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International Journal of Pharmaceutics Jun 2024Nanotechnology-based drug delivery systems, including siRNA, present an innovative approach to treating breast cancer, which disproportionately affects women. These... (Review)
Review
Nanotechnology-based drug delivery systems, including siRNA, present an innovative approach to treating breast cancer, which disproportionately affects women. These systems enable personalized and targeted therapies, adept at managing drug resistance and minimizing off-target effects. This review delves into the current landscape of nanotechnology-derived siRNA transport systems for breast cancer treatment, discussing their mechanisms of action, preclinical and clinical research, therapeutic applications, challenges, and future prospects. Emphasis is placed on the importance of targeted delivery and precise gene silencing in improving therapeutic efficacy and patient outcomes. The review addresses specific hurdles such as specificity, biodistribution, immunological reactions, and regulatory approval, offering potential solutions and avenues for future research. SiRNA drug delivery systems hold promise in revolutionizing cancer care and improving patient outcomes, but realizing their full potential necessitates ongoing research, innovation, and collaboration. Understanding the intricacies of siRNA delivery mechanisms is pivotal for designing effective cancer treatments, overcoming challenges, and advancing siRNA-based therapies for various diseases, including cancer. The article provides a comprehensive review of the methods involved in siRNA transport for therapeutic applications, particularly in cancer treatment, elucidating the complex journey of siRNA molecules from extracellular space to intracellular targets. Key mechanisms such as endocytosis, receptor-mediated uptake, and membrane fusion are explored, alongside innovative delivery vehicles and technologies that enhance siRNA delivery efficiency. Moreover, the article discusses challenges and opportunities in the field, including issues related to specificity, biodistribution, immune response, and clinical translation. By comprehending the mechanisms of siRNA delivery, researchers can design and develop more effective siRNA-based therapies for various diseases, including cancer.
PubMed: 38944167
DOI: 10.1016/j.ijpharm.2024.124403 -
Transplantation and Cellular Therapy Jun 2024Transplant associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic cell transplant (HCT) associated with endothelial injury resulting in severe...
BACKGROUND
Transplant associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic cell transplant (HCT) associated with endothelial injury resulting in severe end organ damage, acute and long-term morbidity, and mortality. Myeloablative conditioning is a known risk factor, though specific causative agents have not been identified. We hypothesized that the combination of cyclophosphamide and thiotepa (CY+TT) is particularly toxic to the endothelium, placing patients at elevated risk for TA-TMA.
METHODS
We conducted a retrospective review of pediatric and young adult patients who received conditioned autologous and allogeneic HCT between 2012 and August 2023 at UCSF Benioff Children's Hospital, San Francisco. We excluded patients undergoing gene therapy or triple tandem transplants for brain tumors. Neuroblastoma tandem transplants were classified a single transplant occurrence. High dose N-acetylcysteine (NAC) prophylaxis was incorporated into the institutional standard of care from December 2016-May 2019 and May 2022-August 2023. Defibrotide was given prophylactically to patients deemed high-risk for sinusoidal obstruction syndrome (SOS) per institutional guidelines or on clinical trial NCT#02851407 for SOS prophylaxis or NCT#03384693 for TA-TMA prophylaxis. Kaplan-Meier analysis was used to estimate the 1-year cumulative incidence of TA-TMA. Univariate analysis was performed for each of the potential risk factors of interest using log-rank tests and bivariate analysis with Cox regression models using backward selection and hazard ratios were built using all covariates with a univariate p-value <0.2 for allogeneic HCT. SPSS (v29) was used to estimate all summary statistics, cumulative incidences, and uni- and bi-variate analyses.
RESULTS
A total of 558 transplants were performed with 43 patients developing TA-TMA, for a 1-year cumulative incidence of 8.6% (95% CI, 5.9-11.3%) and 7.2% (95% CI, 2.9-11.5%) in allogeneic and autologous HCTs, respectively (p=0.62). In allogeneic recipients (n=417), the 1-year cumulative incidence of TA-TMA with CY+TT as part of conditioning was 35.7% (95% CI, 15.7-55.7%) compared to 11.7% (95% CI, 7.2-16.2%) with either CY or TT alone, and 1.2% (95% CI, 0-2.8%) if neither agent was included in the conditioning regimen (p<0.001). Use of either CY or TT (HR=10.14; p=0.002) or CY+TT (HR=35.93; p<0.001), viral infections (HR=4.3; p=0.017) and fungal infections (HR=2.98; p=0.027) were significant factors resulting in increased risk for developing TA-TMA. In subjects undergoing autologous HCT (n=141), the 1-year cumulative incidence of TA-TMA with CY+TT was 19.6% (95% CI, 8.8-30.6%) while TA-TMA did not occur in patients receiving either CY or TT alone or when neither were included (p<0.001). TA-TMA occurred only in patients with neuroblastoma receiving CY+TT as part of their conditioning. For autologous patients who received CY+TT, those who were CMV seronegative at the time of HCT had an incidence of TA-TMA of 6.7% (95% CI, 0.1-15.7%) compared to 38.1% (95% CI, 35-41.2%) for those CMV seropositive (p=0.007).
CONCLUSIONS
These data show that CY or TT alone or in combination as part of pre-transplant conditioning prior to HCT increase the incidence of TA-TMA. Alternative conditioning excluding the combination of CY+TT should be considered whenever possible to limit the development of TA-TMA.
PubMed: 38944154
DOI: 10.1016/j.jtct.2024.06.020 -
The Journal of Heart and Lung... Jun 2024Real-time lung weight (LW) measurement is a simple and non-invasive technique for detecting extravascular lung water during ex vivo lung perfusion (EVLP). We...
BACKGROUND
Real-time lung weight (LW) measurement is a simple and non-invasive technique for detecting extravascular lung water during ex vivo lung perfusion (EVLP). We investigated the feasibility of real-time LW measurement in clinical EVLP as a predictor of transplant suitability and post-transplant outcomes.
METHODS
In our clinical acellular EVLP protocol, real-time LW was measured in 117 EVLP cases from June 2019 to June 2022. The estimated LW gain at each timepoint was calculated using a scale placed under the organ chamber. The lungs were classified into four categories based on LW adjusted for height and compared between suitable and unsuitable cases. The relationship between estimated LW gain and primary graft dysfunction was also investigated.
RESULTS
The estimated LW gain during the EVLP significantly correlated with the LW gain (post EVLP LW - pre EVLP LW) measured on the back table (R=0.61, P<0.01). In the adjusted LW categories 2-4, the estimated LW gain at 0-1 h after EVLP was significantly higher in unsuitable cases than in suitable cases. The area under the curve for the estimated LW gain was ≥0.80. Primary graft dysfunction grade 0-1 had a significantly lower estimated LW gain at 60 min than grades 2-3 (-43 vs. 1 g, P<0.01).
CONCLUSIONS
Real-time lung measurements can predict transplant suitability and post-transplant outcomes by the early detection of extravascular lung water during the initial 1 h of EVLP.
PubMed: 38944131
DOI: 10.1016/j.healun.2024.06.013 -
International Journal of Biological... Jun 2024We study the effect of electrolytes on the stability in aqueous media of spherical lignin particles (LP) and its relevance to Pickering emulsion stabilization. Factors...
We study the effect of electrolytes on the stability in aqueous media of spherical lignin particles (LP) and its relevance to Pickering emulsion stabilization. Factors considered included the role of ionic strength on morphology development, LP size distribution, surface charge, interfacial adsorption, colloidal and wetting behaviors. Stable emulsions are formed at salt concentrations as low as 50 mM, with the highest stability observed at a critical concentration (400 mM). We show salt-induced destabilization of LP aqueous dispersions at an ionic strength >400 mM. At this critical concentration LP flocculation takes place and particulate networks are formed. This has a profound consequence on the stability of LP-stabilized Pickering emulsions, affecting rheology and long-term stability. The results along with quartz microgravimetry and confocal microscopy observations suggest a possible mechanism for stabilization that considers the interfacial adsorption of LP at oil/water interfaces. The often-unwanted colloidal LP destabilization in water ensues remarkably stable Pickering emulsions by the effect of network formation.
PubMed: 38944069
DOI: 10.1016/j.ijbiomac.2024.133504 -
Appetite Jun 2024The aim of this review is to provide an overview of parental communication patterns during mealtimes, with a special emphasis being placed on the differences between...
Parental verbal communication and modeling behavior during mealtimes shape offspring eating behavior - a systematic review with a focus on clinical implications for eating disorders.
OBJECTIVE
The aim of this review is to provide an overview of parental communication patterns during mealtimes, with a special emphasis being placed on the differences between families with and without a history of eating disorders.
METHODS
The systematic review was conducted according to the PRISMA statement. A systematic literature search was carried out in PubMed, PubPsych and PsycINFO and the results were assessed for eligibility by two independent raters using the PICOS criteria. Only studies that included a mealtime observation were considered suitable for analysis of both explicit and implicit parental communication.
RESULTS
The results of the review suggest that mothers communicate more, with more complexity, and with a greater variety of words with their children during mealtimes compared to fathers. The intention and type of communication is diverse and heterogeneous. In general, parents often tried to encourage their children to eat. Verbal modeling and co-eating appeared to be common behaviors. Mothers with a history of eating disorders expressed more negative emotions during eating than mothers without eating disorders. Findings regarding the use of positive comments and controlling speech are contradicting.
DISCUSSION
The review outlines major fields of parent-child communication and modeling behavior around family meals which might be relevant to investigate and integrate into models of intergenerational transmission of eating behavior and disordered eating.
PubMed: 38944057
DOI: 10.1016/j.appet.2024.107584 -
International Journal of Surgery Case... Jun 2024Transverse testicular ectopia (TTE) is a rare congenital condition characterized by migration of both testes through the same inguinal canal and often presents with an...
INTRODUCTION
Transverse testicular ectopia (TTE) is a rare congenital condition characterized by migration of both testes through the same inguinal canal and often presents with an inguinal hernia. TTE is associated with various genitourinary anomalies.
CASE PRESENTATION
A three-year-old boy presented with a non-palpable right testis and a palpable undescended left testis in the left inguinal area. Ultrasound (US) indicated the presence of both testes in the left inguinal canal. In surgery, the two testes were found with separated cord and one hernia sac which was dissected and ligated thus the two cords freed. Next, subdartos pouches were created on both scrotum sides, so that testes placed into the left side first, and then a window created in the scrotal septum which allowed the right testis to be translocated and secured in the right subdartos pouch without tension.
DISCUSSION
TTE is a rare condition and the etiology is not definitively known. TTE usually presents with an inguinal hernia and contralateral cryptorchidism. The diagnosis is made during surgery, but some radiological methods can help in diagnosis. Management is usually surgical and involves interventions such as hernia repair, reduction of the testis and orchiopexy. Continuous monitoring is essential for ensuring postoperative testes health and evaluating the risk of malignancy.
CONCLUSION
TTE should be suspected in cases with unilateral empty scrotum and family history of genital disorders. US is critical for accurately localizing the testes, along with surgical exploration, to proceed with the appropriate surgical intervention.
PubMed: 38943934
DOI: 10.1016/j.ijscr.2024.109949 -
Clinical Psychology Review Jun 2024Personal recovery represents a paradigm shift in mental healthcare. Validated self-report outcome measures (PROMs) are needed to facilitate the transformation towards... (Review)
Review
BACKGROUND
Personal recovery represents a paradigm shift in mental healthcare. Validated self-report outcome measures (PROMs) are needed to facilitate the transformation towards recovery-oriented practices and services. Objectives were to identify published measures and analyze their measurement properties using a standardized methodology.
METHODS
Following the COSMIN guidelines, we conducted a systematic review of personal recovery PROMs in serious mental illness. The MEDLINE, PMC, PsycINFO, PsycARTICLES, PBSC and Scopus electronic databases were searched for articles published between May 2012 and February 2024. Full-text articles from a previous systematic review were also examined.
RESULTS
91 studies were included in the review, describing 25 PROMs. Ten of them had not been identified in previous reviews. Quality of evidence was globally poor for most PROM measurement properties. Very little evidence was found for cross-cultural validity, measurement invariance, measurement error and criterion validity. The Recovery Assessment Scale and Questionnaire about the Process of Recovery showed the strongest evidence for sufficient psychometric data on a wide range of measurement properties.
CONCLUSIONS
Several personal recovery measures are now available. While research is still needed to enhance their validity on some psychometric properties, the current tools appear sufficient to cover most research and clinical needs.
PubMed: 38943916
DOI: 10.1016/j.cpr.2024.102459 -
Acta Psychologica Jun 2024In a context marked by teachers' shortage, prioritizing teachers' well-being emerges as one of the factors that can encourage them to stay in the profession. Well-being...
In a context marked by teachers' shortage, prioritizing teachers' well-being emerges as one of the factors that can encourage them to stay in the profession. Well-being is a multidimensional concept and difficult to define and measure. Moreover, its link with Psychological Capital (PsyCap), a concept that includes personal psychological resources (hope, self-efficacy, resilience, and optimism) (Luthans & Youssef, 2004), has received little attention in the educational sciences. The main objective of this paper is therefore to investigate the links between these two concepts from a theoretical point of view in psychology and educational sciences. For this purpose, the scoping review methodology (Tricco et al., 2018) is mobilized to identify research issues, methodological questions, and the various links between well-being and PsyCap. Based on a systematic review of 376 bibliographic references conducted in the main databases in psychology and educational sciences, 32 articles were selected analysed. The data extracted indicate that these concepts particularly affect teachers (42.11 % of subjects concerned, N = 42,750). In addition, all the sources selected report significant and positive statistical links between well-being and PsyCap. These results suggest possible avenues for research on teachers' well-being.
PubMed: 38943874
DOI: 10.1016/j.actpsy.2024.104370 -
Meat Science Jun 2024The European carcass grading scheme (EUROP) places large emphasis on meat yield and therefore on quantitative traits such as carcass conformation and superficial fat...
The European carcass grading scheme (EUROP) places large emphasis on meat yield and therefore on quantitative traits such as carcass conformation and superficial fat coverage. However, it falls short in considering sensory properties and consumer satisfaction. In contrast, the Meat Standards Australia (MSA) grading scheme considers, among others, animals' ossification, marbling, and ultimate pH as primary indicators of beef eating quality. This study aims to characterize MSA carcass grading scheme applied to the Italian beef production system, considering its significant role in European beef market. The study involved 3204 Charolais, Limousin, and crossbred young bulls and heifers slaughtered in a commercial Italian abattoir. Data collection spanned a broad range of variables, including animal characteristics, MSA traits, and EUROP carcass grading traits. Regardless of the sex of the animal, no significant relationship was observed between MSA traits and EUROP carcass grading scores. Factors such as sex, age, and arrival season at the fattening unit significantly affected most of MSA traits. Females had significantly higher marbling score, and lower ossification score and hump height than males. Animals imported in autumn and winter had significantly lower marbling score, but similar ossification score compared to those imported in spring and summer. Older females had the highest marbling scores. While further research is needed to assess whether the MSA grading scheme can be adapted to all different European rearing systems, results of this study are a prelude to the potential benefits that the MSA grading scheme can bring to the European beef industry.
PubMed: 38943842
DOI: 10.1016/j.meatsci.2024.109575 -
Health Policy (Amsterdam, Netherlands) Jun 2024Acute coronary syndrome (ACS) is a life-threatening condition, with ACS-associated morbidity and mortality causing substantial human and economic challenges to the... (Review)
Review
Acute coronary syndrome (ACS) is a life-threatening condition, with ACS-associated morbidity and mortality causing substantial human and economic challenges to the individual and health services. Due to shared disease determinants, those with ACS have a high risk of comorbid Type 2 diabetes mellitus (T2DM). Despite this, the two conditions are managed separately, duplicating workload for staff and increasing the number of appointments and complexity of patient management plans. This rapid review compared current ACS and T2DM guidelines across Australia, Canada, Europe, Ireland, New Zealand, the UK, and the USA. Results highlighted service overlap, repetition, and opportunities for integrated practice for ACS-T2DM lifestyle management across diet and nutrition, physical activity, weight management, clinical and psychological health. Recommendations are made for potential integration of ACS-T2DM service provision to streamline care and reduce siloed care in the context of the health services for ACS-T2DM and similar comorbid conditions.
PubMed: 38943831
DOI: 10.1016/j.healthpol.2024.105116