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Cases of coronary vasospasm leading to ST-elevation myocardial infarction (STEMI) have been described. However, hypovolemia as an etiology of coronary vasospasm has been rarely reported. We report the case of a 57-year-old male who presented to the hospital with syncope, with electrocardiogram (EKG) findings suggestive of ST elevation in the inferior leads. The catheterization lab was activated, and coronary angiography was performed, which showed no evidence of thrombotic occlusion with diffuse disease in the right coronary artery and left anterior descending artery that resolved with aggressive fluid resuscitation.
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Pericarditis leading to constrictive physiology is rarely diagnosed given its vague presentation. Abnormal diastolic filling from a stiff pericardium brings about signs and symptoms consistent with right-sided heart failure. We report the case of a 57-year-old female who presented with worsening shortness of breath and signs of volume overload. Chest computed tomography showed evidence of pericardial calcifications with pericardial effusion. Further evaluation with right heart catheterization suggested findings diagnostic of constrictive pericarditis.
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CONTEXT: In the renewable industry, pressure-dependent CsPbBr3 perovskite has a lot of potential due to its exceptional properties. Present work revealed the mechanical stability of CsPbBr3 between 0 to 50 GPa. The bandgap of unstressed CsPbBr3 is 2.90 eV, indicating a direct bandgap. Band gap values decrease by increasing external pressure. CsPbBr3 structure showed a direct band gap from 0 to 35 GPa and in-direct from 40 to 50 GPa. The unit cell volume and lattice constants are substantially decreased. Mechanical parameters, i.e., Young's modulus, bulk modulus, anisotropy factor, shear modulus, and poison's ratio are obtained. Under ambient conditions, the mechanical properties of CsPbBr3 showed ductile behavior and with induced pressure, their ductility has significantly improved. By applying stresses ranging from 0 to 50 GPa, the considerable fluctuation in values of dielectric function (imaginary and real), absorption, reflectivity, loss function, refractive index (imaginary and real), and conductivity (imaginary and real), was also identified. When pressure rises, the optical parameters increase and drag in the direction of high energies. Response functions are used to predict the density of states and the phonon lattice dispersion to study the phonon properties. By using the quasi-harmonic Debye model, the thermal effect on the free energy, entropy, enthalpy, and heat capacity were predicted and compared. These results would be useful for theoretical research and indicate how external pressure significantly affects the physical characteristics of CsPbBr3 perovskites, which may open up new possibilities for use in optoelectronic, photonic, and solar cell applications. METHODS: The structural, electrical, mechanical, optical, and thermal properties of cesium lead bromide (CsPbBr3) are investigated by applying external pressure from 0 to 50 GPa, using generalized gradient approximations (GGA) and Perdew-Burke-Ernzerhof (PBE) with CASTEP code built-in material studio by density functional theory (DFT).
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Aim: Hepatic safety data assessment from the TURALIO® (pexidartinib) Risk Evaluation and Mitigation Strategy (tREMS) Program. Methods: Retrospective 3-year assessment (August 2019 to June 2022) of hepatic events from the TURALIO® (pexidartinib) Risk Evaluation and Mitigation Strategy Program. Results: A total of 451 patients, 369 prescribers, 2 wholesalers/distributors and 2 pharmacies were enrolled and certified. Twenty-one (4.7%) patients met the criteria for a hepatic adverse event or laboratory abnormality suggestive of serious and potentially fatal liver injury, all with onset within 2 months of therapy. No new hepatic safety signals were identified. Conclusion: Results are consistent with the phase 3 ENLIVEN trial data. Liver enzyme monitoring, combined with early intervention, including dose modification and discontinuation, conducted in patients treated with pexidartinib mitigate the risk of potential hepatotoxicity.
Safety findings from the 3-year data collected in the TURALIO® Risk Evaluation and Mitigation Strategy ProgramPexidartinib (TURALIO®) is an oral drug that is used to treat adults with tenosynovial giant cell tumor (TGCT) that cannot be fixed with surgery. TGCTs are rare, noncancerous tumors that cause pain, stiffness and difficulty moving. Pexidartinib works by blocking a protein that helps these tumors grow. Before pexidartinib, there were no good treatments for TGCT and surgery often could not remove all the tumors, so they would frequently grow back.Pexidartinib was approved in 2019 after a clinical trial showed it worked well in adults with TGCT. However, pexidartinib can sometimes cause serious liver harm for some patients. To handle this risk, a program called the tREMS (TURALIO® Risk Evaluation and Mitigation Strategy) was established to ensure that pexidartinib is used safely.The tREMS Program teaches doctors, pharmacists and patients about the safe use of pexidartinib and potential liver risks and enrolls patients in a registry to watch their health. Doctors and pharmacies must be certified, and patients need regular liver tests. In the first 3 years, 451 patients and 369 doctors joined the program. Unintended liver issues were found in around 5% of patients, a rate that is about the same as that seen in pexidartinib clinical trials, and no new safety concerns were found. About half of patients with liver issues could reverse them by stopping pexidartinib. No patient had permanent liver damage, needed a transplant or died from liver problems. These results show that the tREMS Program is working well to keep patients with TGCT safe while taking pexidartinib.
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Despite advances in the treatment of atherosclerotic cardiovascular disease, it remains the leading cause of death in patients with diabetes. Even when risk factors are mitigated, the disease progresses, and thus newer targets need to be identified that directly inhibit the underlying pathobiology of atherosclerosis in diabetes. A single cell sequencing approach was utilised to distinguish the proatherogenic transcriptional profile in aortic cells in diabetes using a streptozotocin induced-diabetic Apoe-/- mouse model. Human carotid endarterectomy specimens from individuals with and without diabetes were also evaluated via immunohistochemical analysis. Further mechanistic studies were performed in human aortic endothelial cells and human THP-1 derived macrophages. We then performed a preclinical study using an AP-1 inhibitor in a diabetic Apoe-/- mouse model. Single cell RNA sequencing analysis identified the AP-1 complex as a novel target in diabetes-associated atherosclerosis. AP-1 levels were elevated in carotid endarterectomy specimens from diabetic when compared to non-diabetic individuals. AP-1 was validated as a mechanosensitive transcription factor via immunofluorescence staining for regional heterogeneity of endothelial cells of the aortic region exposed to turbulent blood flow and by performing microfluidics experiments in HAECs. AP-1 inhibition with T-5224 blunted endothelial cell activation as assessed by a monocyte adhesion assay and expression of genes relevant to endothelial function. Furthermore, AP-1 inhibition attenuated foam cell formation. Critically, treatment with T-5224 attenuated atherosclerosis development in diabetic Apoe-/- mice. This study has identified the AP-1 complex as a novel target, inhibition of which treats the underlying pathobiology of atherosclerosis in diabetes.
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Cardiovascular diseases (CVD), including coronary heart disease and stroke, comprise the number one cause of mortality worldwide. A major contributor to CVD is atherosclerosis, which is a low-grade inflammatory disease of vasculature that involves a pathological build-up of plaque within the arterial walls. Studies have shown that regulation of gene expression via transcription factors and epigenetic mechanisms play a fundamental role in transcriptomic changes linked to the development of atherosclerosis. Chromatin remodeling is a reversible phenomenon and studies have supported the clinical application of chromatin-modifying agents for the prevention and treatment of CVD. In addition, pre-clinical studies have identified multiple transcription factors as potential therapeutic targets in combating atherosclerotic CVD. Although interaction between transcription factors and epigenetic mechanisms facilitate gene regulation, a limited number of studies appreciate this crosstalk in the context of CVD. Here, we reviewed this gene regulatory mechanism underappreciated in atherosclerosis, which will highlight the mechanisms underlying novel therapeutics targeting epigenetic modifiers and transcription factors in atherosclerosis.
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Aterosclerose , Epigênese Genética , Fatores de Transcrição , Humanos , Aterosclerose/genética , Aterosclerose/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Animais , Montagem e Desmontagem da Cromatina , Regulação da Expressão Gênica , Metilação de DNA , Predisposição Genética para Doença , Placa AteroscleróticaRESUMO
Cholestasis of pregnancy (CP), or intrahepatic CP (ICP), represents a condition peculiar to pregnancy, marked by impaired bile acid flow and consequent accumulation in the maternal bloodstream. Primarily emerging in the third trimester, CP is linked with considerable risks to both the mother and fetus, including heightened incidences of preterm birth, fetal distress, and stillbirth, alongside maternal complications such as intense pruritus and liver dysfunction. Despite its clinical significance, the etiology of CP, which involves genetic, hormonal, and environmental factors, remains partially understood. This comprehensive review delves into the physiology and pathophysiology of CP, outlines its clinical manifestations and diagnostic criteria, and discusses the associated maternal and fetal complications. Furthermore, it evaluates current management strategies, prognostic implications, and potential long-term effects on maternal and child health. It also explores future research directions, emphasizing the need for advancements in understanding the pathophysiology of CP, developing novel therapeutic interventions, and improving risk stratification models. By offering a thorough overview of CP, this review aims to enhance clinical awareness, guide management practices, and identify areas requiring further investigation, ultimately contributing to better health outcomes for affected women and their babies.
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Thebesian veins are microfistulae that drain the coronary arteries directly into one or more chambers of the heart. Persistence of these anomalous connections into adulthood can lead to shunting of blood away from the myocardium causing typical chest pain symptoms with electrocardiogram changes consistent with ischemia. We describe a case of a 77-year-old female who underwent ischemic evaluation for her symptoms found to have significant Thebesian veins. We also engage in a comprehensive review of the literature finding consistencies in the way these cases are presented in the literature.
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BACKGROUND: Histone modifications play a critical role in chromatin remodelling and regulate gene expression in health and disease. Histone methyltransferases EZH1, EZH2, and demethylases UTX, JMJD3, and UTY catalyse trimethylation of lysine 27 on histone H3 (H3K27me3). This study was designed to investigate whether H3K27me3 triggers hyperglycemia-induced oxidative and inflammatory transcriptional programs in the endothelium. METHODS: We studied human aortic endothelial cells exposed to high glucose (HAEC) or isolated from individuals with diabetes (D-HAEC). RT-qPCR, immunoblotting, chromatin immunoprecipitation (ChIP-qPCR), and confocal microscopy were performed to investigate the role of H3K27me3. We determined superoxide anion (O2-) production by ESR spectroscopy, NF-κB binding activity, and monocyte adhesion. Silencing/overexpression and pharmacological inhibition of chromatin modifying enzymes were used to modulate H3K27me3 levels. Furthermore, isometric tension studies and immunohistochemistry were performed in aorta from wild-type and db/db mice. RESULTS: Incubation of HAEC to high glucose showed that upregulation of EZH2 coupled to reduced demethylase UTX and JMJD3 was responsible for the increased H3K27me3. ChIP-qPCR revealed that repressive H3K27me3 binding to superoxide dismutase and transcription factor JunD promoters is involved in glucose-induced O2- generation. Indeed, loss of JunD transcriptional inhibition favours NOX4 expression. Furthermore, H3K27me3-driven oxidative stress increased NF-κB p65 activity and downstream inflammatory genes. Interestingly, EZH2 inhibitor GSK126 rescued these endothelial derangements by reducing H3K27me3. We also found that H3K27me3 epigenetic signature alters transcriptional programs in D-HAEC and aortas from db/db mice. CONCLUSIONS: EZH2-mediated H3K27me3 represents a key epigenetic driver of hyperglycemia-induced endothelial dysfunction. Targeting EZH2 may attenuate oxidative stress and inflammation and, hence, prevent vascular disease in diabetes.
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Diabetes Mellitus , Hiperglicemia , Camundongos , Animais , Humanos , Histonas , NF-kappa B/metabolismo , Células Endoteliais/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Metilação , Diabetes Mellitus/metabolismo , Hiperglicemia/genética , Hiperglicemia/metabolismo , Endotélio , Glucose/toxicidade , Glucose/metabolismoRESUMO
Owing to the rapidly increasing performance of ternary semiconductors; Aluminium Gallium Arsenide (Al1-xGaxAs; x = 0, 0.25, 0.50, 0.75) has been studied by first-principles calculations in Cambridge Serial Total Energy Package (CASTEP-Code). Density functional theory in the frame of full potential linear augmented plane wave (FP-LAPW) is used. The structural, electronic, and optical behavior of the Zinc Blend (ZB) structure of AlAs with Ga impurity was computed by using generalized gradient approximation (GGA) as exchange potential and Perdew-Burke-Ernzerhof (PBE) as functional. Changes in lattice parameters (a), bulk modulus (66.07-76.85), hardness (5.79-8.91) and machinability (1.36-1.46), band gap energy (Eg), and optical properties are computed and discussed in this work. Lattice parameters and elastic constants showed excellent agreement with the reported data whereas some properties were found to excel much more than the theoretical reports. Remarkable bandgap reduction from 1.7eV to 0.28eV is very encouraging in its low-energy applications in UV and visible ranges. Real (Re) and Imaginary (Img) parts of the dielectric function and refractive index shifts towards lower energy values show good agreement with those of theoretical and experimental works. We contribute to the knowledge and characterization of Al1-xGaxAs facilitating its integration into various technological advancements such as photovoltaic, laser, diodes, and high-frequency transistors.
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Data comparing MANTA device with Perclose device for large bore arterial access closure is limited. We performed meta-analysis to compare safety and efficacy of the two devices in large (⩾14 Fr sheath) arteriotomy closure post-TAVR. Relevant studies were identified via PubMed, Cochrane, and EMBASE databases until June, 2022. Data was analyzed using random effect model to calculate relative odds of VARC-2 defined access-site complications and short-term (in-hospital or 30-day) mortality. A total of 12 studies (2 RCT and 10 observational studies) comprising 2339 patients were included. The odds of major vascular complications (OR 0.99, 95% CI 0.51-1.92; p = 0.98); life threatening and major bleeding (OR 0.77, 95% CI 0.45-1.33; p = 0.35); minor vascular complications (OR 1.37, 95% CI 0.63-2.99; p = 0.43); minor bleeding (OR 0.94, 95% CI 0.57-1.56; p = 0.82); device failure (OR 0.74, 95% CI 0.49-1.11; p = 0.14); hematoma formation (OR 0.76, 95% CI 0.33-1.75; p = 0.52); dissection, stenosis, occlusion, or pseudoaneurysm (OR 1.08, 95% CI 0.71-1.62; p = 0.73) and short-term mortality (OR 1.01, 95% CI 0.55-1.84; p = 0.98) between both devices were similar. MANTA device has a similar efficacy and safety profile compared to Perclose device.
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The study aimed at evaluating the influence of water-chestnut starch-based coatings loaded with rosemary essential oil (REO) at concentrations of 0.10%, 0.25% and 0.50% (w/v) on postharvest cold storage stability of apple var. Golden delicious for 120 days. Average droplet diameter of nanoemulsions was in range of 315-450 nm and it increased with increase in the REO concentration. Minimum weight loss was observed in fruits treated with coating material containing 0.50% REO. Samples coated with starch+0.50% REO exhibited highest firmness value of 68.22 ± 1.02 N under controlled atmosphere storage (CAS). Anthocyanins, ascorbic acid, total phenolic content and antioxidant activity were retained in all samples coated with formulated emulsion. Antifungal assay against Pencillium expansum indicated that 0.50% REO had maximum antifungal activity. Increase in REO concentration from 0.10 to 0.50% in starch coating formulations resulted in reduced lesion diameter in coated samples under both the storage conditions. Lesion diameter (LD) was found highest in control (39.40 ± 0.20 mm) under ambient conditions. Coated fruit samples showed a significant (p≤0.05) reduction in LD under both the ambient and CAS conditions however, more pronounced effect was reported under CAS. Fruits coated with edible coatings enriched with different REO concentrations under CAS exhibited significantly (p≤0.05) lower chilling injury index (ST+0.50%REO < ST+0.25%REO<0.10%REO) compared to control.
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This letter aims to explore the potential impact of the Turkey-Syria earthquake on the psychological well-being of the affected children and adolescents. It emphasises the crucial importance of prompt identification and management of emerging mental health disorders in this vulnerable population. The letter draws on existing research evidence to highlight the need for suitable mental health interventions to mitigate the anticipated suffering of many children and adolescents affected by the earthquake. A comprehensive overview of the mediating factors which may play a role in the extent of the impact of an earthquake on the mental health of children is discussed. A range of appropriate strategies and interventions are recommended and the call for continued global support is renewed. We have concluded that major earthquakes can potentially contribute to the development of mental health disorders among children and adolescents. However, by providing timely and effective support, it is possible to prevent long-term psychological consequences and facilitate early recovery. We propose the urgent implementation of effective mental health interventions in the aftermath of the Turkey-Syria earthquake to foster the recovery and resilience of the affected young population.
Mental health disorders are more prevalent in children affected by earthquakes.Prompt identification of emerging mental health disorders among this population is crucial.Management of the psychological impact in this context must be practical and needs-based.A focused and continued global support response is needed to manage the long-term challenges.
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Terremotos , Transtornos Mentais , Adolescente , Criança , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Saúde Mental , Síria , Turquia , Desastres NaturaisRESUMO
Prosthetic valvular infolding during transcatheter aortic valve implantation (TAVI) is an under-recognized yet significant complication that can occur. Here, we describe the case of a 61-year-old male with a history of heart failure with reduced ejection fraction (HFrEF) and low-flow, low-gradient severe aortic valve stenosis of a bicuspid aortic valve who presented to undergo TAVI. During the procedure, repositioning of the valve resulted in prosthetic valvular infolding and resultant severe aortic regurgitation (AR), culminating in cardiac arrest. Swift balloon valvuloplasty corrected the valve geometry and eliminated any AR, allowing hemodynamic recovery and completion of the procedure. Our case and review highlight methods, both angiographic and echocardiographic, to recognize prosthetic valvular infolding the moment it presents, as well as strategies to correct the infolding with minimal detriment to the patient.
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CONTEXT: A remarkable change in lattice parameters and bulk modulus is achieved by the suitable addition of Al (Al1-x Lax Sb) and In (Al1-x Inx Sb) atoms in the AlSb compound. Electronic responses like band structure, the total partial density of states, and the elemental density of states are thoroughly investigated. The computed values indicate that the binary compound AlSb is an indirect band gap and an optically inactive response. After increasing the doping concentrations (0.25, 0.5, 0.75) of La and In in AlSb, the band gap changes from indirect to direct nature. Hence, Al1-0.75 La0.25 Sb, Al1-0.50 La0.50 Sb, Al1-0.75 In0.25Sb, and Al1-0.50 In0.50Sb become optically active. The illustrious roles of Al-3p and In-4d states on the band gap and nonlinear responses of these compounds are extensively explored by the comparison between the computed results of ultra-soft and norm converging pseudopotentials. The excess specific heat (CV), enthalpy of mixing (Hm), and phonon dispersion curves resulting from the concentrations "x" are estimated in order to investigate the thermodynamic stability responses of the pristine and doped AlSb. The obtained CV and thermal coefficient statistics for Al1-x Lax Sb and Al1-x Inx Sb may be useful for a good mapping of experimental results and examining these compounds' enharmonic responses. There is a valuable change in optical characteristics like dielectric functional, absorption, conductivity, and refractive index due to the addition of (La, In) impurities in AlSb. It is further observed that Al1-0.75 La0.25 Sb, Al1-0.50 La0.50 Sb, Al1-0.75 In0.25Sb, and Al1-0.50 In0.50Sb are significantly mechanically stable compared to pristine AlSb. The above results suggest that Al1-x Lax Sb and Al1-x Inx Sb are high-performance optical materials and can be promising potential candidates for optoelectronic applications. METHODS: The structural, electronic, mechanical, vibrational, and optical responses of the pure and doped Al1-0.75 La0.25 Sb, Al1-0.50 La0.50 Sb, Al1-0.75 In0.25Sb, and Al1-0.50 In0.50Sb are investigated, using Heydscuseria-Ernzerhof screened hybrid functional (HSEO6) and generalized gradient approximation (GGA) with norm-converging and ultra-soft pseudopotential techniques in the density functional theory.
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Eletrônica , Temperatura Alta , Condutividade Elétrica , Termodinâmica , VibraçãoAssuntos
Hospitais Gerais , Serviços de Saúde Mental , Humanos , Adulto , Catar , Pacientes InternadosRESUMO
Autoimmune neuroinflammatory diseases are a group of disorders resulting from abnormal immune responses in the nervous system, causing inflammation and tissue damage. The interleukin (IL) family of cytokines, especially IL-1, IL-6, and IL-17, plays a critical role in the pathogenesis of these diseases. IL-1 is involved in the activation of immune cells, production of pro-inflammatory cytokines, and promotion of blood-brain barrier breakdown. IL-6 is essential for the differentiation of T cells into Th17 cells and has been implicated in the initiation and progression of neuroinflammation. IL-17 is a potent pro-inflammatory cytokine produced by Th17 cells that plays a crucial role in recruiting immune cells to sites of inflammation. This review summarizes the current understanding of the roles of different interleukins in autoimmune neuroinflammatory diseases, including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, neuromyelitis optica, and autoimmune encephalitis, and discusses the potential of targeting ILs as a therapeutic strategy against these diseases. We also highlight the need for further research to better understand the roles of ILs in autoimmune neuroinflammatory diseases and to identify new targets for treating these debilitating diseases.