A systematic review and meta-analysis exploring the efficacy of mindfulness-based interventions on quality of life in people with multiple sclerosis.

BACKGROUND: Quality of life (QoL) is commonly impaired among people with multiple sclerosis (PwMS). The aim of this study was to evaluate via meta-analysis the efficacy of Mindfulness-based interventions (MBIs) for improving QoL in PwMS. METHODS: Eligible randomized controlled trials (RCTs) were identified via searching six major electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, AMED, and PsycINFO) in April 2022. The primary outcome was QoL. Study quality was determined using the Cochrane Collaboration risk of bias tool. Meta-analysis using a random effects model was undertaken. Effect sizes are reported as Standardized Mean Difference (SMD). Prospero ID: 139835. RESULTS: From a total of 1312 individual studies, 14 RCTs were eligible for inclusion in the meta-analysis, total participant n = 937. Most studies included PwMS who remained ambulatory. Cognitively impaired PwMS were largely excluded. Comorbidities were inconsistently reported. Most MBIs were delivered face-to face in group format, but five were online. Eight studies (n = 8) measured MS-specific QoL. In meta-analysis, overall effect size (SMD) for any QoL measure (n = 14) was 0.40 (0.18-0.61), p = 0.0003, I2 = 52%. SMD for MS-specific QoL measures (n = 8) was 0.39 (0.21-0.57), p < 0.0001, I2 = 0%. MBI effect was largest on subscale measures of mental QoL (n = 8), SMD 0.70 (0.33-1.06), p = 0.0002, I2 = 63%. Adverse events were infrequently reported. CONCLUSIONS: MBIs effectively improve QoL in PwMS. The greatest benefits are on mental health-related QoL. However, more research is needed to characterize optimal formatting, mechanisms of action, and effects in PwMS with more diverse social, educational, and clinical backgrounds.

Virtually-delivered Sudarshan Kriya Yoga (SKY) for Canadian veterans with PTSD: A study protocol for a nation-wide effectiveness and implementation evaluation.

BACKGROUND: Post-traumatic stress disorder (PTSD) remains a significant treatment challenge among Canadian veterans. Currently accessible pharmacological and non-pharmacological interventions for PTSD often do not lead to resolution of PTSD as a categorical diagnosis and have significant non-response rates. Sudarshan Kriya Yoga (SKY), a complementary and integrative health (CIH) intervention, can improve symptoms of PTSD. In response to the COVID-19 pandemic, this intervention has pivoted to virtual delivery and may be reaching new sets of participants who face multiple barriers to care. OBJECTIVE: To evaluate the implementation and effectiveness of virtually delivered Sudarshan Kriya Yoga (SKY) on decreasing PTSD symptom severity, symptoms of depression, anxiety, and pain, and improving quality of life in Canadian veterans affected by PTSD. METHODS AND ANALYSIS: Using a mixed-methods approach guided by the RE-AIM framework, we will conduct a hybrid type II effectiveness and implementation study of virtually delivered Sudarshan Kriya Yoga (SKY) for Canadian veterans. Effectiveness will be evaluated by comparing virtually delivered SKY to a waitlist control in a single-blinded (investigator and data analyst) randomized controlled trial (RCT). Change in PTSD symptoms (PCL-5) is the primary outcome and quality of life (SF-36), symptoms of depression (PHQ-9), anxiety (GAD-7), and pain (BPI) are secondary outcomes. The SKY intervention will be conducted over a 6-week period with assessments at baseline, 6-weeks, 12-weeks, and 30 weeks. The reach, effectiveness, adoption, implementation, and maintenance of the intervention will be evaluated through one-on-one semi-structured interviews with RCT participants, SKY instructors, health professionals, and administrators that work with veterans. DISCUSSION: This is the first investigation of the virtual delivery of SKY for PTSD in veterans and aims to determine if the intervention is effective and implementable at scale.

Actinidin diversity: discovery of common and selective substrates for actinidin isoforms and Actinidia cultivars.

The actinidin proteinase family has a striking sequence diversity; isoelectric points range from 3.9 to 9.3. The biological drive for this variation is thought to be actinidin's role as a defense-related protein. In this study we map mutations in the primary sequence onto the 3D structure of the protein and show that the region with the highest diversity is close to the substrate binding groove. Non-conservative substitutions in the active site determine substrate preference and therefore create problems for quantification of actinidin activity. Here we use a peptide substrate library to compare two actinidin isoforms, one from the kiwiberry cultivar 'Hortgem Tahi' (Actinidia arguta), and the other from the familiar kiwifruit cultivar 'Hayward' (Actinidia chinensis var. deliciosa). Among 360 octamer substrates we find one substrate (RVAAGSPI) with the useful property of being readily cleaved by all the functionally active actinidins in a set of A. arguta and A. chinensis var. deliciosa isoforms. In addition, we find that two substrates (LPPKSQPP & ILRDKDNT) have the ability to differentiate different isoforms from a single fruit. We compare actinidins from 'Hayward' and A. arguta for their ability to digest the allergenic gluten peptide (PFPQPQLPY) but find the peptide to be indigestible by all sources of actinidin. The ability to inactivate salivary amylase is shown to be a common trait in Actinidia cultivars due to proteolysis by actinidin and is particularly strong in 'Hortgem Tahi'. A mixture of 10% 'Hortgem Tahi' extract with 90% saliva inactivates 100% of amylase activity within 5 minutes. Conceivably, 'Hortgem Tahi' might lower the glycaemic response in a meal rich in cooked starch.

Mindfulness-based interventions for people with multiple sclerosis: a systematic review and meta-aggregation of qualitative research studies.

PURPOSE: Mindfulness-based interventions (MBIs) are effective treatments for stress, anxiety, and depression in PwMS. However, low adherence and high attrition may limit effectiveness. Qualitative research can provide important insights into MBI acceptability, accessibility, and implementation. This systematic review and meta-aggregation evaluated qualitative research findings on the use of MBIs for PwMS. METHODS: Systematic searches were undertaken in six major electronic databases. Studies using qualitative or mixed methods were included. Two reviewers screened, data extracted, and critically appraised studies. Meta-aggregation was performed following the Joanna Briggs Institute approach, extracting findings, developing categories, and synthesizing findings. RESULTS: Six eligible papers, including 136 PwMS were included in meta-aggregation. 136 findings were extracted, grouped into 17 categories, with four synthesized findings: (1) "accessing mindfulness," (2) "a sense of belonging," (3) "experiencing mindfulness," and (4) "making mindfulness more relevant and sustainable for PwMS." CONCLUSIONS: MBIs for PwMS need to take into consideration disability which can limit accessibility. Online MBIs (synchronous and asynchronous) appear acceptable alternatives to traditional face-to-face courses. However, PwMS benefit from shared (mindful) experiencing and highlight MBI instructors as crucial in helping them understand and practice mindfulness. Involving PwMS in design, delivery, and iterative refinement would make MBIs more relevant to those taking part.IMPLICATIONS FOR REHABILITATIONBoth face-to-face and online Mindfulness-based interventions (MBIs) appear acceptable to PwMS and, ideally, people should be offered a choice in training modality.PwMS derive benefit from undertaking MBIs with their peers, where a sense of camaraderie and belonging develop through shared (mindful) experiences.Instructors delivering MBIs for PwMS should be knowledgeable about the condition; participants describe how the instructor has a key role in helping them practice mindfulness effectively in the context of unpleasant experiences associated with MS.MBIs tailored for PwMS should include a pre-course orientation session, clearly articulate how mindfulness practices can help with MS, provide well-organized course materials in large font size, and deliver individual mindfulness practices flexibly depending on participant need.

Effects of Mindfulness-based interventions on physical symptoms in people with multiple sclerosis - a systematic review and meta-analysis.

BACKGROUND: Physical wellbeing is commonly impaired in people with multiple sclerosis (PwMS). This study aims to update our previous systematic review (2014) and conduct a meta-analysis on the efficacy of Mindfulness-based interventions (MBIs) for improving physical symptoms in PwMS. METHODS: In November 2017 we carried out systematic searches for eligible randomised controlled trials (RCTs) in seven major databases, updating our search in July 2018. We used medical subject headings and key words. Two independent reviewers used pre-defined criteria to screen, data extract, quality appraise, and analyse studies. The Cochrane Collaboration risk of bias tool was used to determine study quality. Physical wellbeing was the main outcome of interest. We used the random effects model for meta-analysis, reporting effect sizes as Standardised Mean Difference (SMD). This study is registered with PROSPERO: CRD42018093171. RESULTS: We identified 10 RCTs as eligible for inclusion in the systematic review (including 678 PwMS), whilst seven RCTs (555 PwMS) had data that could be used in our meta-analyses. In general, comorbidity, disability, ethnicity and socio-economic status were poorly reported. MBIs included manualised and tailored interventions, treatment duration 6-9 weeks, delivered face-to-face and online in groups and also individually. For fatigue, against any comparator SMD was 0.24 (0.08 - 0.41), I2=0%; against active comparators only, SMD was 0.10 (-0.14 - 0.34), I2=0%. For pain SMD was 0.16 (-0.46 - 0.79), I2=77%. Three adverse events occurred across all studies. CONCLUSIONS: MBIs appear to be an effective treatment for fatigue in PwMS. The optimal MBI in this context remains unclear. Further research into MBI optimisation, cost- and comparative-effectiveness is required.

Mindfulness-based interventions for mental well-being among people with multiple sclerosis: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: Impairment of mental well-being (anxiety, depression, stress) is common among people with multiple sclerosis (PwMS). Treatment options are limited, particularly for anxiety. The aim of this study was to update our previous systematic review (2014) and evaluate via meta-analysis the efficacy of mindfulness-based interventions (MBIs) for improving mental well-being in PwMS. METHODS: Systematic searches for eligible randomised controlled trials (RCTs) were carried out in seven major databases (November 2017, July 2018), using medical subject headings and key words. Studies were screened, data extracted, quality appraised and analysed by two independent reviewers, using predefined criteria. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Mental well-being was the primary outcome. Random effects model meta-analysis was performed, with effect size reported as standardised mean difference (SMD). RESULTS: Twelve RCTs including 744 PwMS were eligible for inclusion in the systematic review, eight had data extractable for meta-analysis; n=635. Ethnicity, socioeconomic status, comorbidity and disability were inconsistently reported. MBIs varied from manualised to tailored versions, lasting 6-9 weeks, delivered individually and via groups, both in person and online. Overall SMD for mental well-being (eight studies) was 0.40 (0.28-0.53), p<0.01, I2=28%; against active comparators only (three studies) SMD was 0.17 (0.01-0.32), p<0.05, I2 =0%. Only three adverse events were reported. CONCLUSIONS: MBIs are effective at improving mental well-being in PwMS. More research is needed regarding optimal delivery method, cost-effectiveness and comparative-effectiveness. PROSPERO REGISTRATION NUMBER: CRD42018093171.

Mindfulness-Based Interventions for Young Offenders: a Scoping Review.

Youth offending is a problem worldwide. Young people in the criminal justice system have frequently experienced adverse childhood circumstances, mental health problems, difficulties regulating emotions and poor quality of life. Mindfulness-based interventions can help people manage problems resulting from these experiences, but their usefulness for youth offending populations is not clear. This review evaluated existing evidence for mindfulness-based interventions among such populations. To be included, each study used an intervention with at least one of the three core components of mindfulness-based stress reduction (breath awareness, body awareness, mindful movement) that was delivered to young people in prison or community rehabilitation programs. No restrictions were placed on methods used. Thirteen studies were included: three randomized controlled trials, one controlled trial, three pre-post study designs, three mixed-methods approaches and three qualitative studies. Pooled numbers (n = 842) comprised 99% males aged between 14 and 23. Interventions varied so it was not possible to identify an optimal approach in terms of content, dose or intensity. Studies found some improvement in various measures of mental health, self-regulation, problematic behaviour, substance use, quality of life and criminal propensity. In those studies measuring mindfulness, changes did not reach statistical significance. Qualitative studies reported participants feeling less stressed, better able to concentrate, manage emotions and behaviour, improved social skills and that the interventions were acceptable. Generally low study quality limits the generalizability of these findings. Greater clarity on intervention components and robust mixed-methods evaluation would improve clarity of reporting and better guide future youth offending prevention programs.

Acceptability of mindfulness from the perspective of stroke survivors and caregivers: a qualitative study.

BACKGROUND: Depression is very common among stroke survivors with estimated prevalence rates of approximately 33% among stroke survivors, but treatment options are limited. Mindfulness-Based Stress Reduction (MBSR) is an effective treatment for depression generally, but benefits in stroke patients are unclear. The aim of this study was to determine the feasibility of delivering MBSR to stroke survivors and their caregivers in the community. We conducted a study to gain views of MBSR as a potential treatment option among stroke survivors and their caregivers in the community. METHODS: Participants were recruited from an urban community in Scotland (UK) using newspaper adverts, social media and support groups run by health charities. A 2-h MBSR taster session was delivered by two experienced mindfulness instructors, followed by focus group sessions with all participants on their user experience and suggestions for MBSR modifications for stroke survivors. The focus group sessions were audio recorded and transcribed verbatim. Transcript data were analysed thematically using the framework approach. RESULTS: The study sample consisted of 28 participants (16 females); there were 21 stroke survivors (11 females) and 7 caregivers (5 females). The median age for participants was 60 years.Most participants described the MBSR taster session as a positive experience. The main challenge reported was trying to maintain focus and concentration throughout the MBSR session. Some participants expressed reservations about the duration of standard mindfulness course sessions, suggesting a preference for shorter sessions. The potential for achieving better control over negative thoughts and emotions was viewed as a potential facilitator for future MBSR participation. Participants suggested having an orientation session prior to starting an 8-week course as a means of developing familiarity with the MBSR instructor and other participants. CONCLUSION: It was feasible to recruit 21 stroke survivors and 7 caregivers for MBSR taster sessions in the community. A shorter MBSR session and an orientation session prior to the full course are suggestions for potential MBSR modifications for stroke survivors, which needs further research and evaluation.

Optimising mindfulness-based stress reduction for people with multiple sclerosis.

Objectives To gather views from patients with multiple sclerosis after completing a standard eight-week mindfulness-based stress reduction course and optimise and test a modified version as required. Methods Two successive groups of 25 multiple sclerosis patients received mindfulness-based stress reduction in a wait-list randomised controlled trial. Seventeen participants and two mindfulness-based stress reduction instructors were individually interviewed after the first (standard) course and 16 participants and the same two instructors were interviewed following the second (optimised) course. Interviews were analysed using a thematic approach. Results Mindfulness-based stress reduction was well received in both groups, with participants describing a beneficial shift in awareness. An initial (at times unpleasant) increase in awareness of disability was generally followed by greater acceptance and self-compassion. Other benefits reported included improved relationships, walking and sleep, with less stress and pain. Mindful-movement and mindful walking were problematic in group 1. This component of mindfulness-based stress reduction was simplified in group 2. A pre-course orientation session was introduced, and some organisational changes made based on feedback from group 1. Feedback from group 2 was positive in all these areas. Discussion Mindfulness-based stress reduction appears beneficial to people with multiple sclerosis, albeit mindful-movement required some modification. Contextual and organisational issues also appear important in this population.

Mindfulness-based stress reduction for people with multiple sclerosis - a feasibility randomised controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a stressful condition. Mental health comorbidity is common. Stress can increase the risk of depression, reduce quality of life (QOL), and possibly exacerbate disease activity in MS. Mindfulness-Based Stress Reduction (MBSR) may help, but has been little studied in MS, particularly among more disabled individuals. METHODS: The objective of this study was to test the feasibility and likely effectiveness of a standard MBSR course for people with MS. Participant eligibility included: age > 18, any type of MS, an Expanded Disability Status Scale (EDSS)

Mindfulness-based interventions in epilepsy: a systematic review.

BACKGROUND: Mindfulness based interventions (MBIs) are increasingly used to help patients cope with physical and mental long-term conditions (LTCs). Epilepsy is associated with a range of mental and physical comorbidities that have a detrimental effect on quality of life (QOL), but it is not clear whether MBIs can help. We systematically reviewed the literature to determine the effectiveness of MBIs in people with epilepsy. METHODS: Medline, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Allied and Complimentary Medicine Database, and PsychInfo were searched in March 2016. These databases were searched using a combination of subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed using the Cochrane Collaboration risk of bias tool. RESULTS: Three randomised controlled trials (RCTs) with a total of 231 participants were included. The interventions were tested in the USA (n = 171) and China (Hong Kong) (n = 60). Significant improvements were reported in depression symptoms, quality of life, anxiety, and depression knowledge and skills. Two of the included studies were assessed as being at unclear/high risk of bias - with randomisation and allocation procedures, as well as adverse events and reasons for drop-outs poorly reported. There was no reporting on intervention costs/benefits or how they affected health service utilisation. CONCLUSION: This systematic review found limited evidence for the effectiveness of MBIs in epilepsy, however preliminary evidence suggests it may lead to some improvement in anxiety, depression and quality of life. Further trials with larger sample sizes, active control groups and longer follow-ups are needed before the evidence for MBIs in epilepsy can be conclusively determined.

Conventional and novel body temperature measurement during rest and exercise induced hyperthermia.

Despite technological advances in thermal sensory equipment, few core temperature (TCORE) measurement techniques have met the established validity criteria in exercise science. Additionally, there is debate as to what method serves as the most practically viable, yet upholds the proposed measurement accuracy. This study assessed the accuracy of current and novel TCORE measurement techniques in comparison to rectal temperature (TREC) as a reference standard. Fifteen well-trained subjects (11 male, 4 female) completed 60min of exercise at an intensity equating to the lactate threshold; measured via a discontinuous exercise test. TREC was significantly elevated from resting values (37.2±0.3°C) at the end of moderate intensity exercise (39.6±0.04°C; P=0.001). Intestinal telemetric pill (TPILL) temperature and temporal artery temperature (TTEM) did not differ significantly from TREC at rest or during exercise (P>0.05). However, aural canal temperature (TAUR) and thermal imaging temperature (TIMA) were both significantly lower than TREC (P<0.05). Bland Altman analysis revealed only TPILL was within acceptable limits of agreement (mean bias; 0.04°C), while TTEM, TAUR and TIMA demonstrated mean bias values outside of the acceptable range (>0.27°C). Against TREC, these results support the use of TPILL over all other techniques as a valid measure of TCORE at rest and during exercise induced hyperthermia. Novel findings illustrate that TIMA (when measured at the inner eye canthus) shows poor agreement to TREC during rest and exercise, which is similar to other 'surface' measures.

A nanoparticulate ferritin-core mimetic is well taken up by HuTu 80 duodenal cells and its absorption in mice is regulated by body iron.

BACKGROUND: Iron (Fe) deficiency anemia remains the largest nutritional deficiency disorder worldwide. How the gut acquires iron from nano Fe(III), especially at the apical surface, is incompletely understood. OBJECTIVE: We developed a novel Fe supplement consisting of nanoparticulate tartrate-modified Fe(III) poly oxo-hydroxide [here termed nano Fe(III)], which mimics the Fe oxide core of ferritin and effectively treats iron deficiency anemia in rats. METHODS: We determined transfer to the systemic circulation of nano Fe(III) in iron-deficient and iron-sufficient outbread Swiss mouse strain (CD1) mice with use of (59)Fe-labeled material. Iron deficiency was induced before starting the Fe-supplementation period through reduction of Fe concentrations in the rodent diet. A control group of iron-sufficient mice were fed a diet with adequate Fe concentrations throughout the study. Furthermore, we conducted a hemoglobin repletion study in which iron-deficient CD1 mice were fed for 7 d a diet supplemented with ferrous sulfate (FeSO4) or nano Fe(III). Finally, we further probed the mechanism of cellular acquisition of nano Fe(III) by assessing ferritin formation, as a measure of Fe uptake and utilization, in HuTu 80 duodenal cancer cells with targeted inhibition of divalent metal transporter 1 (DMT1) and duodenal cytochrome b (DCYTB) before exposure to the supplemented iron sources. Differences in gene expression were assessed by quantitative polymerase chain reaction. RESULTS: Absorption (means ± SEMs) of nano Fe(III) was significantly increased in iron-deficient mice (58 ± 19%) compared to iron-sufficient mice (18 ± 17%) (P = 0.0001). Supplementation of the diet with nano Fe(III) or FeSO4 significantly increased hemoglobin concentrations in iron-deficient mice (170 ± 20 g/L, P = 0.01 and 180 ± 20 g/L, P = 0.002, respectively). Hepatic hepcidin mRNA expression reflected the nonheme-iron concentrations of the liver and was also comparable for both nano Fe(III)- and FeSO4-supplemented groups, as were iron concentrations in the spleen and duodenum. Silencing of the solute carrier family 11 (proton-coupled divalent metal ion transporter), member 2 (Slc11a2) gene (DMT1) significantly inhibited ferritin formation from FeSO4 (P = 0.005) but had no effect on uptake and utilization of nano Fe(III). Inhibiting DCYTB with an antibody also had no effect on uptake and utilization of nano Fe(III) but significantly inhibited ferritin formation from ferric nitrilotriacetate chelate (Fe-NTA) (P = 0.04). Similarly, cellular ferritin formation from nano Fe(III) was unaffected by the Fe(II) chelator ferrozine, which significantly inhibited uptake and utilization from FeSO4 (P = 0.009) and Fe-NTA (P = 0.005). CONCLUSIONS: Our data strongly support direct nano Fe(III) uptake by enterocytes as an efficient mechanism of dietary iron acquisition, which may complement the known Fe(II)/DMT1 uptake pathway.

Mindfulness based interventions in multiple sclerosis--a systematic review.

BACKGROUND: Multiple sclerosis (MS) is a stressful condition; depression, anxiety, pain and fatigue are all common problems. Mindfulness based interventions (MBIs) mitigate stress and prevent relapse in depression and are increasingly being used in healthcare. However, there are currently no systematic reviews of MBIs in people with MS. This review aims to evaluate the effectiveness of MBIs in people with MS. METHODS: Systematic searches were carried out in seven major databases, using both subject headings and key words. Papers were screened, data extracted, quality appraised, and analysed by two reviewers independently, using predefined criteria. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Perceived stress was the primary outcome. Secondary outcomes include mental health, physical health, quality of life, and health service utilisation. Statistical meta-analysis was not possible. Disagreements were adjudicated by a third party reviewer. RESULTS: Three studies (n = 183 participants) were included in the final analysis. The studies were undertaken in Wales (n = 16, randomised controlled trial - (RCT)), Switzerland (n = 150, RCT), and the United States (n = 17, controlled trial). 146 (80%) participants were female; mean age (SD) was 48.6 (9.4) years. Relapsing remitting MS was the main diagnostic category (n = 123, 67%); 43 (26%) had secondary progressive disease; and the remainder were unspecified. MBIs lasted 6-8 weeks; attrition rates were variable (5-43%); all employed pre- post- measures; two had longer follow up; one at 3, and one at 6 months. Socio-economic status of participants was not made explicit; health service utilisation and costs were not reported. No study reported on perceived stress. All studies reported quality of life (QOL), mental health (anxiety and depression), physical (fatigue, standing balance, pain), and psychosocial measures. Statistically significant beneficial effects relating to QOL, mental health, and selected physical health measures were sustained at 3- and 6- month follow up. CONCLUSION: From the limited data available, MBIs may benefit some MS patients in terms of QOL, mental health, and some physical health measures. Further studies are needed to clarify how MBIs might best serve the MS population.

A nano-disperse ferritin-core mimetic that efficiently corrects anemia without luminal iron redox activity.

The 2-5 nm Fe(III) oxo-hydroxide core of ferritin is less ordered and readily bioavailable compared to its pure synthetic analogue, ferrihydrite. We report the facile synthesis of tartrate-modified, nano-disperse ferrihydrite of small primary particle size, but with enlarged or strained lattice structure (~2.7Å for the main Bragg peak versus 2.6Å for synthetic ferrihydrite). Analysis indicated that co-precipitation conditions can be achieved for tartrate inclusion into the developing ferrihydrite particles, retarding both growth and crystallization and favoring stabilization of the cross-linked polymeric structure. In murine models, gastrointestinal uptake was independent of luminal Fe(III) reduction to Fe(II) and, yet, absorption was equivalent to that of ferrous sulphate, efficiently correcting the induced anemia. This process may model dietary Fe(III) absorption and potentially provide a side effect-free form of cheap supplemental iron. From the clinical editor: Small size tartrate-modified, nano-disperse ferrihydrite was used for efficient gastrointestinal delivery of soluble Fe(III) without the risk for free radical generation in murine models. This method may provide a potentially side effect-free form iron supplementation.

Sulfinylated azadecalins act as functional mimics of a pollen germination stimulant in Arabidopsis pistils.

Polarized cell elongation is triggered by small molecule cues during development of diverse organisms. During plant reproduction, pollen interactions with the stigma result in the polar outgrowth of a pollen tube, which delivers sperm cells to the female gametophyte to effect double fertilization. In many plants, pistils stimulate pollen germination. However, in Arabidopsis, the effect of pistils on pollen germination and the pistil factors that stimulate pollen germination remain poorly characterized. Here, we demonstrate that stigma, style, and ovules in Arabidopsis pistils stimulate pollen germination. We isolated an Arabidopsis pistil extract fraction that stimulates Arabidopsis pollen germination, and employed ultra-high resolution electrospray ionization (ESI), Fourier-transform ion cyclotron resonance (FT-ICR) and MS/MS techniques to accurately determine the mass (202.126 Da) of a compound that is specifically present in this pistil extract fraction. Using the molecular formula (C10H19NOS) and tandem mass spectral fragmentation patterns of the m/z (mass to charge ratio) 202.126 ion, we postulated chemical structures, devised protocols, synthesized N-methanesulfinyl 1- and 2-azadecalins that are close structural mimics of the m/z 202.126 ion, and showed that they are sufficient to stimulate Arabidopsis pollen germination in vitro (30 µm stimulated approximately 50% germination) and elicit accession-specific response. Although N-methanesulfinyl 2-azadecalin stimulated pollen germination in three species of Lineage I of Brassicaceae, it did not induce a germination response in Sisymbrium irio (Lineage II of Brassicaceae) and tobacco, indicating that activity of the compound is not random. Our results show that Arabidopsis pistils promote germination by producing azadecalin-like molecules to ensure rapid fertilization by the appropriate pollen.

Vitamin D and cardiovascular disease.

The hormonal derivative of vitamin D, 1,25-dihydroxyvitamin D (1,25[OH](2)D) or calcitriol, has been implicated in many physiologic processes beyond calcium and phosphorus homeostasis, and likely plays a role in several chronic disease states, in particular, cardiovascular disease. Experimental data suggest that 1,25(OH)(2)D affects cardiac muscle directly, controls parathyroid hormone secretion, regulates the renin-angiotensin-aldosterone system, and modulates the immune system. Because of these biologic effects, vitamin D deficiency has been associated with hypertension, several types of vascular diseases, and heart failure. We conducted a MEDLINE search of the English-language literature (1950-2008) to identify studies that examined these relationships; additional citations were obtained from the articles retrieved from the literature search. Treatment with vitamin D lowered blood pressure in patients with hypertension and modified the cytokine profile in patients with heart failure. Measurement of serum 25-hydroxyvitamin D concentration usually provides the best assessment of an individual's vitamin D status. Serum levels below 20 ng/ml represent vitamin D deficiency, and levels above 30 ng/ml are considered optimal. Although the observational data linking vitamin D status to cardiovascular disease appear robust, vitamin D supplementation is not recommended as routine treatment for heart disease until definitive prospective, randomized trials can be carried out to assess its effects. However, such supplementation is often appropriate for other reasons and may be beneficial to cardiovascular health in certain patients.

Macro- and micronutrient dyshomeostasis in the adverse structural remodelling of myocardium.

Hypertension and heart failure are worldwide health problems of ever-increasing proportions. A failure of the heart, during either systolic and/or diastolic phases of the cardiac cycle, has its origins rooted in an adverse structural, biochemical, and molecular remodelling of myocardium that involves its cellular constituents, extracellular matrix, and intramural coronary vasculature. Herein we focus on the pathogenic role of a dyshomeostasis of several macro- (i.e. Ca(2+) and Mg(2+)) and micronutrients (i.e. Zn(2+), Se(2+), and vitamin D) in contributing to adverse remodelling of the myocardium and its failure as a pulsatile muscular pump. An improved understanding of how these macro- and micronutrients account for the causes and consequences of adverse myocardial remodelling carries with it the potential of identifying new biomarkers predictive of risk, onset and progression, and response to intervention(s), which could be monitored non-invasively and serially over time. Moreover, such incremental knowledge will serve as the underpinning to the development of novel strategies aimed at preventing and/or regressing the ongoing adverse remodelling of myocardium. The time is at hand to recognize the importance of macro- and micronutrient dyshomeostasis in the evaluation and management of hypertension and heart failure.