In the standard test, the subjects took 400 mg nitrate at 11 a.m., and at noon they ate a standard 700-calorie meal containing 500 mg proline. (In previous tests, proline was given 1 h after or between meals.) Urines were collected for 24 h, and samples were analyzed for NPRO by published methods. This standard test yielded 26 +/- 2 (mean +/- SE) nmol NPRO compared with 5 +/- 1 nmol NPRO when proline alone was taken. In variations of the standard test, NPRO yield was not significantly affected by the subjects' gender, the time at which the standard meal was eaten, the size of the meal, or the drinking of extra water after the meal. Doses of 100 and 200 mg nitrate had lesser effects on NPRO yield than did the dose of 400 mg nitrate. Nitrate (400 mg) produced the most NPRO when it was given 1 h before the meal. Fasting increased NPRO yield by 3-4 times compared to giving proline with a meal. One g of ASC given 5 or 2 h before, with, or 1 or 2 h after the meal with proline inhibited NPRO formation by mean values of 0, 71, 71, 67, and 19%, respectively. Chewing gum or tobacco for 2-3 h after the test meal did not increase NPRO formation or salivary nitrate levels, but salivary nitrite was not taken, chewing tobacco appeared to increase salivary nitrite and nitrate levels. The weak carcinogen N-nitrososarcosine (NSAR) was also detected in some tests, and the standard group showed 21 +/- 3 nmol NSAR. A high NSAR result (44 +/- 7 nmol) for women undergoing the standard test should be reexamined. We discuss applying these results to the conduct of future NPRO tests, as well as their implications for reducing the potential production of carcinogenic nitrosamines in the stomach.

Heterogeneity of endothelial cell function for angiotensin conversion in serial-arranged arterioles.

The involvement of the endothelial cell in the vasoconstriction induced by angiotensin I and II (AI, AII), and norepinephrine (NE) was studied in microvessels of the hamster cheek pouch before and after the following procedures: endothelial impairment by light-dye treatment, inhibition of angiotensin-converting enzyme (ACE), blockade of endothelium-derived relaxing factor (EDRF) and inhibiting prostaglandin (PG) synthesis. The results showed that in large 2nd-order arterioles, endothelial impairment did not affect the vasoconstrictor activity of AII and NE, nor did it alter ACE activity. However, in small 4th-order arterioles, endothelial impairment significantly reduced angiotensin conversion without altering the vasoconstrictor responses to either AII or NE. Thus, the endothelium plays differential roles in the modulation of local angiotensin conversion in these distinct segments of serial-arranged arterioles. Furthermore, it is unlikely that the vasoconstrictor response to AII in these arterioles is modulated by the endothelium through a pathway involving the release of EDRF or PGs.

Herpes simplex virus infections in children.

This paper focuses on the advances that have been made in our understanding of the pathogenesis, diagnosis, treatment, and prevention of herpes simplex virus (HSV) infections. Insights have been gained into the immune defense mechanisms that may be active in protecting the fetus from HSV infection. An animal model that closely mimics human neonatal HSV disease may permit exploration of novel interventional strategies. Brain biopsy for the diagnosis of HSV encephalitis has been supplanted by polymerase chain reaction detection of HSV DNA in the cerebrospinal fluid and, to a lesser extent, by detection of intrathecal HSV-specific antibodies. Prolonged immune activation within the nervous system following HSV encephalitis has been demonstrated and may implicate immune activation in the pathogenesis of HSV-induced neurologic damage. The continuing emergence of antiviral drug resistance further underscores the need for new strategies for treatment and prevention of HSV infections.

Expression of the herpes simplex virus type 2 latency-associated transcript enhances spontaneous reactivation of genital herpes in latently infected guinea pigs.

The latency-associated transcript (LAT) is the only herpes simplex virus (HSV) gene product detectable in latently infected humans and animals. In this report, we show that a 624-bp deletion in the promoter of the HSV-2 LAT had no discernable effect on viral growth in tissue culture or in acute genital infection of guinea pigs, but impaired LAT accumulation and led to a marked decrease in spontaneous genital recurrences when compared with the behavior of wild-type and rescuant strains. Differences in the ability of the mutant to replicate, or in how readily it established or maintained latency did not account for this finding. Thus, HSV LAT expression facilitates the spontaneous reactivation of latent virus.

Quantity of latency-associated transcript produced by herpes simplex virus is not predictive of the frequency of experimental recurrent genital herpes.

The role of the latency-associated transcript (LAT) in control of recurrent herpes simplex virus type 2 (HSV-2) infection was investigated by examining whether LAT concentration in vitro during productive infection or in ganglia during latency correlated with frequency of recurrent genital herpes. Clinical HSV-2 isolates from frequent or infrequent recurrent genital disease produced comparable amounts of glycoprotein D and infected cell polypeptide 0 RNA, but the isolate from frequent disease produced about seven times more LAT. The guinea pig model of genital herpes was used to determine whether the quantity of LAT produced during acute infection in vitro correlated with recurrence phenotype; the frequency of recurrent disease was similar for the 2 clinical isolates. Likewise, there was no correlation between the recurrence phenotype of individual animals and LAT concentration in their ganglia. Thus, while absence of LAT may impair HSV reactivation and recurrence, once a threshold concentration is exceeded, LAT has no further effect on recurrence frequency.

Herpes simplex viremia: report of eight pediatric cases and review of the literature.

Bloodstream infection due to herpes simplex virus (HSV) is rare in the immunocompetent host but may be important in the pathogenesis of disseminated HSV infection in the immunocompromised patient. Using a simple blood-culture method, we detected herpes simplex viremia in eight immunologically compromised or immature children: two neonates, two oncology patients, and four transplant recipients. Only two patients initially exhibited evidence of mucocutaneous HSV infection. Blood was cultured for HSV because of perinatal exposure, for routine surveillance, or for the evaluation of fever, esophagitis, or oral lesions in immunocompromised patients. In five cases HSV was recovered only from the blood; in two other instances blood cultures for HSV were the first positive cultures. The time required for the detection of HSV by blood culture ranged from 1 day to 12 days. In one case viremia was transient and cleared without specific therapy. The other seven cases were treated with intravenous acyclovir; in four of these cases, therapy was initiated because of the positive blood culture. The detection of HSV in blood may promote early initiation of antiviral therapy and thereby improve prognosis.

Detection of varicella-zoster virus DNA in nasopharyngeal secretions of immune household contacts of varicella.

Persons immune to varicella-zoster virus (VZV) are not at risk for developing clinical infection after exposure to varicella. However, the extent to which they might serve as vectors for the transmission of VZV to others is not known. Information in this regard would be important in establishing hospital infection control policies, especially in relation to the care of immunocompromised hosts. A polymerase chain reaction-based detection system was used to detect the presence of VZV DNA in the nasopharyngeal secretions of household contacts of children with varicella. VZV DNA was identified in 4 of 5 immune adults and 1 susceptible sibling when sampled within 3 days of recognition of a household case of varicella. Further investigations are needed to determine whether this represents a limited window of VZV replication in the nasopharynx of immune persons during which they may serve as vectors of VZV.