The structure and evolution of the spider monkey delta-globin gene

We have isolated the delta-globin gene of the New-World spider monkey, Ateles geoffroyi, and compared its nucleotide sequence with those of other primate delta- and beta-globin genes. Among primate delta-globin genes, the rate of nonsynonymous substitutions is much less than the rate of synonymous substitutions. This suggests that primate delta- globin genes may remain under evolutionary conservation, perhaps because hemoglobin A2 has an as yet unknown physiological importance.      

Effect of Natural and ARV-Induced Viral Suppression and Viral Breakthrough on Anti-HIV Antibody Proportion and Avidity in Patients with HIV-1 Subtype B Infection

Background

Viral suppression and viral breakthrough impact the humoral immune response to HIV infection. We evaluated the impact of viral suppression and viral breakthrough on results obtained with two cross-sectional HIV incidence assays.

Methods

All samples were collected from adults in the US who were HIV infected for >2 years. Samples were tested with the BED capture enzyme immunoassay (BED-CEIA) which measures the proportion of IgG that is HIV-specific, and with an antibody avidity assay based on the Genetic Systems 1/2+ O ELISA. We tested 281 samples: (1) 30 samples from 18 patients with natural control of HIV-1 infection known as elite controllers or suppressors (2) 72 samples from 18 adults on antiretroviral therapy (ART), with 1 sample before and 2–6 samples after ART initiation, and (3) 179 samples from 20 virally-suppressed adults who had evidence of viral breakthrough receiving ART (>400 copies/ml HIV RNA) and with subsequent viral suppression.

Results

For elite suppressors, 10/18 had BED-CEIA values <0.8 normalized optical density units (OD-n) and these values did not change significantly over time. For patients receiving ART, 14/18 had BED-CEIA values that decreased over time, with a median decrease of 0.42 OD-n (range 0.10 to 0.63)/time point receiving ART. Three patterns of BED-CEIA values were observed during viral breakthrough: (1) values that increased then returned to pre-breakthrough values when viral suppression was re-established, (2) values that increased after viral breakthrough, and (3) values that did not change with viral breakthrough.

Conclusions

Viral suppression and viral breakthrough were associated with changes in BED-CEIA values, reflecting changes in the proportion of HIV-specific IgG. These changes can result in misclassification of patients with long-term HIV infection as recently infected using the BED-CEIA, thereby influencing a falsely high value for cross-sectional incidence estimates.     

Antibody Maturation and Viral Diversification in HIV-Infected Women

Introduction

The Post-exposure Prophylaxis in Infants (PEPI)-Malawi trial evaluated infant antiretroviral regimens for prevention of post-natal HIV transmission. A multi-assay algorithm (MAA) that includes the BED capture immunoassay, an avidity assay, CD4 cell count, and viral load was used to identify women who were vs. were not recently infected at the time of enrollment (MAA recent, N = 73; MAA non-recent, N = 2,488); a subset of the women in the MAA non-recent group known to have been HIV infected for at least 2 years before enrollment (known non-recent, N = 54). Antibody maturation and viral diversification were examined in these women.

Methods

Samples collected at enrollment (N = 2,561) and 12–24 months later (N = 1,306) were available for serologic analysis using the BED and avidity assays. A subset of those samples was used for analysis of viral diversity, which was performed using a high resolution melting (HRM) diversity assay. Viral diversity analysis was performed using all available samples from women in the MAA recent group (61 enrollment samples, 38 follow-up samples) and the known non-recent group (43 enrollment samples, 22 follow-up samples). Diversity data from PEPI-Malawi were also compared to similar data from 169 adults in the United States (US) with known recent infection (N = 102) and known non-recent infection (N = 67).

Results

In PEPI-Malawi, results from the BED and avidity assays increased over time in the MAA recent group, but did not change significantly in the MAA non-recent group. At enrollment, HIV diversity was lower in the MAA recent group than in the known non-recent group. HRM diversity assay results from women in PEPI-Malawi were similar to those from adults in the US with known duration of HIV infection.

Conclusions

Antibody maturation and HIV diversification patterns in African women provide additional support for use of the MAA to identify populations with recent HIV infection.     

Genetic basis of a spontaneous mutation’s expressivity

Genetic background often influences the phenotypic consequences of mutations, resulting in variable expressivity. How standing genetic variants collectively cause this phenomenon is not fully understood. Here, we comprehensively identify loci in a budding yeast cross that impact the growth of individuals carrying a spontaneous missense mutation in the nuclear-encoded mitochondrial ribosomal gene MRP20. Initial results suggested that a single large effect locus influences the mutation’s expressivity, with 1 allele causing inviability in mutants. However, further experiments revealed this simplicity was an illusion. In fact, many additional loci shape the mutation’s expressivity, collectively leading to a wide spectrum of mutational responses. These results exemplify how complex combinations of alleles can produce a diversity of qualitative and quantitative responses to the same mutation.     

Safety and efficacy of office-based surgery with monitored anesthesia care/sedation in 4778 consecutive plastic surgery procedures

Office-based surgery has several potential benefits over hospital-based surgery, including cost containment, ease of scheduling, and convenience to both patients and surgeons. Scrutiny of office-based surgery by regulators and state-licensing agencies has increased and must be addressed by improved documentation of safety and efficacy. To evaluate the safety and efficacy of the authors' office-based plastic surgery, a review was undertaken of 3615 consecutive patients undergoing 4778 outpatient plastic surgery procedures under monitored anesthesia care/sedation in a single office. The charts of 3615 consecutive patients who had undergone office-based surgery with monitored anesthesia care/sedation between May of 1995 and May of 2000 were reviewed. In all cases, the anesthesia protocol used included sedation with midazolam, propofol, and a narcotic administered by a board-certified registered nurse anesthetist with local anesthesia provided by the surgeon. Charts were reviewed for patient profile, types of procedures, multiple procedures, duration of anesthesia, American Society of Anesthesiologists class, and complications related to anesthesia. Outcomes measured included death, airway compromise, dyspnea, hypotension, venous thrombosis, pulmonary emboli, protracted nausea and vomiting lasting more than 24 hours, and unplanned hospital admissions. Statistical analyses were performed using the Microsoft Excel program and the SAS package. Results were as follows: 92.3 percent of the patients were female and 7.7 percent were male, with a mean age of 42.7 years (range, 3 to 83 years). Patients underwent aesthetic (95.6 percent) and reconstructive (4.4 percent) plastic surgery procedures. Same-session multiple procedures occurred in 24.8 percent of patients. The vast majority of patients were healthy: 84.3 percent of patients were American Society of Anesthesiologists class I, 15.6 percent were class II, and 0.1 percent were class III. The operations required a mean of 111 minutes. There were no deaths, ventilator requirements, deep venous thromboses, or pulmonary emboli. Complications were as follows: 0.05 percent (n = 2) of patients had dyspnea that resolved, 0.2 percent (n = 6) of patients had protracted nausea and vomiting, and 0.05 percent (n = 2) of patients had unplanned hospital admissions (<24 hours). One patient had an emergent intubation. No prolonged adverse effects were noted. There was a 30-day follow-up minimum. Outpatient surgery is an important aspect of plastic surgery. It was shown that office-based surgery with intravenous sedation, performed by board-certified plastic surgeons and nurse anesthetists, is safe. Appropriate accreditation, safe anesthesia protocols, and proper patient selection constitute the basis for safe and efficacious office-based outpatient plastic surgery.