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1.
Proc Natl Acad Sci U S A ; 121(8): e2316969121, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38346197

RESUMEN

SOX8 was linked in a genome-wide association study to human height heritability, but roles in chondrocytes for this close relative of the master chondrogenic transcription factor SOX9 remain unknown. We undertook here to fill this knowledge gap. High-throughput assays demonstrate expression of human SOX8 and mouse Sox8 in growth plate cartilage. In situ assays show that Sox8 is expressed at a similar level as Sox9 in reserve and early columnar chondrocytes and turned off when Sox9 expression peaks in late columnar and prehypertrophic chondrocytes. Sox8-/- mice and Sox8fl/flPrx1Cre and Sox9fl/+Prx1Cre mice (inactivation in limb skeletal cells) have a normal or near normal skeletal size. In contrast, juvenile and adult Sox8fl/flSox9fl/+Prx1Cre compound mutants exhibit a 15 to 20% shortening of long bones. Their growth plate reserve chondrocytes progress slowly toward the columnar stage, as witnessed by a delay in down-regulating Pthlh expression, in packing in columns and in elevating their proliferation rate. SOX8 or SOX9 overexpression in chondrocytes reveals not only that SOX8 can promote growth plate cell proliferation and differentiation, even upon inactivation of endogenous Sox9, but also that it is more efficient than SOX9, possibly due to greater protein stability. Altogether, these findings uncover a major role for SOX8 and SOX9 in promoting skeletal growth by stimulating commitment of growth plate reserve chondrocytes to actively proliferating columnar cells. Further, by showing that SOX8 is more chondrogenic than SOX9, they suggest that SOX8 could be preferred over SOX9 in therapies to promote cartilage formation or regeneration in developmental and degenerative cartilage diseases.


Asunto(s)
Condrocitos , Estudio de Asociación del Genoma Completo , Ratones , Humanos , Animales , Condrocitos/metabolismo , Factor de Transcripción SOX9/genética , Factor de Transcripción SOX9/metabolismo , Regulación de la Expresión Génica , Diferenciación Celular , Proliferación Celular , Factores de Transcripción SOXE/genética , Factores de Transcripción SOXE/metabolismo
2.
Am J Emerg Med ; 78: 188-195, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38301369

RESUMEN

OBJECTIVE: This study aimed to assess the impact of establishing a pre-hospital definitive airway on mortality and morbidity compared with no prehospital airway in cases of severe traumatic brain injury (TBI). BACKGROUND: Traumatic brain injury (TBI) is a global health concern that is associated with substantial morbidity and mortality. Prehospital intubation (PHI) has been proposed as a potential life-saving intervention for patients with severe TBI to mitigate secondary insults, such as hypoxemia and hypercapnia. However, their impact on patient outcomes remains controversial. METHODS: A systematic review and meta-analysis were conducted to assess the effects of prehospital intubation versus no prehospital intubation on morbidity and mortality in patients with severe TBI, adhering to the PRISMA guidelines. RESULTS: 24 studies, comprising 56,543 patients, indicated no significant difference in mortality between pre-hospital and In-hospital Intubation (OR 0.89, 95% CI 0.65-1.23, p = 0.48), although substantial heterogeneity was noted. Morbidity analysis also showed no significant difference (OR 0.83, 95% CI 0.43-1.63, p = 0.59). These findings underscore the need for cautious interpretation due to heterogeneity and the influence of specific studies on the results. CONCLUSION: In summary, an initial assessment did not reveal any apparent disparity in mortality rates between individuals who received prehospital intubation and those who did not. However, subsequent analyses and randomized controlled trials (RCTs) demonstrated that patients who underwent prehospital intubation had a reduced risk of death and morbidity. The dependence on biased observational studies and the need for further replicated RCTs to validate these findings are evident. Despite the intricacy of the matter, it is crucial to intervene during severe airway impairment.


Asunto(s)
Manejo de la Vía Aérea , Lesiones Traumáticas del Encéfalo , Servicios Médicos de Urgencia , Intubación Intratraqueal , Humanos , Lesiones Traumáticas del Encéfalo/terapia , Lesiones Traumáticas del Encéfalo/mortalidad , Servicios Médicos de Urgencia/métodos , Manejo de la Vía Aérea/métodos , Intubación Intratraqueal/métodos
3.
Neurosurg Rev ; 47(1): 146, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38600419

RESUMEN

This critique evaluates a letter to the editor discussing prognostic factors in primary central nervous system lymphoma (PCNSL), focusing on C-reactive protein (CRP) levels, prognostic nutritional index (PNI), and lactate dehydrogenase (LDH)-to-lymphocyte ratio. While the letter provides valuable insights, limitations including reliance on a single-center dataset, lack of consideration for potential confounders, insufficient contextualization within existing literature, and limited discussion of clinical implications are identified. Addressing these limitations is crucial for enhancing the relevance and applicability of the findings in PCNSL management.


Asunto(s)
Proteína C-Reactiva , Neoplasias del Sistema Nervioso Central , Lactato Deshidrogenasas , Linfocitos , Linfoma , Humanos , Proteína C-Reactiva/análisis , Sistema Nervioso Central , Neoplasias del Sistema Nervioso Central/diagnóstico , Lactato Deshidrogenasas/análisis , Linfoma/diagnóstico , Evaluación Nutricional , Pronóstico , Estudios Retrospectivos
4.
Acta Neurochir (Wien) ; 166(1): 121, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38436794

RESUMEN

OBJECTIVE: Acute subdural hematoma (ASDH) stands as a significant contributor to morbidity after severe traumatic brain injuries (TBI). The primary treatment approach for patients experiencing progressive neurological deficits or notable mass effects is the surgical removal of the hematoma, which can be achieved through craniotomy (CO) or decompressive craniectomy (DC). Nevertheless, the choice between these two procedures remains a subject of ongoing debate and controversy. MATERIALS AND METHODS: We conducted a comprehensive literature review, utilizing prominent online databases and manually searching references related to craniotomy and craniectomy for subdural hematoma evacuation up to November 2023. Our analysis focused on outcome variables such as the presence of residual subdural hematoma, the need for revision procedures, and overall clinical outcomes. RESULTS: We included a total of 11 comparative studies in our analysis, encompassing 4269 patients, with 2979 undergoing craniotomy and 1290 undergoing craniectomy, meeting the inclusion criteria. Patients who underwent craniectomy displayed significantly lower scores on the Glasgow Coma Scale (GCS) during their initial presentation. Following surgery, the DC group exhibited a significantly reduced rate of residual subdural (P = 0.009). Additionally, the likelihood of a poor outcome during follow-up was lower in the CO group. Likewise, the mortality rate was lower in the CO group compared to the craniectomy group (OR 0.63, 95% CI 0.41-0.98, I2 = 84%, P = 0.04). CONCLUSION: Our study found that CO was associated with more favorable outcomes in terms of mortality, reoperation rate, and functional outcome while DC was associated with less likelihood of residual subdural hematoma. Upon further investigation of patient characteristics who underwent into either of these interventions, it was very clear that patients in DC cohort have more serious and low pre-op characteristics than the CO group. Nonetheless, brain herniation and advanced age act as independent factor for predicting the outcome irrespective of the intervention.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Craniectomía Descompresiva , Hematoma Subdural Agudo , Humanos , Hematoma Subdural Agudo/cirugía , Hematoma Subdural , Bases de Datos Factuales
9.
Sci Rep ; 14(1): 7548, 2024 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555283

RESUMEN

The target and mechanism of ellagic acid (EA) against rotavirus (RV) were investigated by network pharmacology, computational biology, and surface plasmon resonance verification. The target of EA was obtained from 11 databases such as HIT and TCMSP, and RV-related targets were obtained from the Gene Cards database. The relevant targets were imported into the Venny platform to draw a Venn diagram, and their intersections were visualized. The protein-protein interaction networks (PPI) were constructed using STRING, DAVID database, and Cytoscape software, and key targets were screened. The target was enriched by Gene Ontology (GO) and KEGG pathway, and the 'EA anti-RV target-pathway network' was constructed. Schrodinger Maestro 13.5 software was used for molecular docking to determine the binding free energy and binding mode of ellagic acid and target protein. The Desmond program was used for molecular dynamics simulation. Saturation mutagenesis analysis was performed using Schrodinger's Maestro 13.5 software. Finally, the affinity between ellagic acid and TLR4 protein was investigated by surface plasmon resonance (SPR) experiments. The results of network pharmacological analysis showed that there were 35 intersection proteins, among which Interleukin-1ß (IL-1ß), Albumin (ALB), Nuclear factor kappa-B1 (NF-κB1), Toll-Like Receptor 4 (TLR4), Tumor necrosis factor alpha (TNF-α), Tumor protein p53 (TP53), Recombinant SMAD family member 3 (SAMD3), Epidermal growth factor (EGF) and Interleukin-4 (IL-4) were potential core targets of EA anti-RV. The GO analysis consists of biological processes (BP), cellular components (CC), and molecular functions (MF). The KEGG pathways with the highest gene count were mainly related to enteritis, cancer, IL-17 signaling pathway, and MAPK signaling pathway. Based on the crystal structure of key targets, the complex structure models of TP53-EA, TLR4-EA, TNF-EA, IL-1ß-EA, ALB-EA, NF-κB1-EA, SAMD3-EA, EGF-EA, and IL-4-EA were constructed by molecular docking (XP mode of flexible docking). The MMGBS analysis and molecular dynamics simulation were also studied. The Δaffinity of TP53 was highest in 220 (CYS → TRP), 220 (CYS → TYR), and 220 (CYS → PHE), respectively. The Δaffinity of TLR4 was highest in 136 (THR → TYR), 136 (THR → PHE), and 136 (THR → TRP). The Δaffinity of TNF-α was highest in 150 (VAL → TRP), 18 (ALA → GLU), and 144 (PHE → GLY). SPR results showed that ellagic acid could bind TLR4 protein specifically. TP53, TLR4, and TNF-α are potential targets for EA to exert anti-RV effects, which may ultimately provide theoretical basis and clues for EA to be used as anti-RV drugs by regulating TLR4/NF-κB related pathways.


Asunto(s)
Medicamentos Herbarios Chinos , Rotavirus , Factor de Necrosis Tumoral alfa , Ácido Elágico/farmacología , Interleucina-4 , Resonancia por Plasmón de Superficie , Receptor Toll-Like 4 , Factor de Crecimiento Epidérmico , Farmacología en Red , Simulación del Acoplamiento Molecular , Biología Computacional , Albúminas
10.
J Chromatogr A ; 1730: 465058, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-38876077

RESUMEN

This study investigated the influence of pH on the retention of solutes using a mixed-mode column with carboxyl (-COOH) groups acting as weak cation exchanger bonded to the terminal of C18 ligands (C18-WCX column) and a traditional reversed-phase C18 column. First, a model based on electrostatic theory was derived and successfully used to predict the retention of charged solutes (charged, and ionizable) as a function of mobile phase pH on a C18-WCX column. While the Horváth model predicts the pH-dependent retention of ionizable solutes in reversed-phase liquid chromatography (RPLC) solely based on solute ionization, the developed model incorporates the concept of surface potential generated on the surface of the stationary phase and its variation with pH. To comprehensively understand the adsorption process, adsorption isotherms for these solutes were individually acquired on the C18-WCX and reversed-phase C18 columns. The adsorption isotherms followed the Langmuir model for the uncharged solute and the electrostatically modified Langmuir model for charged solutes. The elution profiles for the single components were calculated from these isotherms using the equilibrium dispersion column model and were found to be in close agreement with the experimental elution profiles. To enable modelling of two-component cases involving charged solute(s), a competitive adsorption isotherm model based on electrostatic theory was derived. This model was later successfully used to calculate the elution profiles of two components for scenarios involving (a) a C18 Column: two charged solutes, (b) a C18 Column: one charged and one uncharged solute, and (c) a C18-WCX Column: two charged solutes. The strong alignment between the experimental and calculated elution profiles in all three scenarios validated the developed competitive adsorption model.


Asunto(s)
Cromatografía de Fase Inversa , Electricidad Estática , Cromatografía de Fase Inversa/métodos , Adsorción , Concentración de Iones de Hidrógeno , Modelos Químicos
11.
Cureus ; 16(2): e53408, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38435198

RESUMEN

BACKGROUND:  Laparoscopic cholecystectomy (LC) is the preferred method for gallstone removal, but bile duct injuries remain a concern. Achieving the critical view of safety (CVS) is pivotal in preventing such injuries. The aim of this study was to compare the rates of difficult LC in those with CVS achieved compared to those with CVS not achieved. METHODS: We performed a single-center prospective study on all patients with ultrasound-confirmed symptomatic gallstones. Patients were excluded if they refused to consent or if they underwent LC for indications other than gallstone disease. Patients were stratified into two groups as CVS not achieved and CVS achieved groups and compared for outcomes. Our primary outcome was the rate of intraoperative difficulty on the modified Nassar scale (MNS). Statistical analysis was performed using SPSS version 25.0 (IBM Corp., Armonk, NY). RESULTS: We included 70 patients who underwent LC for gallstones (CVS not achieved = 24 and CVS achieved = 46). The mean (SD) age was 42.2 (12.3) years, and 73.5% were females. The mean (SD) weight in our study cohort was 74.1 (10.9) kg, and there was no difference between the two groups in terms of the baseline demographic characteristics, disease characteristics, and comorbid conditions (p > 0.05). On univariate analyses, achieving CVS was associated with lower rates of higher-grade operative difficulty on the MNS and lower rates of length of stay of more than one day. CONCLUSION: Achieving CVS is associated with easy LC based on significantly lower Nassar scores. These findings highlight the role of the MNS in the successful identification of the operative difficulty of LC and its correlation with achieving CVS.

12.
Ann Med Surg (Lond) ; 86(4): 2081-2087, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38576932

RESUMEN

Histotripsy is a noninvasive medical technique that uses high-intensity focused ultrasound (HIFU) to treat liver tumours. The two main histotripsy methods are boiling histotripsy and cavitation cloud histotripsy. Boiling histotripsy uses prolonged ultrasound pulses to create small boiling bubbles in the tissue, which leads to the breakdown of the tissue into smaller subcellular fragments. Cavitation cloud histotripsy uses the ultrasonic cavitation effect to disintegrate target tissue into precisely defined liquefied lesions. Both methods show similar treatment effectiveness; however, boiling histotripsy ensures treatment stability by producing a stable boiling bubble with each pulse. The therapeutic effect is ascribed to mechanical damage at the subcellular level rather than thermal damage. This article discusses the mechanisms, treatment parameters, and potential of histotripsy as a minimally invasive procedure that provides precise and controlled subcellular damage.

13.
World J Clin Oncol ; 15(4): 482-495, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38689623

RESUMEN

This comprehensive review delves into the current updates and challenges associated with the management of low-grade gliomas (LGG), the predominant primary tumors in the central nervous system. With a general incidence rate of 5.81 per 100000, gliomas pose a significant global concern, necessitating advancements in treatment techniques to reduce mortality and morbidity. This review places a particular focus on immunotherapies, discussing promising agents such as Zotiraciclib and Lerapolturev. Zotiraciclib, a CDK9 inhibitor, has demonstrated efficacy in glioblastoma treatment in preclinical and clinical studies, showing its potential as a therapeutic breakthrough. Lerapolturev, a viral immunotherapy, induces inflammation in glioblastoma and displays positive outcomes in both adult and pediatric patients. Exploration of immunotherapy extends to Pembrolizumab, Nivolumab, and Entrectinib, revealing the challenges and variabilities in patient responses. Despite promising preclinical data, the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment, emphasizing the critical need to understand resistance mechanisms. The review also covers the success of radiation therapy in pediatric LGG, with evolving techniques, such as proton therapy, showing potential improvements in patient quality of life. Surgical treatment is discussed in the context of achieving a balance between preserving the patient's quality of life and attaining gross total resection, with the extent of surgical resection significantly influencing the survival outcomes. In addition to advancements in cancer vaccine development, this review highlights the evolving landscape of LGG treatment, emphasizing a shift toward personalized and targeted therapies. Ongoing research is essential for refining strategies and enhancing outcomes in the management of LGG.

14.
World Neurosurg X ; 23: 100345, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38511157

RESUMEN

Background: The Entrapped Temporal Horn (ETH) is characterized by localized enlargement of the temporal horn of the lateral ventricle of the brain. This study aimed to investigate the factors, development, prognosis, and effective treatment. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a systematic search was conducted in major research databases. The inclusion criteria included patients of all ages with TTH diagnosis in cohort studies, case series, and case reports. Results: Our study included 160 patients and 49 studies. The major causes of TTH were neoplastic lesions (42.3%), infections (22.3%), and cystic disease (13.08%). Of these cases, 71 were unrelated to cranial surgery, while 89 were unrelated to prior surgeries. Headache was the most common symptom (41.91%), followed by seizures (13.20%), drowsiness (12.50%) and memory loss (11.00%). Surgery was not required in 17 patients. Fenestration of the trapped temporal horn was performed in 24 patients, while VP/VA shunt surgeries were performed in the majority (57 patients) owing to favorable outcomes, lower revision rates, and extensive experience. However, TTH recurred in six of the 21 patients who underwent endoscopic ventriculocisternostomy. Tumors were the main cause, and isolated headache was the most frequent symptom. Ventriculoperitoneal shunts (VPS) are preferred because of their positive outcomes, lower revision rates, and wider expertise. Tumors near the trigonal area pose a higher risk. Conclusion: Although TTH remains a rare condition, VPS continues to be the most widely preferred procedure among surgeons.

15.
Front Neurol ; 15: 1331300, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38725648

RESUMEN

Introduction: Stroke is a significant global health concern, and numerous studies have established a link between depression and an increased risk of stroke. While many investigations explore this link, some overlook its long-term effects. Depression may elevate stroke risk through physiological pathways involving nervous system changes and inflammation. This systematic review and meta-analysis aimed to assess the association between depression and stroke. Methodology: We conducted a comprehensive search of electronic databases (PubMed, Embase, Scopus, and PsycINFO) from inception to 9 April 2023, following the Preferred Reporting Items for Systemic Review and Meta-analysis (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We included all articles assessing the association between different stroke types and depression, excluding post-stroke depression. Two investigators independently extracted data and assessed quality using the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool, utilizing a random-effects model for data synthesis. The primary outcome was the association of depression with stroke, with a secondary focus on the association of antidepressants with stroke. Results: The initial search yielded 10,091 articles, and 44 studies were included in the meta-analysis. The pooled analysis revealed a significant association between depression and stroke risk, with an overall hazard ratio of 1.41 (95% CI 1.32, 1.50; p < 0.00001), indicating a moderately positive effect size. Subgroup analyses showed consistent associations with ischemic stroke (HR = 1.30, 95% CI 1.13, 1.50; p = 0.007), fatal stroke (HR = 1.39, 95% CI 1.24, 1.55; p < 0.000001), and hemorrhagic stroke (HR = 1.33, 95% CI 1.01, 1.76; p = 0.04). The use of antidepressants was associated with an elevated risk of stroke (HR = 1.28, 95% CI 1.05, 1.55; p = 0.01). Conclusion and relevance: This meta-analysis indicates that depression moderately raises the risk of stroke. Given the severe consequences of stroke in individuals with depression, early detection and intervention should be prioritized to prevent it. Systematic review registration: Prospero (CRD42023472136).

16.
Ir J Med Sci ; 193(3): 1495-1503, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38315271

RESUMEN

The ketogenic diet (KD), characterized by high-fat and low-carbohydrate intake, is currently gaining widespread popularity as a treatment for drug-resistant epilepsy (DRE). In addition to the traditional ketogenic diet, several variants have been introduced to enhance compliance and flexibility, such as the modified Atkins diet (MAD) and the low glycemic index diet (LGID). These adaptations aim to provide patients with more manageable and sustainable options while harnessing the potential therapeutic benefits of DRE. The objective of this study is to evaluate the efficacy and safety of the KD in pediatric patients who exhibit DRE. In this study, we conducted a thorough review of existing literature by searching Cochrane, Embase, Medline, and PubMed. Our approach involved predefined criteria for data extraction and the assessment of study quality. Eleven RCTs with 788 participants were included in this study. The pooled effect estimates revealed a significant association between dietary interventions and seizure frequency reduction of > 50% (OR 6.68, 96% CI 3.52, 12.67) and > 90% (OR 4.37, 95% CI 2.04, 9.37). Dietary interventions also increased the odds of achieving seizure freedom (OR 4.13, 95% CI 1.61, 10.60). The common adverse effects included constipation (39.07%) and vomiting (10%). In conclusion, dietary interventions, notably the KD, hold promise for pediatric DRE, reducing seizures and achieving freedom. These non-pharmacological options improve the quality of life of non-responsive and non-surgical patients. The KD has emerged as a potential therapeutic approach. Further research is needed to address the limitations and investigate their long-term effects.


Asunto(s)
Dieta Cetogénica , Epilepsia Refractaria , Humanos , Dieta Cetogénica/métodos , Epilepsia Refractaria/dietoterapia , Niño
17.
J Patient Exp ; 11: 23743735241273564, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39157762

RESUMEN

In the Kingdom of Saudi Arabia, there is an increasing demand for community pharmacists to provide the highest level of clinical knowledge and services. However, evidence regarding Saudi public awareness of the clinical services offered by community pharmacies (CPs) and the barriers to using them is limited. In this cross-sectional study, we used an online questionnaire developed by adapting the Consolidated Framework for Implementation Research. A total of 273 participants completed the survey. Half the participants were generally aware of the availability of some CP services but were not informed about the full range on offer, eg, medication reviews (84%) and online counseling (89%). Most of the participants (69.6%) did not identify differences in the care provided by community pharmacists versus hospital pharmacists (P = 0.02). A commonly reported barrier to using CP services was a general preference for other healthcare professionals to seek pharmaceutical help (85.7%). Many other barriers were also reported, impacting the participants' use of these services. The decision-making authorities should consider improvements to increase patients' awareness and utilization of clinical services and enhance community pharmacists' performance in clinical-oriented pharmaceutical care.

18.
Cureus ; 16(6): e62799, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39036117

RESUMEN

Levosimendan, a novel drug, a calcium-sensitizing inotrope, has emerged as a potential therapeutic modulator for heart failure (HF). This review appraises the efficacy and safety of levosimendan in managing HF, in different clinical settings. The study aims to examine the clinical outcomes reported in the selected trials to determine the effectiveness of levosimendan in improving key parameters related to HF. Seven relevant studies encompassing 1200 participants were identified from three databases. Inclusion criteria included clinical trials that investigated the therapeutic efficacy of levosimendan in the treatment of HF, and studies involving both adult and pediatric participants. Exclusion criteria involved studies with insufficient data, studies other than clinical trials, case reports, letters to the editor, conference papers, grey literature, and studies published in a language other than English. Upon evaluating the included studies, it was found that levosimendan shows improved hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy. Levosimendan enhanced right ventricular (RV) function in patients with RV dysfunction after mitral valve (MV) surgeries and decreased the amount of N-terminal pro-B-type natriuretic peptide (NT-ProBNP) in non-ST elevated myocardial infarction (NSTEMI) patients with elevated NT-proBNP, all without increasing the overall cost or duration of hospitalization. Despite variations in study designs and participant characteristics, evidence suggests levosimendan significantly improves left ventricular ejection fraction (LVEF) and exercise tolerance measured by a six-minute walk distance. Notably, its safety profile appears favorable with minimal arrhythmic events and comparable rates of adverse effects to a placebo. This systematic review highlights levosimendan's promising potential for HF management, warranting further research to solidify its clinical role.

19.
Cureus ; 16(1): e52048, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38344642

RESUMEN

BACKGROUND: Laparoscopic cholecystectomy (LC) is the preferred treatment option in non-complicated symptomatic cholelithiasis. In some cases, the surgery might be complicated by different factors resulting in difficult LC. Ultrasound remains the first-line modality for diagnosing symptomatic cholelithiasis; however, its role in predicting difficult LC remains unclear. The aim of this study was to validate an ultrasonographic scoring system in predicting difficult LC. METHODS: We prospectively enrolled patients undergoing LC in a tertiary care unit over six months. All adult (≥18 years) patients undergoing LC for symptomatic cholelithiasis were included. Patients were excluded if they refused to consent, and those who underwent cholecystectomy for indications other than cholelithiasis. Patients were stratified into two groups based on intra-operative difficulty (easy LC and difficult LC) and were compared. Our primary outcome was radiologic difficulty among these groups. Univariate analysis and kappa statistics were performed. RESULTS: We identified 68 patients with an overall mean (SD) age of 42.2 (12.3) years, a mean (SD) weight of 74.1 (10.9) kg, and 73.5% were female. Of the study cohort, 52 patients had easy LC and 16 patients experienced difficult LC. Amongst the total, 14.7% suffered from diabetes mellitus, 29.4% had hypertension, 7.4% had a known ischemic heart disease, and 63% had a body mass index (BMI) ≥30 kg/m2 with no statistically significant difference between the two groups. On the Chi-square test, there was no statistical difference between the two groups in terms of ultrasonographic difficulty (p>0.05). However, we found a Kappa value of -0.127 (p=0.275) corresponding to a strong disagreement between the intraoperative and ultrasonographic difficulty. CONCLUSION: Despite its role in diagnosing cholelithiasis, an ultrasonographic assessment did not have a role in predicting difficult LC according to the present study. Further studies are required to develop a scoring system for predicting difficult LC based on clinical, laboratory, and ultrasonographic assessment.

20.
J Hazard Mater ; 464: 132917, 2024 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-37979429

RESUMEN

Zearalenone (ZEA) poses severe reproductive toxicity to both humans and animals. Scutellarin has been demonstrated to rescue ZEA-induced apoptosis in mouse ovarian granulosa cells (GCs), but its specific targets remain unclear. In the present study, the potential targets of scutellarin were determined to clarify the mechanisms of scutellarin against ZEA-induced ovarian damage. 287 targets of scutellarin in mouse ovarian GCs were obtained by magnetic nano-probe-based fishing assay and liquid chromatography-tandem mass spectrometry. Wnt5a had the lowest binding free energy with scutellarin at - 8.3 kcal/mol. QRT-PCR and western blot showed that scutellarin significantly increased the Wnt5a and ß-catenin expression compared with the ZEA-treated group, and cleaved-caspase-3 expression was significantly increased in the scutellarin-treated group after interfering with the expression of Wnt5a. The affinity constant (KD) of Wnt5a and scutellarin was 1.7 × 10-5 M. The pull-down assay also demonstrated that scutellarin could specifically bind to Wnt5a protein. Molecular docking results showed that scutellarin could form hydrogen bonds with TRY52, GLN56, and SER90 on Wnt5a protein, and western blot assay confirmed SER90 was an important site for the binding. Scutellarin significantly increased Wnt5a and ß-catenin expression and decreased cleaved-caspase-3 expression in ovarian tissues of mice. In conclusion, scutellarin exerted anti-apoptotic effects on ZEA-induced mouse ovarian GCs by targeting Wnt5a.


Asunto(s)
Zearalenona , Humanos , Femenino , Ratones , Animales , Zearalenona/toxicidad , Proteína Wnt-5a/metabolismo , Proteína Wnt-5a/farmacología , Caspasa 3/genética , Caspasa 3/metabolismo , beta Catenina/metabolismo , beta Catenina/farmacología , Células de la Granulosa/metabolismo , Simulación del Acoplamiento Molecular , Apoptosis
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