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We present the case of a 62-year-old man with severe coronary artery disease who presented to the hospital in refractory ventricular fibrillation cardiac arrest. He showed signs of life despite prolonged resuscitation. We thus decided to initiate extracorporeal cardiopulmonary resuscitation (ECPR). The patient had a known total occlusion of his infrarenal aorta that had been surgically bypassed with a bifemoral-axillary graft. We successfully initiated ECPR via the surgical graft, establishing blood flow to the central circulation through the axillary artery in a peripheral configuration while ensuring blood flow to the left leg via the femoral-femoral graft. The patient was extubated neurologically intact the following day and subsequently underwent coronary artery bypass graft surgery while on extracorporeal membrane oxygenation (ECMO) support. He was subsequently weaned off inotropic support and decannulated from ECMO. He was discharged home neurologically intact and independent in his activities of daily living. This case demonstrates that cannulation for ECPR via a surgical vascular graft is possible and that a total occlusion of the infrarenal aorta in the presence of a surgical bypass is not an absolute contraindication to ECMO.
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Patients with heart failure (HF) and iron deficiency are at increased risk of adverse clinical outcomes. We searched databases for randomised controlled trials that compared IV iron to placebo, in patients with HF with reduced ejection fraction (HFrEF). A total of 7,813 participants, all having HFrEF with 3,998 receiving IV iron therapy, and 3,815 control recipients were included. There was a significant improvement in Kansas City Cardiomyopathy Questionnaire favouring IV iron with MD 7.39, 95% CI [3.55, 11.22], p = 0.0002. Subgroup analysis, based on acute and chronic HF, has displayed a sustained statistical significance. Additionally, a significant increase in the left ventricular ejection fraction % was observed, with MD 3.76, 95% CI [2.32, 5.21], p < 0.00001. A significant improvement in 6-min walk test was noted, with MD 34.87, 95% CI [20.02, 49.72], p < 0.00001. Furthermore, IV iron showed significant improvement in NYHA class, peak VO2, serum ferritin, and haemoglobin levels. Finally, despite the lack of difference in terms of all-cause hospitalisation and HF-related death, IV iron was associated with a significant reduction in HF-related, any cardiovascular reason hospitalisations, and all-cause death; which supports the need for implementation of IV iron as a standard of care in patients with HF and iron deficiency.
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Insuficiência Cardíaca , Ferro , Volume Sistólico , Humanos , Administração Intravenosa , Anemia Ferropriva/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Ferro/administração & dosagem , Ferro/uso terapêutico , Deficiências de FerroRESUMO
Background and Objectives: Patellar tendinopathy is difficult to treat, and when combined with partial rupture, there are additional challenges. The aim of this study was to evaluate the subjective outcome and return-to-sport status after ultrasound (US)- and colour doppler (CD)-guided wide awake local anaesthetic no tourniquet (WALANT) arthroscopic shaving in elite athletes. Material and Methods: Thirty Swedish and international elite athletes (27 males) with a long duration (>1 year) of persistent painful patellar tendinopathy in 35 patellar tendons, not responding to non-surgical treatment, were included. All patients were treated with the same protocol of arthroscopic shaving, including bone removal and debridement of partial rupture, followed by at least 3 months of structured rehabilitation. The VISA-P score and a study-specific questionnaire evaluating physical activity level and subjective satisfaction with the treatment were used for evaluation. Results: At the 2-year follow-up (mean 23, range 8-38 months), 25/30 patients (29/35 tendons) were satisfied with the treatment result and had returned to their pre-injury sport. The mean VISA-P score increased from 37 (range 7-69) before surgery to 80 (range 44-100) after surgery (p < 0.05). There was one drop-out (one tendon). There were no complications. Conclusions: US- and CD-guided WALANT arthroscopic shaving for persistent painful patellar tendinopathy, including bone removal and debridement of partial rupture, followed by structured rehabilitation showed good clinical results in the majority of the elite-level athletes.
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Artroscopia , Ligamento Patelar , Tendinopatia , Humanos , Masculino , Adulto , Feminino , Estudos Prospectivos , Tendinopatia/cirurgia , Artroscopia/métodos , Seguimentos , Ligamento Patelar/lesões , Ligamento Patelar/cirurgia , Atletas , Resultado do Tratamento , Adulto Jovem , Ruptura/cirurgia , Suécia , Ultrassonografia Doppler/métodos , AdolescenteRESUMO
Purpose: Midportion Achilles tendinopathy is a relatively common condition. This study aimed to investigate the presence of a normal Achilles tendon, but a tendinopathic plantaris tendon, in a large and consecutive prospective sample of patients referred to a specialised tendon clinic for midportion Achilles tendon pain not responding to non-surgical treatment. Patients and Methods: A total of 105 consecutive tendons were operated on in 81 patients (62 males) suffering from painful midportion Achilles tendon pain. Clinical examination, ultrasound (US) and colour Doppler (CD) examination, and wide awake local anaesthetic no tourniquet (WALANT) surgery were performed in all patients. Results: For 19/105 (18%) tendons from 14 patients, clinical examination suspected plantaris tendinopathy alone as there was a distinct tenderness on the medial side, but no thickening of the Achilles tendon. US examination followed by surgery confirmed the diagnosis. Conclusion: Midportion Achilles tendon pain is not always related to Achilles tendinopathy since pain related to the plantaris tendon alone was found in almost every fifth patient. Consequently, there is an obvious need for proper examination to identify the pain source and establish a correct diagnosis before treatment.
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Signal regulatory protein-α (SIRPα, SHPS-1, CD172a) expressed on myeloid cells transmits inhibitory signals when it engages its counter-receptor CD47 on an adjacent cell. Elevated CD47 expression on some cancer cells thereby serves as an innate immune checkpoint that limits phagocytic clearance of tumor cells by macrophages and antigen presentation to T cells. Antibodies and recombinant SIRPα constructs that block the CD47-SIRPα interaction on macrophages exhibit anti-tumor activities in mouse models and are in ongoing clinical trials for treating several human cancers. Based on prior evidence that engaging SIRPα can also alter CD47 signaling in some nonmalignant cells, we compared direct effects of recombinant SIRPα-Fc and a humanized CD47 antibody that inhibits CD47-SIRPα interaction (CC-90002) on CD47 signaling in cancer stem cells derived from the MDA-MB- 231 triple-negative breast carcinoma cell line. Treatment with SIRPα-Fc significantly increased the formation of mammospheres by breast cancer stem cells as compared to CC-90002 treatment or controls. Furthermore, SIRPα-Fc treatment upregulated mRNA and protein expression of ALDH1 and altered the expression of genes involved in epithelial/mesenchymal transition pathways that are associated with a poor prognosis and enhanced metastatic activity. This indicates that SIRPα-Fc has CD47-mediated agonist activities in breast cancer stem cells affecting proliferation and metastasis pathways that differ from those of CC-90002. This SIRPα-induced CD47 signaling in breast carcinoma cells may limit the efficacy of SIRPα decoy therapeutics intended to stimulate innate antitumor immune responses.
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Mutations in SETD2 are among the most prevalent drivers of renal cell carcinoma (RCC). We identified a novel single nucleotide polymorphism (SNP) in SETD2, E902Q, within a subset of RCC patients, which manifests as both an inherited or tumor-associated somatic mutation. To determine if the SNP is biologically functional, we used CRISPR-based genome editing to generate the orthologous mutation within the Drosophila melanogaster Set2 gene. In Drosophila, the homologous amino acid substitution, E741Q, reduces H3K36me3 levels comparable to Set2 knockdown, and this loss is rescued by reintroduction of a wild-type Set2 transgene. We similarly uncovered significant defects in spindle morphogenesis, consistent with the established role of SETD2 in methylating α-Tubulin during mitosis to regulate microtubule dynamics and maintain genome stability. These data indicate the Set2 E741Q SNP affects both histone methylation and spindle integrity. Moreover, this work further suggests the SETD2 E902Q SNP may hold clinical relevance.
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Carcinoma de Células Renais , Proteínas de Drosophila , Neoplasias Renais , Animais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Histonas/genética , Histonas/metabolismo , Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Polimorfismo de Nucleotídeo Único , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Fuso Acromático/genética , Fuso Acromático/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismoRESUMO
Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example, JAK2V617F, are common in the population, yet only a minority of carriers develop MPN. Here we show that the inherited polygenic loci that underlie common hematological traits influence JAK2V617F clonal expansion. We identify polygenic risk scores (PGSs) for monocyte count and plateletcrit as new risk factors for JAK2V617F positivity. PGSs for several hematological traits influenced the risk of different MPN subtypes, with low PGSs for two platelet traits also showing protective effects in JAK2V617F carriers, making them two to three times less likely to have essential thrombocythemia than carriers with high PGSs. We observed that extreme hematological PGSs may contribute to an MPN diagnosis in the absence of somatic driver mutations. Our study showcases how polygenic backgrounds underlying common hematological traits influence both clonal selection on somatic mutations and the subsequent phenotype of cancer.
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Transtornos Mieloproliferativos , Neoplasias , Humanos , Mutação , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/diagnóstico , Fenótipo , Janus Quinase 2/genética , Estratificação de Risco GenéticoRESUMO
BACKGROUND: High-pathogenicity avian influenza (HPAI) has become a conservation threat to wild birds. Therefore, suitable vaccine technology and practical application methods require investigation. METHODS: Twenty-four African penguins (Spheniscus demersus) were vaccinated with either a conventional inactivated clade 2.3.4.4b H5N8 HPAI whole virus or a tobacco leaf-produced H5 haemagglutinin-based virus-like particle (VLP). Six birds received a second dose of the inactivated vaccine. Antibody responses were assessed and compared by employing haemagglutination inhibition tests. RESULTS: A second dose of inactivated vaccine was required to induce antibody titres above the level required to suppress virus shedding, while a single dose of VLP vaccine produced these levels by day 14, and one bird still had antibodies on day 430. LIMITATIONS: Bacterial contamination of the VLP vaccine limited the monitoring period and sample size in that treatment group, and it was not possible to perform a challenge study with field virus. CONCLUSION: VLP vaccines offer a more practical option than inactivated whole viruses, especially in logistically challenging situations involving wild birds.
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Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A Subtipo H5N8 , Vacinas contra Influenza , Influenza Aviária , Spheniscidae , Animais , Influenza Aviária/prevenção & controle , Virulência , Galinhas , Vacinação/veterinária , Vacinas de Produtos InativadosRESUMO
Thrombospondin-1 is a secreted matricellular glycoprotein that modulates cell behavior by interacting with components of the extracellular matrix and with several cell surface receptors. Its presence in the extracellular matrix is induced by injuries that cause thrombospondin-1 release from platelets and conditions including hyperglycemia, ischemia, and aging that stimulate its expression by many cell types. Conversely, rapid receptor-mediated clearance of thrombospondin-1 from the extracellular space limits its sustained presence in the extracellular space and maintains sub-nanomolar physiological concentrations in blood plasma. Roles for thrombospondin-1 signaling, mediated by specific cellular receptors or by activation of latent TGFß, have been defined in T and B lymphocytes, natural killer cells, macrophages, neutrophils, and dendritic cells. In addition to regulating physiological nitric oxide signaling and responses of cells to stress, studies in mice lacking thrombospondin-1 or its receptors have revealed important roles for thrombospondin-1 in regulating immune responses in infectious and autoimmune diseases and antitumor immunity.
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Antígeno CD47 , Transdução de Sinais , Animais , Camundongos , Antígeno CD47/metabolismo , Transdução de Sinais/fisiologia , Matriz Extracelular/metabolismo , TrombospondinasRESUMO
Recent randomised trials have shown that clinical outcomes with transcatheter aortic valve implantation (TAVI) are non-inferior to surgical aortic valve replacement (SAVR) in patients with symptomatic aortic stenosis at intermediate to low risk. Health-related quality of life (HrQoL) outcomes in these patient groups remain uncertain. A systematic search of the literature was conducted that included nine trials and 11,295 patients. Kansas City Cardiomyopathy Questionnaire (KCCQ), a heart-failure-specific measure and EuroQol-5D (EQ-5D) (a generic health status tool) changes were the primary outcomes. New York Heart Association (NYHA) classification was the secondary outcome. Improvement in KCCQ scores was greater with TAVI (mean difference (MD)=13.56, 95% confidence interval (CI) 11.67-15.46, p<0.001) at 1 month, as was the improvement in EQ-5D (MD=0.07, 95% CI 0.05-0.08, p<0.001). There was no difference in KCCQ (MD=1.05, 95% CI -0.11 to 2.21, p=0.08) or EQ-5D (MD=-0.01, 95% CI -0.03 to 0.01), p=0.37) at 12 months. NYHA functional class 3/4 was lower in patients undergoing TAVI at 1 month (MD=0.51, 95% CI 0.34-0.78, p=0.002), but there was no difference at 12 months (MD=1.10; 95% CI 0.87-1.38, p=0.43). Overall, TAVI offers early benefit in HRQoL outcomes compared with SAVR, but they are equivalent at 12 months.
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Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Humanos , Qualidade de Vida , Estenose da Valva Aórtica/cirurgia , Valva Aórtica , Risco , Resultado do Tratamento , Fatores de RiscoRESUMO
Sarcopenia is a progressive disorder characterized by age-related loss of skeletal muscle mass and function. Although significant progress has been made over the years to identify the molecular determinants of sarcopenia, the precise mechanisms underlying the age-related loss of contractile function remains unclear. Advances in "omics" technologies, including mass spectrometry-based proteomic and metabolomic analyses, offer great opportunities to better understand sarcopenia. Herein, we performed mass spectrometry-based analyses of the vastus lateralis from young, middle-aged, and older rhesus monkeys to identify molecular signatures of sarcopenia. In our proteomic analysis, we identified proteins that change with age, including those involved in adenosine triphosphate and adenosine monophosphate metabolism as well as fatty acid beta oxidation. In our untargeted metabolomic analysis, we identified metabolites that changed with age largely related to energy metabolism including fatty acid beta oxidation. Pathway analysis of age-responsive proteins and metabolites revealed changes in muscle structure and contraction as well as lipid, carbohydrate, and purine metabolism. Together, this study discovers new metabolic signatures and offers new insights into the molecular mechanisms underlying sarcopenia for the evaluation and monitoring of a therapeutic treatment of sarcopenia.
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Setting priorities in healthcare is always contentious given the array of possible services at primary, secondary, and tertiary levels of care, not to mention potential public health interventions. The central goals in global policy have been reducing inequity within and between countries, protecting vulnerable groups (particularly women and children) and reducing the major communicable diseases which have historically been a major burden in lower- and middle-income countries. Here limited relative and absolute spending on healthcare have spurred a series of initiatives in Global Health over the last 50 years which have led to significant gains in measures of morbidity and mortality. Against this background there remains the continuing question of how to adapt current medical practice in higher income countries for training and planning of services in lower- and middle-income countries. Here, the historical development of Global Health is outlined, and lessons drawn from the surveys of the global burden of disease and health economic analysis to understand how we can apply these principles to define Global Hematology. It remains likely that in lower-income countries effort should be concentrated on developing laboratory services and blood transfusion, to allow safe and effective support for the assessment of treatment of anemia, sickle cell disease, maternal and child health and urgent surgery and obstetric services. However, the principles of Global Health, could also be used for hematological malignancies to develop a framework for Global Hematology for all settings.
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Anemia Falciforme , Hematologia , Criança , Humanos , Feminino , Anos de Vida Ajustados por Qualidade de Vida , Anos de Vida Ajustados por Deficiência , Fortalecimento Institucional , Transfusão de SangueRESUMO
A 12-year-old girl developed a distal femoral shaft fracture treated with lateral trochanteric entry intramedullary nail fixation. The nail was retained after union because of a persistent nonossifying fibroma at the previous fracture site. At 16 months after surgery, marked valgus deformity was noted at the distal femur, with signs of implant haloing and loosening, suggesting repetitive motion and stress concentration of forces at the distal femur. Owing to recognition before skeletal maturity, the valgus was corrected with hemiepiphysiodesis. This finding illustrates the importance of follow-up up to skeletal maturity for pediatric femoral shaft fractures and consideration of routine removal of implants after fracture union to avoid this previously unreported complication.
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Fraturas Femorais Distais , Fraturas do Fêmur , Fixação Intramedular de Fraturas , Feminino , Humanos , Criança , Adolescente , Fixação Intramedular de Fraturas/efeitos adversos , Pinos Ortopédicos/efeitos adversos , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/cirurgia , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Extremidade InferiorRESUMO
BACKGROUND: Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors. METHODS: STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site ("cluster") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions. DISCUSSION: The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency. TRIAL REGISTRATION: ISRCTN: 10412338. Registration date: October 24, 2019.
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Doadores de Sangue , Síncope Vasovagal , Humanos , Medicina Estatal , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/etiologia , Síncope Vasovagal/prevenção & controle , Água , Doação de SangueRESUMO
Sarcopenia is a progressive disorder characterized by age-related loss of skeletal muscle mass and function. Although significant progress has been made over the years to identify the molecular determinants of sarcopenia, the precise mechanisms underlying the age-related loss of contractile function remains unclear. Advances in omics technologies, including mass spectrometry-based proteomic and metabolomic analyses, offer great opportunities to better understand sarcopenia. Herein, we performed mass spectrometry-based analyses of the vastus lateralis from young, middle-aged, and older rhesus monkeys to identify molecular signatures of sarcopenia. In our proteomic analysis, we identified numerous proteins that change with age, including those involved in adenosine triphosphate and adenosine monophosphate metabolism as well as fatty acid beta oxidation. In our untargeted metabolomic analysis, we identified multiple metabolites that changed with age largely related to energy metabolism including fatty acid beta oxidation. Pathway analysis of age-responsive proteins and metabolites revealed changes in muscle structure and contraction as well as lipid, carbohydrate, and purine metabolism. Together, this study discovers new metabolic signatures and offer new insights into the molecular mechanism underlying sarcopenia for the evaluation and monitoring of therapeutic treatment of sarcopenia.
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Introduction: Bromodomain-containing Protein 4 (BRD4) is a transcriptional regulator which coordinates gene expression programs controlling cancer biology, inflammation, and fibrosis. In the context of airway viral infection, BRD4-specific inhibitors (BRD4i) block the release of pro-inflammatory cytokines and prevent downstream epithelial plasticity. Although the chromatin modifying functions of BRD4 in inducible gene expression have been extensively investigated, its roles in post-transcriptional regulation are not well understood. Given BRD4's interaction with the transcriptional elongation complex and spliceosome, we hypothesize that BRD4 is a functional regulator of mRNA processing. Methods: To address this question, we combine data-independent analysis - parallel accumulation-serial fragmentation (diaPASEF) with RNA-sequencing to achieve deep and integrated coverage of the proteomic and transcriptomic landscapes of human small airway epithelial cells exposed to viral challenge and treated with BRD4i. Results: We discover that BRD4 regulates alternative splicing of key genes, including Interferon-related Developmental Regulator 1 (IFRD1) and X-Box Binding Protein 1 (XBP1), related to the innate immune response and the unfolded protein response (UPR). We identify requirement of BRD4 for expression of serine-arginine splicing factors, splicosome components and the Inositol-Requiring Enzyme 1 IREα affecting immediate early innate response and the UPR. Discussion: These findings extend the transcriptional elongation-facilitating actions of BRD4 in control of post-transcriptional RNA processing via modulating splicing factor expression in virus-induced innate signaling.
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Processamento Alternativo , Proteínas Nucleares , Humanos , Proteínas Nucleares/genética , Proteômica , Fatores de Transcrição/genética , Inflamação/genética , Proteínas de Ciclo Celular/genéticaRESUMO
Structurally similar phytochemical compounds may elicit markedly different skin sensitization responses. Eugenol and isoeugenol are natural phenylpropanoids found in various essential oils are frequently used as fragrance ingredients in consumer products due to their pleasing aromatic properties. Both compounds are also skin sensitizers with isoeugenol being a stronger sensitizer than eugenol. The most commonly accepted mechanisms for haptenation by eugenol involve formation of a quinone methide or an ortho-quinone intermediate. The mechanism for the increased skin response to isoeugenol remains elusive, although quinone methide intermediates have been proposed. The recent identification of diastereomeric 7,4'-oxyneolignans as electrophilic, thiol-depleting isoeugenol derivatives has revived interest in the possible role of elusive reactive intermediates associated with the isoeugenol's haptenation process. In the present work, integrated non-animal skin sensitization methods were performed to determine the ability of syn-7,4'-oxyneolignan to promote haptenation and activation of further molecular pathways in keratinocytes and dendritic cells, confirming it as a candidate skin sensitizer. Kinetic NMR spectroscopic studies using dansyl cysteamine (DCYA) confirmed the first ordered nature of the nucleophilic addition for the syn-7,4'-oxyneolignan. Computational studies reaffirmed the "syn" stereochemistry of the isolated 7,4'-oxyneolignans along with that of their corresponding DCYA adducts and provided evidence for the preferential stereoselectivity. A plausible rationale for isoeugenol's strong skin sensitization is proposed based on the formation of a hydroxy quinone methide as a reactive intermediate rather than the previously assumed quinone methide.
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Eugenol , Indolquinonas , Pele/metabolismoRESUMO
INTRODUCTION: The chemokine receptor CXCR4 has been shown to be over-expressed in multiple types of cancer and is usually associated with aggressive phenotypes and poor prognosis. Successfully targeting and imaging the expression level of this receptor in tumours could inform treatment selection and facilitate patient stratification. METHODS: Known conjugates of AMD3100 that are specific to CXCR4 have been radiolabelled with gallium-68 and evaluated in naïve and tumour-bearing mice. Tumour uptake of the radiotracers was compared to the known CXCR4-specific PET imaging agent, [68Ga]Pentixafor. RESULTS: Ex vivo biodistribution in naïve animals showed CXCR4-mediated uptake in the liver with both radiotracers, confirmed by blocking experiments with the high affinity CXCR4 antagonist Cu2CB-Bicyclam (IC50 = 3 nM). PET/CT imaging studies revealed one tracer to have a higher accumulation in the tumour (SUVMean of 0.89 ± 0.14 vs 0.32 ± 0.11). CXCR4-specificity of the best performing tracer was confirmed by administration of a blocking dose of Cu2CB-Bicyclam, showing a 3- and 6-fold decrease in tumour and liver uptake, respectively. CONCLUSION AND ADVANCES IN KNOWLEDGE: This initial study offers some interesting insights on the impact of some structural features on the pharmacokinetics and metabolic stability of the radiotracer. Additionally, as Pentixafor only binds to human CXCR4, the development of CXCR4-targeted imaging agents that bind to the receptor across different species could significantly help with preclinical evaluation of new CXCR4-specific therapeutics.
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Complexos de Coordenação , Ciclamos , Neoplasias , Humanos , Animais , Camundongos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos de Gálio , Distribuição Tecidual , Tomografia por Emissão de Pósitrons/métodos , Peptídeos Cíclicos/farmacocinética , Receptores CXCR4/metabolismoRESUMO
Hyperspectral imaging and spectral analysis quantifies fluorophore concentration during fluorescence-guided surgery1-6. However, acquisition of the multiple wavelengths required to implement these methods can be time-consuming and hinder surgical workflow. To this end, a snapshot hyperspectral imaging system capable of acquiring 64 channels of spectral data simultaneously was developed for rapid hyperspectral imaging during neurosurgery. The system uses a birefringent spectral demultiplexer to split incoming light and redirect wavelengths to different sections of a large format microscope sensor. Its configuration achieves high optical throughput, accepts unpolarized input light and exceeds channel count of prior image-replicating imaging spectrometers by 4-fold. Tissue-simulating phantoms consisting of serial dilutions of the fluorescent agent characterize system linearity and sensitivity, and comparisons to performance of a liquid crystal tunable filter based hyperspectral imaging device are favorable. The new instrument showed comparable, if not improved, sensitivity at low fluorophore concentrations; yet, acquired wide-field images at more than 70-fold increase in frame rate. Image data acquired in the operating room during human brain tumor resection confirm these findings. The new device is an important advance in achieving real-time quantitative imaging of fluorophore concentration for guiding surgery.
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Neoplasias Encefálicas , Neurocirurgia , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Protoporfirinas , Imagem Óptica/métodos , Corantes FluorescentesRESUMO
Background and Objectives: Chronic painful midportion Achilles combined with plantaris tendinopathy can be a troublesome condition to treat. The objective was to prospectively follow patients subjected to ultrasound (US)- and color doppler (CD)-guided wide awake, local anesthetic, no-tourniquet (WALANT) surgery in a private setting. Material and Methods: Twenty-six Swedish patients (17 men and 9 women, mean age 50 years (range 29-62)) and eight international male patients (mean age of 38 years (range 25-71)) with combined midportion Achilles and plantaris tendinopathy in 45 tendons altogether were included. All patients had had >6 months of pain and had tried non-surgical treatment with eccentric training, without effect. US + CD-guided surgical scraping of the ventral Achilles tendon and plantaris removal under local anesthesia was performed on all patients. A 4-6-week rehabilitation protocol with an immediate full-weight-bearing tendon loading regime was used. The VISA-A score and a study-specific questionnaire evaluating physical activity level and subjective satisfaction with the treatment were used for evaluation. Results: At the 1-year follow-up, 32/34 patients (43 tendons) were satisfied with the treatment result and had returned to their pre-injury Achilles tendon loading activity. There were two dropouts (two tendons). For the Swedish patients, the mean VISA-A score increased from 34 (0-64) before surgery to 93 (61-100) after surgery (p < 0.001). There were two complications, one wound rupture and one superficial skin infection. Conclusions: For patients suffering from painful midportion Achilles tendinopathy and plantaris tendinopathy, US + CD-guided surgical Achilles tendon scraping and plantaris tendon removal showed a high satisfaction rate and good functional results 1 year after surgery.