Once foods in the United States were fortified with vitamin D, rickets appeared to have been conquered, and many considered major health problems from vitamin D deficiency resolved. But vitamin D deficiency is common. This review considers the role of vitamin D in skeletal and nonskeletal health and suggests strategies for the prevention and treatment of vitamin D deficiency.

Vitamin D Deficiency

Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes.

Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

Intracellular double-stranded RNA (dsRNA) is a chief sign of replication for many viruses. Host mechanisms detect the dsRNA and initiate antiviral responses. In this report, we identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling, as assessed by functional screening and assays. A helicase domain with intact ATPase activity was responsible for the dsRNA-mediated signaling. The caspase recruitment domain transmitted 'downstream' signals, resulting in the activation of transcription factors NF-kappaB and IRF-3. Subsequent gene activation by these factors induced antiviral functions, including type I interferon production. Thus, RIG-I is key in the detection and subsequent eradication of the replicating viral genomes.

The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses.

As people get older, they may fall more often for a variety of reasons including problems with balance, poor vision, and dementia. Up to 30% may fall in a year. Although one in five falls may require medical attention, less than one in 10 results in a fracture.
This review looked at the healthcare literature to establish which fall prevention interventions are effective for older people living in the community, and included 159 randomised controlled trials with 79,193 participants.  
Group and home-based exercise programmes, usually containing some balance and strength training exercises, effectively reduced falls, as did Tai Chi. Overall, exercise programmes aimed at reducing falls appear to reduce fractures.
Multifactorial interventions assess an individual's risk of falling, and then carry out treatment or arrange referrals to reduce the identified risks. Overall, current evidence shows that this type of intervention reduces the number of falls in older people living in the community but not the number of people falling during follow-up. These are complex interventions, and their effectiveness may be dependent on factors yet to be determined.  
Interventions to improve home safety appear to be effective, especially in people at higher risk of falling and when carried out by occupational therapists. An anti-slip shoe device worn in icy conditions can also reduce falls.
Taking vitamin D supplements does not appear to reduce falls in most community-dwelling older people, but may do so in those who have lower vitamin D levels in the blood before treatment.  
Some medications increase the risk of falling. Three trials in this review failed to reduce the number of falls by reviewing and adjusting medications. A fourth trial involving family physicians and their patients in medication review was effective in reducing falls. Gradual withdrawal of a particular type of drug for improving sleep, reducing anxiety, and treating depression (psychotropic medication) has been shown to reduce falls.
Cataract surgery reduces falls in women having the operation on the first affected eye. Insertion of a pacemaker can reduce falls in people with frequent falls associated with carotid sinus hypersensitivity, a condition which causes sudden changes in heart rate and blood pressure.
In people with disabling foot pain, the addition of footwear assessment, customised insoles, and foot and ankle exercises to regular podiatry reduced the number of falls but not the number of people falling.
The evidence relating to the provision of educational materials alone for preventing falls is inconclusive.

Interventions for preventing falls in older people living in the community

Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method.

シアル酸の影響を除外した特異的な血清過酸化脂質の比色測定法を開発し, 脳血管障害後遺症患者117例と, 健康人129例の血清について測定を行った.新しく確立された方法においては, 低濃度の酸を溶媒として, 硫酸ナトリウムの存在下でTBA反応を行うことがシアル酸の影響を除外するうえで重要と考えられた.本法によって測定した血清過酸化脂質は, 健康人では加齢とともに高値となり, 49歳以下と50～59歳及び60歳以上との間には有意差が認められた.脳血管障害患者の値は, 脳梗塞例, 脳出血例ともに健康人より高く, その差は60歳以上を除いて明瞭であった.また, 血清tocopherolとの間には, 健康人において有意の負の相関関係が認められた.これらの結果は, 老化や動脈硬化性疾患における過酸化脂質の重要性を示すものと考えられる.シアル酸の影響を除外した血清過酸化脂質の比色測定法を開発した.本法は特異的で, 血清過酸化脂質を正確に測定することができる.本法によって測定した血清過酸化脂質は, 健康人では加齢とともに高値となり, 脳血管障害患者の値は健康人に比べて高かった.これらの結果は, 老化や動脈硬化性疾患における過酸化脂質の重要性を示すものと考えられる.

Serum lipid peroxide in cerebrovascular diseases determined by a new colorimetric method

Brain inflammation has been implicated in the development of brain edema and secondary brain damage in ischemia and trauma. Adhesion molecules, cytokines and leukocyte chemoattractants released/presented at the site of blood-brain barrier (BBB) play an important role in mobilizing peripheral inflammatory cells into the brain. Cerebral endothelial cells (CEC) are actively engaged in processes of microvascular stasis and leukocyte infiltration by producing a plethora of pro-inflammatory mediators. When challenged by external stimuli including cytokines and hypoxia, CEC have been shown to release/express various products of arachidonic acid cascade with both vasoactive and pro-inflammatory properties, including prostaglandins, leukotrienes, and platelet-activating factor (PAF). These metabolites induce platelet and neutrophil activation and adhesion, changes in local cerebral blood flow and blood rheology, and increases in BBB permeability. Ischemic CEC have also been shown to express and release bioactive inflammatory cytokines and chemokines, including IL-Iβ, IL-8 and MCP-1. Many of these mediators and ischemia in vitro and in vivo have been shown to up-regulate the expression of both selectin and Ig-families of adhesion molecules in CEC and to facilitate leukocyte adhesion and transmigration into the brain. Collectively, these studies demonstrate a pivotal role of CEC in initiating and regulating inflammatory responses in cerebral ischemia.

Summary
Inflammatory genes/mediators are involved in molecular/biochemical cascades determining stroke outcome. Cerebral endothelial cells, targeted by inflammatory mediators produced in ischemic brain, undergo pro-inflammatory activation by expressing/secreting various inflammatory mediators, thus becoming a source of inflammation themselves. A unique position of the cerebral endothelial cells at the interface between blood and brain establishes their role as principal regulators of peripheral inflammatory cell recruitment into the brain during stroke. Cerebral endothelial cells also exhibit ability to regulate vasomotor responses of brain microcirculation and the permeability of the BBB, both important components of inflammation. Therefore, approaches to attenuate consequences of stroke must take into consideration cerebral endothelial cells as an easily accessible target to interfere with the ischemic brain inflammation.

Inflammatory mediators of cerebral endothelium: a role in ischemic brain inflammation.

Deficiency of plasma platelet-activating factor (PAF) acetylhydrolase is an autosomal recessive syndrome that has been associated with severe asthma in Japanese children. Acquired deficiency has been described in several human diseases usually associated with severe inflammation. PAF acetylhydrolase catalyzes the degradation of PAF and related phospholipids, which have proinflammatory, allergic, and prothrombotic properties. Thus, a deficiency in the degradation of these lipids should increase the susceptibility to inflammatory and allergic disorders. Miwa et al. reported that PAF acetylhydrolase activity is absent in 4% of the Japanese population, which suggests that it could be a common factor in such disorders, but the molecular basis of the defect is unknown. We show that inherited deficiency of PAF acetylhydrolase is the result of a point mutation in exon 9 and that this mutation completely abolishes enzymatic activity. This mutation is the cause of the lack of enzymatic activity as expression in E. coli of a construct harboring the mutation results in an inactive protein. This mutation as a heterozygous trait is present in 27% in the Japanese population. This finding will allow rapid identification of subjects predisposed to severe asthma and other PAF-mediated disorders.

https://dm5migu4zj3pb.cloudfront.net/manuscripts/118000/118733/JCI96118733.pdf

Kei Satoh

Papers

Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method.

Serum lipid peroxide in cerebrovascular diseases determined by a new colorimetric method

Inflammatory mediators of cerebral endothelium: a role in ischemic brain inflammation.

Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase.

Dyslipidemia Associated with Atherosclerotic Disease Systemically Alters Dendritic Cell Mobilization