Comparison of different methods of screening for preterm pre-eclampsia: cohort study.

OBJECTIVE: To compare the predictive performance for pre-eclampsia (PE) of three different first-trimester mathematical models of screening, which combine maternal risk factors with mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF), and two risk scoring systems, based on NICE and ACOG recommendations. METHODS: This was a prospective cohort study performed in eight fetal-medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with singleton pregnancies and non-malformed live fetuses attending their routine ultrasound examination at 11+0 to 13+6 weeks' gestation were invited to participate in the study. Maternal characteristics and medical history were recorded and measurements of MAP, UtA-PI, serum PlGF and pregnancy associated plasma protein-A (PAPP-A) were converted into multiples of the median (MoM). Risks for term, preterm-PE (< 37 weeks' gestation) and early-PE (< 34 weeks' gestation) were calculated according to the FMF competing risks model, the Crovetto et al., logistic regression model, and Serra et al., Gaussian model. Patient classification based on NICE and ACOG guidelines was also performed. We estimated detection rates (DR) with their 95% confidence intervals (CIs) at a fixed 10% screen positive rate (SPR), as well as the area under the receiver operating characteristic curve (AUROC) for preterm-PE, early-PE, and all PE for the three mathematical models. For the scoring systems, we calculated DR and SPR. Risk calibration was also assessed. RESULTS: The study population comprised of 10,110 singleton pregnancies, including 32 (0.3%) that developed early-PE, 72 (0.7%) that developed preterm-PE and 230 (2.3%) of any PE. At fixed 10% SPR, the FMF, Crovetto et al., and Serra et al., detected 82.7% (95% CI, 69.6 to 95.8%), 73.8% (95% CI, 58.7 to 88.9%), and 79.8% (95% CI, 66.1 to 93.5%) of early-PE; 72.7% (95% CI, 62.9 to 82.6%), 69.2% (95% CI, 58.8 to 79.6%), and 74.1% (95% CI, 64.2 to 83.9%) of preterm-PE and 55.1% (95% CI, 48.8 to 61.4%), 47.1% (95% CI, 40.6 to 53.5%), and 53.9% (95% CI, 47.4 to 60.4%) of all PE, respectively. The best correlation between predicted and observed cases was achieved by the FMF model, with an AUROC of 0.911 (95% CI, 0.879 to 0.943), a slope of 0.983 (95% CI, 0.846-1.120) and an intercept of 0.154 (95% CI, -0.091 to 0.397). The NICE criteria identified 46.7% (95% CI, 35.3 to 58.0%) of preterm-PE at 11% SPR and ACOG criteria identified 65.9% (95% CI, 55.4 to 76.4%) of preterm-PE at 33.8% SPR. CONCLUSIONS: The best performance of screening for preterm-PE is achieved by mathematical models that combine maternal factors with MAP, UtA-PI and PlGF, as compared to risk-scoring systems like NICE or ACOG criteria. While all three algorithms show similar results in terms of overall prediction, the FMF model showed the best performance at the individual level. This article is protected by copyright. All rights reserved.

Caracterización metabólica de los cambios pulmonares estructurales en pacientes con hallazgos incidentales sugestivos de neumonía por COVID-19 en estudios 18F-FDG PET/CT. Perspectivas fisiopatológicas de imágenes multimodales obtenidas durante la pandemia / Metabolic characterization of structural lung changes in patients with findings suggestive of incidental COVID-19 pneumonia on 18F-FDG PET/CT: Pathophysiological insights from multimodal images obtained during the pandemic

Objetivo Evaluar la captación metabólica de diferentes signos tomográficos observados en pacientes con hallazgos estructurales incidentales sugestivos de neumonía por COVID-19 mediante PET/TC con 18F-FDG. Material y métodos Se analizaron retrospectivamente 596 estudios PET/TC realizados desde el 21 de febrero de 2020 hasta el 17 de abril de 2020. Tras excluir 37 exploraciones (trazadores PET diferentes a la 18F-FDG y estudios cerebrales), se evaluó la actividad metabólica de varios cambios estructurales integrados en la puntuación CO-RADS mediante el SUVmáx de estudios multimodales con 18F-FDG. Resultados Se incluyeron 43 pacientes r COVID-19 en la 18F-FDG PET/TC (edad media: 68±12,3 años, 22 varones). Los valores de SUVmáx fueron mayores en los pacientes con categorías CO-RADS 5-6 respecto a los de categorías CO-RADS inferiores (6,1±3,0 vs. 3,6±2,1, p=0,004). En los pacientes con CO-RADS 5-6, las opacidades en vidrio deslustrado, la bilateralidad y las consolidaciones mostraron valores de SUVmáx más elevados (valores de la p de 0,01, 0,02 y 0,01, respectivamente). La distribución parcheada y el patrón crazy paving también se asociaron a valores de SUVmáx más elevados (valores de p de 0,002 y 0,01). Tras el análisis multivariable, el SUVmáx se asoció significativamente con un diagnóstico estructural positivo de neumonía por COVID-19 (odds ratio=0,63, intervalo de confianza del 95%=0,41-0,90; p=0,02). La curva ROC del modelo de regresión destinado a confirmar o descartar el diagnóstico estructural de neumonía por COVID-19 mostró un AUC de 0,77 (error estándar=0,072; p=0,003). Conclusiones En aquellos pacientes remitidos a 18F-FDG PET/TC por indicaciones oncológicas y no oncológicas estándar (43/559; 7,7%) durante la pandemia, la obtención de imágenes multimodales es una herramienta útil durante la detección incidental de neumonía (AU)

Purpose To evaluate the metabolic uptake of different tomographic signs observed in patients with incidental structural findings suggestive of COVID-19 pneumonia through 18F-FDG PET/CT. Material and methods We retrospectively analyzed 596 PET/CT studies performed from February 21, 2020 to April 17, 2020. After excluding 37 scans (non-18F-FDG PET tracers and brain studies), we analyzed the metabolic activity of several structural changes integrated in the CO-RADS score using the SUVmax of multimodal studies with 18F-FDG. Results Forty-three patients with 18F-FDG PET/CT findings suggestive of COVID-19 pneumonia were included (mean age: 68±12.3 years, 22 male). SUVmax values were higher in patients with CO-RADS categories 5–6 than in those with lower CO-RADS categories (6.1±3.0 vs. 3.6±2.1, p=0.004). In patients with CO-RADS 5–6, ground-glass opacities, bilaterality and consolidations exhibited higher SUVmax values (p-values of 0.01, 0.02 and 0.01, respectively). Patchy distribution and crazy paving pattern were also associated with higher SUVmax (p-values of 0.002 and 0.01). After multivariate analysis, SUVmax was significantly associated with a positive structural diagnosis of COVID-19 pneumonia (odds ratio=0.63, 95% confidence interval=0.41–0.90; p=0.02). The ROC curve of the regression model intended to confirm or rule out the structural diagnosis of COVID-19 pneumonia showed an AUC of 0.77 (standard error=0.072, p=0.003). Conclusions In those patients referred for standard oncologic and non-oncologic indications (43/559; 7.7%) during pandemic, imaging with 18F-FDG PET/CT is a useful tool during incidental detection of COVID-19 pneumonia. Several CT findings characteristic of COVID-19 pneumonia, specifically those included in diagnostic CO-RADS scores (5–6), were associated with higher SUVmax values (AU)

Evaluation of rectus abdominis muscle strength and width of hernia defect in patients undergoing incisional hernia surgery.

BACKGROUND: The aim of this study was to analyze the strength status of the rectus abdominis muscle in patients with incisional hernia and the relationship between the width of the hernia defect and the strength of the rectus abdominis muscle. METHODS: This is a observational cohort study of patients with medial line incisional hernia (July-October 2022), classified as W2 according to the European Hernia Society (EHS). The data collected were demographic and clinical characteristics related to hernia, and measure of the rectus abdominis muscle strength using an isokinetic dynamometer and a strain gauge. We analyzed the relationship between hernia width and rectus abdominis muscle strength with correlation tests to adjustment by age, sex, BMI, and body composition. RESULTS: A total of 40 patients (64% female) with a mean age of 57.62 years (SD 11) were enrolled in the study. The mean BMI was 29.18 (SD 5.06), with a mean percentage of fat mass of 37.8% (SD 8.47) and a mean percentage of muscle mass of 60.33% (SD 6.43). The maximum width of the hernia defect was 6.59 cm (SD 1.54). In the male group, the mean bending force moment (ISOK_PT) was 94.01 Nw m (SD 34.58), bending force moment relative to body weight (ISOK_PT_Weight) was 103.32 Nw m (SD 37.48), and peak force (PK_90) was 184.71 N (SD 47.01). In the female group, these values were 58.11 Nw m (SD 29.41), 66.48 Nw m (SD 32.44), and 152.50 N (SD 48.49), respectively. Statistically significant differences were observed in the relationship between the data obtained with the isokinetic dynamometer and sex (p = 0.002), as well as between the data obtained with the isokinetic dynamometer and age (p = 0.006). Patients in the 90th percentile (P90) of rectus abdominis muscle strength also had smaller hernia defect widths (p = 0.048). CONCLUSIONS: In this study, age and sex were identified as the most statistically significant predictor variables for rectus abdominis muscle strength. The width of the hernia defect exhibited a trend towards statistical significance.

Metabolic characterization of structural lung changes in patients with findings suggestive of incidental COVID-19 pneumonia on 18F-FDG PET/CT. Pathophysiological insights from multimodal images obtained during the pandemic.

PURPOSE: To evaluate the metabolic uptake of different tomographic signs observed in patients with incidental structural findings suggestive of COVID-19 pneumonia through 18F-FDG PET/CT. MATERIALS AND METHODS: We retrospectively analyzed 596 PET/CT studies performed from February 21, 2020 to April 17, 2020. After excluding 37 scans (non-18F-FDG PET tracers and brain studies), we analyzed the metabolic activity of several structural changes integrated in the CO-RADS score using the SUVmax of multimodal studies with 18F-FDG. RESULTS: Forty-three patients with 18F-FDG PET/CT findings suggestive of COVID-19 pneumonia were included (mean age: 68±12.3 years, 22 male). SUVmax values were higher in patients with CO-RADS categories 5-6 than in those with lower CO-RADS categories (6.1±3.0 vs. 3.6±2.1, p=0.004). In patients with CO-RADS 5-6, ground-glass opacities, bilaterality and consolidations exhibited higher SUVmax values (p-values of 0.01, 0.02 and 0.01, respectively). Patchy distribution and crazy paving pattern were also associated with higher SUVmax (p-values of 0.002 and 0.01). After multivariate analysis, SUVmax was significantly associated with a positive structural diagnosis of COVID-19 pneumonia (odds ratio=0.63, 95% confidence interval=0.41-0.90; p=0.02). The ROC curve of the regression model intended to confirm or rule out the structural diagnosis of COVID-19 pneumonia showed an AUC of 0.77 (standard error=0.072, p=0.003). CONCLUSIONS: In those patients referred for standard oncologic and non-oncologic indications (43/559; 7.7%) during pandemic, imaging with 18F-FDG PET/CT is a useful tool during incidental detection of COVID-19 pneumonia. Several CT findings characteristic of COVID-19 pneumonia, specifically those included in diagnostic CO-RADS scores (5-6), were associated with higher SUVmax values.

Human femur fracture by mechanical compression: Towards the repeatability of bone fracture acquisition.

The increase in life expectancy combined with greater bone fragility over the years is causing a rise in the bone fracture cases. Femur fractures are the most important due to their high mortality rate. This multidisciplinary work is carried out in this context and focuses on the experimental reproduction of human femur fractures by compression. We describe a sequence of steps supervised by orthopaedic surgeons for the correct arrangement of specimens on the system set up to perform the experiment. The device applies force by compression until the human bone is fractured. All tests performed have been monitored and evaluated from different knowledge perspectives. The results obtained have demonstrated the repeatability of the fracture type in a controlled environment as well as identifying the main features involved in this process. In addition, the fractured bones have been digitized to analyze the fracture zone to recreate and evaluate future simulations.

Combined effect of physical exercise and hormone replacement therapy on cardiovascular and metabolic health in postmenopausal women: A systematic review and meta-analysis.

The cardioprotective effect of postmenopausal hormone replacement therapy (HRT) has been demonstrated in several studies. Similarly, physical exercise has yielded positive results. However, the effects of their combination remain inconclusive. This review describes the combined effects of physical exercise and hormone therapy on cardiovascular and metabolic health in postmenopausal women. We searched the Scopus, Web of Science, PubMed, and Embase databases and included randomized controlled trials published up to December 2021 on the combined effects of physical exercise and hormone therapy on cardiovascular and metabolic health in postmenopausal women. We identified 148 articles, of which only seven met the inclusion criteria (386 participants; 91 [23%] HRT + exercise; 104 [27%] HRT; 103 [27%] exercise; 88 [23%] placebo). The combined treatment further decreased systolic blood pressure (SBP) compared to the isolated effect of aerobic training (AT) (mean difference [MD]=-1.69; 95% confidence interval [CI]=-2.65 to -0.72, n=73). Nevertheless, it attenuated the decrease in diastolic blood pressure (DBP) (MD=0.78; 95%CI: 0.22-1.35, n=73), and the increase in peak oxygen consumption (VO2 peak) promoted by exercise (AT + HRT=2.8±1.4 vs AT + placebo=5.8±3.4, P=0.02). The combination of AT and oral HRT improved SBP. However, AT alone seemed to have a better effect on physical fitness and DBP in postmenopausal women.

Temperature inhomogeneities cause the abundance discrepancy in H II regions.

H II regions are ionized nebulae surrounding massive stars. They exhibit a wealth of emission lines that form the basis for estimation of chemical composition. Heavy elements regulate the cooling of interstellar gas, and are essential to the understanding of several phenomena such as nucleosynthesis, star formation and chemical evolution1,2. For over 80 years3, however, a discrepancy exists of a factor of around two between heavy-element abundances derived from collisionally excited lines and those from the weaker recombination lines, which has thrown our absolute abundance determinations into doubt4,5. Here we report observational evidence that there are temperature inhomogeneities within the gas, quantified by t2 (ref. 6). These inhomogeneities affect only highly ionized gas and cause the abundance discrepancy problem. Metallicity determinations based on collisionally excited lines must be revised because these may be severely underestimated, especially in regions of lower metallicity such as those recently observed with the James Webb Space Telescope in high-z galaxies7-9. We present new empirical relations for estimation of temperature and metallicity, critical for a robust interpretation of the chemical composition of the Universe over cosmic time.

Performance of first-trimester combined screening for preterm pre-eclampsia: findings from cohort of 10 110 pregnancies in Spain.

OBJECTIVE: To evaluate the diagnostic accuracy of the Fetal Medicine Foundation (FMF) competing-risks model, incorporating maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and placental growth factor (PlGF) (the 'triple test'), for the prediction at 11-13 weeks' gestation of preterm pre-eclampsia (PE) in a Spanish population. METHODS: This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with a singleton pregnancy and a non-malformed live fetus attending a routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate. Maternal demographic characteristics and medical history were recorded and MAP, UtA-PI, serum PlGF and pregnancy-associated plasma protein-A (PAPP-A) were measured following standardized protocols. Treatment with aspirin during pregnancy was also recorded. Raw values of biomarkers were converted into multiples of the median (MoM), and audits were performed periodically to provide regular feedback to operators and laboratories. Patient-specific risks for term and preterm PE were calculated according to the FMF competing-risks model, blinded to pregnancy outcome. The performance of screening for PE, taking into account aspirin use, was assessed by calculating the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed screen-positive rate (SPR). Risk calibration of the model was assessed. RESULTS: The study population comprised 10 110 singleton pregnancies, including 72 (0.7%) that developed preterm PE. In the preterm PE group, compared to those without PE, median MAP MoM and UtA-PI MoM were significantly higher, and median serum PlGF MoM and PAPP-A MoM were significantly lower. In women with PE, the deviation from normal in all biomarkers was inversely related to gestational age at delivery. Screening for preterm PE by a combination of maternal characteristics and medical history with MAP, UtA-PI and PlGF had a DR, at 10% SPR, of 72.7% (95% CI, 62.9-82.6%). An alternative strategy of replacing PlGF with PAPP-A in the triple test was associated with poorer screening performance for preterm PE, giving a DR of 66.5% (95% CI, 55.8-77.2%). The calibration plot showed good agreement between predicted risk and observed incidence of preterm PE, with a slope of 0.983 (95% CI, 0.846-1.120) and an intercept of 0.154 (95% CI, -0.091 to 0.397). CONCLUSIONS: The FMF model is effective in predicting preterm PE in the Spanish population at 11-13 weeks' gestation. This method of screening is feasible to implement in routine clinical practice, but it should be accompanied by a robust audit and monitoring system, in order to maintain high-quality screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Search for Gamma-Ray Spectral Lines from Dark Matter Annihilation up to 100 TeV toward the Galactic Center with MAGIC.

Linelike features in TeV γ rays constitute a "smoking gun" for TeV-scale particle dark matter and new physics. Probing the Galactic Center region with ground-based Cherenkov telescopes enables the search for TeV spectral features in immediate association with a dense dark matter reservoir at a sensitivity out of reach for satellite γ-ray detectors, and direct detection and collider experiments. We report on 223 hours of observations of the Galactic Center region with the MAGIC stereoscopic telescope system reaching γ-ray energies up to 100 TeV. We improved the sensitivity to spectral lines at high energies using large-zenith-angle observations and a novel background modeling method within a maximum-likelihood analysis in the energy domain. No linelike spectral feature is found in our analysis. Therefore, we constrain the cross section for dark matter annihilation into two photons to ⟨σv⟩≲5×10^{-28} cm^{3} s^{-1} at 1 TeV and ⟨σv⟩≲1×10^{-25} cm^{3} s^{-1} at 100 TeV, achieving the best limits to date for a dark matter mass above 20 TeV and a cuspy dark matter profile at the Galactic Center. Finally, we use the derived limits for both cuspy and cored dark matter profiles to constrain supersymmetric wino models.

Intraoperative metabolic changes associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) causes considerable hemodynamic, respiratory, and metabolic changes during the perioperative period. OBJECTIVES: To evaluate metabolic changes associated with this procedure. Understanding perioperative factors and their association with morbidity may improve the perioperative management of patients undergoing this treatment. METHODS: A retrospective review of a prospectively maintained database was performed. All consecutive unselected patients who underwent CRS plus HIPEC between January 2018 and December 2020 (n = 219) were included. RESULTS: The mean age was 58 ± 11.7 years and 167 (76.3%) were female. The most frequent histology diagnosis was serous ovarian carcinoma 49.3% (n = 108) and colon carcinoma 36.1% (n = 79). Mean peritoneal cancer index was 14.07 ± 10.47. There were significant variations in pH, lactic acid, sodium, potassium, glycemia, bicarbonate, excess bases, and temperature (p < 0.05) between the pre-HIPEC and post-HIPEC periods. The closed HIPEC technique resulted in higher levels of temperature than the open technique (p < 0.05). Age, potassium level post-HIPEC potassium level, and pre-HIPEC glycemia were identified as prognostic factors for morbidity in multivariate analysis. CONCLUSION: The administration of HIPEC after CRS causes significant changes in internal homeostasis. Although the closed technique causes a greater increase in temperature, it is not related to higher morbidity rates. The patient's age, post-HIPEC potassium level, and pre-HIPEC glycemia are predictive factors for morbidity.

Combined effect of physical exercise and hormone replacement therapy on cardiovascular and metabolic health in postmenopausal women: A systematic review and meta-analysis

The cardioprotective effect of postmenopausal hormone replacement therapy (HRT) has been demonstrated in several studies. Similarly, physical exercise has yielded positive results. However, the effects of their combination remain inconclusive. This review describes the combined effects of physical exercise and hormone therapy on cardiovascular and metabolic health in postmenopausal women. We searched the Scopus, Web of Science, PubMed, and Embase databases and included randomized controlled trials published up to December 2021 on the combined effects of physical exercise and hormone therapy on cardiovascular and metabolic health in postmenopausal women. We identified 148 articles, of which only seven met the inclusion criteria (386 participants; 91 [23%] HRT + exercise; 104 [27%] HRT; 103 [27%] exercise; 88 [23%] placebo). The combined treatment further decreased systolic blood pressure (SBP) compared to the isolated effect of aerobic training (AT) (mean difference [MD]=-1.69; 95% confidence interval [CI]=-2.65 to -0.72, n=73). Nevertheless, it attenuated the decrease in diastolic blood pressure (DBP) (MD=0.78; 95%CI: 0.22-1.35, n=73), and the increase in peak oxygen consumption (VO2 peak) promoted by exercise (AT + HRT=2.8±1.4 vs AT + placebo=5.8±3.4, P=0.02). The combination of AT and oral HRT improved SBP. However, AT alone seemed to have a better effect on physical fitness and DBP in postmenopausal women.

Role of the melanocortin system in zebrafish skin physiology.

The agouti-signaling protein (ASIP) acts as both a competitive antagonist and inverse agonist of melanocortin receptors which regulate dorsal-ventral pigmentation patterns in fish. However, the potential role of ASIP in the regulation of additional physiological pathways in the skin is unknown. The skin plays a crucial role in the immune function, acting as a physical limitation against infestation and also as a chemical barrier due to its ability to synthesize and secrete mucus and many immune effector proteins. In this study, the putative role of ASIP in regulating the immune system of skin has been explored using a transgenic zebrafish model overexpressing the asip1 gene (ASIPzf). Initially, the structural changes in skin induced by asip1 overexpression were studied, revealing that the ventral skin of ASIPzf was thinner than that of wild type (WT) animals. A moderate hypertrophy of mucous cells was also found in ASIPzf. Histochemical studies showed that transgenic animals appear to compensate for the lower number of cell layers by modifying the mucus composition and increasing lectin affinity and mucin content in order to maintain or improve protection against microorganism adhesion. ASIPzf also exhibit higher protein concentration under crowding conditions suggesting an increased mucus production under stressful conditions. Exposure to bacterial lipopolysaccharide (LPS) showed that ASIPzf exhibit a faster pro-inflammatory response and increased mucin expression yet severe skin injures and a slight increase in mortality was observed. Electrophysiological measurements show that the ASIP1 genotype exhibits reduced epithelial resistance, an indicator of reduced tissue integrity and barrier function. Overall, not only are ASIP1 animals more prone to infiltration and subsequent infections due to reduced skin epithelial integrity, but also display an increased inflammatory response that can lead to increased skin sensitivity to external infections.

Increased frequency of CD14+HLA-DR-/low cells in type 2 diabetes patients with poor glycemic control.

AIMS: Type 2 diabetes (T2DM) is associated with alterations of the immune response and T2DM patients have an increased risk for infections and certain sorts of cancers. Although CD14+HLA-DR-/low cells have emerged as important mediators of immunosuppression in several pathologies, including cancer and non-malignant diseases, the presence of these cells in T2DM is not fully characterized. METHODS: In this study, we evaluated the frequency of CD14+HLA-DR-/low cells in non-obese T2DM patients and their association with glycemic control. Peripheral blood mononuclear cells were isolated from healthy controls (HC, n = 24) and non-obese T2DM patients (n = 25), the population was evaluated by flow cytometry, and an analysis of correlation between cell frequencies and clinical variables was performed. RESULTS: CD14+HLA-DR-/low monocytes were expanded in patients with T2DM compared to HC regardless of weight. Among the subjects with T2DM, the frequency of CD14+HLA-DR-/low was higher in patients with poor glycemic control (HbA1c > 9%) compared to those with better glycemic control (HbA1c < 9%) and, positively correlated with the years since the diagnosis of T2DM, the age of the patients and the glycemic index. CONCLUSIONS: An increased frequency of CD14+HLA-DR-/low cells in the blood of T2DM patients was recorded. The influence of hyperglycemia seems to be independent of obesity, but related to glycemic control and age.

Protein oxidation marker, α-amino adipic acid, impairs proteome of differentiated human enterocytes: Underlying toxicological mechanisms.

Protein oxidation and oxidative stress are involved in a variety of health disorders such as colorectal adenomas, inflammatory bowel's disease, neurological disorders and aging, among others. In particular, the specific final oxidation product from lysine, the α-amino adipic acid (α-AA), has been found in processed meat products and emphasized as a reliable marker of type II diabetes and obesity. Currently, the underlying mechanisms of the biological impairments caused by α-AA are unknown. To elucidate the molecular basis of the toxicological effect of α-AA, differentiated human enterocytes were exposed to dietary concentrations of α-AA (200 µM) and analyzed by flow cytometry, protein oxidation and proteomics using a Nanoliquid Chromatography-Orbitrap MS/MS. Cell viability was significantly affected by α-AA (p < 0.05). The proteomic study revealed that α-AA was able to alter cell homeostasis through impairment of the Na+/K+-ATPase pump, energetic metabolism, and antioxidant response, among other biological processes. These results show the importance of dietary oxidized amino acids in intestinal cell physiology and open the door to further studies to reveal the impact of protein oxidation products in pathological conditions.

Proteomics reveal the protective effects of chlorogenic acid on Enterococcus faecium Q233 in a simulated pro-oxidant colonic environment.

Certain phytochemicals have been found to promote the beneficial effects of probiotic bacteria although the molecular mechanisms of such interactions are poorly understood. The objective of the present study was to evaluate the impact of the exposure to 0.5 mM chlorogenic acid (CA) on the redox status and proteome of Enterococcus faecium isolated from cheese and challenged with 2.5 mM hydrogen peroxide (H2O2). The bacterium was incubated in anaerobic conditions for 48 h at 37 °C. CA exposure led to a more intense oxidative stress and accretion of bacterial protein carbonyls than those induced by H2O2. The oxidative damage to bacterial proteins was even more severe in the bacterium treated with both CA and H2O2, yet, such combination led to a strengthening of the antioxidant defenses, namely, a catalase-like activity. The proteomic study indicated that H2O2 caused a decrease in energy supply and the bacterium responded by reinforcing the membrane and wall structures and counteracting the redox and pH imbalance. CA stimulated the accretion of proteins related to translation and transcription regulators, and hydrolases. This phytochemical was able to counteract certain proteomic changes induced by H2O2 (i.e. increase of ATP binding cassete (ABC) transporter complex) and cause the increase of Rex, a redox-sensitive protein implicated in controlling metabolism and responses to oxidative stress. Although this protection should be confirmed under in vivo conditions, such effects point to benefits in animals or humans affected by disorders in which oxidative stress plays a major role.

Role of aerobic physical training on cardiac autonomic and morphophysiological dysfunction in hypertensive rats subjected to ovarian hormone deprivation.

Here we investigated the effects of physical training on cardiovascular autonomic control and cardiac morphofunctional parameters in spontaneously hypertensive rats (SHRs) subjected to ovarian hormone deprivation. Forty-eight 10-week-old SHRs were divided into two groups: ovariectomized (OVX, n=24) and sham (SHAM, n=24). Half of each group (n=12) was trained by swimming for 12 weeks (OVX-T and SHAM-T). Cardiac morphology and functionality were assessed using echocardiography, and autonomic parameters were assessed using double pharmacological autonomic block, baroreflex sensitivity (BRS), and analyses of heart rate variability (HRV) and blood pressure variability (BPV). Ovariectomy did not influence the cardiac autonomic tonus balance unlike physical training, which favored greater participation of the vagal autonomic tonus. Ovariectomy and aerobic physical training did not modify HRV and BRS, unlike BPV, for which both methods reduced low-frequency oscillations, suggesting a reduction in sympathetic vascular modulation. Untrained ovariectomized animals showed a reduced relative wall thickness (RWT) and increased diastolic and systolic volumes and left ventricular diameters, resulting in increased stroke volume. Trained ovariectomized animals presented reduced posterior wall thickness and RWT as well as increased final diastolic diameter, left ventricular mass, and stroke volume. Ovarian hormone deprivation in SHRs promoted morphofunctional adaptations but did not alter the evaluation of cardiac autonomic parameters. In turn, aerobic physical training contributed to a more favorable cardiac autonomic balance to the vagal autonomic component and promoted morphological adaptations but had little effect on cardiac functionality.

A single dose of dietary nitrate supplementation protects against endothelial ischemia-reperfusion injury in early postmenopausal women.

The onset of menopause and accompanying changes to ovarian hormones often precedes endothelial dysfunction in women. In particular, accelerated impairments in macrovascular and microvascular function coincide with the loss of estrogen, as does impaired endothelial responses to ischemia-reperfusion (IR) injury. In healthy, early postmenopausal women (n = 12; 3.9 ± 1.5 years since menopause) we tested the hypothesis that acute dietary nitrate (NO3-) supplementation would improve endothelial function and attenuate the magnitude of endothelial dysfunction following whole-arm IR in comparison with placebo. In this randomized, double-blind, placebo-controlled, crossover study we tested participants before and after NO3--rich (BRnitrate) and NO3--depleted (BRplacebo) beetroot juice (BR) consumption, as well as following IR injury, and 15 min after IR to assess recovery. Analyses with repeated-measures general linear models revealed a condition × time interaction for brachial artery flow-mediated dilation (FMD; P = 0.04), and no interaction effect was found for the near-infrared spectroscopy-derived reperfusion slope (P = 0.86). Follow-up analysis showed a significant decline in FMD following IR injury with BRplacebo in comparison with all other timepoints (all, P < 0.05), while this decline was not present with BRnitrate (all, P > 0.05). Our findings demonstrate that a single dose of dietary NO3- minimizes IR-induced macrovascular endothelial dysfunction in healthy, early postmenopausal women, but does not improve resting macrovascular and microvascular function. Trial registration number: NCT03644472. Novelty: In healthy, early postmenopausal women, a single dose of NO3--rich BR can protect against IR-induced endothelial dysfunction. This protection may be due to nitric oxide bioactivity during IR rather than improved endothelial function prior to the IR protocol per se.