Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models.

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.

Lymphovascular Invasion is an Independent Negative Prognostic Factor in Esophageal Adenocarcinoma.

BACKGROUND: The significance of lymphovascular invasion (LVI) in esophageal adenocarcinoma (EAC) has not yet been described. Potential utility as an adjunct to current staging guidelines remains unknown. METHODS: The National Cancer Database was queried from 2006 to 2020. Univariate and multivariable models, Kaplan Meier method, and log-rank test were used. Subgroup analyses by pN stage were conducted. RESULTS: Of 9,689 patients, 23.2% had LVI. LVI was an independent prognostic factor (hazard ratio [HR] 1.401, 95% confidence interval [CI] 1.307-1.502, p < 0.0001) with reduction in median survival to 20.0 months (95% CI 18.9-21.4) from 39.7 months (95% CI 37.8-42.3, p < 0.0001). Multivariable survival analysis adjusted on pN and pT stage found that patients with LVI had decreased survival in a given pN stage (p < 0.001). pN0/LVI+ patients had a similar prognosis to the higher staged pN1/LVI- (28.6 months), although pN1/LVI- patients did slightly worse (p = 0.0135). Additionally, patients with pN1/LVI+ had equivalent survival compared with pN2/LVI- (p = 0.178) as did pN2/LVI+ patients compared with pN3/LVI- (p = 0.995). CONCLUSIONS: In these data, LVI is an independent negative prognostic factor in EAC. LVI was associated with a survival reduction similar to an upstaged nodal status irrespective of T stage. Patients with LVI may be better classified at a higher pN stage.

Lung Transplantation in the United States for COVID-19 Related Lung Disease During the Pandemic (2597/2600).

PURPOSE: Lung transplantation (LTx) is a potential intervention for end-stage COVID-19 lung disease. Current literature is sparse regarding the outcomes of LTx for COVID-19 related acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). This study aims to characterize outcomes and patterns of LTx for COVID-19 related lung disease throughout the pandemic. METHODS: Patients who underwent LTx during the pandemic for COVID-19 related lung disease were retrospectively identified using the UNOS registry. Demographics, as well as outcomes measures and nationwide patterns of care were collected and analyzed. RESULTS: A total of 510 adult cases of LTx for COVID-19 (259 ARDS, 251 PF) were compared to 4,031 without COVID-19 (3,994 PF, 37 ARDS). Patients who received LTx for COVID-19 ARDS did not differ in 2-year survival when compared to those with COVID-19 PF (81.9% vs 77.2%, p = 0.4428). Compared to non-COVID-19 etiologies, COVID-19 ARDS patients had higher rates of stroke (2.3% vs 0%, p = 0.0005), lower rates of graft failure (12.8% vs 36.1%, p = 0.0003) and post-transplant ECMO (29.6% vs 41.7%, p = 0.0002), and improved 2-year survival following LTx (81.9% vs 61.7%, p = 0.0064). No difference in 2-year survival following LTx was observed between patients with COVID-19 and non-COVID-19 PF (77.2% vs 71.8%, p = 0.34). Rates of LTx spiked with variant emergence and declined with rounds of vaccination. CONCLUSION: Our results are consistent with early reports of survival outcomes following LTx for COVID-19 ARDS and PF while providing an increased layer of granularity. LTx may be considered as a safe and effective intervention for COVID-19 lung disease.

Corrigendum: Differential effects of attachment security on visual fixation to facial expressions of emotion in 14-month-old infants: an eye-tracking study.

[This corrects the article DOI: 10.3389/fpsyg.2024.1302657.].

International Trauma Questionnaire and Posttraumatic Cognitions Inventory-9: validity evidence and measurement invariance of their Brazilian versions.

BACKGROUND: The International Trauma Questionnaire (ITQ) is used to measure posttraumatic stress disorder (PTSD) and complex posttraumatic stress disorder (CPTSD) symptoms, and the Posttraumatic Cognitions Inventory-9 (PTCI-9) is used to measure posttraumatic cognitions. Both tools have been translated for use in Brazil. However, the psychometric properties of the Brazilian versions were not investigated, and no study has verified the invariance of these tools for many traumatic event types. OBJECTIVE: This study examined the validity, reliability, and measurement invariance of the Brazilian versions of the ITQ and the PTCI-9 for trauma type, gender, race, age group, education level, and geographical region. METHODS: A total of 2,111 people (67.74% women) participated in an online survey. The scale models were tested via confirmatory factor analyses and measurement invariance through multigroup analyses. Pearson's correlation analyses were used to examine the relationships between PTSD, CPTSD, posttraumatic cognitions, and depressive symptoms. RESULTS: Except for the affective dysregulation factor, the reliabilities of the ITQ and PTCI-9 dimensions were adequate. Models with six correlated dimensions for the ITQ and three correlated dimensions for the PTCI-9 showed adequate fit to the data. The ITQ and PTCI-9 exhibited scalar invariance for gender, race, age group, education level, and geographical region. The ITQ also demonstrated full invariance for trauma type. The factors of both instruments were related to each other and to depressive symptoms, with higher effect sizes for posttraumatic cognitions and complex posttraumatic stress disorder symptoms. CONCLUSION: We recommend using the Brazilian versions of the ITQ and PTCI-9, which are crucial tools for assessing and treating trauma-related disorders.

Extracorporeal membrane oxygenation for general thoracic surgery: case series and narrative review.

Background and Objective: Extracorporeal membrane oxygenation (ECMO) has historically been utilized as a temporary life support option for patients with severe cardiac and pulmonary dysfunction. Recent advancements have enabled the safe application of ECMO in a wider variety of patients; we present a review of its use in patients undergoing general thoracic procedures supported by a case series at our institution. Methods: We review current literature focusing on ECMO applications in thoracic surgery outside of the traditional use. Additionally, we offer three cases of ECMO utilization to illustrate success stories and key lessons learned regarding the use of ECMO in general thoracic surgery. Key Content and Findings: Technologic advancements and enhanced safety profiles have enabled the safe application of ECMO in a wide array of patients far beyond the historic indications of cardiogenic shock and acute respiratory distress syndrome (ARDS). It is now feasible to consider ECMO for management of acute thoracic emergencies, as well as to better facilitate operative safety in complex general thoracic surgical procedures. Both venovenous and venoarterial ECMO can be utilized in carefully selected patients to provide cardiopulmonary support while enabling improved visualization and increased mobilization without concern for respiratory and/or cardiac compromise. Conclusions: Enthusiasm for the use of ECMO has increased in recent years. What was once considered a salvage therapy in cases of life-threatening cardiopulmonary decompensation now plays an increasingly important role in the safe conduct of complex thoracic surgery procedures, provides much needed time for organ recovery, and offers acute resuscitation options. This shift broadens our ability to deliver life-saving care to patients that previously would have otherwise had limited treatment options.

Exploring the potential of bovine colostrum as a bioactive agent in human tissue regeneration: A comprehensive analysis of mechanisms of action and challenges to be overcome.

The study examines bovine colostrum as a potent source of bioactive compounds, particularly growth factors, for tissue regeneration in humans. While previous research has hinted at therapeutic benefits, a comprehensive understanding of its mechanisms remains elusive, necessitating further investigation. This review analyzes nine selected scientific articles on bovine colostrum's bioactive potential in tissue regeneration. In vitro studies highlight its positive impact on cell behavior, including reduced proliferation and induced differentiation. Notably, optimal concentrations and specific colostrum components, such as extracellular vesicles and insoluble milk fat, show more favorable outcomes. In vivo studies underscore bovine colostrum as a promising natural resource for wound healing, despite some studies failing to identify associated benefits. Further research is crucial to unravel the intricate mechanisms, grasp the full potential in regenerative medicine, and develop more effective wound healing therapies. This refined understanding will pave the way for harnessing the complete regenerative potential of bovine colostrum in clinical applications.

Differential effects of attachment security on visual fixation to facial expressions of emotion in 14-month-old infants: an eye-tracking study.

Introduction: Models of attachment and information processing suggest that the attention infants allocate to social information might occur in a schema-driven processing manner according to their attachment pattern. A major source of social information for infants consists of facial expressions of emotion. We tested for differences in attention to facial expressions and emotional discrimination between infants classified as securely attached (B), insecure-avoidant (A), and insecure-resistant (C). Methods: Sixty-one 14-month-old infants participated in the Strange Situation Procedure and an experimental task of Visual Habituation and Visual Paired-Comparison Task (VPC). In the Habituation phase, a Low-Arousal Happy face (habituation face) was presented followed by a VPC task of 6 trials composed of two contrasting emotional faces always involving the same actress: the one used in habituation (trial old face) and a new one (trial new face) portraying changes in valence (Low-Arousal Angry face), arousal (High-Arousal Happy face), or valence + arousal (High-Arousal Angry face). Measures of fixation time (FT) and number of fixations (FC) were obtained for the habituation face, the trial old face, the trial new face, and the difference between the trial old face and the trial new face using an eye-tracking system. Results: We found a higher FT and FC for the trial new face when compared with the trial old face, regardless of the emotional condition (valence, arousal, valence + arousal contrasts), suggesting that 14-month-old infants were able to discriminate different emotional faces. However, this effect differed according to attachment pattern: resistant-attached infants (C) had significantly higher FT and FC for the new face than patterns B and A, indicating they may remain hypervigilant toward emotional change. On the contrary, avoidant infants (A) revealed significantly longer looking times to the trial old face, suggesting overall avoidance of novel expressions and thus less sensitivity to emotional change. Discussion: Overall, these findings corroborate that attachment is associated with infants' social information processing.

Acute Ischaemic Stroke in the Context of Neurosyphilis: How Does Antibiotic Therapy Help, and When Should It Be Given?

Introduction: Neurosyphilis (NS) refers to a central nervous system infection caused by Treponema pallidum. In recent years, there has been an increasing incidence of syphilis; however, NS is uncommon compared to the era before the discovery of penicillin. Manifestations are usually non-specific, ranging from asymptomatic cases to syphilitic meningitis, meningovascular syphilis, general paresis and tabes dorsalis. Meningovascular syphilis can cause an inflammatory arteritis of cerebral arteries, leading to vascular occlusion and cerebral infarction. Case description: We report a case of an ischaemic stroke in a patient with several vascular risk factors, presenting with right hemiparesis, hemihypesthesia and dysarthria. Initial computed tomography with angiography of the head and neck was normal; however, magnetic resonance imaging of the brain revealed a thalamic and internal capsule infarct. Serum T. pallidum antibodies were positive, as well as a rapid plasma reagin test. Cerebrospinal fluid analysis confirmed the diagnosis of neurosyphilis, and the patient was treated with ceftriaxone for 14 days due to a penicillin allergy. Discussion and conclusion: Although there is a high prevalence of stroke in patients with NS, this condition is typically underdiagnosed. Untreated NS carries a higher risk of stroke recurrence compared to other risk factors. Therefore, early diagnosis and treatment are essential. This case highlights the importance of considering NS in stroke victims, even in older patients with several additional vascular risk factors, to prevent recurrence and other complications. LEARNING POINTS: Neurosyphilis (NS) can occur at any stage of syphilis infection, and it can be asymptomatic or symptomatic, presenting as syphilitic meningitis, meningovascular syphilis, general paresis or tabes dorsalis.Ischaemic strokes are a frequent complication of NS, occurring in 14% of the cases. However, only 19% of the cases are correctly diagnosed.NS should be considered as a potential cause of stroke, even in older patients with several other vascular risk factors. This is essential to prevent future strokes, as well as dementia and other complications.

Donor and recipient risk factors for the development of primary graft dysfunction following lung transplantation.

Primary Graft Dysfunction (PGD) is a major cause of both short-term and long-term morbidity and mortality following lung transplantation. Various donor, recipient, and technical risk factors have been previously identified as being associated with the development of PGD. Here, we present a comprehensive review of the current literature as it pertains to PGD following lung transplantation, as well as discussing current strategies to mitigate PGD and future directions. We will pay special attention to recent advances in lung transplantation such as ex-vivo lung perfusion, thoracoabdominal normothermic regional perfusion, and up-to-date literature published in the interim since the 2016 ISHLT consensus statement on PGD and the COVID-19 pandemic.

Exploring the versatility of sesquiterpene biosynthesis in guava plants: a comparative genome-wide analysis of two cultivars.

Psidium guajava L., a fruit crop belonging to the Myrtaceae family, is highly valued for its nutritional and medicinal properties. The family exhibits a diverse chemical profile of essential oils and serves as a valuable resource due to its ecological interactions, adaptability, and dispersal capacity. The Myrtaceae family has been extensively studied for its terpenoids. Genetic studies have focused on foliar terpene yield in species from the Eucalypteae and Melaleucaceae tribes. To understand the evolutionary trends in guava breeding, this study predicted terpene synthase genes (TPS) from different cultivars. Through this analysis, 43 full-length TPS genes were identified, and approximately 77% of them exhibited relative expression in at least one of the five investigated plant tissues (root, leaf, bud, flower, and fruit) of two guava cultivars. We identified intra-species variation in the terpene profile and single nucleotide polymorphisms (SNPs) in twelve TPS genes, resulting in the clustering of 62 genotypes according to their essential oil chemotypes. The high concentration of sesquiterpenes is supported by the higher number of TPS-a genes and their expression. The expansion for TPS sub-families in P. guajava occurred after the expansion of other rosids species. Providing insight into the origin of structural diversification and expansion in each clade of the TPS gene family within Myrtaceae. This study can provide insights into the diversity of genes for specialized metabolites such as terpenes, and their regulation, which can lead to a diverse chemotype of essential oil in different tissues and genotypes. This suggests a mode of enzymatic evolution that could lead to high sesquiterpene production, act as a chemical defense and contribute to the adaptive capacity of this species to different habitats.

Lung Transplant Outcomes for Idiopathic Pulmonary Fibrosis: Are We Improving?

BACKGROUND: After implementation of the Lung Allocation Score in 2005, idiopathic pulmonary fibrosis (IPF) emerged as the most common indication for lung transplantation (LT) in the United States. The age and comorbidity of patients undergoing LT have since increased, and the indications for LT have evolved. However, limited data have been used to analyze more recent outcomes among the IPF population. METHODS: This study analyzed LTs for the primary indication of IPF by using the United Network for Organ Sharing database. An eras-based analysis was performed, comparing patient characteristics, survival, and related outcomes during 2005 to 2009 (era 1) and 2010 to 2014 (era 2) with χ2, Wilcoxon rank sum, and Kaplan-Meier analyses. The study compared 1-year survival from 2005 to 2020 and survival at milestones ranging from 1 month to 5 years. Two adjusted Cox proportional hazards models were conducted: 5-year survival by era and 1-year survival annually from 2010 to 2020. RESULTS: From era 1 (n = 1818) to era 2 (n = 3227), the median age of LT recipients increased from 61 to 63 years (P < .001). The percentage of patients in the intensive care unit before LT climbed from 7.7% to 12.1% (P < .001), and the percentage of patients with diabetes grew from 17.9% to 19.4% (P = .003). Despite increased severity of illness, 5-year survival increased from 51.9% in era 1 to 55.2% in era 2 (P = .02). Adjusted modeling indicated that LT during era 2 featured a 17% hazard reduction compared with era 1 (hazard ratio, 0.83; 95% CI, 0.76-0.91). CONCLUSIONS: Survival is improving for patients undergoing LT for IPF, despite the challenges of transplant recipients with progressively higher risk profiles.

Lung Transplantation for People Living With HIV: Promising Mid-term Outcomes.

BACKGROUND: With increasing life expectancy, patients with HIV are more commonly acquiring other chronic diseases, such as end-stage lung disease, for which transplant may be the only effective solution. Until recently, HIV infection was considered a contraindication to lung transplant (LTx). As LTx in people living with HIV (PLWH) becomes more common, there remain limited data on outcomes in this population. METHODS: Using the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research file, we identified LTx recipients with HIV by either serostatus or nucleic acid testing. A control group of confirmed HIV-negative LTx recipients was propensity score matched on age, body mass index, primary diagnosis, and year of transplant. Patient characteristics, transplant parameters, survival, and postoperative outcomes were compared. RESULTS: Fifty-nine LTx recipients with HIV were identified and compared with 236 HIV-negative controls. Among PLWH, cytomegalovirus status was more frequently positive (76.3% versus 58.9%, P = 0.014), and the median Lung Allocation Score at match was higher (44 versus 39, P = 0.004). PLWH were more likely to undergo dialysis postoperatively (18.6% versus 8.9%, P = 0.033), although other complication rates were similar. Fifty-three percent of LTx for PLWH occurred since 2020. One-year survival for PLWH was 91.2% versus 88.6% for controls ( P = 0.620). Three-year survival for a smaller subset was also not statistically significant (HIV versus control: 82.6% versus 77.8%, respectively, P = 0.687). CONCLUSIONS: There was no difference in 1-y survival for LTx recipients living with HIV compared with a matched control group, supporting this group of patients as viable candidates for LTx.

Predictors of the Social Participation of Adults with Down Syndrome: An Analysis Based on the Biopsychosocial Model of the International Classification of Functioning, Disability, and Health.

OBJECTIVE: The aim of the study is to identify the predictors of social participation in Down syndrome adults from the biopsychosocial model of the International Classification of Functioning, Disability, and Health. METHODS: An exploratory, analytical, cross-sectional study was conducted with Down syndrome adults. The social participation was assessed using the Life Habits Assessment. The independent variables were determined using the International Classification of Functioning, Disability, and Health biopsychosocial model: body functions were assessed by body mass index, cognition function (Mini-Mental State Examination), and lower limbs muscle strength (Sit-to-Stand Test). Activities were assessed by the 8-Foot Up and Go Test. Environmental factors were assessed by the measure of the quality of the environment, and personal factors were assessed by age, sex, and education level. RESULTS: The total Life Habits Assessment score indicates that individuals show moderate restriction in social participation, with major restriction in the education, employment, and responsibilities domains. The 8-Foot Up and Go Test was the best social participation predictor variable, followed by Mini-Mental State Examination, and the Sit-to-Stand Test. Contextual factors were not predictors of participation. CONCLUSIONS: It was concluded that individuals with Down syndrome present the most restrictions to social participation in activities that involve social roles. The predictors influencing social participation are functional mobility, cognition, and lower limb muscle strength.

Uterine Sarcoma With EML4::NTRK3 Fusion: A Spectrum of Mesenchymal Neoplasms Harboring Actionable Gene Fusions.

NTRK gene fusions are part of a paradigm shift in oncology, arising as one of the main genomic alterations with actionability in the so-called "agnostic setting." In gynecologic pathology, the recent description of uterine sarcoma resembling fibrosarcoma and with NTRK rearrangements ( NTRK -rearranged uterine sarcoma) highlights the importance of recognizing clinicopathological cues that can lead to genomic profiling. Herein, we report the case of a 43-year-old woman presenting with vaginal bleeding and pelvic mass. Histopathology of the tumor showed moderately atypical spindle cells arranged in long fascicles reminiscent of fibrosarcoma, along with immunohistochemical positivity for S100, CD34, and pan-tropomyosin receptor kinase. This prompted RNA-sequencing and the finding of a rare EML4::NTRK3 fusion. Clinical, histologic, and molecular findings are described, in addition to discussions regarding differential diagnoses and possible implications of the findings in clinical practice.

Hyperthermic intrapleural chemotherapy: an update.

The safety and efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) as an adjunct to cytoreductive surgery (CRS) in pleural malignancies has been well demonstrated. This is most often described in cases of mesothelioma, thymoma, or other secondary pleural metastases. The utilization of a direct cytotoxic agent with increased penetration secondary to a hyperthermic environment is especially beneficial in pleural malignancy as a microscopic resection remains immensely challenging. Despite favorable outcomes with a limited associated risk profile, there persists a variety in utilization and technique of HITHOC described in current literature. National Comprehensive Cancer Network (NCCN) guidelines state that though intraoperative adjuvant therapies such as HITHOC have been studied, they remain of unclear benefit and definitive recommendations do not currently exist. This ambiguity limits the standardization of HITHOC, thus hindering its further application in a patient population with exceedingly poor outcomes within current guideline-based therapy. As the prevalence of pleural malignancies necessitating CRS with adjuvant HITHOC remains quite low, we believe a task force initiative to further investigate the role of HITHOC in surgical management of pleural malignancies would enable wider utility of this promising technique. Additionally, we propose that the creation of a pleural cancer index could aid in standardization of HITHOC in those with pleural malignancy.

Modelling the effect of defects and cracks in solar cells' performance using the d1MxP discrete model.

Renewable energies are increasingly playing an important role in the world's energy supply. Society demands new solutions to solve environmental issues caused by fossil fuels. The importance of photovoltaic technology has been increasing and consequently, the necessity to have more accurate models to characterise the performance of solar cells during their entire lifetime has rose as well. Performance problems may appear during devices' lifetimes associated with factors, such as weather conditions or faulty installation. Cracking might occur, leading to abrupt reductions on the produced power, quite difficult and expensive to fix. The I-V curves of a defected or cracked solar cell might not have the shape imposed by the usual models as 1M5P. In this article, cracked c-Si solar cells are modelled using a novel model: d1MxP. This model is based on the discretisation of the diode's response on models as 1M5P. Instead of imposing a shape and compute some parameters to fit it on experimental data, the proposed model connects every two points. The results suggest a better fit using the proposed model in comparison with the 1M5P, not only in the original curves, but also modelling cracked cells. As consequence of a better fitting, the computation of important figures of merit as maximum power point or fill factor, reveals to be more precise. It is concluded that the proposed model might characterise the performance of a solar cell, even cracked, which is a huge advance aiming the possibility of simulating complex problems during the cells' operation lifetime.

Clinical outcomes of stage-IV non-small-cell lung cancer in young patients and the impact of tumor markers.

INTRODUCTION: Non-Small Cell Lung Cancer (NSCLC) diagnosed at a younger age have patterns of care, responses to treatment, and outcomes not entirely clear. A particular feature includes more advanced stages at diagnosis. Our objective was to characterize these young patients with advanced disease and evaluate the impact of targeted therapies. METHODS: Analyzing our cohort of 18,252 newly diagnosed NSCLC patients, we defined Young-age versus Norm-age based on the age distribution at the time of diagnosis. Stage-IV patients were investigated on their clinical information and outcomes; deaths were considered lung cancer-related. Primary outcome was overall survival (OS). Multivariate Cox models were built to evaluate independent prognostic factors in comparative age groups. RESULTS: We found 4,267 patients with stage-IV NSCLC (359 Young-age; 3,908 Norm-age). Young patients had predominance of females (52.6% vs. 43.3%, P = 0.001), never-smokers (43.2% vs. 14.8%, P < 0.001), and adenocarcinoma (73.5% vs. 62.5%, P < 0.001). Mean OS was 21.1 months in the Young and 15.1 months in Norm, respectively (P < 0.001). Young patients were more often treated with surgery (6.7% vs. 5.0%), chemotherapy (53.2% vs. 44.1%), and targeted therapy (10.6% vs. 5.7%). Molecular studies were assessed in patients when the mutation tests became clinically available (93 Young, 875 Norm) and revealed a critical role of targeted therapy in the improved survival of both age groups. DISCUSSION: Young patients with stage-IV NSCLC have a specific profile and benefit more when treated with surgery and targeted therapy. Molecular testing is critical in this population, where improved survival was identified. A more aggressive approach to this population needs to be considered.