A missense mutation in TRAPPC6A leads to build-up of the protein, in patients with a neurodevelopmental syndrome and dysmorphic features.

Childhood onset clinical syndromes involving intellectual disability and dysmorphic features, such as polydactyly, suggest common developmental pathways link seemingly unrelated phenotypes. We identified a consanguineous family of Saudi origin with varying complex features including intellectual disability, speech delay, facial dysmorphism and polydactyly. Combining, microarray based comparative genomic hybridisation (CGH) to identify regions of homozygosity, with exome sequencing, led to the identification of homozygous mutations in five candidate genes (RSPH6A, ANKK1, AMOTL1, ALKBH8, TRAPPC6A), all of which appear to be pathogenic as predicted by Proven, SIFT and PolyPhen2 and segregate perfectly with the disease phenotype. We therefore looked for differences in expression levels of each protein in HEK293 cells, expressing either the wild-type or mutant full-length cDNA construct. Unexpectedly, wild-type TRAPPC6A appeared to be unstable, but addition of the proteasome inhibitor MG132 stabilised its expression. Mutations have previously been reported in several members of the TRAPP complex of proteins, including TRAPPC2, TRAPPC9 and TRAPPC11, resulting in disorders involving skeletal abnormalities, intellectual disability, speech impairment and developmental delay. TRAPPC6A joins a growing list of proteins belonging to the TRAPP complex, implicated in clinical syndromes with neurodevelopmental abnormalities

Characterization of Leucaena (<em>Leucaena leucephala</em>) oil by direct analysis in real time (DART) ion source and gas chromatography

For the first time, we report the characterization of triacylglycerols and fatty acids in Leucaena (Leucaena leucephala) oil [LUCO], an unexplored nontraditional non-medicinal plant belonging to the family Fabaceae. LUCO was converted to fatty acid methyl esters (FAMEs). We analyzed the triacylglycerols (TAGs) of pure LUCO and their FAMEs by time-of-flight mass spectrometry (TOF-MS) followed by multivariate analysis for discrimination among the FAMEs. Our investigations for the analysis of LUCO samples represent noble features of glycerides. A new type of ion source, coupled with high-resolution TOF-MS was applied for the comprehensive analysis of triacylglycerols. The composition of fatty acid based LUCO oil was studied using Gas Chromatography (GC-FID). The major fatty acid components of LUCO oil are linoleic acid (52.08%) oleic acid (21.26%), palmitic acid (7.91%) and stearic acid (6.01%). A metal analysis in LUCO was done by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The structural elucidation and thermal stability of LUCO were studied by FT-IR, 1H NMR, 13C NMR spectroscopic techniques and TGA-DSC, respectively. We also measured the cytotoxicity of LUCO

Current Landscape of Temporary Percutaneous Mechanical Circulatory Support Technology

Mechanical circulatory support devices provide hemodynamic support to patients who present with cardiogenic shock. These devices work using different mechanisms to provide univentricular or biventricular support. There is a growing body of evidence supporting use of these devices as a goal for cardiac recovery or as a bridge to definitive therapy, but definitive, well-powered studies are still needed. Mechanical circulatory support devices are increasingly used using shock team and protocols, which can help clinicians in decision making, balancing operator and institutional experience and expertise. The aim of this article is to review commercially available mechanical circulatory support devices, their profiles and mechanisms of action, and the evidence available regarding their use

Comparative therapeutic efficacy of Olea europaea L. leaf extract and bone marrow-derived mesenchymal stem cells in ameliorating streptozotocin-induced hepatic and splenic damage in pregnant Rats: Mechanisms of antioxidant and anti-apoptotic protection

Mesenchymal stem cells (MSCs) are multipotent stromal cells with remarkable plasticity, enabling them to differentiate into various tissue-specific cell types. MSCs play a pivotal role in tissue repair, hematopoiesis and immunomodulation. This study aimed to evaluate and compare the protective effects of olive leaf extract (OLE), bone marrow-derived mesenchymal stem cells (BM-MSCs) and their combination against hepatic and splenic toxicity in a rat model of gestational diabetes induced by streptozotocin (STZ). Histopathological and immunohistochemical analyses of liver and spleen tissues were conducted to assess these effects. Methods: Pregnant female rats were divided into five groups (n = 10 per group): Control group: Rats received STZ at a dose of 35 mg/kg body weight. OLE group: Rats were administered olive leaf extract (OLE) at 200 mg/kg body weight. GD + OLE group: Rats with STZ-induced gestational diabetes (GD) were treated with OLE (200 mg/kg body weight). GD + MSCs group: Rats with STZ-induced GD were treated with BM-MSCs. GD + OLE + MSCs group: Rats with STZ-induced GD were treated with both OLE and BM-MSCs. Results: STZ administration induced significant histopathological and immunohistochemical alterations in the liver and spleen tissues of pregnant femal rats. Treatment with OLE, BM-MSCs, or their combination markedly ameliorated these STZ-induced deteriorations, with the combined treatment showing the most pronounced protective effects. Conclusion: The findings demonstrate that both BM-MSCs and OLE exert protective effects against hepatotoxicity and splenic toxicity in a rat model of gestational diabetes. The combination of OLE and BM-MSCs exhibited synergistic benefits, highlighting their potential as therapeutic agents for mitigating organ damage in gestational diabetes

Caracterización del aceite de Leucaena (Leucaena leucocephala) por análisis directo en tiempo real (DART) y cromatografía de gases

For the first time, we report the characterization of triacylglycerols and fatty acids in Leucaena (Leucaena leucephala) oil [LUCO], an unexplored nontraditional non-medicinal plant belonging to the family Fabaceae. LUCO was converted to fatty acid methyl esters (FAMEs). We analyzed the triacylglycerols (TAGs) of pure LUCO and their FAMEs by time-of-flight mass spectrometry (TOF-MS) followed by multivariate analysis for discrimination among the FAMEs. Our investigations for the analysis of LUCO samples represent noble features of glycerides. A new type of ion source, coupled with high-resolution TOF-MS was applied for the comprehensive analysis of triacylglycerols. The composition of fatty acid based LUCO oil was studied using Gas Chromatography (GC-FID). The major fatty acid components of LUCO oil are linoleic acid (52.08%) oleic acid (21.26%), palmitic acid (7.91%) and stearic acid (6.01%). A metal analysis in LUCO was done by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The structural elucidation and thermal stability of LUCO were studied by FT-IR, 1H NMR, 13C NMR spectroscopic techniques and TGA-DSC, respectively. We also measured the cytotoxicity of LUCO.Se presenta por primera vez la caracterización de triacilgliceroles y ácidos grasos del aceite de Leucaena (Leucaena leucephala) [LUCO], una planta no medicinal, no tradicional y no explorada, perteneciente a la familia Fabaceae. Se analizaron triacilgliceroles (TAGs) de LUCO y sus FAMEs por espectrometría de masas de tiempo de vuelo (TOF-MS) seguido de análisis multivariante para discriminación entre los FAME. Nuestras investigaciones para el análisis de muestras de LUCO presentaron características propias de los glicéridos. Un nuevo tipo de fuente de iones, junto con alta resolución TOF-MS se aplicó para el análisis exhaustivo de triacilgliceroles. La composición de aceite de LUCO basado en ácidos grasos se estudió usando Cromatografía de Gas (GC-FID). Los principales componentes de ácidos grasos del aceite LUCO fueron, linoleico (52,08%), oleico (21,26%), palmítico (7,91%) y esteárico 6,01%. El análisis de metales se realizó mediante Espectrometría de Plasma Acoplado Inductivamente a Masas (ICP-MS). La elucidación estructural y la estabilidad térmica de LUCO se estudiaron mediante FT-IR, 1H NMR, técnicas espectroscópicas de 13C NMR y TGA-DSC, respectivamente. También se midió la citotoxicidad de LUCO

TCT-175 Safety and Complications Associated With the Use of Protamine in Percutaneous Coronary Intervention

Background: There is a paucity of data on the use of protamine after percutaneous coronary intervention (PCI). Methods: We conducted a retrospective analysis of 168 patients who underwent PCI from 2015 to 2021. All patients received protamine intra- or immediately after index PCI. We evaluated baseline characteristics, intraprocedural characteristics including heparin dosing and protamine dosing, and complications such as acute stent thrombosis (ST), dissection, perforation, and access-site bleeding. The primary outcome was the incidence of acute ST, subacute ST, and other thrombotic complications. Secondary outcomes included mortality within 24 hours and within 28 days of the index procedure. Results: One hundred sixty-eight patients were included. The mean age of patients was 72 ± 12.1 years, and 36% were women. The majority of patients received antiplatelet therapy prior to the index procedure (90%), and the average ejection fraction (EF) was 50% ± 14.3%. Of the 33 insulin-dependent patients (20%), only 1 (0.5%) used neutral protamine Hagedorn insulin. One hundred fifteen of the procedures (68%) were elective, and the average procedure time was 3 hours 21 minutes (SD 1 hour 43 minutes). Fifty-nine patients underwent rotational, orbital, or laser atherectomy (27, 23, and 9 patients, respectively). An average of 2.59 ± 1.38 stents were deployed, and intravascular ultrasound was used in 96 patients (57%). An average protamine dose of 32 mg was administered. Seventy-three patients (43%) had coronary perforations, and 19 (11%) had pericardial effusions requiring pericardiocentesis. Twenty-one patients (13%) had coronary dissections following PCI, and 6 (4%) had access-site bleeding requiring transfusion. Three patients (2%) underwent urgent cardiac surgery. Eight (5%) died within 24 hours of PCI, and 6 (3.5%) died within 28 days of PCI. Four patients (2%) had acute ST, no patients experienced subacute ST, and 1 patient (0.5%) developed arterial thrombosis (common femoral artery). Conclusions: Use protamine in PCI typically occurred because of intraprocedural complications. In our series, protamine was tolerated well in the majority of patients, but 3% of patients experienced coronary or arterial thrombosis, warranting caution when using protamine in these challenging scenarios. Categories: CORONARY: Stents: Drug-Elutin

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05-1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4-7 days or ≥ 8 days of 1.25 (1.04-1.48), p = 0.015 and 1.31 (1.11-1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Failed Manta Closure Device After High-Risk PCI

Although the collagen-based Manta closure device (Teleflex) is a safe and effective option to close large-bore arterial access sites, complications can occur in at-risk cohorts, as seen in this clinical scenario. It is important for clinicians to share these complications as new technology is introduced