Dietary Magnesium and Genetic Interactions in Diabetes and Related Risk Factors: A Brief Overview of Current Knowledge

Nutritional genomics has exploded in the last decade, yielding insights—both nutrigenomic and nutrigenetic—into the physiology of dietary interactions and our genes. Among these are insights into the regulation of magnesium transport and homeostasis and mechanisms underlying magnesium’s role in insulin and glucose handling. Recent observational evidence has attempted to examine some promising research avenues on interaction between genetics and dietary magnesium in relation to diabetes and diabetes risk factors. This brief review summarizes the recent evidence on dietary magnesium’s role in diabetes and related traits in the presence of underlying genetic risk, and discusses future potential research directions

Nonlinear optics of fibre event horizons

The nonlinear interaction of light in an optical fibre can mimic the physics at an event horizon. This analogue arises when a weak probe wave is unable to pass through an intense soliton, despite propagating at a different velocity. To date, these dynamics have been described in the time domain in terms of a soliton-induced refractive index barrier that modifies the velocity of the probe. Here, we complete the physical description of fibre-optic event horizons by presenting a full frequency-domain description in terms of cascaded four-wave mixing between discrete single-frequency fields, and experimentally demonstrate signature frequency shifts using continuous wave lasers. Our description is confirmed by the remarkable agreement with experiments performed in the continuum limit, reached using ultrafast lasers. We anticipate that clarifying the description of fibre event horizons will significantly impact on the description of horizon dynamics and soliton interactions in photonics and other systems.Comment: 7 pages, 5 figure

Use of antihypertensive drugs and risk of keratinocyte carcinoma: A meta‐analysis of observational studies

Purpose Current epidemiologic evidence on the association between antihypertensive drugs and keratinocyte carcinoma (KC) risk is inconsistent. We sought to quantify this association by meta‐analysis of observational studies. Methods We systematically reviewed observational studies published through August 2016 and reported the KC risk (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) associated with antihypertensive drugs, including diuretics, angiotensin‐converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta‐adrenergic blocking agents (β‐blockers), and calcium channel blockers (CCBs). Random‐effects meta‐analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI). Results Ten eligible studies were included. Compared with nonuse, diuretic use was significantly associated with increased risk of both BCC (OR, 1.10; 95% CI, 1.01‐1.20) and SCC (OR, 1.40; 95% CI, 1.19‐1.66). Use of β‐blockers or CCBs was associated with increased risk of BCC (but not SCC); the OR with β‐blockers was 1.09 (95% CI, 1.04‐1.15) and with CCBs was 1.15 (95% CI, 1.09‐1.21). Use of ACE inhibitors or ARBs was associated with decreased risk of both BCC (OR, 0.53; 95% CI, 0.39‐0.71) and SCC (OR, 0.58; 95% CI, 0.42‐0.80) in high‐risk individuals. Conclusions Current evidence indicates that use of diuretics might be associated with increased risk of KC, while ACE inhibitors or ARBs might be associated with decreased risk in high‐risk individuals. β‐blockers or CCBs might be positively associated with BCC risk. Further postmarketing surveillance studies and investigations to clarify the possible underlying mechanisms are warranted

A simplified, Langendorff-free method for concomitant isolation of viable cardiac myocytes and non-myocytes from the adult mouse heart

Rationale: Cardiovascular disease represents a global pandemic. The advent of and recent advances in mouse genomics, epigenomics, and transgenics offer ever-greater potential for powerful avenues of research. However, progress is often constrained by unique complexities associated with the isolation of viable myocytes from the adult mouse heart. Current protocols rely on retrograde aortic perfusion using specialized Langendorff apparatus, which poses considerable logistical and technical barriers to researchers and demands extensive training investment. Objective: To identify and optimize a convenient, alternative approach, allowing the robust isolation and culture of adult mouse cardiac myocytes using only common surgical and laboratory equipment. Methods and Results: Cardiac myocytes were isolated with yields comparable to those in published Langendorff-based methods, using direct needle perfusion of the LV ex vivo and without requirement for heparin injection. Isolated myocytes can be cultured antibiotic free, with retained organized contractile and mitochondrial morphology, transcriptional signatures, calcium handling, responses to hypoxia, neurohormonal stimulation, and electric pacing, and are amenable to patch clamp and adenoviral gene transfer techniques. Furthermore, the methodology permits concurrent isolation, separation, and coculture of myocyte and nonmyocyte cardiac populations. Conclusions: We present a novel, simplified method, demonstrating concomitant isolation of viable cardiac myocytes and nonmyocytes from the same adult mouse heart. We anticipate that this new approach will expand and accelerate innovative research in the field of cardiac biology. </jats:sec

Strong Interplay between Stripe Spin Fluctuations, Nematicity and Superconductivity in FeSe

Elucidating the microscopic origin of nematic order in iron-based superconducting materials is important because the interactions that drive nematic order may also mediate the Cooper pairing. Nematic order breaks fourfold rotational symmetry in the iron plane, which is believed to be driven by either orbital or spin degrees of freedom. However, as the nematic phase often develops at a temperature just above or coincides with a stripe magnetic phase transition, experimentally determining the dominant driving force of nematic order is difficult. Here, we use neutron scattering to study structurally the simplest iron-based superconductor FeSe, which displays a nematic (orthorhombic) phase transition at $T_s=90$ K, but does not order antiferromagnetically. Our data reveal substantial stripe spin fluctuations, which are coupled with orthorhombicity and are enhanced abruptly on cooling to below $T_s$. Moreover, a sharp spin resonance develops in the superconducting state, whose energy (~4 meV) is consistent with an electron boson coupling mode revealed by scanning tunneling spectroscopy, thereby suggesting a spin fluctuation-mediated sign-changing pairing symmetry. By normalizing the dynamic susceptibility into absolute units, we show that the magnetic spectral weight in FeSe is comparable to that of the iron arsenides. Our findings support recent theoretical proposals that both nematicity and superconductivity are driven by spin fluctuations.Comment: 19 pages, 8 figure

Low serum magnesium concentrations are associated with a high prevalence of premature ventricular complexes in obese adults with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Premature ventricular complexes (PVC) predict cardiovascular mortality among several adult populations. Increased arrhythmia prevalence has been reported during controlled magnesium (Mg) depletion studies in adults. We thus hypothesized that serum magnesium (sMg) concentrations are inversely associated with the prevalence of PVC in adults at high cardiovascular risk.</p> <p>Methods</p> <p>Anthropometric, demographic and lifestyle characteristics were assessed in 750 Cree adults, aged > 18 yrs, who participated in an age-stratified, cross-sectional health survey in Quebec, Canada. Holter electrocardiograms recorded heart rate variability and cardiac arrhythmias for two consecutive hours. Multivariate logistic regression was used to evaluate the associations between sMg and PVC.</p> <p>Results</p> <p>PVC prevalence in adults with hypomagnesemia (sMg ≤ 0.70 mmol/L) was more than twice that of adults without hypomagnesemia (50% vs. 21%, <it>p </it>= 0.015); results were similar when adults with cardiovascular disease history were excluded. All hypomagnesemic adults with PVC had type 2 diabetes (T2DM). Prevalence of PVC declined across the sMg concentration gradient in adults with T2DM only (<it>p </it>< 0.001 for linear trend). In multivariate logistic regressions adjusted for age, sex, community, body mass index, smoking, physical activity, alcohol consumption, kidney disease, antihypertensive and cholesterol lowering drug use, and blood docosahexaenoic acid concentrations, the odds ratio of PVC among T2DM subjects with sMg > 0.70 mmol/L was 0.24 (95% CI: 0.06-0.98) <it>p </it>= 0.046 compared to those with sMg ≤ 0.70 mmol/L.</p> <p>Conclusions</p> <p>sMg concentrations were inversely associated with the prevalence of PVC in patients with T2DM in a dose response manner, indicating that suboptimal sMg may be a contributor to arrhythmias among patients with T2DM.</p

Pathogenic Mutations in Cancer-Predisposing Genes: A Survey of 300 Patients with Whole-Genome Sequencing and Lifetime Electronic Health Records

Background: It is unclear whether and how whole-genome sequencing (WGS) data can be used to implement genomic medicine. Our objective is to retrospectively evaluate whether WGS can facilitate improving prevention and care for patients with susceptibility to cancer syndromes. Methods and Findings: We analyzed genetic mutations in 60 autosomal dominant cancer-predisposition genes in 300 deceased patients with WGS data and nearly complete long-term (over 30 years) medical records. To infer biological insights from massive amounts of WGS data and comprehensive clinical data in a short period of time, we developed an in-house analysis pipeline within the SeqHBase software framework to quickly identify pathogenic or likely pathogenic variants. The clinical data of the patients who carried pathogenic and/or likely pathogenic variants were further reviewed to assess their clinical conditions using their lifetime EHRs. Among the 300 participants, 5 (1.7%) carried pathogenic or likely pathogenic variants in 5 cancer-predisposing genes: one in APC, BRCA1, BRCA2, NF1, and TP53 each. When assessing the clinical data, each of the 5 patients had one or more different types of cancers, fully consistent with their genetic profiles. Among these 5 patients, 2 died due to cancer while the others had multiple disorders later in their lifetimes; however, they may have benefited from early diagnosis and treatment for healthier lives, had the patients had genetic testing in their earlier lifetimes. Conclusions: We demonstrated a case study where the discovery of pathogenic or likely pathogenic germline mutations from population-wide WGS correlates with clinical outcome. The use of WGS may have clinical impacts to improve healthcare delivery

Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III

Background: Magnesium plays an essential role in the synthesis and metabolism of vitamin D and magnesium supplementation substantially reversed the resistance to vitamin D treatment in patients with magnesium-dependent vitamin-D-resistant rickets. We hypothesized that dietary magnesium alone, particularly its interaction with vitamin D intake, contributes to serum 25-hydroxyvitamin D (25(OH)D) levels, and the associations between serum 25(OH)D and risk of mortality may be modified by magnesium intake level. Methods: We tested these novel hypotheses utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2001 to 2006, a population-based cross-sectional study, and the NHANES III cohort, a population-based cohort study. Serum 25(OH)D was used to define vitamin D status. Mortality outcomes in the NHANES III cohort were determined by using probabilistic linkage with the National Death Index (NDI). Results: High intake of total, dietary or supplemental magnesium was independently associated with significantly reduced risks of vitamin D deficiency and insufficiency respectively. Intake of magnesium significantly interacted with intake of vitamin D in relation to risk of both vitamin D deficiency and insufficiency. Additionally, the inverse association between total magnesium intake and vitamin D insufficiency primarily appeared among populations at high risk of vitamin D insufficiency. Furthermore, the associations of serum 25(OH)D with mortality, particularly due to cardiovascular disease (CVD) and colorectal cancer, were modified by magnesium intake, and the inverse associations were primarily present among those with magnesium intake above the median. Conclusions: Our preliminary findings indicate it is possible that magnesium intake alone or its interaction with vitamin D intake may contribute to vitamin D status. The associations between serum 25(OH)D and risk of mortality may be modified by the intake level of magnesium. Future studies, including cohort studies and clinical trials, are necessary to confirm the findings