Resolution of infection status of human immunodeficiency virus (HIV)- seroindeterminate donors and high-risk seronegative individuals with polymerase chain reaction and virus culture: absence of persistent silent HIV type 1 infection in a high-prevalence area

To address concerns over the prevalence of silent (antibody-negative) infections among blood donors and high-risk populations, a combination of proviral amplification by polymerase chain reaction (PCR) and viral isolation by co-culture techniques was employed to resolve the human immunodeficiency virus type 1 (HIV-1) infection status of well-characterized groups of suspect blood donors and others identified in the blood bank setting. No silent infections were found in 65 follow-up samples from 26 persistently HIV-1-seroindeterminate blood donors, 16 persistently seronegative heterosexual partners of infected transfusion recipients, and 6 high-risk seronegative homosexual men identified through donor look-back investigations. In contrast, 21 seropositive controls tested positive. These results suggest a low prevalence of persistently silent infections in at-risk populations, even in high HIV prevalence regions. The PCR assay, with a co-detected internal positive control, and appropriate confirmatory algorithms, was found to be a useful direct assay to rule out infection, especially in concert with confirmatory virus isolation.     

Alzheimer's disease and blood–brain barrier function—Why have anti-β-amyloid therapies failed to prevent dementia progression?

Proteopathies of the brain are defined by abnormal, disease-inducing protein deposition that leads to functional abrogation and death of neurons. Immunization trials targeting the removal of amyloid-β plaques in Alzheimer's disease have so far failed to stop the progression of dementia, despite autopsy findings of reduced plaque load. Here, we summarize current knowledge of the relationship between AD pathology and blood–brain barrier function, and propose that the activation of the excretion function of the blood–brain barrier might help to achieve better results in trials targeting the dissolution of cerebral amyloid-β aggregates. We further discuss a possible role of oligomers in limiting the efficacy of immunotherapy.     

The place of premedication in pediatric practice

Behind the multiple arguments for and against the use of premedication, sedative drugs in children is a noble principle that of minimizing psychological trauma related to anesthesia and surgery. However, several confounding factors make it very difficult to reach didactic evidence-based conclusions. One of the key confounding issues is that the nature of expectations and responses for both parent and child vary greatly in different environments around the world. Studies applicable to one culture and to one hospital system (albeit multicultural) may not apply elsewhere. Moreover, the study of hospital-related distress begins at the start of the patient's journey and ends long after hospital discharge; it cannot be focused completely on just the moment of anesthetic induction. Taking an example from actual practice experience, the trauma caused by the actual giving of a premedication to a child who absolutely does not want it and may struggle may not be recorded in a study but could form a significant component of overall effect and later psychological pathology. Clearly, attitudes by health professionals and parents to the practice of routine pediatric premedication, vary considerably, often provoking strong opinions. In this pro–con article we highlight two very different approaches to premedication. It is hoped that this helps the reader to critically re-evaluate a practice, which was universal historically and now in many centers is more selective.     

Neural correlates of pre‐attentive processing of pattern deviance in professional musicians

Pre‐attentive registration of aberrations in predictable sound patterns is attributed to the temporal cortex. However, electrophysiology suggests that frontal areas become more important when deviance complexity increases. To play an instrument in an ensemble, professional musicians have to rely on the ability to detect even slight deviances from expected musical patterns and therefore have highly trained aural skills. Here, we aimed to identify the neural correlates of experience‐driven plasticity related to the processing of complex sound features. We used functional magnetic resonance imaging in combination with an event‐related oddball paradigm and compared brain activity in professional musicians and non‐musicians during pre‐attentive processing of melodic contour variations. The melodic pattern consisted of a sequence of five tones each lasting 50 ms interrupted by silent interstimulus intervals of 50 ms. Compared to non‐musicians, the professional musicians showed enhanced activity in the left middle and superior temporal gyri, the left inferior frontal gyrus and in the right ventromedial prefrontal cortex in response to pattern deviation. This differential brain activity pattern was correlated with behaviorally tested musical aptitude. Our results thus support an experience‐related role of the left temporal cortex in fast melodic contour processing and suggest involvement of the prefrontal cortex. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Does the Under- or Overrepresentation of Minority Physicians across Geographical Areas Affect the Location Decisions of Minority Physicians?

Objective. To determine whether variation in the representation of minority physicians across geographical areas in California affects the location decisions of minority physicians.
Data Sources. We analyzed data on 9,806 residents and 53,606 patient-care physicians from the 1997–2003 American Medical Association Masterfiles for California along with data from the California Department of Finance, RAND, and other sources.
Study Design. We estimated departure models using linear probability models and destination models using conditional logit. Each model controlled for physician and county characteristics. Parameters of interest include the interactions of physician race/ethnicity with area-level minority physician representation for the corresponding race/ethnicity.
Principal Findings. Departure models show that black and Hispanic physicians are more likely to remain in an area as the level of representation of physicians from their respective groups worsens. The destination models show that black, Asian, and Hispanic physicians tend to move to areas where the level of representation is similar to that of their previous location.
Conclusions. Black and Hispanic physicians are influenced by the level of representation of physicians from their respective groups in their location decisions and tend to locate where needed.     

Remodeling of ACL Allografts is Inhibited by Peracetic Acid Sterilization

Sterilization of allografts for anterior cruciate ligament (ACL) reconstruction has become an important prerequisite to prevent disease transmission. However, current sterilization techniques impair the biological or mechanical properties of such treated grafts. Peracetic acid (PAA) has been successfully used to sterilize bone allografts without these disadvantages and does not impair the mechanical properties of soft tissue grafts in vitro. We asked whether PAA sterilization would influence recellularization, restoration of crimp length and pattern, and revascularization of ACL grafts during early healing. We used an in vivo sheep model for open ACL reconstruction. We also correlated the histologic findings with the restoration of anteroposterior stability and structural properties during load-to-failure testing. PAA slowed remodeling activity at 6 and 12 weeks compared to nonsterilized allografts and autografts. The mechanical properties of PAA grafts were also reduced compared to these control groups at both time points. We conclude PAA sterilization currently should not be used to sterilize soft tissue grafts typically used in ACL reconstruction. Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. This study was funded by research grants of the Charité Research Funds and the Musculoskeletal Transplant Foundation. Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.     

Treatment of actinic keratoses with birch bark extract: a pilot study

Background: Birch bark contains a variety of apoptosis‐inducing and anti‐inflammatory substances such as betulinic acid, betulin, oleanolic acid and lupeol. Therefore, birch bark extract may be effective in the treatment of actinic keratoses. To address this issue, a pilot study using a standardized birch bark ointment was performed. Methods: Twenty‐eight patients with actinic keratoses were enrolled in this prospective, non‐randomized pilot study. Fourteen patients were treated with birch bark ointment only; fourteen patients received a combination therapy with cryotherapy and birch bark ointment. Treatment response was assessed clinically after two months. Results: Clearing of more than 75 % of the lesions was seen in 79 % of the patients treated with birch bark ointment monotherapy. The response rate of the combined treatment modality was 93 %. Therapy with birch bark ointment was well tolerated. Conclusion: In this pilot study, a standardized birch bark extract was effective in the treatment of actinic keratoses. This therapy is easy to perform and it has no side effects. Birch bark ointment may be a new therapeutic option for actinic keratoses.     

Characterization of the sensitizing potential of chemicals by in vitro analysis of dendritic cell activation and skin penetration

Development of in vitro models to identify sensitizing chemicals receives public interest since animal testing should be avoided whenever possible. In this article we analyze two essential properties of sensitizing chemicals: skin penetration and dendritic cell (DC) activation. Activation of immature DC derived from peripheral blood monocytes was evaluated by flow cytometric analysis of CD86 positive cells and quantitative measurement of interleukin-1beta and aquaporin P3 gene expression. The sensitizer 2,4,6-trinitrobenzenesulfonic acid induced a concentration-dependent response for all parameters, whereas the irritant sodium lauryl sulfate did not. When two related aromatic amines, p-toluylenediamine (PTD) and hydroxyethyl-p-phenylenediamine (HE-PPD) were tested, both induced substantial DC activation indicating their potential sensitizing properties. These findings contrasted with in vivo results: in murine local lymph node assays (LLNA) PTD, but not HE-PPD, was sensitizing using acetone/aqua/olive oil as vehicle. Skin penetration measurement revealed that this was due to bioavailability differences. On retesting HE-PPD in the LLNA using the penetration enhancer dimethylsulfoxide as vehicle, it induced a specific response. We conclude that in vitro analysis of DC activation capability of the two selected chemicals demonstrates that prediction of skin sensitization potential is possible provided that skin penetration data indicate sufficient bioavailability of the test compound.