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1.
Case Rep Gastroenterol ; 18(1): 306-312, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015519

RESUMO

Introduction: Acute upper gastrointestinal bleeding is one of the most common medical emergencies that present to the hospital, and delineating the underlying etiology is essential to provide adequate definitive treatment. The purpose of this case report was to review the diagnosis and treatment of a rare complication known as radiation-induced hemorrhagic gastritis (RIHG) that can occur in patients with prior radiation exposure. The motivation for this study arose from the identification of a case within our institution. Case Presentation: The study involved a review of the diagnosis and management of a patient who presented with anemia and recurrent episodes of gastrointestinal bleeding at our institution after undergoing treatment for metastatic biliary adenocarcinoma. With the advent of new therapies, we aimed to investigate the various techniques utilized to manage these patients and highlight the importance of maintaining a high index of suspicion for RIHG as a potential etiology of gastrointestinal bleeding in patients with a relevant medical history of radiation exposure. Despite the literature review, we found that there is a lack of guidelines in the approach to the management of these patients. Conclusion: This case report underscores the rarity of radiation-induced gastritis and the complications that may arise from its diagnosis, including recurrent GI bleeding. Further investigation into identifying definitive treatment and creating guidelines for its management is desperately needed.

2.
Eur Radiol ; 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39030374

RESUMO

OBJECTIVES: The revised European Society of Musculoskeletal Radiology (ESSR) consensus guidelines on soft tissue tumor imaging represent an update of 2015 after technical advancements, further insights into specific entities, and revised World Health Organization (2020) and AJCC (2017) classifications. This second of three papers covers algorithms once histology is confirmed: (1) standardized whole-body staging, (2) special algorithms for non-malignant entities, and (3) multiplicity, genetic tumor syndromes, and pitfalls. MATERIALS AND METHODS: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements that had undergone interdisciplinary revision were scored online by the level of agreement (0 to 10) during two iterative rounds, that could result in 'group consensus', 'group agreement', or 'lack of agreement'. RESULTS: The three sections contain 24 statements with comments. Group consensus was reached in 95.8% and group agreement in 4.2%. For whole-body staging, pulmonary MDCT should be performed in all high-grade sarcomas. Whole-body MRI is preferred for staging bone metastasis, with [18F]FDG-PET/CT as an alternative modality in PET-avid tumors. Patients with alveolar soft part sarcoma, clear cell sarcoma, and angiosarcoma should be screened for brain metastases. Special algorithms are recommended for entities such as rhabdomyosarcoma, extraskeletal Ewing sarcoma, myxoid liposarcoma, and neurofibromatosis type 1 associated malignant peripheral nerve sheath tumors. Satisfaction of search should be avoided in potential multiplicity. CONCLUSION: Standardized whole-body staging includes pulmonary MDCT in all high-grade sarcomas; entity-dependent modifications and specific algorithms are recommended for sarcomas and non-malignant soft tissue tumors. CLINICAL RELEVANCE STATEMENT: These updated ESSR soft tissue tumor imaging guidelines aim to provide support in decision-making, helping to avoid common pitfalls, by providing general and entity-specific algorithms, techniques, and reporting recommendations for whole-body staging in sarcoma and non-malignant soft tissue tumors. KEY POINTS: An early, accurate, diagnosis is crucial for the prognosis of patients with soft tissue tumors. These updated guidelines provide best practice expert consensus for standardized imaging algorithms, techniques, and reporting. Standardization can improve the comparability examinations and provide databases for large data analysis.

3.
J Craniomaxillofac Surg ; 52(8): 906-913, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38997869

RESUMO

In children with juvenile idiopathic arthritis (JIA), the temporomandibular joint (TMJ) can be involved. To prevent TMJ damage due to inflammation, early recognition is important, for which contrast-enhanced magnetic resonance imaging (MRI) is the gold standard. In this study, the interobserver reliability and construct validity of the Juvenile Idiopathic Arthritis Magnetic Resonance Scoring System for Temporomandibular Joints (JAMRIS-TMJ) was assessed. Two radiologists independently examined 38 MRIs using the JAMRIS-TMJ scoring system. Inter-observer reliability was assessed by Cohen's (weighted) kappa (κ), 95% confidence intervals (CIs) and absolute agreement (%). Construct validity was assessed by correlation between the JAMRIS-TMJ items and TMJ involvement, active maximum interincisal mouth opening (AMIO), and anterior maximum voluntary bite force (AMVBF). The interobserver reliability for the JAMRIS-TMJ items varied from poor to good (κ = 0.18-0.61). Joint enhancement had the highest reliability (κ = 0.61). Correlations were found between TMJ involvement, AMIO, and the JAMRIS-TMJ items, although variation between radiologists and TMJ side existed. No correlation was found between AMVBF and the JAMRIS-TMJ items for both radiologists. The strongest correlations were found between most of the JAMRIS-TMJ items and AMIO. Our findings support the utility of AMIO as a clinical measure of TMJ status in children with JIA.


Assuntos
Artrite Juvenil , Imageamento por Ressonância Magnética , Transtornos da Articulação Temporomandibular , Humanos , Artrite Juvenil/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Criança , Feminino , Masculino , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Reprodutibilidade dos Testes , Adolescente , Variações Dependentes do Observador , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/patologia , Amplitude de Movimento Articular/fisiologia , Pré-Escolar , Força de Mordida
5.
J Eval Clin Pract ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39031802

RESUMO

RATIONALE: Healthcare systems remain disease oriented despite growing sustainability concerns caused by inadequate management of patients with multimorbidity. Comprehensive care programmes (CCPs) can play an important role in streamlining care delivery, but large differences in setup and results hinder firm conclusions on their effectiveness. Many elements for successful implementation of CCPs are identified, but strategies to overcome barriers and embed programmes within health systems remain unknown. AIMS AND OBJECTIVES: To address this knowledge gap through a detailed study of implementing a CCP in a Dutch hospital setting, including patient experiences, facilitators, barriers and ways to overcome those barriers. Additionally, this study aims to explore effects on patient satisfaction and healthcare use. METHODS: A qualitative study design with 39 semistructured interviews and focus groups between July 2020 and February 2023 with 16 patients and 17 involved professionals. Additionally, effects on quantitative outcomes for patient satisfaction (PACIC-20) and healthcare use were explored. RESULTS: Professionals expressed a wide range of topics related to implementation and ways to overcome barriers at hospital and system level. Alterations in the design to accommodate varying care demands, focus on inclusions through referrals, and lack of long-term support and appropriate financing were key topics. Patients expressed varying experiences, stated a strong desire for comprehensive information, and emphasised the importance of trust in caregivers. Patient satisfaction showed no effects, while healthcare use showed slight decreases in trends, but patient numbers were limited. CONCLUSION: The introduction of a CCP is feasible, and exploratory analysis on effectiveness shows lower hospital care use without decreasing patient satisfaction. However, this is accompanied by several challenges that show current fragmented systems still do not support implementation of integrated care initiatives. Overcoming those comes with substantial costs and may require a strong bottom-up implementation within a motivated team and actions on all levels of healthcare systems.

6.
Eur J Cancer ; 208: 114209, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-39018631

RESUMO

BACKGROUND: Adolescents and young adults (AYAs) with Ewing sarcoma have a worse prognosis than children. Population-based survival evaluations stratifying findings by important clinical factors are, however, limited. This Dutch population study comprehensively compared survival of children and AYAs with Ewing sarcoma over three decades considering diagnostic period, tissue of origin, tumor site, and disease stage. METHODS: Data on all children (0-17 years, N = 463) and AYAs (18-39 years, N = 379) diagnosed with Ewing sarcoma in the Netherlands between 1990-2018 were collected from the Netherlands Cancer Registry with follow-up until February 2023. Five-year relative survival was calculated using the cohort method. Multivariable analyses were conducted through Poisson regression. RESULTS: Children with Ewing sarcoma had a significantly higher 5-year relative survival than AYAs (65 % vs. 44 %). An increasing trend in survival was noted reaching 70 % in children and 53 % in AYAs in 2010-2018. Results were similar for Ewing bone sarcoma and extraosseous Ewing sarcoma. AYAs had a poorer prognosis than children for most tumor sites and regardless of disease stage. Survival probabilities were 60 % vs. 78 % for localized disease and 20 % vs. 33 % for metastatic disease. Multivariable-regression analysis, adjusted for follow-up time, diagnostic period, sex, disease stage, and tumor site, confirmed increased excess mortality among AYAs compared with children (excess HR: 1.7, 95 % CI: 1.3-2.1). CONCLUSIONS: Despite survival improvements since the 1990s, AYAs with Ewing sarcoma in the Netherlands continue to fare considerably worse than children. This survival disparity was present irrespective of tissue of origin, tumor site, and disease stage.

7.
J Med Educ Curric Dev ; 11: 23821205241262684, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882026

RESUMO

BACKGROUND: Animated videos have become popular in teaching medical students, although there is a certain lack of evidence concerning its efficacy. Surgery seems to be an ideal field for its application, since animations are very helpful to understand anatomic structures and complex procedures. The aim of this study was to investigate the effects of animated videos compared to textbooks on learning gain. METHODS: A prospective 2-arm cohort study with 5th-year medical students was conducted during their 2-week surgical training module. The initial cohort of students received textbook sections on 3 major topics in visceral surgery as learning medium (text cohort). During the following semester, the second cohort of students received 3 animated whiteboard videos (animated videos) containing equivalent content (video cohort). All participants completed a multiple-choice test consisting of 15 questions on the learning content at baseline (pre-test) and after the learning period (post-test) and answered an additional evaluation questionnaire. RESULTS: Both cohorts were similar in their descriptive data and demonstrated significant learning gain during the 2-week learning period. The video cohort achieved better results (80% vs 73% correct answers; P = .028) and a higher learning gain (17% vs 11%; P = .034) in the post-test compared to the text cohort. The estimated learning time was longer in the video cohort (62 min vs 37 min; P < .001) and watching the videos resulted in higher learning gain (21% vs 6%; P < .001). Subgroups with higher learning gain by video learning were female gender (20% vs 11%; P = .040), native German speakers (18% vs 11%; P = .009), students without prior surgical experience (19% vs 12%; P = .033) and those undecided concerning a surgical career (22% vs 9%; P = .020). Interestingly, "low digital orientation" students benefited from videos (22% vs 13%; P = .021), whereas "high digital orientation" students did not. CONCLUSIONS: Animated videos increase medical students' learning gain and interest in surgery.

8.
Pulm Circ ; 14(2): e12401, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38887741

RESUMO

Pulmonary hypertension (PH) is associated with adverse outcomes in chronic kidney disease (CKD) patients. Our study suggests mildly elevated pulmonary vascular resistance ( > 2 to ≤ 3) is independently associated with major adverse cardiovascular events at 1-year follow-up. Early diagnosis of precapillary PH in CKD patients can potentially improve clinical outcomes.

9.
Sci Rep ; 14(1): 12882, 2024 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839796

RESUMO

SARS-CoV2 infection results in a range of disease severities, but the underlying differential pathogenesis is still not completely understood. At presentation it remains difficult to estimate and predict severity, in particular, identify individuals at greatest risk of progression towards the most severe disease-states. Here we used advanced models with circulating serum analytes as variables in combination with daily assessment of disease severity using the SCODA-score, not only at single time points but also during the course of disease, to correlate analyte levels and disease severity. We identified a remarkably strong pro-inflammatory cytokine/chemokine profile with high levels for sCD163, CCL20, HGF, CHintinase3like1 and Pentraxin3 in serum which correlated with COVID-19 disease severity and overall outcome. Although precise analyte levels differed, resulting biomarker profiles were highly similar at early and late disease stages, and even during convalescence similar biomarkers were elevated and further included CXCL3, CXCL6 and Osteopontin. Taken together, strong pro-inflammatory marker profiles were identified in patients with COVID-19 disease which correlated with overall outcome and disease severity.


Assuntos
Biomarcadores , COVID-19 , Ativação de Macrófagos , Índice de Gravidade de Doença , COVID-19/sangue , COVID-19/imunologia , Humanos , Biomarcadores/sangue , Masculino , Feminino , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Citocinas/sangue , Síndrome da Liberação de Citocina/sangue , Adulto , Idoso , Componente Amiloide P Sérico/metabolismo , Componente Amiloide P Sérico/análise , Proteína C-Reativa
10.
Cureus ; 16(5): e60950, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38910607

RESUMO

INTRODUCTION: Ensuring patients follow preoperative and postoperative instructions is vital for maximizing surgical success. This pilot study investigates the feasibility of using monetary incentives through a nudge engine application-based model of omnichannel communication to prompt adherence to preoperative and postoperative instructions. METHODS: Over a six-month period, we conducted a longitudinal study employing the TheraPay® Rewards app at Maimonides Medical Center in Brooklyn, United States. Our recruitment efforts targeted English and Spanish-speaking patients with smartphones through in-person visits and phone calls. Participants received a $15 credit on a gift card for each completed task. The tasks included preoperative validations such as obtaining primary care physician clearance, completing preoperative assessments, undergoing preoperative scans with accompanying compact disks (CDs), and discontinuing specific medications. Postoperative validations included attending postoperative visits, proper incision care, discontinuation of narcotics at three weeks, and initiation of the first physical therapy session. RESULTS: We enrolled 16 patients with a mean age of 59.5 years (SD 11.68), the majority being male (n = 10, 62.5%). Preoperatively, task completion rates ranged from 83% to 100%. Postoperatively, rates varied from 20% to 100%. Preoperative task adherence averaged at 98.7% (SD 2.2%), while postoperative adherence averaged 60% (SD 21%). CONCLUSION: Our study indicates that financial incentives delivered through a gamified approach effectively encourage patients to complete essential preoperative tasks, suggesting a promise for enhancing adherence. Nonetheless, the decrease in postoperative task adherence highlights the necessity for careful implementation. Future investigations should compare cancellation rates and outcome measures to gain deeper insights into the effectiveness of app-based incentives in improving surgical outcomes and patient adherence.

11.
J Intell ; 12(6)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38921691

RESUMO

Standard learning assessments like multiple-choice questions measure what students know but not how their knowledge is organized. Recent advances in cognitive network science provide quantitative tools for modeling the structure of semantic memory, revealing key learning mechanisms. In two studies, we examined the semantic memory networks of undergraduate students enrolled in an introductory psychology course. In Study 1, we administered a cumulative multiple-choice test of psychology knowledge, the Intro Psych Test, at the end of the course. To estimate semantic memory networks, we administered two verbal fluency tasks: domain-specific fluency (naming psychology concepts) and domain-general fluency (naming animals). Based on their performance on the Intro Psych Test, we categorized students into a high-knowledge or low-knowledge group, and compared their semantic memory networks. Study 1 (N = 213) found that the high-knowledge group had semantic memory networks that were more clustered, with shorter distances between concepts-across both the domain-specific (psychology) and domain-general (animal) categories-compared to the low-knowledge group. In Study 2 (N = 145), we replicated and extended these findings in a longitudinal study, collecting data near the start and end of the semester. In addition to replicating Study 1, we found the semantic memory networks of high-knowledge students became more interconnected over time, across both domain-general and domain-specific categories. These findings suggest that successful learners show a distinct semantic memory organization-characterized by high connectivity and short path distances between concepts-highlighting the utility of cognitive network science for studying variation in student learning.

12.
Int J Obes (Lond) ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879729

RESUMO

BACKGROUND AND OBJECTIVES: Dual amylin and calcitonin receptor agonists (DACRAs) are therapeutic candidates in the treatment of obesity with beneficial effects on weight loss superior to suppression of food intake. Hence, suggesting effects on energy expenditure by possibly targeting mitochondria in metabolically active tissue. METHODS: Male rats with HFD-induced obesity received a DACRA, KBP-336, every third day for 8 weeks. Upon study end, mitochondrial respiratory capacity (MRC), - enzyme activity, - transcriptional factors, and -content were measured in perirenal (pAT) and inguinal adipose tissue. A pair-fed group was included to examine food intake-independent effects of KBP-336. RESULTS: A vehicle-corrected weight loss (23.4 ± 2.8%) was achieved with KBP-336, which was not observed to the same extent with the food-restricted weight loss (12.4 ± 2.8%) (P < 0.001). Maximal coupled respiration supported by carbohydrate and lipid-linked substrates was increased after KBP-336 treatment independent of food intake in pAT (P < 0.01). Moreover, oligomycin-induced leak respiration and the activity of citrate synthase and ß-hydroxyacetyl-CoA-dehydrogenase were increased with KBP-336 treatment (P < 0.05). These effects occurred without changes in mitochondrial content in pAT. CONCLUSIONS: These findings demonstrate favorable effects of KBP-336 on MRC in adipose tissue, indicating an increased energy expenditure and capacity to utilize fatty acids. Thus, providing more mechanistic insight into the DACRA-induced weight loss.

13.
J Clin Invest ; 134(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828727

RESUMO

Calcineurin inhibitors (CNIs) constitute the backbone of modern acute graft-versus-host disease (aGVHD) prophylaxis regimens but have limited efficacy in the prevention and treatment of chronic GVHD (cGVHD). We investigated the effect of CNIs on immune tolerance after stem cell transplantation with discovery-based single-cell gene expression and T cell receptor (TCR) assays of clonal immunity in tandem with traditional protein-based approaches and preclinical modeling. While cyclosporin and tacrolimus suppressed the clonal expansion of CD8+ T cells during GVHD, alloreactive CD4+ T cell clusters were preferentially expanded. Moreover, CNIs mediated reversible dose-dependent suppression of T cell activation and all stages of donor T cell exhaustion. Critically, CNIs promoted the expansion of both polyclonal and TCR-specific alloreactive central memory CD4+ T cells (TCM) with high self-renewal capacity that mediated cGVHD following drug withdrawal. In contrast to posttransplant cyclophosphamide (PT-Cy), CSA was ineffective in eliminating IL-17A-secreting alloreactive T cell clones that play an important role in the pathogenesis of cGVHD. Collectively, we have shown that, although CNIs attenuate aGVHD, they paradoxically rescue alloantigen-specific TCM, especially within the CD4+ compartment in lymphoid and GVHD target tissues, thus predisposing patients to cGVHD. These data provide further evidence to caution against CNI-based immune suppression without concurrent approaches that eliminate alloreactive T cell clones.


Assuntos
Inibidores de Calcineurina , Doença Enxerto-Hospedeiro , Isoantígenos , Células T de Memória , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/patologia , Animais , Camundongos , Isoantígenos/imunologia , Inibidores de Calcineurina/farmacologia , Doença Crônica , Células T de Memória/imunologia , Tacrolimo/farmacologia , Linfócitos T CD4-Positivos/imunologia , Ciclosporina/farmacologia , Feminino , Linfócitos T CD8-Positivos/imunologia , Subpopulações de Linfócitos T/imunologia
14.
Proc Natl Acad Sci U S A ; 121(27): e2406734121, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38913897

RESUMO

The Merovingian period (5th to 8th cc AD) was a time of demographic, socioeconomic, cultural, and political realignment in Western Europe. Here, we report the whole-genome shotgun sequence data of 30 human skeletal remains from a coastal Late Merovingian site of Koksijde (675 to 750 AD), alongside 18 remains from two Early to Late Medieval sites in present-day Flanders, Belgium. We find two distinct ancestries, one shared with Early Medieval England and the Netherlands, while the other, minor component, reflecting likely continental Gaulish ancestry. Kinship analyses identified no large pedigrees characteristic to elite burials revealing instead a high modularity of distant relationships among individuals of the main ancestry group. In contrast, individuals with >90% Gaulish ancestry had no kinship links among sampled individuals. Evidence for population structure and major differences in the extent of Gaulish ancestry in the main group, including in a mother-daughter pair, suggests ongoing admixture in the community at the time of their burial. The isotopic and genetic evidence combined supports a model by which the burials, representing an established coastal nonelite community, had incorporated migrants from inland populations. The main group of burials at Koksijde shows an abundance of >5 cM long shared allelic intervals with the High Medieval site nearby, implying long-term continuity and suggesting that similarly to Britain, the Early Medieval ancestry shifts left a significant and long-lasting impact on the genetic makeup of the Flemish population. We find substantial allele frequency differences between the two ancestry groups in pigmentation and diet-associated variants, including those linked with lactase persistence, likely reflecting ancestry change rather than local adaptation.


Assuntos
Linhagem , Humanos , História Medieval , Bélgica , Sepultamento/história , Genética Populacional/métodos , Feminino , Masculino , DNA Antigo/análise , Inglaterra , Migração Humana , Arqueologia , Países Baixos , Genoma Humano
15.
Immunity ; 57(7): 1648-1664.e9, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38876098

RESUMO

Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-major histocompatibility complexes (MHCs), though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient T cell receptor (TCR) frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4+ T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigens presented by gastrointestinal epithelium during an alloreactive response. The microbiota serves as a source of cognate antigens that contribute to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics.


Assuntos
Doença Enxerto-Hospedeiro , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/microbiologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T CD4-Positivos/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Microbiota/imunologia , Seleção Clonal Mediada por Antígeno , Transplante Homólogo , Teorema de Bayes , Transplante de Células-Tronco/efeitos adversos , Camundongos Endogâmicos BALB C , Microbioma Gastrointestinal/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
17.
Front Cell Dev Biol ; 12: 1379714, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872928

RESUMO

Chronic inflammatory enteropathies (CIEs) are an important group of diseases in dogs and involve complex pathogenetic aspects. Endoscopy and histopathology are vital for documenting the disease but are less useful for subclassifying CIEs and predicting the response to treatment. However, healing of the mucosal disease process (deep remission) and ultrastructural evaluation of the mucosa have received little attention in canine CIE. Given that canine CIE shares many similarities with inflammatory bowel diseases (IBDs) in human patients-and presents a good spontaneous disease model for human IBD-this perspective article evaluates the literature on ultrastructural lesions in canine CIE and human IBD and offers future directions for the study of ultrastructural mucosal lesions in canine CIE. Such lesions might have a higher sensitivity of detection than structural changes revealed upon light microscopy and may even precede or remain after the resolution of the clinical signs and histologic lesions.

18.
ACS Biomater Sci Eng ; 10(6): 3747-3758, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38753577

RESUMO

Improving the clinical translation of nanomedicine requires better knowledge about how nanoparticles interact with biological environments. As researchers are recognizing the importance of understanding the protein corona and characterizing how nanocarriers respond in biological systems, new tools and techniques are needed to analyze nanocarrier-protein interactions, especially for smaller size (<10 nm) nanoparticles like polyamidoamine (PAMAM) dendrimers. Here, we developed a streamlined, semiquantitative approach to assess dendrimer-protein interactions using a nondenaturing electrophoresis technique combined with mass spectrometry. With this protocol, we detect fluorescently tagged dendrimers and proteins simultaneously, enabling us to analyze when dendrimers migrate with proteins. We found that PAMAM dendrimers mostly interact with complement proteins, particularly C3 and C4a, which aligns with previously published data, verifying that our approach can be used to isolate and identify dendrimer-protein interactions.


Assuntos
Dendrímeros , Dendrímeros/química , Dendrímeros/metabolismo , Estudo de Prova de Conceito , Eletroforese , Humanos , Proteínas/química , Proteínas/metabolismo , Nanopartículas/química , Ligação Proteica
19.
Faraday Discuss ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38766993

RESUMO

Collisions of optically centrifuged CO2 molecules with J = 244-282 (Erot = 22 800-30 300 cm-1) are investigated with high-resolution transient IR absorption spectroscopy to reveal collisional and orientational phenomena of molecules with hyper-thermal rotational energies. The optical centrifuge is a non-resonant optical excitation technique that uses ultrafast, 800 nm chirped pulses to drive molecules to extreme rotational states through sequential Raman transitions. The extent of rotational excitation is controlled by tuning the optical bandwidth of the excitation pulses. Frequencies of 30 R-branch ν3 fundamental IR probe transitions are measured for the J = 186-282 states of CO2, expanding beyond previously reported IR transitions up to J = 128. The optically centrifuged molecules have oriented angular momentum and unidirectional rotation. Polarization-sensitive transient IR absorption of individual rotational states of optically centrifuged molecules and their collision products reveals information about collisional energy transfer, relaxation kinetics, and dynamics of rotation-to-translation energy transfer. The transient IR probe also measures the extent of polarization anisotropy. Rotational energy transfer for lower energy molecules is discussed in terms of statistical models and a comparison highlights the role of increasing energy gap with J and angular momentum of the optically centrifuged molecules.

20.
BMC Prim Care ; 25(1): 106, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575887

RESUMO

BACKGROUND: Dyspepsia is a commonly encountered clinical condition in Dutch general practice, which is often treated through the prescription of acid-reducing medication (ARM). However, recent studies indicate that the majority of chronic ARM users lack an indication for their use and that their long-term use is associated with adverse outcomes. We developed a patient-focussed educational intervention aiming to reduce low-value (chronic) use of ARM. METHODS: We conducted a randomized controlled study, and evaluated its effect on the low-value chronic prescription of ARM using data from a subset (n = 26) of practices from the Nivel Primary Care Database. The intervention involved distributing an educational waiting room posters and flyers informing both patients and general practitioners (GPs) regarding the appropriate indications for prescription of an ARM for dyspepsia, which also referred to an online decision aid. The interventions' effect was evaluated through calculation of the odds ratio of a patient receiving a low-value chronic ARM prescription over the second half of 2021 and 2022 (i.e. pre-intervention vs. post-intervention). RESULTS: In both the control and intervention groups, the proportion of patients receiving chronic low-value ARM prescriptions slightly increased. In the control group, it decreased from 50.3% in 2021 to 49.7% in 2022, and in the intervention group it increased from 51.3% in 2021 to 53.1% in 2022. Subsequent statistical analysis revealed no significant difference in low-value chronic prescriptions between the control and intervention groups (Odds ratio: 1.11 [0.84-1.47], p > 0.05). CONCLUSION: Our educational intervention did not result in a change in the low-value chronic prescription of ARM; approximately half of the patients of the intervention and control still received low-value chronic ARM prescriptions. The absence of effect might be explained by selection bias of participating practices, awareness on the topic of chronic AMR prescriptions and the relative low proportion of low-value chronic ARM prescribing in the intervention as well as the control group compared to an assessment conducted two years prior. TRIAL REGISTRATION: 10/31/2023 NCT06108817.


Assuntos
Dispepsia , Medicina Geral , Clínicos Gerais , Humanos , Prescrições de Medicamentos , Educação de Pacientes como Assunto , Países Baixos
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