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1.
Neurochem Int ; 177: 105769, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38761855

RESUMEN

Neuroinflammation stands as a critical player in the pathogenesis of diverse neurological disorders, with microglial cells playing a central role in orchestrating the inflammatory landscape within the central nervous system. Cannabidiol (CBD) has gained attention for its potential to elicit anti-inflammatory responses in microglia, offering promising perspectives for conditions associated with neuroinflammation. Here we investigated whether the NLRP3 inflammasome and inducible nitric oxide synthase (iNOS) are involved in the protective effects of CBD, and if their modulation is dependent on cannabinoid receptor 2 (CB2) and PPARγ signalling pathways. We found that treatment with CBD attenuated pro-inflammatory markers in lipopolysaccharide (LPS)-challenged BV2 microglia in a CB2- and PPARγ-dependent manner. At a molecular level, CBD inhibited the LPS-induced pro-inflammatory responses by suppressing iNOS and NLRP3/Caspase-1-dependent signalling cascades, resulting in reduced nitric oxide (NO), interleukin-1ß (IL-1ß), and tumour necrosis factor-alpha (TNF-α) concentrations. Notably, the protective effects of CBD on NLRP3 expression, Caspase-1 activity, and IL-1ß concentration were partially hindered by the antagonism of both CB2 receptors and PPARγ, while iNOS expression and NO secretion were dependent exclusively on PPARγ activation, with no CB2 involvement. Interestingly, CBD exhibited a protective effect against TNF-α increase, regardless of CB2 or PPARγ activation. Altogether, these findings indicate that CB2 receptors and PPARγ mediate the anti-inflammatory effects of CBD on the NLRP3 inflammasome complex, iNOS activity and, ultimately, on microglial phenotype. Our results highlight the specific components responsible for the potential therapeutic applications of CBD on neuroinflammatory conditions.


Asunto(s)
Cannabidiol , Inflamasomas , Inflamación , Lipopolisacáridos , Microglía , Proteína con Dominio Pirina 3 de la Familia NLR , Óxido Nítrico Sintasa de Tipo II , PPAR gamma , Receptor Cannabinoide CB2 , PPAR gamma/metabolismo , Animales , Microglía/efectos de los fármacos , Microglía/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Cannabidiol/farmacología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Lipopolisacáridos/toxicidad , Ratones , Receptor Cannabinoide CB2/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/inducido químicamente , Inflamación/prevención & control , Línea Celular , Antiinflamatorios/farmacología
2.
Nature ; 628(8007): 342-348, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38538790

RESUMEN

Climate change could pose an urgent threat to pollinators, with critical ecological and economic consequences. However, for most insect pollinator species, we lack the long-term data and mechanistic evidence that are necessary to identify climate-driven declines and predict future trends. Here we document 16 years of abundance patterns for a hyper-diverse bee assemblage1 in a warming and drying region2, link bee declines with experimentally determined heat and desiccation tolerances, and use climate sensitivity models to project bee communities into the future. Aridity strongly predicted bee abundance for 71% of 665 bee populations (species × ecosystem combinations). Bee taxa that best tolerated heat and desiccation increased the most over time. Models forecasted declines for 46% of species and predicted more homogeneous communities dominated by drought-tolerant taxa, even while total bee abundance may remain unchanged. Such community reordering could reduce pollination services, because diverse bee assemblages typically maximize pollination for plant communities3. Larger-bodied bees also dominated under intermediate to high aridity, identifying body size as a valuable trait for understanding how climate-driven shifts in bee communities influence pollination4. We provide evidence that climate change directly threatens bee diversity, indicating that bee conservation efforts should account for the stress of aridity on bee physiology.


Asunto(s)
Abejas , Cambio Climático , Desecación , Ecosistema , Calor , Animales , Abejas/anatomía & histología , Abejas/clasificación , Abejas/fisiología , Biodiversidad , Tamaño Corporal/fisiología , Calentamiento Global , Modelos Biológicos , Plantas , Polinización/fisiología , Masculino , Femenino
3.
Chempluschem ; : e202300717, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38406894

RESUMEN

Two BODIPY-C60 -peptide assemblies were synthesized by CuAAC reactions of BODIPY-C60 dyads and a helical peptide functionalized with a terminal alkyne group and an azide group, respectively. The helical peptide within these assemblies was functionalized at its other end by a disulfide group, allowing formation of self-assembled monolayers (SAMs) on gold surfaces. Characterizations of these SAMs, as well as those of reference molecules (BODIPY-C60 -alkyl, C60 -peptide and BODIPY-peptide), were carried out by PM-IRRAS and cyclic voltammetry. BODIPY-C60 -peptide SAMs are more densely packed than BODIPY-C60 -alkyl and BODIPY-peptide based SAMs. These findings were attributed to the rigid peptide helical conformation along with peptide-peptide and C60 -C60 interactions within the monolayers. However, less dense monolayers were obtained with the target assemblies compared to the C60 -peptide, as the BODIPY entity likely disrupts organization within the monolayers. Finally, electron transfer kinetics measurements by ultra-fast electrochemistry experiments demonstrated that the helical peptide is a better electron mediator in comparison to alkyl chains. This property was exploited along with those of the BODIPY-C60 dyads in a photo-current generation experiment by converting the resulting excited and/or charge separated states from photo-illumination of the dyad into electrical energy.

4.
Clin Cancer Res ; 30(8): 1544-1554, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38334950

RESUMEN

PURPOSE: There are no effective treatment strategies for children with highest-risk posterior fossa group A ependymoma (PFA). Chromosome 1q gains (1q+) are present in approximately 25% of newly diagnosed PFA tumors, and this number doubles at recurrence. Seventy percent of children with chromosome 1q+ PFA will die because of the tumor, highlighting the urgent need to develop new therapeutic strategies for this population. EXPERIMENTAL DESIGN: In this study, we utilize 1q+ PFA in vitro and in vivo models to test the efficacy of combination radiation and chemotherapy in a preclinical setting. RESULTS: 5-fluorouracil (5FU) enhances radiotherapy in 1q+ PFA cell lines. Specifically, 5FU increases p53 activity mediated by the extra copy of UCK2 located on chromosome 1q in 1q+ PFA. Experimental downregulation of UCK2 resulted in decreased 5FU sensitivity in 1q+ PFA cells. In in vitro studies, a combination of 5FU, retinoid tretinoin (ATRA), and radiation provided the greatest reduction in cellular proliferation and greatest increase in markers of apoptosis in 1q+ PFA cell lines compared with other treatment arms. Similarly, in vivo experiments demonstrated significant enhancement of survival in mice treated with combination radiation and 5FU and ATRA. CONCLUSIONS: These results are the first to identify a chromosome 1q+ specific therapy approach in 1q+ PFA. Existing phase I studies have already established single-agent pediatric safety and dosages of 5FU and ATRA, allowing for expedited clinical application as phase II trials for children with high-risk PFA.


Asunto(s)
Ependimoma , Neoplasias Infratentoriales , Niño , Humanos , Animales , Ratones , Neoplasias Infratentoriales/genética , Neoplasias Infratentoriales/patología , Neoplasias Infratentoriales/terapia , Resultado del Tratamiento , Ependimoma/genética , Ependimoma/terapia , Fluorouracilo , Cromosomas/metabolismo
5.
Artículo en Inglés | MEDLINE | ID: mdl-38344951

RESUMEN

WHAT IS KNOWN ON THE SUBJECT?: The term 'complex emotional needs' (CEN) is used here to describe people with difficulties and needs that are often associated with the diagnostic label of 'personality disorder'. People with CEN might use out of hours services such as emergency departments and Crisis Resolution/Home Treatment (CRHT) teams more often when experiencing a mental health crisis. Very little is understood about the experiences of both those receiving, and those delivering care, for people with CEN within CRHT settings. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: There are differences between priorities for those delivering and those receiving care within CRHT settings. CRHT staff members are likely to focus more upon those aspects of their role relating to risk issues. managing resources, anxieties and the expectations of others. Service users, meanwhile, focus upon the caring relationship, wanting staff to listen to them, and to feel supported and reassured. In the papers reviewed, service users experiencing CEN did not always feel 'listened to' or 'taken seriously' especially in relation to risk issues and decision-making. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Relating the findings to mental health nursing and CEN within the context of CRHT, to better understand the person experiencing a mental health crisis, mental health nurses need to focus more upon the person and when making decisions around their care and must be aware of the potential for power imbalances. Collaborative 'sense-making' in relation to a person's risk behaviours may help. ABSTRACT: Background A growing body of qualitative evidence focusing upon the experiences of care within Crisis Resolution/Home Treatment (CRHT) is emerging; however, a firm evidence base regarding both the giving and receiving of care for those with complex emotional needs (CEN) in this context is yet to be established. Objective A qualitative evidence synthesis was used to develop a comprehensive understanding of how crisis care for people with CEN is experienced by both those giving and receiving care, within the context of CRHT. Method Findings from 19 research papers considering both clinician and service users' experiential accounts of CRHT were synthesised using meta-ethnography. Findings Both the giving and receiving of care within a CRHT context was experienced across four related meta-themes: 'contextual', 'functional', 'relational' and 'decisional'. Discussion Service user accounts focused upon relational aspects, highlighting a significance to their experience of care. Meanwhile, clinicians focused more upon contextual issues linked to the management of organisational anxieties and resources. For those with CEN, a clinician's focus upon risk alone highlighted power differentials in the caring relationship. Conclusions There is a need for nurses to connect with the experience of the person in crisis, ensuring a better balance between contextual issues and relational working.

6.
Neuro Oncol ; 26(1): 178-190, 2024 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-37503880

RESUMEN

BACKGROUND: High-grade gliomas (HGG) in young children pose a challenge due to favorable but unpredictable outcomes. While retrospective studies broadened our understanding of tumor biology, prospective data is lacking. METHODS: A cohort of children with histologically diagnosed HGG from the SJYC07 trial was augmented with nonprotocol patients with HGG treated at St. Jude Children's Research Hospital from November 2007 to December 2020. DNA methylome profiling and whole genome, whole exome, and RNA sequencing were performed. These data were integrated with histopathology to yield an integrated diagnosis. Clinical characteristics and preoperative imaging were analyzed. RESULTS: Fifty-six children (0.0-4.4 years) were identified. Integrated analysis split the cohort into four categories: infant-type hemispheric glioma (IHG), HGG, low-grade glioma (LGG), and other-central nervous system (CNS) tumors. IHG was the most prevalent (n = 22), occurred in the youngest patients (median age = 0.4 years), and commonly harbored receptor tyrosine kinase gene fusions (7 ALK, 2 ROS1, 3 NTRK1/2/3, 4 MET). The 5-year event-free (EFS) and overall survival (OS) for IHG was 53.13% (95%CI: 35.52-79.47) and 90.91% (95%CI: 79.66-100.00) vs. 0.0% and 16.67% (95%CI: 2.78-99.74%) for HGG (p = 0.0043, p = 0.00013). EFS and OS were not different between IHG and LGG (p = 0.95, p = 0.43). Imaging review showed IHGs are associated with circumscribed margins (p = 0.0047), hemispheric location (p = 0.0010), and intratumoral hemorrhage (p = 0.0149). CONCLUSIONS: HGG in young children is heterogeneous and best defined by integrating histopathological and molecular features. Patients with IHG have relatively good outcomes, yet they endure significant deficits, making them good candidates for therapy de-escalation and trials of molecular targeted therapy.


Asunto(s)
Neoplasias Encefálicas , Glioma , Niño , Lactante , Humanos , Preescolar , Estudios Retrospectivos , Estudios Prospectivos , Proteínas Tirosina Quinasas , Proteínas Proto-Oncogénicas , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/diagnóstico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética
7.
Insects ; 14(11)2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37999044

RESUMEN

Rapid and accurate identification of Anthonomus grandis subspecies is crucial for effective management and eradication. Current diagnostic methods have limitations in terms of time to diagnosis (up to seven days) and can yield ambiguous results. Here, we present the validation of a custom TaqMan SNP Genotyping Assay for the rapid and accurate identification of A. grandis grandis (boll weevil) and A. g. thurberiae (thurberia weevil) subspecies. To validate the assay, we conducted three main experiments: (1) a sensitivity test to determine the DNA concentration range at which the assay performs, (2) a non-target specificity test to ensure no amplification in non-target weevils (false positives), and (3) an accuracy test comparing the results of the new assay to previously established methods. These experiments were carried out in parallel at three independent facilities to confirm the robustness of the assay to variations in equipment and personnel. We used DNA samples from various sources, including field-collected specimens, museum specimens, and previously isolated DNA. The assay demonstrated high sensitivity (PCR success with ≥0.05 ng/µL DNA template), specificity (0.02 false positive rate), and accuracy (97.7%) in diagnosing boll weevil and thurberia weevil subspecies. The entire workflow, including DNA extraction, assay preparation, PCR run time, and data analysis, can be completed within a single workday (7-9 h) by a single technician. The deployment of this assay as a diagnostic tool could benefit boll weevil management and eradication programs by enabling same-day diagnosis of trap-captured or intercepted weevil specimens. Furthermore, it offers a more reliable method for identifying unknown specimens, contributing to the overall effectiveness of boll weevil research and control efforts.

8.
Curr Neurol Neurosci Rep ; 23(12): 849-856, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37921944

RESUMEN

PURPOSE OF REVIEW: Diffuse midline gliomas (DMGs) generally carry a poor prognosis, occur during childhood, and involve midline structures of the central nervous system, including the thalamus, pons, and spinal cord. RECENT FINDINGS: To date, irradiation has been shown to be the only beneficial treatment for DMG. Various genetic modifications have been shown to play a role in the pathogenesis of this disease. Current treatment strategies span targeting epigenetic dysregulation, cell cycle, specific genetic alterations, and the immune microenvironment. Herein, we review the complex features of this disease as it relates to current and past therapeutic approaches.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/metabolismo , Glioma/genética , Glioma/terapia , Sistema Nervioso Central/metabolismo , Médula Espinal/metabolismo , Médula Espinal/patología , Tálamo , Microambiente Tumoral
9.
Crim Behav Ment Health ; 33(6): 401-414, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37817329

RESUMEN

BACKGROUND: Although forensic psychiatry is recognised as a full medical speciality in the UK, training in it is not routinely offered to medical students. With growth both in forensic psychiatry and availability of medical school places, it is a good time to explore the nature and quality of experience already available. AIMS: 1. To map the literature against the guideline for reporting evidence-based practice educational interventions and teaching checklist. 2. To critically review research and scholarship. 3. To identify gaps in evidence-based education for medical students in forensic psychiatry. METHOD: A systematic search of three bibliographic databases from inception to December 2021 was undertaken using keywords related to medical students and forensic psychiatry between December 2021 and March 2022. The search was supplemented by citation and hand searching. RESULTS: Eight articles were identified. Collectively, they suggest that education and teaching were implemented at a local level and not linked to theories of learning. Exposure to forensic psychiatry stimulated positive attitudes, which amplified interest in psychiatry. There was insufficient evidence to determine optimal undergraduate education and teaching practice in forensic psychiatry. CONCLUSIONS: Forensic psychiatry appears to have much to offer the medical undergraduate as part of core learning in psychiatry, including universal skills and knowledge such as ethical decision-making and handling emotions. There appears to be considerable opportunity for education, teaching and research innovation in undergraduate education and teaching in forensic psychiatry. Interesting areas for development include simulated and coproduced education.


Asunto(s)
Psiquiatría , Estudiantes de Medicina , Humanos , Psiquiatría Forense , Psiquiatría/educación , Estudiantes , Curriculum
12.
Drug Discov Today ; 28(7): 103628, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37230284

RESUMEN

Fatty acid binding protein 5 (FABP5, or epidermal FABP) is an intracellular chaperone of fatty acid molecules that regulates lipid metabolism and cell growth. In patient-derived tumours, FABP5 expression is increased up to tenfold, often co-expressed with other cancer-related proteins. High tumoral FABP5 expression is associated with poor prognosis. FABP5 activates transcription factors (TFs) leading to increased expression of proteins involved in tumorigenesis. Genetic and pharmacological preclinical studies show that inhibiting FABP5 reduces protumoral markers, whereas elevation of FABP5 promotes tumour growth and spread. Thus, FABP5 might be a valid target for novel therapeutics. The evidence base is currently strongest for liver, prostate, breast, and brain cancers, and squamous cell carcinoma (SCC), which could represent relevant patient populations for any drug discovery programme.


Asunto(s)
Neoplasias , Masculino , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Ácidos Grasos/metabolismo , Proliferación Celular , Hígado/metabolismo , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo
13.
Adv Neonatal Care ; 23(5): 401-408, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37018178

RESUMEN

BACKGROUND: Increased noxious noise leads to adverse short-term and long-term effects on the growing neonate. The American Academy of Pediatrics recommends maintaining a noise level of less than 45 decibels (dBA). The average baseline noise level in an open-pod neonatal intensive care unit (NICU) was 62.6 dBA. PURPOSE: The purpose of this pilot project was to reduce the average noise levels by 39% at the end of an 11-week period. METHODS: The location of the project was in a large, high-acuity level IV open-pod layout NICU that consisted of 4 pods, one of which was cardiac-focused. The average baseline noise level in the cardiac pod was 62.6 dBA in a 24-hour period. Noise levels were not monitored before this pilot project. This project was implemented over an 11-week period. Several modes of education were used for parents and staff. Post-education, Quiet Times were implemented at set times twice daily. Noise levels were monitored for 4 weeks during Quiet Times, with weekly noise level updates for staff. General noise levels were collected a final time to evaluate the overall change in the average noise levels. RESULTS: At the end of the project, noise levels decreased from 62.6 dBA to 54 dBA, a 13.7% reduction. IMPLICATIONS FOR PRACTICE AND RESEARCH: At the end of this pilot project it was noted that: Online modules were the best way to educate staff. Parents should be included in the implementation of quality improvement. Healthcare providers need to know and understand that they can make preventative changes to improve the outcomes of the population.


Asunto(s)
Unidades de Cuidado Intensivo Neonatal , Mejoramiento de la Calidad , Recién Nacido , Humanos , Niño , Proyectos Piloto , Ruido/prevención & control , Personal de Salud
14.
Clin Cancer Res ; 29(14): 2651-2667, 2023 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-36780194

RESUMEN

PURPOSE: Anaplastic lymphoma kinase (ALK) aberrations have been identified in pediatric-type infant gliomas, but their occurrence across age groups, functional effects, and treatment response has not been broadly established. EXPERIMENTAL DESIGN: We performed a comprehensive analysis of ALK expression and genomic aberrations in both newly generated and retrospective data from 371 glioblastomas (156 adult, 205 infant/pediatric, and 10 congenital) with in vitro and in vivo validation of aberrations. RESULTS: ALK aberrations at the protein or genomic level were detected in 12% of gliomas (45/371) in a wide age range (0-80 years). Recurrent as well as novel ALK fusions (LRRFIP1-ALK, DCTN1-ALK, PRKD3-ALK) were present in 50% (5/10) of congenital/infant, 1.4% (3/205) of pediatric, and 1.9% (3/156) of adult GBMs. ALK fusions were present as the only candidate driver in congenital/infant GBMs and were sometimes focally amplified. In contrast, adult ALK fusions co-occurred with other oncogenic drivers. No activating ALK mutations were identified in any age group. Novel and recurrent ALK rearrangements promoted STAT3 and ERK1/2 pathways and transformation in vitro and in vivo. ALK-fused GBM cellular and mouse models were responsive to ALK inhibitors, including in patient cells derived from a congenital GBM. Relevant to the treatment of infant gliomas, we showed that ALK protein appears minimally expressed in the forebrain at perinatal stages, and no gross effects on perinatal brain development were seen in pregnant mice treated with the ALK inhibitor ceritinib. CONCLUSIONS: These findings support use of brain-penetrant ALK inhibitors in clinical trials across infant, pediatric, and adult GBMs. See related commentary by Mack and Bertrand, p. 2567.


Asunto(s)
Glioblastoma , Glioma , Ratones , Animales , Quinasa de Linfoma Anaplásico/genética , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Glioma/tratamiento farmacológico
15.
Neuro Oncol ; 25(1): 199-210, 2023 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-35604410

RESUMEN

BACKGROUND: The incidence and biology of IDH1/2 mutations in pediatric gliomas are unclear. Notably, current treatment approaches by pediatric and adult providers vary significantly. We describe the frequency and clinical outcomes of IDH1/2-mutant gliomas in pediatrics. METHODS: We performed a multi-institutional analysis of the frequency of pediatric IDH1/2-mutant gliomas, identified by next-generation sequencing (NGS). In parallel, we retrospectively reviewed pediatric IDH1/2-mutant gliomas, analyzing clinico-genomic features, treatment approaches, and outcomes. RESULTS: Incidence: Among 851 patients with pediatric glioma who underwent NGS, we identified 78 with IDH1/2 mutations. Among patients 0-9 and 10-21 years old, 2/378 (0.5%) and 76/473 (16.1%) had IDH1/2-mutant tumors, respectively. Frequency of IDH mutations was similar between low-grade glioma (52/570, 9.1%) and high-grade glioma (25/277, 9.0%). Four tumors were graded as intermediate histologically, with one IDH1 mutation. Outcome: Seventy-six patients with IDH1/2-mutant glioma had outcome data available. Eighty-four percent of patients with low-grade glioma (LGG) were managed observantly without additional therapy. For low-grade astrocytoma, 5-year progression-free survival (PFS) was 42.9% (95%CI:20.3-63.8) and, despite excellent short-term overall survival (OS), numerous disease-related deaths after year 10 were reported. Patients with high-grade astrocytoma had a 5-year PFS/OS of 36.8% (95%CI:8.8-66.4) and 84% (95%CI:50.1-95.6), respectively. Patients with oligodendroglioma had excellent OS. CONCLUSIONS: A subset of pediatric gliomas is driven by IDH1/2 mutations, with a higher rate among adolescents. The majority of patients underwent upfront observant management without adjuvant therapy. Findings suggest that the natural history of pediatric IDH1/2-mutant glioma may be similar to that of adults, though additional studies are needed.


Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Glioma , Adulto , Adolescente , Humanos , Niño , Estudios Retrospectivos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Glioma/genética , Glioma/terapia , Astrocitoma/genética , Mutación , Genómica , Isocitrato Deshidrogenasa/genética
16.
Gels ; 10(1)2023 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-38247741

RESUMEN

Osseous disease accounts for over half of chronic pathologies, but there is a limited supply of autografts, the gold standard; hence, there is a demand for new synthetic biomaterials. Herein, we present the use of a promising, new dairy-derived biomaterial: whey protein isolate (WPI) in the form of hydrogels, modified with the addition of different concentrations of the biotechnologically produced protein-like polymeric substance poly-γ-glutamic acid (γ-PGA) as a potential scaffold for tissue regeneration. Raman spectroscopic analysis demonstrated the successful creation of WPI-γ-PGA hydrogels. A cytotoxicity assessment using preosteoblastic cells demonstrated that the hydrogels were noncytotoxic and supported cell proliferation from day 3 to 14. All γ-PGA-containing scaffold compositions strongly promoted cell attachment and the formation of dense interconnected cell layers. Cell viability was significantly increased on γ-PGA-containing scaffolds on day 14 compared to WPI control scaffolds. Significantly, the cells showed markers of osteogenic differentiation; they synthesised increasing amounts of collagen over time, and cells showed significantly enhanced alkaline phosphatase activity at day 7 and higher levels of calcium for matrix mineralization at days 14 and 21 on the γ-PGA-containing scaffolds. These results demonstrated the potential of WPI-γ-PGA hydrogels as scaffolds for bone regeneration.

17.
J Physician Assist Educ ; 33(4): 296-301, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36409238

RESUMEN

INTRODUCTION: Given the 2019 Physician Assistant National Certifying Exam (PANCE) blueprint update from the National Commission on the Certification of Physician Assistants, it is imperative that programs conduct analyses of student performance metrics and PANCE scores. The purpose of this multi-institutional study was to examine the relationship between PANCE scores and student performance metrics/attributes from PA program graduates from 2017-2019. METHODS: A multiple linear regression was calculated to predict PANCE score indicators based on student attributes and performance metrics from 3 PA programs. Metrics included: PAEA End of Rotation exams, PACKRAT scores, academic performance in clinical medicine didactic courses, cumulative grade point average, and select demographic and admissions attributes (age, sex, and first generation to attend college). Descriptive statistics were employed to provide contextual information and an overview of the included data points. RESULTS: A significant regression equation was found with r-square of 0.709. Clinical Medicine II didactic course grades, PACKRAT I & II scores, and PAEA End of Rotation Exam scores in Family Medicine and Internal Medicine were all significant predictors of PANCE score. DISCUSSION: In consideration of the Accreditation Review Commission on Education for the Physician Assistant (ARC-PA) Standards and expectations for ongoing self-assessment, including PANCE analysis, this research was timely and necessary. To date, there is very limited research regarding student performance metrics given the PANCE blueprint update in 2019, and these data are critical to aid programs in ongoing development and best preparation for learners.


Asunto(s)
Asistentes Médicos , Humanos , Asistentes Médicos/educación , Benchmarking , Estudiantes , Universidades , Medicina Familiar y Comunitaria
20.
Acta Neuropathol ; 144(4): 733-746, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35982322

RESUMEN

Methylation profiling has radically transformed our understanding of tumors previously called central nervous system primitive neuro-ectodermal tumors (CNS-PNET). While this marks a momentous step toward defining key differences, reclassification has thrown treatment into disarray. To shed light on response to therapy and guide clinical decision-making, we report outcomes and molecular features of children with CNS-PNETs from two multi-center risk-adapted studies (SJMB03 for patients ≥ 3 years; SJYC07 for patients < 3 years) complemented by a non-protocol institutional cohort. Seventy patients who had a histological diagnosis of CNS-PNET or CNS embryonal tumor from one of the new categories that has supplanted CNS-PNET were included. This cohort was molecularly characterized by DNA methylation profiling (n = 70), whole-exome sequencing (n = 53), RNA sequencing (n = 20), and germline sequencing (n = 28). Clinical characteristics were detailed, and treatment was divided into craniospinal irradiation (CSI)-containing (SJMB03 and SJMB03-like) and CSI-sparing therapy (SJYC07 and SJYC07-like). When the cohort was analyzed in its entirety, no differences were observed in the 5-year survival rates even when CSI-containing therapy was compared to CSI-sparing therapy. However, when analyzed by DNA methylation molecular grouping, significant survival differences were observed, and treatment particulars provided suggestions of therapeutic response. Patients with CNS neuroblastoma with FOXR2 activation (CNS-NB-FOXR2) had a 5-year event-free survival (EFS)/overall survival (OS) of 66.7% ± 19.2%/83.3% ± 15.2%, and CIC rearranged sarcoma (CNS-SARC-CIC) had a 5-year EFS/OS both of 57.1% ± 18.7% with most receiving regimens that contained radiation (focal or CSI) and multidrug chemotherapy. Patients with high-grade neuroepithelial tumor with BCOR alteration (HGNET-BCOR) had abysmal responses to upfront chemotherapy-only regimens (5-year EFS = 0%), but survival extended with salvage radiation after progression [5-year OS = 53.6% ± 20.1%]. Patients with embryonal tumor with multilayered rosettes (ETMR) or high-grade glioma/glioblastoma multiforme (HGG/GBM) did not respond favorably to any modality (5-year EFS/OS = 10.7 ± 5.8%/17.9 ± 7.2%, and 10% ± 9.0%/10% ± 9.0%, respectively). As an accompaniment, we have assembled this data onto an interactive website to allow users to probe and query the cases. By reporting on a carefully matched clinical and molecular cohort, we provide the needed insight for future clinical management.


Asunto(s)
Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Glioblastoma , Neoplasias de Células Germinales y Embrionarias , Tumores Neuroectodérmicos Primitivos , Neoplasias Encefálicas/terapia , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/terapia , Niño , Factores de Transcripción Forkhead , Hospitales , Humanos , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/terapia
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