Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial.

Objective: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. Methods: A multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 µg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 µg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes. Results: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy. Conclusion: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. Clinical Trial Registration: RPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.

Examining the associations between microglia genetic capacity, early life exposures and white matter development at the level of the individual.

There are inter-individual differences in susceptibility to the influence of early life experiences for which the underlying neurobiological mechanisms are poorly understood. Microglia play a role in environmental surveillance and may influence individual susceptibility to environmental factors. As an index of neurodevelopment, we estimated individual slopes of mean white matter fractional anisotropy (WM-FA) across three time-points (age 4.5, 6.0, and 7.5 years) for 351 participants. Individual variation in microglia reactivity was derived from an expression-based polygenic score(ePGS) comprised of Single Nucleotide Polymorphisms (SNPs) functionally related to the expression of microglia-enriched genes.A higher ePGS denotes an increased genetic capacity for the expression of microglia-related genes, and thus may confer a greater capacity to respond to the early environment and to influence brain development. We hypothesized that this ePGS would associate with the WM-FA index of neurodevelopment and moderate the influence of early environmental factors.Our findings show sex dependency, where a significant association between WM-FA and microglia ePGS was only obtained for females.We then examined associations with perinatal factors known to decrease (optimal birth outcomes and familial conditions) or increase (systemic inflammation) the risk for later mental health problems.In females, individuals with high microglia ePGS showed a negative association between systemic inflammation and WM-FA and a positive association between more advantageous environmental conditions and WM-FA. The microglia ePGS in females thus accounted for variations in the influence of the quality of the early environment on WM-FA.Finally, WM-FA slopes mediated the association of microglia ePGS with interpersonal problems and social hostility in females. Our findings suggest the genetic capacity for microglia function as a potential factor underlying differential susceptibility to early life exposuresthrough influences on neurodevelopment.

Thermal sensitivity of Rhinella arenarum tadpole at low concentrations of dimethoate pesticides.

One of the main causes of contamination of aquatic environments, which affects biotic communities, is the use of pesticides in agricultural regions. Amphibians are considered good bio-indicators of aquatic pollution, because they are one of the most susceptible groups to pollution. Several studies suggest that both pollution and climate change produce synergistic effects in amphibians which amplify the toxicity afecting survival, and malformations with an increase in temperature. We studied the sensitivity of sublethal concentrations of dimethoate in Rhinella arenarum tadpoles on two fitness related thermal traits including locomotor swimming performance and thermal tolerance limits (CTmax = critical thermal maximum and CTmin = critical thermal minimum). The locomotor performance of R. arenarum tadpoles decreased with increasing sublethal dimethoate concentrations up to ∼60 % at intermediates dimethoate concentration. The tadpoles showed a tendency to decrease their tolerance to high temperatures (CTmax) with increasing dimethoate concentration around ∼0.5 °C, however no significant differences were found among treatments. Similarly, tadpoles showed decreases in their cold resistance (CTmin) with dimethoate concentrations, around 1 °C the high concentrations of dimethoate. The increase of atypical climatic events, such as heat waves may put R. arenarum tadpoles at greater risk when exposed to dimethoate. Our results show that the sublethal concentrations of the dimethoate pesticide may affect the fitness and survival of the larvae of R. arenarum in natural, and seminatural enviroments.

Neonatal Nucleus Accumbens Microstructure Modulates Individual Susceptibility to Preconception Maternal Stress in Relation to Externalizing Behaviors.

OBJECTIVE: Maternal stress influences in utero brain development and is a modifiable risk factor for offspring psychopathologies. Reward circuitry dysfunction underlies various internalizing and externalizing psychopathologies. This study examined (1) the association between maternal stress and microstructural characteristics of the neonatal nucleus accumbens (NAcc), a major node of the reward circuitry, and (2) whether neonatal NAcc microstructure modulates individual susceptibility to maternal stress in relation to childhood behavioral problems. METHOD: K-means longitudinal cluster analysis was performed to determine trajectories of maternal stress measures (Perceived Stress Scale [PSS], hair cortisol) from preconception to the third trimester. Neonatal NAcc microstructural measures (orientation density index [ODI] and intracellular volume fraction [ICVF]) were compared across trajectories. We then examined the interaction between maternal stress and neonatal NAcc microstructure on child internalizing and externalizing behaviors, assessed between ages 3 and 4 years. RESULTS: Two trajectories of maternal stress magnitude ("low"/"high") were identified for both PSS (n = 287) and hair cortisol (n = 336). Right neonatal NAcc ODI (rNAcc-ODI) was significantly lower in "low" relative to "high" PSS trajectories (n = 77, p = .04). PSS at preconception had the strongest association with rNAcc-ODI (r = 0.293, p = .029). No differences in NAcc microstructure were found between hair cortisol trajectories. A significant interaction between preconception PSS and rNAcc-ODI on externalizing behavior was observed (n = 47, p = .047). CONCLUSION: Our study showed that the preconception period contributes to in utero NAcc development, and that NAcc microstructure modulates individual susceptibility to preconception maternal stress in relation to externalizing problems.

Screen time, brain network development and socio-emotional competence in childhood: moderation of associations by parent-child reading.

BACKGROUND: Screen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent-child reading in mitigating the effects of screen time. METHODS: We examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence. Lastly, we tested if parent-child reading time was a moderator of the link between screen time and brain network topology. RESULTS: Infant screen time was significantly associated with the emotion processing-cognitive control network integration (p = 0.005). This network integration also significantly mediated the association between screen time and both measures of socio-emotional competence (BRIEF-2 Emotion Regulation Index, p = 0.04; SEARS total score, p = 0.04). Parent-child reading time significantly moderated the association between screen time and emotion processing-cognitive control network integration (ß = -0.640, p = 0.005). CONCLUSION: Our study identified emotion processing-cognitive control network integration as a plausible biological pathway linking screen time in infancy and later socio-emotional competence. We also provided novel evidence for the role of parent-child reading in moderating the association between screen time and topological brain restructuring in early childhood.

Effects of Two Different Low-Volume Resistance Training Programs Applied During the Off-Season Period on the Speed-Power Performance of Elite Youth Soccer Players.

ABSTRACT: Loturco, I, Nunes, RFH, Lampert, RR, Silva, RLP, Hespanhol, JE, Novack, LF, Conde, JHS, Pereira, LA, and McGuigan, MR. Effects of two different low-volume resistance training programs applied during the off-season period on the speed-power performance of elite youth soccer players. . J Strength Cond Res 38(3): 571-576, 2024-The aim of this study was to analyze the changes in the speed-power performance of elite youth soccer players submitted to 2 different low-volume resistance training programs during the off-season period. Twenty under-17 players were randomly allocated to "traditional nonballistic" or "ballistic training" groups. Countermovement jump (CMJ), 20-m sprinting speed, and half-squat (HS) power tests were performed after the final match of the season (pretesting session) and at the beginning of the subsequent season (post-testing session), after 4 weeks of detraining. Between-group differences were assessed using a 2-way ANOVA with repeated measures followed by the Tukey's post hoc test. Performance variations were individually analyzed with the use of the "true changes" calculation. At post-tests, CMJ height and HS power remained unchanged ( p > 0.05) but similar and significant improvements in sprint speed were observed in both groups ( p < 0.05). However, notably, a larger number of players in the ballistic group exhibited "true changes" in HS power (i.e., 55 vs. 33%, compared with the traditional group, respectively). In conclusion, either low-volume ballistic or traditional resistance training schemes were able to increase sprint speed and maintain power output during a short interseason break in youth soccer players. Despite this apparent similarity, at the individual level, ballistic movements were more efficient at improving lower-body power. Practitioners can use the strategies described here to improve the sprint and power performance of soccer players during short periods of soccer-specific training cessation.

Prediction by uterine artery Doppler screening of small-for-gestational-age neonates at 19-24 weeks' gestation.

OBJECTIVE: Small-for-gestational-age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA-PI) at 19-24 weeks' gestation to predict the delivery of a SGA neonate in a Chinese population. METHODS: This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19-24 weeks' gestation. SGA was defined as birth weight below the 10th centile according to the INTERGROWTH-21st fetal growth standards. The performance of UtA-PI to predict the delivery of a SGA neonate was assessed using receiver-operating-characteristics (ROC)-curve analysis. RESULTS: We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA-PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA-PI were 64.4% (95% CI, 61.5-67.3%) and 75.8% (95% CI, 69.3-82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA-PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA). CONCLUSIONS: This is the first Chinese study to evaluate the role of UtA-PI at 19-24 weeks' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA-PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Music for pain relief of minor procedures in term neonates.

BACKGROUND: Music for neonatal pain has not been exclusively studied in term neonates in a well-designed trial compared to the standard of care. This study aims to assess the effectiveness of music intervention as an adjuvant in relieving acute pain in term newborns undergoing minor painful procedures. METHODS: This randomized, controlled, blinded trial included any term neonate undergoing heel prick. Both control and intervention groups received oral sucrose 2 min before heel prick. Intervention group was exposed to 'Bedtime Mozart' lullaby recorded music via bedside speakers. Pain was measured using Neonatal Infant Pain Scale (NIPS) at 1-min intervals. Investigators were blinded using noise-canceling headphones that played random music. RESULTS: A total of 100 neonates were enrolled. Mean gestational age was 39.2 weeks, and mean duration of the procedure was 113 s. Music group was found to have significantly lower pain scores [OR = 0.42 (0.31, 0.56), p < 0.001]. Baseline NIPS scores were similar across groups and there was no interaction effect between groups and time. When NIPS were categorized as pain and no pain, there continued to be statistically significant lower NIPS scores in the music group (p < 0.001). CONCLUSION: Recorded music, in addition to sucrose, is efficacious in reducing pain, encouraging its use in term neonates. IMPACT: Recorded music effectively reduces pain induced by minor procedures in term neonates. Clinical studies have shown that live and recorded music induces changes in vital signs and pain scores in the NICU's predominantly preterm population. Most of these studies were also conducted in the white ethnic population. Our study objectively proves reduction in pain scores by using recorded music in a randomized, controlled, blinded study of predominantly non-white, term neonates. Recorded music is effective in reducing acute pain in term neonates and can be widely used even in low-resource nurseries.

Sand and grass surfaces are equally effective in promoting positive adaptations in the sprint performance of elite young soccer players.

This study compared the effects of two sprint-jump training programmes, performed on either sand or grass surfaces, on the sprint and jump performance of elite young soccer players over an 8-week training period. Fifteen under-20 soccer players were randomly allocated to the sand (n = 7) or grass (n = 8) group. Athletes performed 12 training sessions, comprising vertical and horizontal jump exercises, and linear and change-of-direction (COD) sprint drills. Pre- and post-measurements were completed in the following order: vertical jump, sprint speed at 10 m and 17 m, curve sprint (CS), and modified Zigzag COD tests. Between-group differences were determined using a two-way ANOVA with repeated measures and effect sizes (ES). No improvements in jump performance were found in either group. Significant increases were observed in the sand group for acceleration in 0-10 m and for 10- and 17-m linear sprint velocity (ES = 1.15, 1.16, and 1.81, respectively; P < 0.05). In contrast, no significant differences were detected for acceleration and linear sprint velocity in the grass group, comparing pre- and post-tests (ES ranging from 0.01 to 0.47; P > 0.05). Both sand and grass groups revealed similar increases in the CS and COD velocities after the training period (ES ranging from 0.98 to 1.93; P < 0.05). In conclusion, sprint-jump training programmes performed on both grass and sand surfaces elicited significant improvements in CS and COD performances, whereas acceleration and linear sprint velocity increased only in the sand group, after a short-term training period. The sand training surface was proven to be a practical strategy to improve sprint performance in all its forms in soccer players, which is of great interest and importance for coaches and sport scientists working in elite soccer.

Effect of pesticides on phosphorylation of tau protein, and its influence on Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and neurodegenerative illness which results in alterations in cognitive development. It is characterized by loss/dysfunction of cholinergic neurons, and formation of amyloid plaques, and formation of neurofibrillary tangles, among other changes, due to hyperphosphorylation of tau-protein. Exposure to pesticides in humans occurs frequently due to contact with contaminated food, water, or particles. Organochlorines, organophosphates, carbamates, pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment. The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein, and its cognitive implications in the development of AD. It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198, Ser199, Ser202, Thr205, Ser396 and Ser404. Contact with these chemicals altered the enzymatic activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta, and protein phosphatase-2A. Moreover, it altered the expression of the microtubule associated protein tau gene, and changed levels of intracellular calcium. These changes affected tau protein phosphorylation and neuroinflammation, and also increased oxidative stress. In addition, the exposed subjects had poor level of performance in tests that involved evaluation of novelty, as test on verbal, non-verbal, spatial memory, attention, and problem-solving skills.

Tic-Tac: A Translational Approach in Mechanisms Associated with Irregular Heartbeat and Sinus Rhythm Restoration in Atrial Fibrillation Patients.

Atrial fibrillation (AF) is a prevalent cardiac condition predominantly affecting older adults, characterized by irregular heartbeat rhythm. The condition often leads to significant disability and increased mortality rates. Traditionally, two therapeutic strategies have been employed for its treatment: heart rate control and rhythm control. Recent clinical studies have emphasized the critical role of early restoration of sinus rhythm in improving patient outcomes. The persistence of the irregular rhythm allows for the progression and structural remodeling of the atria, eventually leading to irreversible stages, as observed clinically when AF becomes permanent. Cardioversion to sinus rhythm alters this progression pattern through mechanisms that are still being studied. In this review, we provide an in-depth analysis of the pathophysiological mechanisms responsible for maintaining AF and how they are modified during sinus rhythm restoration using existing therapeutic strategies at different stages of clinical investigation. Moreover, we explore potential future therapeutic approaches, including the promising prospect of gene therapy.

White matter alterations in Attention-Deficit/Hyperactivity Disorder (ADHD): a systematic review of 129 diffusion imaging studies with meta-analysis.

Aberrant anatomical brain connections in attention-deficit/hyperactivity disorder (ADHD) are reported inconsistently across diffusion weighted imaging (DWI) studies. Based on a pre-registered protocol (Prospero: CRD42021259192), we searched PubMed, Ovid, and Web of Knowledge until 26/03/2022 to conduct a systematic review of DWI studies. We performed a quality assessment based on imaging acquisition, preprocessing, and analysis. Using signed differential mapping, we meta-analyzed a subset of the retrieved studies amenable to quantitative evidence synthesis, i.e., tract-based spatial statistics (TBSS) studies, in individuals of any age and, separately, in children, adults, and high-quality datasets. Finally, we conducted meta-regressions to test the effect of age, sex, and medication-naïvety. We included 129 studies (6739 ADHD participants and 6476 controls), of which 25 TBSS studies provided peak coordinates for case-control differences in fractional anisotropy (FA)(32 datasets) and 18 in mean diffusivity (MD)(23 datasets). The systematic review highlighted white matter alterations (especially reduced FA) in projection, commissural and association pathways of individuals with ADHD, which were associated with symptom severity and cognitive deficits. The meta-analysis showed a consistent reduced FA in the splenium and body of the corpus callosum, extending to the cingulum. Lower FA was related to older age, and case-control differences did not survive in the pediatric meta-analysis. About 68% of studies were of low quality, mainly due to acquisitions with non-isotropic voxels or lack of motion correction; and the sensitivity analysis in high-quality datasets yielded no significant results. Findings suggest prominent alterations in posterior interhemispheric connections subserving cognitive and motor functions affected in ADHD, although these might be influenced by non-optimal acquisition parameters/preprocessing. Absence of findings in children may be related to the late development of callosal fibers, which may enhance case-control differences in adulthood. Clinicodemographic and methodological differences were major barriers to consistency and comparability among studies, and should be addressed in future investigations.

Zinc deficiency and a high-fat diet during growth: Metabolic and adipocyte alterations in rats.

BACKGROUND AND AIMS: To evaluate the effects of a high-fat diet during post-weaning growth on intermediate metabolism and retroperitoneal adipose tissue, in adult male rats exposed to adequate or deficient zinc intake during prenatal and postnatal life. METHODS AND RESULTS: Female Wistar rats were fed low- or control-zinc diets from pregnancy to offspring weaning. Male offspring born from control mothers were fed either control or high-fat, control-zinc diets for 60 days. Male offspring born from zinc deficient mothers were fed either low-zinc or high-fat, low-zinc diets for 60 days. At 74 days of life, oral glucose tolerance test was performed. In 81-day-old offspring, blood pressure, lipid profile, plasmatic lipid peroxidation and serum adiponectin level were determined. In retroperitoneal adipose tissue, we evaluated oxidative stress, morphology and adipocytokines mRNA expression. Low-zinc diet induced adipocytes hypertrophy, increased oxidative stress, and decreased adiponectin mRNA expression in adipose tissue. Low-zinc diet increased systolic blood pressure, triglyceridemia, plasmatic lipid peroxidation and glycemia at 3 h after glucose overload. Animals fed high-fat or high-fat, low-zinc diets showed adipocytes hypertrophy, decreased adiponectin mRNA expression, and increased leptin mRNA expression and oxidative stress in adipose tissue. They also exhibited decreased serum adiponectin levels, increased triglyceridemia, plasmatic lipid peroxidation and area under the oral glucose tolerance curve. High-fat, low-zinc diet induced greater alterations in adipocyte hypertrophy, leptin mRNA expression and glucose tolerance test than high-fat diet. CONCLUSION: Zinc deficiency since early stages of intrauterine life could increase susceptibility to metabolic alterations induced by high-fat diets during postnatal life.

A multicentre study on grey matter morphometric biomarkers for classifying early schizophrenia and parkinson's disease psychosis.

Psychotic symptoms occur in a majority of schizophrenia patients and in ~50% of all Parkinson's disease (PD) patients. Altered grey matter (GM) structure within several brain areas and networks may contribute to their pathogenesis. Little is known, however, about transdiagnostic similarities when psychotic symptoms occur in different disorders, such as in schizophrenia and PD. The present study investigated a large, multicenter sample containing 722 participants: 146 patients with first episode psychosis, FEP; 106 individuals in at-risk mental state for developing psychosis, ARMS; 145 healthy controls matching FEP and ARMS, Con-Psy; 92 PD patients with psychotic symptoms, PDP; 145 PD patients without psychotic symptoms, PDN; 88 healthy controls matching PDN and PDP, Con-PD. We applied source-based morphometry in association with receiver operating curves (ROC) analyses to identify common GM structural covariance networks (SCN) and investigated their accuracy in identifying the different patient groups. We assessed group-specific homogeneity and variability across the different networks and potential associations with clinical symptoms. SCN-extracted GM values differed significantly between FEP and Con-Psy, PDP and Con-PD, PDN and Con-PD, as well as PDN and PDP, indicating significant overall grey matter reductions in PD and early schizophrenia. ROC analyses showed that SCN-based classification algorithms allow good classification (AUC ~0.80) of FEP and Con-Psy, and fair performance (AUC ~0.72) when differentiating PDP from Con-PD. Importantly, the best performance was found in partly the same networks, including the thalamus. Alterations within selected SCNs may be related to the presence of psychotic symptoms in both early schizophrenia and PD psychosis, indicating some commonality of underlying mechanisms. Furthermore, results provide evidence that GM volume within specific SCNs may serve as a biomarker for identifying FEP and PDP.

First draft genome of Thecaphora frezii, causal agent of peanut smut disease.

OBJECTIVES: The fungal pathogen Thecaphora frezii Carranza & Lindquist causes peanut smut, a severe disease currently endemic in Argentina. To study the ecology of T. frezii and to understand the mechanisms of smut resistance in peanut plants, it is crucial to know the genetics of this pathogen. The objective of this work was to isolate the pathogen and generate the first draft genome of T. frezii that will be the basis for analyzing its potential genetic diversity and its interaction with peanut cultivars. Our research group is working to identify peanut germplasm with smut resistance and to understand the genetics of the pathogen. Knowing the genome of T. frezii will help analyze potential variants of this pathogen and contribute to develop enhanced peanut germplasm with broader and long-lasting resistance. DATA DESCRIPTION: Thecaphora frezii isolate IPAVE 0401 (here referred as T.f.B7) was obtained from a single hyphal-tip culture, its DNA was sequenced using Pacific Biosciences Sequel II (PacBio) and Illumina NovaSeq6000 (Nova). Data from both sequencing platforms were combined and the de novo assembling estimated a 29.3 Mb genome size. Completeness of the genome examined using Benchmarking Universal Single-Copy Orthologs (BUSCO) showed the assembly had 84.6% of the 758 genes in fungi_odb10.

Coronary Artery Disease in Systemic Lupus Erythematosus: What Do the Facts Say?

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect any organ with a predisposition for women of reproductive age. It is related to a higher risk of cardiovascular events, increasing it up to 50 times in young people, and 30% of deaths are attributed to coronary artery disease. The risk of developing cardiovascular disease in SLE is related not only to traditional cardiovascular risks factors such as advanced age, hypertension, dyslipidemia, and diabetes but also to disease-specific factors, such as degree of activity, autoantibodies, organ damage, and treatment. Accelerated atherosclerosis is one of the main contributors to pathogenesis. Manifestations range from angina to acute myocardial infarction and sudden death. Markers have been studied for the detection of subclinical disease and stratification of these patients, as well as different treatment options to improve the cardiovascular prognosis of the disease.

Shikonin alleviates collagen-induced arthritis mice by inhibiting M1 macrophage polarization.

OBJECTIVE: To investigate the effects of shikonin (SKN) on M1 and M2 polarization of macrophages both and . METHODS: Collagen-induced arthritis (CIA) in male DBA/1 mice were treated with a dose of 4 mg/kg/day of SKN for 23 d ( = 6/group). The histopathology of inflamed joints in CIA mice was evaluated to test the anti-arthritic effect of SKN. M1/M2 polarization of macrophages induced by lipopolysaccharide (LPS) and interferon (IFN)-γ or interleukin (IL)-4 and IL-13, were used to assess the effect of SKN (0.05, 0.1, and 0.2 µM). The effect of SKN on the protein expression of nitric oxide synthase, arginase, CD68, and CD206 was evaluated using western blot analysis. RESULTS: The results of this study revealed that SKN delayed the arthritis feet symptom score, reduced the incidence rate of arthritis, and relieved the inflammation of joints in CIA mice. SKN inhibited M1 macrophage polarization but did not affect M2 macrophage polarization in the joints of CIA mice. Moreover, SKN inhibited M1 polarization induced by LPS and IFN-γ, but did not affect M2 polarization induced by IL-4 and IL-13. CONCLUSION: These findings suggest that SKN alleviated CIA through inhibiting M1 macrophage polarization and has great potential as a new drug for RA treatment.

Near-Room-Temperature Magnetoelectric Coupling via Spin Crossover in an Iron(II) Complex.

Magnetoelectric coupling is achieved near room temperature in a spin crossover FeII molecule-based compound, [Fe(1bpp)2 ](BF4 )2 . Large atomic displacements resulting from Jahn-Teller distortions induce a change in the molecule dipole moment when switching between high-spin and low-spin states leading to a step-wise change in the electric polarization and dielectric constant. For temperatures in the region of bistability, the changes in magnetic and electrical properties are induced with a remarkably low magnetic field of 3 T. This result represents a successful expansion of magnetoelectric spin crossovers towards ambient conditions. Moreover, the observed 0.3-0.4 mC m-2 changes in the H-induced electric polarization suggest that the high strength of the coupling obtained via this route is accessible not just at cryogenic temperatures but also near room temperature, a feature that is especially appealing in the light of practical applications.

Hydrogen sulfide and miR21 are suitable biomarkers of hypoxic exposure.

Hypoxia is the reduction of alveolar partial pressure of oxygen ([Formula: see text]). Military members and people who practice recreational activities from moderate to high altitudes are at risk for hypoxic exposure. Hypoxemia's signs and symptoms vary from asymptomatic to severe responses, such as excessive hypoxic ventilatory responses and residual neurobehavioral impairment. Therefore, it is essential to identify hypoxia-induced biomarkers to indicate people with exposure to hypoxia. Advances have been made in understanding physiological responses to hypoxia, including elevations in circulating levels of endothelin 1 (ET-1) and microRNA 21 (miR-21) and reduction in circulating levels of hydrogen sulfide (H2S). Although the levels of these factors change upon exposure to hypoxia, it is unclear if these changes are sustained on return to normoxia. We hypothesize that hypoxia-induced ET-1 and miR-21 remain elevated, whereas hypoxia-reduction in H2S sustains after returning to normoxic conditions. To test this hypothesis, we exposed male rats to 6 h of 12% O2 and measured circulating levels of ET-1 and miR-21, pre, during, and posthypoxia. We found that ET-1 plasma levels increased in response to hypoxia but returned to normal levels within 30 min after the restoration of normoxia. miR-21 plasma levels and transdermal H2S emissions decreased in response to hypoxia, remaining decreased on return to normoxia, thus following the biomarker criteria. Therefore, this study supports a unique role for plasma miR21 and transdermal H2S as hypoxia biomarkers that could be used to identify individuals after exposure to hypoxia.