The Role of Magnesium in Parkinson's Disease: Status Quo and Implications for Future Research.

Neurodegenerative diseases represent an increasing economic, social, and, above all, medical burden worldwide. The second most prevalent disease in this category is Parkinson's disease, surpassed only by Alzheimer's. It is a treatable but still incurable systemic disease with a pathogenesis that has not yet been elucidated. Several theories are currently being developed to explain the causes and progression of Parkinson's disease. Magnesium is one of the essential macronutrients and is absolutely necessary for life as we know it. The magnesium cation performs several important functions in the cell in the context of energetic metabolism, substrate metabolism, cell signalling, and the regulation of the homeostasis of other ions. Several of these cellular processes have been simultaneously described as being disrupted in the development and progression of Parkinson's disease. The relationship between magnesium homeostasis and the pathogenesis of Parkinson's disease has received little scientific attention to date. The aim of this review is to summarise and critically evaluate the current state of knowledge on the possible role of magnesium in the pathogenesis of Parkinson's disease and to outline possible future directions for research in this area.

Brain of miyoshi myopathy/dysferlinopathy patients presents with structural and metabolic anomalies.

Miyoshi myopathy/dysferlinopathy (MMD) is a rare muscle disease caused by DYSF gene mutations. Apart from skeletal muscles, DYSF is also expressed in the brain. However, the impact of MMD-causing DYSF variants on brain structure and function remains unexplored. To investigate this, we utilized magnetic resonance (MR) modalities (MR volumetry and 31P MR spectroscopy) in a family with seven children, four of whom have the illness. The MMD siblings showed distinct differences from healthy controls: (1) a significant (p < 0.001) right-sided volume asymmetry (+ 232 mm3) of the inferior lateral ventricles; and (2) a significant (p < 0.001) decrease in [Mg2+], along with a modified energy metabolism profile and altered membrane turnover in the hippocampus and motor and premotor cortices. The patients' [Mg2+], energy metabolism, and membrane turnover measures returned to those of healthy relatives after a month of 400 mg/day magnesium supplementation. This work is the first to describe anatomical and functional abnormalities characteristic of neurodegeneration in the MMD brain. Therefore, we call for further examination of brain functions in larger cohorts of MMD patients and testing of magnesium supplementation, which has proven to be an effective corrective approach in our study.

Disturbances in Muscle Energy Metabolism in Patients with Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease type of motor neuron disorder characterized by degeneration of the upper and lower motor neurons resulting in dysfunction of the somatic muscles of the body. The ALS condition is manifested in progressive skeletal muscle atrophy and spasticity. It leads to death, mostly due to respiratory failure. Within the pathophysiology of the disease, muscle energy metabolism seems to be an important part. In our study, we used blood plasma from 25 patients with ALS diagnosed by definitive El Escorial criteria according to ALSFR-R (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) criteria and 25 age and sex-matched subjects. Aside from standard clinical biochemical parameters, we used the NMR (nuclear magnetic resonance) metabolomics approach to determine relative plasma levels of metabolites. We observed a decrease in total protein level in blood; however, despite accelerated skeletal muscle catabolism characteristic for ALS patients, we did not detect changes in plasma levels of essential amino acids. When focused on alterations in energy metabolism within muscle, compromised creatine uptake was accompanied by decreased plasma creatinine. We did not observe changes in plasma levels of BCAAs (branched chain amino acids; leucine, isoleucine, valine); however, the observed decrease in plasma levels of all three BCKAs (branched chain alpha-keto acids derived from BCAAs) suggests enhanced utilization of BCKAs as energy substrate. Glutamine, found to be increased in blood plasma in ALS patients, besides serving for ammonia detoxification, could also be considered a potential TCA (tricarboxylic acid) cycle contributor in times of decreased pyruvate utilization. When analyzing the data by using a cross-validated Random Forest algorithm, it finished with an AUC of 0.92, oob error of 8%, and an MCC (Matthew's correlation coefficient) of 0.84 when relative plasma levels of metabolites were used as input variables. Although the discriminatory power of the system used was promising, additional features are needed to create a robust discriminatory model.

Gut Microbiota and Serum Metabolites in Individuals with Class III Obesity Without Type 2 Diabetes Mellitus: Pilot Analysis.

Background: Gut microbial composition seems to change in association with prediabetes. The purpose of this prospective cross-sectional study was to compare the composition of gut microbiota and energy metabolites between individuals with class III obesity but without type 2 diabetes mellitus (OB) and healthy normal weight controls. Methods: The subjects of this prospective cross-sectional study were participants recruited from a previous clinical trial (No: NCT02325804), with intervention focused on weight loss. We recruited 19 OB [mean age ± standard deviation (SD) was 35.4 ± 7.0 years, mean body mass index (BMI) ± SD was 48.8 ± 6.7 kg/m2] and 23 controls (mean age ± SD was 31.7 ± 14.8 years, mean BMI ± SD was 22.2 ± 1.7 kg/m2). Their fecal microbiota was categorized using specific primers targeting the V1-V3 region of 16S rDNA, whereas serum metabolites were characterized by nuclear magnetic resonance spectroscopy. Multivariate statistical analysis and Random Forest models were applied to discriminate predictors with the highest variable importance. Results: We observed a significantly lower microbial α-diversity (P = 0.001) and relative abundance of beneficial bacterium Akkermansia (P = 0.001) and the short-chain fatty acid-producing bacteria Eubacterium hallii (P = 0.019), Butyrivibrio (P = 0.024), Marvinbryantia (P = 0.010), and Coprococcus (P = 0.050) and a higher abundance of the pathogenic bacteria Bilophila (P = 0.018) and Fusobacterium (P = 0.022) in OB compared with controls. Notably, the Random Forest machine learning analysis identified energy metabolites (citrate and acetate), HOMA-IR, and insulin as important predictors capable of discriminating between OB and controls. Conclusions: Our results suggest that changes in gut microbiota and in serum acetate and citrate are additional promising biomarkers before progression to Type 2 diabetes. The non-invasive manipulation of gut microbiota composition in OB through a healthy lifestyle, thus, offers a new approach for managing class III obesity and associated disorders. ClinicalTrials.gov identifier: NCT02325804.

Imaging Methods Applicable in the Diagnostics of Alzheimer's Disease, Considering the Involvement of Insulin Resistance.

Alzheimer's disease (AD) is an incurable neurodegenerative disease and the most frequently diagnosed type of dementia, characterized by (1) perturbed cerebral perfusion, vasculature, and cortical metabolism; (2) induced proinflammatory processes; and (3) the aggregation of amyloid beta and hyperphosphorylated Tau proteins. Subclinical AD changes are commonly detectable by using radiological and nuclear neuroimaging methods such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). Furthermore, other valuable modalities exist (in particular, structural volumetric, diffusion, perfusion, functional, and metabolic magnetic resonance methods) that can advance the diagnostic algorithm of AD and our understanding of its pathogenesis. Recently, new insights into AD pathoetiology revealed that deranged insulin homeostasis in the brain may play a role in the onset and progression of the disease. AD-related brain insulin resistance is closely linked to systemic insulin homeostasis disorders caused by pancreas and/or liver dysfunction. Indeed, in recent studies, linkages between the development and onset of AD and the liver and/or pancreas have been established. Aside from standard radiological and nuclear neuroimaging methods and clinically fewer common methods of magnetic resonance, this article also discusses the use of new suggestive non-neuronal imaging modalities to assess AD-associated structural changes in the liver and pancreas. Studying these changes might be of great clinical importance because of their possible involvement in AD pathogenesis during the prodromal phase of the disease.

Oxidative stress parameters and their relation to motor subtype of Parkinson's disease and levodopa treatment status.

Parkinson's disease (PD) is an oxidative stress-linked neurodegenerative disorder, with the highest prevalence among seniors. The objective of this study were: (1) to analyse levels of following oxidative stress parameters: total antioxidant capacity (TAC), uric acid (UA), total glutathione (tGSH), bilirubin (Bil) and albumin (Alb), in blood of PD patients and healthy controls; (2) to find possible associations of examined oxidative stress parameters with PD subtypes and levodopa treatment status; and (3) to evaluate power and relevance of the aforementioned oxidative stress parameter for the prediction of onset and progression of PD by utilizing Random Forest machine learning (RFML). Oxidative stress parameters were determined in 125 PD patients and 55 healthy controls. Evaluated with frequentist statistics, our data revealed that UA is the only oxidative stress parameter associated with PD. However, when the PD cohort was divided in gender-dependent manner, tGSH and Bil were also significantly associated with PD in subgroup of female patients. RFML rendered no predictive power of any of the tested oxidative stress parameters in respect to PD, its subtypes, and/or status of levodopa treatment. In conclusion, despite the positive association of UA with PD (in complete cohort of PD patients) and of tGSH and Bil with PD but only in female patients, these oxidative stress parameters are of no use in clinical practice due to the lack of the predictive/diagnostic power.

SLC41A1 knockout mice display normal magnesium homeostasis.

Transcellular Mg2+ reabsorption in the distal convoluted tubule (DCT) of the kidneys plays an important role in maintaining systemic Mg2+ homeostasis. SLC41A1 is a Na+/Mg2+ exchanger that mediates Mg2+ efflux from cells and is hypothesized to facilitate basolateral extrusion of Mg2+ in the DCT. In this study, we generated a SLC41A1 knockout mouse model to examine the role of SLC41A1 in Mg2+ homeostasis. Slc41a1-/- mice exhibited similar serum and urine Mg2+ levels as their wild-type littermates. Dietary restriction of Mg2+ resulted in reduced serum Mg2+ concentration and urinary Mg2+ excretion, which was similar in the wild-type and knockout groups. Expression of genes encoding Mg2+ channels and transporters such as transient receptor potential melastatin 6 (Trpm6), transient receptor potential melastatin 7 (Trpm7), cyclin and CBS domain divalent metal cation transport mediator 2 (Cnnm2), and Slc41a3 were unchanged based on genotype. We investigated the potential redundancy of SLC41A1 and its homolog SLC41A3 by generating a double knockout mouse. Although Slc41a3-/- knockout mice showed significantly reduced serum Mg2+ compared with wild-type and Slc41a1-/- knockout groups, double knockout mice displayed similar serum Mg2+ levels as Slc41a3-/- knockout mice. In conclusion, our data show that SLC41A1 is not involved in the regulation of systemic Mg2+ homeostasis in mice. Our data also demonstrate that SLC41A1 does not compensate for the loss of SLC41A3, suggesting different functions of these SLC41 proteins in vivo.NEW & NOTEWORTHY SLC41A1 has been hypothesized to mediate Mg2+ extrusion in the distal convoluted tubule and thus regulate Mg2+ homeostasis. This study investigated the role of SLC41A1 in Mg2+ homeostasis in vivo using a transgenic mouse model. Our results demonstrate that SLC41A1 is not required to maintain normal Mg2+ balance in mice. We also show that SLC41A3 is more important than SLC41A1 in regulating systemic Mg2+ levels.

Recommendation on an updated standardization of serum magnesium reference ranges.

PURPOSE: Serum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members' hospitals and laboratories, presenting an urgent need for standardization. METHODS: We gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide. RESULTS: Serum magnesium levels designating "hypomagnesemia" differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from "normal" populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used "normal" ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD. CONCLUSIONS: Widely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L).

Effect of High-intensity Training and Probiotics on Gut Microbiota Diversity in Competitive Swimmers: Randomized Controlled Trial.

BACKGROUND: Physical exercise has favorable effects on the structure of gut microbiota and metabolite production in sedentary subjects. However, little is known whether adjustments in an athletic program impact overall changes of gut microbiome in high-level athletes. We therefore characterized fecal microbiota and serum metabolites in response to a 7-week, high-intensity training program and consumption of probiotic Bryndza cheese. METHODS: Fecal and blood samples and training logs were collected from young competitive male (n = 17) and female (n = 7) swimmers. Fecal microbiota were categorized using specific primers targeting the V1-V3 region of 16S rDNA, and serum metabolites were characterized by NMR-spectroscopic analysis and by multivariate statistical analysis, Spearman rank correlations, and Random Forest models. RESULTS: We found higher α-diversity, represented by the Shannon index value (HITB-pre 5.9 [± 0.4]; HITB-post 6.4 [± 0.4], p = 0.007), (HIT-pre 5.5 [± 0.6]; HIT-post 5.9 [± 0.6], p = 0.015), after the end of the training program in both groups independently of Bryndza cheese consumption. However, Lactococcus spp. increased in both groups, with a higher effect in the Bryndza cheese consumers (HITB-pre 0.0021 [± 0.0055]; HITB-post 0.0268 [± 0.0542], p = 0.008), (HIT-pre 0.0014 [± 0.0036]; HIT-post 0.0068 [± 0.0095], p = 0.046). Concomitant with the increase of high-intensity exercise and the resulting increase of anaerobic metabolism proportion, pyruvate (p[HITB] = 0.003; p[HIT] = 0.000) and lactate (p[HITB] = 0.000; p[HIT] = 0.030) increased, whereas acetate (p[HITB] = 0.000; p[HIT] = 0.002) and butyrate (p[HITB] = 0.091; p[HIT] = 0.019) significantly decreased. CONCLUSIONS: Together, these data demonstrate a significant effect of high-intensity training (HIT) on both gut microbiota composition and serum energy metabolites. Thus, the combination of intensive athletic training with the use of natural probiotics is beneficial because of the increase in the relative abundance of lactic acid bacteria.

Gut Microbiome Suffers from Hematopoietic Stem Cell Transplantation in Childhood and Its Characteristics Are Positively Associated with Intra-Hospital Physical Exercise.

Gut microbiome impairment is a serious side effect of cancer treatment. The aim of this study was to identify the effects of hematopoietic stem cell transplantation (HSCT) treatment on gut microbiota composition in children with acute lymphoblastic leukemia (ALL). Fecal microbiotas were categorized using specific primers targeting the V1-V3 region of 16S rDNA in eligible pediatric ALL patients after HSCT (n = 16) and in healthy controls (Ctrl, n = 13). An intra-hospital exercise program was also organized for child patients during HSCT treatment. Significant differences in gut microbiota composition were observed between ALL HSCT and Ctrl with further negative effects. Plasma C-reactive protein correlated positively with the pathogenic bacteria Enterococcus spp. and negatively with beneficial bacteria Butyriccocus spp. or Akkermansia spp., respectively (rs = 0.511, p = 0.05; rs = -0.541, p = 0.04; rs = -0.738, p = 0.02). Bacterial alpha diversity correlated with the exercise training characteristics. Therefore, specific changes in the microbiota of children were associated with systemic inflammation or the ability to exercise physically during HSCT treatment.

Alzheimer's Disease-Associated SNP rs708727 in SLC41A1 May Increase Risk for Parkinson's Disease: Report from Enlarged Slovak Study.

SLC41A1 (A1) SNPs rs11240569 and rs823156 are associated with altered risk for Parkinson's disease (PD), predominantly in Asian populations, and rs708727 has been linked to Alzheimer's disease (AD). In this study, we have examined a potential association of the three aforementioned SNPs and of rs9438393, rs56152218, and rs61822602 (all three lying in the A1 promoter region) with PD in the Slovak population. Out of the six tested SNPs, we have identified only rs708727 as being associated with an increased risk for PD onset in Slovaks. The minor allele (A) in rs708727 is associated with PD in dominant and completely over-dominant genetic models (ORD = 1.36 (1.05-1.77), p = 0.02, and ORCOD = 1.34 (1.04-1.72), p = 0.02). Furthermore, the genotypic triplet GG(rs708727) + AG(rs823156) + CC(rs61822602) might be clinically relevant despite showing a medium (h ≥ 0.5) size difference (h = 0.522) between the PD and the control populations. RandomForest modeling has identified the power of the tested SNPs for discriminating between PD-patients and the controls to be essentially zero. The identified association of rs708727 with PD in the Slovak population leads us to hypothesize that this A1 polymorphism, which is involved in the epigenetic regulation of the expression of the AD-linked gene PM20D1, is also involved in the pathoetiology of PD (or universally in neurodegeneration) through the same or similar mechanism as in AD.

Bioaccessibility and Bioavailability of Minerals in Relation to a Healthy Gut Microbiome.

Adequate amounts of a wide range of micronutrients are needed by body tissues to maintain health. Dietary intake must be sufficient to meet these micronutrient requirements. Mineral deficiency does not seem to be the result of a physically active life or of athletic training but is more likely to arise from disturbances in the quality and quantity of ingested food. The lack of some minerals in the body appears to be symbolic of the modern era reflecting either the excessive intake of empty calories or a negative energy balance from drastic weight-loss diets. Several animal studies provide convincing evidence for an association between dietary micronutrient availability and microbial composition in the gut. However, the influence of human gut microbiota on the bioaccessibility and bioavailability of trace elements in human food has rarely been studied. Bacteria play a role by effecting mineral bioavailability and bioaccessibility, which are further increased through the fermentation of cereals and the soaking and germination of crops. Moreover, probiotics have a positive effect on iron, calcium, selenium, and zinc in relation to gut microbiome composition and metabolism. The current literature reveals the beneficial effects of bacteria on mineral bioaccessibility and bioavailability in supporting both the human gut microbiome and overall health. This review focuses on interactions between the gut microbiota and several minerals in sport nutrition, as related to a physically active lifestyle.

Strenuous Physical Training, Physical Fitness, Body Composition and Bacteroides to Prevotella Ratio in the Gut of Elderly Athletes.

Regular physical activity seems to have a positive effect on the microbiota composition of the elderly, but little is known about the added possible benefits of strenuous endurance training. To gain insight into the physiology of the elderly and to identify biomarkers associated with endurance training, we combined different omics approaches. We aimed to investigate the gut microbiome, plasma composition, body composition, cardiorespiratory fitness, and muscle strength of lifetime elderly endurance athletes (LA) age 63.5 (95% CI 61.4, 65.7), height 177.2 (95% CI 174.4, 180.1) cm, weight 77.8 (95% CI 75.1, 80.5) kg, VO2max 42.4 (95% CI 39.8, 45.0) ml.kg-1.min-1 (n = 13) and healthy controls age 64.9 (95% CI 62.1, 67.7), height 174.9 (95% CI 171.2, 178.6) cm, weight 83.4 (95% CI 77.1, 89.7) kg, VO2max 28.9 (95% CI 23.9, 33.9), ml.kg-1.min-1 (n = 9). Microbiome analysis was performed on collected stool samples further subjected to 16S rRNA gene analysis. NMR-spectroscopic analysis was applied to determine and compare selected blood plasma metabolites mostly linked to energy metabolism. The machine learning (ML) analysis discriminated subjects from the LA and CTRL groups using the joint predictors Bacteroides 1.8E + 00 (95% CI 1.1, 2.5)%, 3.8E + 00 (95% CI 2.7, 4.8)% (p = 0.002); Prevotella 1.3 (95% CI 0.28, 2.4)%, 0.1 (95% CI 0.07, 0.3)% (p = 0.02); Intestinimonas 1.3E-02 (95% CI 9.3E-03, 1.7E-02)%, 5.9E-03 (95% CI 3.9E-03, 7.9E-03)% (p = 0.002), Subdoligranulum 7.9E-02 (95% CI 2.5E-02, 1.3E-02)%, 3.2E-02 (95% CI 1.8E-02, 4.6E-02)% (p = 0.02); and the ratio of Bacteroides to Prevotella 133 (95% CI -86.2, 352), 732 (95% CI 385, 1079.3) (p = 0.03), leading to an ROC curve with AUC of 0.94. Further, random forest ML analysis identified VO2max, BMI, and the Bacteroides to Prevotella ratio as appropriate, joint predictors for discriminating between subjects from the LA and CTRL groups. Although lifelong endurance training does not bring any significant benefit regarding overall gut microbiota diversity, strenuous athletic training is associated with higher cardiorespiratory fitness, lower body fat, and some favorable gut microbiota composition, all factors associated with slowing the rate of biological aging.

Atypical presentation of Charcot-Marie-Tooth disease type 1C with a new mutation: a case report.

BACKGROUND: Charcot-Marie-Tooth 1C (CMT1C) is a rare form of dominantly inherited CMT1 neuropathy caused by a mutated gene encoding lipopolysaccharide-induced tumour necrosis alpha factor (LITAF). CASE PRESENTATION: We report a 56-year-old patient with an atypical clinical phenotype of CMT1C, which started as progressive weakness of a single upper limb resembling acquired inflammatory neuropathy. Nerve conduction studies (NCS) and temporarily limited and partial effects of immunotherapy supported the diagnosis of inflammatory neuropathy. Significant progression of polyneuropathy, despite intensive long-lasting immunotherapy, together with repeatedly negative auxiliary investigations (CSF, MRI and antibodies) and genetic testing results finally led to the diagnosis of CMT1C neuropathy. CONCLUSIONS: CMT1C should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy.

A Possible Preventive Role of Physically Active Lifestyle during the SARS-CoV-2 Pandemic; Might Regular Cold-Water Swimming and Exercise Reduce the Symptom Severity of COVID-19?

The objective of this study was to investigate the incidence and course of COVID-19 and the risk of an upper respiratory tract infection in a group of people with physically active lifestyles. Data were collected anonymously using an online survey platform during December 2020. The age of participants ranged from 18 to 65 years. Out of 2343 participants, 11.5% overcame COVID-19 infection. Relative to the control group (CTRL), physically active, cold-water swimmers (PACW) did not exhibit a lower risk of incidence for COVID-19 (RR 1.074, CI 95% (0.710-1.625). However, PACW had a higher chance of having an asymptomatic course of COVID-19 (RR 2.321, CI 95% (0.836-6.442); p < 0.05) and a higher chance of only having an acute respiratory infection once or less per year than CTRL (RR 1.923, CI 95% (1.1641-2.253); p < 0.01). Furthermore, PACW exhibited a lower incidence of acute respiratory infection occurring more than twice per year (RR 0.258, CI 95% (0.138-0.483); p < 0.01). Cold-water swimming and physical activity may not lessen the risk of COVID-19 in recreational athletes. However, a physically active lifestyle might have a positive effect on the rate of incidence of acute respiratory infection and on the severity of COVID-19 symptoms.

The Combined Influence of Magnesium and Insulin on Central Metabolic Functions and Expression of Genes Involved in Magnesium Homeostasis of Cultured Bovine Adipocytes.

At the onset of lactation, dairy cows suffer from insulin resistance, insulin deficiency or both, similar to human diabetes, resulting in lipolysis, ketosis and fatty liver. This work explored the combined effects of different levels of magnesium (0.1, 0.3, 1 and 3 mM) and insulin (25, 250 and 25,000 pM) on metabolic pathways and the expression of magnesium-responsive genes in a bovine adipocyte model. Magnesium starvation (0.1 mM) and low insulin (25 pM) independently decreased or tended to decrease the accumulation of non-polar lipids and uptake of the glucose analog 6-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-6-deoxyglucose (6-NBDG). Activity of glycerol 3-phosphate dehydrogenase (GPDH) was highest at 25 pM insulin and 3 mM magnesium. Expression of SLC41A1 and SLC41A3 was reduced at 0.1 mM magnesium either across insulin concentrations (SLC41A1) or at 250 pM insulin (SLC41A3). MAGT1 expression was reduced at 3 mM magnesium. NIPA1 expression was reduced at 3 mM and 0.1 mM magnesium at 25 and 250 pM insulin, respectively. Expression of SLC41A2, CNNM2, TRPM6 and TRPM7 was not affected. We conclude that magnesium promotes lipogenesis in adipocytes and inversely regulates the transcription of genes that increase vs. decrease cytosolic magnesium concentration. The induction of GAPDH activity by surplus magnesium at low insulin concentration can counteract excessive lipomobilization.

The Efficacy of Short-Term Weight Loss Programs and Consumption of Natural Probiotic Bryndza Cheese on Gut Microbiota Composition in Women.

Weight loss interventions with probiotics have favourable effects on gut microbiota composition and derived metabolites. However, little is known about whether the consumption of natural probiotics, such as Bryndza cheeses, brings similar benefits. The purpose of the study was to find the effect of short-term weight loss programs and Bryndza cheese consumption on the structure of the gut microbiota, microbiota-derived metabolites and body composition in middle-aged women. We conducted a randomised controlled intervention study. Twenty-two female participants with a body fat percentage ≥25% underwent a short weight loss program (4 weeks). Subjects were randomised to either the control or intervention group according to diet. The intervention group comprised 13 participants, whose diet contained 30 g of "Bryndza" cheese daily (WLPB). The control group comprised nine participants without the regular consumption of Bryndza cheese (WLP) in their diet. Both interventions lead to a significant and favourable change of BMI, body fat, waist circumference and muscle mass. Moreover, the relative abundance of Erysipelotrichales significantly increased in both groups. However, the relative abundance of lactic acid bacteria (Lactobacillales, Streptococcaceae, Lactococcus and Streptococcus) significantly increased only in the WLPB group. Furthermore, short-chain fatty acid producers Phascolarctobacterium and Butyricimonas increased significantly in the WLPB group. A short-term weight loss program combined with Bryndza cheese consumption improves body composition and increases the abundance of lactic acid bacteria and short-chain fatty acid producers in middle-aged women.

Beneficial effects of an alkaline topical treatment in patients with mild atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is the most common cause of eczema. The skin condition affects millions of people worldwide. Severe cases of AD demand systemic treatment, but most AD cases rely on local therapy with topical corticosteroids, emollients, and moisturizing agents to alleviate eczema. Commonly, derma-cosmetics with a pH around 5.5 are used to treat eczematous lesions (EL). However, evidence is currently amassing that the use of mildly alkaline topical creams is beneficial for AD-related eczema treatment because of its effect on the inflammation in the skin. AIMS: To test an alkaline two-phase care concept for the treatment of eczema. PATIENTS/METHODS: An open-label study of 25 patients with eczema associated with mild AD. Patients were treated with Alkaline Build Up Caring Cream INTENSIVE and Alkaline Build Up Caring Cream PLUS+ (both Siriderma® ) for eight weeks. Dermatological, biochemical, and questionnaire-based examinations were conducted prior to the trial and after its completion. RESULTS: Topical administration of slightly alkaline creams led to small and statistically insignificant increases of skin pH. Clinical examination at the end of the observation period revealed a significant decrease of total eczematous-affected skin area, a significant decrease in average severity scores of EL, and significant improvements in patient-reported outcome parameters. Blood tests did not reveal any significant changes, except for small but significant increases in IL-8 and monocytes. CONCLUSION: Mildly alkaline topical creams seem to provide soothing effects on eczema-related skin inflammation and thus might contribute to treatment of local symptoms of eczema in patients with mild AD.