Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 20.777
Filter
1.
BMC Nurs ; 23(1): 455, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961487

ABSTRACT

BACKGROUND: The first waves of the COVID-19 pandemic had a negative impact on health systems and health professionals, due to the high number of cases and a lack of preparation. The aim of this study was to understand how nurses working in hospital units and in intensive care perceived the performance of nurse managers and senior hospital management during the first two waves of the pandemic. METHODS: The phenomenological approach proposed by Giorgi was used to investigate perceptions of the performance of nurse managers and senior hospital management during the first two waves of the COVID-19 pandemic in Spain. Fourteen clinical nurses who worked on the front line in inpatient units or intensive care units of the Health Services of Extremadura and Madrid in the first (March-April 2020) and second (October-November 2020) waves of the COVID-19 pandemic participated in this study. The data was collected through semi-structured interviews, following a script of themes, in a theoretical sample of nurses who were worked during the pandemic. RESULTS: Two main themes emerged from the analysis of the data: (1) perceptions about the performance of nurse managers and senior hospital managers during the first and second waves of the pandemic (health system failure; belief that senior hospital management professionals could have managed the pandemic better; recognizing the efforts of middle management (nursing supervisors); insufficient institutional support) and (2) strategies employed by nurses to compensate for the weaknesses in pandemic management. CONCLUSIONS: The clinical nurses perceived that the nurse managers demonstrated better management of the pandemic than the hospital's senior management, which they attribute to their proximity, empathy, accessibility, and ability to mediate between them and the senior management. The nurses also believe that the senior management of the hospitals was to blame for organisational failures and the poor management of the pandemic.

2.
Biodivers Data J ; 12: e124603, 2024.
Article in English | MEDLINE | ID: mdl-38966039

ABSTRACT

Background: The family Synallactidae comprises mostly deep-sea forms and is the least-studied large taxon amongst deep-sea cucumbers. They are part of the abyssal megafauna and play an important role in modifying the sediment landscape and structuring the communities that live within it. The family embraces the genus Synallactes, which contains approximately twenty-five species from the Pacific, Atlantic (six species), Indian (seven species) and Antarctic Oceans (one species). New information: Synallactesmcdanieli sp. nov. is described from the Northeast Pacific, Knight Inlet, British Columbia, Canada to Kodiak Island, Gulf of Alaska, USA, at depths from 21 to 438 m. This new species is unique amongst the species of the genus Synallactes because of the number and arrangement of dorsal papillae, number of Polian vesicles, together with the entire ossicle arrangement. In addition, this species has the shallowest bathymetric distribution ever recorded for this genus.

3.
Heliyon ; 10(12): e32546, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38975228

ABSTRACT

Understanding the molecular and physical complexity of the tissue microenvironment (TiME) in the context of its spatiotemporal organization has remained an enduring challenge. Recent advances in engineering and data science are now promising the ability to study the structure, functions, and dynamics of the TiME in unprecedented detail; however, many advances still occur in silos that rarely integrate information to study the TiME in its full detail. This review provides an integrative overview of the engineering principles underlying chemical, optical, electrical, mechanical, and computational science to probe, sense, model, and fabricate the TiME. In individual sections, we first summarize the underlying principles, capabilities, and scope of emerging technologies, the breakthrough discoveries enabled by each technology and recent, promising innovations. We provide perspectives on the potential of these advances in answering critical questions about the TiME and its role in various disease and developmental processes. Finally, we present an integrative view that appreciates the major scientific and educational aspects in the study of the TiME.

4.
Cureus ; 16(6): e61876, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38975555

ABSTRACT

Influenza B infection, although primarily recognized for respiratory symptoms, can lead to rare but severe cardiac complications such as pericardial effusion and cardiac tamponade. We present a case of a 33-year-old female with morbid obesity who initially exhibited flu-like symptoms, was subsequently diagnosed with influenza B infection, and was discharged with symptomatic treatment. Despite initial discharge, she returned with worsening weakness, gastrointestinal symptoms, and shortness of breath. Imaging studies confirmed pericardial effusion with early signs of tamponade, necessitating an emergent intervention. The patient underwent subxiphoid pericardial window and fluid removal, followed by colchicine treatment to prevent recurrence. Our case highlights the importance of recognizing and promptly managing rare influenza-related complications, particularly in patients without significant comorbidities. It underscores the value of a proactive approach, utilizing point-of-care ultrasound and echocardiography for early diagnosis and intervention to mitigate mortality and morbidity risks associated with pericarditis and cardiac tamponade secondary to influenza B.

5.
Mycologia ; : 1-17, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976827

ABSTRACT

A new and threatened polypore species, Bondarzewia loguerciae, is described from the cloud forests of southern Brazil. It is characterized by single-pileate basidiomata that grow on dead branches and along living stems of standing trunks and present a context with dark lines and resinous tubes. When growing in axenic culture, this species also develops chlamydospores. We provide an illustrated morphological description and molecular analysis. Our specimens from Brazil form a monophyletic group among other species of the Southern Hemisphere. The conservation status of B. loguerciae is assessed and published as "Critically Endangered" based on the International Union for Conservation of Nature  (IUCN) criteria. Additionally, a key to the species is provided.

6.
Methods Mol Biol ; 2816: 87-100, 2024.
Article in English | MEDLINE | ID: mdl-38977591

ABSTRACT

Laparotomy (EL) is one of the most common procedures performed among surgical specialties. Previous research demonstrates that surgery is associated with an increased inflammatory response. Low psoas muscle mass and quality markers are associated with increased mortality rates after emergency laparotomy. Analysis of lipid mediators in serum and muscle by using liquid chromatography-mass spectrometry (LC-MS)-based lipidomics has proven to be a sensitive and precise technique. In this chapter, we describe an LC-MS/MS protocol for the profiling and quantification of signaling lipids formed from Eicosapentaenoic Acid (EPA) and Eicosatetranoic acid (ETA) by 5, 12, or 15 lipoxynases. This protocol has been developed for and validated in serum and muscle samples in a mouse model of surgical stress caused by laparotomy.


Subject(s)
Aging , Laparotomy , Lipidomics , Tandem Mass Spectrometry , Animals , Mice , Lipidomics/methods , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Aging/metabolism , Stress, Physiological , Disease Models, Animal , Lipids/analysis , Lipids/blood , Lipid Metabolism
7.
Exp Brain Res ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980339

ABSTRACT

The reticular thalamic nucleus (RTN) is a thin shell that covers the dorsal thalamus and controls the overall information flow from the thalamus to the cerebral cortex through GABAergic projections that contact thalamo-cortical neurons (TC). RTN neurons receive glutamatergic afferents fibers from neurons of the sixth layer of the cerebral cortex and from TC collaterals. The firing mode of RTN neurons facilitates the generation of sleep-wake cycles; a tonic mode or desynchronized mode occurs during wake and REM sleep and a burst-firing mode or synchronized mode is associated with deep sleep. Despite the presence of cannabinoid receptors CB1 (CB1Rs) and mRNA that encodes these receptors in RTN neurons, there are few works that have analyzed the participation of endocannabinoid-mediated transmission on the electrical activity of RTN. Here, we locally blocked or activated CB1Rs in ketamine anesthetized rats to analyze the spontaneous extracellular spiking activity of RTN neurons. Our results show the presence of a tonic endocannabinoid input, since local infusion of AM 251, an antagonist/inverse agonist, modifies RTN neurons electrical activity; furthermore, local activation of CB1Rs by anandamide or WIN 55212-2 produces heterogeneous effects in the basal spontaneous spiking activity, where the main effect is an increase in the spiking rate accompanied by a decrease in bursting activity in a dose-dependent manner; this effect is inhibited by AM 251. In addition, previous activation of GABA-A receptors suppresses the effects of CB1Rs on reticular neurons. Our results show that local activation of CB1Rs primarily diminishes the burst firing mode of RTn neurons.

8.
Cureus ; 16(6): e61600, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38962589

ABSTRACT

Background Although demographic and clinical factors such as age, certain comorbidities, and sex have been associated with COVID-19 outcomes, these studies were largely conducted in urban populations affiliated with large academic medical centers. There have been very few studies focusing on rural populations that also characterize broader changes in inflammatory cytokines and chemokines. Methodology A single-center study was conducted between June 2020 and March 2021 in Abilene, Texas, USA. Patients were included if they presented to the hospital for treatment of COVID-19, had extra biological materials from routine care available, and were between the ages of 0 to 110 years. There were no exclusion criteria. Patient characteristics, symptom presentation, and clinical laboratory results were extracted from electronic health records. Blood specimens were analyzed by protein microarray to quantitate 40 immunological biomarkers. Results A total of 122 patients were enrolled, of whom 81 (66%) were admitted to the general non-critical inpatient unit, 37 (30%) were admitted to the intensive or critical care units, and four (3.2%) were treated outpatient. Most hospitalized COVID-19 patients in this rural population were elderly, male, obese, and retired individuals. Predominant symptoms for non-critical patients were shortness of breath, fever, and fatigue. Ferritin levels for outpatient patients were lower on average than those in an inpatient setting and lactate dehydrogenase (LDH) levels were noted to be lower in non-critical and outpatient than those in the intensive care unit setting. Inflammatory biomarkers were positively correlated and consistent with inflammatory cascade. Interleukin (IL)-10 was positively correlated while platelet-derived growth factor was negatively correlated with inflammatory biomarkers. Patients ≥65 years had significantly higher levels of LDH and seven cytokines/chemokines (granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin IL-1b, IL-6, IL-10, IL-11, macrophage inflammatory protein (MIP)-1d, and IL-8) while levels of five other immune molecules (intercellular adhesion molecule 1 (ICAM-1), monocyte chemoattractant protein 1 (MCP-1), tissue inhibitor of metalloproteinase 2 (TIMP-2), IL-2, and IL-4) were significantly lower compared to those <65 years. Females had significantly higher levels of LDH and 10 cytokines/chemokines (GM-CSF, IL-1b, IL-6, IL-10, IL-11, IL-15, IL-16, MIP-1a, MIP-1d, and IL-8) while levels of TIMP-2 and IL-4 were significantly lower than male patients. Conclusions The clinical characteristics of this rural cohort of hospitalized patients differed somewhat from nationally reported data. The contributions of social, environmental, and healthcare access factors should be investigated. We identified age and sex-associated differences in immunological response markers that warrant further investigation to identify the underlying molecular mechanisms and impact on COVID-19 pathogenesis.

9.
Biomark Med ; : 1-15, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982732

ABSTRACT

Dermatologic disorders, affecting the integumentary system, involve diverse molecular mechanisms such as cell proliferation, apoptosis, inflammation and immune responses. Long noncoding RNAs, particularly Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), are crucial regulators of gene expression. MALAT1 influences inflammatory responses, immune cell function and signaling pathways, impacting various physiological and pathological processes, including dermatologic disorders. Dysregulation of MALAT1 is observed in skin conditions like psoriasis, atopic dermatitis and systemic lupus erythematosus. However, its precise role remains unclear. This review consolidates knowledge on MALAT1's impact on skin biology and pathology, emphasizing its potential diagnostic and therapeutic implications in dermatologic conditions.


[Box: see text].

10.
Am J Psychiatry ; : appiajp20230980, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38982828

ABSTRACT

OBJECTIVE: The authors sought to assess the prosocial, entactogen effects of ketamine. METHODS: Pleasure from social situations was assessed in a sample of participants with treatment-resistant depression from randomized, double-blind, placebo-controlled studies, using four items of the Snaith-Hamilton Pleasure Scale (SHAPS) at five time points over 1 week following treatment with ketamine (0.5 mg/kg intravenously) or placebo. The primary endpoint was postinfusion self-reported pleasure on the four SHAPS items pertaining to social situations, including the item on helping others, between the ketamine and placebo groups. In a rodent experiment, the impact of ketamine on helping behavior in rats was assessed using the harm aversion task. The primary endpoint was a reduction in lever response rate relative to baseline, which indicated the willingness of rats to forgo obtaining sucrose to help protect their cage mate from electric shock. RESULTS: Relative to placebo, ketamine increased ratings of feeling pleasure from being with family or close friends, seeing other people's smiling faces, helping others, and receiving praise, for 1 week following treatment. In the rodent experiment, during the harm aversion task, ketamine-treated rats maintained lower response rates relative to baseline to a greater extent than what was observed in vehicle-treated rats for 6 days posttreatment and delivered fewer shocks overall. CONCLUSIONS: In patients with treatment-resistant depression, ketamine treatment was associated with increased pleasure from social situations, such as feeling pleasure from helping others. Ketamine-treated rats were more likely to protect their cage mate from harm, at the cost of obtaining sucrose. These findings suggest that ketamine has entactogen effects.

11.
Angew Chem Int Ed Engl ; : e202409527, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38959351

ABSTRACT

We investigate the inhibition mechanism between pomotrelvir and the SARS-CoV-2 main protease using molecular mechanics and quantum mechanics / molecular mechanics simulations. Alchemical transformations where each Pi group of pomotrelvir was transformed into its counterpart in nirmatrelvir were performed to unravel the individual contribution of each group to the binding and reaction processes. We have shown that while a γ-lactam ring is preferred at position P1, a δ-lactam ring is a reasonable alternative. For the P2 position, tertiary amines are preferred with respect to secondary amines. Flexible side chains at P2 position can disrupt the preorganization of the active site, favouring the exploration of non-reactive conformations. The substitution of the P2 group of pomotrelvir by that of nirmatrelvir resulted in a compound, named as C2, that presents better binding free energy and a higher population of reactive conformations in the Michaelis complex. Analysis of the chemical reaction to form the covalent complex has shown a similar reaction mechanism and activation free energies for pomotrelvir, nirmatrelvir and C2. We hope that these findings could be useful to design better inhibitors to fight present and future variants of SARS-CoV-2 virus.

12.
Article in English | MEDLINE | ID: mdl-38958827

ABSTRACT

The increasing aging of the population combined with improvements in cancer detection and care has significantly improved the survival and quality of life of cancer patients. These benefits are hampered by the increase of cardiovascular diseases being heart failure the most frequent manifestation of cardiotoxicity and becoming the major cause of morbidity and mortality among cancer survivor. Current strategies to prevent cardiotoxicity involves different approaches such as optimal management of CV risk factors, use of statins and/or neurohormonal medications, and, in some cases, even the use of chelating agents. As a class, SGLT2-i have revolutionized the therapeutic horizon of HF patients independently of their ejection fraction or glycemic status. There is an abundance of data from translational and observational clinical studies supporting a potential beneficial role of SGLT2-i in mitigating the cardiotoxic effects of cancer patients receiving anthracyclines. These findings underscore the need for more robust clinical trials to investigate the effect on cardiovascular outcomes of the prophylactic SGLT2-i treatment in patients undergoing cancer treatment.

13.
J Theor Biol ; : 111894, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992463

ABSTRACT

In this paper, we explore the effects of biological (pathological) and mechanical damage on bone tissue within a benchmark model. Using the Finite Element Methodology, we analyze and numerically test the model's components, capabilities, and performance under physiologically and pathologically relevant conditions. Our findings demonstrate the model's effectiveness in simulating bone remodeling processes and self-repair mechanisms for micro-damage induced by biological internal conditions and mechanical external ones within bone tissue. This article is the second part of a series, where the first part presented the mathematical model and the biological and physical significance of the terms used in a simplified benchmark model. It explored the bone remodeling model's application, implementation, and results under physiological conditions.

14.
J Prosthodont ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992883

ABSTRACT

PURPOSE: This systematic review and meta-analysis aimed to evaluate the depth distortion and angular deviation of fully-guided tooth-supported static surgical guides (FTSG) in partially edentulous arches compared to partially guided surgical guides or freehand. MATERIAL AND METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in the Open Science Framework (OSF). The formulated population, intervention, comparison, and outcome (PICO) question was: "In partially edentulous arches, what are the depth distortion and angular deviation of FTSG compared to partially guided surgical guides or freehand?" The search strategy involved four main electronic databases, and an additional manual search was completed in November 2023 by following an established search strategy. Initial inclusion was based on titles and abstracts, followed by a detailed review of selected studies, and clinical studies that evaluated the angular deviations or depth distortion in FTSG in partial arches, compared to partially guided surgical guides or freehand, were included. In FTSG, two surgical approaches were compared: open flap and flapless techniques, and two digital methods were assessed for surgical guide design with fiducial markers or dental surfaces. A qualitative analysis for clinical studies was used to assess the risk of bias. The certainty of the evidence was assessed according to the grading of recommendations, assessment, development, and evaluations (GRADE) system. In addition, a single-arm meta-analysis of proportion was performed to evaluate the angular deviation of freehand and FTSG. RESULTS: Ten studies, published between 2018 and 2023, met the eligibility criteria. Among them, 10 studies reported angular deviations ranging from -0.32° to 4.96° for FTSG. Regarding FTSG surgical approaches, seven studies examined the open flap technique for FTSG, reporting mean angular deviations ranging from 2.03° to 4.23°, and four studies evaluated flapless FTSG, reporting angular deviations ranging from -0.32° to 3.38°. Six studies assessed the freehand surgical approach, reporting angular deviations ranging from 1.40° to 7.36°. The mean depth distortion ranged between 0.19 mm to 2.05 mm for open flap FTSG, and between 0.15 mm to 0.45 mm for flapless FTSG. For partially guided surgical guides, two studies reported angular deviations ranging from 0.59° to 3.44°. Seven studies were eligible for meta-analysis, focusing on the FTSG in open flap technique, with high heterogeneity (I2 (95%CI) = 92.3% (88.7%-96.4%)). In contrast, heterogeneity was low in studies comparing freehand versus FTSG in open flap techniques (I2 (95%CI) = 21.3% (0.0%-67.8%)), favoring the FTSG surgical approach. CONCLUSION: In partially edentulous arches, FTSG systems exhibited less angular deviation than freehand and partially guided surgical guides. Flapless surgical approaches were associated with reduced angular deviation and depth distortion, suggesting a potential preference for the FTSG method in these procedures.

15.
J Nutr ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39019158

ABSTRACT

BACKGROUND: Absorption of tryptophan (TRP) across the gut epithelium is potentially modulated by competing large neutral amino acids (LNAAs), which could affect the appearance of TRP and its metabolites in the bloodstream. OBJECTIVES: This study aimed to determine, in a growing pig model of an adult human, the absorption of TRP and other LNAAs from the gastrointestinal tract, and plasma appearance of TRP, LNAAs and TRP metabolites , in response to dietary proteins varying in TRP content. METHODS: Pigs were adapted for seven days to each of four diets that differed in their protein source and TRP content: 1) alpha-lactalbumin (AL; 9.95mg TRP/g diet DM), 2) whey protein (6.59mg TRP/g), 3) casein (3.73mg TRP/g), or 4) zein (0.14mg TRP/g). On day 8, after a 12h fast, pigs received a test meal consisting of 45g protein, or a protein-free meal, and were euthanized 0 (baseline), 1, 2, 3, 4, or 6h later (n=6 pigs at each time in each meal group). Tryptophan and LNAA absorption from the small intestine, and appearance of TRP, LNAAs and TRP metabolites (melatonin, serotonin, kynurenine pathway metabolites), in the portal vein and systemic circulation, were determined. RESULTS: AL intake resulted in sustained elevated plasma TRP concentrations after an overnight fast. The amount of TRP absorbed was dose-dependently related to protein TRP content (p=0.028), with fastest rates for pigs fed AL (371mg/h). Portal and systemic plasma TRP, TRP/LNAA and the TRP metabolites were highest (p≤0.05) after AL intake , and remained above baseline levels for ∼4h postprandially. Absorption rates of TRP correlated with postprandial plasma TRP and TRP metabolites(p≤0.05). CONCLUSIONS: In adult humans, postprandial plasma TRP and TRP metabolite concentrations can likely be modulated by the TRP content of the meal.

16.
Reg Anesth Pain Med ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39019502

ABSTRACT

BACKGROUND: There is potential for adverse events from corticosteroid injections, including increase in blood glucose, decrease in bone mineral density and suppression of the hypothalamic-pituitary axis. Published studies note that doses lower than those commonly injected provide similar benefit. METHODS: Development of the practice guideline was approved by the Board of Directors of American Society of Regional Anesthesia and Pain Medicine with several other societies agreeing to participate. The scope of guidelines was agreed on to include safety of the injection technique (landmark-guided, ultrasound or radiology-aided injections); effect of the addition of the corticosteroid on the efficacy of the injectate (local anesthetic or saline); and adverse events related to the injection. Based on preliminary discussions, it was decided to structure the topics into three separate guidelines as follows: (1) sympathetic, peripheral nerve blocks and trigger point injections; (2) joints; and (3) neuraxial, facet, sacroiliac joints and related topics (vaccine and anticoagulants). Experts were assigned topics to perform a comprehensive review of the literature and to draft statements and recommendations, which were refined and voted for consensus (≥75% agreement) using a modified Delphi process. The United States Preventive Services Task Force grading of evidence and strength of recommendation was followed. RESULTS: This guideline deals with the use and safety of corticosteroid injections for sympathetic, peripheral nerve blocks and trigger point injections for adult chronic pain conditions. All the statements and recommendations were approved by all participants after four rounds of discussion. The Practice Guidelines Committees and Board of Directors of the participating societies also approved all the statements and recommendations. The safety of some procedures, including stellate blocks, lower extremity peripheral nerve blocks and some sites of trigger point injections, is improved by imaging guidance. The addition of non-particulate corticosteroid to the local anesthetic is beneficial in cluster headaches but not in other types of headaches. Corticosteroid may provide additional benefit in transverse abdominal plane blocks and ilioinguinal/iliohypogastric nerve blocks in postherniorrhaphy pain but there is no evidence for pudendal nerve blocks. There is minimal benefit for the use of corticosteroids in trigger point injections. CONCLUSIONS: In this practice guideline, we provided recommendations on the use of corticosteroids in sympathetic blocks, peripheral nerve blocks, and trigger point injections to assist clinicians in making informed decisions.

17.
Article in English | MEDLINE | ID: mdl-39017965

ABSTRACT

BACKGROUND: Conflicting results have been published considering the diagnostic performance of head-up tilt test (HUTT) in patients with hypertrophic cardiomyopathy (HCM). We aimed to conduct a meta-analysis to evaluate the diagnostic value of HUTT in the evaluation of unexplained syncope in patients with HCM. METHODS: We performed a structured systematic database search using the following keywords: hypertrophic cardiomyopathy, syncope, unexplained syncope, head-up tilt test, tilt table test, tilt testing, orthostatic stress, autonomic function, autonomic response. Studies in which the HUTT was used to define autonomic dysfunction in patients with syncope at baseline or without syncope were included in the final analysis. RESULTS: A total of 252 HCM patients from 6 studies (159 patients without a history of syncope and 93 with a history of syncope, respectively) were evaluated. HUTT was positive in 50 (19.84%) of 252 patients (in 21 of 93 patients (22.58%) with a history of syncope and in 29 of 159 patients (18.24%) without a history of syncope, respectively). The pooled total sensitivity and specificity of the HUTT for detecting syncope were 22.1% (14.8-35.1%) and 83.6% (73.2-91.6%), respectively. The summary receiver operator curve showed that HUTT had an only modest discriminative ability for syncope with an area under the curve value of 0.565 (0.246-0.794). CONCLUSION: Although HUTT has significant limitations in diagnosis of unexplained syncope in patients with HCM, it may still be used to determine hypotensive susceptibility. Other autonomic tests can be used in diagnostic workflow in this population.

18.
Nat Commun ; 15(1): 5884, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39003270

ABSTRACT

The early phases of clathrin mediated endocytosis are organized through a highly complex interaction network mediated by clathrin associated sorting proteins (CLASPs) that comprise long intrinsically disordered regions (IDRs). AP180 is a CLASP exclusively expressed in neurons and comprises a long IDR of around 600 residues, whose function remains partially elusive. Using NMR spectroscopy, we discovered an extended and strong interaction site within AP180 with the major adaptor protein AP2, and describe its binding dynamics at atomic resolution. We find that the 70 residue-long site determines the overall interaction between AP180 and AP2 in a dynamic equilibrium between its bound and unbound states, while weaker binding sites contribute to the overall affinity at much higher concentrations of AP2. Our data suggest that this particular interaction site might play a central role in recruitment of adaptors to the clathrin coated pit, whereas more transient and promiscuous interactions allow reshaping of the interaction network until cargo uptake inside a coated vesicle.


Subject(s)
Adaptor Protein Complex 2 , Clathrin , Endocytosis , Monomeric Clathrin Assembly Proteins , Protein Binding , Adaptor Protein Complex 2/metabolism , Clathrin/metabolism , Binding Sites , Monomeric Clathrin Assembly Proteins/metabolism , Monomeric Clathrin Assembly Proteins/genetics , Humans , Animals , Magnetic Resonance Spectroscopy , Clathrin-Coated Vesicles/metabolism , Intrinsically Disordered Proteins/metabolism , Intrinsically Disordered Proteins/chemistry , Intrinsically Disordered Proteins/genetics
19.
Bol Med Hosp Infant Mex ; 81(Supl 2): 1-28, 2024.
Article in English | MEDLINE | ID: mdl-39009029

ABSTRACT

Infantile hemangioma is a benign vascular tumor, the most common in childhood, whose natural evolution is the disappearance of the lesion in the pediatric age and which has effective and safe treatments that limit its growth and favor its disappearance at younger ages. Infantile hemangioma continues to be a reason for attention to complications, due to erroneous diagnoses, lack of knowledge of the condition, late referral or fear of the effects of the medications used for its treatment. Furthermore, its presence is normalized without taking into account that it can cause uncertainty, anxiety, feelings of guilt and, as a consequence, a significant impact on the quality of life, mainly in the parents or caregivers of the child. The need for a clinical practice guideline in our country arises from the high presentation of late-remitted complications in infantile hemangioma even with the availability of adequate treatments, the continuous evolution of medicine and the appearance of new evidence. Throughout the guide you will find recommendations regarding the diagnosis, treatment and follow-up of patients with infantile hemangioma, taking into account the paraclinical tests that can be performed, topical or systemic management options, as well as adjuvant therapies. For the first time, objective tools for patient follow-up are included in a guide for the management of infantile hemangioma, as well as to help the first contact doctor in timely referral.


El hemangioma infantil es un tumor vascular benigno, el más frecuente de la infancia, cuya evolución natural favorece la desaparición de la lesión en la misma edad pediátrica y que cuenta con tratamientos eficaces y seguros que limitan su crecimiento y favorecen su desaparición a edades más tempranas. Continúa siendo motivo de atención de complicaciones, debido a diagnósticos erróneos, desconocimiento del padecimiento, referencia tardía o temor de los efectos de los fármacos utilizados para su tratamiento. Además, se normaliza su presencia sin tomar en cuenta que puede llegar a causar incertidumbre, ansiedad, sentimientos de culpa y, como consecuencia, importante afectación de la calidad de vida, principalmente en los padres o cuidadores del niño. La necesidad de una guía de práctica clínica en nuestro país surge ante la alta presentación de complicaciones del hemangioma infantil referidas de manera tardía aun con la disponibilidad de tratamientos adecuados, la evolución continua de la medicina y la aparición de nueva evidencia. A lo largo de la guía se encontrarán recomendaciones en relación con el diagnóstico, el tratamiento y el seguimiento de los pacientes con hemangioma infantil, tomando en cuenta los paraclínicos que pueden realizarse, las opciones de manejo tópico o sistémico, y las terapias adyuvantes. Por primera vez se incluyen en una guía para el manejo del hemangioma infantil herramientas objetivas para el seguimiento de los pacientes, así como para ayudar al médico de primer contacto en su referencia oportuna.


Subject(s)
Hemangioma , Humans , Infant , Follow-Up Studies , Hemangioma/diagnosis , Hemangioma/therapy , Mexico , Quality of Life
20.
EuroIntervention ; 20(14): e898-e904, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007830

ABSTRACT

The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y12 inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y12 inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y12 inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y12 inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.


Subject(s)
Anticoagulants , Atrial Fibrillation , Hemorrhage , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Anticoagulants/adverse effects , Administration, Oral , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Hemorrhage/chemically induced , Aspirin/therapeutic use , Aspirin/administration & dosage , Aspirin/adverse effects , Dual Anti-Platelet Therapy/methods , Male , Female , Aged , Purinergic P2Y Receptor Antagonists/administration & dosage , Purinergic P2Y Receptor Antagonists/adverse effects , Purinergic P2Y Receptor Antagonists/therapeutic use , Treatment Outcome , Middle Aged
SELECTION OF CITATIONS
SEARCH DETAIL
...