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Search Results (424)

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14 pages, 320 KiB  
Article
Outcomes and Complications of Posterior Fossa Surgery in Sitting Versus Park-Bench Positions
by Oana Maria Radu, Georgeta Magdalena Balaci, Daniel Corneliu Leucuța, Vlad Ioan Moisescu, Cristina Munteanu and Ioan Ștefan Florian
Medicina 2024, 60(11), 1855; https://doi.org/10.3390/medicina60111855 - 12 Nov 2024
Viewed by 347
Abstract
Background/Objectives: Patient positioning during surgery can influence intra- and postoperative complications. Therefore, we assessed the impact of the sitting and park-bench positions on anesthetic parameters and complications in neurosurgical patients. Methods and Patients: For this retrospective study, 314 adults who underwent [...] Read more.
Background/Objectives: Patient positioning during surgery can influence intra- and postoperative complications. Therefore, we assessed the impact of the sitting and park-bench positions on anesthetic parameters and complications in neurosurgical patients. Methods and Patients: For this retrospective study, 314 adults who underwent neurosurgical procedures for posterior fossa pathologies were divided into two groups: sitting (n = 231) and park-bench (n = 83). The following data were collected, monitored, recorded, and compared: age, sex, tumor type, surgical approach, cardiovascular and respiratory complications, and postoperative surgical complications. The association of hypotension with the position was further investigated through multivariate logistic regression models by adjusting for CO2 decrease, desaturation, and documented gas embolism. Results: The average age was significantly lower in the sitting group (55 years, interquartile range (IQR) = 43–63; female proportion = 59.74%) than in the park-bench group (62 years, IQR = 45–74; female proportion = 57.83%) (p < 0.001). Cerebellopontine angle tumors were detected in 37.23% of the patients who underwent an operation in the sitting position and in 7.26% who underwent an operation in the park-bench position (p < 0.001). Patients in the sitting position had significantly greater anesthetic complication (91.77% vs. 71.08%, p < 0.001), hypotension (61.9% vs. 16.87%), and >2 mmHg CO2 decrease (35.06% vs. 15.66%, p < 0.001) incidences. Hypoxemia and death occurred more frequently in the park-bench group (8.43% vs. 1.73% and 6.03% vs. 1.3%, respectively). Conclusions: Compared with the park-bench position, the sitting position was associated with a greater specific anesthetic complication incidence and lower postoperative mortality rate, indicating a need for careful risk-benefit assessment when selecting each individual patient’s surgical position. Full article
14 pages, 1659 KiB  
Article
Assessing the Efficacy and Safety of Extubation Protocols in the Intensive Care Unit Following Transoral Robotic Surgery for Obstructive Sleep Apnea Syndrome: A Retrospective Cohort Study
by Andreaserena Recchia, Marco Cascella, Massimiliano Copetti, Alessio Barile, Elena Giovanna Bignami, Aurelio D’Ecclesia, Antonio Izzi, Aldo Manuali, Vincenzo Marchello, Giuseppe Mincolelli and Alfredo Del Gaudio
J. Clin. Med. 2024, 13(22), 6786; https://doi.org/10.3390/jcm13226786 - 11 Nov 2024
Viewed by 358
Abstract
Background: There is a notable lack of protocols addressing extubation techniques in transoral robotic surgery (TORS) for obstructive sleep apnea (OSA). Methods: This retrospective cohort study enrolled patients who underwent TORS for OSA between March 2015 and December 2021 and were [...] Read more.
Background: There is a notable lack of protocols addressing extubation techniques in transoral robotic surgery (TORS) for obstructive sleep apnea (OSA). Methods: This retrospective cohort study enrolled patients who underwent TORS for OSA between March 2015 and December 2021 and were managed with different extubation approaches. The patients were divided into two groups: high-flow nasal cannula (HFNC) therapy and conventional oxygen therapy. The use of an airway exchange catheter (AEC) was investigated. Results: The application of HFNC use versus conventional oxygen therapy led only to a statistical reduction in extubation time (p = 0.024); length of stay in the intensive care unit (ICU) and the episodes of desaturation below 95% were reduced, but data are non-statistically significant. Similarly, the application of an AEC led to a reduction in extubation time in hours (p = 0.008) and length of stay in the ICU (p = 0.024). Conclusions: In patients with OSA who underwent TORS, the use of an HFNC, with or without an AEC, resulted in a significant reduction in extubation time without major adverse events. Additionally, HFNC utilization may decrease desaturation episodes during extubation. Despite limitations, based on the findings of this preliminary investigation, the combination of an HFNC and an AEC emerges as a promising strategy for enhancing the safety and efficacy of extubation protocols in this patient population. Full article
(This article belongs to the Section Pulmonology)
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<p>The course of the retrospective study. Abbreviations: airway exchange catheter, AEC; high-flow nasal cannula, HFNC; intensive care unit, ICU.</p>
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<p>Study flowchart. Abbreviations: TORS, transoral robotic surgery; ICU, intensive care unit; HFNC, high-flow nasal cannula.</p>
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<p>Bar plot of the propensity scores (PSs) distribution between the two groups. The x-axis represents the two groups being compared (Conventional and HFNC). The y-axis represents the density or proportion of patients within specific ranges of PSs. The bars indicate the distribution of propensity scores for each group. Each bar’s height corresponds to the proportion of patients in that group who fall within a specific range of PSs. The alignment of bars between the two groups shows how similar the groups are in terms of their PSs after matching. The graph shows that the PSs of the two groups have been balanced. The bars for the Conventional and HFNC groups should align closely, indicating that the matching process has successfully created comparable groups.</p>
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<p>Extubation time with and without high-flow nasal cannula (HFNC). Legend: * <span class="html-italic">p</span> &lt; 0.005.</p>
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<p>Extubation times with and without an airway exchange catheter (AEC). Legend: * <span class="html-italic">p</span> &lt; 0.005.</p>
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<p>Intensive care unit (ICU) stays with and without an airway exchange catheter (AEC). Legend: * <span class="html-italic">p</span> &lt; 0.005.</p>
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35 pages, 3808 KiB  
Review
Oxylipins Derived from PUFAs in Cardiometabolic Diseases: Mechanism of Actions and Possible Nutritional Interactions
by Duygu Ağagündüz, Özge Yeşildemir, Emine Koçyiğit, Tevfik Koçak, Buket Özen Ünaldı, Gamze Ayakdaş and Ferenc Budán
Nutrients 2024, 16(22), 3812; https://doi.org/10.3390/nu16223812 - 7 Nov 2024
Viewed by 762
Abstract
Oxylipins are oxidized fatty acids, both saturated and unsaturated, formed through pathways that involve singlet oxygen or dioxygen-mediated oxygenation reactions and are primarily produced by enzyme families such as cyclooxygenases, lipoxygenases, and cytochrome P450. These lipid-based complex bioactive molecules are pivotal signal mediators, [...] Read more.
Oxylipins are oxidized fatty acids, both saturated and unsaturated, formed through pathways that involve singlet oxygen or dioxygen-mediated oxygenation reactions and are primarily produced by enzyme families such as cyclooxygenases, lipoxygenases, and cytochrome P450. These lipid-based complex bioactive molecules are pivotal signal mediators, acting in a hormone-like manner in the pathophysiology of numerous diseases, especially cardiometabolic diseases via modulating plenty of mechanisms. It has been reported that omega-6 and omega-3 oxylipins are important novel biomarkers of cardiometabolic diseases. Moreover, collected literature has noted that diet and dietary components, especially fatty acids, can modulate these oxygenated lipid products since they are mainly derived from dietary omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) or linoleic acid and α-linolenic by elongation and desaturation pathways. This comprehensive review aims to examine their correlations to cardiometabolic diseases and how diets modulate oxylipins. Also, some aspects of developing new biomarkers and therapeutical utilization are detailed in this review. Full article
(This article belongs to the Special Issue Bioactive Lipids and Metabolism Disease)
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<p>Summary of oxylipins synthesized from PUFAs. PUFA: Polyunsaturated fatty acids, LA: Linoleic acid, GLA: γ-linolenic acid, DGLA: Dihomo-γ-linolenic acid, AdA: Adrenic acid, AA: Arachidonic acid, ALA: α-Linolenic acid, EPA: Eicosapentaenoic acid, DHA: Docosapentaenoic acid, COX: Cyclooxygenase, LOX: Lipoxygenase, CYP: Cytochrome P450, HpODE: hydroperoxy-octadecadienoic acid, HODE: Hydroxy-octadecadienoic acid, EpOME: Epoxy-octadecenoic acid, diHOME: Dihydroxy-octadecenoic acid, HOTrE: Hydroxy-octadecatrienoic acid, HpETrE: Hydroperoxy-eicosatrienoic acid, EpEDE: Epoxy-eicosadienoic acid, DiHEDE: Dihydroxy-eicosadienoic acid, HETE: Hydroxy-eicosatetraenoic acid, DiHETE: Dihydroxy-eicosatetraenoic acid, DiHETrE: Dihydroxy-eicosatrienoic acid, HpETE: Hydroperoxy-eicosatetraenoic acid, EET: Epoxyeicosatrienoic acids, HpOTre: hydroperoxy-octadecatrienoic acid, EpODE: Epoxy-octadecadienoic acid, HpOTrE: Hydroperoxy-octadecatrienoic acid, HpEPE: Hydroperoxy-eicosapentaenoic acid, HEPE: hydroxy-eicosapentaenoic acid, DiHEPE: dihydroxy-eicosapentaenoic acid, EpETE: Epoxy-eicosatetraenoic acid, HpDoHE: Hydroperoxy-docosahexaenoic acid, HDoHE: Hydroxy-docosahexaenoic acid, DiHDoHE: Dihydroxy-docosahexaenoic acidEpDPE: Epoxy-docosapentaenoic acid, DiHDPE: Dihydroxy-docosapentaenoic acid.</p>
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<p>The role of chronic low-grade inflammation in revealing the relationships between oxylipins and cardiometabolic diseases.</p>
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<p>Possible dietary modulation of PUFA-derived oxylipins and their cardiometabolic effects which depends on consumed PUFA types and amounts. PUFAs: Polyunsaturated fatty acids.</p>
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<p>The oxylipins and its impact on diabetes. COX: Cyclooxygenase; CYP: Cytochromes P450; HHE: 4-Hydroxy-2-hexenal; HNE: 4-Hydroxy-2-nonenal; LOX: Lipoxygenase; MaR: Maresin; <span class="html-italic">n</span>-3: omega 3 fatty acids; <span class="html-italic">n</span>-6: omega 6 fatty acids; PD/NPD: Protectin/neuroprotectin; PUFA: Polyunsaturated fatty acid; Rv: Resolvin; PUFAs: Polyunsaturated fatty acids.</p>
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<p>Functions of oxylipins in vascular control. 20-HETE, 20-hydroxy-5,8,11,14-eicosatetraenoic acid; GPR132, G protein-coupled receptor 132; OxLDL, Oxidized Low-density Lipoprotein;IL-1β, Interleukin-1 beta; FABP4, Fatty Acid-Binding Protein 4; PPARγ, Peroxisome proliferator-activated receptor gamma; ERK1/2, extracellular signal-regulated kinase 1/2; PKC, Protein kinase C; NF-κB, nuclear factor-kappa B; NO, nitric oxide; AGT, Angiotensinogen; ACE, angiotensin-converting enzyme; TNF-α, Tumor necrosis factor alpha; IL-6, Interleukin-6; sEH, soluble epoxide hydrolase enzyme; PI3K, hosphatidylinositol-3 kinase; ICAM-1, intracellular adhesion molecule; VCAM-1, vascular cell adhesion molecule 1 1.</p>
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<p>The relationship between NAFLD and oxylipins.</p>
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<p>The relationship between CKD and oxylipins.</p>
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17 pages, 3756 KiB  
Systematic Review
The Diagnostic Accuracy of Overnight Oximetry for Pediatric Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis
by Serena Incerti Parenti, Maria Lavinia Bartolucci, Andrea Fiordelli, Pierangelo Gigola, Corrado Paganelli and Giulio Alessandri-Bonetti
Appl. Sci. 2024, 14(22), 10208; https://doi.org/10.3390/app142210208 - 7 Nov 2024
Viewed by 331
Abstract
Polysomnography (PSG) is the gold standard for the diagnosis of pediatric obstructive sleep apnea (OSA); however, high costs and limited availability restrict its use for routine screening. This systematic review and meta-analysis investigated the accuracy of overnight oximetry for the diagnosis of pediatric [...] Read more.
Polysomnography (PSG) is the gold standard for the diagnosis of pediatric obstructive sleep apnea (OSA); however, high costs and limited availability restrict its use for routine screening. This systematic review and meta-analysis investigated the accuracy of overnight oximetry for the diagnosis of pediatric OSA. Studies evaluating overnight oximetry against PSG-derived apnea-hypopnea index (AHI) in subjects aged ≤18 years were considered in the qualitative analysis and evaluated with the QUADAS-2 tool. Only oximetry parameters adopted by at least four studies using the currently accepted diagnostic thresholds for pediatric OSA (AHI of 1, 5 and 10 events/h) were included for quantitative analyses. A bivariate meta-analysis was used to estimate sensitivity and specificity, as well as to construct summary receiver operator characteristic curves. The positive and negative predictive values were calculated. A total of 28 studies (9122 participants) were included in qualitative analyses. Only 3% oxygen desaturation index (ODI3) was eligible for the quantitative analyses (six studies, 1276 participants). As OSA severity increases sensitivity, specificity and the negative predictive value also increase, reaching values of 79%, 84%, and 89% at AHI ≥ 10, respectively. Oximetry displays a good performance as a screening tool for pediatric OSA, especially with moderate-to-severe disease. ODI3 is particularly effective at ruling out OSA in children who test negative. Full article
(This article belongs to the Section Applied Dentistry and Oral Sciences)
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<p>Flowchart of the study selection process.</p>
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<p>Quality appraisal of the studies included in the systematic review using the QUADAS-2 tool [<a href="#B13-applsci-14-10208" class="html-bibr">13</a>,<a href="#B14-applsci-14-10208" class="html-bibr">14</a>,<a href="#B15-applsci-14-10208" class="html-bibr">15</a>,<a href="#B23-applsci-14-10208" class="html-bibr">23</a>,<a href="#B24-applsci-14-10208" class="html-bibr">24</a>,<a href="#B25-applsci-14-10208" class="html-bibr">25</a>,<a href="#B26-applsci-14-10208" class="html-bibr">26</a>,<a href="#B27-applsci-14-10208" class="html-bibr">27</a>,<a href="#B28-applsci-14-10208" class="html-bibr">28</a>,<a href="#B29-applsci-14-10208" class="html-bibr">29</a>,<a href="#B30-applsci-14-10208" class="html-bibr">30</a>,<a href="#B31-applsci-14-10208" class="html-bibr">31</a>,<a href="#B32-applsci-14-10208" class="html-bibr">32</a>,<a href="#B33-applsci-14-10208" class="html-bibr">33</a>,<a href="#B34-applsci-14-10208" class="html-bibr">34</a>,<a href="#B35-applsci-14-10208" class="html-bibr">35</a>,<a href="#B36-applsci-14-10208" class="html-bibr">36</a>,<a href="#B37-applsci-14-10208" class="html-bibr">37</a>,<a href="#B38-applsci-14-10208" class="html-bibr">38</a>,<a href="#B39-applsci-14-10208" class="html-bibr">39</a>,<a href="#B40-applsci-14-10208" class="html-bibr">40</a>,<a href="#B41-applsci-14-10208" class="html-bibr">41</a>,<a href="#B42-applsci-14-10208" class="html-bibr">42</a>,<a href="#B43-applsci-14-10208" class="html-bibr">43</a>,<a href="#B44-applsci-14-10208" class="html-bibr">44</a>,<a href="#B45-applsci-14-10208" class="html-bibr">45</a>,<a href="#B46-applsci-14-10208" class="html-bibr">46</a>,<a href="#B47-applsci-14-10208" class="html-bibr">47</a>].</p>
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<p>Forest plot of studies adopting ODI3 as parameter to define abnormal oximetry recordings. CI, confidence interval; FN, false negative; FP, false positive; TN, true negative; TP, true positive [<a href="#B24-applsci-14-10208" class="html-bibr">24</a>,<a href="#B26-applsci-14-10208" class="html-bibr">26</a>,<a href="#B30-applsci-14-10208" class="html-bibr">30</a>,<a href="#B33-applsci-14-10208" class="html-bibr">33</a>,<a href="#B34-applsci-14-10208" class="html-bibr">34</a>,<a href="#B39-applsci-14-10208" class="html-bibr">39</a>].</p>
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<p>SROC curves of studies based on ODI3 as oximetry parameter: 95% confidence region (full line area), 95% prediction region (dashed line area), studies (circles), summary point (black dot) and summary curve (full line).</p>
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11 pages, 282 KiB  
Article
One Year Follow-Up Assessment of Impact of Rigorous Diet Regimen and Adequate C-PAP Therapy on Obese Patients with Obstructive Sleep Apnea Syndrome: A Retrospective Study
by Pierluigi Carratù, Silvano Dragonieri, Vitaliano Nicola Quaranta, Onofrio Resta, Piero Portincasa, Vincenzo Ostilio Palmieri and Giovanna Elisiana Carpagnano
J. Clin. Med. 2024, 13(21), 6360; https://doi.org/10.3390/jcm13216360 - 24 Oct 2024
Viewed by 426
Abstract
Background/Objectives: This study evaluated the impact of continuous positive airway pressure (C-PAP) therapy combined with a rigorous diet regimen on obese patients with obstructive sleep apnea syndrome (OSAS). Methods: Sixty obese patients (BMI ≥ 30) diagnosed with severe OSAS were recruited in order [...] Read more.
Background/Objectives: This study evaluated the impact of continuous positive airway pressure (C-PAP) therapy combined with a rigorous diet regimen on obese patients with obstructive sleep apnea syndrome (OSAS). Methods: Sixty obese patients (BMI ≥ 30) diagnosed with severe OSAS were recruited in order to establish the evaluation of CPAP therapy with different extents of adherence to a rigorous diet regimen. After one year, significant improvements were observed. Results: BMI reduced by 12.32%, apnea–hypopnea index (AHI) by 22.04%, oxygen desaturation index (ODI) by 15.87%, total sleep time with oxygen saturation below 90% (TST90%) by 25.2%, and Epworth Sleepiness Scale (ESS) scores by 21.74%. Patients were, then, divided into three groups, based on adherence to the restricted diet, as well as to the correct use of the nocturnal C-PAP, showing different reductions in BMI, AHI, ODI, TST90%, and ESS, according to their adherence, based on the sum of % reduction in BMI + AHI into three groups. Conclusions: These findings underscore the effectiveness of combining C-PAP therapy with a strict diet in improving OSAS symptoms and overall health in obese patients. Future studies with larger cohorts and longer follow-up periods are needed to confirm these results and explore the long-term benefits of this integrated approach. Full article
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<p>Comparison among groups, 95% CI of BMI + AHI negative improvement into three groups of patients.</p>
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21 pages, 9245 KiB  
Article
6-Gingerol Inhibits De Novo Lipogenesis by Targeting Stearoyl-CoA Desaturase to Alleviate Fructose-Induced Hepatic Steatosis
by Pan Li, Tingting Wang, Hongmei Qiu, Ruoyu Zhang, Chao Yu and Jianwei Wang
Int. J. Mol. Sci. 2024, 25(20), 11289; https://doi.org/10.3390/ijms252011289 - 20 Oct 2024
Viewed by 856
Abstract
Metabolic-associated fatty liver disease (MAFLD), also known as non-alcoholic fatty liver disease (NAFLD), is a worldwide liver disease without definitive or widely used therapeutic drugs in clinical practice. In this study, we confirm that 6-gingerol (6-G), an active ingredient of ginger (Zingiber [...] Read more.
Metabolic-associated fatty liver disease (MAFLD), also known as non-alcoholic fatty liver disease (NAFLD), is a worldwide liver disease without definitive or widely used therapeutic drugs in clinical practice. In this study, we confirm that 6-gingerol (6-G), an active ingredient of ginger (Zingiber officinale Roscoe) in traditional Chinese medicine (TCM), can alleviate fructose-induced hepatic steatosis. It was found that 6-G significantly decreased hyperlipidemia caused by high-fructose diets (HFD) in rats, and reversed the increase in hepatic de novo lipogenesis (DNL) and triglyceride (TG) levels induced by HFD, both in vivo and in vitro. Mechanistically, chemical proteomics and cellular thermal shift assay (CETSA)–proteomics approaches revealed that stearoyl-CoA desaturase (SCD) is a direct binding target of 6-G, which was confirmed by further CETSA assay and molecular docking. Meanwhile, it was found that 6-G could not alter SCD expression (in either mRNA or protein levels), but inhibited SCD activity (decreasing the desaturation levels of fatty acids) in HFD-fed rats. Furthermore, SCD deficiency mimicked the ability of 6-G to reduce lipid accumulation in HF-induced HepG2 cells, and impaired the improvement in hepatic steatosis brought about by 6-G treatment in HFD supplemented with oleic acid diet-induced SCD1 knockout mice. Taken together, our present study demonstrated that 6-G inhibits DNL by targeting SCD to alleviate fructose diet-induced hepatic steatosis. Full article
(This article belongs to the Special Issue Nutrients and Active Substances in Natural Products)
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<p>6-G reduces the lipid accumulation in HF-induced HepG2 cells. (<b>A</b>) MTT assay. (<b>B</b>) Cellular TG. (<b>C</b>) ORO staining of HepG2 cells. (<b>D</b>) ORO staining of cellular extract of HepG2 cells in DMSO. (<b>E</b>) OD intensity of the cellular extract with ORO staining at wavelength of 490 nm. 6-G-L: 5 μM 6-G; 6-G-M: 10 μM 6-G; 6-G-H: 20 μM 6-G. Data are expressed as mean ± SD, <span class="html-italic">n</span> = 3 independent experiments. ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>6-G ameliorates metabolic syndrome and hepatic steatosis in HFD-induced disease in rats. (<b>A</b>) Body weight. (<b>B</b>) Serum TG. (<b>C</b>) Serum TC. (<b>D</b>) Liver TG. (<b>E</b>) Liver TC. (<b>F</b>) Ratio of liver/body weight in rats. (<b>G</b>) Liver pathology of rats, including liver images and HE, ORO, Masson staining. ND: normal diet; HFD: high-fructose diet; 6-G-L: 0.1 mg/kg; 6-G-H: 0.4 mg/kg. Data are expressed as mean ± SEM, <span class="html-italic">n</span> = 8 rats per group. ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05. N.S: no significant differences.</p>
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<p>6-G binds directly to SCD. (<b>A</b>) Differentially expressed proteins identified by CESTA-integrated quantitative proteomics analysis between 6-G and DMSO treatments. (<b>B</b>) Venn analysis of the targets identified by chemical proteomics and CETSA proteomics. (<b>C</b>) Efficiency evaluation of magnetic capture (chemical proteomics) by SDS-PAGE. The upper image displays Coomassie blue staining of SDS-PAGE while the lower image shows Western blot verification. Lane 1 represents the lysate of HF-induced HepG2 cells as a loading control, lane 2 exhibits the lysate captured by the functionalization of azide-MMs as a negative control, lane 3 indicates the lysate captured by the Al-6G-MMs. (<b>D</b>) CETSA assay for validation. The left panel shows SCD protein levels after heat treatment at different temperatures, the right panel shows SCD levels after treatment with different concentrations of 6-G at 55 °C. (<b>E</b>) Molecular docking. The left image exhibits the overall view for docking and the right image shows the detailed view. The yellow stick represents 6-G molecule, blue carton represents SCD protein, blue lines represent hydrogen bonding, and gray dashed lines stand for hydrophobic interactions. Data are expressed as mean ± STD, <span class="html-italic">n</span> = 3 independent experiments. ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>6-G suppresses SCD activity independently of SCD expression regulation. (<b>A</b>) Relative mRNA expression of SCD in rat livers. (<b>B</b>,<b>C</b>) SCD protein levels in rat livers. (<b>D</b>) SCD mRNA levels in HepG2 cells. (<b>E</b>,<b>F</b>) SCD protein expression in HepG2 cells. (<b>G</b>) Heatmap of the representative FFAs. FFAs: free fatty acids. (<b>H</b>,<b>I</b>) Ratios of C16:1N7/C16:0, C18:1N9/C18:0 in rat livers, showing SCD activity. Data are presented as mean ± SEM (in vivo, <span class="html-italic">n</span> ≥ 6/group) and mean ± STD (in vitro, <span class="html-italic">n</span> = 3 independent experiments). ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05, N.S: no significant differences.</p>
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<p>6-G alleviates SCD-mediated DNL and lipid accumulation in HF-induced HepG2 cells. (<b>A</b>,<b>B</b>) Knockdown efficiency of SCD at mRNA and protein levels by qRT-PCR and Western blot. (<b>C</b>) Relative expression of intracellular TG content to control (si-NC). (<b>D</b>) ORO staining. (<b>E</b>) Relative levels of intracellular free fatty acids to control. (<b>F</b>,<b>G</b>) Effect of SCD knockdown on AMPK and CPT1α levels, with or without 6-G treatment. siNC: blank siRNA, siSCD: knockdown of SCD by siRNA. Data are presented as mean ± STD, <span class="html-italic">n</span> = 3 independent experiments. ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05, N.S: no significant differences.</p>
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<p>6-G improves fructose-induced hepatic steatosis of mice in a SCD1-dependent manner. (<b>A</b>) SCD1 expression in WT and <span class="html-italic">SCD1<sup>−/−</sup></span> mice. (<b>B</b>) Scheme of mouse groupings and 6-G treatment. (<b>C</b>) Body weight of mice. (<b>D</b>) Ratio of liver/body weight. (<b>E</b>) Liver TG. (<b>F</b>) Liver ORO staining. (<b>G</b>) Liver TC. 6-G: 0.8 mg/kg. <span class="html-italic">n</span> ≥ 5 mice for each group. Data are expressed as mean ± SEM, ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05, N.S: no significant differences.</p>
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<p>Experimental procedures of chemical proteomics approach to identify the direct binding targets of 6-G. DMF: N, N-Dimethylformamide; Sulfo-SADP: sulfosuccinimidyl (4-azido-phenyldithio) propionate.</p>
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<p>Technology roadmap of CETSA-integrated proteomics. Cell lysate was obtained from HF-induced HepG2 cells.</p>
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13 pages, 306 KiB  
Article
FADS1 Genetic Variant and Omega-3 Supplementation Are Associated with Changes in Fatty Acid Composition in Red Blood Cells of Subjects with Obesity
by Samantha Desireé Reyes-Pérez, Karina González-Becerra, Elisa Barrón-Cabrera, José Francisco Muñoz-Valle, Juan Armendáriz-Borunda and Erika Martínez-López
Nutrients 2024, 16(20), 3522; https://doi.org/10.3390/nu16203522 - 17 Oct 2024
Viewed by 774
Abstract
Introduction: Obesity is characterized by low-grade chronic inflammation, which can be modulated by lipid mediators derived from omega-3 (n-3) polyunsaturated fatty acids (PUFA). Obesity is a multifactorial disease, where genetic and environmental factors strongly interact to increase its development. In this [...] Read more.
Introduction: Obesity is characterized by low-grade chronic inflammation, which can be modulated by lipid mediators derived from omega-3 (n-3) polyunsaturated fatty acids (PUFA). Obesity is a multifactorial disease, where genetic and environmental factors strongly interact to increase its development. In this context, the FADS1 gene encodes the delta-5 desaturase protein, which catalyzes the desaturation of PUFA. The rs174547 genetic variant of FADS1 has been associated with alterations in lipid metabolism, particularly with decreases in eicosapentaenoic acid (EPA) and arachidonic acid (AA) concentrations. Objective: To analyze the effect of an n-3-supplemented diet on the fatty acid profile and composition in red blood cells (RBCs) of obese subjects carrying the rs174547 variant of the FADS1 gene. Methodology: Seventy-six subjects with obesity were divided into two groups: omega-3 (1.5 g of n-3/day) and placebo (1.5 g of sunflower oil/day). The dietary intervention consisted of a four-month follow-up. Anthropometric, biochemical, and dietary variables were evaluated monthly. The total fatty acid profile in RBC was determined using gas chromatography. The rs174547 variant was analyzed through allelic discrimination. Results: The n-3 index (O3I) increased at the end of the intervention in both groups. Subjects carrying the CC genotype showed significant differences (minor increase) in n-6, n-3, total PUFA, EPA, DHA, and the O3I in RBCs compared to TT genotype carriers in the n-3 group. Conclusions: The diet supplemented with EPA and DHA is ideal for providing the direct products that bypass the synthesis step affected by the FADS1 rs174547 variant in subjects carrying the CC genotype. The O3I confirmed an increase in n-3 fatty acids in RBCs at the end of the intervention. Full article
(This article belongs to the Section Nutritional Epidemiology)
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11 pages, 1077 KiB  
Article
Comparing the Effects of Two Surfactant Administration Methods: Minimally Invasive Surfactant Therapy (MIST) with Intubation (INSURE) in Infants with Respiratory Distress Syndrome
by Hassan Boskabadi, Maryam Behmadi, Gholamali Maamouri, Tina Loghmani and Abdolrasoul Rangrazi
Adv. Respir. Med. 2024, 92(5), 384-394; https://doi.org/10.3390/arm92050036 - 11 Oct 2024
Viewed by 786
Abstract
Background: The aim of this study is to investigate and compare the effects of administering a surfactant through a fine intra-tracheal catheter during spontaneous breathing with the usual INSURE method in premature infants. Materials and Methods: In this clinical trial, premature babies with [...] Read more.
Background: The aim of this study is to investigate and compare the effects of administering a surfactant through a fine intra-tracheal catheter during spontaneous breathing with the usual INSURE method in premature infants. Materials and Methods: In this clinical trial, premature babies with respiratory distress syndrome who required surfactant administration were randomly assigned to two groups: an intervention group (MIST) and a control group (INSURE). The treatment results were compared in terms of complications related to treatment (desaturation, apnea, bradycardia, and surfactant reflux), respiratory complications (requirement for mechanical ventilation, duration of nCPAP, duration of oxygen requirement, frequency of pneumothorax, and pulmonary hemorrhage), complications related to prematurity (incidence of IVH, NEC, BPD, and PDA), the need for a second dose of surfactant, and the duration of hospitalization. Results: a total of 160 premature babies with a gestational age of 26–34 weeks were randomly divided into two groups. The results showed that the need for mechanical ventilation, the duration of CPAP needed, and the duration of oxygen therapy were significantly lower in the MIST group than in the INSURE group. Additionally, the incidence of BPD was less common in the MIST group compared to the INSURE group. However, surfactant reflux was more common in the MIST group than in the INSURE group. There were no significant differences between the two groups in other outcomes, including the length of hospital stay and complications such as IVH, PDA, NEC, pneumothorax, and pulmonary hemorrhage. Conclusion: The results of this research demonstrate that the less invasive method of surfactant therapy (MIST) is a feasible, effective, and low-risk alternative to the INSURE method. Full article
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<p>Feeding tube used in the MIST technique.</p>
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<p>Consort flow chart.</p>
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16 pages, 1928 KiB  
Article
Acute Fatigue Impairs Heart Rate Variability and Resting Muscle Oxygen Consumption Kinetics
by Aldo A. Vasquez-Bonilla, Rodrigo Yáñez-Sepúlveda, Marcelo Tuesta, Eduardo Báez-San Martin, Matías Monsalves-Álvarez, Jorge Olivares-Arancibia, Daniel Duclos-Bastías, Catalina Recabarren-Dueñas and Fernando Alacid
Appl. Sci. 2024, 14(20), 9166; https://doi.org/10.3390/app14209166 - 10 Oct 2024
Viewed by 921
Abstract
This study evaluated the influence of acute fatigue on heart rate variability (HRV) and muscle oxygen saturation (SmO2) at rest, as well as the reliability of SmO2 data measured using near-infrared spectroscopy (NIRS) during a vascular occlusion test (VOT). Twelve [...] Read more.
This study evaluated the influence of acute fatigue on heart rate variability (HRV) and muscle oxygen saturation (SmO2) at rest, as well as the reliability of SmO2 data measured using near-infrared spectroscopy (NIRS) during a vascular occlusion test (VOT). Twelve physically active subjects participated. Measurements included perceived muscle soreness using the visual analog scale (VAS pain), HRV parameters, variables of resting SmO2 (desaturation and resaturation), and reoxygenation kinetics (mean response time, MRT) through a VOT-NIRS located in the vastus lateralis (VL). Measurements were taken at three points: 24 h before, before exhaustive exercise, and 30 min after exhaustive exercise. The results indicated that acute fatigue increased resting muscle oxygen consumption in desaturation (+22 SmO2) and resaturation (+18 SmO2), improved MRT (−15 s), and elevated sympathetic nervous system (SNS) activity, as observed in the R-R interval (−262 ms) and SNS index (+0.5). HRV significantly influenced desaturation (r2 = 0.69), resaturation (r2 = 0.60), and MRT (r2 = 0.54). Reliability was established with an ICC of 0.49 and 0.63 for desaturation and resaturation, respectively. Real changes in desaturation and resaturation should be considered ≥ 7% SmO2 at rest and ≥ 11% SmO2 to avoid daily fatigue interference. In conclusion, acute fatigue increases resting SmO2 consumption and is associated with higher SNS activity and increased VAS pain. Full article
(This article belongs to the Special Issue Research of Sports Medicine on Health Care)
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<p>Protocol design. <b>Note.</b> (<b>a</b>) VAS pain = Visual Analog Scale; (<b>b</b>) HRV = Heart Rate Variability; (<b>c</b>) VOT-NIRS = Vascular Occlusion Test using Near-Infrared Spectroscopy. Protocol of fatigue induction 10 × 10 repetitions of plyometric jumps from a 0.6 m box (10 s between jumps, 1 min between sets). The measurement protocol was carried out at the three measurement points.</p>
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<p>Visualization of vascular occlusion test. <b>Note.</b> Baseline = Average values of the 30 s before starting VOT-NIRS; Desaturation = SmO<sub>2</sub> decrease during the ischemic period (3 min); Resaturation = SmO<sub>2</sub> increase during the recovery period; Reactive hyperemia = SmO<sub>2</sub> increase compared to baseline values. Reoxygenation Kinetics = Oxygen utilization rate based on mean response time (MRT), which is equal to the sum of the delay time (DT) and the time constant (Tau).</p>
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<p>Multiple linear regressions between heart rate variability and resting muscle oxygen consumption. <b>Note.</b> The regression model included the following HRV residual analysis as an independent variable and dependent variable: (<b>a</b>) desaturation, (<b>b</b>) resaturation, (<b>c</b>) hyperemia, and (<b>d</b>) MRT. The condition (without fatigue or with fatigue) was included as a factor that modulates the multiple regression.</p>
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<p>Correlation between perceived muscle pain and resting muscle oxygen consumption measured with VOT-NIRS. <b>Note.</b> The correlation analysis is shown in the graphs: (<b>a</b>) desaturation, (<b>b</b>) resaturation, (<b>c</b>) hyperemia, and (<b>d</b>) MRT.</p>
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14 pages, 5797 KiB  
Article
The Role of Biopolymers on the Water Retention Capacity of Stabilized Sand
by Ahmed M. Al-Mahbashi and Abdullah Almajed
Sustainability 2024, 16(19), 8612; https://doi.org/10.3390/su16198612 - 4 Oct 2024
Viewed by 764
Abstract
The application of biopolymers for sand stabilization has recently gained attention due to their natural composition, which makes them both environmentally friendly and of reasonable cost. Measuring the soil–water retention curve (SWRC) of biopolymers-treated sand is essential for the design, modeling, and interpretation [...] Read more.
The application of biopolymers for sand stabilization has recently gained attention due to their natural composition, which makes them both environmentally friendly and of reasonable cost. Measuring the soil–water retention curve (SWRC) of biopolymers-treated sand is essential for the design, modeling, and interpretation of the unsaturated behavior of these materials. Unsaturated shear strength, unsaturated flow, and associated retention capacity are well addressed and evaluated using SWRC. Therefore, this study examined the possible effects of biopolymers—sodium alginate (SA), guar gum (GG), and pectin (P) on the SWRC and retention capacity for stabilized sand. Apart from natural sand, three different concentrations were investigated for each biopolymer. The SWRCs were measured over the entire practical range of suction using a combination of three techniques: hanging column for low suction measurement, axis translation techniques for moderate suction measurement, and vapor equilibrium technique for high suction measurement. The results indicate significant changes in SWRC, and a new series of micropores was developed, this, in turn, extends the desaturation zone of treated sand from a low suction range (i.e., 30 kPa) to moderate to high suction levels (i.e., 10,000 kPa). The saturated water content (ws) was slightly reduced, air entry values (AEVs), and residual suction (sr) significantly increased and multiplied up to 200 and 75 times respectively. The retention capacity increased, exhibiting a dependency between the biopolymer type and suction range. The results are of great significance for both practitioner engineers and researchers in predicting the unsaturated soil functions of treated sand. Full article
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<p>Gradation curve of the sand used in this study.</p>
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<p>Testing devices for the considered techniques: (<b>a</b>) hanging column, (<b>b</b>) pressure plate extractor, and (<b>c</b>) saturated salt solutions.</p>
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<p>Equilibrium process under different salt solutions, using the vapor equilibrium technique.</p>
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<p>Effect of biopolymer percentage on SWRCs: (<b>a</b>) sodium alginate, (<b>b</b>) pectin, and (<b>c</b>) guar gum.</p>
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<p>Effect of biopolymer percentage on SWRCs: (<b>a</b>) sodium alginate, (<b>b</b>) pectin, and (<b>c</b>) guar gum.</p>
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<p>A typical SWRC with its identified zones.</p>
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<p>SEM images of (<b>a</b>) natural sand, (<b>b</b>,<b>c</b>) specimens treated with SA, and (<b>d</b>) specimens treated with P.</p>
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<p>Effect of biopolymer type on SWRCs of sand at different biopolymer dosages: (<b>a</b>) 1%, (<b>b</b>) 3%, and (<b>c</b>) 5%.</p>
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<p>Changes induced by biopolymers in the main characteristics of SWRCs: (<b>a</b>) <span class="html-italic">w</span><sub>s</sub>, (<b>b</b>) AEV1, (<b>c</b>) AEV2, and (<b>d</b>) <span class="html-italic">s</span><sub>r</sub>.</p>
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20 pages, 3234 KiB  
Article
Severity Ranking of Missense and Frameshift Genetic Variants in SCD1 by In Silico and In Vitro Functional Analysis
by Hanna K. Susán, Gabriella Orosz, Veronika Zámbó, Miklós Csala and Éva Kereszturi
Nutrients 2024, 16(19), 3259; https://doi.org/10.3390/nu16193259 - 26 Sep 2024
Viewed by 977
Abstract
Background: A considerable proportion of the symptoms associated with excessive dietary intake can be attributed to systemic imbalances in lipid metabolism. The prominent toxicity of saturated fatty acids has been repeatedly demonstrated and sheds light on the protective role of stearoyl-CoA desaturase-1 (SCD1), [...] Read more.
Background: A considerable proportion of the symptoms associated with excessive dietary intake can be attributed to systemic imbalances in lipid metabolism. The prominent toxicity of saturated fatty acids has been repeatedly demonstrated and sheds light on the protective role of stearoyl-CoA desaturase-1 (SCD1), the key enzyme for fatty acid desaturation. SCD1 protein expression is regulated at the levels of transcription, translation, and degradation. However, the modulating effect of the variability of the human genome must also be taken into account. Therefore, we aimed to ascertain whether natural missense or frameshift mutations in SCD1 (p.H125P, p.M224L, p.A333T, p.R253AfsTer7) could influence the expression, degradation, or function of the enzyme. Methods: In silico and in vitro experiments were conducted to comprehensively evaluate the consequences associated with each genetic variation, with the objective of using the results to propose a risk or severity ranking of SCD1 variants. Results: As anticipated, the p.R253AfsTer7 variant was identified as the most deleterious in structural, functional, and quantitative terms. The p.H125P variant also reduced the desaturation capacity of the enzyme in accordance with the predicted structural alterations and augmented degradation resulting from folding complications. This was aggravated by increased mRNA instability and accompanied by mild endoplasmic reticulum stress induction. The p.A333T protein exhibited an intermediate phenotype, whereas p.M224L showed no deleterious effects and even increased the amount of SCD1. Conclusions: In conclusion, the large-scale identification of genetic variations needs to be supplemented with comprehensive functional characterization of these variations to facilitate adequate personalized prevention and treatment of lipid metabolism-related conditions. Full article
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<p>Localization of genetic variations in the SCD1 gene and protein. (<b>A</b>): Exons are numbered with Arabic numerals; the rs ID of each variant is also indicated. (<b>B</b>): The crystal structure of the wild-type human SCD1 was obtained from the Protein Data Bank (file 4ZYO). The image was rendered with DeepView/Swiss-Pdb Viewer version 4.0.2. The positions of the amino acids affected by genetic variations were indicated by different colors (red, yellow, light blue, and pink), and one of the catalytic Zn<sup>2+</sup> ions was highlighted in dark blue. The substrate stearoyl-CoA is also shown in the active site in green.</p>
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<p>Prediction of the effect of SCD1 genetic variants. (<b>A</b>): Diagrammatic representation of the overall effect of SCD1 variations predicted by ten different prediction tools. The scale of impact ranges from 0 to 100%, with higher values indicating more adverse effects. Red, orange, or green markers represent a damaging, intermediate, or benign predicted effect, respectively, according to the classification of the corresponding program. (<b>B</b>): Predicted structural effect of p.H125P variant. The crystal structure of the wild-type human SCD1 was downloaded from the Protein Data Bank (file 4ZYO). The 3D structure of p.H125P SCD1 variant was predicted by I-TASSER. Images were generated with DeepView/Swiss-Pdb Viewer version 4.0.2. Amino acid 125 is indicated in red, Zn<sup>2+</sup> ion in dark blue, and stearoyl-CoA in green.</p>
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<p>Desaturated profile upon overexpression of p.H125P, p.M224L, p.A333T, and p.R253AfsTer7 SCD1 variants. Transiently transfected HEK293T cells were collected, and the FA profile was measured by GC-MS after sample preparation, as described in the <span class="html-italic">Materials and Methods</span> section. The quantities of (<b>A</b>) palmitate, (<b>B</b>) stearate, (<b>C</b>) oleate, (<b>D</b>) palmitoleate, and (<b>E</b>) vaccenate were normalized to the total protein content of the samples and are presented as mean values ± S.D.; n = 3. The given FA content of the wild-type SCD1 was considered to be 100%. Statistical analysis was performed using the Tukey–Kramer multiple comparisons test. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01. (<b>F</b>): The enzymes interconverting the highlighted FAs. ELOVL6: fatty acid elongase 6; Ctrl: control.</p>
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<p>Expression of SCD1 variants in transiently transfected HEK293T and SK-N-FI cells. The HEK293T and SK-N-FI cells were collected and subjected to the requisite processing 24 h following the transfection. Aliquots of cell lysates (10 µg protein) were loaded onto a 12% SDS–polyacrylamide gel and, after electrophoresis, transferred to an Immobilon-P membrane. SCD1 was detected using either anti-SCD1 (<b>A</b>) or anti-Glu-Glu tag (<b>B</b>) antibody in HEK293T cells. The amount of the Glu-Glu-tagged SCD1 mutant proteins was also assessed in SK-N-FI cells (<b>C</b>). Actin was used as a loading control. Representative immunoblots of three independent experiments are shown. Band intensities were quantified by densitometry, and the SCD1/Actin ratios are presented as bar graphs. The quantity of the wild-type SCD1 protein was considered to be 100%. Data are shown as mean values ± S.D. Statistical analysis was performed with the Tukey–Kramer multiple comparisons test. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001. Ctrl: control.</p>
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<p>mRNA level and stability of <span class="html-italic">SCD1</span> variants. (<b>A</b>): mRNA levels were measured in transiently transfected HEK293T cells. (<b>B</b>): After 24 h since transfection, HEK293T cells were treated with actinomycin D (5 µg/mL) for 0, 2, 3, 6, 9, or 24 h. The samples were harvested and prepared as described in the Materials and Methods. qPCR was carried out using <span class="html-italic">GAPDH</span> and <span class="html-italic">SCD1</span> sequence-specific primers, as indicated in the Materials and Methods and <a href="#app1-nutrients-16-03259" class="html-app">Supplementary Table S2</a>. The diagram depicts the outcome of at least three independent assessments, wherein the quantity of the wild-type <span class="html-italic">SCD1</span> mRNA was considered to be 100%. Statistical analysis was performed with the Tukey–Kramer multiple comparisons test. Data are shown as mean values ± S.D. ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001. Ctrl: control.</p>
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<p>Effect of proteasome inhibitor on the levels of SCD1 variants. HEK293T cells were transiently transfected with wild-type, p.H125P, and p.A333T SCD1 constructs and treated with 2 µM MG132 for 24 h. Aliquots of cell lysates (10 µg) were loaded onto a 12% SDS–polyacrylamide gel and, after electrophoresis, transferred to an Immobilon-P membrane. SCD1 was detected using an anti-Glu-Glu tag antibody. Actin was used as a loading control. Representative immunoblots of three independent experiments are shown. Band intensities were quantified by densitometry, and the SCD1/Actin ratios are presented as bar graphs. The quantity of the wild-type SCD1 protein was considered to be 100%. Data are shown as mean values ±S.D. Statistical analysis was performed with the Tukey–Kramer multiple comparisons test. Ctrl: control.</p>
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<p>Intracellular aggregation (<b>A</b>) and protease sensitivity (<b>B</b>) of wild-type, p.H125P, and p.A333T SCD1. Glu-Glu-tagged forms of wild-type and mutant SCD1 were expressed in HEK293T cells. At 24 h after transfection, cells were harvested, and lysates were prepared, as described in the Materials and Methods. Aliquots of samples (10 µg) were loaded onto a 12% SDS–polyacrylamide gel and, after electrophoresis, transferred to an Immobilon-P membrane. SCD1 was detected using an anti-Glu-Glu tag antibody. Representative immunoblots of three independent experiments are shown. Band intensities were quantified by densitometry and are presented as bar graphs. The quantity of wild-type SCD1 protein was considered to be 100%. Data are shown as mean values ± S.D. Statistical analysis was performed with the Tukey–Kramer multiple comparisons test. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001; Ctrl: control.</p>
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<p>ER stress markers in HEK293T cells expressing wild-type or mutant SCD1 proteins. (<b>A</b>): BiP, CHOP, and PDI protein levels in cell lysates (10 µg total protein) were analyzed by immunoblotting, as described in the Materials and Methods. Actin was used as loading control. Representative immunoblots of three independent experiments are shown. (<b>B</b>): The extent of <span class="html-italic">XBP1</span> splicing was determined by qPCR. Expression of <span class="html-italic">GAPDH</span> was measured as a reference control, as described in the Materials and Methods. This Figure shows the results of three independent measurements, where the amount of <span class="html-italic">sXBP1</span> mRNA in wild-type SCD1 samples was considered to be 100%. Statistical analysis was performed with the Tukey–Kramer multiple comparisons test. * <span class="html-italic">p</span> &lt; 0.05; *** <span class="html-italic">p</span> &lt; 0.001; Ctrl: control.</p>
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<p>Summary of the scalable functional impact of SCD1 genetic variants. The colors red, orange, and green indicate harmful, moderate, and benign effects, respectively. The direction of the arrow represents the direction of change. Checkmarks indicate no difference from the wild-type SCD1, while dashes indicate no data.</p>
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17 pages, 5709 KiB  
Review
Flexible versus Rigid Bronchoscopy for Tracheobronchial Foreign Body Removal in Children: A Comparative Systematic Review and Meta-Analysis
by Alaa Safia, Uday Abd Elhadi, Rawnk Bader, Ashraf Khater, Marwan Karam, Taiser Bishara, Saqr Massoud, Shlomo Merchavy and Raed Farhat
J. Clin. Med. 2024, 13(18), 5652; https://doi.org/10.3390/jcm13185652 - 23 Sep 2024
Viewed by 647
Abstract
The removal of foreign bodies (FBs) from the airways of children is a critical procedure that can avert serious complications. While both flexible and rigid bronchoscopy techniques are employed for this purpose, their comparative efficacy and safety remain subjects of debate. Therefore, we [...] Read more.
The removal of foreign bodies (FBs) from the airways of children is a critical procedure that can avert serious complications. While both flexible and rigid bronchoscopy techniques are employed for this purpose, their comparative efficacy and safety remain subjects of debate. Therefore, we conducted this investigation to compare between both procedures. Studies comparing flexible to rigid bronchoscopy (n = 14) were identified by searching PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar. We performed comparative meta-analyses of reported presentation characteristics and clinical outcomes, using fixed- and random-effects models. A diverse range of FB types and locations were identified. No difference was observed in the success rate of FB removal between flexible and rigid bronchoscopy (logOR = 0.27; 95%CI: −1.91:2.45). The rate of negative first bronchoscopy was higher in the flexible compared to the rigid group (logOR = 2.68; 95%CI: 1.68:3.67). Conversion rates to the alternative method were higher in the flexible bronchoscopy group. The overall complication rates were similar between both methods; however, the risk of desaturation was significantly lower with flexible bronchoscopy (logOR = −2.22; 95%CI: −3.36:−1.08). Flexible bronchoscopy was associated with a shorter length of hospital stay. The choice of bronchoscopy technique should be tailored to individual case characteristics. Full article
(This article belongs to the Section Otolaryngology)
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<p>PRISMA diagram showing the results of the literature search and screening processes. * records identified during the initial database search before duplicate identification and removal; ** excluded records during the title/abstract screening phase.</p>
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<p>Forest plot showing the difference in successful foreign body extraction between flexible and rigid bronchoscopy [<a href="#B5-jcm-13-05652" class="html-bibr">5</a>,<a href="#B6-jcm-13-05652" class="html-bibr">6</a>,<a href="#B7-jcm-13-05652" class="html-bibr">7</a>,<a href="#B21-jcm-13-05652" class="html-bibr">21</a>,<a href="#B22-jcm-13-05652" class="html-bibr">22</a>,<a href="#B25-jcm-13-05652" class="html-bibr">25</a>,<a href="#B27-jcm-13-05652" class="html-bibr">27</a>].</p>
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<p>Forest plot showing the difference in failed foreign body extraction between flexible and rigid bronchoscopy [<a href="#B5-jcm-13-05652" class="html-bibr">5</a>,<a href="#B6-jcm-13-05652" class="html-bibr">6</a>,<a href="#B7-jcm-13-05652" class="html-bibr">7</a>,<a href="#B21-jcm-13-05652" class="html-bibr">21</a>,<a href="#B22-jcm-13-05652" class="html-bibr">22</a>,<a href="#B26-jcm-13-05652" class="html-bibr">26</a>].</p>
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<p>Forest plot showing the difference in negative first bronchoscopy between flexible and rigid bronchoscopy [<a href="#B5-jcm-13-05652" class="html-bibr">5</a>,<a href="#B23-jcm-13-05652" class="html-bibr">23</a>,<a href="#B25-jcm-13-05652" class="html-bibr">25</a>].</p>
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<p>Forest plot showing the difference in conversion between flexible and rigid bronchoscopy [<a href="#B5-jcm-13-05652" class="html-bibr">5</a>,<a href="#B6-jcm-13-05652" class="html-bibr">6</a>,<a href="#B7-jcm-13-05652" class="html-bibr">7</a>,<a href="#B21-jcm-13-05652" class="html-bibr">21</a>,<a href="#B22-jcm-13-05652" class="html-bibr">22</a>,<a href="#B23-jcm-13-05652" class="html-bibr">23</a>,<a href="#B25-jcm-13-05652" class="html-bibr">25</a>,<a href="#B26-jcm-13-05652" class="html-bibr">26</a>,<a href="#B27-jcm-13-05652" class="html-bibr">27</a>,<a href="#B28-jcm-13-05652" class="html-bibr">28</a>].</p>
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<p>Forest plot showing the difference in operative time between flexible and rigid bronchoscopy [<a href="#B6-jcm-13-05652" class="html-bibr">6</a>,<a href="#B7-jcm-13-05652" class="html-bibr">7</a>,<a href="#B21-jcm-13-05652" class="html-bibr">21</a>,<a href="#B27-jcm-13-05652" class="html-bibr">27</a>].</p>
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<p>Forest plot showing the difference in length of hospital stay between flexible and rigid bronchoscopy [<a href="#B6-jcm-13-05652" class="html-bibr">6</a>,<a href="#B21-jcm-13-05652" class="html-bibr">21</a>,<a href="#B25-jcm-13-05652" class="html-bibr">25</a>].</p>
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<p>Forest plot showing the difference in total complications between flexible and rigid bronchoscopy [<a href="#B5-jcm-13-05652" class="html-bibr">5</a>,<a href="#B6-jcm-13-05652" class="html-bibr">6</a>,<a href="#B7-jcm-13-05652" class="html-bibr">7</a>,<a href="#B13-jcm-13-05652" class="html-bibr">13</a>,<a href="#B15-jcm-13-05652" class="html-bibr">15</a>,<a href="#B20-jcm-13-05652" class="html-bibr">20</a>,<a href="#B21-jcm-13-05652" class="html-bibr">21</a>,<a href="#B22-jcm-13-05652" class="html-bibr">22</a>,<a href="#B23-jcm-13-05652" class="html-bibr">23</a>,<a href="#B25-jcm-13-05652" class="html-bibr">25</a>,<a href="#B27-jcm-13-05652" class="html-bibr">27</a>,<a href="#B28-jcm-13-05652" class="html-bibr">28</a>].</p>
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<p>Forest plot showing the difference in major complications between flexible and rigid bronchoscopy [<a href="#B6-jcm-13-05652" class="html-bibr">6</a>,<a href="#B23-jcm-13-05652" class="html-bibr">23</a>,<a href="#B24-jcm-13-05652" class="html-bibr">24</a>,<a href="#B28-jcm-13-05652" class="html-bibr">28</a>].</p>
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<p>Forest plot showing the difference in death between flexible and rigid bronchoscopy [<a href="#B6-jcm-13-05652" class="html-bibr">6</a>,<a href="#B22-jcm-13-05652" class="html-bibr">22</a>,<a href="#B23-jcm-13-05652" class="html-bibr">23</a>,<a href="#B28-jcm-13-05652" class="html-bibr">28</a>].</p>
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8 pages, 218 KiB  
Brief Report
Avoided and Avoidable Deaths with the Use of COVID-19 Convalescent Plasma in Italy during the First Two Years of Pandemic
by Massimo Franchini, Arturo Casadevall, Quigly Dragotakes and Daniele Focosi
Life 2024, 14(9), 1207; https://doi.org/10.3390/life14091207 - 23 Sep 2024
Cited by 1 | Viewed by 560
Abstract
Italy was the first western country to be hit by the COVID-19 pandemic and has suffered nearly 200,000 deaths so far during the four years of the pandemic. In March 2020, Italy first deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Despite [...] Read more.
Italy was the first western country to be hit by the COVID-19 pandemic and has suffered nearly 200,000 deaths so far during the four years of the pandemic. In March 2020, Italy first deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Despite this initial effort, the proportion of COVID-19 patients treated with CCP during the first two years of the pandemic (2020–2021) was very low (approximately 2% of individuals hospitalized for COVID-19). In this study, we estimated the number of actual inpatient lives saved by CCP treatment in Italy using national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimated the potential number of lives saved if CCP had been deployed to 100% of hospitalized patients or used in 15% to 75% of outpatients. According to these models, CCP usage in 2020–2021 saved between 385–1304 lives, but this number would have increased to 17,751–60,079 if 100% of inpatients had been transfused with CCP. Similarly, broader (15–75%) usage in outpatients could have prevented 21,187–190,689 hospitalizations (desaturating hospitals) and 6144–81,926 deaths. These data have important implications for convalescent plasma use in future infectious disease emergencies. Full article
19 pages, 4197 KiB  
Article
Polyamine Pathway Inhibitor DENSPM Suppresses Lipid Metabolism in Pheochromocytoma Cell Line
by Hans K. Ghayee, Kaylie A. Costa, Yiling Xu, Heather M. Hatch, Mateo Rodriguez, Shelby C. Straight, Marian Bustamante, Fahong Yu, Fatima Smagulova, John A. Bowden and Sergei G. Tevosian
Int. J. Mol. Sci. 2024, 25(18), 10029; https://doi.org/10.3390/ijms251810029 - 18 Sep 2024
Viewed by 1205
Abstract
Pheochromocytomas (PCCs) are tumors arising from chromaffin cells in the adrenal medulla, and paragangliomas (PGLs) are tumors derived from extra-adrenal sympathetic or parasympathetic paraganglia; these tumors are collectively referred to as PPGL cancer. Treatment for PPGL primarily involves surgical removal of the tumor, [...] Read more.
Pheochromocytomas (PCCs) are tumors arising from chromaffin cells in the adrenal medulla, and paragangliomas (PGLs) are tumors derived from extra-adrenal sympathetic or parasympathetic paraganglia; these tumors are collectively referred to as PPGL cancer. Treatment for PPGL primarily involves surgical removal of the tumor, and only limited options are available for treatment of the disease once it becomes metastatic. Human carriers of the heterozygous mutations in the succinate dehydrogenase subunit B (SDHB) gene are susceptible to the development of PPGL. A physiologically relevant PCC patient-derived cell line hPheo1 was developed, and SDHB_KD cells carrying a stable short hairpin knockdown of SDHB were derived from it. An untargeted metabolomic approach uncovered an overactive polyamine pathway in the SDHB_KD cells that was subsequently fully validated in a large set of human SDHB-mutant PPGL tumor samples. We previously reported that treatment with the polyamine metabolism inhibitor N1,N11-diethylnorspermine (DENSPM) drastically inhibited growth of these PCC-derived cells in culture as well as in xenograft mouse models. Here we explored the mechanisms underlying DENSPM action in hPheo1 and SDHB_KD cells. Specifically, by performing an RNAseq analysis, we have identified gene expression changes associated with DENSPM treatment that broadly interfere with all aspects of lipid metabolism, including fatty acid (FA) synthesis, desaturation, and import/uptake. Furthermore, by performing an untargeted lipidomic liquid chromatography–mass spectrometry (LC/MS)-based analysis we uncovered specific groups of lipids that are dramatically reduced as a result of DENSPM treatment. Specifically, the bulk of plasmanyl ether lipid species that have been recently reported as the major determinants of cancer cell fate are notably decreased. In summary, this work suggests an intersection between active polyamine and lipid pathways in PCC cells. Full article
(This article belongs to the Special Issue Molecular Aspects of Adrenal Diseases and Carcinoma)
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<p>Functional annotation as “biological process”, “cellular localization” or “molecular function” of genes identified as downregulated by the RNA-seq analysis of DENSPM treated hPheo1 (<b>A</b>) or SDHB_KD (<b>B</b>) cells. Bars were sorted by adjusted <span class="html-italic">p</span>-values; the length of each bar represents the number of genes in each group. The fatty acid metabolism category is indicated by a red frame.</p>
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<p>Relative gene expression of lipid-associated genes from the RNA-Seq analysis of hPheo1 (<b>A</b>) and SDHB_KD (<b>B</b>) cells. The means and SEMs for the number of reads corresponding to either untreated (white bars) or DENSPM-treated (grey bars) cells are shown; black squares represent individual observation. All sets are highly significant (<span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Relative gene expression of select lipid-associated genes identified by RNA-seq was confirmed by qRT-PCR. Relative gene expression corresponding to either untreated (dark gray bars) or DENSPM-treated (light grey bars) cells is shown. The data are presented as means and SEMs. ****, <span class="html-italic">p</span> &lt; 0.0001; ***, <span class="html-italic">p</span> &lt; 0.001; **, <span class="html-italic">p</span> &lt; 0.01 *, <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Western blot analysis of FADS2, SCD, and SREBP1 protein expression in hPheo1 (left) and SDHB_KD (right) cells untreated (−) or treated (+) with 10 µM DENSPM.</p>
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<p>Heatmap of the 9 genes (including 6 genes associated with lipid metabolism, green box) that are differentially expressed between PPGL (underlined), ACC, and Prostate Cancer (PC) tumors. Transcript names are shown along the right axis. Red: increased expression, blue: decreased expression.</p>
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<p>(<b>A</b>) A volcano plot of the LC/MS analysis of lipid composition in untreated vs. 10 µM DENSPM-treated hPheo1 Cells (fold change = 2.0; <span class="html-italic">p</span>-value = 0.05, FDR adjusted). (<b>B</b>) A Pie chart shows the significantly altered lipids by (sub)class. Note that the majority of the lipids belong to the plasmanyl class.</p>
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<p>(<b>A</b>) A volcano plot of the LC/MS analysis of lipid composition in untreated vs. 10 µM DENSPM-treated <span class="html-italic">SDHB</span>_KD Cells (Fold change = 2.0; <span class="html-italic">p</span>-value = 0.05, FDR adjusted). (<b>B</b>) A Pie chart shows the significantly altered lipids by (sub)class. Red box: significantly increased lipids by (sub)class. Blue box: significantly decreased lipids by (sub)class. Note that the majority of downregulated lipids belong to the plasmanyl class.</p>
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<p>Most common saturated and unsaturated fatty acids within the significantly changed lipids (<a href="#ijms-25-10029-f006" class="html-fig">Figure 6</a> and <a href="#ijms-25-10029-f007" class="html-fig">Figure 7</a>) in hPheo1 (Orange) and SDHB_KD cells (Blue) treated with DENSPM. Fatty acid classes comprising over 10% of the significant lipids are included. No significant changes between hPheo1 and SDHB_KD cells were noted.</p>
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14 pages, 1002 KiB  
Article
COVID-19 Mortality among Hospitalized Patients: Survival, Associated Factors, and Spatial Distribution in a City in São Paulo, Brazil, 2020
by Marília Jesus Batista, Carolina Matteussi Lino, Carla Fabiana Tenani, Adriano Pires Barbosa, Maria do Rosário Dias de Oliveira Latorre and Evaldo Marchi
Int. J. Environ. Res. Public Health 2024, 21(9), 1211; https://doi.org/10.3390/ijerph21091211 - 14 Sep 2024
Viewed by 796
Abstract
The aims of this study were to analyze patient survival, identify the prognostic factors for patients with COVID-19 deaths considering the length of hospital stay, and evaluate the spatial distribution of these deaths in the city of Jundiaí, São Paulo, Brazil. We examined [...] Read more.
The aims of this study were to analyze patient survival, identify the prognostic factors for patients with COVID-19 deaths considering the length of hospital stay, and evaluate the spatial distribution of these deaths in the city of Jundiaí, São Paulo, Brazil. We examined prognostic variables and survival rates of COVID-19 patients hospitalized at a reference hospital in Jundiaí, Brazil. A retrospective cohort of hospitalized cases from April to July of 2020 was included. Descriptive analysis, Kaplan–Meier curves, univariate and multivariate Cox regression, and binary logistic regression models were used. Among the 902 reported and confirmed cases, there were 311 deaths (34.5%). The median survival was 27 days, and the mean for those discharged was 46 days. Regardless of the length of hospital stay, desaturation, immunosuppression, age over 60, kidney disease, hypertension, lung disease, and hypertension were found to be independent predictors of death in both Cox and logistic regression models. Full article
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<p>Kaplan–Meier cumulative survival curve of hospitalized COVID-19 patients, Jundiaí-SP, 2020.</p>
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<p>Prevalence of cases of death due to COVID-19 (<span class="html-italic">n</span> = 311) according to demographic density in each neighborhood, Jundiaí-SP, 2020. Note: The point on the map indicates the location in the municipality in the State of São Paulo, Brazil.</p>
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