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1.
Org Lett ; 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39303224

ABSTRACT

2-Chloro-1-(1-ethoxyvinyl)pyridinium triflate and several other bench-stable N-(1-alkoxyvinyl) 2-halopyridinium triflates have been developed as reagents for the synthesis of valuable 2-aminopyridine scaffolds via unusually mild SNAr substitutions with amine nucleophiles. Advantages of this approach include an operationally simple mix-and-stir procedure at room temperature or mild heat and ambient atmosphere and without the need for transition metal catalysts, coupling reagents, or high-boiling solvents. The stable N-(1-ethoxyvinyl) moiety serves as a dual SNAr-activating group and pyridine N-protecting group that can be cleaved under thermal, acidic, or oxidative conditions. Preliminary results of other nucleophilic substitutions using oxygen-, sulfur-, and carbon-based nucleophiles are also demonstrated.

2.
Clin Breast Cancer ; 24(7): 620-629, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39117504

ABSTRACT

BACKGROUND: Risk-reducing mastectomy is recommended for high-risk patients but may have significant psychological consequences. This study aimed to determine the differences in anxiety, depressive symptomatology, body image and quality of life in women with an increased risk of breast cancer immediately before and after undergoing risk-reducing mastectomy. METHODS: Eighty-eight women with an increased risk of breast cancer due to BRCA1/2 mutations or a previous cancer diagnosis participated in this study. Instruments used were the Hospital Anxiety and Depression Scale, Body Image Scale and the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and Breast 23, administered 15-30 days before and after surgery. RESULTS: Following surgery, there was an immediate and significant worsening in anxiety, depressive symptomatology and body image. There was a significant deterioration in global, physical, role, and social functioning, as well as in body image and sexual enjoyment scales. Additionally, there were increases in fatigue, nausea and vomiting, constipation, dyspnoea, insomnia, appetite loss, perceived financial difficulties, pain, systemic therapy side effects, and breast and arm symptoms. However, there was an improvement in future perspective. These changes occurred independently of whether participants had a cancer diagnosis or BRCA1/2 mutation. CONCLUSION: Risk-reducing mastectomies have immediate psychological consequences. While these procedures improve future health perspective, they increase anxiety and depressive symptomatology and decrease body image and quality of life, regardless of cancer diagnosis or BRCA1/2 mutation. These findings highlight the psychological consequences of such surgical procedures, emphasizing the need for comprehensive psychological interventions both before and after surgery.


Subject(s)
Anxiety , Body Image , Breast Neoplasms , Depression , Quality of Life , Humans , Female , Breast Neoplasms/surgery , Breast Neoplasms/psychology , Middle Aged , Adult , Body Image/psychology , Anxiety/psychology , Anxiety/etiology , Depression/psychology , Depression/etiology , Mastectomy/psychology , Mastectomy/adverse effects , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Prophylactic Mastectomy/psychology , Mutation , Surveys and Questionnaires , Aged , Genetic Predisposition to Disease , Follow-Up Studies
3.
Heliyon ; 10(15): e34922, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39145028

ABSTRACT

The concept of security is becoming a global challenge, and governments, stakeholders, corporate societies, and individuals must urgently create a reasonable protection mechanism for good. Therefore, a real-time surveillance system is essential for detection, tracking, and monitoring. Many studies have attempted to provide better solutions but more research and better approaches are essential. This study presents a real-time framework for object detection and tracking for security surveillance systems. The system has been designed based on approximate median filtering, component labeling, background subtraction, and deep learning approaches. The new algorithms for object detection, tracking, and recognition have been implemented using Python and integrated with C# programming languages for ease of use. A software application framework is designed, implemented, and evaluated. The experimental results based on MOT-Challenge performance metrics show that the proposed algorithms have much better performance in terms of accuracy and precision on the MOT15, MOT16, and MOT17 datasets compared to state-of-the-art approaches. This framework also provides an accurate and effective means of monitoring and recognizing moving objects. The software development, including the design of the framework user interfaces, is coded in the C# programming language and integrated with Python using Microsoft Visual Studio (2019 edition). The integration is performed to provide a convenient user interface and to enable the execution of the framework as a standard and standalone software application. Future studies will consider the dynamic scalability of the framework to accommodate different surveillance application areas in overcrowded scenarios. Multiple data sources are integrated to enhance the performance for different scene times, locations, and weather conditions. Furthermore, other object-detection techniques such as You Only Look Once (YOLO) and its variants shall be considered in future studies. These techniques allow the framework to adapt to complex situations in which security surveillance is challenging.

4.
J Community Psychol ; 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39148301

ABSTRACT

Intimate partner violence (IPV) is a public health problem. In Spain, although the prevalence of IPV is greater in immigrant women than in Spanish-born women, immigrant women seem to access services to a lesser extent. This study aimed to explore and compare perceptions of barriers to and strategies for seeking formal help among Spanish-born and immigrant women IPV survivors. A qualitative study was conducted based on three focus groups with women of Spanish (n = 9), Romanian (n = 4), and Latin American (n = 4) origin. The thematic analysis was supported by Atlas.ti. Three categories and 12 subcategories were identified: general characteristics of help-seeking behavior (e.g., children as the main motivating factor), barriers (e.g., immigrant status, fear of the perpetrator), and strategies for accessing services (e.g., increasing education). Differences in help-seeking behavior were found between groups. Relevant information for professionals to improve women's access to IPV support services is provided.

5.
Access Microbiol ; 6(7)2024.
Article in English | MEDLINE | ID: mdl-39130742

ABSTRACT

The study presents the whole genome sequence of the carotenoid-producing Paracoccus sp. NFXS7, isolated from a marine saltern in Setúbal, Portugal. The carotenoid-producing strain NFXS7 contains homologs of the crt genes involved in astaxanthin biosynthesis, making it a promising candidate for biotechnological applications.

6.
PeerJ ; 12: e17713, 2024.
Article in English | MEDLINE | ID: mdl-39006017

ABSTRACT

Background: Biodiversity, crucial for understanding ecosystems, encompasses species richness, composition, and distribution. Ecological and environmental factors, such as habitat type, resource availability, and climate conditions, play pivotal roles in shaping species diversity within and among communities, categorized into alpha (within habitat), beta (between habitats), and gamma (total regional) diversity. Hummingbird communities are influenced by habitat, elevation, and seasonality, making them an ideal system for studying these diversities, shedding light on mutualistic community dynamics and conservation strategies. Methods: Over a year-long period, monthly surveys were conducted to record hummingbird species and their visited flowering plants across four habitat types (oak forest, juniper forest, pine forest, and xerophytic shrubland) in Tlaxcala, Mexico. Three locations per habitat type were selected based on conservation status and distance from urban areas. True diversity measures were used to assess alpha, beta, and gamma diversity of hummingbirds and their floral resources. Environmental factors such as altitude and bioclimatic variables were explored for their influence on beta diversity. Results: For flowering plants, gamma diversity encompassed 34 species, with oak forests exhibiting the highest richness, while xerophytic shrublands had the highest alpha diversity. In contrast, for hummingbirds, 11 species comprised the gamma diversity, with xerophytic shrublands having the highest richness and alpha diversity. Our data reveal high heterogeneity in species abundance among habitats. Notably, certain floral resources like Loeselia mexicana and Bouvardia ternifolia emerge as key species in multiple habitats, while hummingbirds such as Basilinna leucotis, Selasphorus platycercus, and Calothorax lucifer exhibit varying levels of abundance and habitat preferences. Beta diversity analyses unveil habitat-specific patterns, with species turnover predominantly driving dissimilarity in composition. Moreover, our study explores the relationships between these diversity components and environmental factors such as altitude and climate variables. Climate variables, in particular, emerge as significant contributors to dissimilarity in floral resource and hummingbird communities, highlighting the influence of environmental conditions on species distribution. Conclusions: Our results shed light on the complex dynamics of hummingbird-flower mutualistic communities within diverse habitats and underscore the importance of understanding how habitat-driven shifts impact alpha, beta, and gamma diversity. Such insights are crucial for conservation strategies aimed at preserving the delicate ecological relationships that underpin biodiversity in these communities.


Subject(s)
Biodiversity , Birds , Ecosystem , Birds/physiology , Animals , Mexico , Flowers
7.
Nutrients ; 16(14)2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39064723

ABSTRACT

(1) Background: Bariatric surgery has demonstrated the capacity to improve metabolic-associated fatty liver disease (MAFLD) in patients with morbid obesity. In addition, the Mediterranean diet contains anti-inflammatory, anti-oxidative, and anti-fibrotic components, promoting a beneficial effect on MAFLD. This study aimed to assess the improvement of MAFLD, specifically liver steatosis, in morbidly obese patients undergoing Roux-en-Y gastric bypass (RYGB) and following a hypocaloric Mediterranean-like diet. (2) Methods: A prospective observational pilot study of 20 patients undergoing RYGB was conducted. The participants underwent a magnetic resonance spectroscopy study 2 weeks before the surgical act and one year postoperatively to assess the percentage of lipid content (PLC). The adherence to the Mediterranean diet was determined by the KIDMED test 1 year after surgery. (3) Results: Mean baseline PLC was 14.2 ± 9.4%, and one year after surgery, it decreased to 4.0 ± 1.8% (p < 0.001). A total of 12 patients (60%) were within the range of moderate adherence to the Mediterranean diet, whereas 8 patients (40%) showed a high adherence. The patients with high adherence to the Mediterranean diet presented significantly lower values of postoperative PLC. (4) Conclusions: Liver steatosis significantly reduces after RYGB. This reduction is further improved when associated with a high adherence to a Mediterranean diet.


Subject(s)
Diet, Mediterranean , Gastric Bypass , Magnetic Resonance Spectroscopy , Obesity, Morbid , Humans , Female , Obesity, Morbid/surgery , Obesity, Morbid/diet therapy , Adult , Prospective Studies , Middle Aged , Pilot Projects , Magnetic Resonance Spectroscopy/methods , Non-alcoholic Fatty Liver Disease/surgery , Postoperative Period , Treatment Outcome
8.
Front Endocrinol (Lausanne) ; 15: 1372716, 2024.
Article in English | MEDLINE | ID: mdl-39015178

ABSTRACT

Introduction: This study in Argentina evaluated the impact of the growzen™ buddy smartphone app on adherence to recombinant human growth hormone (r-hGH) treatment. Methods: The adherence data, invitation dates with a link to the app, app activation dates, and height measurements entered were extracted from the growzen™ digital health ecosystem. Patients with 12 months of adherence data, aged ≥2 years at treatment start, and aged <19 years were selected both before and after app implementation. Mean adherence was classified as optimal (≥85%) versus suboptimal (<85%). Adherence before and after implementation and the pre-post effect on adherence were assessed. Results: Data for 830 patients were available. Prior to app implementation, the proportion of patients with optimal adherence was 68% (n = 348/515). Following the app implementation, out of 315 patients, 302 (96%) received an invitation with a link to the app, 225 (71%) activated their account, and 127 (40%) entered height data in the first year. There was a significant early increase in the proportion of patients with optimal adherence following implementation: 82% (n = 258/315), p < 0.001. After implementation, the proportion of patients with optimal adherence included 80% (n = 78/98) of those with an active account who did not enter height measurements and 89% (n = 113/127) of those who did. There was a significant and positive pre-post app effect on adherence (p < 0.01) in patients with an active account. Discussion: Our results show that using the growzen™ buddy app has a rapid and positive impact on adherence to r-hGH treatment, and patients who were more engaged with the app demonstrated better adherence.


Subject(s)
Human Growth Hormone , Medication Adherence , Mobile Applications , Recombinant Proteins , Smartphone , Humans , Argentina , Male , Female , Retrospective Studies , Human Growth Hormone/therapeutic use , Human Growth Hormone/administration & dosage , Medication Adherence/statistics & numerical data , Adolescent , Child , Recombinant Proteins/therapeutic use , Child, Preschool , Young Adult , Adult
9.
Nat Commun ; 15(1): 4235, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762489

ABSTRACT

Inflammation induced by lung infection is a double-edged sword, moderating both anti-viral and immune pathogenesis effects; the mechanism of the latter is not fully understood. Previous studies suggest the vasculature is involved in tissue injury. Here, we report that expression of Sparcl1, a secreted matricellular protein, is upregulated in pulmonary capillary endothelial cells (EC) during influenza-induced lung injury. Endothelial overexpression of SPARCL1 promotes detrimental lung inflammation, with SPARCL1 inducing 'M1-like' macrophages and related pro-inflammatory cytokines, while SPARCL1 deletion alleviates these effects. Mechanistically, SPARCL1 functions through TLR4 on macrophages in vitro, while TLR4 inhibition in vivo ameliorates excessive inflammation caused by endothelial Sparcl1 overexpression. Finally, SPARCL1 expression is increased in lung ECs from COVID-19 patients when compared with healthy donors, while fatal COVID-19 correlates with higher circulating SPARCL1 protein levels in the plasma. Our results thus implicate SPARCL1 as a potential prognosis biomarker for deadly COVID-19 pneumonia and as a therapeutic target for taming hyperinflammation in pneumonia.


Subject(s)
COVID-19 , Endothelial Cells , Lung , Macrophage Activation , SARS-CoV-2 , Animals , Humans , COVID-19/immunology , COVID-19/virology , COVID-19/metabolism , COVID-19/pathology , Mice , Endothelial Cells/metabolism , Endothelial Cells/virology , Endothelial Cells/immunology , SARS-CoV-2/physiology , Lung/virology , Lung/pathology , Lung/immunology , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Calcium-Binding Proteins/metabolism , Calcium-Binding Proteins/genetics , Mice, Inbred C57BL , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Pneumonia, Viral/metabolism , Male , Macrophages/metabolism , Macrophages/immunology , Female , Mice, Knockout , Extracellular Matrix Proteins
10.
Nanomedicine ; 58: 102749, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38719107

ABSTRACT

New adjuvant strategies are needed to improve protein-based subunit vaccine immunogenicity. We examined the potential to use nanostructure of 6-O-ascorbyl palmitate to formulate ovalbumin (OVA) protein and an oligodeoxynucleotide (CpG-ODN) (OCC). In mice immunized with a single dose, OCC elicited an OVA-specific immune response superior to OVA/CpG-ODN solution (OC). Rheological studies demonstrated OCC's self-assembling viscoelastic properties. Biodistribution studies indicated that OCC prolonged OVA and CpG-ODN retention at injection site and lymph nodes, reducing systemic spread. Flow-cytometry assays demonstrated that OCC promoted OVA and CpG-ODN co-uptake by Ly6ChiCD11bhiCD11c+ monocytes. OCC and OC induced early IFN-γ in lymph nodes, but OCC led to higher concentration. Conversely, mice immunized with OC showed higher serum IFN-γ concentration compared to those immunized with OCC. In mice immunized with OCC, NK1.1+ cells were the IFN-γ major producers, and IFN-γ was essential for OVA-specific IgG2c switching. These findings illustrate how this nanostructure improves vaccine's response.


Subject(s)
Nanostructures , Oligodeoxyribonucleotides , Ovalbumin , Vaccines, Subunit , Animals , Nanostructures/chemistry , Vaccines, Subunit/immunology , Vaccines, Subunit/chemistry , Vaccines, Subunit/pharmacokinetics , Mice , Oligodeoxyribonucleotides/chemistry , Oligodeoxyribonucleotides/pharmacokinetics , Ovalbumin/immunology , Ovalbumin/chemistry , Female , Mice, Inbred C57BL , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacokinetics , Interferon-gamma/metabolism , Tissue Distribution , Ascorbic Acid/analogs & derivatives
11.
EMBO Rep ; 25(6): 2635-2661, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38730210

ABSTRACT

Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established. Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients. Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function.


Subject(s)
Interleukins , Obesity , T-Lymphocytes, Regulatory , Thermogenesis , p38 Mitogen-Activated Protein Kinases , Animals , Interleukins/metabolism , Obesity/metabolism , Mice , Humans , p38 Mitogen-Activated Protein Kinases/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , TOR Serine-Threonine Kinases/metabolism , Signal Transduction , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Inflammation/metabolism , Male , Mice, Inbred C57BL , Mice, Knockout
12.
Int J Mol Sci ; 25(7)2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38612435

ABSTRACT

This study presents the synthesis of four series of novel hybrid chalcones (20,21)a-g and (23,24)a-g and six series of 1,3,5-triazine-based pyrimido[4,5-b][1,4]diazepines (28-33)a-g and the evaluation of their anticancer, antibacterial, antifungal, and cytotoxic properties. Chalcones 20b,d, 21a,b,d, 23a,d-g, 24a-g and the pyrimido[4,5-b][1,4]diazepines 29e,g, 30g, 31a,b,e-g, 33a,b,e-g exhibited outstanding anticancer activity against a panel of 60 cancer cell lines with GI50 values between 0.01 and 100 µM and LC50 values in the range of 4.09 µM to >100 µM, several of such derivatives showing higher activity than the standard drug 5-fluorouracil (5-FU). On the other hand, among the synthesized compounds, the best antibacterial properties against N. gonorrhoeae, S. aureus (ATCC 43300), and M. tuberculosis were exhibited by the pyrimido[4,5-b][1,4]diazepines (MICs: 0.25-62.5 µg/mL). The antifungal activity studies showed that triazinylamino-chalcone 29e and triazinyloxy-chalcone 31g were the most active compounds against T. rubrum and T. mentagrophytes and A. fumigatus, respectively (MICs = 62.5 µg/mL). Hemolytic activity studies and in silico toxicity analysis demonstrated that most of the compounds are safe.


Subject(s)
Chalcones , Isocyanates , Mycobacterium tuberculosis , Chalcones/pharmacology , Antifungal Agents/pharmacology , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Azepines/pharmacology , Fluorouracil , Neisseria gonorrhoeae , Triazines/pharmacology
13.
Cureus ; 16(3): e56973, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38665747

ABSTRACT

We present a case of an obese 56-year-old male with obstructive sleep apnea (OSA), obesity hypoventilation syndrome (OHS), and pituitary macroadenoma, who underwent nasal endoscopic trans-sphenoidal resection. Surgery was performed under general anesthesia, uneventfully as planned. The patient experienced, however, delayed emergence despite receiving adequate neuromuscular blockade agent reversal. Extubation was performed and the patient was transferred to the recovery room on a Venturi mask (50% fraction of inspired oxygen, FIO2)and 93% saturation. Postoperatively, the patient was complaining of acute pain that did not resolve with non-opioid medications and a low morphine dose (0.035 mg/kg) for pain management was administered. Subsequently, he developed severe respiratory depression, requiring intubation. After three hours, the patient was extubated, transferred to the intensive care unit, and discharged five days later. Although the patient recovered favorably, this case highlights the risks of administering opioids to patients with OSA and OHS. To our knowledge, this is the first case reporting extreme respiratory depression secondary to the administration of a very low dose of morphine in patients with these comorbidities. Therefore, it is essential to be cautious with the use of opioids and to explore multimodal pain relief methods for these patients.

14.
ASAIO J ; 70(9): 758-766, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38446842

ABSTRACT

Mechanical circulatory support (MCS) as a bridge to lung transplant is an infrequent but accepted pathway in patients who have refractory end-stage pulmonary failure. The American Association of Thoracic Surgeons Expert Consensus Guidelines, published in 2023, recommends venovenous (VV) extracorporeal membrane oxygenation (ECMO) as the initial configuration for those patients who have failed conventional medical therapy, including mechanical ventilation, while waiting for lung transplantation and needing MCS. Alternatively, venoarterial (VA) ECMO can be used in patients with acute right ventricular failure, hemodynamic instability, or refractory respiratory failure. With the advancement in percutaneous venopulmonary (VP) ECMO cannulation techniques, this option is becoming an attractive configuration as bridge to lung transplantation. This configuration enhances stability of the right ventricle, prevents recirculation with direct introduction of pulmonary artery oxygenation, and promotes hemodynamic stability during mobility, rehabilitation, and sedation-weaning trials before lung transplantation. Here, we present a case series of eight percutaneous VP ECMO as bridge to lung transplant with all patients mobilized, awake, and successfully transplanted with survival to hospital discharge.


Subject(s)
Extracorporeal Membrane Oxygenation , Lung Transplantation , Humans , Extracorporeal Membrane Oxygenation/methods , Lung Transplantation/methods , Male , Female , Adult , Respiratory Insufficiency/therapy , Respiratory Insufficiency/surgery , Respiratory Insufficiency/etiology , Middle Aged
15.
Appl Opt ; 63(7): B16-B23, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38437251

ABSTRACT

Thickness measurements of objects, especially transparent and semi-transparent objects, are essential for their characterization and identification. However, in the case of occluded objects, the optical thickness determination becomes difficult, and an indirect way must be devised. Thermal loading of the objects changes their opto-thermal properties, which will be reflected as a change in their optical thickness. The key to quantifying such occluded objects lies in collecting these opto-thermal signatures. This could be achieved by imaging the changes occurring to a probe wavefront passing through the object while it is being thermally loaded. Digital holographic interferometry is an ideal tool for observing phase changes, as it can be used to compare wavefronts recorded at different instances of time. Lens-less Fourier transform digital holographic imaging provides the phase information from a single Fourier transform of the recorded hologram and can be used to quantify occluded phase objects. Here we describe a technique for the measurement of change in optical thickness of thermally loaded occluded phase samples using lens-less Fourier transform digital holography and machine learning. The advantage of the proposed technique is that it is a single shot, lens-less imaging modality for quasi-real-time quantification of phase samples behind thin occlusions.

16.
J Thorac Cardiovasc Surg ; 168(3): 712-721.e2, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38199292

ABSTRACT

OBJECTIVE: Lung transplant for acute respiratory distress syndrome in patients supported with extracorporeal membrane oxygenation was rare before 2020, but was rapidly adopted to rescue patients with COVID-19 with lung failure. This study aims to compare the outcomes of patients who underwent lung transplant for COVID-associated acute respiratory distress syndrome and non-COVID acute respiratory distress syndrome, and to assess the impact of type and duration of extracorporeal membrane oxygenation support on survival. METHODS: Using the United Network for Organ Sharing database, we identified 311 patients with acute respiratory distress syndrome who underwent lung transplant from 2007 to 2022 and performed a retrospective analysis of the patients who required extracorporeal membrane oxygenation preoperatively, stratified by COVID-associated acute respiratory distress syndrome and non-COVID acute respiratory distress syndrome listing diagnoses. The primary outcome was 1-year survival. Secondary outcomes included the effect of type and duration of extracorporeal membrane oxygenation on survival. RESULTS: During the study period, 236 patients with acute respiratory distress syndrome and preoperative extracorporeal membrane oxygenation underwent lung transplant; 181 patients had a listing diagnosis of COVID-associated acute respiratory distress syndrome (77%), and 55 patients had a listing diagnosis of non-COVID acute respiratory distress syndrome (23%). Patients with COVID-associated acute respiratory distress syndrome were older, were more likely to be female, had higher body mass index, and spent longer on the waitlist (all P < .02) than patients with non-COVID acute respiratory distress syndrome. The 2 groups had similar 1-year survival (85.8% vs 81.1%, P = .2) with no differences in postoperative complications. Patients with COVID-associated acute respiratory distress syndrome required longer times on extracorporeal membrane oxygenation pretransplant (P = .02), but duration of extracorporeal membrane oxygenation support was not a predictor of 1-year survival (P = .2). CONCLUSIONS: Despite prolonged periods of pretransplant extracorporeal membrane oxygenation support, selected patients with acute respiratory distress syndrome can undergo lung transplant safely with acceptable short-term outcomes. Appropriate selection criteria and long-term implications require further analysis.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Lung Transplantation , Respiratory Distress Syndrome , Humans , Extracorporeal Membrane Oxygenation/mortality , COVID-19/complications , COVID-19/mortality , Lung Transplantation/mortality , Lung Transplantation/adverse effects , Female , Male , Middle Aged , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/diagnosis , Retrospective Studies , Treatment Outcome , Adult , Time Factors , Aged , SARS-CoV-2 , Risk Factors
17.
Sci Adv ; 10(3): eadk6524, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38241373

ABSTRACT

Pulmonary hypertension (PH) can affect both pulmonary arterial tree and cardiac function, often leading to right heart failure and death. Despite the urgency, the lack of understanding has limited the development of effective cardiac therapeutic strategies. Our research reveals that MCJ modulates mitochondrial response to chronic hypoxia. MCJ levels elevate under hypoxic conditions, as in lungs of patients affected by COPD, mice exposed to hypoxia, and myocardium from pigs subjected to right ventricular (RV) overload. The absence of MCJ preserves RV function, safeguarding against both cardiac and lung remodeling induced by chronic hypoxia. Cardiac-specific silencing is enough to protect against cardiac dysfunction despite the adverse pulmonary remodeling. Mechanistically, the absence of MCJ triggers a protective preconditioning state mediated by the ROS/mTOR/HIF-1α axis. As a result, it preserves RV systolic function following hypoxia exposure. These discoveries provide a potential avenue to alleviate chronic hypoxia-induced PH, highlighting MCJ as a promising target against this condition.


Subject(s)
Hypertension, Pulmonary , Animals , Humans , Mice , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/drug therapy , Hypoxia , Lung , Myocardium , Pulmonary Artery , Swine
18.
Am J Respir Crit Care Med ; 209(1): 91-100, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37734031

ABSTRACT

Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy-defined donor smoking as a risk factor for PGD and mortality. Objectives: We aimed to more accurately assess the impact of donor smoke exposure on PGD and mortality using quantitative smoke exposure biomarkers. Methods: We performed a multicenter prospective cohort study of lung transplant recipients enrolled in the Lung Transplant Outcomes Group cohort between 2012 and 2018. PGD was defined as grade 3 at 48 or 72 hours after lung reperfusion. Donor smoking was defined using accepted thresholds of urinary biomarkers of nicotine exposure (cotinine) and tobacco-specific nitrosamine (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL]) in addition to clinical history. The donor smoking-PGD association was assessed using logistic regression, and survival analysis was performed using inverse probability of exposure weighting according to smoking category. Measurements and Main Results: Active donor smoking prevalence varied by definition, with 34-43% based on urinary cotinine, 28% by urinary NNAL, and 37% by clinical documentation. The standardized risk of PGD associated with active donor smoking was higher across all definitions, with an absolute risk increase of 11.5% (95% confidence interval [CI], 3.8% to 19.2%) by urinary cotinine, 5.7% (95% CI, -3.4% to 14.9%) by urinary NNAL, and 6.5% (95% CI, -2.8% to 15.8%) defined clinically. Donor smoking was not associated with differential post-lung transplant survival using any definition. Conclusions: Donor smoking associates with a modest increase in PGD risk but not with increased recipient mortality. Use of lungs from smokers is likely safe and may increase lung donor availability. Clinical trial registered with www.clinicaltrials.gov (NCT00552357).


Subject(s)
Lung Transplantation , Primary Graft Dysfunction , Smoking , Tissue Donors , Humans , Biomarkers , Cotinine , Lung Transplantation/adverse effects , Primary Graft Dysfunction/epidemiology , Prospective Studies , Smoking/adverse effects
19.
Mol Nutr Food Res ; 68(1): e2300508, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37933702

ABSTRACT

SCOPE: Extra virgin olive oil has numerous cardiopreventive effects, largely due to its high content of (poly)phenols such as hydroxytyrosol (HT). However, some animal studies suggest that its excessive consumption may alter systemic lipoprotein metabolism. Because human lipoprotein metabolism differs from that of rodents, this study examines the effects of HT in a humanized mouse model that approximates human lipoprotein metabolism. METHODS AND RESULTS: Mice are treated as follows: control diet or diet enriched with HT. Serum lipids and lipoproteins are determined after 4 and 8 weeks. We also analyzed the regulation of various genes and miRNA by HT, using microarrays and bioinformatic analysis. An increase in body weight is found after supplementation with HT, although food intake was similar in both groups. In addition, HT induced the accumulation of triacylglycerols but not cholesterol in different tissues. Systemic dyslipidemia after HT supplementation and impaired glucose metabolism are observed. Finally, HT modulates the expression of genes related to lipid metabolism, such as Pltp or Lpl. CONCLUSION: HT supplementation induces systemic dyslipidemia and impaired glucose metabolism in humanized mice. Although the numerous health-promoting effects of HT far outweigh these potential adverse effects, further carefully conducted studies are needed.


Subject(s)
Dyslipidemias , Phenylethyl Alcohol , Humans , Mice , Animals , Olive Oil/pharmacology , Dyslipidemias/etiology , Phenylethyl Alcohol/pharmacology , Lipoproteins , Disease Models, Animal , Glucose
20.
J Heart Lung Transplant ; 43(4): 633-641, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38065239

ABSTRACT

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Accurate prediction of PGD risk could inform donor approaches and perioperative care planning. We sought to develop a clinically useful, generalizable PGD prediction model to aid in transplant decision-making. METHODS: We derived a predictive model in a prospective cohort study of subjects from 2012 to 2018, followed by a single-center external validation. We used regularized (lasso) logistic regression to evaluate the predictive ability of clinically available PGD predictors and developed a user interface for clinical application. Using decision curve analysis, we quantified the net benefit of the model across a range of PGD risk thresholds and assessed model calibration and discrimination. RESULTS: The PGD predictive model included distance from donor hospital to recipient transplant center, recipient age, predicted total lung capacity, lung allocation score (LAS), body mass index, pulmonary artery mean pressure, sex, and indication for transplant; donor age, sex, mechanism of death, and donor smoking status; and interaction terms for LAS and donor distance. The interface allows for real-time assessment of PGD risk for any donor/recipient combination. The model offers decision-making net benefit in the PGD risk range of 10% to 75% in the derivation centers and 2% to 10% in the validation cohort, a range incorporating the incidence in that cohort. CONCLUSION: We developed a clinically useful PGD predictive algorithm across a range of PGD risk thresholds to support transplant decision-making, posttransplant care, and enrich samples for PGD treatment trials.


Subject(s)
Lung Transplantation , Primary Graft Dysfunction , Humans , Risk Factors , Risk Assessment , Primary Graft Dysfunction/diagnosis , Primary Graft Dysfunction/epidemiology , Prospective Studies , Retrospective Studies
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