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Rationale: In the upper respiratory tract, replicating (culturable) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recoverable for â¼4-8 days after symptom onset, but there is a paucity of data about the frequency and duration of replicating virus in the lower respiratory tract (i.e., the human lung).Objectives: We undertook lung tissue sampling (needle biopsy) shortly after death in 42 mechanically ventilated decedents during the Beta and Delta waves. An independent group of 18 ambulatory patients served as a control group.Methods: Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, and immunohistochemistry.Measurements and Main Results: Thirty-eight percent (16 of 42) of mechanically ventilated decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 wk) after symptom onset. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection (P < 0.05). Nasopharyngeal culture was negative in 23.1% (6 of 26) of decedents despite lung culture positivity. This hitherto undescribed biophenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary proinflammatory response but with concurrent viral culture positivity.Conclusions: Concurrent rather than sequential active viral replication continues to drive a heightened proinflammatory response in the human lung beyond the second week of illness and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe coronavirus disease (COVID-19).
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COVID-19 , SARS-CoV-2 , Humanos , Pulmão , Teste para COVID-19 , Replicação ViralRESUMO
Fundamental frequency ( fo) is the most perceptually salient vocal acoustic parameter, yet little is known about how its perceptual influence varies across societies. We examined how fo affects key social perceptions and how socioecological variables modulate these effects in 2,647 adult listeners sampled from 44 locations across 22 nations. Low male fo increased men's perceptions of formidability and prestige, especially in societies with higher homicide rates and greater relational mobility in which male intrasexual competition may be more intense and rapid identification of high-status competitors may be exigent. High female fo increased women's perceptions of flirtatiousness where relational mobility was lower and threats to mating relationships may be greater. These results indicate that the influence of fo on social perceptions depends on socioecological variables, including those related to competition for status and mates.
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Voz , Adulto , Humanos , Masculino , Feminino , Homicídio , Percepção Social , Parceiros SexuaisRESUMO
Experimental in vitro models that capture pathophysiological characteristics of human tumours are essential for basic and translational cancer biology. Here, we describe a fully synthetic hydrogel extracellular matrix designed to elicit key phenotypic traits of the pancreatic environment in culture. To enable the growth of normal and cancerous pancreatic organoids from genetically engineered murine models and human patients, essential adhesive cues were empirically defined and replicated in the hydrogel scaffold, revealing a functional role of laminin-integrin α3/α6 signalling in establishment and survival of pancreatic organoids. Altered tissue stiffness-a hallmark of pancreatic cancer-was recapitulated in culture by adjusting the hydrogel properties to engage mechano-sensing pathways and alter organoid growth. Pancreatic stromal cells were readily incorporated into the hydrogels and replicated phenotypic traits characteristic of the tumour environment in vivo. This model therefore recapitulates a pathologically remodelled tumour microenvironment for studies of normal and pancreatic cancer cells in vitro.
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Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/metabolismo , Animais , Matriz Extracelular , Humanos , Hidrogéis/metabolismo , Camundongos , Organoides , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Microambiente TumoralRESUMO
BACKGROUND: Acute hematogenous osteomyelitis (AHO) is a relatively common condition in children, and identifying the offending pathogen with blood or tissue cultures aids in diagnosis and medical management while reducing treatment failure. Recent 2021 AHO clinical practice guidelines from the Pediatric Infectious Disease Society recommend obtaining routine tissue cultures, particularly in cases with negative blood cultures. The purpose of this study was to identify variables associated with positive tissue cultures when blood cultures are negative. METHODS: Children with AHO from 18 pediatric medical centers throughout the United States through the Children's ORthopaedic Trauma and Infection Consortium for Evidence-based Study were evaluated for predictors of positive tissue cultures when blood cultures were negative. Cutoffs of predictors were determined with associated sensitivity and specificity. RESULTS: One thousand three children with AHO were included, and in 688/1003 (68.6%) patients, both blood cultures and tissue cultures were obtained. In patients with negative blood cultures (n=385), tissue was positive in 267/385 (69.4%). In multivariate analysis, age ( P <0.001) and C-reactive protein (CRP) ( P =0.004) were independent predictors. With age >3.1 years and CRP >4.1 mg/dL as factors, the sensitivity of obtaining a positive tissue culture when blood cultures were negative was 87.3% (80.9-92.2%) compared with 7.1% (4.4-10.9%) if neither of these factors was present. There was a lower ratio of methicillin-resistant Staphylococcus aureus in blood culture-negative patients who had a positive tissue culture 48/188 (25.5%), compared with patients who had both positive blood and tissue cultures 108/220 (49.1%). CONCLUSION: AHO patients with CRP ≤ 4.1 mg/dL and age under 3.1 years are unlikely to have clinical value from tissue biopsy that exceeds the morbidity associated with this intervention. In patients with CRP > 4.1 mg/dL and age over 3.1 years, obtaining a tissue specimen may add value; however, it is important to note that effective empiric antibiotic coverage may limit the utility of positive tissue cultures in AHO. LEVEL OF EVIDENCE: Level III-Retrospective comparative study.
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Staphylococcus aureus Resistente à Meticilina , Osteomielite , Criança , Humanos , Pré-Escolar , Proteína C-Reativa/análise , Hemocultura , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Osteomielite/complicações , Doença AgudaRESUMO
BACKGROUND: Pediatric acute hematogenous osteomyelitis (AHO) outcomes are highly dependent on the disease severity. Recently, the A-SCORE and C-SCORE, were proposed as predictors of an acute complicated course and chronic morbidity, respectively. The purpose of this study was to externally validate the A-SCORE and C-SCORE at a single institution. METHODS: This IRB-approved retrospective chart review included AHO patients admitted at a tertiary referral hospital between October 1, 2015 and December 31, 2019. The inclusion criteria were ages 0 to 18 and clinical response to treatment. The exclusion criteria were immunocompromised status or penetrating inoculation. RESULTS: The A-SCORE demonstrated an area under the receiver operator curve (ROC area) of >86% with regards to all acute complications. It also demonstrated sensitivities >85% and specificities >92% at the cut-off of 4 (Youden index) for all acute complications. The C-SCORE demonstrated an ROC area of 100% with regards to chronic osteomyelitis. It also demonstrated sensitivities >70% and specificities >93% for the chronic morbidity variables seen in our population at the cut-off of 3 (Youden index.). CONCLUSIONS: These novel composite clinical scores, in combination with clinical judgment, could help guide early care decisions. The A-SCORE and C-SCORE are useful risk stratification tools in the management of pediatric AHO and in predicting acute complicated courses or chronic sequelae of AHO, respectively. These scoring systems, if integrated into standardized pediatric AHO guidelines, can allow clinicians to stratify the AHO population and guide clinical decision making. LEVEL OF EVIDENCE: Level III (prognostic study, retrospective chart review).
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Osteomielite , Doença Aguda , Adolescente , Criança , Pré-Escolar , Hospitalização , Humanos , Lactente , Recém-Nascido , Osteomielite/epidemiologia , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: The surgical indications to manage children with acute hematogenous osteomyelitis (AHO) remain poorly defined. The purpose of this study was to identify if practice pattern variation exists in the surgical management of pediatric AHO among tertiary pediatric medical centers across the United States. A secondary purpose was to evaluate variables that may impact the rate of surgical intervention among these institutions. METHODS: Children with AHO were retrospectively analyzed between January 1, 2010, and December 31, 2016, from 18 pediatric medical centers throughout the United States. The rates of surgery were identified. Admission vitals, labs, weight-bearing status, length of stay, and readmission rates were compared between those who did and did not undergo surgery. Multivariate regression and classification and regression tree analyses were performed to identify the variables that were associated with surgical intervention. RESULTS: Of the 1003 children identified with AHO in this retrospective, multicenter database, 619/1003 (62%) were treated surgically. Multivariate analysis revealed institution, inability to ambulate, presence of multifocal infection, elevated admission C-reactive protein, increased admission platelet count, and location of the osteomyelitis were significant predictors of surgery (P<0.01). Patients who underwent surgery were more than twice as likely to have a recurrence or readmission and stayed a median of 2 days longer than those who did not have surgery. In the classification and regression tree analysis, 2 distinct patterns of surgical intervention were identified based on institution, with 12 institutions operating in most cases (72%), regardless of clinical factors. A second cohort of 6 institutions operated less routinely, with 47% receiving surgery overall. At these 6 institutions, patients without multifocal infection only received surgery 26% of the time, which increased to 74% with multifocal infection and admission erythrocyte sedimentation rate >37.5 mm/h. CONCLUSIONS: This study is the first to objectively identify significant differences in the rates of surgical management of pediatric AHO across the United States. Variation in the surgical management of AHO appears to be driven primarily based on institutional practice. Twelve institutions operated on 72% of patients, regardless of the severity of disease, indicating that the institution custom or dogma may drive the surgical indications. Six institutions relied more on clinical judgment with significant variability in rates of surgical intervention (26% vs. 74%), depending on the severity of the disease. Surgical intervention is associated with increased recurrence, readmission, and hospital length of stay. As a result of these findings, it is essential to prospectively study the appropriate surgical indications and measure the outcomes in children with pediatric AHO. LEVEL OF EVIDENCE: Level III.
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Osteomielite , Doença Aguda , Sedimentação Sanguínea , Criança , Hospitalização , Humanos , Osteomielite/tratamento farmacológico , Osteomielite/cirurgia , Estudos RetrospectivosRESUMO
Sarcomas are a rare group of mesenchymal cancers comprising over 70 different histological subtypes. For the majority of these diseases, the molecular understanding of the basis of their initiation and progression remains unclear. As such, limited clinical progress in prognosis or therapeutic regimens have been made over the past few decades. Proteomics techniques are being increasingly utilised in the field of sarcoma research. Proteomic research efforts have thus far focused on histological subtype characterisation for the improvement of biological understanding, as well as for the identification of candidate diagnostic, predictive, and prognostic biomarkers for use in clinic. However, the field itself is in its infancy, and none of these proteomic research findings have been translated into the clinic. In this review, we provide a brief overview of the proteomic strategies that have been employed in sarcoma research. We evaluate key proteomic studies concerning several rare and ultra-rare sarcoma subtypes including, gastrointestinal stromal tumours, osteosarcoma, liposarcoma, leiomyosarcoma, malignant rhabdoid tumours, Ewing sarcoma, myxofibrosarcoma, and alveolar soft part sarcoma. Consequently, we illustrate how routine implementation of proteomics within sarcoma research, integration of proteomics with other molecular profiling data, and incorporation of proteomics into clinical trial studies has the potential to propel the biological and clinical understanding of this group of complex rare cancers moving forward.
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Proteoma , Proteômica , Sarcoma/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores , Descoberta de Drogas , Humanos , Terapia de Alvo Molecular , Proteômica/métodos , Sarcoma/diagnóstico , Sarcoma/tratamento farmacológico , Sarcoma/etiologiaRESUMO
AIMS: The current study aimed to explore differences in adverse outcomes between youth and adolescents with fetal alcohol spectrum disorder (FASD) living in child welfare care (i.e., foster care or group home) with those living with their biological parent(s) or with adoptive or other family member(s) in Canada. METHODS: Data gathered from the Canadian National FASD Database were used for analysis. A total of 665 youth and adolescents with a clinical diagnosis of FASD under the age of 18 living in child welfare care, with biological, adoptive or other family members, were included in the sample. Key areas examined included living situation, legal problems, experience of sexual or physical abuse, mental health (anxiety, conduct disorder, mood disorder and post-traumatic stress disorder) and suicidal ideation. Descriptive statistics and chi-square comparisons were utilized to explore these differences. RESULTS: Results revealed a significantly higher rate of reported sexual and physical abuse among individuals in child welfare care compared with those living with biological parents or with adoptive or other family member(s). Rates of difficulty with the law were also higher among those in child welfare care compared with adoptive/other family members. Conversely, the rate of mood disorders was significantly higher among those living with adoptive/other family members compared with child welfare care. Results highlight similar rates of reported suicidal ideation/attempts across all living situations, as well as mental health concerns. CONCLUSIONS: Results offer rare insight into the lives of youth and adolescents under age 18 with diagnosed FASD who reside in child welfare care in contrast to those living with biological parent(s) or with adoptive or other family members. These findings increase our awareness of the complexity of mental health concerns and suicide risk across all living environments. Results have further implications for policy, practice and clinical intervention.
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Transtornos do Espectro Alcoólico Fetal , Adolescente , Canadá/epidemiologia , Criança , Proteção da Criança , Feminino , Transtornos do Espectro Alcoólico Fetal/epidemiologia , Humanos , Saúde Mental , Gravidez , Ideação SuicidaRESUMO
OBJECTIVES: We measured carbon and nitrogen isotopic ratios in a contemporary population, and tested how the isotopic variability relates to measures of socioeconomic status (e.g., household wealth) and anthropometric measures (e.g., standardized height-for-age and weight-for-age z-scores). METHODS: Hair samples from individuals living in the Bosawas Biosphere Reserve in Nicaragua were analyzed for δ13 C and δ15 N, and these data were examined in relation to individual (e.g., age, sex, anthropometrics) and household (e.g., household size, wealth) variables. RESULTS: We found through mixed-effects modeling that δ13 C and δ15 N varied predictably with individual age and household wealth. δ13 C and δ15 N did not, however, improve models predicting variation in individual anthropometric measures. CONCLUSION: These results indicate that, although there is a relationship between diet (δ13 C and δ15 N) and socioeconomic variables, these dietary differences are not the main cause of health differences in this population.
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Dieta , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Classe Social , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Demografia , Feminino , Humanos , Masculino , Nicarágua , Adulto JovemRESUMO
In the United States, legislative actions in over 28 states require radiologists to notify women who undergo breast screening mammography of their breast density. This has led to increased public interest in supplemental screening, but radiologists have not come to a consensus on a supplemental screening modality. In choosing between the most common options, whole-breast ultrasonography (US) and magnetic resonance (MR) imaging, one must weigh the benefits and drawbacks of each modality, as increased cancer detection may be accompanied by increased examination costs and biopsy rates. There has been recent interest in molecular breast imaging (MBI) for supplemental screening because of its high sensitivity, as well as its high specificity. This article describes how MBI fits into clinical practice alongside digital breast tomosynthesis (DBT), targeted US, and MR imaging. The authors describe their approach to breast cancer screening, which uses DBT as the primary imaging modality. DBT is complemented by automated density calculations and supplemented with functional imaging techniques, including MR imaging or MBI, for women with dense breasts. An algorithm based on the patient's breast cancer risk is used to determine if either MR imaging or MBI for supplemental screening is appropriate. MBI is also used as a problem-solving tool for the evaluation of clinical indications following complex mammography or US, or for unexplained physical findings. This article describes aspects related to implementing MBI in clinical practice, including the clinical workflow, patient management, radioactive tracer administration, and procedure reimbursement. © RSNA, 2017.
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Neoplasias da Mama/diagnóstico por imagem , Imagem Molecular/métodos , Resolução de Problemas , Adulto , Idoso , Algoritmos , Biópsia , Densidade da Mama , Tomada de Decisões , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Mamografia , Pessoa de Meia-Idade , Ohio , Doses de Radiação , Medição de Risco , Sensibilidade e Especificidade , Software , Ultrassonografia MamáriaRESUMO
OBJECTIVE: The Affordable Care Act places primary care at the cornerstone of health maintenance. It is believed that increasing access to primary health care providers will limit emergency department (ED) use. This study examines woman's health-related ED visits by patients enrolled in an obstetric/gynecologic (OB/GYN) clinic. METHODS: A database was created combining patient information from a hospital-affiliated OB/GYN clinic and the electronic medical records from the ED of the affiliated hospital. This database was used to evaluate woman's health-related ED use by patients registered in this OB/GYN clinic compared with patients not affiliated with the clinic. RESULTS: Over an 23-month period, there were 41,791 ED visits made by 21,223 individual women >12 years of age. A total of 7251 (17.4%) of the ED visits were for OB/GYN-related conditions. There were 6430 individual women registered at the OB/GYN clinic, 1411 (22.0%) of whom made 2415 woman's health-related visits to the ED. Of the OB/GYN-related ED visits by clinic patients, 1794 (74.3%) were made during weekdays and 1023 (42.3%) were made during hours when the clinic was open for care. Study patients had diagnostic studies beyond a urine analysis or pregnancy test performed during 61% of ED visits, with an admission rate of 2%. CONCLUSION: Enrollment with a primary care provider alone does not eliminate the need for ED use in women with health-related conditions.
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Serviço Hospitalar de Emergência/estatística & dados numéricos , Ginecologia , Obstetrícia , Atenção Primária à Saúde/estatística & dados numéricos , Saúde da Mulher , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Recursos HumanosRESUMO
BACKGROUND: Adolescents and young adult (AYA) patients with soft tissue tumours including sarcomas are an underserved group with disparities in treatment outcomes. METHODS: To define the molecular features between AYA and older adult (OA) patients, we analysed the proteomic profiles of a large cohort of soft tissue tumours across 10 histological subtypes (AYA n = 66, OA n = 243), and also analysed publicly available functional genomic data from soft tissue tumour cell lines (AYA n = 5, OA n = 8). RESULTS: Biological hallmarks analysis demonstrates that OA tumours are significantly enriched in MYC targets compared to AYA tumours. By comparing the patient-level proteomic data with functional genomic profiles from sarcoma cell lines, we show that the mRNA splicing pathway is an intrinsic vulnerability in cell lines from OA patients and that components of the spliceosome complex are independent prognostic factors for metastasis free survival in AYA patients. CONCLUSIONS: Our study highlights the importance of performing age-specific molecular profiling studies to identify risk stratification tools and targeted agents tailored for the clinical management of AYA patients.
Soft tissue tumours are cancers that develop in the connective and supporting tissues of the body, such as muscle or fat. These tumours arise in patients across the entire age range. However, improvements in survival outcomes in adolescent and young adult (AYA) patients have lagged behind outcomes in older adults (OA) and children. To better understand the biology of AYA patients with soft tissue tumours, we analysed protein profiles across 10 different types. We identified biological differences between AYA and OA patients and report an age-specific signature that can potentially be used to help predict which AYA patients are more likely to have aggressive cancers that will spread to other parts of the body. Our study highlights the importance of performing age-specific studies to identify new tools to predict patient outcomes and potentially find more suitable treatments.
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PURPOSE: The landscape of extracellular matrix (ECM) alterations in soft tissue sarcomas (STS) remains poorly characterized. We aimed to investigate the tumor ECM and adhesion signaling networks present in STS and their clinical implications. EXPERIMENTAL DESIGN: Proteomic and clinical data from 321 patients across 11 histological subtypes were analyzed to define ECM and integrin adhesion networks. Subgroup analysis was performed in leiomyosarcomas (LMS), dedifferentiated liposarcomas (DDLPS), and undifferentiated pleomorphic sarcomas (UPS). RESULTS: This analysis defined subtype-specific ECM profiles including enrichment of basement membrane proteins in LMS and ECM proteases in UPS. Across the cohort, we identified three distinct coregulated ECM networks which are associated with tumor malignancy grade and histological subtype. Comparative analysis of LMS cell line and patient proteomic data identified the lymphocyte cytosolic protein 1 cytoskeletal protein as a prognostic factor in LMS. Characterization of ECM network events in DDLPS revealed three subtypes with distinct oncogenic signaling pathways and survival outcomes. Evaluation of the DDLPS subtype with the poorest prognosis nominates ECM remodeling proteins as candidate antistromal therapeutic targets. Finally, we define a proteoglycan signature that is an independent prognostic factor for overall survival in DDLPS and UPS. CONCLUSIONS: STS comprise heterogeneous ECM signaling networks and matrix-specific features that have utility for risk stratification and therapy selection, which could in future guide precision medicine in these rare cancers.
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Matriz Extracelular , Proteômica , Sarcoma , Humanos , Matriz Extracelular/metabolismo , Sarcoma/patologia , Sarcoma/genética , Sarcoma/metabolismo , Proteômica/métodos , Prognóstico , Feminino , Masculino , Transdução de Sinais , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND: High-risk soft tissue sarcomas of the extremities and trunk wall (eSTS), as defined by the Sarculator nomogram, are more likely to benefit from (neo)adjuvant anthracycline-based therapy compared to low/intermediate-risk patients. The biology underpinning these differential treatment outcomes remain unknown. METHODS: We analysed proteomic profiles and clinical outcomes of 123 eSTS patients. A Cox model for overall survival including the Sarculator was fitted to individual data to define four risk groups. A DNA replication protein signature-Sarcoma Proteomic Module 6 (SPM6) was evaluated for association with clinicopathological factors and risk groups. SPM6 was added as a covariate together with Sarculator in a multivariable Cox model to assess improvement in prognostic risk stratification. RESULTS: DNA replication and cell cycle proteins were upregulated in high-risk versus very low-risk patients. Evaluation of the functional effects of CRISPR-Cas9 gene knockdown of proteins enriched in high-risk patients using the cancer cell line encyclopaedia database identified candidate drug targets. SPM6 was significantly associated with tumour malignancy grade (p = 1.6e-06), histology (p = 1.4e-05) and risk groups (p = 2.6e-06). Cox model analysis showed that SPM6 substantially contributed to a better calibration of the Sarculator nomogram (Index of Prediction Accuracy = 0.109 for Sarculator alone versus 0.165 for Sarculator + SPM6). CONCLUSIONS: Risk stratification of patient with STS is defined by distinct biological pathways across a range of cancer hallmarks. Incorporation of SPM6 protein signature improves prognostic risk stratification of the Sarculator nomogram. This study highlights the utility of integrating protein signatures for the development of next-generation nomograms.
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Extremidades , Nomogramas , Proteômica , Sarcoma , Humanos , Masculino , Feminino , Sarcoma/metabolismo , Sarcoma/genética , Sarcoma/patologia , Sarcoma/mortalidade , Pessoa de Meia-Idade , Prognóstico , Proteômica/métodos , Extremidades/patologia , Medição de Risco/métodos , Adulto , Idoso , Tronco , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
Osteoarticular infections (OAI) are a significant cause of morbidity and mortality. Cultures and serology are some of the gold standards for identifying infection but are often unable to provide a timely diagnosis or a diagnosis at all. Genetic testing offers capabilities that other modalities lack. Polymerase chain reaction has multiple versions with various costs and turnaround times. This technology has become implemented in multiple pediatric center OAI diagnostic protocols. There is sufficient literature documenting effectiveness in certain clinical situations, especially with fastidious organism diagnosis, but significant limitation still exists. Metagenomic next-generation sequencing is an unbiased or hypothesis-free modality with the capability to detect the genetic material of bacteria, viruses, parasites, fungi, and humans from a single sample. Potential benefits include pathogen identification unaffected by antimicrobial administration, detection of fastidious organisms more quickly, delineation of pathogens in polymicrobial infections, antimicrobial susceptibility, and avoidance of invasive procedures. It is a resource-intensive modality with little standardization of the complex processes. Appropriate use and definitive clinical impact have yet to be determined.
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Phytochemicals are promising therapeutics for various neurodegenerative disorders, including Parkinson's disease (PD). However, their efficacy, pharmacokinetic properties, and penetration across the blood-brain barrier can be improved using delivery systems such as nanoparticles. We reviewed recently published work in which nanoparticles were used to deliver phytochemicals toward PD treatment. The studies show that nanoparticles not only improve the pharmacological effect of the phytochemicals but also enable targeting to the brain and crossing of the blood-brain barrier. Various ligands were added to the nanoparticles to improve blood-brain barrier transportation. The promising findings from the published studies reveal that more research into nanophytomedicine approaches as therapeutic targets for PD is warranted, especially since they have the potential to protect against key features of PD, including α-synuclein aggregation, mitochondrial dysfunction, and dopaminergic neuronal death. Furthermore, future directions should involve smart designs to tailor nanoparticles for improved therapeutic delivery by modifying their features, such as architecture, surface and material properties, targeting ligands, and responsiveness.
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Soft tissue sarcomas (STS) are rare and diverse mesenchymal cancers with limited treatment options. Here we undertake comprehensive proteomic profiling of tumour specimens from 321 STS patients representing 11 histological subtypes. Within leiomyosarcomas, we identify three proteomic subtypes with distinct myogenesis and immune features, anatomical site distribution and survival outcomes. Characterisation of undifferentiated pleomorphic sarcomas and dedifferentiated liposarcomas with low infiltrating CD3 + T-lymphocyte levels nominates the complement cascade as a candidate immunotherapeutic target. Comparative analysis of proteomic and transcriptomic profiles highlights the proteomic-specific features for optimal risk stratification in angiosarcomas. Finally, we define functional signatures termed Sarcoma Proteomic Modules which transcend histological subtype classification and show that a vesicle transport protein signature is an independent prognostic factor for distant metastasis. Our study highlights the utility of proteomics for identifying molecular subgroups with implications for risk stratification and therapy selection and provides a rich resource for future sarcoma research.
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Hemangiossarcoma , Leiomiossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Proteômica , Sarcoma/genética , Leiomiossarcoma/genéticaAssuntos
Resgate Aéreo , Anticonvulsivantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Eclampsia/tratamento farmacológico , Serviços Médicos de Emergência , Ambulâncias , Eclampsia/diagnóstico , Feminino , Humanos , Labetalol/uso terapêutico , Trabalho de Parto Induzido , Lorazepam/uso terapêutico , Sulfato de Magnésio/uso terapêutico , Gravidez , Terceiro Trimestre da Gravidez , População Rural , Convulsões , Transporte de Pacientes , Adulto JovemRESUMO
Sarcomas are rare and heterogeneous malignancies. Owing to their low prevalence and limited capacity to conduct large-scale clinical trials, understanding the molecular mechanisms of sarcomagenesis has become important in determining appropriate treatment. The Cancer Genome Atlas soft tissue sarcoma (STS) project (TCGA-SARC) was the largest and most comprehensive attempt to profile the genomics of multiple STS subtypes. TCGA-SARC made huge contributions to disease understanding. Since the publication of TCGA-SARC, numerous studies have used molecular profiling to assess STS biology. Herein molecular profiling studies in STS are reviewed and future directions with regard to omics profiling in STS research are discussed.
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Sarcoma , Neoplasias de Tecidos Moles , Humanos , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologiaRESUMO
Purpose: This study aims to describe the incidence of postoperative urinary retention among pediatric patients undergoing orthopedic surgery and identify risk factors. Methods: The Pediatric Health Information System was used to identify children aged 1−18 years who underwent orthopedic surgery. Collected from each patient's record were demographic information, principal procedure during hospitalization, the presence of neurologic/neuromuscular conditions and other complex chronic medical conditions, the total postoperative length of stay, and the presence of postoperative urinary retention. Results: The overall incidence of postoperative urinary retention was 0.38%. Children with complex chronic neuromuscular conditions (OR 11.54 (95% CI 9.60−13.88), p = < 0.001) and complex chronic non-neuromuscular medical conditions (OR 5.07 (95% CI 4.11−6.25), p ≤ 0.001) had a substantially increased incidence of urinary retention. Surgeries on the spine (OR 3.98 (95% CI 3.28−4.82, p ≤ 0.001) and femur/hip (OR 3.63 (95% CI 3.03−4.36), p ≤ 0.001) were also associated with an increased incidence. Conclusions: Children with complex chronic neuromuscular conditions have a substantially increased risk of experiencing postoperative urinary retention. Complex chronic non-neuromuscular medical conditions and surgeries to the spine, hip, and femur also carry a notably increased risk.