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1.
Case Rep Ophthalmol ; 15(1): 36-40, 2024.
Article En | MEDLINE | ID: mdl-38196924

Introduction: Silicone oil (SO) is a crucial agent used as an intraocular tamponade in the treatment of complex vitreoretinal diseases. Despite its effectiveness, SO is prone to emulsification, which can lead to significant and sometimes irreversible complications in both the anterior and posterior segments of the eye. The detection and monitoring of SO emulsification are therefore of paramount importance. Traditional imaging modalities have limitations in visualizing SO, leading to the exploration of more advanced imaging techniques. This study introduces the application of dynamic infrared confocal scanning laser ophthalmoscopy (IRcSLO) for this purpose and evaluates its effectiveness. Case Presentation: We report on 2 patients who underwent pars plana vitrectomy with subsequent SO injection for the management of retinal detachment. Postsurgery, both patients were imaged using the Heidelberg Retina Tomography Spectralis IRcSLO. The focus was on the visualization of the SO status, including the presence and distribution of emulsified SO droplets. The IRcSLO imaging technique demonstrated its capability to effectively visualize emulsified SO droplets. Interestingly, this was also true for cases where the SO had been removed. The emulsified droplets were observed as micron-sized, spherical entities with a nonuniform distribution throughout the vitreous cavity. Conclusion: Dynamic IRcSLO has proven to be an effective imaging modality for visualizing the emulsification of SO, offering a novel perspective into the characterization of SO droplets. It facilitates the analysis of droplet count, motility, and precise localization within the vitreous cavity. The findings from the case presentations underscore the variability of SO emulsification patterns and the sensitivity of IRcSLO in detecting even minuscule emulsified droplets. This imaging technique has significant potential for future research, particularly in understanding the timing of emulsification, the factors contributing to it, and the development of possible preventive strategies. Additionally, it allows for a more in-depth analysis of the behavior of emulsified SO droplets across different SO viscosities, which could be instrumental in optimizing patient outcomes.

2.
Heliyon ; 9(9): e19604, 2023 Sep.
Article En | MEDLINE | ID: mdl-37810139

This study aims to evaluate the safety, biocompatibility, and functionality of a new accommodative intraocular lens (IOL) (LUZ, patent PCT/ES2016/070,813) after implantation in rabbit eyes. LUZ (Study) and EyeCee® plus a capsular ring (Control) were implanted in rabbits (n = 8 each) after phacoemulsification. Intraoperative follow-up, long-term clinical follow-up, and functional IOL studies were carried out periodically for up to 180 days. A macroscopic examination of the eyeballs to reveal abnormalities and determine the implant centering and a microscopic examination to semi-quantify cell and tissue response were performed. Statistical analysis of the collected data was finally achieved. During follow-up, no significant changes in the general condition nor the clinical evaluation were observed between both groups. However, Study IOL remained centered throughout the study and did not present severe complications as observed in the Control group. Functional studies did not reveal significant differences between both materials. Study showed better centering, fewer adhesions, and maintenance of an opening capsular bag compared to the Control. Local biological effects caused by Study implantation are minimal and comparable to the Control. Therefore, LUZ showed no clinical signs or histological response of adverse reaction to the implanted material, according to UNE-EN ISO 11979-5 and 10993-6. Functionality must be confirmed in another animal species with greater lens accommodation capacity than the rabbit. LUZ keeps the capsular bag open, favoring its centering and avoiding fibrosis and adherence to the bag; this allows potential accommodation of this IOL and theoretically enables the patient to focus dynamically.

3.
Cephalalgia ; 43(9): 3331024231201576, 2023 09.
Article En | MEDLINE | ID: mdl-37728578

BACKGROUND: Since the first description of nummular headache (NH), more than 500 cases have been described, delineating its clinical phenotype and response to treatment. However, data on the natural history of NH and outcomes during long-term follow-up are not currently available. The present study aimed to describe the long-term outcomes and follow-up of a large series of patients with NH. METHODS: A descriptive observational ambisective study with a series of cases was conducted. The study population included adult patients with primary NH and a minimum of 12 months of follow-up. Demographic variables, previous medical history, clinical phenotype, diagnosis and treatment of NH, temporal pattern, and long-term evolution were analysed. RESULTS: In total, 168 patients were enrolled and followed for a median [interquartile range (IQR)] of 80.5 (55-118.5) months. The temporal pattern after NH onset was chronic in 67.9% and, at diagnosis, the median (IQR) number of pain days per month was 20 [10-30] days with 138 (82.1%) patients with ≥8 days of pain per month. Preventive treatment was needed by 112 (66.7%) patients. The most frequently used drugs were gabapentin (69/112; 61.6%), onabotulinumtoxinA (38/112; 33.9%), amitriptyline (31/112; 27.7%) and lamotrigine (21/112; 18.7%). Response to preventive treatment was at least partial in 91/112 (81.3%) patients. At the end of follow-up, 81 (48.2%) patients had inactive NH. Of patients with active NH, the median (IQR) number of headache days per month was 3 (1-12) days and patients had ≥8 days of pain in 35 (20.8%) cases. CONCLUSIONS: Long-term outcomes of NH were positive in most patients. After a median of 6.7 years of follow-up, 48% of cases were inactive. Two-thirds of patients required preventive treatment, and 80% of them were treatment-responsive. In NH cases that remained symptomatic, the headache frequency was lower, and the proportion of patients with chronic NH decreased from 68% to 11%.


Headache Disorders , Headache , Adult , Humans , Amitriptyline , Follow-Up Studies , Headache/drug therapy , Headache/epidemiology , Pain
4.
Gut ; 72(3): 472-483, 2023 03.
Article En | MEDLINE | ID: mdl-35580962

OBJECTIVE: p63 is a transcription factor within the p53 protein family that has key roles in development, differentiation and prevention of senescence, but its metabolic actions remain largely unknown. Herein, we investigated the physiological role of p63 in glucose metabolism. DESIGN: We used cell lines and mouse models to genetically manipulate p63 in hepatocytes. We also measured p63 in the liver of patients with obesity with or without type 2 diabetes (T2D). RESULTS: We show that hepatic p63 expression is reduced on fasting. Mice lacking the specific isoform TAp63 in the liver (p63LKO) display higher postprandial and pyruvate-induced glucose excursions. These mice have elevated SIRT1 levels, while SIRT1 knockdown in p63LKO mice normalises glycaemia. Overexpression of TAp63 in wild-type mice reduces postprandial, pyruvate-induced blood glucose and SIRT1 levels. Studies carried out in hepatocyte cell lines show that TAp63 regulates SIRT1 promoter by repressing its transcriptional activation. TAp63 also mediates the inhibitory effect of insulin on hepatic glucose production, as silencing TAp63 impairs insulin sensitivity. Finally, protein levels of TAp63 are reduced in obese persons with T2D and are negatively correlated with fasting glucose and homeostasis model assessment index. CONCLUSIONS: These results demonstrate that p63 physiologically regulates glucose homeostasis.


Diabetes Mellitus, Type 2 , Sirtuin 1 , Trans-Activators , Animals , Mice , Glucose/metabolism , Liver/metabolism , Pyruvates/metabolism , Sirtuin 1/metabolism , Trans-Activators/metabolism
5.
Front Pharmacol ; 14: 1310463, 2023.
Article En | MEDLINE | ID: mdl-38283844

Introduction: Ala®sil infusion was on the market for clinical use under the Medical Devices Directive (MDD) 93/42/EEC as an irrigating solution based on polydimethylsiloxane (PDMS). The product was withdrawn in 2016, and to the best of our knowledge, it did not cause any health damage. Methods: A bibliographic review and experimental analysis were conducted to evaluate whether this CE-marked product could have been used in patients under the current Medical Device Regulation (MDR) 2017/745. Analytical results from gas chromatography-mass spectrometry (GC-MS) and matrixassisted laser desorption ionization (MALDI) were performed. Citotoxicity studies were also carried out. Results: Only one study related to Ala®sil clinical use was found, describing a pilot series of five patients. The authors rated the product as not helpful in three out of the five cases for internal searching of retinal breaks and in four out of the five cases for drainage of subretinal fluid. No other scientific papers or documentation was found regarding Ala®sil's safety. Nevertheless, the product was introduced in the market after achieving the CE marking. GC-MS and MALDI showed that the polymer has a low molecular weight of 1,000 g/mol. Several linear and cyclic low-molecular-weight components (LMWCs) were identified as impurities ranging from L3 to D8, with a molecular weight below 600 g/mol. The Ala®sil sample was found to be cytotoxic after 24 h of cell culture but non-cytotoxic after 72 h, probably due to the cellular regeneration capacity of an immortalized cell line. Tissular cytotoxicity revealed an increased apoptosis rate but without morphological modifications. Discussion: Although Ala®sil cannot be classified as cytotoxic, this substance appears to increase retinal cell death processes. This study supports the notion that the MDDwas not functioning adequately to ensure the safety of medical devices. However, the current MDR 2017/745 imposes stricter standards to prevent the commercialization of medical devices without high-quality preclinical and clinical information, as well as precise clinical verification for their use, information not available for Ala®sil infusion.

6.
Aten Primaria ; 54 Suppl 1: 102462, 2022 10.
Article Es | MEDLINE | ID: mdl-36435581

The update of the preventive activities for this year 2022 in the field of infectious diseases is of special relevance due to the importance that prevention has gained and more specifically, vaccination as a tool to control the pandemic caused by the SARS-CoV-2 virus declared on March 11, 2020. The pandemic has focused much of the prevention efforts on its containment, but the importance of maintaining high vaccination coverage of the rest of the recommended vaccines to maintain good control of vaccine-preventable diseases and avoid complications in particularly vulnerable patients should not be forgotten. In this year's review we present a practical document with the aim of providing tools to primary care professionals who work with adults, to make the indication of each vaccine whether it is systematically recommended or if it is because the patient belongs to some risk group due to their condition or underlying pathology. In this way, throughout the document, we will comment on the most innovative aspects of systematic vaccination (flu, pneumococcus, meningococcal vaccines and vaccines against the human papillomavirus [HPV]), the new vaccines (pandemic vaccines against COVID-19, vaccines against herpes zoster of subunits, vaccines against monkeypox) and the recommended vaccines according to risk condition (pregnancy and lactation, travelers, patients with immunosuppression or underlying pathology).


COVID-19 , Vaccines , Adult , Pregnancy , Female , Humans , COVID-19 Vaccines , COVID-19/prevention & control , SARS-CoV-2 , Vaccination
7.
Nat Metab ; 4(7): 901-917, 2022 07.
Article En | MEDLINE | ID: mdl-35879461

Early-life determinants are thought to be a major factor in the rapid increase of obesity. However, while maternal nutrition has been extensively studied, the effects of breastfeeding by the infant on the reprogramming of energy balance in childhood and throughout adulthood remain largely unknown. Here we show that delayed weaning in rat pups protects them against diet-induced obesity in adulthood, through enhanced brown adipose tissue thermogenesis and energy expenditure. In-depth metabolic phenotyping in this rat model as well as in transgenic mice reveals that the effects of prolonged suckling are mediated by increased hepatic fibroblast growth factor 21 (FGF21) production and tanycyte-controlled access to the hypothalamus in adulthood. Specifically, FGF21 activates GABA-containing neurons expressing dopamine receptor 2 in the lateral hypothalamic area and zona incerta. Prolonged breastfeeding thus constitutes a protective mechanism against obesity by affecting long-lasting physiological changes in liver-to-hypothalamus communication and hypothalamic metabolic regulation.


Breast Feeding , Obesity , Animals , Female , Fibroblast Growth Factors , Humans , Hypothalamus/metabolism , Liver/metabolism , Mice , Obesity/metabolism , Obesity/prevention & control , Rats
8.
Comunidad (Barc., Internet) ; 24(1)marzo 2022. graf, tab
Article Es | IBECS | ID: ibc-206275

Las personas ancianas que viven en las residencias geriátricas son una población de alto riesgo de sufrir importantes consecuencias de la pandemia por SARS-CoV-2, por lo que se analiza una población de ancianas de una institución geriátrica durante la primera ola de la pandemia y se describe el brote epidémico que sufrieron. La población de estudio fue de 157 residentes de una institución geriátrica durante un brote de infección por SARS-CoV-2. Se hizo un estudio prospectivo realizando un seguimiento diario por el equipo del centro de salud. Durante el seguimiento, se realizaron test de PCR para SARS-CoV-2, así como determinación de anticuerpos totales y disgregados. En la población anciana, la sintomatología inespecífica retrasa el diagnóstico y contribuye a la propagación del proceso. Se necesitan pautas de prevención muy estrictas y un control precoz de los casos positivos ya que la pandemia ha demostrado que son en estas residencias donde se produce mayor letalidad. (AU)


The elderly living in nursing homes are a high-risk population who have been negatively impacted by the SARS-CoV-2 pandemic. A population of elderly women from a nursing home was analysed during the first wave of the pandemic, describing the epidemic outbreak they suffered during this first wave. The study population was 157 residents of a geriatric institution during an outbreak of SARS-CoV-2 infection. A prospective study was conducted with daily monitoring by a team from the health centre. During the follow-up, the PCR test for SARS-CoV-2 was performed, as well as a detection of antibodies and disaggregates. In the elderly population, nonspecific symptoms delay a diagnosis and contribute to the spread of the process. Very strict prevention guidelines are needed, along with the early control of positive cases, since the pandemic has shown that it is these residences where the greatest fatality has occurred. (AU)


Humans , Coronavirus Infections/epidemiology , Pandemics , Primary Health Care , Severe acute respiratory syndrome-related coronavirus , Aged
9.
Stroke ; 53(3): 976-986, 2022 03.
Article En | MEDLINE | ID: mdl-35130716

BACKGROUND: Cavernous cerebral malformations can arise because of mutations in the CCM1, CCM2, or CCM3 genes, and lack of Cdc42 has also been reported to induce these malformations in mice. However, the role of the CCM3 (cerebral cavernous malformation 3)-associated kinases in cavernoma development is not known, and we, therefore, have investigated their role in the process. METHODS: We used a combination of an in vivo approach, using mice genetically modified to be deficient in the CCM3-associated kinases STK24 and STK25 (serine/threonine kinases 24 and 25), and the in vitro model of human endothelial cells in which expression of STK24 and STK25 was inhibited by RNA interference. RESULTS: Mice deficient for both Stk24 and Stk25, but not for either of them individually, developed aggressive vascular lesions with the characteristics of cavernomas at an early age. Stk25 deficiency also gave rise to vascular anomalies in the context of Stk24 heterozygosity. Human endothelial cells deficient for both kinases phenocopied several of the consequences of CCM3 loss, and single STK25 deficiency also induced KLF2 expression, Golgi dispersion, altered distribution of ß-catenin, and appearance of stress fibers. CONCLUSIONS: The CCM3-associated kinases STK24 and STK25 play a major role in the inhibition of cavernoma development.


Central Nervous System Neoplasms/genetics , Germinal Center Kinases/genetics , Hemangioma, Cavernous, Central Nervous System/genetics , Human Umbilical Vein Endothelial Cells/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Protein Serine-Threonine Kinases/genetics , Animals , Central Nervous System Neoplasms/metabolism , Germinal Center Kinases/metabolism , Hemangioma, Cavernous, Central Nervous System/metabolism , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Mice , Mice, Knockout , Phosphorylation , Protein Serine-Threonine Kinases/metabolism
10.
Graefes Arch Clin Exp Ophthalmol ; 260(7): 2103-2110, 2022 Jul.
Article En | MEDLINE | ID: mdl-35122500

BACKGROUND: Acute retinal toxicity has been demonstrated to be associated with the intraoperative use of perfluorocarbon liquids (PFCLs), especially perfluorooctane (PFO). Recently, several cases of PFO-associated blindness have been reported in Spain, Holland, France, Italy, the Middle East, and South America. METHODS: As a result, a new ISO guideline (ISO 16672:2020) was drafted, discussed, approved, and released in 2019. This recent ISO16672:2020 guideline recommends performing direct cytotoxicity tests as an option along with chemical analysis to measure PFCL quality (purity and safety). RESULTS: In this review paper, it has been emphasized why an appropriate biological test, specifically direct exposure of PFCL to live cells, for measuring cytotoxicity must be performed with each PFCL batch along with chemical analysis. CONCLUSIONS: The paper intends to compile all available information to discuss possible approaches for avoiding adverse clinical cases in future.


Fluorocarbons , Retinal Detachment , Fluorocarbons/toxicity , France , Humans , Italy , Middle East , Retinal Detachment/chemically induced , Retinal Detachment/surgery , Spain
11.
J Hepatol ; 77(1): 15-28, 2022 07.
Article En | MEDLINE | ID: mdl-35167910

BACKGROUND & AIMS: The pathogenesis of liver fibrosis requires activation of hepatic stellate cells (HSCs); once activated, HSCs lose intracellular fatty acids but the role of fatty acid oxidation and carnitine palmitoyltransferase 1A (CPT1A) in this process remains largely unexplored. METHODS: CPT1A was found in HSCs of patients with fibrosis. Pharmacological and genetic manipulation of CPT1A were performed in human HSC cell lines and primary HCSs. Finally, we induced fibrosis in mice lacking CPT1A specifically in HSCs. RESULTS: Herein, we show that CPT1A expression is elevated in HSCs of patients with non-alcoholic steatohepatitis, showing a positive correlation with the fibrosis score. This was corroborated in rodents with fibrosis, as well as in primary human HSCs and LX-2 cells activated by transforming growth factor ß1 (TGFß1) and fetal bovine serum (FBS). Furthermore, both pharmacological and genetic silencing of CPT1A prevent TGFß1- and FBS-induced HSC activation by reducing mitochondrial activity. The overexpression of CPT1A, induced by saturated fatty acids and reactive oxygen species, triggers mitochondrial activity and the expression of fibrogenic markers. Finally, mice lacking CPT1A specifically in HSCs are protected against fibrosis induced by a choline-deficient high-fat diet, a methionine- and choline-deficient diet, or treatment with carbon tetrachloride. CONCLUSIONS: These results indicate that CPT1A plays a critical role in the activation of HSCs and is implicated in the development of liver fibrosis, making it a potentially actionable target for fibrosis treatment. LAY SUMMARY: We show that the enzyme carnitine palmitoyltransferase 1A (CPT1A) is elevated in hepatic stellate cells (HSCs) in patients with fibrosis and mouse models of fibrosis, and that CPT1A induces the activation of these cells. Inhibition of CPT1A ameliorates fibrosis by preventing the activation of HSCs.


Carnitine O-Palmitoyltransferase , Hepatic Stellate Cells , Animals , Carnitine O-Palmitoyltransferase/genetics , Carnitine O-Palmitoyltransferase/metabolism , Choline , Fatty Acids/metabolism , Fibrosis , Hepatic Stellate Cells/metabolism , Humans , Liver/pathology , Liver Cirrhosis/metabolism , Liver Cirrhosis/prevention & control , Mice
12.
Acta Ophthalmol ; 100(4): e864-e880, 2022 Jun.
Article En | MEDLINE | ID: mdl-34846097

Silicone oil (SO) still represents the main choice for long-term intraocular tamponade in complicated vitreoretinal surgery. This review compared the complications associated with the use of SO and other vitreous substitutes after pars plana vitrectomy in patients with different underlying diseases. Meta-analysis was conducted in accordance with PRISMA guidelines. We retrieved randomized clinical trials (RCTs), retrospective case-control and cohort studies evaluating the risk of using SO, published between 1994 and 2020, conducting a computer-based search of the following databases: PubMed, Web of Science, Scopus and Embase. Primary outcome was the rate of complications such as intraocular hypertension, retinal re-detachment, unexpected vision loss or hypotony. Secondary outcome was to compare the rate of adverse events of different SO viscosities, especially emulsification. Forty-three articles were included. There were significant differences in intraocular hypertension (p = 0.0002, OR = 1.66; 95% CI = 1.27-2.18) and the rate of retinal re-detachment (p < 0.0009, OR = 0.65; 95% CI = 0.50-0.64) between SO and other agents, including placebo. However, there were no differences in other complication rates. Silicone oil (SO)-emulsification rate was non-significantly higher in low than high SO viscosity, and results from other complications were comparable in both groups. The high quality of most of the studies included in this study is noteworthy, which provides some certainty to the conclusions. Among them is the high variability of the SO residence time. The fact that ocular hypertension and not hypotension is related to SO use. A clear relationship is not found for the so-called unexplained vision loss, which affects a significant percentage of eyes. Re-detachment cases are less if SO is used and that surprisingly there does not seem to be a relationship in the percentage of emulsification between the low- and high-viscosity silicones. All these data warrant more standardized prospective studies.


Hypertension , Retinal Detachment , Vitreoretinal Surgery , Humans , Hypertension/complications , Retinal Detachment/etiology , Retrospective Studies , Silicone Oils/adverse effects , Vitrectomy/adverse effects , Vitreoretinal Surgery/adverse effects
13.
J Clin Med ; 12(1)2022 Dec 23.
Article En | MEDLINE | ID: mdl-36614923

Nummular headache (NH) is a primary headache characterized by superficial coin-shaped pain. NUMITOR (NCT05475769) is an observational study evaluating the responder rate of preventive drugs in NH patients. The treatment response was assessed between weeks 8 and 12 compared with the baseline. Patients were included between February 2002 and October 2022. Demographic and clinical variables were assessed; treatment response was estimated by 50%, 30%, and 75% responder rates and treatment discontinuation due to inadequate tolerability. A total of 183 out of 282 patients fulfilled eligibility criteria and completed the study. Patients were aged 49.5 (standard deviation (SD): 16.8) years, and 60.7% were female. NH phenotype was a parietal circular pain of four centimeters' diameter, moderate intensity, and oppressive quality. At baseline, patients had 25 (interquartile range) pain days per month. Preventive treatment was used by 114 (62.3%) patients. The highest 50% and 75% responder rates corresponded to onabotulinumtoxinA (62.5%, 47.5%), followed by gabapentin (43.7%, 35.2%). Oral preventive drugs were not tolerated by 12.9-25%. The present study provides class IV evidence of the effectiveness of oral preventive drugs and onabotulinumtoxinA in the treatment of primary NH. OnabotulinumtoxinA was the most effective and best-tolerated drug, positioning it as first-line treatment of NH.

14.
Transl Vis Sci Technol ; 10(14): 17, 2021 12 01.
Article En | MEDLINE | ID: mdl-34919130

Purpose: High frequency of cataracts and the requirements of new European Union regulations for medical devices require the availability of preclinical models to adequately evaluate anterior lens capsule dyes before their use in patients. Herein, we describe an ex vivo method to quantifiably evaluate the macroscopic and microscopic staining effectiveness of anterior lens capsule dyes using porcine eyes. Methods: Commercially available trypan blue-based products or physiological saline solution (negative control) was injected into porcine eyes. Anterior pole and lens (after extraction) were macroscopically photographed, and the images were quantitatively analyzed. Lenses were histologically processed, and the staining intensity microscopically was semiquantified. Results: Macroscopic evaluation of the anterior pole revealed bluish staining of the anterior capsule; however, this coloring cannot be macroscopically discerned after lens extraction. Quantitative image analyses showed significant (P < 0.01) staining of the lens capsule compared to the negative control, but not significant (P > 0.05) between the products tested. Quantitative analysis of dying on lens images could not be performed. Microscopic semiquantification of the capsule staining intensity allows us to appreciate differences between products. Conclusions: The described method is a quick and useful tool for macroscopic evaluation by surgeons to choose an anterior capsule staining for use during everyday surgeries, and a more specific microscopic evaluation also allows us to determine the effectiveness and usefulness of these products. Translational Relevance: This method satisfies preclinical effectiveness evaluations required by European Union regulations and complements the safety and toxicity evaluations that new products must guarantee before they enter the market and are used in clinical practice.


Anterior Capsule of the Lens , Lens Capsule, Crystalline , Animals , Anterior Capsule of the Lens/diagnostic imaging , Coloring Agents , Humans , Staining and Labeling , Swine , Trypan Blue
15.
Nat Commun ; 12(1): 5068, 2021 08 20.
Article En | MEDLINE | ID: mdl-34417460

p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.


Acetylglucosamine/metabolism , Glucose/metabolism , Liver/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Base Sequence , Caloric Restriction , Cell Line , Colforsin/pharmacology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Epinephrine/metabolism , Glucagon/metabolism , Glucocorticoids/metabolism , Gluconeogenesis/drug effects , Glycosylation , Hepatocytes/drug effects , Hepatocytes/metabolism , Humans , Hydrocortisone/metabolism , Hyperglycemia/complications , Hyperglycemia/metabolism , Insulin Resistance , Intracellular Signaling Peptides and Proteins/metabolism , Liver/drug effects , Mice, Inbred C57BL , Mice, Knockout , Obesity/complications , Obesity/metabolism , Phosphoenolpyruvate Carboxykinase (GTP)/metabolism , Promoter Regions, Genetic/genetics , Protein Binding/drug effects , Protein Stability/drug effects , Pyruvic Acid/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription, Genetic/drug effects , Tumor Suppressor Protein p53/genetics
16.
Sci Rep ; 11(1): 14674, 2021 07 19.
Article En | MEDLINE | ID: mdl-34282206

To estimate the frequency of headache in patients with confirmed COVID-19 and characterize the phenotype of headache attributed to COVID-19, comparing patients depending on the need of hospitalization and sex, an observational study was done. We systematically screened all eligible patients from a reference population of 261,431 between March 8 (first case) and April 11, 2020. A physician administered a survey assessing demographic and clinical data and the phenotype of the headache. During the study period, 2194 patients out of the population at risk were diagnosed with COVID-19. Headache was described by 514/2194 patients (23.4%, 95% CI 21.7-25.3%), including 383/1614 (23.7%) outpatients and 131/580 (22.6%) inpatients. The headache phenotype was studied in detail in 458 patients (mean age, 51 years; 72% female; prior history of headache, 49%). Headache was the most frequent first symptom of COVID-19. Median headache onset was within 24 h, median duration was 7 days and persisted after 1 month in 13% of patients. Pain was bilateral (80%), predominantly frontal (71%), with pressing quality (75%), of severe intensity. Systemic symptoms were present in 98% of patients. Headache frequency and phenotype was similar in patients with and without need for hospitalization and when comparing male and female patients, being more intense in females.Trial registration: This study was supported by the Institute of Health Carlos III (ISCIII), code 07.04.467804.74011 and Regional Health Administration, Gerencia Regional de Salud, Castilla y Leon (GRS: 2289/A/2020).


COVID-19/complications , Headache/virology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pain , Phenotype , Young Adult
17.
Pain Med ; 22(11): 2718-2727, 2021 Nov 26.
Article En | MEDLINE | ID: mdl-34022054

BACKGROUND: Nummular headache (NH) is defined in the International Classification of Headache Disorders (ICHD) by the presence of localized pain circumscribed to a small round area of the scalp, not better accounted by any other diagnosis. As in many other primary headache disorders, secondary cases might occur. To date, 13 secondary cases have been published. We aim to present a long series of secondary NH and review the literature of symptomatic NH. PATIENTS AND METHODS: Retrospective analysis of an observational prospective cohort in a headache unit located in a tertiary hospital. We included patients that fulfilled ICHD criteria and were attributed to a secondary cause. We describe the clinical characteristics, the underlying causes, and the response to treatment. RESULTS: We included 274 NH patients; eight of them (2.9%) were considered secondary. In one patient the underlying cause was subcutaneous, as for six cases the lesion was located in the bone (two hemangiomas, one osteoma, three different types of cysts), and in one was intracranial but closely related with internal diploe (cavernoma). Among our patients with secondary NH, a preventive therapy was not always needed and, when required, gabapentin or onabotulinumtoxinA were used with positive response. CONCLUSIONS: Secondary NH phenotype overlaps primary NH. Therefore, we recommend routine imaging study in every NH patient. Concerning treatment, it was not necessary to remove the underlying lesion to control the pain and many cases responded to the same prophylactics as primary NH cases.


Headache Disorders , Headache , Gabapentin/therapeutic use , Headache/drug therapy , Humans , Prospective Studies , Retrospective Studies
18.
iScience ; 24(2): 102071, 2021 Feb 19.
Article En | MEDLINE | ID: mdl-33554072

Excessive consumption of high-fructose diets is associated with insulin resistance, obesity, and non-alcoholic fatty liver disease (NAFLD). However, fructose differentially affects hepatic regulation of lipogenesis in males and females. Hence, additional studies are necessary in order to find strategies taking gender disparities in fructose-induced liver damage into consideration. Although the eighth member of facilitated glucose transporters (GLUT8) has been linked to fructose-induced macrosteatosis in female mice, its contribution to the inflammatory state of NAFLD remains to be elucidated. Combining pharmacological, biochemical, and proteomic approaches, we evaluated the preventive effect of targeted liver GLUT8 silencing on liver injury in a mice female fructose-induced non-alcoholic steatohepatitis female mouse model. Liver GLUT8-knockdown attenuated fructose-induced ER stress, recovered liver inflammation, and dramatically reduced fatty acid content, in part, via the omega oxidation. Therefore, this study links GLUT8 with liver inflammatory response and suggests GLUT8 as a potential target for the prevention of NAFLD.

19.
Rev. clín. med. fam ; 14(1): 12-17, Feb. 2021. tab
Article Es | IBECS | ID: ibc-230094

Objetivo: evaluar y comparar el cumplimiento terapéutico entre los diferentes anticoagulantes orales. Diseño: estudio descriptivo transversal. Emplazamiento: Atención Primaria. Zona Básica de Salud de Bargas. Participantes: se incluyó a pacientes que llevasen más de 6 meses en tratamiento con anticoagulantes orales, pertenecientes a seis cupos de Medicina Familiar. Se excluyó a pacientes desplazados, incapaces de tomar la medicación de forma autónoma, ingresados o fallecidos durante el estudio. Mediciones principales: las variables estudiadas fueron: edad, sexo, nivel educativo, unidad familiar, tiempo de tratamiento, tipo de anticoagulante, efectos secundarios, polimedicación, tipo de receta, educación para la salud y cumplimiento terapéutico. Se realizó estadística descriptiva y analítica. Resultados: se evaluaron 110 pacientes con una edad media de 73,02 (desviación estándar [DE]: 12,06) años. Un 29,1% en tratamiento con anticoagulantes orales de acción directa (ACOD). La mediana de tiempo de tratamiento fue de 47 meses (rango intercuartílico: 16-77,25), el 84,5% eran polimedicados (7,36 ± 3,96 fármacos de media). Fueron cumplidores en total el 81,81% (intervalo de confianza [IC] 95% 73,32-88,52%). El 93,75% fue cumplidor con ACOD (IC 95% 79,19-99,23%) frente al 76,92% con acenocumarol (IC 95% 66,00-85,71%) (p = 0,055). El cumplimiento en polimedicados fue del 86%, frente al 58,8% en no polimedicados (p = 0,02). Conclusión: Nuestro estudio ha mostrado una aparente mayor adherencia terapéutica en los pacientes tratados con ACODs con respecto a los tratados con acenocumarol. La adherencia al tratamiento es mayor en los pacientes polimedicados.(AU)


Aim: To evaluate and compare treatment compliance among different oral anticoagulants. Design: Transversal descriptive study. Location: Primary Care. Bargas Basic Healthcare Area. Participants: Patients in treatment with oral anticoagulants more than 6 months who belonged to six Family Medicine quotas were included. Displaced patients, those unable to take medication autonomously, admitted to hospital or who died during the study were excluded. Primary endpoints: The variables studied were: age, sex, educational level, family unit, treatment time, type of anticoagulant, side effects, polymedication, type of prescription, education for health and treatment compliance. Descriptive statistics and analysis were performed. Results: 110 patients with a mean age of 73.02 (SD: 12.06) years old were studied. A total of 29.1% were in treatment with oral anticoagulants (OACs). Median treatment time was 47 months (interquartile range: 16-77.25). A total of 84.5% were polymedicated (7.36±3.96 drugs on average). In total 81.81% (95%CI 73.32-88.52%) were compliant. A total of 93.75% complied with OACs (95%CI 79.19-99.23%) compared to 76.92% with acenocumarol (95%CI 66.00-85.71%) (p=0.055). Compliance in polymedicated patients was 86% compared to 58.8% in non-polymedicated patients (p=0.02). Conclusion: Our study revealed an apparent greater treatment adherence in patients treated with OACs in regard to those treated with acenocumarol. Treatment adherence is greater in polymedicated patients.(AU)


Humans , Male , Female , Treatment Adherence and Compliance , Primary Health Care , Factor Xa Inhibitors , Atrial Fibrillation , Anticoagulants/administration & dosage , Warfarin/administration & dosage , Epidemiology, Descriptive , Cross-Sectional Studies , Family Practice
20.
Rev. clín. med. fam ; 14(1): 40-42, Feb. 2021. ilus
Article Es | IBECS | ID: ibc-230100

El síndrome del cascanueces es la compresión de la vena renal izquierda. Presentamos el caso clínico de una paciente con cifras elevadas de presión arterial en relación con el ejercicio, a partir de lo cual se inicia el estudio y es diagnosticada de dicho síndrome. El tratamiento puede ser conservador o quirúrgico. Con este artículo queremos recalcar la importancia de los y las especialistas en Medicina Familiar y Comunitaria en el diagnóstico y seguimiento de esta patología, como posible causa de hipertensión arterial, ya que es la primera asistencia sanitaria que recibe el paciente y valora si es oportuno o o no su derivación para estudio.(AU)


Renal Nutcracker Syndrome is compression of the left renal vein. We report a patient with high blood pressure in regard to exercise, whereby the study was commenced and this syndrome diagnosed. Treatment may be conservative or surgical. By means of this paper we wish to stress the importance of the family doctor on diagnosis and follow up of this pathology, as a possible cause of blood pressure, because this is the first healthcare the patient receives and who deems the patient's referral for study as suitable.(AU)


Humans , Female , Adult , Primary Health Care , Renal Nutcracker Syndrome , Proteinuria , Renal Veins , Hematuria , Arterial Pressure , Inpatients , Physical Examination , Symptom Assessment , Hypertension , Exercise
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