[Translated article] Knowledge of biological therapy in patients with immune-mediated diseases. BIOINFO study.

OBJECTIVE: To determine the degree of knowledge about biological therapy and biosimilars in patients with immune-mediated inflammatory diseases treated in Outpatient Pharmaceutical Care Units. METHODS: Observational, prospective, and multicenter study during the period May 2020-March 2021. A survey (9 questions) was conducted before starting treatment in which the patients' level of knowledge about biological therapy and biosimilars was assessed. RESULTS: A total of 169 patients were included in the study. The average value for the different questions was 3.3±0.6 out of 5, while the average final result was 29.4 points out of 45. 64.5% of the patients had an acceptable level before starting the medication (>27 points). The multivariate analysis showed a statistically significant correlation (p<.05) with a better score at the beginning of treatment in those patients whose prescribing service was Rheumatology. CONCLUSIONS: In general, the level of knowledge prior to biological therapy in patients is acceptable, being higher in dosage and administration technique related-factors and what is related to the dosage and administration technique and where to find information related to the medication; the worst rated were those on biosimilars-related. The factor of being followed by rheumatology, was associated with better knowledge.

Evaluation of the effects of a gamified, fully immersive and stroke-specific virtual reality intervention for improving disability and quality of life in patients with stroke in the subacute phase: study protocol of the RESET randomised trial.

Stroke is the leading cause of disability and the second cause of death worldwide. The increasing burden of stroke underscores the importance of optimising rehabilitation protocols. Virtual reality (VR) can improve poststroke prognosis. A VR software combining gamification, full immersion and stroke specificity (ie, the Development and validation of a novel viRtual rEality software for improving diSability and quality of lifE in patients with sTroke (RESET) software) might substantially improve disability and quality of life (QoL). However, this technology is still very scarce. The RESET trial aims to assess the effects of an early 10-week gamified, fully immersive and stroke-specific VR intervention (ie, starting at week 3 poststroke) on disability and QoL in people with stroke in the subacute phase. People with ischaemic or haemorrhagic stroke (n=94) aged ≥ 18 years will be randomised to receive (1) usual care (UC), (2) commercial VR or (3) gamified, fully immersive and stroke-specific VR (RESET). The three groups will receive UC (ie, three sessions/week of 90 min of standard rehabilitation). The VR groups will additionally receive three VR sessions of 20 min per week. The outcome measures will be assessed at baseline (week 2 from stroke occurrence), week 13 (approximately 90 days from the event) and week 26 (approximately 6 months from the event). The primary outcome is disability measured with the Barthel Index. Secondary outcomes include QoL, upper-extremity and lower-extremity motor function, gross manual dexterity, handgrip strength and cognitive function. This study will unravel the effects of a gamified, fully immersive and stroke-specific VR software on disability and QoL in patients with stroke in the early subacute phase.Trial registration number: NCT06132399.

Expression of pro- and anti-inflammatory cytokines during anti-proprotein convertase subtilisin/kexin type 9 therapy in patients with statin-resistant familial hypercholesterolemia.

Background: Some clinical dyslipidemia cases do not respond to statins, known as statin-resistant familial hypercholesterolemia (SR-FH), in which patients are under a high cardiovascular risk despite statin therapy. Therefore, novel therapeutic alternatives are required. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce cholesterol levels and cardiovascular disease risk, particularly in patients with SR-FH, where PCSK9i may differentially affect pro- and anti-inflammatory mediators depending on the clinical setting. Aim: To evaluate the effect of PCSK9i treatment on pro- and anti-inflammatory cytokines in patients with SR-FH. Methods: Before-after comparison, quasi-experimental, single-center study in patients with SR-FH. Blood samples were processed to obtain complete blood counts of glycated hemoglobin and serum lipid levels. Flow cytometry was performed to characterize baseline circulating M1- and M2-macrophages and monocytes. Multiplexing of plasma samples was used to compare plasma fraktaline, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha. The endpoints were lower serum lipid levels and pro-inflammatory mediator modification. Results: Twenty patients with SR-FH, aged 58 years and most of them males, were included, with a mean body-mass index of 26.4 and showing ischemic heart disease and similar values of baseline M1- and M2-macrophages and monocytes. Six-month iPSCK-9 therapy considerably reduced LDLc, increased anti-inflammatory cytokine (IL-4), and modified pro-inflammatory cytokine (TNF-alpha and MCP-1) levels. No notable effects were observed for the other markers. Conclusion: PCSK9i therapy exerted subclinical anti-inflammatory and anti-atherogenic effects, indicating potential benefits for clinical outcomes.

Development and Evaluation of the Reliability of a Semi-Quantitative Food Frequency Questionnaire to Assess the Intake in the Serbian Population.

Assessing dietary habits with validated questionnaires is crucial for achieving reliable results in health research. The aim of this study was the development and validation of a semi-quantitative food frequency questionnaire (FFQ) in an 18-30-year-old Serbian population. A total of 93 participants completed the FFQ and three 24 h dietary recalls (24 hR). Pearson and intraclass correlations between FFQ and 24 hR intakes were assessed and were de-attenuated and energy-adjusted. Bland-Altman plots were generated, and quintiles of energy, water, fiber, and macronutrient intake were analyzed with contingency tables. Adjustments for sex differences were included. The validity of the FFQ varied, with significant correlations for energy, carbohydrates, cholesterol, and vitamin B12, vitamin C and vitamin D. Misclassification rates were generally low. Bland-Altman plots indicated good agreement between methods. It can be concluded that the validated FFQ is a promising tool for dietary assessment in the Serbian population. Results for several nutrients align closely with previous studies. The new FFQ is a useful tool for dietary assessment in the Serbian population.

Effects of a Two-Year Lifestyle Intervention on Intrahepatic Fat Reduction and Renal Health: Mitigation of Inflammation and Oxidative Stress, a Randomized Trial.

Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease observed in clinical practice worldwide. This disorder has been independently associated with an increased risk of developing chronic kidney disease (CKD). The aim of this study was to evaluate whether a 2-year intervention based on a Mediterranean diet (MedDiet) and physical activity focussed on reducing intrahepatic fat contents (IFC) was associated with a decreased risk of CKD. Forty adults (50% women) residing in Mallorca, aged 48 to 60 years, diagnosed with MAFLD were recruited. Participants were divided into two groups based on whether they improved IFC measured by nuclear magnetic resonance. Anthropometric and clinical parameters improved in responders, including reduced weight, body mass index (BMI), and waist circumference. Only responders showed improvements in lipid profile and liver enzymes. Haematological parameters showed favourable changes in both groups. Oxidative stress and inflammatory biomarkers differed between groups. Responders had lower plasma interleukine-18 (IL-18) levels, but higher erythrocyte malonaldehyde (MDA) levels. Non-responders showed increased erythrocyte catalase and superoxide dismutase activity. After 2 years, non-responders had higher serum creatinine, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) levels, while responders showed reductions in these parameters together with uric acid and urine albumin-to-creatinine ratio (UACR). Positive correlations were found between changes in IFC and kidney injury biomarkers, including MDRD and serum creatinine levels. In conclusion, a healthy diet based on the Mediterranean dietary pattern and lifestyle promotes significant improvements in parameters related to cardiovascular, hepatic, and renal health.

Central diabetes insipidus (vasopressin deficiency) after surgery for pituitary tumours: a systematic review and meta-analysis.

OBJECTIVE: Central diabetes insipidus or vasopressin deficiency (AVP-D) is the most frequent water balance disorder after transsphenoidal surgery (TSS) with variable prevalence amongst studies. We aimed to determine rates of newly developed transient or permanent AVP-D in patients with pituitary tumours treated with TSS. DESIGN AND METHODS: We performed systematic review of Medline, Embase, and Cochrane Library between January 1, 2000 and January 31, 2021 for studies reporting on outcomes for pituitary adenoma, craniopharyngioma, and Rathke's cleft cyst (RCC) after TSS and providing definition of post-operative AVP-D. We pooled the results as proportions with 95% confidence intervals (CIs) using Freeman-Tukey transformation random effects meta-analysis. RESULTS: From 11 694 studies, 51 were included. Rates of transient or permanent AVP-D were: 17% (95% CI, 13-21) and 3% (95% CI, 2-5) in total group, 16% (95% CI, 12-21) and 2% (95% CI, 2-3) in pituitary adenomas, 31% (95% CI, 24-39) and 30% (95% CI, 22-39) in craniopharyngiomas, and 35% (95% CI, 16-57) and 14% (95% CI, 6-23) in RCCs, respectively. Based on diagnostic criteria, rates of transient or permanent AVP-D were: For hypotonic polyuria, 14% (95% CI, 8-22) and 3% (95% CI, 1-4), for hypotonic polyuria and hypernatraemia, 21% (95% CI, 13-29) and 5% (95% CI, 2-11), and for desmopressin administration, 22% (95% CI, 15-29) and 9% (95% CI, 0-30), respectively. CONCLUSIONS: Following TSS, a small proportion of patients with pituitary adenoma have permanent AVP-D (2%), but prevalence reaches 30% in ones with craniopharyngioma and 14% in those with RCC. Diagnostic criteria for post-operative AVP-D remain variable affecting reported rates of this condition.

Long-Term Impact of Nutritional Intervention with Increased Polyphenol Intake and Physical Activity Promotion on Oxidative and Inflammatory Profiles in Patients with Metabolic Syndrome.

Obesity and overweight pose significant risks to health, contributing to the prevalence of chronic conditions like type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). The current study aimed to assess the impact of a 6-year nutritional and lifestyle intervention on oxidative and inflammatory markers in individuals aged 55 to 75, specifically those at high risk of CVD. A study was carried out in a group of 80 participants with metabolic syndrome (MetS) residing in Mallorca, Spain, who underwent nutritional intervention based on a low-calorie Mediterranean diet (MedDiet) and promotion of physical activity. Before and after the intervention, several parameters including anthropometric data, haematological factors, blood pressure, and physical activity level were measured. Oxidative and inflammatory biomarkers in plasma were analysed. After the 6-year intervention, participants who managed to reduce their body mass index (BMI) had greater reductions in abdominal obesity, waist to heigh ratio (WHtR), diastolic blood pressure, and glucose levels, and increased high density protein cholesterol (HDL-c) compared to those who did not reduce BMI. This higher reduction in BMI was related to reduced energy intake and increased adherence to MedDiet, with greater polyphenol intake, and total physical activity (PA). Furthermore, improvements in oxidative stress and proinflammatory status were observed in participants who reduced their BMI. Significant reductions in the activity of the prooxidant enzyme, myeloperoxidase (MPO), levels of the lipid oxidation marker, malondialdehyde (MDA), and the proinflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1,) were found in those who reduced their BMI. In contrast, participants who did not improve their BMI exhibited higher levels of proinflammatory markers such as MCP-1 and tumour necrosis factor α (TNFα), as well as increased activity of the antioxidant enzyme catalase (CAT). Current findings suggest that an effective way to reduce BMI is a hypocaloric MedDiet combined with tailored physical activity to improve oxidative stress and proinflammatory status, and potentially reducing the risk of CVD.

Influence of the COVID-19 pandemic on the incidence of eating disorders.

INTRODUCTION: Eating disorders (EDs) develop more frequently in young females. Following the COVID-19 pandemic, there has been evidence of an increase in children and adolescents, with an earlier onset and a worse body weight and nutritional status. The aim of this study was to determine whether this trend has also been observed in our region over the past 6 years. MATERIAL AND METHODS: We conducted a retrospective and descriptive cohort study in paediatric patients with a diagnosis of ED, referred during the 3 years preceding and following the declaration of the state of alarm due to the pandemic. We analysed and compared clinical, anthropometric and laboratory variables and bioelectrical impedance and bone density data. RESULTS: Of the 129 patients in the sample, 28 were referred before the lockdown period and 101 after. When we compared these groups, we found a longer time elapsed from onset to the initial assessment (mean delay, 11.87 [SD, 6.75] vs. 6.64 [SD, 4.36] months), a greater hospitalization rate (14.1% vs. 10.1%), and lower vitamin D values (mean level, 28.19 [SD, 9.95] vs. 34.39 [SD, 11.87] ng/mL) in the post-lockdown group. We also found a greater frequency of self-harm suicide attempts in these patients. CONCLUSIONS: This study confirms the increasing trend in EDs in children and adolescents in our area. Moreover, we found differences in the clinical characteristics and time elapsed to diagnosis compared to the patients referred to the hospital before the pandemic.

Knowledge of biological therapy for patients with immune-mediated diseases. BIOINFO Study. / Conocimiento de la terapia biológica en pacientes con enfermedades inmunomediadas. Estudio BIOINFO.

OBJECTIVE: To determine the degree of knowledge about biological therapy and biosimilars in patients with immune-mediated inflammatory diseases treated in Outpatient Pharmaceutical Care Units. METHODS: Observational, prospective and multicenter study during the period May 2020-March 2021. A survey (9 questions) was conducted before starting treatment in which the patients' level of knowledge about biological therapy and biosimilars was assessed. RESULTS: A total of 169 patients were included in the study. The average value for the different questions was 3.3 ± 0.6 out of 5, while the average final result was 29.4 points out of 45. Sixty-four percent of the patients had an acceptable level before starting the medication (>27 points). The multivariate analysis showed a statistically significant correlation (p<0.05) with a better score at the beginning of treatment in those patients whose prescribing service was Rheumatology. CONCLUSIONS: In general, the level of knowledge prior to biological therapy in patients is acceptable, being higher in dosage and administration technique related-factors and what is related to the dosage and administration technique and where to find information related to the medication; the worst rated were those on biosimilars-related. The factor of being followed by rheumatology, was associated with better knowledge.

Therapeutic Effect of Alpha Lipoic Acid in a Rat Preclinical Model of Preeclampsia: Focus on Maternal Signs, Fetal Growth and Placental Function.

Chronic hypertension is a major risk factor for preeclampsia (PE), associated with significant maternal and neonatal morbidity. We previously demonstrated that pregnant stroke-prone spontaneously hypertensive rats (SHRSP) display a spontaneous PE-like phenotype with distinct placental, fetal, and maternal features. Here, we hypothesized that supplementation with alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy could ameliorate the PE phenotype in this model. To test this hypothesis, timed pregnancies were established using 10 to 12-week-old SHRSP females (n = 19-16/group), which were assigned to two treatment groups: ALA (injected intraperitoneally with 25 mg/kg body weight ALA on gestation day (GD1, GD8, and GD12) or control, receiving saline following the same protocol. Our analysis of maternal signs showed that ALA prevented the pregnancy-dependent maternal blood pressure rise (GD14 blood pressure control 169.3 ± 19.4 mmHg vs. 146.1 ± 13.4 mmHg, p = 0.0001) and ameliorated renal function, as noted by the increased creatinine clearance and improved glomerular histology in treated dams. Treatment also improved the fetal growth restriction (FGR) phenotype, leading to increased fetal weights (ALA 2.19 ± 0.5 g vs. control 1.98 ± 0.3 g, p = 0.0074) and decreased cephalization indexes, indicating a more symmetric fetal growth pattern. This was associated with improved placental efficiency, decreased oxidative stress marker expression on GD14, and serum soluble fms-like tyrosine kinase 1 (sFlt1) levels on GD20. In conclusion, ALA supplementation mitigated maternal signs and improved placental function and fetal growth in SHRSP pregnancies, emerging as a promising therapy in pregnancies at high risk for PE.

Characterization and modulation of voltage-gated potassium channels in human lymphocytes in schizophrenia.

BACKGROUND: It is known that the immune system is dysregulated in schizophrenia, having a state similar to chronic neuroinflammation. The origin of this process is unknown, but it is known that T and B lymphocytes, which are components of the adaptive immune system, play an important role in the pathogenic mechanisms of schizophrenia. METHODS: We analysed the membrane of PBMCs from patients diagnosed with schizophrenia through proteomic analysis (n = 5 schizophrenia and n = 5 control). We found the presence of the Kv1.3 voltage-gated potassium channel and its auxiliary subunit ß1 (KCNAB1) and ß2 (KCNAB2). From a sample of 90 participants, we carried out a study on lymphocytes with whole-cell patch-clamp experiments (n = 7 schizophrenia and n = 5 control), western blot (n = 40 schizophrenia and n = 40 control) and confocal microscopy to evaluate the presence and function of different channels. Kv in both cells. RESULTS: We demonstrated the overexpression of Kv1.1, Kv1.2, Kv1.3, Kv1.6, Kv4.2, Kv4.3 and Kv7.2 channels in PBMCs from patients with schizophrenia. This study represents a groundbreaking exploration, as it involves an electrophysiological analysis performed on T and B lymphocytes from patients diagnosed of schizophrenia compared to healthy participants. We observed that B lymphocytes exhibited an increase in output current along with greater peak current amplitude and voltage conductance curves among patients with schizophrenia compared with healthy controls. CONCLUSIONS: This study showed the importance of the B lymphocyte in schizophrenia. We know that the immune system is altered in schizophrenia, but the physiological mechanisms of this system are not very well known. We suggest that the B lymphocyte may be relevant in the pathophysiology of schizophrenia and that it should be investigated in more depth, opening a new field of knowledge and possibilities for new treatments combining antipsychotics and immunomodulators. The limitation is that all participants received antipsychotic medication, which may have influenced the differences observed between patients and controls. This implies that more studies need to be done where the groups can be separated according to the antipsychotic drug.

Monastrol suppresses invasion and metastasis in human colorectal cancer cells by targeting fascin independent of kinesin-Eg5 pathway.

Rearrangement of the actin cytoskeleton is a prerequisite for carcinoma cells to develop cellular protrusions, which are required for migration, invasion, and metastasis. Fascin is a key protein involved in actin bundling and is expressed in aggressive and invasive carcinomas. Additionally, fascin appears to be involved in tubulin-binding and microtubule rearrangement. Pharmacophoric-based in silico screening was performed to identify compounds with better fascin inhibitory properties than migrastatin, a gold-standard fascin inhibitor. We hypothesized that monastrol displays anti-migratory and anti-invasive properties via fascin blocking in colorectal cancer cell lines. Biophysical (thermofluor and ligand titration followed by fluorescence spectroscopy), biochemical (NMR), and cellular assays (MTT, invasion of human tissue), as well as animal model studies (zebrafish invasion) were performed to characterize the inhibitory effect of monastrol on fascin activity. In silico analysis revealed that monastrol is a potential fascin-binding compound. Biophysical and biochemical assays demonstrated that monastrol binds to fascin and interferes with its actin-bundling activity. Cell culture studies, including a 3D human myoma disc model, showed that monastrol inhibited fascin-driven cytoplasmic protrusions as well as invasion. In silico, confocal microscopy, and immunoprecipitation assays demonstrated that monastrol disrupted fascin-tubulin interactions. These anti-invasive effects were confirmed in vivo. In silico confocal microscopy and immunoprecipitation assays were carried out to test whether monastrol disrupted the fascin-tubulin interaction. This study reports, for the first time, the in vitro and in vivo anti-invasive properties of monastrol in colorectal tumor cells. The number and types of interactions suggest potential binding of monastrol across actin and tubulin sites on fascin, which could be valuable for the development of antitumor therapies.

Comparing the clinical applicability of wavefront phase imaging in keratoconus versus normal eyes.

The aim of this work is to quantitatively assess the wavefront phase of keratoconic eyes measured by the ocular aberrometer t·eyede (based on WaveFront Phase Imaging Sensor), characterized by a lateral resolution of 8.6 µm without requiring any optical element to sample the wavefront information. We evaluated the parameters: root mean square error, Peak-to-Valley, and amplitude of the predominant frequency (Fourier Transform analysis) of a section of the High-Pass filter map in keratoconic and healthy cohorts. Furthermore, we have analyzed keratoconic eyes that presented dark-light bands in this map to assess their period and orientation with the Fourier Transform. There are significant statistical differences (p value < 0.001) between healthy and keratoconic eyes in the three parameters, demonstrating a tendency to increase with the severity of the disease. Otherwise, the quantification of the bands reveals that the width is independent of eye laterality and keratoconic stage as orientation, which tends to be oblique. In conclusion, the quantitative results obtained with t·eyede could help to diagnose and monitor the progression of keratoconus.

Effectiveness and safety of COVID-19 vaccines on maternal and perinatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Major databases between December 2019 and January 2023. STUDY SELECTION: Nine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included. QUALITY ASSESSMENT, DATA EXTRACTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs. RESULTS: Sixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I2=87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I2=92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women). CONCLUSION: COVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women. PROSPERO REGISTRATION NUMBER: CRD42020178076.

Effects of Regular Exercise on the Biochemical, Oxidative, and Inflammatory Profiles and Quality of Life in Older Spaniards with Metabolic Syndrome.

Metabolic syndrome increases the risk of developing diabetes and cardiovascular disease. The regular practice of physical activity is a crucial factor for healthy aging and for controlling and preventing chronic diseases. To assess the effects of regular physical activity on the biochemical and inflammatory profiles, as well as the quality of life of older adults diagnosed with metabolic syndrome. Participants (aged 55-70 years; living in the Balearic Islands, Spain) were divided into two groups (n = 50 each) according to the degree of physical activity measured by metabolic equivalents of task (METs). Anthropometric parameters, blood pressure, biochemical and hematological parameters, and inflammatory biomarkers were measured. Beck Depression Inventory and adherence to the Mediterranean diet questionnaires, as well as the Dietary Inflammatory Index, chair test, health-related quality of life (HRQoL), and Rapid Assessment of Physical Activity, were also determined. The characterization of the patients was similar in both groups, showing a homogeneous sample. The group with the highest METs experienced a decrease in depression and an increase in the intensity of physical activity. Adherence to the Mediterranean diet and HRQoL physical dimensions increased in participants with the highest METs, also showing a decrease in glycemia and glycosylated hemoglobin values. Inflammatory biomarkers, including tumor necrosis factor alpha, interleukin-6, interleukin-1ß, and osteoprotegerin, decreased in patients practicing more physical activity. High levels of physical activity are related to a healthier lifestyle, characterized by high adherence to the Mediterranean diet, decreased depressive behavior, oxidative stress, and inflammatory status in older people with metabolic syndrome.

Impact of Adherence to the Mediterranean Diet on Antioxidant Status and Metabolic Parameters in NAFLD Patients: A 24-Month Lifestyle Intervention Study.

BACKGROUND: The Mediterranean Diet (MedDiet) is recognized as a healthy dietary pattern. Non-alcoholic fatty liver disease (NAFLD) is characterized by the excessive accumulation of fat in the liver. OBJECTIVES: To assess the antioxidant status in erythrocytes, plasma, and peripheral blood mononuclear cells (PBMCs) of NAFLD patients following a 24-month lifestyle intervention based on the MedDiet. Adult patients (n = 40; aged 40-60 years) diagnosed with NAFLD by magnetic resonance imaging were divided into two groups based on their adherence to the MedDiet. Consumption was assessed using a validated 143-item semiquantitative Food Frequency Questionnaire. Anthropometrics, biochemistry parameters, intrahepatic fat contents (IFC), antioxidants, and inflammatory biomarkers were measured in plasma and erythrocytes before and after the intervention. RESULTS: After the intervention, body mass index (BMI) and plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-chol), triglycerides, malondialdehyde (MDA), and cytokeratin-18 (CK18) decreased, and high-density lipoprotein cholesterol (HDL-chol) increased. Participants with high adherence to MedDiet showed lower IFC, hepatic enzyme (AST, ALT, and GGT), glycemia, oxidase LDL (oxLDL) plasma levels, and erythrocyte MDA levels. Higher antioxidant activity (erythrocyte catalase-CAT, superoxide dismutase-SOD, glutathione peroxidase-GPx, glutathione reductase-GRd, and total glutathione-GSH as well as PBMCs-CAT gene expression) was observed in these patients, along with a reduction of PBMCs reactive oxygen species production and Toll-like receptor 4 (TLR4) expression. Inverse associations were observed between adherence to the MedDiet and BMI, glycemia, AST, IFC, and CK18 plasma levels and oxLDL, CAT, SOD, and GRd activities in erythrocytes. A significant linear regression was observed between adherence to the MedDiet and antioxidant score. CONCLUSIONS: Adherence to the MedDiet is associated with improved plasma and PBMC antioxidant and inflammatory biomarker profiles and high antioxidant defences in erythrocytes.

Novel Leptin-Cardiac TRH pathway responsible for the cardiac alterations in the Hyperleptinemic obesity.

The association between hypertension and obesity-induced cardiac damage is usually accepted. However, no studies have been focused on cardiac alterations in obesity, independently of blood pressure increase. It is well known that Cardiac TRH induces Left Ventricular Hypertrophy (LVH) and fibrosis, and its inhibition prevents the development of hypertrophy. Also, it has been described that the adiponectin leptin induces TRH expression. Thus, we hypothesized that in obesity, the increase in TRH induced by hyperleptinemia is responsible for LVH, until now mostly attributed to pressure load. We studied obese Agouti mice suffering from hypertension with hyperleptinemia and found a significant LVH development with increased TRH gene expression. Consequently, we found higher fibrotic (collagens and TGF-ß) and hypertrophic markers (BNP and ß-MHC) expression vs lean black controls. As pressure could explain these results, we treated obese mice with diuretic (hydrochlorothiazide 20 mg/kg/day) since weaning. Diuretic treatment was successful as the diuretic group was normotensive in contrast to control obese mice. Nevertheless, both groups showed LVH development, higher cardiac precursor TRH gene and peptide expressions and elevated fibrotic and hypertrophic markers expression, pointing out that obesity-induced LVH is not due to hypertension. In addition, we performed Cardiac TRH inhibition by specific siRNA injection compared to control siRNA treatment and evaluated cardiac damage. As expected, expressions and protein increase in hypertrophic and fibrotic markers observed in the AG mouse with the native cTRH system were not seen in the AG mouse with the cTRH silencing. Indeed, the AG + TRH-siRNA group showed hypertrophic markers expression and fibrosis measurements similar to the lean BL mice. On the whole, these results point out that the novel Leptin-Cardiac TRH pathway is responsible for the cardiac alterations present in hyperleptinemic obesity, independent of blood pressure, and cTRH long-term silencing since early stages totally prevent LVH development and cardiac fibrosis.

Effect of a nutritional intervention based on an energy-reduced Mediterranean diet on environmental impact.

OBJECTIVE: To estimate the environmental impact of a dietary intervention based on an energy-reduced Mediterranean diet (MedDiet) after one year of follow-up. METHODS: Baseline and 1-year follow-up data were used for 5800 participants aged 55-75 years with metabolic syndrome in the PREDIMED-Plus study. Food intake was estimated through a validated semiquantitative food consumption frequency questionnaire, and adherence to the MedDiet was estimated through the Diet Score. Using the EAT-Lancet Commission tables we assessed the influence of dietary intake on environmental impact (through five indicators: greenhouse gas emissions (GHG), land use, energy used, acidification and potential eutrophication). Using multivariable linear regression models, the association between the intervention and changes in each of the environmental factors was assessed. Mediation analyses were carried out to estimate to what extent changes in each of 2 components of the intervention, namely adherence to the MedDiet and caloric reduction, were responsible for the observed reductions in environmental impact. RESULTS: We observed a significant reduction in the intervention group compared to the control group in acidification levels (-13.3 vs. -9.9 g SO2-eq), eutrophication (-5.4 vs. -4.0 g PO4-eq) and land use (-2.7 vs. -1.8 m2). Adherence to the MedDiet partially mediated the association between intervention and reduction of acidification by 15 %, eutrophication by 10 % and land use by 10 %. Caloric reduction partially mediated the association with the same factors by 55 %, 51 % and 38 % respectively. In addition, adherence to the MedDiet fully mediated the association between intervention and reduction in GHG emissions by 56 % and energy use by 53 %. CONCLUSIONS: A nutritional intervention based on consumption of an energy-reduced MedDiet for one year was associated with an improvement in different environmental quality parameters.