Ecological divergence and speciation in common bottlenose dolphins in the western South Atlantic.

Coastal and offshore ecotypes of common bottlenose dolphins have been recognized in the western South Atlantic, and it is possible that trophic niche divergence associated with social interactions is leading them to genetic and phenotypic differentiation. The significant morphological differentiation observed between these ecotypes suggests they represent two different subspecies. However, there is still a need to investigate whether there is congruence between morphological and genetic data to rule out the possibility of ecophenotypic variation accompanied by gene flow. Mitochondrial DNA (mtDNA) control region sequence data and 10 microsatellite loci collected from stranded and biopsied dolphins sampled in coastal and offshore waters of Brazil as well as 106 skulls for morphological analyses were used to determine whether the morphological differentiation was supported by genetic differentiation. There was congruence among the data sets, reinforcing the presence of two distinct ecotypes. The divergence may be relatively recent, however, given the moderate values of mtDNA nucleotide divergence (dA = 0.008), presence of one shared mtDNA haplotype and possibly low levels of gene flow (around 1% of migrants per generation). Results suggest the ecotypes may be in the process of speciation and reinforce they are best described as two different subspecies until the degree of nuclear genetic divergence is thoroughly evaluated: Tursiops truncatus gephyreus (coastal ecotype) and T. t. truncatus (offshore ecotype). The endemic distribution of T. t. gephyreus in the western South Atlantic and number of anthropogenic threats in the area reinforces the importance of protecting this ecotype and its habitat.

Canine orosomucoid (alpha-1 acid glycoprotein) variants and their influence on drug plasma protein binding.

Orosomucoid polymorphisms influence plasma drug binding in humans; however, canine variants and their effect on drug plasma protein binding have not yet been reported. In this study, the orosomucoid gene (ORM1) was sequenced in 100 dogs to identify the most common variant and its allele frequency determined in 1,464 dogs (from 64 breeds and mixed-breed dogs). Plasma protein binding extent of amitriptyline, indinavir, verapamil, and lidocaine were evaluated by equilibrium dialysis using plasma from ORM1 genotyped dogs (n = 12). Free and total drug plasma concentrations were quantified by liquid chromatography-mass spectrometry. From the five polymorphisms identified in canine ORM1, two were nonsynonymous. The most common was c.70G>A (p.Ala24Thr) with an allele frequency of 11.2% (n = 1464). Variant allele frequencies varied by breed, reaching 74% in Shetland Sheepdogs (n = 21). Free drug fractions did not differ significantly (p > .05; Mann-Whitney U) between plasma collected from dogs with c.70AA (n = 4) and those with c.70GG (n = 8) genotypes. While c.70G>A did not affect the extent of plasma protein binding in our study, the potential biological and pharmacological implication of this newly discovered ORM1 variant in dogs should be further investigated.

Canine Albumin Polymorphisms and Their Impact on Drug Plasma Protein Binding.

Drug binding to plasma proteins is routinely determined during drug development. Albumin polymorphisms c.1075G>T (p.Ala359Ser) and c.1422A>T (p.Glu474Asp) were previously shown to alter plasma protein binding of a drug candidate (D01-4582, 4-[1-[3-chloro-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidine-2-yl]methoxybenzoic acid) in a colony of Beagles. Our study investigated the hypothesis that drug-protein binding in plasma from dogs with the albumin H1 (reference) allele would be greater than in plasma from dogs with the albumin H2 allele (c.1075G>T and c.1422A>T) (n = 6 per group). The plasma protein binding extent of four drugs (D01-4582, celecoxib, mycophenolic acid, and meloxicam) was evaluated using ultracentrifugation or equilibrium dialysis. Free and total drug concentrations were analyzed by liquid chromatography-mass spectrometry. The albumin gene coding region was sequenced in 100 dogs to detect novel gene variants, and H1/H2 allele frequency was determined in a large and varied population (n = 1446 from 61 breeds and mixed-breed dogs). For meloxicam, H1 allele plasma had statistically significant higher free drug fractions (P = 0.041) than H2 allele plasma. No significant difference was identified for plasma protein binding of D01-4582, celecoxib, or mycophenolic acid. c.1075G>T and c.1422A>T were the most common single nucleotide polymorphisms in canine albumin, present concurrently in most study dogs and occasionally identified independently. Our findings suggest a potential influence of c.1075G>T and c.1422A>T on plasma protein binding. This influence should be confirmed in vivo and for additional drugs. Based on our results, albumin genotyping should be considered for canine research subjects to improve interpretation of pharmacokinetic data generated during the drug development process for humans and dogs.

Influence of the SPECT calibration source position on the absorbed dose calculation for 131I-NaI therapy using GATE simulations.

Many research groups have studied nuclear medicine image quantification to improve its accuracy in dose estimation. This work aims to evaluate the influence of the source calibration position for absorbed dose calculation for a 131I-NaI therapy using Monte Carlo (MC) simulations. The calibration approach consisted of a cylindrical phantom filled with water. A cylindrical 131I source with 361.1 ± 3.6 kBq ml-1 was positioned at the center of the phantom and its outer part. Images were acquired with 150 00 counts per projection image acquired with SPECT detector (high counts density-HCD) and 3000 counts per projection (low counts density-LCD). MC simulations, performed with GATE code, were validated by comparing the S values of a water sphere uniformly filled with 131I, as from the sphere model of OLINDA/EXM 1.1. Calibration factors deviation between central and peripheral calibrations is more significant for HCD (18.3%) than for LCD images (3.7%). The 3D dose distribution map obtained from GATE resulted in a dose factor equal to 1.5 × 10-3 mGy/(MBq.s). For both HCD and LCD images, the commonly used approach, which employs the central source calibration to obtain the dose from a peripheral source, resulted in dose overestimation. Results suggest that organ dose calculation can be improved considering the organ position in the field of view. Finally, patients' radiation protection in dosimetry studies could be improved considering the calibration source position, due to the superior accuracy in dose calculation.

Experimental evidence for adaptive divergence in response to a warmed habitat reveals roles for morphology, allometry and parasite resistance.

Ectotherms are expected to be particularly vulnerable to climate change-driven increases in temperature. Understanding how populations adapt to novel thermal environments will be key for informing mitigation plans. We took advantage of threespine stickleback (Gasterosteus aculeatus) populations inhabiting adjacent geothermal (warm) and ambient (cold) habitats to test for adaptive evolutionary divergence using a field reciprocal transplant experiment. We found evidence for adaptive morphological divergence, as growth (length change) in non-native habitats related to head, posterior and total body shape. Higher growth in fish transplanted to a non-native habitat was associated with morphological shape closer to native fish. The consequences of transplantation were asymmetric with cold sourced fish transplanted to the warm habitat suffering from lower survival rates and greater parasite prevalence than warm sourced fish transplanted to the cold habitat. We also found divergent shape allometries that related to growth. Our findings suggest that wild populations can adapt quickly to thermal conditions, but immediate transitions to warmer conditions may be particularly difficult.

Aging-dependent mitochondrial bioenergetic impairment in the skeletal muscle of NNT-deficient mice.

Overall health relies on features of skeletal muscle that generally decline with age, partly due to mechanisms associated with mitochondrial redox imbalance and bioenergetic dysfunction. Previously, aged mice genetically devoid of the mitochondrial NAD(P)+ transhydrogenase (NNT, encoded by the nicotinamide nucleotide transhydrogenase gene), an enzyme involved in mitochondrial NADPH supply, were shown to exhibit deficits in locomotor behavior. Here, by using young, middle-aged, and older NNT-deficient (Nnt-/-) mice and age-matched controls (Nnt+/+), we aimed to investigate how muscle bioenergetic function and motor performance are affected by NNT expression and aging. Mice were subjected to the wire-hang test to assess locomotor performance, while mitochondrial bioenergetics was evaluated in fiber bundles from the soleus, vastus lateralis and plantaris muscles. An age-related decrease in the average wire-hang score was observed in middle-aged and older Nnt-/- mice compared to age-matched controls. Although respiratory rates in the soleus, vastus lateralis and plantaris muscles did not significantly differ between the genotypes in young mice, the rates of oxygen consumption did decrease in the soleus and vastus lateralis muscles of middle-aged and older Nnt-/- mice. Notably, the soleus, which exhibited the highest NNT expression level, was the muscle most affected by aging, and NNT loss. Additionally, histology of the soleus fibers revealed increased numbers of centralized nuclei in older Nnt-/- mice, indicating abnormal morphology. In summary, our findings suggest that NNT expression deficiency causes locomotor impairments and muscle dysfunction during aging in mice.

Proliferating Astrocytes in Primary Culture Do Not Depend upon Mitochondrial Respiratory Complex I Activity or Oxidative Phosphorylation.

Understanding the role of astrocytes in the development of the nervous system and neurodegenerative disorders implies a necessary knowledge of the oxidative metabolism of proliferating astrocytes. The electron flux through mitochondrial respiratory complexes and oxidative phosphorylation may impact the growth and viability of these astrocytes. Here, we aimed at assessing to which extent mitochondrial oxidative metabolism is required for astrocyte survival and proliferation. Primary astrocytes from the neonatal mouse cortex were cultured in a physiologically relevant medium with the addition of piericidin A or oligomycin at concentrations that fully inhibit complex I-linked respiration and ATP synthase, respectively. The presence of these mitochondrial inhibitors for up to 6 days in a culture medium elicited only minor effects on astrocyte growth. Moreover, neither the morphology nor the proportion of glial fibrillary acidic protein-positive astrocytes in culture was affected by piericidin A or oligomycin. Metabolic characterization of the astrocytes showed a relevant glycolytic metabolism under basal conditions, despite functional oxidative phosphorylation and large spare respiratory capacity. Our data suggest that astrocytes in primary culture can sustainably proliferate when their energy metabolism relies only on aerobic glycolysis since their growth and survival do not require electron flux through respiratory complex I or oxidative phosphorylation.

Testing the predictability of morphological evolution in contrasting thermal environments.

Gaining the ability to predict population responses to climate change is a pressing concern. Using a "natural experiment," we show that testing for divergent evolution in wild populations from contrasting thermal environments provides a powerful approach, and likely an enhanced predictive power for responses to climate change. Specifically, we used a unique study system in Iceland, where freshwater populations of threespine sticklebacks (Gasterosteus aculeatus) are found in waters warmed by geothermal activity, adjacent to populations in ambient-temperature water. We focused on morphological traits across six pairs from warm and cold habitats. We found that fish from warm habitats tended to have a deeper mid-body, a subterminally orientated jaw, steeper craniofacial profile, and deeper caudal region relative to fish from cold habitats. Our common garden experiment showed that most of these differences were heritable. Population age did not appear to influence the magnitude or type of thermal divergence, but similar types of divergence between thermal habitats were more prevalent across allopatric than sympatric population pairs. These findings suggest that morphological divergence in response to thermal habitat, despite being relatively complex and multivariate, are predictable to a degree. Our data also suggest that the potential for migration of individuals between different thermal habitats may enhance nonparallel evolution and reduce our ability to predict responses to climate change.

Consequences and implications of the coronavirus disease (COVID-19) on pregnancy and newborns: A comprehensive systematic review and meta-analysis.

BACKGROUND: Pregnant patients are potentially vulnerable to COVID-19. OBJECTIVES: To clarify the clinical features of COVID-19 and analyze maternal/fetal morbidity and mortality and the obstetric and neonatal outcomes of pregnant patients. SEARCH STRATEGY: Embase, PubMed, Web of Science, CINAHAL, LILACS, Google Scholar, and Scopus. SELECTION CRITERIA: Articles published from December 2019 to February 2021. DATA COLLECTION AND ANALYSIS: The reviewers extracted relevant data from the full-text. Data synthesis was performed using the R-4.1.0 Project for Statistical Computing for Windows. The meta-analysis of the included studies was carried out using the random-effects model (DerSimonian and Laird). Heterogeneity was measured using I2 analysis. RESULTS: A total of 70 studies included 10 047 pregnant women with COVID-19, of whom 71.6% were in their third trimester. The most common symptoms were fever, cough, chest pain, dyspnea, and fatigue. Most newborns were delivered preterm (24%, 95% confidence interval [CI] 0.17-0.34, I2  = 93%) and via cesarean delivery (42%, 95% CI 0.38-0.47, I2  = 92%). There were 108 maternal mortalities (2%, 95% CI 0.01-0.03, I2  = 54%) and 50 abortions (5%, 95% CI 0.03-0.09, I2  = 73%). The neonatal outcomes included fetal distress (11%, 95% CI 0.06-0.19, I2  = 91%), birth weight (15%, 95% CI 0.10-0.21, I2  = 76%), APGAR <7 (19%, 95% CI 0.12-0.28, I2  = 43%), admission to the neonatal intensive care unit (28%, 95% CI 0.17-0.43, I2  = 90%), and fetal mortality (2%, 95% CI 0.01-0.03, I2  = 46%). CONCLUSION:  There was no evidence of severe acute respiratory syndrome coronavirus-2 in the placenta, breast milk, umbilical cord, and amniotic fluid of pregnant patients. PROSPERO registration number: CRD42020181519.

A pilot study of transdermal gabapentin in cats.

BACKGROUND: Clinical use of gabapentin has increased; transdermal delivery in cats is incompletely studied. OBJECTIVE: To evaluate if gabapentin permeates feline skin in vitro and in vivo and to determine if pain scores improve after administration. ANIMALS: In vitro: cadaver skin from 6 cats; phase 1: 8 young, healthy client-owned cats; phase 2: 15 client-owned geriatric cats. METHODS: In vitro, gabapentin applied every q12h to ear or cervical skin in diffusion cells. Samples collected at 0, 2, 4, 12, and 24 hours after application. Phase 1: Cats assigned to 1 of 4 groups: 5 mg/kg or 10 mg/kg applied q8h for 5 days to either ear or cervical skin. Serum samples collected predose, and after 1 and 5 days. Phase 2: 10 mg/kg applied q8h for 5 days. Two validated pain scores recorded predose, and after days 1, 5, and 8. Serum samples collected predose, and after days 1 and 5. Samples were frozen at -80°C for concentration analysis utilizing a validated high-performance liquid chromatography mass-spectrometry method. RESULTS: Gabapentin was identified in all samples. Significant differences in gabapentin concentrations were observed from day 1 to day 5 (P < .02) and in pain scores from predose to day 5 (P < .05) and day 1 to day 5 (P < .05). No differences in pain scores were observed from predose to day 8 (P = .3). CONCLUSIONS AND CLINICAL RELEVANCE: Gabapentin in a transdermal base penetrates feline skin in vitro, is absorbed systemically in cats, and may help decrease pain scores.

Physical methods for the treatment of genitourinary syndrome of menopause: A systematic review.

BACKGROUND: Genitourinary syndrome of menopause (GSM) negatively affects sexual function and quality of life. Techniques like laser and radiofrequency are being used to manage GSM, particularly in women with contraindications for hormone therapy. OBJECTIVES: To verify whether the physical methods of laser and radiofrequency can be recommended as safe and effective options for the treatment of GSM/urinary urgency or incontinence in pre- and postmenopausal women. SEARCH STRATEGY: Databases were comprehensively searched using combinations of the following keywords in any language: "postmenopause"; "genitourinary syndrome of menopause"; "vaginal atrophy"; "radiofrequency"; and "laser." SELECTION CRITERIA: Full articles of case-control, cross-sectional, cohort, randomized clinical trials, and quasi-randomized or controlled clinical trials were included. DATA COLLECTION AND ANALYSIS: All authors independently evaluated the design of the studies for quality of reporting, risk of bias, and quality of evidence. MAIN RESULTS: Of the included 49 studies, 37 were on the CO2 laser, 10 on the Erbium laser, and two on radiofrequency. CONCLUSIONS: Laser and radiofrequency therapy could be promising and safe therapeutic options for GSM/urinary incontinence. However, the study findings cannot be generalized until new randomized clinical trials are performed that confirm the strength of the evidence. This review has been registered with PROSPERO: CRD42020141913.

Organic solvents alter photophysiological and oxidative stress profiles of the coral Zoanthus sp. - Towards an optimization of ecotoxicological protocols.

Coral reefs are declining, affected by climate change and escalating anthropogenic pressures, such as pollution or habitat alteration. Consequently, ecotoxicological assays with tropical corals have increased, specifically towards the study of emergent or persistent pollutants. However, standardized methodology to test for corals is non-existent, and their response to organic solvents, recurrently required in ecotoxicological appraisals, remains unknown. Therefore, we aimed to establish a threshold for the safe use of the selected solvents in ecotoxicological studies with these organisms. We assessed the oxidative stress response (antioxidant response and oxidative damage), cellular energy allocation and photophysiology of the photosynthetic coral Zoanthus sp. (Anthozoa, Hexacorallia) exposed to six doses of three different organic solvents (ethanol, methanol and dimethyl sulfoxide - DMSO). Our results suggest that the coral is more sensitive to methanol and DMSO than to ethanol. Methanol and DMSO LOEC were 0.01 mL L-1 affecting maximum quantum yield (Fv/Fm) and glutathione S-transferase (GST) activity, respectively, while for ethanol was 0.03 mL L-1, influencing Fv/Fm. Despite the higher tolerance of Zoanthus sp. to ethanol, 2.9 mL L-1 of this organic solvent was the only treatment causing mortality. Based on these findings, thresholds for the use of organic solvents with tropical corals can now be adopted. Nevertheless, species specificities should not be overlooked.

Experimental dataset supporting the physical and mechanical characterization of industrial base tissue papers.

Tissue paper is defined by its physical and mechanical properties, namely: high softness, low grammage, high bulk and high liquid absorption capacity. It is expected that the production of tissue paper will continue to grow, which increases the importance of better understanding the processes involved in its production as well as its optimization [1]. The experimental data presented in this article, are the physical-mechanical characterization of a group of 13 industrial base tissue papers, which were collected at the end of the tissue paper machine on Portuguese factories. These samples vary in grammage, composition and creping [2], enabling a later evaluation of the crepe type [3] and its relationship with the final properties of the tissue paper.

Agmatine potentiates antidepressant and synaptic actions of ketamine: Effects on dendritic arbors and spines architecture and Akt/S6 kinase signaling.

We investigated the ability of agmatine to potentiate the antidepressant-like and synaptic effects of ketamine in mice. Agmatine (0.1 and 1 mg/kg, p.o.) and ketamine (1 and 10 mg/kg, i.p.) produced an antidepressant-like effect in the tail suspension test. The combination of agmatine (0.01 mg/kg, p.o.) and ketamine (0.1 mg/kg, i.p.), at subthreshold doses, produced an antidepressant-like effect 1 h, 24 h and 7d after treatment. Western blot analysis from prefrontal cortex tissue showed that the combined treatment, after 1 h, increased p70S6K and GluA1, and reduced synapsin 1 phosphorylation. Additionally, after 24 h, Akt, p70S6K, GluA1, and synapsin 1 phosphorylation; and PSD95 immunocontent increased (which persisted for up to 7d). Dendritic architecture analysis of the prefrontal cortex revealed that the combined treatment improved dendritic arbor complexity (after 24 h, up to 7d), and increased spine density (after 1 h, up to 24 h). Morphometric analysis revealed a filopodia-shaped dendrite spine upregulation after 1 h. A predominance of stubby, mushroom, branched and filopodia; and a reduction in thin protrusions were observed after 24 h. Finally, mushroom-shaped dendritic spines predominance increased after 7d. Agmatine potentiated ketamine's antidepressant, and dendritic arbors and spines remodeling effects in a time-dependent manner. Our data indicate Akt/p70S6K signaling as a likely target for these effects.

An adaptive CSP filter to investigate user independence in a 3-class MI-BCI paradigm.

This paper describes the implementation of a Brain Computer Interface (BCI) scheme using a common spatial patterns (CSP) filter in combination with a Recursive Least Squares (RLS) approach to iteratively update the coefficients of the CSP filter. The proposed adaptive CSP (ACSP) algorithm is made more robust by introducing regularization using Diagonal Loading (DL), and thus will be able to significantly reduce the length of training sessions when introducing new patients to the BCI system. The system is tested on a 4-class multi-limb motor imagery (MI) data set from the BCI competition IV (2a), and a more complex single limb 3-class MI dataset recorded in-house. The latter dataset is produced to mimic an upper limb rehabilitation session, e.g., after stroke. The findings indicate that when extensive calibration data is available, the ACSP performs comparably to the CSP (kappa value of 0.523 and 0.502, respectively, for the 4-class problem); for reduced calibration sessions, the ACSP significantly improved the performance of the system (up to 4-fold). The proposed paradigm proved feasible and the ACSP algorithm seems to enable a user or semi user independent scenario, where the need for long system calibration sessions without feedback is eliminated.

Radiation of the Tnt1 retrotransposon superfamily in three Solanaceae genera.

BACKGROUND: Tnt1 was the first active plant retrotransposon identified in tobacco after nitrate reductase gene disruption. The Tnt1 superfamily comprises elements from Nicotiana (Tnt1 and Tto1) and Lycopersicon (Retrolyc1 and Tlc1) species. The study presented here was conducted to characterise Tnt1-related sequences in 20 wild species of Solanum and five cultivars of Solanum tuberosum. RESULTS: Tnt1-related sequences were amplified from total genomic DNA using a PCR-based approach. Purified fragments were cloned and sequenced, and clustering analysis revealed three groups that differ in their U3 region. Using a network approach with a total of 453 non-redundant sequences isolated from Solanum (197), Nicotiana (140) and Lycopersicon (116) species, it is demonstrated that the Tnt1 superfamily can be treated as a population to resolve previous phylogenetic multifurcations. The resulting RNAseH network revealed that sequences group according to the Solanaceae genus, supporting a strong association with the host genome, whereas tracing the U3 region sequence association characterises the modular evolutionary pattern within the Tnt1 superfamily. Within each genus, and irrespective of species, nearly 20% of Tnt1 sequences analysed are identical, indicative of being part of an active copy. The network approach enabled the identification of putative "master" sequences and provided evidence that within a genus these master sequences are associated with distinct U3 regions. CONCLUSION: The results presented here support the hypothesis that the Tnt1 superfamily was present early in the evolution of Solanaceae. The evidence also suggests that the RNAseH region of Tnt1 became fixed at the host genus level whereas, within each genus, propagation was ensured by the diversification of the U3 region. Different selection pressures seemed to have acted on the U3 and RNAseH modules of ancestral Tnt1 elements, probably due to the distinct functions of these regions in the retrotransposon life cycle, resulting in both co evolution and adaptation of the element population with its host.

Genetic divergence between two phenotypically distinct bottlenose dolphin ecotypes suggests separate evolutionary trajectories.

Due to their worldwide distribution and occupancy of different types of environments, bottlenose dolphins display considerable morphological variation. Despite limited understanding about the taxonomic identity of such forms and connectivity among them at global scale, coastal (or inshore) and offshore (or oceanic) ecotypes have been widely recognized in several ocean regions. In the Southwest Atlantic Ocean (SWA), however, there are scarce records of bottlenose dolphins differing in external morphology according to habitat preferences that resemble the coastal-offshore pattern observed elsewhere. The main aim of this study was to analyze the genetic variability, and test for population structure between coastal (n = 127) and offshore (n = 45) bottlenose dolphins sampled in the SWA to assess whether their external morphological distinction is consistent with genetic differentiation. We used a combination of mtDNA control region sequences and microsatellite genotypes to infer population structure and levels of genetic diversity. Our results from both molecular marker types were congruent and revealed strong levels of structuring (microsatellites FST = 0.385, p < .001; mtDNA FST =  0.183, p < .001; ΦST = 0.385, p < .001) and much lower genetic diversity in the coastal than the offshore ecotype, supporting patterns found in previous studies elsewhere. Despite the opportunity for gene flow in potential "contact zones", we found minimal current and historical connectivity between ecotypes, suggesting they are following discrete evolutionary trajectories. Based on our molecular findings, which seem to be consistent with morphological differentiations recently described for bottlenose dolphins in our study area, we recommend recognizing the offshore bottlenose dolphin ecotype as an additional Evolutionarily Significant Unit (ESU) in the SWA. Implications of these results for the conservation of bottlenose dolphins in SWA are also discussed.

TCF7L2 polymorphism is associated with low nitric oxide release, endothelial dysfunction and enhanced inflammatory response after myocardial infarction.

BACKGOUND: The favorable effects of insulin during myocardial infarction (MI) remain unclear due to the divergence between mechanistic studies and clinical trials of exogenous insulin administration. The rs7903146 polymorphism of the transcription factor 7-like 2 (TCF7L2) gene is associated with attenuated insulin secretion. METHODS: In non-diabetic patients with ST-elevation MI (STEMI), using such a model of genetically determined down-regulation of endogenous insulin secretion we investigated the change in plasma insulin, C-peptide, interleukin-2 (IL-2), C-reactive protein (CRP), and nitric oxide (NOx) levels between admission (D1) and the fifth day after MI (D5). Coronary angiography and flow-mediated dilation (FMD) were performed at admission and 30 days after MI, respectively. Homeostasis Model Assessment estimated insulin secretion (HOMA2%ß) and insulin sensitivity (HOMA2%S). RESULTS: Although glycemia did not differ between genotypes, carriers of the T-allele had lower HOMA2%ß and higher HOMA2%S at both D1 and D5. As compared with non-carriers, T-allele carriers had higher plasma IL-2 and CRP at D5, higher intracoronary thrombus grade, lower FMD and NOx change between D1 and D5 and higher 30-day mortality. CONCLUSION: In non-diabetic STEMI patients, the rs7903146 TCF7L2 gene polymorphism is associated with lower insulin secretion, worse endothelial function, higher coronary thrombotic burden, and higher short-term mortality. GENERAL SIGNIFICANCE: During the acute phase of MI, a lower capacity of insulin secretion may influence clinical outcome.

Glycosylated hemoglobin is associated with decreased endothelial function, high inflammatory response, and adverse clinical outcome in non-diabetic STEMI patients.

OBJECTIVE: Chronic dysglycemia was recently identified as a predictor for adverse outcomes in patients with ST-elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention. Data for non-diabetic patients who underwent thrombolysis is scarce. In this context, we aimed to study the effect of HbA1c on cardiovascular outcome after STEMI. METHODS: A prospective cohort of 326 non-diabetic STEMI individuals was used for the analyses. We measured plasma glucose, hemoglobin A1c [HbA1c], lipid profile, C-reactive protein (CRP), and nitrate/nitrite (NOx) upon admission and five days after STEMI (D5). Flow-mediated dilation (FMD) was performed 30 days after STEMI. During clinical follow-up, we assessed patients for incident diabetes (progression to HbA1c ≥ 6.5%) and major adverse cardiac events (MACE), defined as a composite of fatal and non-fatal MI, sudden cardiac death, and angina requiring hospitalization. RESULTS: Using ROC-curve analysis, a 5.8% HbA1c best predicted MACE with a sensitivity of 75% and specificity of 53% (AUC 0.673, p = 0.001). Patients were categorized as high HbA1c if ≥ 5.8% and low HbA1c if <5.8%. Compared with patients with low HbA1c, those with high HbA1c presented with 20% higher CRP-D5 (p = 0.009) and 19% higher ΔCRP (p = 0.01), a 32% decrease in ΔNOx (p < 0.001), and 33% lower FMD (p < 0.001). After a median follow-up of 1.9 (1.1-2.8) years, patients with high HbA1c had more incident diabetes (HR 2.3 95% CI 1.01-5.2; p = 0.048) and MACE (HR 3.32 95% CI 1.09-10.03; p = 0.03). CONCLUSION: Non-diabetic STEMI patients with high HbA1c present with decreased endothelial function and increased inflammatory response and long-term risk of MACE.

Face pictures reduce behavioural, autonomic, endocrine and neural indices of stress and fear in sheep.

Faces are highly emotive stimuli and we find smiling or familiar faces both attractive and comforting, even as young babies. Do other species with sophisticated face recognition skills, such as sheep, also respond to the emotional significance of familiar faces? We report that when sheep experience social isolation, the sight of familiar sheep face pictures compared with those of goats or inverted triangles significantly reduces behavioural (activity and protest vocalizations), autonomic (heart rate) and endocrine (cortisol and adrenaline) indices of stress. They also increase mRNA expression of activity-dependent genes (c-fos and zif/268) in brain regions specialized for processing faces (temporal and medial frontal cortices and basolateral amygdala) and for emotional control (orbitofrontal and cingulate cortex), and reduce their expression in regions associated with stress responses (hypothalamic paraventricular nucleus) and fear (central and lateral amygdala). Effects on face recognition, emotional control and fear centres are restricted to the right brain hemisphere. Results provide evidence that face pictures may be useful for relieving stress caused by unavoidable social isolation in sheep, and possibly other animal species, including humans. The finding that sheep, like humans, appear to have a right brain hemisphere involvement in the control of negative emotional experiences also suggests that functional lateralization of brain emotion systems may be a general feature in mammals.