Scoliosis circa 2000: radiologic imaging perspective

Plain film imaging remains important for the diagnosis and surveillance of scoliosis, as well as for the detection of complications after surgery. Advances in CT and MR imaging have greatly improved the ability to detect or confirming nonidiopathic causes of scoliosis, including abnormalities within the spinal canal. Three-dimensional thinking has become more important in evaluating and understanding scoliosis.     

Mitochondrial repair of 8-oxoguanine and changes with aging

Reactive oxygen species (ROS) are formed in all living organisms as a by-product of normal metabolism (endogenous sources) and as a consequence of exposure to environmental compounds (exogenous sources). Endogenous ROS are largely formed during oxidative phosphorylation in the mitochondria and, therefore, mitochondrial DNA (mtDNA) is at particularly high risk of ROS-induced damage. Mitochondria are essential for cell viability, and oxidative damage to mtDNA has been implicated as a causative factor in a wide variety of degenerative diseases, and in cancer and aging. One of the most common oxidative DNA lesions is 7,8-dihydro-8-oxoguanine (8-oxoG), which can introduce G/C to T/A transversions after DNA replication. Oxidative DNA base lesions, including 8-oxoG, are repaired primarily by the base excision repair (BER) pathway. While we know much about how this pathway functions in processing the nuclear DNA lesions, little is yet known about BER in mitochondria. We have used a number of different approaches to explore the mechanisms of DNA damage processing in the mtDNA. We have been able to demonstrate that mammalian mitochondria efficiently remove 8-oxoG from their genome, and that the efficiency of 8-oxoG incision increases with age in rats and mice. Yet 8-oxoG accumulates in mtDNA during aging. Changes in mitochondrial function with age have been observed in several organisms and accumulation of DNA lesions in mtDNA with age may be an underlying cause for numerous age-associated diseases including cancer.     

The AWS from a parent's point of view:

The parents of 36 people with mental handicaps were interviewed concerning their views on more integrated services for their relatives. Most were in favour of such developments, but considerable opposition was expressed in a number of areas, especially in relation to day care and education. Parents of those with more severe handicaps tended to be least in favour of integration. Some implications for consumer involvement in the AWS are discussed.     

Antibodies to Crucial Epitopes on HSV-2 Glycoprotein D as a Guide to Dosing an mRNA Genital Herpes Vaccine

The toxicity of mRNA-lipid nanoparticle (LNP) vaccines depends on the total mRNA-LNP dose. We established that the maximum tolerated dose of our trivalent mRNA-LNP genital herpes vaccine was 10 μg/immunization in mice. We then evaluated one of the mRNAs, gD2 mRNA-LNP, to determine how much of the 10 μg total dose to assign to this immunogen. We immunized mice with 0.3, 1.0, 3.0, or 10 μg of gD2 mRNA-LNP and measured serum IgG ELISA, neutralizing antibodies, and antibodies to six crucial gD2 epitopes involved in virus entry and spread. Antibodies to crucial gD2 epitopes peaked at 1 μg, while ELISA and neutralizing titers continued to increase at higher doses. The epitope results suggested no immunologic benefit above 1 μg of gD2 mRNA-LNP, while ELISA and neutralizing titers indicated higher doses may be useful. We challenged the gD2 mRNA-immunized mice intravaginally with HSV-2. The 1-μg dose provided total protection, confirming the epitope studies, and supported assigning less than one-third of the trivalent vaccine maximum dose of 10 μg to gD2 mRNA-LNP. Epitope mapping as performed in mice can also be accomplished in phase 1 human trials to help select the optimum dose of each immunogen in a multivalent vaccine.     

Innovation and Integrity: Desiderata and Future Directions for Prevention and Intervention Science

This article summarizes essential implications of the papers within this special issue and discusses directions for future prevention and intervention research on conceptual issues, methodological and transfer-related challenges and opportunities. We identify a need to move from programs to principles in intervention research and encourage the implementation of research on potential mechanisms underlying intervention effectiveness. In addition, current methodological issues in intervention research are highlighted, including advancements in methodology and statistical procedures, extended outcome assessments, replication studies, and a thorough examination of potential biases. We further discuss transfer-related issues, for example the need for more research on the flexibility and adaptability of programs and intervention approaches as well as more general problems in knowledge translation reasoning the need for enhanced communication between practitioners, policy makers, and researchers. Finally, we briefly touch on the need to discuss the relation between single intervention programs, the mental health system, and changes of contextual conditions at the macro level.     

Using gas chromatography and mass spectrometry to determine 25-hydroxyvitamin D levels for clinical assessment of vitamin D deficiency

Vitamin D is responsible for multiple metabolic functions in humans. Rickets are the most common disease caused by vitamin D deficiency. It is caused by poor calcium intake resulting in poor serum-ionized calcium. The purpose of this study is to develop a rapid, sensitive, and feasible method to determine the 25-hydroxy-vitamin D3 (25(OH)D3) levels in blood samples for clinical assessment. In this study, gas chromatography coupled mass spectrometry with trimethylsilyl derivatization (TMS-GC-MS) is the most suitable protocol for quantitative analyses of 25(OH)D3. Performance of method was evaluated and compared with liquid chromatography and immunoassay. Method validation has been carried out with plasma specimens. The limit of quantitation of TMS-GC-MS method is 1.5 ppb with good linear correlation. Furthermore, the dietary intake and nutritional status of vegetarian and non-vegetarians in Taiwan were assessed by our validated method. As a result, this vitamin D nutrition survey demonstrates that most Taiwanese people have insufficient vitamin D. Due to dietary habits; the male vegans may have the highest risk of vitamin D deficiency.