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Scientific Reports Jun 2024Plekhm2 is a protein regulating endosomal trafficking and lysosomal distribution. We recently linked a recessive inherited mutation in PLEKHM2 to a familial form of...
Plekhm2 is a protein regulating endosomal trafficking and lysosomal distribution. We recently linked a recessive inherited mutation in PLEKHM2 to a familial form of dilated cardiomyopathy and left ventricular non-compaction. These patients' primary fibroblasts exhibited abnormal lysosomal distribution and autophagy impairment. We therefore hypothesized that loss of PLEKHM2 impairs cardiac function via autophagy derangement. Here, we characterized the roles of Plekhm2 in the heart using global Plekhm2 knockout (PLK2-KO) mice and cultured cardiac cells. Compared to littermate controls (WT), young PLK2-KO mice exhibited no difference in heart function or autophagy markers but demonstrated higher basal AKT phosphorylation. Older PLK2-KO mice had body and heart growth retardation and increased LC3II protein levels. PLK2-KO mice were more vulnerable to fasting and, interestingly, impaired autophagy was noted in vitro, in Plekhm2-deficient cardiofibroblasts but not in cardiomyocytes. PLK2-KO hearts appeared to be less sensitive to pathological hypertrophy induced by angiotensin-II compared to WT. Our findings suggest a role of Plekhm2 in murine cardiac autophagy. Plekhm2 deficiency impaired autophagy in cardiofibroblasts, but the autophagy in cardiomyocytes is not critically dependent on Plekhm2. The absence of Plekhm2 in mice appears to promote compensatory mechanism(s) enabling the heart to manage angiotensin-II-induced stress without detrimental consequences.
Topics: Animals; Mice; Autophagy; Cells, Cultured; Fibroblasts; Mice, Knockout; Myocardium; Myocytes, Cardiac; Phosphorylation; Protein Serine-Threonine Kinases
PubMed: 38942823
DOI: 10.1038/s41598-024-65670-5 -
The Science of the Total Environment Jun 2024Hammam Faraun (HF) geothermal site in Egypt shows potential for addressing energy demand and fossil fuel shortages. This study utilizes abandoned oil well logs, seismic...
Hammam Faraun (HF) geothermal site in Egypt shows potential for addressing energy demand and fossil fuel shortages. This study utilizes abandoned oil well logs, seismic data, and surface geology to assess HF geothermal energy resources. Seismic interpretation identified a significant clysmic fault parallel to Hammam Faraun fault (HFF), named CLB fault. The two faults together create a renewable geothermal cycle through circulation of mixed formation-sea waters. Petrophysics revealed two main geothermal reservoirs: the Nubian sandstone reservoir and the Eocene Thebes carbonate reservoir with water saturation values approaching 100 %. Corrected borehole temperatures indicated reservoir temperatures around 120 °C and 140 °C for the Thebes and Nubian reservoirs, respectively. Fracture analysis and stress state provided insights into subsurface fractures. A geomechanical model demonstrated the impact of different stresses and pore pressure on geothermal fluid flow. NE-SW oriented fractures showed a higher dilation tendency due to aquathermal expansion. The integrated conceptual geothermal model suggested a magma chamber beneath HF as the heat source, related to Oligo-Miocene volcanic activity. The breached relay ramp and fault-related open fracture system serve as pathways for geothermal fluids. Evaluation of the geothermal potential utilized volumetric calculations and Monte Carlo simulation. The estimated hot water volumes were 1.72 km, 4.242 km, and 5.332 km for the Nubian reservoir in the onshore part, Thebes reservoir in the offshore part, and Nubian reservoir in the offshore part, respectively. The results indicate a medium enthalpy resource suitable for electricity generation using a Kalina geothermal power plant. The predicted geothermal power output is promising, with an average power output of 9.64 MWe, 21.38 MWe, and 43.76 MWe for the Nubian reservoir in the onshore part, Thebes reservoir in the offshore part, and Nubian reservoir in the offshore part, respectively. These outputs can potentially supply electricity to approximately 12,000, 29,000 and 53,000 households, respectively.
PubMed: 38942302
DOI: 10.1016/j.scitotenv.2024.174283 -
Annals of Ibadan Postgraduate Medicine Apr 2024The white cerebellum sign (WCS) is a classical but rare radiological finding usually associated with irreversible diffuse hypoxic-ischemic cerebral injury. Very few...
INTRODUCTION
The white cerebellum sign (WCS) is a classical but rare radiological finding usually associated with irreversible diffuse hypoxic-ischemic cerebral injury. Very few cases exist in the literature globally, especially from the West African region, as a potential hallmark of poor prognostic outcome. We describe the white cerebellum sign in a Nigerian pediatric patient, managed for severe head injury.
CASE PRESENTATION
A fourteen-year old boy presented to our emergency department with loss of consciousness following a pedestrian road traffic accident. Physical examination revealed a critically ill boy with fever, hypotension, tachycardia, gasping respiration, GCS 3, bilateral dilated unreactive pupils, absent corneal, gag and oculocephalic reflexes. He was thus diagnosed of severe traumatic brain injury and brainstem dysfunction. He had endotracheal intubation, ventilatory and inotropic support. Cranial computerized tomography scan of the patient showed radiological features in keeping with the WCS. His clinical status remained poor until he suffered a cardiac arrest about twelve hours after admission.
CONCLUSION
WCS has been reported in relation to child abuse, anoxic-ischemic brain injury, inflammatory and metabolic brain disorders and trauma. It is a classical radiological description of diffuse cerebral edema alongside relatively normal cerebellar hemispheres and brainstem. Management of this pathology is symptomatic, and aims to ameliorate the associated raised intracranial pressure, control seizures and prevent cerebral infarction. The index patient, who presented 24 hours after severe head injury with associated early post-traumatic seizures, respiratory failure and brainstem dysfunction, had an unfavourable outcome consistent with previous reports of WCS. We have reported the rare but classical white cerebellum sign. It remains a grave prognosticator of cerebral injury and should be sought for in the neuroimaging of patients with acute brain insults.
PubMed: 38939880
DOI: No ID Found -
JACC. Advances Apr 2024
PubMed: 38939679
DOI: 10.1016/j.jacadv.2024.100881 -
JACC. Advances Apr 2024Neoaortic root dilatation (NeoARD) and neoaortic regurgitation (NeoAR) are common sequelae following the arterial switch operation (ASO) for transposition of the great...
BACKGROUND
Neoaortic root dilatation (NeoARD) and neoaortic regurgitation (NeoAR) are common sequelae following the arterial switch operation (ASO) for transposition of the great arteries.
OBJECTIVES
The authors aimed to estimate the cumulative incidence of NeoAR, assess whether larger neoaortic root dimensions were associated with NeoAR, and evaluate factors associated with the development of NeoAR during long-term follow-up.
METHODS
Electronic databases were systematically searched for articles that assessed NeoAR and NeoARD after ASO, published before November 2022. The primary outcome was NeoAR, classified based on severity categories (trace, mild, moderate, and severe). Cumulative incidence was estimated from Kaplan-Meier curves, neoaortic root dimensions using Z-scores, and risk factors were evaluated using random-effects meta-analysis.
RESULTS
Thirty publications, comprising a total of 6,169 patients, were included in this review. Pooled estimated cumulative incidence of ≥mild NeoAR and ≥moderate NeoAR at 30-year follow-up were 67.5% and 21.4%, respectively. At last follow-up, neoaortic Z-scores were larger at the annulus (mean difference [MD]: 1.17, 95% CI: 0.52-1.82, < 0.001; MD: 1.38, 95% CI: 0.46-2.30, = 0.003) and root (MD: 1.83, 95% CI: 1.16-2.49, < 0.001; MD: 1.84, 95% CI: 1.07-2.60, < 0.001) in patients with ≥mild and ≥moderate NeoAR, respectively, compared to those without NeoAR. Risk factors for the development of any NeoAR included prior pulmonary artery banding, presence of a ventricular septal defect, aorto-pulmonary mismatch, a bicuspid pulmonary valve, and NeoAR at discharge.
CONCLUSIONS
The risks of NeoARD and NeoAR increase over time following ASO surgery. Identified risk factors for NeoAR may alert the clinician that closer follow-up is needed. (Risk factors for neoaortic valve regurgitation after arterial switch operation: a meta-analysis; CRD42022373214).
PubMed: 38939665
DOI: 10.1016/j.jacadv.2024.100878 -
Cureus May 2024This case report explores the complexities involved in the diagnosis and management of asymptomatic mitral regurgitation (MR) in a 64-year-old male presenting with an...
This case report explores the complexities involved in the diagnosis and management of asymptomatic mitral regurgitation (MR) in a 64-year-old male presenting with an incidental systolic murmur. Torrential MR with flail mitral valve (MV) segments was identified through comprehensive imaging and clinical evaluation, including echocardiography and catheterization. The discussion highlights the nuances of surgical timing, emphasizing the importance of tailored approaches based on left ventricular (LV) function and dilation. This report sheds light on the evolving landscape of managing asymptomatic MR, underscoring the need for balancing surveillance with proactive intervention to optimize patient outcomes.
PubMed: 38939291
DOI: 10.7759/cureus.61191 -
DEN Open Apr 2025A 79-year-old Japanese woman, who had undergone pancreaticoduodenectomy 6 months prior to presentation owing to pancreatic cancer, complained of jaundice with high...
A 79-year-old Japanese woman, who had undergone pancreaticoduodenectomy 6 months prior to presentation owing to pancreatic cancer, complained of jaundice with high fever. Computed tomography revealed proximal bile duct dilatation with complete hepaticojejunostomy anastomotic stricture (HJAS). We performed a single-balloon endoscopy for biliary drainage. The presence of a scar-like feature surrounding the anastomosis was identified as the HJAS. White-light imaging during single-balloon endoscopy revealed that the HJAS contained a milky whitish area (MWA), suggesting that a membranous and fibrosis layer affected continuous inflammation around the center of the anastomosis (within a scar-like feature). Endoscopic dilatation was performed using an endoscopic injection needle, with the MWA used as an indicator. A 23-gauge endoscopic injection needle was used to penetrate the center of the blind lumen within the MWA, and a pinhole was created in the stricture. After confirming the position of the proximal bile duct using a contrast medium with the needle, an endoscopic guidewire with a cannula was inserted into the pinhole. A through-the-scope sequential balloon dilator was used to dilate the stricture, and a plastic stent was inserted into the proximal bile duct. This endoscopic intervention led to positive outcomes. In cases of complete HJAS occlusion, an endoscopic approach to the bile duct is difficult because the anastomotic opening of the HJAS is not visible. Thus, puncturing within the MWA, which can be used as a scar-like landmark within a complete membranous HJAS, is considered a useful endoscopic strategy.
PubMed: 38939119
DOI: 10.1002/deo2.396 -
EJVES Vascular Forum 2024Treatment of complex aortic aneurysms with the laser fenestration (ISLF) technique involves implantation of a balloon expandable stent graft (bSG) in the created...
OBJECTIVE
Treatment of complex aortic aneurysms with the laser fenestration (ISLF) technique involves implantation of a balloon expandable stent graft (bSG) in the created fenestration. Adequate expansion of this bSG is of importance both to achieve seal and to ensure target vessel stability. This experimental study assessed the expansion rate of different bSGs in the ISLF setting using intravascular ultrasound (IVUS).
METHODS
A commercially available aortic endograft was used to test the laser fenestration technique (Zenith Alpha, Cook Medical LLC, Bloomington, IN, USA). The ISLF was stented with the following bSGs: two Gore Viabahn VBX balloon expandable endoprostheses (WL Gore & Associates, Bloomington, IL, USA), three BeGraft Peripheral and three BeGraft Plus (Bentley InnoMed GmbH; Hechingen, Germany), and three Advanta V12 (Atrium, Hudson, NH, USA). The bSGs were expanded in three steps: (1) nominal, (2) rated burst pressure, and (3) dilation with a non-compliant balloon at 15 atmospheres. After each step, an IVUS assessment of the bSG minimum diameter and the area at the fenestration (FA) and in a fully expanded segment distal to the fenestration (SA) was performed. A mean of the three IVUS measurements was used as the value for comparison. An insufficient bSG expansion was defined as a mean of FA/SA of <0.8 (i.e., <80% expansion).
RESULTS
The VBX was the only bSG that could be expanded to its intended diameter (i.e., at least 80%) at nominal pressure. The BeGraft Peripheral and BeGraft Plus had the lowest degree of expansion after nominal and rated burst pressure. All bSGs that were tested reached a sufficient expansion degree after using a higher pressure balloon.
CONCLUSION
In this experiment, dilation up to nominal pressure showed satisfactory expansion only for the VBX. The consistency of the results when applied to the different types of stent grafts that were analysed reflects structural stent graft specific issues to consider when choosing the right device in cases of ISLF.
PubMed: 38939115
DOI: 10.1016/j.ejvsvf.2024.05.008 -
JACS Au Jun 2024Electrochemical energy conversion devices, such as water and carbon dioxide electrolyzers, offer significant advantages in achieving net-zero emissions and in mitigating...
Electrochemical energy conversion devices, such as water and carbon dioxide electrolyzers, offer significant advantages in achieving net-zero emissions and in mitigating further increases in global temperature. However, their widespread adoption necessitates enhancements in performance and durability. Microporous layers (MPLs) have been gaining attention as a promising means to enhance the performance and durability of membrane-electrode-assembly (MEA) based electrolyzers, but their nontrivial mechanisms and complexity in fabrication pose challenges for optimizing the microporous layer structure experimentally. This study introduces a stochastic model for generating MPLs in application to electrolyzers. The model produces 3D reconstructions of MPLs, with porosity and particle size as input parameters, and is capable of generating biased MPLs by taking the pre-existing 3D reconstruction as an input. The model applies a dilation and erosion algorithm to replicate sinter-necks formed in the MPL during the sintering process, and captures their impact on structural and transport properties. In this work, three types of MPLs are generated by using the presented model, which include single-layer MPLs, MPLs with pore formers, and bilayer MPLs. Surface roughness analysis and pore network simulations on the MPLs highlight the significance of particle size in the MPL design. Using finer particles at higher porosities are favored over using larger particles at lower porosities. Such findings are examples of the valuable insights offered from the presented stochastic model, and the model will guide seminal discovery of next-generation MPLs that will greatly progress the shift toward net-zero electrochemical energy conversion technologies.
PubMed: 38938814
DOI: 10.1021/jacsau.4c00199 -
JACC. Advances Nov 2023
PubMed: 38938713
DOI: 10.1016/j.jacadv.2023.100650