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1.
Bol. latinoam. Caribe plantas med. aromát ; 23(4): 523-533, jul. 2024. tab
Article in English | LILACS | ID: biblio-1538056

ABSTRACT

Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.


De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.


Subject(s)
Plant Leaves/chemistry , Croton/chemistry , Plant Extracts/metabolism , Plant Extracts/chemistry , Plant Structures/metabolism , Plant Structures/chemistry , Plant Leaves/metabolism , Croton/metabolism , Anti-Inflammatory Agents , Antioxidants
2.
Cureus ; 16(3): e55582, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38576694

ABSTRACT

Schwannomas, also known as neurilemomas, are peripheral nerve sheath neoplasms. They can be sporadic or associated with genetic syndromes including neurofibromatosis type 2 (NF2). Schwannomas may lead to symptoms by exerting pressure on nearby structures, such as nerve and muscle fibers. In this study, we present the case of a 22-year-old female with a history of NF2 who, upon examination, presented with a visibly enlarged salmon-colored mass involving the left inferior rectus that she had since the age of 12 years. Ocular examinations revealed a small left hypertropia and exotropia in all gazes. Magnetic resonance imaging confirmed bilateral involvement of the inferior rectus muscles. She had a partial excisional biopsy of the mass involving the left inferior rectus muscle that confirmed the presence of schwannoma. This case highlights the importance of comprehensive evaluation of sensory and motor functions as well as considering orbital schwannomas in cases of strabismus, especially within the context of neurofibromatosis.

4.
Sci Rep ; 14(1): 5219, 2024 03 03.
Article in English | MEDLINE | ID: mdl-38433228

ABSTRACT

The error of estimated glomerular filtration rate (eGFR) and its consequences in predialysis are unknown. In this prospective multicentre study, 315 predialysis patients underwent measured GFR (mGFR) by the clearance of iohexol and eGFR by 52 formulas. Agreement between eGFR and mGFR was evaluated by concordance correlation coefficient (CCC), total deviation index (TDI) and coverage probability (CP). In a sub-analysis we assessed the impact of eGFR error on decision-making as (i) initiating dialysis, (ii) preparation for renal replacement therapy (RRT) and (iii) continuing clinical follow-up. For this sub-analysis, patients who started RRT due to clinical indications (uremia, fluid overload, etc.) were excluded. eGFR had scarce precision and accuracy in reflecting mGFR (average CCC 0.6, TDI 70% and cp 22%) both in creatinine- and cystatin-based formulas. Variations -larger than 10 ml/min- between mGFR and eGFR were frequent. The error of formulas would have suggested (a) premature preparation for RTT in 14% of stable patients evaluated by mGFR; (b) to continue clinical follow-up in 59% of subjects with indication for RTT preparation due to low GFRm and (c) to delay dialysis in all asymptomatic patients (n = 6) in whom RRT was indicated based on very low mGFR. The error of formulas in predialysis was frequent and large and may have consequences in clinical care.


Subject(s)
Continuous Renal Replacement Therapy , Renal Dialysis , Humans , Glomerular Filtration Rate , Prospective Studies , Creatinine
5.
Mol Phylogenet Evol ; 194: 108031, 2024 May.
Article in English | MEDLINE | ID: mdl-38360081

ABSTRACT

Our knowledge of the systematics of the papilionoid legume tribe Brongniartieae has greatly benefitted from recent advances in molecular phylogenetics. The tribe was initially described to include species marked by a strongly bilabiate calyx and an embryo with a straight radicle, but recent research has placed taxa from the distantly related core Sophoreae and Millettieae within it. Despite these advances, the most species-rich genera within the Brongniartieae are still not well studied, and their morphological and biogeographical evolution remains poorly understood. Comprising 35 species, Harpalyce is one of these poorly studied genera. In this study, we present a comprehensive, multi-locus molecular phylogeny of the Brongniartieae, with an increased sampling of Harpalyce, to investigate morphological and biogeographical evolution within the group. Our results confirm the monophyly of Harpalyce and indicate that peltate glandular trichomes and a strongly bilabiate calyx with a carinal lip and three fused lobes are synapomorphies for the genus, which is internally divided into three distinct ecologically and geographically divergent lineages, corresponding to the previously recognized sections. Our biogeographical reconstructions demonstrate that Brongniartieae originated in South America during the Eocene, with subsequent pulses of diversification in South America, Mesoamerica, and Australia. Harpalyce also originated in South America during the Miocene at around 20 Ma, with almost synchronous later diversification in South America and Mexico/Mesoamerica beginning 10 Ma, but mostly during the Pliocene. Migration of Harpalyce from South to North America was accompanied by a biome and ecological shift from savanna to seasonally dry forest.


Subject(s)
Fabaceae , Phylogeny , Fabaceae/genetics , Grassland , Forests , Ecosystem , Bayes Theorem , Phylogeography
6.
Front Immunol ; 15: 1328212, 2024.
Article in English | MEDLINE | ID: mdl-38384462

ABSTRACT

Background: Anaphylaxis manifests as a severe immediate-type hypersensitivity reaction initiated through the immunological activation of target B-cells by allergens, leading to the release of mediators. However, the well-known underlying pathological mechanisms do not fully explain the whole variety of clinical and immunological presentations. We performed a systemic review of proteomic and metabolomic studies and analyzed the extracted data to improve our understanding and identify potential new biomarkers of anaphylaxis. Methods: Proteomic and metabolomic studies in both human subjects and experimental models were extracted and selected through a systematic search conducted on databases such as PubMed, Scopus, and Web of Science, up to May 2023. Results: Of 137 retrieved publications, we considered 12 for further analysis, including seven on proteome analysis and five on metabolome analysis. A meta-analysis of the four human studies identified 118 proteins with varying expression levels in at least two studies. Beside established pathways of mast cells and basophil activation, functional analysis of proteomic data revealed a significant enrichment of biological processes related to neutrophil activation and platelet degranulation and metabolic pathways of arachidonic acid and icosatetraenoic acid. The pathway analysis highlighted also the involvement of neutrophil degranulation, and platelet activation. Metabolome analysis across different models showed 13 common metabolites, including arachidonic acid, tryptophan and lysoPC(18:0) lysophosphatidylcholines. Conclusion: Our review highlights the underestimated role of neutrophils and platelets in the pathological mechanisms of anaphylactic reactions. These findings, derived from a limited number of publications, necessitate confirmation through human studies with larger sample sizes and could contribute to the development of new biomarkers for anaphylaxis. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024506246.


Subject(s)
Anaphylaxis , Humans , Arachidonic Acid , Proteomics , Allergens , Biomarkers
8.
EBioMedicine ; 99: 104911, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38168585

ABSTRACT

BACKGROUND: The high variability in clinical and metabolic presentations of inborn errors of cobalamin (cbl) metabolism (IECM), such as the cblC/epicblC types with combined deficits in methylmalonyl-coA mutase (MUT) and methionine synthase (MS), are not well understood. They could be explained by the impaired expression/activity of enzymes from other metabolic pathways. METHODS: We performed metabolomic, genomic, proteomic, and post-translational modification (PTM) analyses in fibroblasts from three cblC cases and one epi-cblC case compared with three cblG cases with specific MS deficits and control fibroblasts. FINDINGS: CblC patients had metabolic profilings consistent with altered urea cycle, glycine, and energy mitochondrial metabolism. Metabolomic analysis showed partial disruption and increased glutamate/ketoglutarate anaplerotic pathway of the tricarboxylic acid cycle (TCA), in patient fibroblasts. RNA-seq analysis showed decreased expression of MT-TT (mitochondrial tRNA threonine), MT-TP (mitochondrial tRNA proline), OXCT1 (succinyl CoA:3-oxoacid CoA transferase deficiency), and MT-CO1 (cytochrome C oxidase subunit 1). Proteomic changes were observed for key mitochondrial enzymes, including NADH:ubiquinone oxidoreductase subunit A8 (NDUFA8), carnitine palmitoyltransferase 2 (CPT2), and ubiquinol-cytochrome C reductase, complex III subunit X (UQCR10). Propionaldehyde addition in ornithine aminotransferase was the predominant PTM in cblC cells and could be related with the dramatic cellular increase in propionate and methylglyoxalate. It is consistent with the decreased concentration of ornithine reported in 3 cblC cases. Whether the changes detected after multi-omic analyses underlies clinical features in cblC and cblG types of IECM, such as peripheral and central neuropathy, cardiomyopathy, pulmonary hypertension, development delay, remains to be investigated. INTERPRETATION: The omics-related effects of IECM on other enzymes and metabolic pathways are consistent with the diversity and variability of their age-related metabolic and clinical manifestations. PTMs are expected to produce cumulative effects, which could explain the influence of age on neurological manifestations. FUNDING: French Agence Nationale de la Recherche (Projects PREDICTS and EpiGONE) and Inserm.


Subject(s)
Multiomics , Vitamin B 12 , Humans , Vitamin B 12/metabolism , Proteomics , Oxidoreductases/metabolism , Fibroblasts/metabolism , RNA, Transfer/metabolism
9.
Colorectal Dis ; 26(1): 145-196, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38050857

ABSTRACT

AIM: The primary aim of the European Society of Coloproctology (ESCP) Guideline Development Group (GDG) was to produce high-quality, evidence-based guidelines for the management of cryptoglandular anal fistula with input from a multidisciplinary group and using transparent, reproducible methodology. METHODS: Previously published methodology in guideline development by the ESCP has been replicated in this project. The guideline development process followed the requirements of the AGREE-S tool kit. Six phases can be identified in the methodology. Phase one sets the scope of the guideline, which addresses the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula in adult patients presenting to secondary care. The target population for this guideline are healthcare practitioners in secondary care and patients interested in understanding the clinical evidence available for various surgical interventions for anal fistula. Phase two involved formulation of the GDG. The GDG consisted of 21 coloproctologists, three research fellows, a radiologist and a methodologist. Stakeholders were chosen for their clinical and academic involvement in the management of anal fistula as well as being representative of the geographical variation among the ESCP membership. Five patients were recruited from patient groups to review the draft guideline. These patients attended two virtual meetings to discuss the evidence and suggest amendments. In phase three, patient/population, intervention, comparison and outcomes questions were formulated by the GDG. The GDG ratified 250 questions and chose 45 for inclusion in the guideline. In phase four, critical and important outcomes were confirmed for inclusion. Important outcomes were pain and wound healing. Critical outcomes were fistula healing, fistula recurrence and incontinence. These outcomes formed part of the inclusion criteria for the literature search. In phase five, a literature search was performed of MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews by eight teams of the GDG. Data were extracted and submitted for review by the GDG in a draft guideline. The most recent systematic reviews were prioritized for inclusion. Studies published since the most recent systematic review were included in our analysis by conducting a new meta-analysis using Review manager. In phase six, recommendations were formulated, using grading of recommendations, assessment, development, and evaluations, in three virtual meetings of the GDG. RESULTS: In seven sections covering the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula, there are 42 recommendations. CONCLUSION: This is an up-to-date international guideline on the management of cryptoglandular anal fistula using methodology prescribed by the AGREE enterprise.


Subject(s)
Anus Diseases , Rectal Fistula , Adult , Humans , Abscess , Systematic Reviews as Topic , Rectal Fistula/diagnosis , Rectal Fistula/surgery , Wound Healing , Treatment Outcome
11.
Matern Child Health J ; 28(1): 5-10, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38142261

ABSTRACT

INTRODUCTION: Adverse childhood experiences (ACEs) are common and have been associated with poor developmental outcomes. We aimed to investigate the relationship between early ACE exposure, subsequent diagnosis of developmental delay, and receipt of developmental delay services by young children. In addition, we aimed to assess the impact of health-promoting behaviors such as breastfeeding and daily reading on these relationships. METHODS: In this cross-sectional analysis of nationally-representative data from the 2017-2018 National Survey of Children's Health, we examined the relationship between ACEs, prior breastfeeding, daily reading, and developmental delay diagnosis among 7837 children aged 3-5 years, using multivariate logistic regression to adjust for family, personal, and sociodemographic characteristics. RESULTS: We found a dose-dependent relationship between ACEs and developmental delay diagnosis; compared to those without ACEs, developmental delay was more common among those with either one ACE (aOR = 2.03, 95% CI 1.17-3.52) or two or more ACEs (aOR = 2.34, 95% CI 1.25-4.37). Neither breastfeeding (exclusively breastfed for 6 months vs. never breastfed aOR = 0.70, 95% CI 0.33-1.46) nor daily reading (no reading versus daily reading aOR = 1.15, CI 0.57-2.33) were associated with incidence of developmental delay among study participants. There was no significant difference in receipt of services intended to meet developmental needs between children with and without ACEs. DISCUSSION: Children with very early ACE exposure are at increased risk for diagnosis of developmental delay. Early screening for ACEs and developmental delay may mitigate the early developmental manifestations of ACE exposure in vulnerable children.


As poor developmental outcomes are related to ACEs, children aged 3­5 years should be routinely screened for ACE exposure. Although breastfeeding and daily reading have multiple benefits to children, they do not adequately mitigate the developmental delays associated with ACE exposure.


Subject(s)
Adverse Childhood Experiences , Child , Female , Humans , Child, Preschool , Cross-Sectional Studies , Breast Feeding , Child Health
12.
Metabolism ; 150: 155738, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37981189

ABSTRACT

Inborn errors of metabolism (IEMs) are a group of more than 1000 inherited diseases that are individually rare but have a cumulative global prevalence of 50 per 100,000 births. Recently, it has been recognized that like common diseases, patients with rare diseases can greatly vary in the manifestation and severity of symptoms. Here, we review omics-driven approaches that enable an integrated, holistic view of metabolic phenotypes in IEM patients. We focus on applications of Constraint-based Reconstruction and Analysis (COBRA), a widely used mechanistic systems biology approach, to model the effects of inherited diseases. Moreover, we review evidence that the gut microbiome is also altered in rare diseases. Finally, we outline an approach using personalized metabolic models of IEM patients for the prediction of biomarkers and tailored therapeutic or dietary interventions. Such applications could pave the way towards personalized medicine not just for common, but also for rare diseases.


Subject(s)
Metabolism, Inborn Errors , Humans , Metabolism, Inborn Errors/genetics , Rare Diseases/genetics , Precision Medicine , Phenotype , Systems Analysis
13.
Int J Mol Sci ; 24(24)2023 Dec 18.
Article in English | MEDLINE | ID: mdl-38139462

ABSTRACT

Glioma cells exhibit genetic and metabolic alterations that affect the deregulation of several cellular signal transduction pathways, including those related to glucose metabolism. Moreover, oncogenic signaling pathways induce the expression of metabolic genes, increasing the metabolic enzyme activities and thus the critical biosynthetic pathways to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates that are essential to accomplish the biosynthetic needs of glioma cells. In this review, we aim to explore how dysregulated metabolic enzymes and their metabolites from primary metabolism pathways in glioblastoma (GBM) such as glycolysis and glutaminolysis modulate anabolic and catabolic metabolic pathways as well as pro-oncogenic signaling and contribute to the formation, survival, growth, and malignancy of glioma cells. Also, we discuss promising therapeutic strategies by targeting the key players in metabolic regulation. Therefore, the knowledge of metabolic reprogramming is necessary to fully understand the biology of malignant gliomas to improve patient survival significantly.


Subject(s)
Glioblastoma , Glioma , Humans , Glioblastoma/genetics , Glioblastoma/metabolism , Glutamine/metabolism , Metabolic Reprogramming , Glycolysis/physiology , Glioma/pathology , Signal Transduction , Apoptosis , Cell Proliferation/physiology
14.
J Exp Orthop ; 10(1): 143, 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38133843

ABSTRACT

PURPOSE: To evaluate if the size of Humeral Hill-Sachs Defects (HSDs) increases during reduction in the emergency department (ED) in subjects that have a first-time anterior shoulder dislocation. METHODS: Subjects more than 18 years old presenting to the ED a first-time anterior shoulder dislocation were included. A computed tomography was performed prior to any reduction attempt (Pre-CT). The shoulder was reduced in the emergency room with intraarticular lidocaine; if two attempts failed, the shoulder was reduced under anaesthesia. A second CT was performed after reduction of the shoulder (Post-CT). CT were evaluated using the Osirix software. A 3-dimensional reconstruction of the humeral head was performed and the maximum width of the humeral defect, maximum depth of the humeral defect and total volume of the humeral defect were measured. The relative increase in size was calculated. RESULTS: Twenty subjects were included in the study. All subjects presented HSDs in the Pre-CT that had a width of a median of 9.9(interquartile range:2.9)mm, a depth of 7.0(3.0]mm and a volume of 355(333)mm2. The HSD in the Post-CT had a width of 10.9(3.0)mm (an increase of 7.23[8.5]%, significant differences, p = 0.0001) a depth of 7.2(2.7)mm (an increase of 9.93[20.7]%, significant differences, p < 0.0001) and a volume of 469(271) mm2 (an increase of 27.5[26.9]%, significant differences, p < 0.0001). There were size increases larger than 25% in 15/20 (75%) of subjects. CONCLUSION: Standard reduction manoeuvres performed in a first-time anterior shoulder dislocation increase the size of the HSD. This increase in size is larger than 25% in four out of five cases. LEVEL OF EVIDENCE: IV, prospective cases series study.

15.
Nutrients ; 15(21)2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37960203

ABSTRACT

Hyperammonemia is characterized by the excessive accumulation of ammonia in the body as a result of the loss of liver detoxification, leading to the development of hepatic encephalopathy (HE). These metabolic alterations carry cognitive and motor deficits and cause neuronal damage, with no effective treatment at present. In this study, we aimed to evaluate the effect of two subacute oral administrations of flaxseed oil (0.26 and 0.52 mL/kg) on short- and long-term memory, visuospatial memory, locomotor activity, motor coordination, and the neuronal morphology of the prefrontal cortex (PFC) via tests on Wistar rats with hyperammonemia. The goal was to identify its role in the regulation of cerebral edema, without liver damage causing cerebral failure. In contrast with an ammonium-rich diet, flaxseed oil and normal foods did not cause cognitive impairment or motor alterations, as evidenced in the short-term and visuospatial memory tests. Furthermore, the flaxseed oil treatment maintained a regular neuronal morphology of the prefrontal cortex, which represents a neuroprotective effect. We conclude that the oral administration of flaxseed oil prevents cognitive and motor impairments as well as neuronal alterations in rats with hyperammonemia, which supports the potential use of this oil to ameliorate the changes that occur in hepatic encephalopathy.


Subject(s)
Flax , Hepatic Encephalopathy , Hyperammonemia , Rats , Animals , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/prevention & control , Hepatic Encephalopathy/metabolism , Rats, Wistar , Linseed Oil/pharmacology , Hyperammonemia/complications , Cognition
16.
Molecules ; 28(22)2023 Nov 18.
Article in English | MEDLINE | ID: mdl-38005378

ABSTRACT

A multi-objective optimization was performed using response surface methodology to obtain a high-value-added product, pectin enriched in polyphenols, from pomegranate peel. For this purpose, a green extraction technique that combines citric acid and ultrasound was carried out considering three variables: time, pH, and temperature. The extraction procedure was optimized using the Box-Behnken design, these being the most suitable conditions, with an extraction time of 34.16 min, a pH of 2.2, and a temperature of 89.87 °C. At this point, the pectin yield was 31.89%, with a total retained polyphenol content of 15.84 mg GAE/g pectin. In addition, the water activity, ash content, equivalent weight, methoxyl content, and degree of esterification were determined for the pectin obtained at the optimal point. This study demonstrates that polyphenol-enriched pectin can be obtained from pomegranate peel via an eco-friendly and efficient method, and that it presents similar properties to commercial pectin, preserving its quality and with potential use as an ingredient or food supplement with a high nutritional value. This work contributes to developing sustainable strategies to valorize pomegranate agro-industrial waste and produce high-value functional ingredients.


Subject(s)
Pectins , Pomegranate , Pectins/chemistry , Polyphenols , Industrial Waste , Temperature
17.
Rev Alerg Mex ; 70(4): 113-120, 2023 Sep.
Article in Spanish | MEDLINE | ID: mdl-37933921

ABSTRACT

Objective: To assess the reproducibility of symptoms in drug challenge tests. Methods: The study included patients with positive cutaneous or challenge test throughout 2019. For each patient, clinical suspicion according to Karch-Lasagna algorithm was registered. Primary outcome was the reproducibility of symptoms in the provocation tests using a paired analysis of data with McNemar test. Results: Eighty-nine patients were included, 16 of them presented more than one positive test. Thirty were skin tests positive and 75 reacted to provocation tests. Eighty nine percent of patients who reacted in challenge test were probably or possibly reactors according to Karch-Lasagna scale. Symptoms of initial reaction did not differ from those triggered in challenge tests. Conclusions: Karch-Lasagna scale is useful in predicting the response to drug provocation tests. In most of the positive studies, results were suggested by clinical history and no differences were found between symptoms triggered in challenge test and that referred to in the previous reaction.


Objetivo: Evaluar la reproducibilidad de los síntomas en pruebas de exposición con fármacos. Métodos: Estudio retrospectivo, efectuado en pacientes con prueba cutánea o exposición positiva, atendidos en 2019. De cada paciente se registró la sospecha clínica según el algoritmo de Karch-Lasagna. El resultado principal fue la reproducibilidad de síntomas en las pruebas de exposición, mediante el análisis de datos emparejado con prueba de McNemar. Resultados: Se incluyeron 89 pacientes, y de estos 16 reportaron varias pruebas positivas. Se obtuvieron 30 pruebas cutáneas y 75 de exposición positivas. En el 89% de las pruebas de exposición positivas, las reacciones iniciales se clasificaron en probables o posibles, según la escala de Karch-Lasagna. Los síntomas reportados en la reacción inicial no difirieron de los de las pruebas de exposición. Conclusiones: La escala de Karch-Lasagna es un método útil para predecir la respuesta en las pruebas de exposición con fármacos. En la mayor parte de las pruebas positivas, los resultados fueron sugeridos por la historia clínica, sin diferencias entre la manifestación de síntomas en la prueba de exposición versus los referidos en la reacción inicial.


Subject(s)
Reproducibility of Results , Humans , Skin Tests
18.
Clin Epigenetics ; 15(1): 158, 2023 10 05.
Article in English | MEDLINE | ID: mdl-37798757

ABSTRACT

BACKGROUND: MTR gene encodes the cytoplasmic enzyme methionine synthase, which plays a pivotal role in the methionine cycle of one-carbon metabolism. This cycle holds a significant importance in generating S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), the respective universal methyl donor and end-product of epigenetic transmethylation reactions. cblG type of inherited disorders of vitamin B12 metabolism due to mutations in MTR gene exhibits a wide spectrum of symptoms, including a retinopathy unresponsive to conventional therapies. METHODS: To unveil the underlying epigenetic pathological mechanisms, we conducted a comprehensive study of epigenomic-wide alterations of DNA methylation by NGS of bisulfited retinal DNA in an original murine model with conditional Mtr deletion in retinal tissue. Our focus was on postnatal day 21, a critical developmental juncture for ocular structure refinement and functional maturation. RESULTS: We observed delayed eye opening and impaired visual acuity and alterations in the one-carbon metabolomic profile, with a notable dramatic decline in SAM/SAH ratio predicted to impair DNA methylation. This metabolic disruption led to epigenome-wide changes in genes involved in eye development, synaptic plasticity, and retinoid metabolism, including promoter hypermethylation of Rarα, a regulator of Lrat expression. Consistently, we observed a decline in cone photoreceptor cells and reduced expression of Lrat, Rpe65, and Rdh5, three pivotal genes of eye retinoid metabolism. CONCLUSION: We introduced an original in vivo model for studying cblG retinopathy, which highlighted the pivotal role of altered DNA methylation in eye development, cone differentiation, and retinoid metabolism. This model can be used for preclinical studies of novel therapeutic targets.


Subject(s)
Retinal Cone Photoreceptor Cells , Retinal Diseases , Mice , Animals , Retinal Cone Photoreceptor Cells/metabolism , Mice, Transgenic , Epigenome , DNA Methylation , S-Adenosylmethionine/metabolism , Retinal Diseases/metabolism , Carbon/metabolism , Retinoids/metabolism
19.
Clin Transl Oncol ; 2023 Oct 03.
Article in English | MEDLINE | ID: mdl-37787973

ABSTRACT

Watch-and-wait has emerged as a new strategy for the management of rectal cancer when a complete clinical response is achieved after neoadjuvant therapy. In an attempt to standardize this new clinical approach, initiated by the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), and with the participation of the Spanish Association of Coloproctology (AECP), the Spanish Society of Pathology (SEAP), the Spanish Society of Gastrointestinal Endoscopy (SEED), the Spanish Society of Radiation Oncology (SEOR), and the Spanish Society of Medical Radiology (SERAM), we present herein a consensus on a watch-and-wait approach for the management of rectal cancer. We have focused on patient selection, the treatment schemes evaluated, the optimal timing for evaluating the clinical complete response, the oncologic outcomes after the implementation of this strategy, and a protocol for surveillance of these patients.

20.
Healthcare (Basel) ; 11(19)2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37830642

ABSTRACT

BACKGROUND: Fall prevention is an important indicator of the quality of patient care. Prevention includes the use of adequate footwear. Our objective is to determine the differences in the number of falls between patients with "adequate footwear" and "non slip socks", and their associated consequences, to support their use in the prevention of falls among hospitalized patients. METHODS: This is an observational prospective study on inpatient falls. Patient characteristics, fall circumstances, and injuries were collected through Clinical Report Forms, a review of fall reports, and medical records. Admitted patients over 18 years old were recruited from Geriatric and Internal Medicine Units over a brief period of 3 months. RESULTS: A total of 158 hospitalized patients were recruited. In total, 77 patients (48.73%) were assigned to the non-slip socks group, and 81 (51.27%) were assigned to the adequate footwear group. There were 21 falls during the study period, all of which were experienced by the adequate footwear group (p < 0.0001). The mean age of the patients who fell was 83.14 (range 60-100) years old. The most frequent reasons for admission among the patients who fell were COVID-19 infection (19%) and oncological complications (19%). Overall, 61.9% of patients had a high risk of falling. Most falls (76.1%) occurred in patient rooms, and most of these occurred while wandering around. The most frequent reason for falls was slipping (14/21). For 16 of 21 patients, falls did not have immediate consequences, while 5 had contusions and 1 suffered a wound. Nobody needed to be admitted to the ER or suffered external hemorrhages or loss of consciousness. CONCLUSIONS: Non-slip socks represent an adequate alternative to well-fitting rubber-soled footwear. It seems that non-slip socks could prevent falls among hospitalized patients; nevertheless, further studies are necessary to clarify their role in preventing hospital falls and reducing injury rates.

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