RESUMEN

Adeno-associated viruses (AAV) are promising vectors for gene therapy due to their efficacy in vivo. However, there is room for improvement to address key limitations such as the pre-existing immunity to AAV in patients, high-dose toxicity, and relatively low efficiency for some cell types. This study introduces a metabolic engineering approach, using knockout of the enzyme phosphatidylserine synthase 1 (PTDSS1) to increase the abundance of extracellular vesicle-enclosed AAV (EV-AAV) relative to free AAV in the supernatant of producer cells, simplifying downstream purification processes. The lipid-engineered HEK293T-ΔPTDSS1 cell line achieved a 42.7-fold enrichment of EV-AAV9 compared to free AAV9 in the supernatant. The rational genetic strategy also led to a 300-fold decrease of free AAV in supernatant compared to wild-type HEK293T. The membrane-engineered EV-AAV9 (mEV-AAV9) showed unique envelope composition alterations, including cholesterol enrichment and improved transduction efficiency in human AC16 cardiomyocytes by 1.5-fold compared to conventional EV-AAV9 and by 11-fold compared to non-enveloped AAV9. Robust in-vivo transduction four weeks after intraparenchymal administration of mEV-AAV9 was observed in the murine brain. This study shows promise in the potential of lipid metabolic engineering strategies to improve the efficiency and process development of enveloped gene delivery vectors. Keywords: membrane engineering, EV-AAV, upstream, downstream.

RESUMEN

BACKGROUND: Kidney transplant recipients are at higher risk of infections due to immunosuppression, especially in the perioperative period after receiving induction therapy. Administration of iron has been linked to bacterial infections. This study investigated if receipt of intravenous iron at the time of kidney transplant increased bacterial infections post-transplant. METHODS: This single-center, retrospective study compared patients who received intravenous iron at the time of kidney transplant to those who did not. Patients were followed for 12 weeks after transplant. The primary outcome was incidence of bacterial infections following transplant; hemoglobin and transfusion needs were also examined. RESULTS: A total of 416 patients who received intravenous iron were compared to 416 patients who did not. Bacterial infections were similar between groups (14.4% iron group vs. 15.9% non-iron group). Intravenous iron did not influence bacterial infections on univariable or multivariable analyses when other infection confounders were accounted for. Patients who did not receive intravenous iron required more packed red blood cell transfusions in the 3 months following transplantation, but this was driven by factors other than intravenous iron as demonstrated by a post-hoc analysis. CONCLUSIONS: Intravenous iron did not increase the risk of bacterial infections in the immediate post-kidney transplant setting. Bacterial infections after transplant were associated with female sex, increasing age at transplant, receipt of transfusions, and increased duration of urinary catheters.

RESUMEN

Animals at early life stages are generally more sensitive to environmental stress than adults. This is especially true of oviparous vertebrates that develop in variable environments with little or no parental care. These organisms regularly experience environmental fluctuations as part of their natural development, but climate change is increasing the frequency and intensity of these events. The developmental plasticity of oviparous vertebrates will therefore play a critical role in determining their future fitness and survival. In this Review, we discuss and compare the phenotypic consequences of chronic developmental hypoxia on the cardiovascular system of oviparous vertebrates. In particular, we focus on species-specific responses, critical windows, thresholds for responses and the interactive effects of other stressors, such as temperature and hypercapnia. Although important progress has been made, our Review identifies knowledge gaps that need to be addressed if we are to fully understand the impact of climate change on the developmental plasticity of the oviparous vertebrate cardiovascular system.

Asunto(s)

Sistema Cardiovascular , Cambio Climático , Hipoxia , Estrés Fisiológico , Vertebrados , Animales , Hipoxia/fisiopatología , Vertebrados/fisiología , Vertebrados/crecimiento & desarrollo , Sistema Cardiovascular/crecimiento & desarrollo , Sistema Cardiovascular/fisiopatología , Oviparidad , Adaptación Fisiológica

RESUMEN

The cognitive model of suicide proposes that biased cognitive processes contribute to suicidal thoughts and behaviors, and initial evidence suggests that attentional bias to suicide-congruent cues may predict suicidal behavior beyond established clinical risk factors. To date, much less work has explored the potential role of interpretation biases in the development and prediction of suicide risk. The present study assessed the psychometric properties, including reliability, concurrent validity, and predictive validity, of a novel adaptation of the Word Sentence Association Paradigm (WSAP) to assess suicide-suicide interpretation biases. In a sample of 239 psychiatric inpatients, including patients with no recent suicidal ideation or lifetime attempts (n = 35), those with recent suicide attempts (n = 29), and those with recent suicidal ideation (n = 174), participants completed the modified WSAP as well as self-reported suicidal ideation and attempts for the subsequent 6 months. Although the WSAP demonstrated good reliability, evidence of concurrent and prospective validity (in terms of self-reported suicidal ideation and attempts) was limited. Specifically, the clinical groups did not differ from one another on any measure of interpretation bias, nor did suicide-specific interpretation endorsements predict concurrent or future suicidal ideation when controlling for dysphoric interpretation bias. However, suicide-specific interpretation biases were uniquely associated with a history of a lifetime suicide attempt. Future work should further clarify the extent and specificity of the relationship between suicide-specific interpretation biases and clinical outcomes.

Asunto(s)

Psicometría , Ideación Suicida , Intento de Suicidio , Humanos , Femenino , Masculino , Adulto , Intento de Suicidio/psicología , Reproducibilidad de los Resultados , Persona de Mediana Edad , Adulto Joven , Sesgo Atencional , Suicidio/psicología , Pruebas de Asociación de Palabras

RESUMEN

Altered ankyrin-R (AnkR; encoded by ANK1) expression is associated with diastolic function, left ventricular remodeling, and heart failure with preserved ejection fraction (HFpEF). First identified in erythrocytes, the role of AnkR in other tissues, particularly the heart, is less studied. Here, we identified the expression of both canonical and small isoforms of AnkR in the mouse myocardium. We demonstrate that cardiac myocytes primarily express small AnkR (sAnkR), whereas cardiac fibroblasts predominantly express canonical AnkR. As canonical AnkR expression in cardiac fibroblasts is unstudied, we focused on expression and localization in these cells. AnkR is expressed in both the perinuclear and cytoplasmic regions of fibroblasts with considerable overlap with the trans-Golgi network protein 38, TGN38, suggesting a potential role in trafficking. To study the role of AnkR in fibroblasts, we generated mice lacking AnkR in activated fibroblasts (Ank1-ifKO mice). Notably, Ank1-ifKO mice fibroblasts displayed reduced collagen compaction, supportive of a novel role of AnkR in normal fibroblast function. At the whole animal level, in response to a heart failure model, Ank1-ifKO mice displayed an increase in fibrosis and T-wave inversion compared with littermate controls, while preserving cardiac ejection fraction. Collagen type I fibers were decreased in the Ank1-ifKO mice, suggesting a novel function of AnkR in the maturation of collagen fibers. In summary, our findings illustrate the novel expression of AnkR in cardiac fibroblasts and a potential role in cardiac function in response to stress.

Asunto(s)

Ancirinas , Fibroblastos , Insuficiencia Cardíaca , Ratones Noqueados , Animales , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/genética , Ancirinas/metabolismo , Ancirinas/genética , Ratones , Fibroblastos/metabolismo , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Masculino , Fibrosis , Ratones Endogámicos C57BL

RESUMEN

BACKGROUND: Unfettered movement among habitats is crucial for fish to access patchily distributed resources and complete their life cycle, but many riverscapes in the American Southwest are fragmented by dams and dewatering. The endangered Rio Grande silvery minnow (Hybognathus amarus, RGSM) persists in a fragmented remnant of its former range (ca. 5%), and its movement ecology is understudied. METHODS: We tracked movements of hatchery-reared RGSM, tagged with passive integrated transponder tags, using stationary and mobile antennas from 2019 to 2022. We quantified probability of movement and total distance moved by RGSM released above and below a dam. We then assessed how well two prevailing riverine movement theories (i.e., restricted movement paradigm [RMP] and colonization cycle hypothesis [CCH]) explained RGSM movement patterns. RESULTS: We detected 36.8% of released RGSM (n = 37,215) making at least one movement. Movements were leptokurtic and substantially greater than expected based on the RMP for both stationary (1.7-5.9 m) and mobile (30.3-77.8 m) individuals. On average, RGSM were detected at large for 75 days and moved a total of 12.2 rkm within a year. The maximum total distance moved by RGSM was 103 rkm. Similarly, we observed a multimodal distribution of detected range sizes with a mean detected range of 2.4 rkm and a maximum detected range of 78.2 rkm. We found little support for an upstream movement bias, as expected under the CCH, and most movements (74%) were directed downstream. CONCLUSIONS: Our data suggest RGSM are highly mobile, with the ability to make long-distance movements. Neither movement theory adequately described movement patterns of RGSM; instead, our findings support a nomadic movement pattern and an apparent drift paradox matching recent studies of other pelagic-broadcast spawning minnows where populations persist upstream despite experiencing downstream drift as larvae. Resolution of the drift paradox may be achieved through further, targeted studies into different aspects of the species' life history. Quantification of RGSM movement provides crucial insights into the species' movement ecology and may help define the appropriate scale of recovery efforts.

RESUMEN

BACKGROUND: Head and neck cancers (HNC) present diagnostic challenges due to multifocal disease manifestations, posing difficulties in distinguishing between metastatic disease and second primary malignancies (SPM). This complexity underscores the need for advanced diagnostic approaches. Emerging technologies, such as next-generation sequencing (NGS) and molecular classifier assays, show promise in providing precise insights into the diverse etiologies of HNC. METHOD: In this article, we employed NGS and molecular classifier assays to delve into three distinct clinical cases. The objective was to showcase the instrumental role of these technologies in facilitating accurate diagnoses and differentiating between metastatic disease and SPM in HNC cases. RESULTS: The results of this series highlight the effectiveness of NGS and molecular classifier assays in enhancing diagnostic accuracy for HNC and contributing to the precise differentiation of disease etiologies. The utilization of these advanced technologies proved instrumental in avoiding unnecessary interventions and paved the way for more targeted and effective treatment strategies. CONCLUSION: Our findings underscore the necessity of incorporating advanced molecular testing technologies into the diagnostic and therapeutic approaches for HNC, thereby championing a more nuanced and effective approach to managing these complex cases.

RESUMEN

Introduction Peripartum cardiomyopathy (PPCM) is defined as an idiopathic left ventricular failure with reduced ejection fraction (EF <45%) that affects women in the last month of pregnancy or in the months after giving birth. The pathophysiology remains elusive, resulting in complications with varied severity; one of the most concerning complications is thromboembolism, specifically pulmonary embolism (PE). The purpose of this study was to characterize and evaluate the real-world prevalence, predictors, and outcomes of PE in PPCM. Methods The data were derived from the National Inpatient Sample (NIS) database from January 2016 to December 2019. The primary outcomes assessed were baseline and hospital admission characteristics and comorbidities for patients with PPCM with or without PE. Outcomes for PPCM patients with PE and predictors of mortality for PPCM were also analyzed. Results PE developed in 105 of 4,582 patients with PPCM (2.3%). Patients with PPCM and PE had longer hospital stays (10.86 days ± 1.4 vs. 5.73 ± 0.2 days, p = 0.001) and total charges ($169,487 ± $39,628 vs. $86,116 ± $3,700, p = 0.001). Patients with PE had a higher burden of coagulopathy (13.3% vs. 3.0%, p = 0.01), intracardiac thrombus (6.7% vs. 1.6%, p = 0.01), and iron deficiency anemia (21.0% vs. 12.6%, p = 0.01). Patients without PE were found to have a higher burden of preeclampsia (14.7% vs. 1.9%, p = 0.01) and obstructive sleep apnea (5.4% vs. 1.0%, p = 0.045). Predictors of mortality in patients with PPCM included cardiogenic shock (aOR 13.42, 95% CI 7.50-24.03, p = 0.05), PE (aOR 6.60, 95% CI 2.506-17.39, p = 0.05), non-ST-elevation myocardial infarction (NSTEMI; aOR 3.57, 95% CI 1.35-9.44, p = 0.05), chronic kidney disease (aOR 3.23, 95% CI 1.68-6.22, p = 0.05), and atrial fibrillation (aOR 2.57; 95% CI 1.25-5.30, p = 0.05). Conclusion Although an uncommon complication, PE in PPCM demonstrates an association with higher mortality and financial burden. Along with PE, we found predictors of mortality in PPCM to include atrial fibrillation, NSTEMI, chronic kidney disease, and cardiogenic shock.

RESUMEN

Systemic administration of adeno-associated virus (AAV) vectors for spinal cord gene therapy has challenges including toxicity at high doses and pre-existing immunity that reduces efficacy. Intrathecal (IT) delivery of AAV vectors into cerebral spinal fluid can avoid many issues, although distribution of the vector throughout the spinal cord is limited, and vector entry to the periphery sometimes initiates hepatotoxicity. Here we performed biopanning in non-human primates (NHPs) with an IT injected AAV9 peptide display library. We identified top candidates by sequencing inserts of AAV DNA isolated from whole tissue, nuclei, or nuclei from transgene-expressing cells. These barcoded candidates were pooled with AAV9 and compared for biodistribution and transgene expression in spinal cord and liver of IT injected NHPs. Most candidates displayed increased retention in spinal cord compared with AAV9. Greater spread from the lumbar to the thoracic and cervical regions was observed for several capsids. Furthermore, several capsids displayed decreased biodistribution to the liver compared with AAV9, providing a high on-target/low off-target biodistribution. Finally, we tested top candidates in human spinal cord organoids and found them to outperform AAV9 in efficiency of transgene expression in neurons and astrocytes. These capsids have potential to serve as leading-edge delivery vehicles for spinal cord-directed gene therapies.

Asunto(s)

Dependovirus , Terapia Genética , Vectores Genéticos , Médula Espinal , Dependovirus/genética , Animales , Médula Espinal/metabolismo , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Humanos , Terapia Genética/métodos , Transgenes , Técnicas de Transferencia de Gen , Cápside/metabolismo , Distribución Tisular , Inyecciones Espinales , Transducción Genética , Macaca mulatta , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo

RESUMEN

Recent shifts in societal attitudes towards cannabis have led to a dramatic increase in consumption rates in many Western countries, particularly among young people. This trend has shed light on a significant link between cannabis use disorder (CUD) and pathological reactive aggression, a condition involving disproportionate aggressive and violent reactions to minor provocations. The discourse on the connection between cannabis use and aggression is frequently enmeshed in political and legal discussions, leading to a polarized understanding of the causative relationship between cannabis use and aggression. However, integrative analyses from both human and animal research indicate a complex, bidirectional interplay between cannabis misuse and pathological aggression. On the one hand, emerging research reveals a shared genetic and environmental predisposition for both cannabis use and aggression, suggesting a common underlying biological mechanism. On the other hand, there is evidence that cannabis consumption can lead to violent behaviors while also being used as a self-medication strategy to mitigate the negative emotions associated with pathological reactive aggression. This suggests that the coexistence of pathological aggression and CUD may result from overlapping vulnerabilities, potentially creating a self-perpetuating cycle where each condition exacerbates the other, escalating into externalizing and violent behaviors. This article aims to synthesize existing research on the intricate connections between these issues and propose a theoretical model to explain the neurobiological mechanisms underpinning this complex relationship.

RESUMEN

BACKGROUND: The transfer of pediatric patients with testicular torsion from community hospitals to pediatric centers can be a time and resource-intensive step toward emergent surgical intervention. OBJECTIVE: We sought to describe trends of patient transfer in our state and compare clinical outcomes and health system costs between patients transferred and treated primarily at a pediatric center. STUDY DESIGN: This retrospective cohort study compared patients aged 1-18 years who presented directly to a pediatric center to those transferred for acute testicular torsion from 2018 to 2023. Exclusion criteria included age <1 year, non-urgent surgery, and admission from clinic. Patient age, BMI, Tanner stage, ASA class, insurance coverage, and presentation time were covariates. Group characteristics and times from symptom onset to initial ED presentation to surgery were compared via two-sided Student's t-tests. Clinical outcomes (orchiectomy, testicular atrophy) were compared via Fisher's exact tests. Costs from transferring hospitals were estimated from costs at our institution, and medical transport costs were extrapolated from contract prices between transport agencies and the pediatric center to compare total episode-of-care cost. RESULTS: A total of 133 cases (37 primaries, 96 transfers) met inclusion criteria. Transfers increased over the study period (67%-75%). There were no significant differences in age, Tanner stage, ASA score, BMI, or time of day of presentation between groups. Median transfer distance was 12 miles (IQR 7-22) and time was 1 h (IQR 1-2). More than half of cases (53%) were transferred due to hospital policy regarding surgical treatment of minors, and 25% due to lack of urology coverage. Time from initial ED site to OR was nearly doubled for the transfer group (median 4.5 vs 2.5 h, p = 0.02). Despite a higher rate of orchiectomy in the primary group (43 vs 22%, p = 0.01), this difference was not significant after stratification by symptom duration. The estimated average cost of care for patients transferred was twice that of primary patients ($15,082 vs $6898). DISCUSSION: Transfer of pediatric patients in our state for testicular torsion has increased in recent years. Hospital policies and local urology coverage are primary drivers of patient transfer which nearly doubled time to surgical intervention and more than doubled cost of care. Clinical outcomes were driven by delayed presentation. CONCLUSION: Transfer of pediatric patients for testicular torsion nearly doubles time to surgical intervention and more than doubles cost of care. Restrictive hospital policies and gaps in rural hospital urology coverage present opportunities to improve the quality and efficiency of care for these children.

RESUMEN

Despite binding similar cis elements in multiple locations, a single transcription factor (TF) often performs context-dependent functions at different loci. How factors integrate cis sequence and genomic context is still poorly understood and has implications for off-target effects in genetic engineering. The Drosophila context-dependent TF chromatin-linked adaptor for male-specific lethal proteins (CLAMP) targets similar GA-rich cis elements on the X-chromosome and at the histone gene locus but recruits very different, locus-specific factors. We discover that CLAMP leverages information from both cis element and local sequence to perform context-specific functions. Our observations imply the importance of other cues, including protein-protein interactions and the presence of additional cofactors.

Asunto(s)

Proteínas de Drosophila , Factores de Transcripción , Animales , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Cromosoma X/genética , Masculino , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Histonas/metabolismo , Histonas/genética , Cromatina/metabolismo , Cromatina/genética

RESUMEN

[This corrects the article DOI: 10.1016/j.omtm.2022.06.012.].

RESUMEN

Introduction: The field of urology is predominantly male; however, there has been an increasing number of women in the workforce. Peak reproductive years frequently overlap with residency training and early attending career timelines. Exposure to ionizing radiation is a common occupational hazard in many procedural specialties. The use of radiation, for example, in interventional cardiology and interventional radiology, has shown little adjustments in practice patterns, with no adverse outcomes reported among pregnant physicians in their fields in the setting of appropriate radiation safety measures. The impact of radiation exposure during pregnancy for urologists is largely unknown. Our objective was to determine attitudes and practices of urologists related to radiation exposure and to characterize the experience of urologists who have previously been pregnant. Methods: An anonymous online survey was distributed through relevant society membership bases, which included the Endourological Society and the Society for Women in Urology, and social media. Demographics, practice patterns, and changes to practice patterns were recorded for respondents. Statistical analysis was performed in R studio. Results: There were 384 respondents, 255 of whom identified as women. Of these, 164 had been previously pregnant. Female respondents were younger, completed training more recently, and were more likely to have adjusted their caseload due to radiation concerns compared with their male counterparts. Of women who had been pregnant, few had access to policies for who to notify (19%), policies for safety precautions (22%), custom-fitted lead (35%), and maternity lead (20%). Most women (66%) relied on their own research for guidance on radiation safety during pregnancy, while some (41%) also used information from colleagues or mentors. Forty-six percent of women would have taken greater precautions during pregnancy than they did. Conclusions: Access to the appropriate tools to safely navigate pregnancy is inconsistent among practicing urologists. Evidence-based guidelines are needed to better empower pregnant urologists.

Asunto(s)

Exposición Profesional , Pautas de la Práctica en Medicina , Exposición a la Radiación , Urólogos , Humanos , Femenino , Embarazo , Pautas de la Práctica en Medicina/estadística & datos numéricos , Masculino , Encuestas y Cuestionarios , Exposición a la Radiación/efectos adversos , Adulto , Percepción , Persona de Mediana Edad , Urología , Actitud del Personal de Salud

RESUMEN

The interest in mass-rearing black soldier fly (Hermetia illucens) larvae for food and feed is rapidly increasing. This is partly sparked by the ability of the larvae to efficiently valorise a wide range of organic waste and by-products. Primarily, research has focused on the larval stage, hence underprioritizing aspects of the adult biology, and knowledge on reproduction-related traits such as egg production is needed. We investigated the impact of different organic waste and by-products as larval diets on various life-history traits of adult black soldier flies in a large-scale experimental setup. We reared larvae on four different diets: spent Brewer's grain, ground carrots, Gainesville diet, and ground oranges. Traits assessed were development time to pupa and adult life-stages, adult body mass, female lifespan, egg production, and egg hatch. Larval diet significantly impacted development time to pupa and adult, lifespan, body size, and egg production. In general, flies reared on Brewer's grain developed up to 4.7 d faster, lived up to 2.3 d longer, and produced up to 57% more eggs compared to flies reared on oranges on which they performed worst for these traits. There was no effect of diet type on egg hatch, suggesting that low-nutritious diets, i.e. carrots and oranges, do not reduce the quality but merely the quantity of eggs. Our results demonstrate the importance of larval diet on reproductive output and other adult traits, all important for an efficient valorisation of organic waste and by-products, which is important for a sustainable insect-based food and feed production.

Asunto(s)

Larva , Reproducción , Animales , Femenino , Rasgos de la Historia de Vida , Dieta , Dípteros/fisiología , Residuos/análisis , Masculino , Simuliidae/crecimiento & desarrollo

RESUMEN

Experience during childbirth is an important predictor of mothers' later well-being. Using the framework of Self-Determination Theory and, we hypothesized that the degree to which women felt autonomy over their choices during childbirth would be reflected in their later confidence as parents, termed Parental Self-Efficacy (PSE). We assessed PSE as well as depressive symptoms before birth (T1, approximately 36 weeks pregnant) and after birth (T2, approximately 5 weeks postpartum). Perceptions of autonomy during childbirth were measured at T2 using the Perceived Control in Childbirth scale. Using hierarchical linear regression, we found that mothers' perceived autonomy during childbirth predicted their postpartum PSE, controlling for prenatal PSE, pre- and postnatal depression, number of childbirth interventions, and overall birth satisfaction. These data suggest that care providers' support for women's autonomy in childbirth impacts how women feel about themselves as mothers in the postpartum months.

RESUMEN

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

Asunto(s)

Complejo I de Transporte de Electrón , Inflamación , Microglía , Enfermedades Neuroinflamatorias , Animales , Femenino , Humanos , Masculino , Ratones , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/patología , Modelos Animales de Enfermedad , Transporte de Electrón/efectos de los fármacos , Complejo I de Transporte de Electrón/antagonistas & inhibidores , Complejo I de Transporte de Electrón/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Microglía/efectos de los fármacos , Microglía/metabolismo , Microglía/patología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Multiómica , Células Mieloides/metabolismo , Células Mieloides/patología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

Our group recently developed a family of side-chain amino acid-functionalized poly(S-alkyl-l-homocysteines), Xaa-CH (Xaa = generic amino acid), which possess the ability to form environmentally responsive coacervates in water. In an effort to further study how the molecular structure affects polypeptide coacervate formation, we prepared side-chain amino acid-functionalized poly(S-alkyl-rac-cysteines), Xaa-rac-C, via post-polymerization modification of poly(dehydroalanine), ADH. The use of the ADH platform allowed straightforward synthesis of a diverse range of side-chain amino acid-functionalized polypeptides via direct reaction of unprotected l-amino acid 2-mercaptoethylamides with ADH. Despite their differences in the main-chain structure, we found that Xaa-rac-C can form coacervates with properties similar to those seen with Xaa-CH. These results suggest that the incorporation of side-chain amino acids onto polypeptides may be a way to generally favor coacervation. The incorporation of l-methionine in Met-rac-C allowed the preparation of coacervates with improved stability against high ionic strength media. Further, the presence of additional thioether groups in Met-rac-C resulted in an increased solubility change upon oxidation allowing facile reversible redox switching of coacervate formation in aqueous media.

Asunto(s)

Alanina/análogos & derivados , Aminoácidos , Péptidos , Péptidos/química , Alanina/química , Cisteína

RESUMEN

INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME) approved the first pain medicine fellowship programs over three decades ago, designed around a pharmacological philosophy. Following that, there has been a rise in the transition of pain medicine education toward a multidisciplinary interventional model based on a tremendous surge of contemporaneous literature in these areas. This trend has created variability in clinical experience and education amongst accredited pain medicine programs with minimal literature evaluating the differences and commonalities in education and experience of different pain medicine fellowships through Program Director (PD) experiences. This study aims to gather insight from pain medicine fellowship program directors across the country to assess clinical and interventional training, providing valuable perspectives on the future of pain medicine education. METHODS: This study involved 56 PDs of ACGME-accredited pain fellowship programs in the United States. The recruitment process included three phases: advanced notification, invitation, and follow-up to maximize response rate. Participants completed a standard online questionnaire, covering various topics such as subcategory fields, online platforms for supplemental education, clinical experience, postgraduate practice success, and training adequacy. RESULTS: Surveys were completed by 39/56 (69%) standing members of the Association of Pain Program Directors (APPD). All PDs allowed fellows to participate in industry-related and professional society-related procedural workshops, with 59% encouraging these workshops. PDs emphasized the importance of integrity, professionalism, and diligence for long-term success. Fifty-four percent of PDs expressed the need for extension of fellowship training to avoid supplemental education by industry or pain/spine societies. CONCLUSION: This study highlights the challenge of providing adequate training in all Pain Medicine subtopics within a 12-month pain medicine fellowship. PDs suggest the need for additional training for fellows and discuss the importance of curriculum standardization.

RESUMEN

The kleptoparasitic pea crab Zaops ostreum lives within the gills of bivalves, including the economically important eastern oyster Crassostrea virginica. Previous research along the east coast of central Florida has found an average of 2.3 pieces of plastic per oyster. The goals of our research were to determine if filter-feeding oysters transfer microfibers to Z. ostreum via the crab: 1) actively consuming plastic particles, or 2) passively becoming entangled in microfibers. Our results show that both occur. While only 11.6 % of Z. ostreum (total n = 122) consumed microfibers, those that did had up to 14 pieces in their soft tissues. Similarly, only 7.4 % of Z. ostreum had microfibers entangled around their appendages. Mean lengths of consumed and entangled fibers were similar, 1.9 and 2.7 mm, respectively. Additional research is needed to understand the positive and negative impacts of microfibers associated with pea crabs on both species.

Asunto(s)

Braquiuros , Crassostrea , Animales , Florida , Ingestión de Alimentos