Innovative DNA vaccine for human papillomavirus (HPV)-associated head and neck cancer

Human papillomavirus (HPV), particularly type 16, has been associated with a subset of head and neck cancers. The viral-encoded oncogenic proteins E6 and E7 represent ideal targets for immunotherapy against HPV-associated head and neck cancers. DNA vaccines have emerged as attractive approaches for immunotherapy due to its simplicity, safety and ease of preparation. Intradermal administration of DNA vaccine by means of gene gun represents an efficient method to deliver DNA directly into dendritic cells for priming antigen-specific T cells. We have previously shown that a DNA vaccine encoding an invariant chain (Ii), in which the class II-associated Ii peptide (CLIP) region has been replaced by a Pan-DR-epitope (PADRE) sequence to form Ii-PADRE, is capable of generating PADRE-specific CD4+ T cells in vaccinated mice. In the current study, we hypothesize that a DNA vaccine encoding Ii-PADRE linked to E6 (Ii-PADRE-E6) will further enhance E6-specific CD8+ T cell immune responses through PADRE-specific CD4+ T-helper cells. We found that mice vaccinated with Ii-PADRE-E6 DNA generated comparable levels of PADRE-specific CD4+ T-cell immune responses, as well as significantly stronger E6-specific CD8+ T-cell immune responses and antitumor effects against the lethal challenge of E6-expressing tumor compared with mice vaccinated with Ii-E6 DNA. Taken together, our data indicate that vaccination with Ii-E6 DNA with PADRE replacing the CLIP region is capable of enhancing the E6-specific CD8+ T-cell immune response generated by the Ii-E6 DNA. Thus, Ii-PADRE-E6 represents a novel DNA vaccine for the treatment of HPV-associated head and neck cancer and other HPV-associated malignancies.     

V.R. Khanolkar: father of pathology and medical research in India

Vasant Ramji Khanolkar was the first pathologist in India. He made major contributions to the epidemiology and understanding of cancer, blood groups, and leprosy. He was the first to show the existence of dhoti cancers, and was among the earliest to demonstrate the carcinogenicity of tobacco and the use of needle aspiration cytology for the diagnosis of neoplasms. He was an acclaimed teacher and was on the boards of numerous international organizations. He was a bibliophile and his writings are Oslerian in style. He serves as a role model to the few in India who are aware of him. He deserves to be called the "Father of pathology and medical research in India."     

Recognition of personally familiar scenes in patients with very mild Alzheimer's disease: effects of spatial frequency and luminance

Many community-residing patients with Alzheimer's disease (AD) have way-finding problems, particularly at twilight or on rainy days. In an attempt to understand the mechanism, we prepared pictures of street scenes, including 8 personally familiar and 8 unfamiliar, divided into Low Spatial Frequency (LSF) and Low Luminance (LL) conditions to simulate foggy or rainy days and nighttime. Each picture was presented from the most difficult (level 10) to the easiest (level 1). The participants, including 20 very mild AD patients and 20 normal controls (NC) with equal basic visual acuity, were asked to judge whether a picture was familiar or not and to describe how they came to that conclusion. The accuracy of familiar scene recognition was measured by the number of pictures successfully recognized and the ability thereof by the level needed. Compared with NC, AD patients showed poorer accuracy (2.7 ± 0.2 versus 3.6 ± 0.1, mean ± SEM, p = 0.003 under LSF; 2.8 ± 0.2 versus 3.8 ± 0.1, p = 0.001 under LL) and poorer ability (2.2 ± 0.4 versus 4.3 ± 0.4 p = 0.000 under LSF; 2.9 ± 0.3 versus 5.2 ± 0.5, p = 0.000 under LL) for both conditions. The AD patients used a global element to help judge when personally familiar scenes were displayed, which was the method NC usually adopted when presented with novel scenes. In summary, this study demonstrated poorer recognition ability in very mild AD patients when personally familiar street scenes were displayed, and the underlying mechanisms may include impaired visual search performance and efficiency. The deficits also reflect their difficulty in real life situations when their familiar environments become blurred or dark.     

Patient safety in rehabilitation medicine: traumatic brain injury

This article describes patient safety after traumatic brain injury (TBI). Patient safety in rehabilitation after TBI is important. Thorough assessment on initial evaluation, vigilance for medical and procedural errors, appropriate communication between medical professionals, and evaluation of systems-based practices increases patient safety. It is the responsibility of the rehabilitation treatment team to ensure that appropriate measures are taken to reduce risk of adverse events. This article is intended to promote discussion of patient safety after TBI within rehabilitation teams and to help improve outcomes throughout the spectrum of recovery.