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1.
Hepatol Commun ; 8(11)2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39392768

RESUMO

Zinc homeostasis could play a role in compensated advanced chronic liver disease, and its supplementation has been linked to improvement in liver function, a decrease of hepatic complications, and reduction in HCC incidence. Compensated advanced chronic liver disease encompasses a heterogeneous group of patients with variable risks of clinically significant portal hypertension and clinical events. The ANTICIPATE model is a validated model for stratifying these risks. Our aim is to demonstrate that zinc administration can reduce the rate and risk of presenting clinical events (first decompensation, HCC, death, and liver transplantation). This study protocol describes an ongoing phase III, national, multicenter, randomized, double-blind clinical trial that will enroll 300 patients to receive either the trial treatment (zinc acexamate) or placebo. An inclusion period of 42 months is planned, with a minimum follow-up of 2 years. Our principal hypothesis is that zinc could modify the natural history of patients with compensated advanced chronic liver disease, with an overall improvement in prognosis.


Assuntos
Zinco , Humanos , Método Duplo-Cego , Zinco/uso terapêutico , Zinco/administração & dosagem , Prognóstico , Suplementos Nutricionais , Doença Crônica , Feminino , Hepatopatias/complicações , Masculino , Neoplasias Hepáticas/tratamento farmacológico , Pessoa de Meia-Idade , Transplante de Fígado
2.
Artigo em Inglês | MEDLINE | ID: mdl-39261212

RESUMO

Interest in remimazolam has surged in recent years, thanks to its advantageous pharmacologic profile. This ultra-short-acting benzodiazepine is noted for its rapid onset and termination of action, organ-independent elimination, availability of a reversal agent, and excellent hemodynamic stability. Although the use of remimazolam has been explored in various anesthesia settings and procedures, data on its application in cardiovascular anesthesia and catheterization laboratory procedures remain limited. This review evaluates the latest literature to assess remimazolam's role in cardiovascular anesthesia across different settings and procedures. The analysis shows that remimazolam offers anesthesia without significant hemodynamic instability and a reduced need for vasopressors, with an incidence of perioperative adverse events comparable to that of other agents. These findings are relevant for both the induction and maintenance of general anesthesia in catheterization laboratory procedures and general anesthesia in elective cardiac surgery. Although further research is needed to fully understand remimazolam's role in cardiovascular anesthesia, its favorable hemodynamic and safety profile suggests that it is a promising option for cardiac anesthesiologists in both the catheterization laboratory and the operating room.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39214797

RESUMO

Heart failure (HF) remains a public health concern affecting millions of individuals worldwide. Despite recent advances in device-related therapies, the prognosis for patients with chronic HF remains poor with significant long-term risk of morbidity and mortality. Left ventricular assist devices (LVADs) have transformed the landscape of advanced HF management, offering circulatory support as destination therapy or as a bridge for heart transplantation. Among the latest generation of LVADs, the HeartMate 3 has gained popularity due to improved clinical outcomes and lower risk of serious adverse events when compared with previous similar devices. The ELEVATE (Evaluating the HeartMate 3 with Full MagLev Technology in a Post-Market Approval Setting) Registry and the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial represent landmark investigations into the performance and comparative effectiveness of the HeartMate 3 LVAD. This review provides a comprehensive synthesis of the safety and efficacy of the 2-year and 5-year HeartMate LVAD outcomes, highlighting key findings, methodological considerations, implications for clinical practice, and future directions.

4.
AME Case Rep ; 8: 72, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091539

RESUMO

Background: Well-differentiated liposarcoma arising from the paratesticular region is rare, with only a few hundred cases reported in the literature. Due to their unexpected location, these tumors are often confused for common pathologies found in the groin, including inguinal hernia, seroma, or lymphoma. Standardized diagnostic and treatment pathways have not been established for patients with paratesticular liposarcoma, thereby elevating the importance of sharing our experience. Case Description: This case describes the presentation of a 65-year-old man with a well-differentiated liposarcoma of the spermatic cord. Diagnosis was made after he underwent open herniorrhaphy to repair what was presumed to be a recurrent left inguinal hernia. Although a recommendation for formal oncologic resection and orchiectomy was made, the patient elected to proceed with watchful waiting and remains well up to last known contact. Conclusions: Paratesticular liposarcoma remains a rare clinical entity. While a few hundred cases have been reported in the literature, only a handful describe its presentation masked as an early recurrence of a groin hernia. Wide local resection along with orchiectomy and potential radiation therapy have been the mainstay of treatment. Clinicians should maintain a healthy level of suspicion for this uncommon pathology, especially in cases where patients present with early recurrence of an inguinal hernia.

5.
Heliyon ; 10(15): e34990, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39144990

RESUMO

Rhus aromatica inhabits humid oak and oakpine forests in the State of Michoacán (Mexico). The fruit of R. aromatica is edible and is traditionally used in the preparation of soft drinks, ice pops, ice creams and 'atole'. The objective of the present investigation was to carry out a physical and chemical characterization and analysis of the antioxidant capacity of fruit. For the physical characterization, the equatorial and longitudinal diameter, weight and percentage of pulp were determined. In the chemical characterization, a proximal analysis was carried out, quantification of polyphenols and flavonoids was performed, and the antioxidant capacity was determined. The results showed that the fruit had a longitudinal diameter of 6.58 ± 1.02 mm, an equatorial diameter of 7.17 ± 0.66, a weight of 55.22 ± 5.47 mg, and a 40 % pulp proportion. The chemical characterization analysis indicated 8.7 % moisture, 30.6 % lipids, 8.7 % proteins, 29.4 % total sugars, 3.8 % ashes and 18.7 % crude fibre, 3.1 °Brix, pH 3.1, 1.92 % acidity total and a caloric intake of 4.27 kcal/g. The polyphenol content was higher in 60 % ethanol extracts with 88.6 ± 50.89 mg EAG/g; for flavonoids from extracts with 100 % acetone, it was 26.52 ± 0.65 mg EQ/g, and the total carotenoid content was 46.37 mg/100 g. The total antioxidant activity was higher in extracts with 80 % acetone, with 87.17 % inhibition of the DPPH radical and 90 % inhibition of ABTS without showing a significant difference with the different solvents used. The lowest IC50 values were presented in 100 % ethanol and 60 % methanol extracts for the DPPH radical and for the ABTS radical were the 80 % ethanol and 60 % methanol extracts. The lipid, protein, carotenoid, and polyphenol contents and antioxidant capacity of the fruit of R. aromatica were as high as those of other fruits consumed in the human diet.

6.
Interv Neuroradiol ; : 15910199241273973, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39165193

RESUMO

Lumbar synovial cysts (LSC) that protrude into the spinal canal can cause lower back pain, neurogenic claudication, and radiculopathy. Often diagnosed in the elderly population (typically ∼60 years of age) with a slight preponderance for females, their underlying etiology is thought to be due to degeneration of the adjacent facet joint, with the most common location at the level of L4-L5. Treatment of LSC can be conservative (with NSAIDs and physical therapy), percutaneous (with rupture), or surgically (with decompression with or without fusion). Percutaneous treatment of LSC involves rupturing the cyst by injecting it with steroids and local anesthetics. Although this option is less invasive than surgery, multiple studies have documented recurrence with this method and patients eventually undergoing surgical intervention. In this report, we document a case where a patient who presented with a symptomatic LSC underwent successful percutaneous treatment with bleomycin.

7.
Cancer Manag Res ; 16: 781-789, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39010861

RESUMO

Purpose: Lung cancer is the leading cause of cancer-related deaths worldwide. However, with the optimization of screening strategies and advances in treatment, mortality has been decreasing in recent years. In this study, we describe non-small cell lung cancer patients diagnosed between 2021 and 2022 at a high-complexity hospital in Latin America, as well as the immunohistochemistry techniques used to screen for ROS1 rearrangements, in the context of the recent approval of crizotinib for the treatment of ROS1 rearrangements in non-small cell lung cancer in Colombia. Methods: A descriptive cross-sectional study was conducted. Sociodemographic, clinical, and molecular pathology information from non-small cell lung cancer individuals who underwent immunohistochemistry to detect ROS1 rearrangements between 2021 and 2022 at Fundación Valle del Lili (Cali, Colombia) was recorded. The clinical outcomes of confirmed ROS1 rearrangements in non-small cell lung cancer patients were reported. Results: One hundred and thirty-six patients with non-small cell lung cancer were included. The median age at diagnosis was 69.8 years (interquartile range 61.9-77.7). At diagnosis, 69.8% (n = 95) were at stage IV. ROS1 immunohistochemistry was performed using the monoclonal D4D6 antibody clone in 54.4% (n = 74) of the cases, while 45.6% (n = 62) were done with the monoclonal SP384 antibody clone. Two patients were confirmed to have ROS1 rearrangements in non-small cell lung cancer using next-generation sequencing and received crizotinib. On follow-up at months 5.3 and 7.0, one patient had a partial response, and the other had oligo-progression, respectively. Conclusion: Screening for ROS1 rearrangements in non-small cell lung cancer is imperative, as multiple prospective studies have shown improved clinical outcomes with tyrosine kinase inhibitors. Given the recent approval of crizotinib in Colombia, public health policies must be oriented toward early detection of driver mutations and prompt treatment. Additionally, future approvals of newly tested tyrosine kinase inhibitors should be anticipated.

8.
J Cardiothorac Surg ; 19(1): 323, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849906

RESUMO

BACKGROUND: Marfan Syndrome is an autosomal dominant disease caused by pathogenetic variants in the FBN1 gene. The progressive dilatation of the aorta and the potential risk of acute aortic syndromes influence the prognosis of these patients. We aim to describe population characteristics, long-term survival, and re-intervention patterns in patients who underwent aortic surgery with a previously confirmed clinical diagnosis of Marfan Syndrome in a middle-income country. METHODS: A retrospective single-center case series study was conducted. All Marfan Syndrome patients who underwent aortic procedures from 2004 until 2021 were included. Qualitative variables were frequency-presented, while quantitative ones adopted mean ± standard deviation. A subgroup analysis between elective and emergent procedures was conducted. Kaplan-Meier plots depicted cumulative survival and re-intervention-free. Control appointments and government data tracked out-of-hospital mortality. RESULTS: Fifty patients were identified. The mean age was 38.79 ± 14.41 years, with a male-to-female ratio of 2:1. Common comorbidities included aortic valve regurgitation (66%) and hypertension (50%). Aortic aneurysms were observed in 64% without dissection and 36% with dissection. Surgical procedures comprised elective (52%) and emergent cases (48%). The most common surgery performed was the David procedure (64%), and the Bentall procedure (14%). The in-hospital mortality rate was 4%. Complications included stroke (10%), and acute kidney injury (6%). The average follow-up was 8.88 ± 5.78 years. Survival rates at 5, 10, and 15 years were 89%, 73%, and 68%, respectively. Reintervention rates at 1, 2.5, and 5 years were 10%, 14%, and 17%, respectively. The emergent subgroup was younger (37.58 ± 14.49 years), had the largest number of Stanford A aortic dissections, presented hemodynamic instability (41.67%), and had a higher requirement of reinterventions in the first 5 years of follow-up (p = 0.030). CONCLUSION: In our study, surveillance programs played a pivotal role in sustaining high survival rates and identifying re-intervention requirements. However, challenges persist, as 48% of the patients required emergent surgery. Despite not affecting survival rates, a greater requirement for reinterventions was observed, emphasizing the necessity of timely diagnosis. Enhanced educational initiatives for healthcare providers and increased patient involvement in follow-up programs are imperative to address these concerns.


Assuntos
Síndrome de Marfan , Humanos , Síndrome de Marfan/complicações , Síndrome de Marfan/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Dissecção Aórtica/cirurgia , Adulto Jovem , Aneurisma Aórtico/cirurgia
9.
Acta Neurochir (Wien) ; 166(1): 243, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822878

RESUMO

BACKGROUND: Trigeminal schwannoma is a rare type of tumor that arises from the Schwann cells of the trigeminal nerve. METHOD: We present a case of a patient with a giant V2 trigeminal schwannoma with painful swelling in the left maxilla. A complete resection using a combined open maxillectomy and endoscopic endonasal approach was performed. CONCLUSION: This case highlights the importance of a multidisciplinary approach to perform a combined open and endoscopic approach for safe resection while preserving adequate speech and swallowing.


Assuntos
Neoplasias dos Nervos Cranianos , Neurilemoma , Humanos , Neoplasias dos Nervos Cranianos/cirurgia , Neoplasias dos Nervos Cranianos/patologia , Neoplasias dos Nervos Cranianos/diagnóstico por imagem , Endoscopia/métodos , Maxila/cirurgia , Maxila/diagnóstico por imagem , Cirurgia Endoscópica por Orifício Natural/métodos , Neurilemoma/cirurgia , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , Resultado do Tratamento , Nervo Trigêmeo/cirurgia , Nervo Trigêmeo/patologia , Doenças do Nervo Trigêmeo/cirurgia , Doenças do Nervo Trigêmeo/patologia
10.
Bol. méd. Hosp. Infant. Méx ; 81(3): 143-150, may.-jun. 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1568901

RESUMO

Abstract Chronic kidney disease (CKD) has severe consequences on the quality and expectancy of life and is considered a major health problem worldwide. This is, especially relevant in pediatric patients, as they have unique characteristics and a mortality rate 30 times higher (in advanced stages) than healthy people. This review aims to define the minimum components for the diagnostic approach and monitoring of CKD in the pediatric population from primary health care to promote comprehensive care and adequate risk management. For this purpose, we performed a systematic review of the literature with a panel of experts. Based on the evidence, to optimize the definition, diagnosis, and timely treatment of CKD in the pediatric population, we formulated 21 recommendations. These were approved by the research team and peer-reviewed by clinical experts. They will facilitate the definition of the diagnostic approach for CKD in the pediatric population in primary health-care settings, allowing for timely treatment intervention, comprehensive care, and monitoring of this disease.


Resumen La enfermedad renal crónica (ERC) tiene graves consecuencias en la calidad y la esperanza de vida, y se considera un importante problema de salud a nivel mundial. Esto es especialmente relevante en pacientes pediátricos, ya que presenta características únicas y una tasa de mortalidad en etapas avanzadas que es 30 veces mayor que en personas sanas. El objetivo de esta revisión fue definir los componentes mínimos para el abordaje diagnóstico y para el seguimiento de la ERC en la población pediátrica desde la atención primaria en salud, con el fin de promover la atención integral y una adecuada gestión del riesgo. Para esto, se realizó una revisión sistemática de la literatura con panel de discusión de expertos. Basándonos en la evidencia, y con el objetivo de optimizar la definición, diagnóstico y tratamiento oportuno de la ERC en la población pediátrica, se formularon 21 recomendaciones. Estas fueron aprobadas por el equipo desarrollador y los pares expertos clínicos evaluadores, y permitirán definir de manera oportuna el abordaje diagnóstico de la ERC en la población pediátrica desde la atención primaria en salud, facilitando la intervención temprana, una atención integral y el seguimiento de esta patología.

11.
bioRxiv ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38746126

RESUMO

Copper (Cu) is an essential trace element required for respiration, neurotransmitter synthesis, oxidative stress response, and transcriptional regulation. Imbalance in Cu homeostasis can lead to several pathological conditions, affecting neuronal, cognitive, and muscular development. Mechanistically, Cu and Cu-binding proteins (Cu-BPs) have an important but underappreciated role in transcription regulation in mammalian cells. In this context, our lab investigates the contributions of novel Cu-BPs in skeletal muscle differentiation using murine primary myoblasts. Through an unbiased synchrotron X-ray fluorescence-mass spectrometry (XRF/MS) metalloproteomic approach, we identified the murine cysteine rich intestinal protein 2 (mCrip2) in a sample that showed enriched Cu signal, which was isolated from differentiating primary myoblasts derived from mouse satellite cells. Immunolocalization analyses showed that mCrip2 is abundant in both nuclear and cytosolic fractions. Thus, we hypothesized that mCrip2 might have differential roles depending on its cellular localization in the skeletal muscle lineage. mCrip2 is a LIM-family protein with 4 conserved Zn2+-binding sites. Homology and phylogenetic analyses showed that mammalian Crip2 possesses histidine residues near two of the Zn2+-binding sites (CX2C-HX2C) which are potentially implicated in Cu+-binding and competition with Zn2+. Biochemical characterization of recombinant human hsCRIP2 revealed a high Cu+-binding affinity for two and four Cu+ ions and limited redox potential. Functional characterization using CRISPR/Cas9-mediated deletion of mCrip2 in primary myoblasts did not impact proliferation, but impaired myogenesis by decreasing the expression of differentiation markers, possibly attributed to Cu accumulation. Transcriptome analyses of proliferating and differentiating mCrip2 KO myoblasts showed alterations in mRNA processing, protein translation, ribosome synthesis, and chromatin organization. CUT&RUN analyses showed that mCrip2 associates with a select set of gene promoters, including MyoD1 and metallothioneins, acting as a novel Cu-responsive or Cu-regulating protein. Our work demonstrates novel regulatory functions of mCrip2 that mediate skeletal muscle differentiation, presenting new features of the Cu-network in myoblasts.

12.
Reproduction ; 168(1)2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38758690

RESUMO

In brief: The endocrine disruptor, nonylphenol (NP) increases 20:4n-6 release in Sertoli cells via PKA/cPLA2 activation. Our data show that lipid metabolism could be a target of NP-induced abnormal reproductive outcomes. Abstract: Nonylphenol (NP), an endocrine-disrupting chemical, is an environmental contaminant, and many notorious effects on male fertility have been reported in animal models and wild-type species. Here, we evaluated the effects of NP in follicle-stimulating hormone (FSH) signal transduction pathways and lipid metabolism using an in vitro model of rat Sertoli cell (SC) primary culture. Results show that an acute (1 h) SC exposure to NP (10 µM) increased the intra- and extra-cellular concentrations of free fatty acids (FFAs), mainly arachidonic acid (20:4n-6). Phosphatidylinositol seemed to be the major phospholipid source of this 20:4n-6 release by activation of the protein kinase A (PKA)/cytoplasmic phospholipase A2 (cPLA2) pathway. NP also increased diacylglycerols (DAG) levels and the expression (mRNA) of cyclooxygenase 2 (Cox2) and prostaglandin E2 (PGE2) levels. It is noteworthy that accumulation of lipid droplets took place after 24 h NP exposition, which was prevented by both a PKA inhibitor and a PLA2 inhibitor. Like FSH, NP triggers the release of 20:4n-6, which is a substrate for PGE2 synthesis via PKA/PLA2 activation. In addition, NP induces the formation of DAG, which could be required as a cofactor of the PKC-mediated activation of the COX2 inflammatory pathway. Our findings suggest that NP alters lipid homeostasis in SCs by inducing the activation of pro-inflammatory pathways that may trigger adverse effects in testis physiology over time. Concomitantly, the SC enhances the acylation of surplus FFAs (including 20:4n-6) in neutral lipids as a protective mechanism to shield itself from lipotoxicity and pro-inflammatory signals.


Assuntos
Ácido Araquidônico , Proteínas Quinases Dependentes de AMP Cíclico , Disruptores Endócrinos , Fenóis , Fosfolipases A2 , Células de Sertoli , Animais , Masculino , Células de Sertoli/metabolismo , Células de Sertoli/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Fenóis/farmacologia , Ratos , Ácido Araquidônico/metabolismo , Disruptores Endócrinos/farmacologia , Fosfolipases A2/metabolismo , Células Cultivadas , Metabolismo dos Lipídeos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Hormônio Foliculoestimulante/metabolismo
13.
J Vasc Surg ; 80(2): 480-489.e5, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38608966

RESUMO

OBJECTIVE: Comorbid chronic kidney disease (CKD) is associated with worse outcomes for patients with chronic limb-threatening ischemia (CLTI). However, comparative effectiveness data are limited for lower extremity bypass (LEB) vs peripheral vascular intervention (PVI) in patients with CLTI and CKD. We aimed to evaluate (1) 30-day all-cause mortality and amputation and (2) 5-year all-cause mortality and amputation for LEB vs PVI in patients with comorbid CKD. METHODS: Individuals who underwent LEB and PVI were queried from the Vascular Quality Initiative with Medicare claims-linked outcomes data. Propensity scores were calculated using 13 variables, and a 1:1 matching method was used. The mortality risk at 30 days and 5 years in LEB vs PVI by CKD was assessed using Kaplan-Meier and Cox proportional hazards models, with interaction terms added for CKD. For amputation, cumulative incidence functions and Fine-Gray models were used to account for the competing risk of death, with interaction terms for CKD added. RESULTS: Of 4084 patients (2042 per group), the mean age was 71.0 ± 10.8 years, and 69.0% were male. Irrespective of CKD status, 30-day mortality (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.63-1.42, P = .78) was similar for LEB vs PVI, but LEB was associated with a lower risk of 30-day amputation (sub-HR [sHR]: 0.66, 95% CI: 0.44-0.97, P = .04). CKD status, however, did not modify these results. Similarly, LEB vs PVI was associated with a lower risk of 5-year mortality (HR: 0.79, 95% CI: 0.71-0.88, P < .001) but no difference in 5-year amputation (sHR: 1.03, 95% CI: 0.89-1.20, P = .67). CKD status did not modify these results. CONCLUSIONS: Regardless of CKD status, patients had a lower risk of 5-year all-cause mortality and 30-day amputation with LEB vs PVI. Results may help inform preference-sensitive treatment decisions on LEB vs PVI for patients with CLTI and CKD, who may commonly be deemed too high risk for surgery.


Assuntos
Amputação Cirúrgica , Isquemia Crônica Crítica de Membro , Comorbidade , Salvamento de Membro , Doença Arterial Periférica , Insuficiência Renal Crônica , Humanos , Amputação Cirúrgica/mortalidade , Amputação Cirúrgica/efeitos adversos , Masculino , Feminino , Idoso , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Fatores de Tempo , Medição de Risco , Estados Unidos/epidemiologia , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/cirurgia , Doença Arterial Periférica/complicações , Doença Arterial Periférica/diagnóstico , Idoso de 80 Anos ou mais , Isquemia Crônica Crítica de Membro/cirurgia , Isquemia Crônica Crítica de Membro/mortalidade , Isquemia Crônica Crítica de Membro/complicações , Estudos Retrospectivos , Resultado do Tratamento , Pessoa de Meia-Idade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Extremidade Inferior/irrigação sanguínea , Enxerto Vascular/mortalidade , Enxerto Vascular/efeitos adversos , Bases de Dados Factuais , Medicare , Isquemia/mortalidade , Isquemia/cirurgia , Isquemia/diagnóstico , Procedimentos Cirúrgicos Vasculares/mortalidade , Procedimentos Cirúrgicos Vasculares/efeitos adversos
14.
Anal Chem ; 96(19): 7444-7451, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38684052

RESUMO

Next-generation sequencing offers highly multiplexed and accurate detection of nucleic acid sequences but at the expense of complex workflows and high input requirements. The ease of use of CRISPR-Cas12 assays is attractive and may enable highly accurate detection of sequences implicated in, for example, cancer pathogenic variants. CRISPR assays often employ end-point measurements of Cas12 trans-cleavage activity after Cas12 activation by the target; however, end point-based methods can be limited in accuracy and robustness by arbitrary experimental choices. To overcome such limitations, we develop and demonstrate here an accurate assay targeting a mutation of the epidermal growth factor gene implicated in lung cancer (exon 19 deletion). The assay is based on characterizing the kinetics of Cas12 trans-cleavage to discriminate the mutant from wild-type targets. We performed extensive experiments (780 reactions) to calibrate key assay design parameters, including the guide RNA sequence, reporter sequence, reporter concentration, enzyme concentration, and DNA target type. Interestingly, we observed a competitive reaction between the target and reporter molecules that has important consequences for the design of CRISPR assays, which use preamplification to improve sensitivity. Finally, we demonstrate the assay on 18 tumor-extracted amplicons and 100 training iterations with 99% accuracy and discuss discrimination parameters and models to improve wild type versus mutant classification.


Assuntos
Deleção de Genes , Genes erbB-1 , Técnicas de Genotipagem , Técnicas de Genotipagem/instrumentação , Técnicas de Genotipagem/métodos , Técnicas de Genotipagem/normas , Genes Reporter/genética , Genes erbB-1/genética , Humanos , RNA Guia de Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Reprodutibilidade dos Testes
15.
J Cardiothorac Vasc Anesth ; 38(7): 1577-1586, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38580478

RESUMO

Consensus statements recommend the use of norepinephrine and/or vasopressin for hypotension in cardiac surgery. However, there is a paucity of data among other surgical subgroups and vasopressin analogs. Therefore, the authors conducted a systematic review of randomized controlled trials (RCTs) to compare vasopressin-receptor agonists with norepinephrine for hypotension among those undergoing surgery with general anesthesia. This review was registered prospectively (CRD42022316328). Literature searches were conducted by a medical librarian to November 28, 2023, across MEDLINE, EMBASE, CENTRAL, and Web of Science. The authors included RCTs enrolling adults (≥18 years of age) undergoing any surgery under general anesthesia who developed perioperative hypotension and comparing vasopressin receptor agonists with norepinephrine. The risk of bias was assessed by the Cochrane risk of bias tool for randomized trials (RoB-2). Thirteen (N = 719) RCTs were included, of which 8 (n = 585) enrolled patients undergoing cardiac surgery. Five trials compared norepinephrine with vasopressin, 4 trials with terlipressin, 1 trial with ornipressin, and the other 3 trials used vasopressin as adjuvant therapy. There was no significant difference in all-cause mortality. Among patients with vasoplegic shock after cardiac surgery, vasopressin was associated with significantly lower intensive care unit (N = 385; 2 trials; mean 100.8 v 175.2 hours, p < 0.005; median 120 [IQR 96-168] v 144 [96-216] hours, p = 0.007) and hospital lengths of stay, as well as fewer cases of acute kidney injury and atrial fibrillation compared with norepinephrine. One trial also found that terlipressin was associated with a significantly lower incidence of acute kidney injury versus norepinephrine overall. Vasopressin and norepinephrine restored mean arterial blood pressure with no significant differences; however, the use of vasopressin with norepinephrine was associated with significantly higher mean arterial blood pressure versus norepinephrine alone. Further high-quality trials are needed to determine pooled treatment effects, especially among noncardiac surgical patients and those treated with vasopressin analogs.


Assuntos
Hipotensão , Norepinefrina , Vasoconstritores , Humanos , Norepinefrina/uso terapêutico , Hipotensão/tratamento farmacológico , Hipotensão/epidemiologia , Vasoconstritores/uso terapêutico , Vasopressinas/uso terapêutico , Receptores de Vasopressinas/agonistas , Adulto , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Resultado do Tratamento
16.
J Phys Act Health ; 21(6): 578-585, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561000

RESUMO

INTRODUCTION: Lack of physical activity (PA) is associated with obesity, diabetes, hypertension, cardiovascular diseases, and cancer. Parenting practices influence PA in young children. However, there is little evidence available for adolescents. We examined whether parenting practices were associated with out-of-school PA (OSPA) in US adolescents. METHODS: This cross-sectional 2019 study analyzed data from the 2014 FLASHE study, a web-based, quota-sampled survey of parent-adolescent dyads. Inclusion required survey completion and parents to live with their teen (ages 12-17 y old). Physically limited adolescents were excluded. Dyads were stratified by teen age. Exposures included parental modeling, monitoring, facilitation, restriction, guided choice, and pressure. The outcomes of interest were OSPA Youth Activity Profile scores. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using adjusted logistic regressions. RESULTS: A total of 1109 dyads were included. Guided choice increased odds of OSPA for 15- to 17-year-olds (OR = 2.12; 95% CI, 1.17-3.84). Facilitation increased odds of OSPA for 12- to 14-year-olds (OR = 2.21; 95% CI, 1.13-4.33). Monitoring decreased odds of OSPA for 15- to 17-year-olds (OR = 0.34; 95% CI, 0.20-0.57) and 12- to 14-year-olds (OR = 0.45; 95% CI, 0.27-0.74). Friend support increased odds of OSPA in 15- to 17-year-olds (OR = 4.03; 95% CI, 2.29-7.08) and 12- to 14-year-olds (OR = 3.05; 95% CI 1.69-5.51). CONCLUSION: Future interventions should prioritize (1) shared decision making for older teens, (2) access to PA opportunities for younger adolescents, and (3) promoting peer PA and friend support for everyone.


Assuntos
Exercício Físico , Poder Familiar , Humanos , Adolescente , Masculino , Feminino , Estudos Transversais , Poder Familiar/psicologia , Criança , Estados Unidos , Inquéritos e Questionários , Relações Pais-Filho
17.
Heliyon ; 10(8): e29391, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38638972

RESUMO

In this study was examined the response of carbon steel to atmospheric corrosion after one-year exposure in Valle de Aburrá, a subregion located in northwestern Colombia. The study involved the assessment of material mass loss and corrosion rate, the characterization of atmospheric aggressiveness, and the analysis of the morphology and composition of corrosion products in five different sites. Climatological and meteorological factors were assessed by testing for chloride content, sulfur dioxide levels, and time of wetness (TOW). The analysis of corrosion products was conducted using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Raman spectroscopy. Based on corrosion rates, two sites exhibited a more aggressive environment, with a corrosivity category of C3, while the remaining sites were categorized as C2. The study confirmed the presence of lepidocrocite and goethite phases on the surface of carbon steel at all test sites. Data analysis revealed that both the TOW and the industrial activity significantly influence the corrosion of this metal.

18.
Vascular ; : 17085381241247881, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630458

RESUMO

OBJECTIVES: Coronary artery disease (CAD) and abdominal aortic aneurysm (AAA) are common arterial pathologies that might occur simultaneously; however, there is not enough evidence about the optimal strategy for patients with concomitant indications of coronary artery bypass grafting (CABG) and open repair of the AAA (AAOR). This study aims to present the outcomes in low and moderate cardiac surgical risk patients who underwent one-stage or two-stage elective CABG and AAOR in a middle-income country. METHODS: An observational, retrospective case series study was conducted. Patients who had low and moderate cardiac surgical risk (less than 8% mortality risk on the STS score) and had the concomitant indication for CABG and AAOR between December 2005 and August 2021 were included. Patients were assigned to one of three strategies: Group 1 underwent one-stage surgery for CABG and AAOR, Group 2 underwent two-stage surgery within the same in-patient stay, and Group 3 underwent two-stage surgery in a new in-patient stay within 6 months. RESULTS: Twenty seven, patients with simultaneous requirements of CABG and AAOR were identified, with a mean age of 69.5 ± 6.1 years and 92.6% were male. The most common comorbidities were hypertension at 77.8% and dyslipidemia at 55.6%. The average mortality risk calculated by the STS score was 2.09% ± 1.53%. In Group 1 (n = 9), 1/9 had in-hospital mortality and no reinterventions were needed. In Group 2 (n = 10), 1/10 had in-hospital mortality, and the most common postoperative complication was acute kidney injury 2/10. Furthermore, 2/10 required a reintervention. In Group 3 (n = 8), no in-hospital mortality was present, however, complications such as sepsis, atrial fibrillation, and acute kidney injury occurred in 2/8 patients each, and 2/8 required a reintervention. CONCLUSION: Patients with CAD and AAA that need a concomitant surgical correction with CABG and an AAOR are uncommon in contemporary practice, given the advances in endovascular therapy. When indicated, one-stage surgery can be performed in patients with low cardiac surgical risk, proper patient selection plays a fundamental role and might be performed in experienced centers. However, two-staged surgeries at the same or different inpatient stay may be considered for asymptomatic AAA with close monitoring during the postoperative period. These findings can hold significance for addressing sociodemographic barriers in low and middle-income countries. More robust and extensive studies are needed to make clear comparisons between the different strategies.

19.
Rev. invest. clín ; Rev. invest. clín;76(2): 65-79, Mar.-Apr. 2024. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1569948

RESUMO

ABSTRACT Excess body weight has become a global epidemic and a significant risk factor for developing chronic diseases, which are the leading causes of worldwide morbidities. Adipose tissue (AT), primarily composed of adipocytes, stores substantial amounts of energy and plays a crucial role in maintaining whole-body glucose and lipid metabolism. This helps prevent excessive body fat accumulation and lipotoxicity in peripheral tissues. In addition, AT contains endothelial cells and a substantial population of immune cells (constituting 60-70% of non-adipocyte cells), including macrophages, T and B lymphocytes, and natural killer cells. These resident immune cells engage in crosstalk with adipocytes, contributing to the maintenance of metabolic and immune homeostasis in AT. An exacerbated inflammatory response or inadequate immune resolution can lead to chronic systemic low-grade inflammation, triggering the development of metabolic alterations and the onset of chronic diseases. This review aims to elucidate the regulatory mechanisms through which immune cells influence AT function and energy homeostasis. We also focus on the interactions and functional dynamics of immune cell populations, highlighting their role in maintaining the delicate balance between metabolic health and obesity-related inflammation. Finally, understanding immunometabolism is crucial for unraveling the pathogenesis of metabolic diseases and developing targeted immunotherapeutic strategies. These strategies may offer innovative avenues in the rapidly evolving field of immunometabolism. (Rev Invest Clin. 2024;76(2):65-79)

20.
Hepatology ; 80(2): 403-417, 2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-38377466

RESUMO

BACKGROUND AND AIMS: Patients with alcohol-associated hepatitis (AH) have an altered fecal metabolome, including reduced microbiota-derived tryptophan metabolites, which function as ligands for aryl hydrocarbon receptor (AhR). The aim of this study was to assess serum AhR ligand activity in patients with AH. APPROACH AND RESULTS: The study included 74 controls without AUD, 97 patients with AUD, and 330 patients with AH from 2 different multicenter cohorts (InTeam: 134, AlcHepNet: 196). Serum AhR activity was evaluated using an AhR reporter assay with HepG2-Lucia cells incubated with serum for 24 hours. Serum AhR activity was significantly higher in patients with AH compared with both controls (1.59 vs. 0.96-fold change, p < 0.001) and patients with AUD (1.59 vs. 0.93, p < 0.001). In both AH cohorts, patients with AhR activity ≥ 2.09 had significantly lower cumulative survival rates at 30, 60, 90, and 180 days compared to those with AhR activity < 2.09. When serum AhR activity was used to further stratify patients with severe AH, the cumulative 30, 60, 90, and 180-day survival rates for patients with severe AH and the AhR activity ≥ 2.09 group were all significantly lower than those with an AhR activity < 2.09 group. CONCLUSIONS: Serum AhR activity was significantly higher in patients with AH compared with controls and individuals with AUD, and this increased activity was associated with higher mortality. Consequently, serum AhR activity holds potential as a prognostic marker.


Assuntos
Hepatite Alcoólica , Receptores de Hidrocarboneto Arílico , Humanos , Receptores de Hidrocarboneto Arílico/sangue , Receptores de Hidrocarboneto Arílico/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Hepatite Alcoólica/mortalidade , Hepatite Alcoólica/sangue , Adulto , Estudos de Casos e Controles , Fatores de Transcrição Hélice-Alça-Hélice Básicos/sangue , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Taxa de Sobrevida , Células Hep G2 , Idoso , Biomarcadores/sangue
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