Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 943
Filter
1.
Am J Obstet Gynecol MFM ; : 101422, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38969177

ABSTRACT

BACKGROUND: Research on the definition of fetal growth restriction has focused on predicting adverse perinatal outcomes. A significant limitation of this approach is that the individual outcomes of interest could be related to the condition and the treatment. Evaluation of outcomes that reflect the pathophysiology of fetal growth restriction may overcome this limitation. OBJECTIVE: To compare the diagnostic performance of the fetal growth restriction definitions established by the International Society for Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine to predict placental histopathological findings associated with placental insufficiency and a composite adverse neonatal outcome. STUDY DESIGN: In this retrospective cohort study of singleton pregnancies, the International Society for Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine guidelines were used to identify pregnancies with fetal growth restriction and a corresponding control group. The primary outcome was the prediction of placental histopathological findings associated with placental insufficiency, defined as lesions associated with maternal vascular malperfusion. A composite adverse neonatal outcome (i.e., umbilical artery pH≤7.1, Apgar score at 5 minutes ≤4, neonatal intensive care unit admission, hypoglycemia, respiratory distress syndrome requiring mechanical ventilation, intrapartum fetal distress requiring expedited delivery, and perinatal death) was investigated as a secondary outcome. Sensitivity, specificity, positive and negative predictive values, and the areas under the receiver-operating-characteristics curves were determined for each fetal growth restriction definition. Logistic regression models were used to assess the association between each definition and the studied outcomes. A subgroup analysis of the diagnostic performance of both definitions stratifying the population in early and late fetal growth restriction was also performed. RESULTS: Both societies' definitions showed a similar diagnostic performance as well as a significant association with the primary (International Society for Ultrasound in Obstetrics and Gynecology adjusted odds ratio 3.01 [95% confidence interval 2.42, 3.75]; Society for Maternal-Fetal Medicine adjusted odds ratio 2.85 [95% confidence interval 2.31, 3.51]) and secondary outcomes (International Society for Ultrasound in Obstetrics and Gynecology adjusted odds ratio 1.95 [95% confidence interval 1.56, 2.43]; Society for Maternal-Fetal Medicine adjusted odds ratio 2.12 [95% confidence interval 1.70, 2.65]). Furthermore, both fetal growth restriction definitions had a limited discriminatory capacity for placental histopathological findings of maternal vascular malperfusion and the composite adverse neonatal outcome (area under the receiver-operating-characteristics curve International Society for Ultrasound in Obstetrics and Gynecology 0.63 [95% confidence interval 0.61, 0.65], 0.59 [95% confidence interval 0.56, 0.61]; area under the receiver-operating-characteristics Society for Maternal-Fetal Medicine 0.63 [95% confidence interval 0.61, 0.66], 0.60 [95% confidence interval 0.57, 0.62]). CONCLUSIONS: The International Society for Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine fetal growth restriction definitions have limited discriminatory capacity for placental histopathological findings associated with placental insufficiency and a composite adverse neonatal outcome.

2.
Pract Radiat Oncol ; 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38944806

ABSTRACT

PURPOSE: SBRT-Spanish Group-05 (ClinicalTrials.gov.Identifier: NCT02192788) is a collaborative (SBRT-SG, Grupo de Investigación Clínica en Oncología Radioterápica, and Sociedad Española de Oncología Radioterápica) prospective multicenter phase II trial testing stereotactic body radiation therapy (SBRT) and androgen deprivation therapy (ADT) in patients with oligorecurrent prostate cancer. METHODS AND MATERIALS: Two cohorts of patients with prostate cancer in an oligorecurrent stage (hormone-sensitive in the principal cohort and castration-resistant in the exploratory cohort) were assigned to receive ADT and SBRT for at least 24 months from the time of the enrollment. Concomitant treatment with chemotherapy, abiraterone, or enzalutamide was not allowed. Oncologic outcomes were assessed in both cohorts. Toxicity was prospectively analyzed. RESULTS: From 2014 to 2019, 81 patients with a total of 126 lesions from 14 centers met the inclusion criteria, 14 of whom were castration-resistant. With a median follow-up of 40 months (12-58 months), 3-year local recurrence-free survival was 92.5% (95% CI, 79.9%-96.3%) and 85.7% (95% CI, 48.2%-95.6%) in the principal and exploratory cohorts, respectively. In the principal cohort, biochemical relapse-free survival and metastasis progression-free survival at 1, 2, and 3 years were 91% (95% CI, 81%-95.8%), 73.7% (95% CI, 61.1%-82.8%), 50.6% (95% CI, 36.2%-63.3%), and 92% (95% CI, 83%-97%), 81% (95% CI, 70%-89%), and 67% (95% CI, 53%-77%), respectively. In the exploratory cohort, metastasis progression-free survival at 1, 2, and 3 years was 64% (95% CI, 34%-83%), 43% (95% CI, 18%-66%), and 26% (95% CI, 7%-51%), respectively. None of the patients developed grade III or higher toxicity or symptoms related to local progression, and only 2 (2.4%) patients developed grade II toxicity. CONCLUSIONS: The combination of SBRT and ADT is safe and shows favorable clinical outcomes in patients with hormone-sensitive and castration-resistant prostate cancer. Validation studies are needed in patients with castration-resistant prostate cancer.

3.
JMIR Form Res ; 8: e51094, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896841

ABSTRACT

BACKGROUND: The Mediterranean diet has been linked to reduced risk for several cardiometabolic diseases. The lack of a clear definition of the Mediterranean diet in the scientific literature and the documented proliferation of nutrition misinformation on the internet suggest the potential for confusion among consumers seeking web-based Mediterranean diet information. OBJECTIVE: We conducted a social media content analysis of information about the Mediterranean diet on the influential social media platform, TikTok, to examine public discourse about the diet and identify potential areas of misinformation. We then analyzed these findings in the context of health promotion to identify potential challenges and opportunities for the use of TikTok in promoting the Mediterranean diet for healthy living. METHODS: The first-appearing 202 TikTok posts that resulted from a search of the hashtag #mediterraneandiet were downloaded and qualitatively examined. Post features and characteristics, poster information, and engagement metrics were extracted and synthesized across posts. Posts were categorized as those created by health professionals and those created by nonhealth professionals based on poster-reported credentials. In addition to descriptive statistics of the entire sample, we compared posts created by professionals and nonprofessionals for content using chi-square tests. RESULTS: TikTok posts varied in content, but posts that were developed by health professionals versus nonprofessionals were more likely to offer a definition of the Mediterranean diet (16/106, 15.1% vs 2/96, 2.1%; P=.001), use scientific citations to support claims (26/106, 24.5% vs 0/96, 0%; P<.001), and discuss specific nutrients (33/106, 31.1% vs 6/96, 6.3%; P<.001) and diseases related to the diet (27/106, 25.5% vs 5/96, 5.2%; P<.001) compared to posts created by nonhealth professionals. CONCLUSIONS: Social media holds promise as a venue to promote the Mediterranean diet, but the variability in information found in this study highlights the need to create clear definitions about the diet and its components when developing Mediterranean diet interventions that use new media structures.

4.
Chem Commun (Camb) ; 60(55): 7065-7068, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38904167

ABSTRACT

The electrochemical reduction of nitroarenes allows direct access to manifold nitrogen containing heterocycles. This work reports the simple and direct electro-organic synthesis of 18 different examples of 2H,4H-4-hydroxy-1,4-benzoxazin-3-ones in up to 81% yield. The scalability of the method was demonstrated on a gram-scale.

5.
Euro Surveill ; 29(23)2024 Jun.
Article in English | MEDLINE | ID: mdl-38847120

ABSTRACT

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-ß-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five bla NDM-1-carrying-P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a bla NDM-1-carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised bla NDM-1-carrying-P. stuartii and the third bla NDM-5-carrying-P. stuartii. The bla NDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The bla NDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring bla NDM-1, bla OXA-10, bla CMY-16, rmtC and armA, which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Multiple, Bacterial , Enterobacteriaceae Infections , Microbial Sensitivity Tests , Multilocus Sequence Typing , Plasmids , Providencia , Whole Genome Sequencing , beta-Lactamases , Humans , Ukraine/epidemiology , beta-Lactamases/genetics , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/drug therapy , Drug Resistance, Multiple, Bacterial/genetics , Providencia/genetics , Providencia/isolation & purification , Providencia/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Europe/epidemiology , Plasmids/genetics , Male , Adult , Female , Middle Aged , Aged , Young Adult
6.
Vaccines (Basel) ; 12(6)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38932350

ABSTRACT

Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health challenge affecting millions in Latin America and worldwide. Although significant progress has been made in vector control, no vaccine exists to prevent infection or mitigate disease pathogenesis. We developed a rationally designed chimeric protein vaccine, N-Tc52/TSkb20, incorporating immunodominant epitopes from two T. cruzi antigens, the amino-terminal portion of Tc52 and the TSkb20 epitope derived from trans-sialidase. The objectives of this study were to construct and characterize the antigen and evaluate its protective potential in an immunoprophylactic murine model of T. cruzi infection. The N-Tc52/TSkb20 protein was recombinantly expressed in E. coli and its identity was confirmed using mass spectrometry and Western blotting. Immunization with the chimeric protein significantly controlled parasitemia and reduced the heart, colon, and skeletal muscle parasite burdens compared to non-vaccinated mice. Protection was superior to vaccination with the individual parental antigen components. Mechanistically, the vaccine induced potent CD8+ T-cell and IFNγ responses against the incorporated epitopes and a protective IgG antibody profile. A relatively low IL-10 response favored early parasite control. These results validate the promising multi-epitope approach and support the continued development of this type of rational vaccine design strategy against Chagas disease.

8.
Mol Metab ; 85: 101962, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38815625

ABSTRACT

OBJECTIVE: p63 is a transcription factor involved in multiple biological functions. In the liver, the TAp63 isoform induces lipid accumulation in hepatocytes. However, the role of liver TAp63 in the progression of metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis is unknown. METHODS: We evaluated the hepatic p63 levels in different mouse models of steatohepatitis with fibrosis induced by diet. Next, we used virogenetic approaches to manipulate the expression of TAp63 in adult mice under diet-induced steatohepatitis with fibrosis and characterized the disease condition. Finally, we performed proteomics analysis in mice with overexpression and knockdown of hepatic TAp63. RESULTS: Levels of TAp63, but not of ΔN isoform, are increased in the liver of mice with diet-induced steatohepatitis with fibrosis. Both preventive and interventional strategies for the knockdown of hepatic TAp63 significantly ameliorated diet-induced steatohepatitis with fibrosis in mice fed a methionine- and choline-deficient diet (MCDD) and choline deficient and high fat diet (CDHFD). The overexpression of hepatic TAp63 in mice aggravated the liver condition in mice fed a CDHFD. Proteomic analysis in the liver of these mice revealed alteration in multiple proteins and pathways, such as oxidative phosphorylation, antioxidant activity, peroxisome function and LDL clearance. CONCLUSIONS: These results indicate that liver TAp63 plays a critical role in the progression of diet-induced steatohepatitis with fibrosis, and its inhibition ameliorates the disease.


Subject(s)
Fatty Liver , Liver Cirrhosis , Liver , Mice, Inbred C57BL , Animals , Mice , Liver/metabolism , Liver/pathology , Male , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Fatty Liver/metabolism , Fatty Liver/pathology , Disease Models, Animal , Diet, High-Fat/adverse effects , Trans-Activators/metabolism , Trans-Activators/genetics , Proteomics , Methionine/deficiency , Methionine/metabolism
9.
Sci Total Environ ; 932: 173045, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38734098

ABSTRACT

The main objective of this study was to develop and test a method of separating externally deposited Mn oxyhydroxides and co-precipitated elements from samples of aquatic moss (the moss Fontinalis antipyretica). The method, which uses 0.1 M hydroxylamine to dissolve the oxyhydroxides, was tested with samples collected in rivers with slightly acidic, well­oxygenated waters, where high rates of Mn precipitation occur. The method was effective (it extracted up to 84 % of the Mn) and selective (Fe oxyhydroxides were not extracted). The elements Ba, Cd, Zn and Ni were associated with the Mn oxyhydroxides, while Al, As, Cr, Cu, Fe, Hg and Pb were not. Deposition of Mn therefore increased the concentration of some elements in the moss samples. However, as Mn precipitation depends on Eh and pH, which are independent of the concentrations of the elements in water, the relationship between water and moss element concentrations is not clear (i.e. the data are noisy). This is a problem in biomonitoring studies, which assume a close relationship between element concentrations in moss and water. The value of the proposed extraction method is that it can be used to correct the effect of Mn deposition. We present an example of this correction applied to the Cd concentrations in the test data. We found that the noise introduced by the Mn, including age-related effects (observed by comparing concentrations in 0-2.5 and 2.2-5.0 cm sections from the shoot apex), can be reduced. Additionally, the correction revealed recent increases in Cd concentrations in one site that were not observed in the uncorrected data. Another finding of interest was the low content of total Mn and different extractability (of most elements) observed in moss samples collected in alkaline waters. Finally, we discuss how future studies designed for different environmental scenarios can benefit from application of the proposed method.


Subject(s)
Bryophyta , Environmental Monitoring , Trace Elements , Water Pollutants, Chemical , Trace Elements/analysis , Water Pollutants, Chemical/analysis , Environmental Monitoring/methods , Bryophyta/chemistry , Manganese/analysis , Bryopsida/chemistry
10.
Ann Hematol ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38763941

ABSTRACT

REHem-AR was created in 2013. The progressive implementation of neonatal screening for haemoglobinopathies in Spanish autonomous communities where the registry had not been implemented, as well as the addition of new centres during this period, has considerably increased the sample of patients covered. In this study, we update our previous publication in this area, after a follow-up of more than 5 years. An observational, descriptive, multicentre and ambispective study of adult and paediatric patients with haemoglobinopathies and rare anaemias registered in REHem was performed. The data are from a cross-sectional analysis performed on 1 June, 2023. The study population comprised 1,756 patients, of whom 1,317 had SCD, 214 had thalassaemia and 224 were diagnosed with another condition. Slightly more than one third of SCD patients (37%) were diagnosed based on neonatal bloodspot screening, and the mean age at diagnosis was 2.5 years; 71% of thalassaemia patients were diagnosed based on the presence of anaemia. Vaso-occlusive crisis and acute chest syndrome continue to be the most frequent complications in SCD. HSCT was performed in 83 patients with SCD and in 50 patients with thalassaemia. Since the previous publication, REHem-AR has grown in size by more than 500 cases. SCD and TM are less frequent in Spain than in other European countries, although the data show that rare anaemias are frequent within rare diseases. REHem-AR constitutes an important structure for following the natural history of rare anaemias and enables us to calculate investment needs for current and future treatments.

11.
Front Allergy ; 5: 1384140, 2024.
Article in English | MEDLINE | ID: mdl-38720769

ABSTRACT

Progesterone is an endogenous hormone, produced by the adrenal cortex, the gonads and in women, its source is the corpus luteum. Progesterone is produced in the late phase of the menstrual cycle, when implantation of the zygote does not occur, the corpus luteum involutes and the release of progesterone is suppressed, thus initiating menstruation. Progestogen Hypersensitivity were initially identified as hormone allergy and were related to endogenous reactions to hormones and alteration of ovarian function. Skin manifestations such as dermatitis or urticaria were initially reported and described as progesterone autoimmune dermatitis, although the immune-mediated mechanism was not clear. Currently there is no standardization for in vivo or in vitro tests for Progestogen Hypersensitivity diagnosis. In this review, we will address the different diagnostic methods of this disease.

12.
Infection ; 2024 May 04.
Article in English | MEDLINE | ID: mdl-38703288

ABSTRACT

BACKGROUND: Community-acquired (CA) and healthcare-associated (HCA) infections caused by carbapenemase-producing Enterobacterales (CPE) are not well characterized. The objective was to provide detailed information about the clinical and molecular epidemiological features of nosocomial, HCA and CA infections caused by carbapenemase-producing Klebsiella pneumoniae (CP-Kp) and Escherichia coli (CP-Ec). METHODS: A prospective cohort study was performed in 59 Spanish hospitals from February to March 2019, including the first 10 consecutive patients from whom CP-Kp or CP-Ec were isolated. Patients were stratified according to acquisition type. A multivariate analysis was performed to identify the impact of acquisition type in 30-day mortality. RESULTS: Overall, 386 patients were included (363 [94%] with CP-Kp and 23 [6%] CP-Ec); in 296 patients (76.3%), the CPE was causing an infection. Acquisition was CA in 31 (8.0%) patients, HCA in 183 (47.4%) and nosocomial in 172 (48.3%). Among patients with a HCA acquisition, 100 (54.6%) had been previously admitted to hospital and 71 (38.8%) were nursing home residents. Urinary tract infections accounted for 19/23 (82.6%), 89/130 (68.5%) and 42/143 (29.4%) of CA, HCA and nosocomial infections, respectively. Overall, 68 infections (23%) were bacteremia (8.7%, 17.7% and 30.1% of CA, HCA and nosocomial, respectively). Mortality in infections was 28% (13%, 14.6% and 42.7% of CA, HCA and nosocomial, respectively). Nosocomial bloodstream infections were associated with increased odds for mortality (adjusted OR, 4.00; 95%CI 1.21-13.19). CONCLUSIONS: HCA and CA infections caused by CPE are frequent and clinically significant. This information may be useful for a better understanding of the epidemiology of CPE.

13.
Front Cell Infect Microbiol ; 14: 1390966, 2024.
Article in English | MEDLINE | ID: mdl-38817448

ABSTRACT

Introduction: Carbapenemase-Producing Escherichia coli (CP-Eco) isolates, though less prevalent than other CP-Enterobacterales, have the capacity to rapidly disseminate antibiotic resistance genes (ARGs) and cause serious difficult-to-treat infections. The aim of this study is phenotypically and genotypically characterizing CP-Eco isolates collected from Spain to better understand their resistance mechanisms and population structure. Methods: Ninety representative isolates received from 2015 to 2020 from 25 provinces and 59 hospitals Spanish hospitals were included. Antibiotic susceptibility was determined according to EUCAST guidelines and whole-genome sequencing was performed. Antibiotic resistance and virulence-associated genes, phylogeny and population structure, and carbapenemase genes-carrying plasmids were analyzed. Results and discussion: The 90 CP-Eco isolates were highly polyclonal, where the most prevalent was ST131, detected in 14 (15.6%) of the isolates. The carbapenemase genes detected were bla OXA-48 (45.6%), bla VIM-1 (23.3%), bla NDM-1 (7.8%), bla KPC-3 (6.7%), and bla NDM-5 (6.7%). Forty (44.4%) were resistant to 6 or more antibiotic groups and the most active antibiotics were colistin (98.9%), plazomicin (92.2%) and cefiderocol (92.2%). Four of the seven cefiderocol-resistant isolates belonged to ST167 and six harbored bla NDM. Five of the plazomicin-resistant isolates harbored rmt. IncL plasmids were the most frequent (45.7%) and eight of these harbored bla VIM-1. bla OXA-48 was found in IncF plasmids in eight isolates. Metallo-ß-lactamases were more frequent in isolates with resistance to six or more antibiotic groups, with their genes often present on the same plasmid/integron. ST131 isolates were associated with sat and pap virulence genes. This study highlights the genetic versatility of CP-Eco and its potential to disseminate ARGs and cause community and nosocomial infections.


Subject(s)
Anti-Bacterial Agents , Bacterial Proteins , Escherichia coli Infections , Escherichia coli , Microbial Sensitivity Tests , Phylogeny , Plasmids , beta-Lactamases , Spain/epidemiology , beta-Lactamases/genetics , Humans , Escherichia coli Infections/microbiology , Escherichia coli Infections/epidemiology , Escherichia coli/genetics , Escherichia coli/isolation & purification , Escherichia coli/drug effects , Escherichia coli/enzymology , Plasmids/genetics , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Genetic Heterogeneity , Whole Genome Sequencing , Virulence Factors/genetics , Genotype , Carbapenem-Resistant Enterobacteriaceae/genetics , Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Carbapenem-Resistant Enterobacteriaceae/drug effects , Carbapenem-Resistant Enterobacteriaceae/enzymology , Carbapenem-Resistant Enterobacteriaceae/classification , Drug Resistance, Multiple, Bacterial/genetics , Virulence/genetics
14.
Hepatology ; 2024 May 19.
Article in English | MEDLINE | ID: mdl-38761407

ABSTRACT

BACKGROUND AND AIMS: Mitochondrial antiviral signaling protein (MAVS) is a critical regulator that activates the host's innate immunity against RNA viruses, and its signaling pathway has been linked to the secretion of proinflammatory cytokines. However, the actions of MAVS on inflammatory pathways during the development of metabolic dysfunction-associated steatotic liver disease (MASLD) have been little studied. APPROACH AND RESULTS: Liver proteomic analysis of mice with genetically manipulated hepatic p63, a transcription factor that induces liver steatosis, revealed MAVS as a target downstream of p63. MAVS was thus further evaluated in liver samples from patients and in animal models with MASLD. Genetic inhibition of MAVS was performed in hepatocyte cell lines, primary hepatocytes, spheroids, and mice. MAVS expression is induced in the liver of both animal models and people with MASLD as compared with those without liver disease. Using genetic knockdown of MAVS in adult mice ameliorates diet-induced MASLD. In vitro, silencing MAVS blunts oleic and palmitic acid-induced lipid content, while its overexpression increases the lipid load in hepatocytes. Inhibiting hepatic MAVS reduces circulating levels of the proinflammatory cytokine TNFα and the hepatic expression of both TNFα and NFκß. Moreover, the inhibition of ERK abolished the activation of TNFα induced by MAVS. The posttranslational modification O -GlcNAcylation of MAVS is required to activate inflammation and to promote the high lipid content in hepatocytes. CONCLUSIONS: MAVS is involved in the development of steatosis, and its inhibition in previously damaged hepatocytes can ameliorate MASLD.

15.
Metabolism ; 157: 155932, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38729600

ABSTRACT

BACKGROUND: Obesity-induced hypogonadism (OIH) is a prevalent, but often neglected condition in men, which aggravates the metabolic complications of overweight. While hypothalamic suppression of Kiss1-encoded kisspeptin has been suggested to contribute to OIH, the molecular mechanisms for such repression in obesity, and the therapeutic implications thereof, remain unknown. METHODS: A combination of bioinformatic, expression and functional analyses was implemented, assessing the role of the evolutionary-conserved miRNAs, miR-137 and miR-325, in mediating obesity-induced suppression of hypothalamic kisspeptin, as putative mechanism of central hypogonadism and metabolic comorbidities. The implications of such miR-137/325-kisspeptin interplay for therapeutic intervention in obesity were also explored using preclinical OIH models. RESULTS: MiR-137/325 repressed human KISS1 3'-UTR in-vitro and inhibited hypothalamic kisspeptin content in male rats, while miR-137/325 expression was up-regulated, and Kiss1/kisspeptin decreased, in the medio-basal hypothalamus of obese rats. Selective over-expression of miR-137 in Kiss1 neurons reduced Kiss1/ kisspeptin and partially replicated reproductive and metabolic alterations of OIH in lean mice. Conversely, interference of the repressive actions of miR-137/325 selectively on Kiss1 3'-UTR in vivo, using target-site blockers (TSB), enhanced kisspeptin content and reversed central hypogonadism in obese rats, together with improvement of glucose intolerance, insulin resistance and cardiovascular and inflammatory markers, despite persistent exposure to obesogenic diet. Reversal of OIH by TSB miR-137/325 was more effective than chronic kisspeptin or testosterone treatments in obese rats. CONCLUSIONS: Our data disclose that the miR-137/325-Kisspeptin repressive interaction is a major player in the pathogenesis of obesity-induced hypogonadism and a putative druggable target for improved management of this condition and its metabolic comorbidities in men suffering obesity. SIGNIFICANCE STATEMENT: Up to half of the men suffering obesity display also central hypogonadism, an often neglected complication of overweight that can aggravate the clinical course of obesity and its complications. The mechanisms for such obesity-induced hypogonadism remain poorly defined. We show here that the evolutionary conserved miR137/miR325 tandem centrally mediates obesity-induced hypogonadism via repression of the reproductive-stimulatory signal, kisspeptin; this may represent an amenable druggable target for improved management of hypogonadism and other metabolic complications of obesity.


Subject(s)
Hypogonadism , Hypothalamus , Kisspeptins , MicroRNAs , Obesity , MicroRNAs/genetics , MicroRNAs/metabolism , Hypogonadism/genetics , Hypogonadism/metabolism , Hypogonadism/complications , Kisspeptins/genetics , Kisspeptins/metabolism , Animals , Obesity/metabolism , Obesity/complications , Obesity/genetics , Male , Rats , Hypothalamus/metabolism , Humans , Mice , Rats, Wistar , Comorbidity
16.
Pharmaceuticals (Basel) ; 17(5)2024 May 06.
Article in English | MEDLINE | ID: mdl-38794158

ABSTRACT

Stanhopea tigrina Bateman ex Lindl. (Orchidaceae) is an orchid endemic to Mexico, known as "Calavera" or "calaverita", in the Huasteca Potosina (central region of Mexico). This plant species is used for the folk treatment of mental disorders and urological kidney disorders, according to the ethnomedicinal information obtained in this study. Ethanolic extracts of leaves (HE) and pseudobulb (PE) were obtained by microwave-assisted extraction (MAE). Gas Chromatography coupled with Mass Spectrometry (GC-MS) was used to carry out the chemical characterization of HE and PE. The pharmacological effects (antioxidant, diuretic, anxiolytic, locomotor, hypnotic, and sedative) of HE and PE were evaluated. The possible mechanism of action of the anxiolytic-like activity induced by HE was assessed using inhibitors of the GABAergic, adrenergic, and serotonergic systems. The possible mechanism of the diuretic action of HE was assessed using prostaglandin inhibitory antagonists and nitric oxide synthase (NOS) blockers. HE at 50 and 100 mg/kg exerted anxiolytic-like activity without inducing hypnosis or sedation. Flumazenil, prazosin, and ketanserin inhibited the anxiolytic-like activity shown by HE, which suggests the participation of GABA, α1-adrenergic receptors, and 5-HT2 receptors, respectively. The diuretic effect was reversed by the non-selective NOS inhibitor L-NAME, which caused the reduction in nitric oxide (NO). These results demonstrate that the ethanolic extract of S. tigrina leaves exhibited anxiolytic-like activity and diuretic effects without inducing hypnosis or sedation. This work validates the medicinal uses of this orchid species.

17.
Nutrients ; 16(10)2024 May 11.
Article in English | MEDLINE | ID: mdl-38794689

ABSTRACT

There is scarce evidence on sociodemographic and lifestyle characteristics that may explain adherence to different dietary patterns (DPs) during pregnancy. Our aims were to identify dietary patterns in a sample of pregnant Mexican women and to describe their association with selected sociodemographic and lifestyle characteristics. This is a secondary cross-sectional analysis of 252 mothers of children that participated as controls in a hospital-based case-control study of childhood leukemia. We obtained parents' information about selected sociodemographic characteristics, as well as alcohol and tobacco consumption. We also obtained dietary information during pregnancy. We identified DPs using cluster and factor analyses and we estimated their association with characteristics of interest. We identified two DPs using cluster analysis, which we called "Prudent" and "Non healthy", as well as three DPs through factor analysis, namely "Prudent", "Processed foods and fish", and "Chicken and vegetables". Characteristics associated with greater adherence to "Prudent" patterns were maternal education, older paternal age, not smoking, and being a government employee and/or uncovered population. Likewise, the "Processed foods and fish" pattern was associated with greater maternal and paternal education, as well as those with less household overcrowding. We did not identify sociodemographic variables related to the "Chicken and Vegetables" pattern. Our results may be useful to identify target populations that may benefit from interventions aimed to improve individual dietary decisions during pregnancy.


Subject(s)
Diet , Life Style , Humans , Female , Mexico , Pregnancy , Adult , Cross-Sectional Studies , Diet/statistics & numerical data , Socioeconomic Factors , Feeding Behavior , Sociodemographic Factors , Case-Control Studies , Young Adult , Maternal Nutritional Physiological Phenomena , Dietary Patterns
18.
Front Public Health ; 12: 1371505, 2024.
Article in English | MEDLINE | ID: mdl-38655508

ABSTRACT

The incidence of cancer in Europe has been increasing in recent years. Despite this, cancer prevention has remained a low priority in health policies. Cancer is one of the main causes of mortality among people experiencing homelessness, who continue to have difficulties accessing prevention programs. A strategy that has been tested to favor cancer prevention is the health navigator figure. The objective of CANCERLESS project is to implement this model among populations experiencing homelessness in four European countries to foster the prevention and early detection of cancer. In this perspective, a presentation of CANCERLESS project is made, and its ethical aspects are discussed according to the ethics of public health, the ethics of care, solidarity, relational autonomy, and the social recognition of the virtue of just generosity. The ethical foundations of CANCERLESS project are rooted in social justice and in equity in access to health systems in general and cancer screening programs in particular. The ethics of public health guided by utilitarianism are insufficient in serving the interests of the most disadvantaged groups of the population. Hence, it is necessary to resort to relational bioethics that includes the ethics of care and solidarity and that recognizes the moral identity of socially excluded persons, reaffirming their position of equality in society. Relational autonomy therefore provides a broader conception by including the influence of living conditions in decisions. For this reason, the CANCERLESS project opts for a dialogue with those affected to incorporate their preferences and values into decisions about cancer prevention.


Subject(s)
Ill-Housed Persons , Neoplasms , Humans , Neoplasms/prevention & control , Early Detection of Cancer/ethics , Europe , Social Justice , Public Health/ethics , Health Services Accessibility/ethics
19.
Int J Mol Sci ; 25(7)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38612521

ABSTRACT

The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory impairments. In addition, by employing drug repurposing approaches, it was demonstrated that dihydroergotamine (DHE), an FDA drug approved to treat migraines, inhibits Histamine N Methyl Transferase (HNMT), the enzyme responsible for the inactivation of histamine in the brain. For this reason, in the present work, the effect of DHE on histamine levels in the hippocampus and its effects on memory was evaluated, employing the scopolamine-induced amnesia model, the Novel Object Recognition (NOR) paradigm, and the Morris Water Maze (MWM). Furthermore, the role of histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists in the improvement in memory produced by DHE in the scopolamine-induced amnesia model was evaluated. Results showed that the rats that received DHE (10 mg/kg, i.p.) showed increased histamine levels in the hippocampus after 1 h of administration but not after 5 h. In behavioral assays, it was shown that DHE (1 mg/kg, i.p.) administered 20 min before the training reversed the memory impairment produced by the administration of scopolamine (2 mg/kg, i.p.) immediately after the training in the NOR paradigm and MWM. Additionally, the effects in memory produced by DHE were blocked by pre-treatment with pyrilamine (20 mg/kg, i.p.) administered 30 min before the training in the NOR paradigm and MWM. These findings allow us to demonstrate that DHE improves memory in a scopolamine-induced amnesia model through increasing histamine levels at the hippocampus due to its activity as an HNMT inhibitor.


Subject(s)
Dihydroergotamine , Scopolamine , Animals , Rats , Histamine , Amnesia/chemically induced , Amnesia/drug therapy , Brain , Memory Disorders/chemically induced , Memory Disorders/drug therapy , Histamine H2 Antagonists
20.
Breastfeed Med ; 19(5): 349-356, 2024 May.
Article in English | MEDLINE | ID: mdl-38469624

ABSTRACT

Background: Obesity is characterized as a low-grade chronic inflammatory state, marked by elevated inflammatory biomarkers. Breast milk (BM) is rich in nutritional elements, vitamins, minerals, immunological factors, and bioactive components. These bioactive components, capable of influencing biological processes, may vary in concentration based on maternal body composition. Research Aim/Question(s): This study aimed to explore the association between pro-inflammatory cytokine levels (interleukin-1 beta [IL-1ß], interleukin-6 [IL-6], and tumor necrosis factor-alpha [TNF-α]) in human colostrum and maternal body composition, as analyzed through bioelectrical impedance vector analysis (BIVA). Method: In this cross-sectional study, 117 healthy postpartum participants were included, with each group (normal weight, overweight, and obese) comprising 39 individuals, as classified by BIVA. Colostrum samples were collected within the first 24 hours postpartum. Results: IL-1ß levels did not significantly differ across the groups, with concentrations of 69.5 ± 103 pg/mL in normal-weight, 79.7 ± 97.9 pg/mL in overweight, and 68.7 ± 108 pg/mL in obese women. IL-6 levels were significantly higher in the overweight group (55 ± 72.4 pg/mL) than in the normal-weight (48.1 ± 74.1 pg/mL) and obese groups (28.9 ± 36.2 pg/mL) (p = 0.02). Similarly, TNF-α levels were higher in the overweight group, with concentrations of 58.7 ± 74.9 pg/mL, than in the normal-weight group, with concentrations of 38.6 ± 95.4 pg/mL, and 52.6 ± 115 pg/mL in obese women (p = 0.02). Conclusion: This study shows that IL-6 and TNF-α concentrations were statistically higher in the colostrum of overweight women, suggesting that maternal body composition may influence the inflammatory profile of BM.


Subject(s)
Body Composition , Colostrum , Interleukin-1beta , Interleukin-6 , Obesity , Postpartum Period , Tumor Necrosis Factor-alpha , Humans , Female , Colostrum/chemistry , Adult , Cross-Sectional Studies , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Interleukin-6/analysis , Interleukin-1beta/analysis , Interleukin-1beta/metabolism , Obesity/metabolism , Overweight/metabolism , Pregnancy , Milk, Human/chemistry , Biomarkers/analysis , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...