Diet Supplementation with Polyphenol-Rich Salicornia ramosissima Extracts Protects against Tissue Damage in Experimental Models of Cerebral Ischemia

Salicornia; Ischemia; NeuroprotectionSalicornia; Isquemia; NeuroprotecciónSalicornia; Isquèmia; NeuroproteccióStrokes are the second most common cause of death worldwide and a leading cause of disability. Regular consumption of polyphenols has been shown to reduce the risk of suffering a cardiovascular event. For this reason, we have investigated the protective effect of Salicornia ramosissima, a seasonal halophyte that synthetizes high amounts of bioactive compounds, including polyphenols, in response to environmental stress. Aqueous, hydroalcoholic, and ethanolic extracts were prepared to investigate if dietary supplementation prior to ischemic challenge can prevent subsequent damage using two animal models. First, we screened the protective effect against hypoxia–reoxygenation in Drosophila melanogaster and observed that both ethanolic and hydroalcoholic extracts protected flies from the deleterious effects of hypoxia. Second, we confirmed the protective effect of S. ramosissima ethanolic extract against brain ischemia using the transient middle cerebral artery occlusion mice model. Four weeks of oral supplementation with the ethanolic extract before artery occlusion reduced infarct volume and lowered the plasma levels of the DNA peroxidant product 8-hydroxydeoxyguanosine. Phytochemical profiling of S. ramosissima ethanolic extract revealed 50 compounds. Thus, it represents a valuable source of bioactive compounds that show promising disease-modifying activities and could be further developed as an effective food supplement for the prevention or treatment of neurovascular disorders.The authors received financial support from “CSF-Proyectos estratégicos de I+D+i. Proyectos cofinanciados en un 80% por fondos del Programa Operativo FEDER de Andalucía 2014–2020”, grant number PE-0527-2019. This research was partially funded by “Consejería de Transformación Económica, Industria, Conocimiento y Universidades (CTEICU) y 80% cofinanciados por la UE, PO FEDER Andalucía 2014-2020”, grant number [PY20_01351]. C.d.R. received financial support from the Sara Borrell program funded by ISCIII, grant number [CD21/00148]

Effects of a long-term lifestyle intervention on metabolically healthy women with obesity: Metabolite profiles according to weight loss response

BACKGROUND & AIMS: The benefits of weight loss in subjects with metabolically healthy obesity (MHO) are still a matter of controversy. We aimed to identify metabolic fingerprints and their associated pathways that discriminate women with MHO with high or low weight loss response after a lifestyle intervention, based on a hypocaloric Mediterranean diet (MedDiet) and physical activity. METHODS: A UPLC-Q-Exactive-MS/MS metabolomics workflow was applied to plasma samples from 27 women with MHO before and after 12 months of a hypocaloric weight loss intervention with a MedDiet and increased physical activity. The subjects were stratified into two age-matched groups according to weight loss: 10% (high weight loss group, HWL). Random forest analysis was performed to identify metabolites discriminating between the LWL and the HWL as well as within-status effects. Modulated pathways and associations between metabolites and anthropometric and biochemical variables were also investigated. RESULTS: Thirteen metabolites discriminated between the LWL and the HWL, including 1,5-anhydroglucitol, carotenediol, 3-(4-hydroxyphenyl)lactic acid, N-acetylaspartate and several lipid species (steroids, a plasmalogen, sphingomyelins, a bile acid and long-chain acylcarnitines). 1,5-anhydroglucitol, 3-(4-hydroxyphenyl)lactic acid and sphingomyelins were positively associated with weight variables whereas N-acetylaspartate and the plasmalogen correlated negatively with them. Changes in very long-chain acylcarnitines and hydroxyphenyllactic levels were observed in the HWL and positively correlated with fasting glucose, and changes in levels of the plasmalogen negatively correlated with insulin resistance. Additionally, the cholesterol profile was positively associated with changes in acid hydroxyphenyllactic, sphingolipids and 1,5-AG. CONCLUSIONS: Higher weight loss after a hypocaloric MedDiet and increased physical activity for 12 months is associated with changes in the plasma metabolome in women with MHO. These findings are associated with changes in biochemical variables and may suggest an improvement of the cardiometabolic risk profile in those patients that lose greater weight. Further studies are needed to investigate whether the response of those subjects with MHO to this intervention differs from those with unhealthy obesity

Impact in Plasma Metabolome as Effect of Lifestyle Intervention for Weight-Loss Reveals Metabolic Benefits in Metabolically Healthy Obese Women

Little is known regarding metabolic benefits of weight loss (WL) on the metabolically healthy obese (MHO) patients. We aimed to examine the impact of a lifestyle weight loss (LWL) treatment on the plasma metabolomic profile in MHO individuals. Plasma samples from 57 MHO women allocated to an intensive LWL treatment group (TG, hypocaloric Mediterranean diet and regular physical activity, n = 30) or to a control group (CG, general recommendations of a healthy diet and physical activity, n = 27) were analyzed using an untargeted 1H NMR metabolomics approach at baseline, after 3 months (intervention), and 12 months (follow-up). The impact of the LWL intervention on plasma metabolome was statistically significant at 3 months but not at follow-up and included higher levels of formate and phosphocreatine and lower levels of LDL/VLDL (signals) and trimethylamine in the TG. These metabolites were also correlated with WL. Higher myo-inositol, methylguanidine, and 3-hydroxybutyrate, and lower proline, were also found in the TG; higher levels of hippurate and asparagine, and lower levels of 2-hydroxybutyrate and creatine, were associated with WL. The current findings suggest that an intensive LWL treatment, and the consequent WL, leads to an improved plasma metabolic profile in MHO women through its impact on energy, amino acid, lipoprotein, and microbial metabolism. Keywords: NMR; hypocaloric diet; metabolically healthy obesity; metabolomics; physical activity

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.European Journal of Human Genetics advance online publication, 4 February 2015; doi:10.1038/ejhg.2014.283

Helicitogenesis: WIMPy baryogenesis with sterile neutrinos and other realizations

We propose a mechanism for baryogenesis from particle decays or annihilations that can work at the TeV scale. Some heavy particles annihilate or decay into a heavy sterile neutrino N (with M ≳ 0.5 TeV) and a ¿light¿ one ν (with m ≪ 100 GeV), generating an asymmetry among the two helicity degrees of freedom of ν. This asymmetry is partially transferred to Standard Model leptons via fast Yukawa interactions and reprocessed into a baryon asymmetry by the electroweak sphalerons. We illustrate this mechanism in a WIMPy baryogenesis model where the helicity asymmetry is generated in the annihilation of dark matter. This model connects the baryon asymmetry, dark matter, and neutrino masses. Moreover it also complements previous studies on general requirements for baryogenesis from dark matter annihilation. Finally we discuss other possible realizations of this helicitogenesis mechanism

The effect of blast furnace slag/fly ash ratio on setting, strength, and shrinkage of alkali-activated pastes and concretes

The aim of this study was to determine the effects of partial fly ash substitution in to a series of alkali-activated concrete based on a high-MgO blast furnace slag BFS. Mixes were activated with various amounts of sodium silicate at alkali modulus (mass ratio SiO2/Na2O) values of 1.0, 0.5, and 0.25. The results showed that, an increase in the fly ash content extended the initial setting time but had very little effect on the final setting time, although the early age compressive strength was decreased. The fly ash addition had no effect on the drying shrinkage but lowered the autogenous shrinkage. The mixes activated with sodium silicate at a lower alkali modulus showed a significantly higher autogenous shrinkage but lower drying shrinkage values. Severe micro cracking of the binder matrix was observed only for mixes without fly ash, activated with sodium silicate solution at higher alkali modulus. Decreasing the alkali modulus resulted in a higher autogenous shrinkage, less micro cracking and a more homogenous structure due to more extensive formation of sodium-aluminate-silicate-hydrate gel (N-A-S-H), promoted by the addition, and more extensive reaction of the fly ash

Performance of two questionnaires to measure treatment adherence in patients with Type-2 Diabetes

<p>Abstract</p> <p>Background</p> <p>Most valid methods to measure treatment adherence require time and resources, and they are not easily applied in highly demanding Primary Health Care Clinics (PHCC). The objective of this study was to determine sensitivity, specificity, predictive values, likelihood ratios, and post-test probabilities of two novel questionnaires as proxy measurements of treatment adherence in Type-2 diabetic patients.</p> <p>Methods</p> <p>Two questionnaires were developed by a group of experts to identify the patient's medical prescription knowledge (knowledge) and their attitudes toward treatment adherence (attitudes) as proxy measurements of adherence. The questionnaires were completed by patients receiving care in PHCC pertaining to the Mexican Institute of Social Security in Aguascalientes (Mexico). Pill count was used as gold standard. Participants were selected randomly, and their oral hypoglycemic prescriptions were studied. The main outcome measures for each questionnaire were sensitivity, specificity, predictive values, likelihood ratios, and post-test probabilities, all as an independent questionnaire test and in a serial analysis.</p> <p>Results</p> <p>Adherence prevalence was 27.0% using pill count. Knowledge questionnaire showed the highest sensitivity (68.1%) and negative predictive value (82.2%), the lowest negative likelihood ratio (0.58) and post-test probability for a negative result (0.16). Serial analysis showed the highest specificity (77.4%) and positive predictive value (40.1%) as well as the highest positive likelihood ratio (1.8) and post-test probability for a positive result (0.39).</p> <p>Conclusion</p> <p>Medical Prescription Knowledge questionnaire showed the best performance as proxy measurement to identify non-adherence in type 2 diabetic patients regarding negative predictive value, negative likelihood ratio, and post-test probability for a negative result. However, Medical Prescription Knowledge questionnaire performance may change in contexts with higher adherence prevalence. Therefore, more research is needed before using this method in other contexts.</p

TIPIT: A randomised controlled trial of thyroxine in preterm infants under 28 weeks gestation: Magnetic Resonance Imaging and Magnetic Resonance Angiography protocol

<p>Abstract </p> <p>Background</p> <p>Infants born at extreme prematurity are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone described as hypothyroxinaemia, which is recognised to be a frequent phenomenon in these infants. Derangements of critical thyroid function during the sensitive window in prematurity when early development occurs, may have a range of long term effects for brain development. Further research in preterm infants using neuroimaging techniques will increase our understanding of the specificity of the effects of hypothyroxinaemia on the developing foetal brain. This is an explanatory double blinded randomised controlled trial which is aimed to assess the effect of thyroid hormone supplementation on brain size, key brain structures, extent of myelination, white matter integrity and vessel morphology, somatic growth and the hypothalamic-pituitary-adrenal axis.</p> <p>Methods</p> <p>The study is a multi-centred double blinded randomised controlled trial of thyroid hormone supplementation in babies born below 28 weeks' gestation. All infants will receive either levothyroxine or placebo until 32 weeks corrected gestational age. The primary outcomes will be width of the sub-arachnoid space measured using cranial ultrasound and head circumference at 36 weeks corrected gestational age. The secondary outcomes will be thyroid hormone concentrations, the hypothalamic pituitary axis status and auxological data between birth and expected date of delivery; thyroid gland volume, brain size, volumes of key brain structures, extent of myelination and brain vessel morphology at expected date of delivery and markers of morbidity which include duration of mechanical ventilation and/or oxygen requirement and chronic lung disease.</p> <p><b>Trial registration</b></p> <p>Current Controlled Trials ISRCTN89493983</p

Recent progress in low-carbon binders

The development of low-carbon binders has been recognized as a means of reducing the carbon footprint of the Portland cement industry, in response to growing global concerns over CO2 emissions from the construction sector. This paper reviews recent progress in the three most attractive low-carbon binders: alkali-activated, carbonate, and belite-ye'elimite-based binders. Alkali-activated binders/materials were reviewed at the past two ICCC congresses, so this paper focuses on some key developments of alkali-activated binders/materials since the last keynote paper was published in 2015. Recent progress on carbonate and belite-ye'elimite-based binders are also reviewed and discussed, as they are attracting more and more attention as essential alternative low-carbon cementitious materials. These classes of binders have a clear role to play in providing a sustainable future for global construction, as part of the available toolkit of cements