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Background/objectives: Metabolic dysfunction-associated fatty liver disease (MAFLD) is currently the most common cause of chronic liver disease. Systemic inflammatory status and peripheral metabolic symptoms in the clinical picture have an impact on gut commensal bacteria., Methods: Our designed clinical trial was based on a cohort of patients with MAFLD whose diet included the daily consumption of 400 g of "Navelina" oranges for 28 days, compared with a control group of patients with the same pathologic conditions whose diet did not include the consumption of oranges and other foods containing similar nutrients/micronutrients. We used 16S metataxonomics and GC/MS analyses to identify taxa and urine/fecal VOCs, respectively., Results: A set of micronutrients from the diet were inspected, and some specific fatty acids were identified as the main contributors in terms of cluster sample separation. Metataxonomics and metabolomics profiles were obtained, and a stringent statistical approach allowed for the identification of significant taxa/VOCs, which emerged from pairwise group comparisons in both fecal and urine samples., Conclusions: In conclusion, a set of taxa/VOCs can be directly referred to as a marker of dysbiosis status and other comorbidities that, together, make up the pathologic burden associated with MAFLD. The investigated variables can be a target of therapeutic strategies.

Background : Consumption of flavonoid-rich orange juice has been shown to reduce adiposity and liver steatosis in murine models of diet-induced obesity. However, little is known about the effects of whole orange intake, independent of body weight changes, on liver function and steatosis in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). The goal is to understand the direct impact of orange consumption on metabolic health. Methods : Sixty-two men and women aged 30-65 with MASLD (Controlled Attenuation Parameter, (CAP) > 275 dB/m) were randomly assigned to consume either 400 g of whole oranges or non-citrus fruits daily for 4 weeks. Baseline evaluations included medical assessments, blood tests, and body composition. Liver health was assessed using transient elastography (FibroScan ® ) for steatosis and fibrosis, conducted by blinded personnel. This clinical trial was registered at ClinicalTrials.gov (NCT05558592). Results : After 4 weeks of orange supplementation, liver steatosis decreased in the treatment group, with 70.9% showing steatosis compared to 100% in controls ( p < 0.004), indicating a 30% reduction in liver disease prevalence. There were no significant changes in fibrosis or plasma liver enzymes, though plasma gamma glutaril transferase (GGT) levels decreased significantly. Body weight, waist circumference, body composition, lipid profile, fasting glucose, insulin, and C-reactive protein levels remained unchanged. Dietary analysis revealed no change in caloric intake, but vitamins C, A, thiamine, and riboflavin increased in the orange group. Conclusions : Our findings suggest that phytochemical-rich foods, especially whole fruits like oranges, may enhance liver function as an adjunct treatment for MASLD. The notable reduction in liver steatosis prevalence occurred independently of body weight changes. Further studies are needed to investigate the long-term effects of orange supplementation on steatosis and fibrosis progression and to identify the specific bioactive compounds and mechanisms involved.

Background: Hypertensive disorders of pregnancy and fetal growth restriction share common etiopathological origins and could be caused by maternal hemodynamic maladaptation to pregnancy., Objective: The aim of our study is to evaluate if there is a correlation between maternal hemodynamic detected by UltraSonic Cardiac Output Monitor (USCOM ® ) during the first trimester and the pregnancy outcome., Study Design: We recruited a nonconsecutive series of women in the first trimester of pregnancy with no previous history of hypertensive disorders. We measured the pulsatility index uterine arteries and performed a hemodynamic evaluation by USCOM ® device. After delivery, we reported the development of hypertensive disorders or intrauterine fetal growth restriction later during gestation., Results: A total of 187 women were enrolled during the first trimester; 17 (9%) developed gestational hypertension or preeclampsia while 11 (6%) delivered a restricted growth fetus. Mean uterine artery pulsatility index above the 95th percentile was significantly more frequent in both women who developed hypertension and those with fetal growth restriction compared to controls. Hemodynamic parameters (reduced cardiac output and increased total vascular resistance) were significantly different in the group that developed hypertensive disorders, compared to uncomplicated pregnancy. ROC curves demonstrated the usefulness of uterine artery pulsatility index in the prediction of fetal growth restriction, while hemodynamic parameters were significantly associated to the development of hypertensive disorders., Conclusions: Hemodynamic maladaptation to pregnancy may predispose to the development of hypertension, while we demonstrated a significative relationship between growth restriction and mean uterine pulsatility index. Further studies are needed to assess the value of hemodynamics evaluation in screening protocols of preeclampsia.

It is generally accepted that diet-derived polyphenols are bioactive compounds with several potentially beneficial effects on human health. In general, polyphenols have several chemical structures, and the most representative are flavonoids, phenolic acids, and stilbenes. It should be noted that the beneficial effects of polyphenols are closely related to their bioavailability and bioaccessibility, as many of them are rapidly metabolized after administration. Polyphenols-with a protective effect on the gastrointestinal tract-promote the maintenance of the eubiosis of the intestinal microbiota with protective effects against gastric and colon cancers. Thus, the benefits obtained from dietary supplementation of polyphenols would seem to be mediated by the gut microbiota. Taken at certain concentrations, polyphenols have been shown to positively modulate the bacterial component, increasing Lactiplantibacillus spp. and Bifidobacterium spp. involved in the protection of the intestinal barrier and decreasing Clostridium and Fusobacterium , which are negatively associated with human well-being. Based on the diet-microbiota-health axis, this review aims to describe the latest knowledge on the action of dietary polyphenols on human health through the activity of the gut microbiota and discusses micro-encapsulation of polyphenols as a strategy to improve the microbiota.

Exosomes produced by hepatocytes upon lipotoxic insult play a relevant role in pathogenesis of nonalcoholic fatty liver disease (NAFLD), suggesting an inflammatory response by the activation of monocytes and macrophages and accelerating the disease progression. In the pathogenesis of NAFLD and liver fibrosis, the endogenous cannabinoids and their major receptors CB1 and CB2 appear to be highly involved. This study aimed at evaluating the expression of cannabinoids receptors (CB1R and CB2R) in plasma-derived exosomes extracted from patients with NAFLD, as well as investigating the in vitro effects of the circulating exosomes in cultured human HepaRG cells following their introduction into the culture medium. The results demonstrated that plasma-derived exosomes from NAFLD patients are vehicles for the transport of CB1R and are able to modulate CB receptors' expression in HepaRG cells. In particular, circulating exosomes from NAFLD patients are inflammatory drivers for HepaRG cells, acting through CB1R activation and the downregulation of CB2R. Moreover, CB1R upregulation was associated with increased expression levels of PPAR-γ, a well-known mediator of liver tissue injury. In conclusion, this study provides evidence for CB1R transport by exosomes and suggests that the in vitro effects of circulating exosomes from NAFLD patients are mediated by the expression of cannabinoid receptors.

Background: Preeclampsia is a main obstetric disease and could be caused by the inability of the woman hemodynamic system to face the cardiovascular effort required by gestation., Objective: The aim of the present study is to evaluate the correlation between maternal hemodynamic parameters detected by UltraSonic Cardiac Output Monitor (USCOM ® ) and ultrasound or biochemical parameters in women during the first-trimester screening of chromosomal abnormalities., Methods: This was a prospective observational study with 162 women enrolled during the first-trimester ultrasound, recording demographic, biochemical and ultrasound data, including the pulsatility index of uterine arteries (UTPI). Hemodynamic indices were obtained using the USCOM ® system. We also analyzed the outcomes of pregnancy of those women who delivered in our clinic., Results: As for the correlation between biochemical and ultrasound parameters, pregnancy-associated plasma protein A (PAPP-A) relates inversely with the mean UTPI ( r s -0.298, p  < .001). We also reported a statistically significant correlation between the mean UTPI and the maternal haemodynamic parameters detected by USCOM ® (higher values of mean UTPI are associated with lower values of indexed cardiac output, CO, and higher indexed peripheral resistances, TVR). When comparing women with higher UTPI and TVR or lower CO to patients who had regular values of these parameters, we noticed that between these groups there were significant differences in all the remaining hemodynamic parameters, including inotropy index and stroke volume, as well as in the biochemical values of PAPP-A. Analyzing postpartum data, if we combine the onset of hypertensive disorders and fetal growth restriction, the most predictive parameter is indexed TVR., Conclusion: Our study confirmed the correlation between PAPP-A and placental function, expressed through the determination of the pulsatility index of the uterine arteries. Moreover, we found a clear correlation between biochemical markers, placental function and maternal hemodynamics, since the first trimester of pregnancy. The inclusion of maternal hemodynamic evaluation could be useful in the screening protocols of preeclampsia. If we combine the onset of hypertensive disorders and of fetal growth restriction, the most predictive parameter is indexed total vascular resistances.

Background: The detection of increased nuchal translucency is crucial for the assessment risk of aneuploidies and other fetal anomalies., Objective: This study aimed to investigate the ability of a transverse view of the fetal head to detect increased fetal nuchal translucency at 11 to 13 weeks of gestation., Study Design: This was a prospective study enrolling a nonconsecutive series of women who attended our outpatient clinic from January 2020 to April 2021 for combined screening and were examined by operators certified by the Fetal Medicine Foundation. In each patient, nuchal translucency measurements were obtained both from a median sagittal view and from a transverse view. A second sonologist blinded to the results of the first examination obtained another measurement to assess intermethod and interobsever reproducibility., Results: A total of 1023 women were enrolled. An excellent correlation was found between sagittal and transverse nuchal translucency measurements, with a mean difference of 0.01 mm (95% confidence interval, -0.01 to 0.02). No systematic difference was found between the 2 techniques. The inter-rater reliability (intraclass correlation coefficient, 0.957; 95% confidence interval, 0.892-0.983) and intrarater reliability (intraclass correlation coefficient, 0.976; 95% confidence interval, 0.941-0.990) of axial measurements were almost perfect. Transverse measurements of 3.0 mm identified all cases with sagittal measurements of ≥3.0 with a specificity of 99.7%; transverse measurements of >3.2 mm identified all cases with sagittal measurements of 3.5 mm with a specificity of 99.7%. The time required to obtain transverse nuchal translucency measurements was considerably shorter than for sagittal measurements, particularly when the fetus had an unfavorable position., Conclusion: When the sonogram is performed by an expert sonologist, the difference in nuchal translucency measurement obtained with a transverse or sagittal plane is minimal. Increased nuchal translucency can be reliably identified by using transverse views, and in some cases, this may technically be advantageous., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Grape pomace (GP)-the major by-product of winemaking processes-still contains bioactive molecules with known beneficial properties for human health, such as an antiradical scavenging activity or an antiproliferative activity of tumors. In vitro studies have demonstrated that GP polyphenols specifically influence colon cancer cell proliferation. In addition to previously published work, we tested the phenolic compounds of Aglianico GP following an in vitro simulated gastrointestinal digestion on colorectal cancer cell lines at different degrees of differentiation. Our experiments, using HT29 and SW480 cells, confirmed the anti-proliferative effect of GP gastrointestinal digested extract and provided intriguing insights on the way it influences the cancer cell features (i.e., viability, proliferation, and apoptosis). We observed that Aglianico GP extract showed a great ability to affect cell proliferation and apoptosis. Interestingly, both HT29 and SW480 cells produced a significant increase in Bax, and a significant increase in the Bax/Bcl-2 ratio and caspase-3. The gastrointestinal digested GP extract was previously characterized both for antioxidant activity and phenolic composition. As a result, the TPC and the antioxidant activity reached high values in the Aglianico GP digested extract, and the main compounds assessed by UHPLC-DAD were anthocyanins, phenolic acids, and flavonoids. This work shed light on the use of digested GP extract as a dietary ingredient, a very sustainable source of nutritional compounds with potential health benefits for colon cancer cell proliferation.

Objectives: Up to 32% of women experience anatomic recurrence after conservative surgery for endometriomas, while pain recurs in 10-40% of cases. Long-term postoperative hormonal therapy is recommended to prevent disease recurrence. We evaluated the efficacy of long-term therapy with estroprogestins (EPs) or progestins (Ps) in preventing endometrioma recurrence, as identifiable cysts and subjective symptoms, after laparoscopic excision., Design: This retrospective cohort study included 375 women submitted to laparoscopic endometrioma excision. Women were followed up at 6 and 12 months and then yearly after surgery. Based on postoperative medical therapy, women were divided into 4 groups: nonusers, cyclic EP users, continuous EP users, and progestogen users. Materials, Setting, Methods: Anamnestic and anthropometric characteristics were collected as well as clinical and surgical data. Gynecological examination, and transvaginal and transabdominal ultrasound scans were performed. Pain (numerical rating score >5) and endometrioma recurrence at ultrasound (ovarian cyst with typical sonographic features ≥10 mm in mean diameter) were recorded at each examination. The reoperation rate in women with recurrence was investigated., Results: The median follow-up was 3.7 years with a maximum of 16.7 years. Most patients used EPs (119 cyclic and 61 continuous users), 95 used P, and 100 were nonusers. In 135 women (36%), endometriotic cyst recurrence was diagnosed, with a mean diameter of 18.7 ± 10.8 mm (range 10-55 mm). The median recurrent cyst-free time was 7.9 years (95% CI 5.8-10.8). Dysmenorrhea was the first symptom to reappear, affecting 162 patients (43.2%). Upon multivariable regression analysis, continuous users had a lower risk of relapse (OR 0.56, 95% CI 0.32-0.99), in terms of both cysts and symptom recurrence, than patients who received no medications. The reoperation rate was 16.2%., Limitations: The main limitation of this study is its retrospective design. Also, women switching therapies throughout the follow-up period were sorted into one of the study groups based on the longest treatment taken, without considering the discontinuation rates., Conclusions: Long-term EPs, administered in a continuous regimen and starting immediately after conservative surgery for endometriomas, seem to reduce the disease recurrence risk., (© 2021 S. Karger AG, Basel.)

Background: Although its efficacy is well known, the high economic cost of erythropoietin (EPO) raises the question of pharmacoeconomics in HD. An optimal Hb level with the lowest dosage of EPO seams to be correlated to the way of administration and an adequate iron supplementation., Methods: The study evaluates the influence of iron supplementation on the control of EPO-related expenses., Results: A serum ferritin level higher than 50 pg/ml in hemodialysis patients on chronic EPO therapy turned out to be adequate to keep an optimal Hb level. Our data show that this value, as far as pharmacoeconomic is concerned, is highly underestimated., Conclusions: A higher i.v. iron supplementation correlates with a significant raise of serum ferritin level and saves on EPO-related expenses up to 1 million/per patient/per year.

Oxidative modification of proteins is of great importance because of their biological role in transport, enzyme activity, immune response and membrane fluidity. This study investigated the redox status of proteins in plasma, erythrocyte and erythrocyte ghosts of chronic alcoholics; a comparison with subjects affected by chronic viral hepatitis and healthy controls was also performed. Compared to the other groups, chronic active alcoholics showed significant increase of plasma, erythrocyte and erythrocyte ghost concentrations of carbonyl proteins, marker of protein oxidative damage. Also, a significant correlation was noted between daily alcohol intake and plasma levels of carbonyl proteins. The incubation of fresh human plasma with acetaldehyde, but not with ethanol, led to a significant increase of the carbonyl protein production. In conclusion, plasma, erythrocyte and membrane proteins are oxidatively modified in active chronic alcoholics; these changes seem to be related to acetaldehyde rather than ethanol toxicity.