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Gastrointestinal Endoscopy Jun 2024
PubMed: 38942334
DOI: 10.1016/j.gie.2024.06.028 -
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 -
The Journal of Heart and Lung... Jun 2024Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that...
BACKGROUND
Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools.
METHODS
Consecutive incident PAH patients aged ≥ 18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n=152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n=143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n=201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n=519 patients). Risk stratification was based on on the ESC/ERS 3-strata model and REVEAL 2.0 score.
RESULTS
These phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% C.I. 1.6-2.8, p<0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% C.I. 0.18-0.47, p<0.001).
CONCLUSIONS
Echocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients.
PubMed: 38942159
DOI: 10.1016/j.healun.2024.06.003 -
Phytomedicine : International Journal... Jun 2024Hypoxic pulmonary vascular remodeling (HPVR) is a key pathological feature of hypoxic pulmonary hypertension (HPH). Oxygen-sensitive potassium (K) channels in pulmonary...
BACKGROUND
Hypoxic pulmonary vascular remodeling (HPVR) is a key pathological feature of hypoxic pulmonary hypertension (HPH). Oxygen-sensitive potassium (K) channels in pulmonary artery smooth muscle cells (PASMCs) play a crucial role in HPVR. Luteolin (Lut) is a plant-derived flavonoid compound with variety of pharmacological actions. Our previous study found Lut alleviated HPVR in HPH rat.
PURPOSE
To elucidate the mechanism by which Lut mitigated HPVR, focusing on oxygen-sensitive voltage-dependent potassium channel 1.5 (Kv1.5).
METHODS
HPH rat model was established using hypobaric chamber to simulate 5000 m altitude. Isolated perfused/ventilated rat lung, isolated pulmonary arteriole ring was utilized to investigate the impact of Lut on K channels activity. Kv1.5 level in lung tissue and pulmonary arteriole of HPH rat was assessed. CyclinD1, CDK4, PCNA, Bax, Bcl-2, cleaved caspase-3 levels in lung tissue of HPH rat were tested. The effect of Lut on Kv1.5, cytoplasmic free calcium concentration ([Ca]), CyclinD1, CDK4, PCNA, Bax/Bcl-2 was examined in PASMCs under hypoxia, with DPO-1 as a Kv1.5 specific inhibitor. The binding affinity between Lut and Kv1.5 in PASMCs was detected by drug affinity responsive target stability (DARTS). The overexpression of KCNA5 gene (encoding Kv1.5) in HEK293T cells was utilized to confirm the interaction between Lut and Kv1.5. Furthermore, the impact of Lut on mitochondrial structure, SOD, GSH, GSH-Px, MDA and HIF-1α levels were evaluated in lung tissue of HPH rat and PASMCs under hypoxia.
RESULTS
Lut dilated pulmonary artery by directly activating Kv and Ca-activated K channels (K) in smooth muscle. Kv1.5 level in lung tissue and pulmonary arteriole of HPH rat was upregulated by Lut. Lut downregulated CyclinD1, CDK4, PCNA while upregulating Bax/Bcl-2/caspase-3 axis in lung tissue of HPH rat. Lut decreased [Ca], reduced CDK4, CyclinD1, PCNA, increased Bax/Bcl-2 ratio, in PASMCs under hypoxia, by upregulating Kv1.5. The binding affinity and the interaction between Lut and Kv1.5 was verified in PASMCs and in HEK293T cells. Lut also decreased [Ca] and inhibited proliferation via targeting Kv1.5 of HEK293T cells under hypoxia. Furthermore, Lut protected mitochondrial structure, increased SOD, GSH, GSH-Px, decreased MDA, in lung tissue of HPH rat. Lut downregulated HIF-1α level in both lung tissue of HPH rat and PASMCs under hypoxia.
CONCLUSION
Lut alleviated HPVR by promoting vasodilation of pulmonary artery, reducing cellular proliferation, and inducing apoptosis through upregulating of Kv1.5 in PASMCs.
PubMed: 38941817
DOI: 10.1016/j.phymed.2024.155840 -
Scientific Reports Jun 2024Telocytes are closely associated with the regulation of tissue smooth muscle dynamics in digestive system disorders. They are widely distributed in the biliary system...
Telocytes are closely associated with the regulation of tissue smooth muscle dynamics in digestive system disorders. They are widely distributed in the biliary system and exert their influence on biliary motility through mechanisms such as the regulation of CCK and their electrophysiological effects on smooth muscle cells. To investigate the relationship between telocytes and benign biliary diseases,such as gallbladder stone disease and biliary dilation syndrome, we conducted histopathological analysis on tissues affected by these conditions. Additionally, we performed immunohistochemistry and immunofluorescence double staining experiments for telocytes. The results indicate that the quantity of telocytes in the gallbladder and bile duct is significantly lower in pathological conditions compared to the control group. This reveals a close association between the decrease in telocyte quantity and impaired gallbladder motility and biliary fibrosis. Furthermore, further investigations have shown a correlation between telocytes in cholesterol gallstones and cholecystokinin-A receptor (CCK-AR), suggesting that elevated cholesterol levels may impair telocytes, leading to a reduction in the quantity of CCK-AR and ultimately resulting in impaired gallbladder motility.Therefore, we hypothesize that telocytes may play a crucial role in maintaining biliary homeostasis, and their deficiency may be associated with the development of benign biliary diseases, including gallstone disease and biliary dilation.
Topics: Telocytes; Cholelithiasis; Humans; Gallbladder; Female; Male; Bile Ducts; Middle Aged; Aged; Dilatation, Pathologic
PubMed: 38942924
DOI: 10.1038/s41598-024-65776-w -
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; Autophagy; Mice, Knockout; Fibroblasts; Mice; Myocytes, Cardiac; Protein Serine-Threonine Kinases; Myocardium; Cells, Cultured; Phosphorylation
PubMed: 38942823
DOI: 10.1038/s41598-024-65670-5 -
Heart, Lung & Circulation Jun 2024Acute pulmonary embolism (PE) is a significant cause of mortality in the hospital setting. The objective of this study was to outline the long-term outcomes after...
AIM
Acute pulmonary embolism (PE) is a significant cause of mortality in the hospital setting. The objective of this study was to outline the long-term outcomes after surgical and non-surgical management for patients with massive and submassive PE.
METHODS
Population cohort observational study evaluating all patients who presented to three tertiary hospitals in the state of Western Australia with access to cardiothoracic services over 5 years (2013-2018). Reviewed notes of all patients as well as radiology, linked mortality data and all available echocardiography studies at the primary hospital.
RESULTS
In total, 245 patients were identified, of which 41 received surgical management and 204 non-surgical management; demographic data was similar. Clinically, the surgical group had higher rates of shock requiring vasopressors, severe bradycardia, or cardiopulmonary resuscitation prior to intervention. The 28-day mortality was not statistically significantly different between the surgical embolectomy group (2/41 [4.2%]) and the non-surgical group (17/201 [8.3%]) (p=0.382). There was no difference in 12-month mortality, including when this was adjusted for vasopressors, right ventricular (RV) strain, troponin, and brain natriuretic peptide. In the massive PE sub-group, 28-day mortality was not significantly different: 2/29 (6.9%) surgical group vs 7/34 (20.2%) non-surgical group (p=0.064). Higher rates of severe RV impairment and dilatation were present in the surgical group. All patients with available echocardiography studies at outpatient follow-up returned to normal or mild RV impairment.
CONCLUSION
Patients who presented with massive or submassive PE had similar outcomes whether treated with surgical or non-surgical management. Surgical embolectomy is a safe option in a cardiothoracic centre setting.
PubMed: 38942622
DOI: 10.1016/j.hlc.2024.03.014 -
American Journal of Physiology. Heart... Jun 2024Brief, repeated cycles of limb ischaemia and reperfusion (ischaemic preconditioning; IPC) can protect against vascular insult. Few papers have considered the effect of...
Brief, repeated cycles of limb ischaemia and reperfusion (ischaemic preconditioning; IPC) can protect against vascular insult. Few papers have considered the effect of IPC on resting vascular function, and no single study has simultaneously considered the local (trained arm) and remote (untrained arm) effect of a single session of IPC, and following repeated sessions. We determined macrovascular (allometrically-scaled flow mediated dilation; FMD) and microvascular (cutaneous vascular conductance; CVC) function in healthy adults before, immediately post, 20 min post and 24 h post a single session of IPC (4 x 5 min of single arm ischaemia). These outcomes also were re-measured 24 h after 6 IPC sessions, performed over 2 weeks. FMD and CVC increased in both arms 20 min post (FMD mean difference (MD) 1.1%, < 0.001; CVC MD 0.08 AU, = 0.004) but not 24 hour post (FMD MD -0.2%, = 0.459; CVC MD -0.02 AU, = 0.526) a single session of IPC, with no differences between trained and untrained arms. Whilst FMD did not increase 24 h after one IPC session, it was elevated in both arms 24 h after the sixth session (MD 1.2%, = 0.009). CVC was not altered in either arm 24 h after the last IPC session. These data indicate that the local and remote effect of IPC on vascular health may be equivalent, and that the benefits to FMD may be greater with sustained training compared to a single IPC exposure.
PubMed: 38940917
DOI: 10.1152/ajpheart.00315.2024 -
Circulation Jun 2024Waitlist mortality (WM) remains elevated in pediatric heart transplantation. Allocation policy is a potential tool to help improve WM. This study aims to identify...
BACKGROUND
Waitlist mortality (WM) remains elevated in pediatric heart transplantation. Allocation policy is a potential tool to help improve WM. This study aims to identify patients at highest risk for WM to potentially inform future allocation policy changes.
METHODS
The Pediatric Heart Transplant Society database was queried for patients <18 years of age indicated for heart transplantation between January 1, 2010 to December 31, 2021. was defined as death while awaiting transplant or removal from the waitlist due to clinical deterioration. Because WM is low after the first year, analysis was limited to the first 12 months on the heart transplant list. Kaplan-Meier analysis and log-rank testing was conducted to compare unadjusted survival between groups. Cox proportional hazard models were created to determine risk factors for WM. Subgroup analysis was performed for status 1A patients based on body surface area (BSA) at time of listing, cardiac diagnosis, and presence of mechanical circulatory support.
RESULTS
In total 5974 children met study criteria of which 3928 were status 1A, 1012 were status 1B, 963 were listed status 2, and 65 were listed status 7. Because of the significant burden of WM experienced by 1A patients, further analysis was performed in only patients indicated as 1A. Within that group of patients, those with smaller size and lower eGFR had higher WM, whereas those patients without congenital heart disease or support from a ventricular assist device (VAD) at time of listing had decreased WM. In the smallest size cohort, cardiac diagnoses other than dilated cardiomyopathy were risk factors for WM. Previous cardiac surgery was a risk factor in the 0.3 to 0.7 m and >0.7 m BSA groups. VAD support was associated with lower WM other than in the single ventricle cohort, where VAD was associated with higher WM. Extracorporeal membrane oxygenation and mechanical ventilation were associated with increased risk of WM in all cohorts.
CONCLUSIONS
There is significant variability in WM among status-1A patients. Potential refinements to current allocation system should factor in the increased WM risk we identified in patients supported by extracorporeal membrane oxygenation or mechanical ventilation, single ventricle congenital heart disease on VAD support and small children with congenital heart disease, restrictive cardiomyopathy, or hypertrophic cardiomyopathy.
PubMed: 38939965
DOI: 10.1161/CIRCULATIONAHA.123.068189 -
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