Vitamin B12 Deficiency and Hyperhomocysteinemia in Outpatients with Stroke or Transient Ischemic Attack: a cohort study at an academic medical centre

Objective We sought to assess the current magnitude of the opportunity for secondary stroke prevention with B vitamins. Design A cohort study. Setting The Urgent TIA (Transient Ischaemic Attack) Clinic at an academic medical centre. Main outcome measures We assessed the prevalence of biochemical vitamin B 12 deficiency (B 12 Def, serum B 12 \u3c156 pmol/L), hyperhomocysteinaemia (HHcy; plasma total homocysteine [tHcy] \u3e14 μmol/L) and metabolic B 12 deficiency (MetB 12 Def, serum B 12 \u3c258 pmol/L and HHcy) between 2002 and 2017, by age group and by stroke subtype. Results Data were available in 4055 patients. B 12 Def was present in 8.2% of patients overall; it declined from 10.9% of patients referred before 2009 to 5.4% thereafter (p=0.0001). MetB 12 Def was present in 10.6% of patients, and HHcy was present in 19.1% of patients. Among the patients aged ≥80 years, MetB 12 Def was present in 18.1% and HHcy in 35%. Among the 3410 patients whose stroke subtype was determined, HHcy was present in 18.4% of patients: 23.3% of large artery atherosclerosis, 18.1% of cardioembolic, 16.3% of small vessel disease, 10.8% of other unusual aetiologies and 13.6% of undetermined subtypes (p=0.0001). Conclusions Despite a decline in our referral area since 2009, B 12 Def, MetB 12 Def and HHcy remain common in patients with stroke/TIA. Because these conditions are easily treated and have serious consequences, all patients with stroke/TIA should have their serum B 12 and tHcy measured

Clinically relevant safety issues associated with St. John's wort product labels

<p>Abstract</p> <p>Background</p> <p>St. John's wort (SJW), used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA.</p> <p>Methods</p> <p>Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings.</p> <p>Results</p> <p>Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of <it>a priori </it>safety issues included on a product label was 1.91 (range 0–8) for 23.9% completeness.</p> <p>Conclusion</p> <p>The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements.</p

Shedding light on plant litter decomposition: Advances, implications and new directions in understanding the role of photodegradation

Litter decomposition contributes to one of the largest fluxes of carbon (C) in the terrestrial biosphere and is a primary control on nutrient cycling. The inability of models using climate and litter chemistry to predict decomposition in dry environments has stimulated investigation of non-traditional drivers of decomposition, including photodegradation, the abiotic decomposition of organic matter via exposure to solar radiation. Recent work in this developing field shows that photodegradation may substantially influence terrestrial C fluxes, including abiotic production of carbon dioxide, carbon monoxide and methane, especially in arid and semi-arid regions. Research has also produced contradictory results regarding controls on photodegradation. Here we summarize the state of knowledge about the role of photodegradation in litter decomposition and C cycling and investigate drivers of photodegradation across experiments using a meta-analysis. Overall, increasing litter exposure to solar radiation increased mass loss by 23% with large variation in photodegradation rates among and within ecosystems. This variation was tied to both litter and environmental characteristics. Photodegradation increased with litter C to nitrogen (N) ratio, but not with lignin content, suggesting that we do not yet fully understand the underlying mechanisms. Photodegradation also increased with factors that increased solar radiation exposure (latitude and litter area to mass ratio) and decreased with mean annual precipitation. The impact of photodegradation on C (and potentially N) cycling fundamentally reshapes our thinking of decomposition as a solely biological process and requires that we define the mechanisms driving photodegradation before we can accurately represent photodegradation in global C and N models. © 2012 US Government

The Potential Mechanisms of Exercise-induced Cognitive Protection: A Literature Review.

Dementia has become a major health concern for the aging population of the United States. Studies indicate that participation in moderate exercise, with training, has been shown to have a beneficial impact on cognition. Thus, exercise and its effects on cognitive function has become an important area of research. This review summarizes the current literature on the potential mechanisms of the benefits of exercise for cognitive function

Metabolic, inflammatory, and microvascular determinants of white matter disease and cognitive decline.

White Matter Disease is increasingly being recognized as an important cause of cognitive decline and dementia. Various investigations have linked chronic diet-related conditions to the development of white matter lesions, which appear as white matter hyperintensities on T2-weighted magnetic resonance imaging (MRI) scans of the brain. Thus, it can be postulated that the metabolic, inflammatory, and microvascular changes accompanying a western diet, hyperlipidemia, hypertension, and diabetes mellitus type II (DMII) are potential mediators in the development and progression of white matter disease, which in turn contributes to the development and progression of cognitive decline. This review will examine evidence for potential metabolic, inflammatory, and microvascular determinants of white matter disease and cognitive decline. Specifically, we will focus on the effects of altered insulin signaling in diabetes, obesity-induced oxidative stress, neuroinflammation, arterial stiffness due to hypertension, ischemia secondary to cerebral small vessel disease, and blood brain barrier disturbances

Sex-Specific Response of the Brain Free Oxylipin Profile to Soluble Epoxide Hydrolase Inhibition.

Oxylipins are the oxidation products of polyunsaturated fatty acids and have been implicated in neurodegenerative disorders, including dementia. Soluble epoxide hydrolase (sEH) converts epoxy-fatty acids to their corresponding diols, is found in the brain, and its inhibition is a treatment target for dementia. In this study, male and female C57Bl/6J mice were treated with an sEH inhibitor (sEHI), trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), for 12 weeks to comprehensively study the effect of sEH inhibition on the brain oxylipin profile, and modulation by sex. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure the profile of 53 free oxylipins in the brain. More oxylipins were modified by the inhibitor in males than in females (19 versus 3, respectively) and favored a more neuroprotective profile. Most were downstream of lipoxygenase and cytochrome p450 in males, and cyclooxygenase and lipoxygenase in females. The inhibitor-associated oxylipin changes were unrelated to serum insulin, glucose, cholesterol, or female estrous cycle. The inhibitor affected behavior and cognitive function as measured by open field and Y-maze tests in males, but not females. These findings are novel and important to our understanding of sexual dimorphism in the brain's response to sEHI and may help inform sex-specific treatment targets

Inhibition of perilipin 2 expression reduces pro-inflammatory gene expression and increases lipid droplet size

Our lab previously demonstrated that triglyceride-rich lipoprotein (TGRL) lipolysis products induce lipid droplet formation and pro-inflammatory gene expression in monocytes. We hypothesized that the inhibition of perilipin 2 expression in THP-1 monocytes would reduce lipid droplet formation and suppress pro-inflammatory gene expression induced by TGRL lipolysis products. In the current study, we use microarray analysis to identify gene expression altered by TGRL lipolysis products in THP-1 monocytes. We confirmed the expression of selected genes by quantitative reverse transcription PCR and characterized lipid droplet formation in these cells after exposure to TGRL lipolysis products. Using siRNA inhibition of perilipin 2 expression, we examined the role of perilipin 2 in the response of THP-1 monocytes to TGRL lipolysis products. We found that perilipin 2 siRNA increased the intracellular triglyceride content, increased the size of lipid droplets, and reduced pro-atherogenic and pro-inflammatory gene expression. We saw a reduction of serum/glucocorticoid kinase 1, v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (avian), chemokine (C-C motif) ligand 3, and interleukin 8 gene expression induced by TGRL lipolysis products. This study supports previous findings that reduction of perilipin 2 expression is protective against atherogenesis, while finding an unexpected increase in lipid droplet size with reduced perilipin 2 expression