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The geologically rapid appearance of fossils of modern animal phyla within Cambrian strata is a defining characteristic of the history of life on Earth. However, temporal calibration of the base of the Cambrian Period remains uncertain within millions of years, which has resulted in mounting challenges to the concept of a discrete Cambrian explosion. We present precise zircon U-Pb dates for the lower Wood Canyon Formation, Nevada. These data demonstrate the base of the Cambrian Period, as defined by both ichnofossil biostratigraphy and carbon isotope chemostratigraphy, was younger than 533 Mya, at least 6 My later than currently recognized. This new geochronology condenses previous age models for the Nemakit-Daldynian (early Cambrian) and, integrated with global records, demonstrates an explosive tempo to the early radiation of modern animal phyla.
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Evolução Biológica , Madeira , Animais , Nevada , Fósseis , Isótopos de CarbonoRESUMO
Myelin is a multilayered membrane that tightly wraps neuronal axons, enabling efficient, high-speed signal propagation. The axon and myelin sheath form tight contacts, mediated by specific plasma membrane proteins and lipids, and disruption of these contacts causes devastating demyelinating diseases. Using two cell-based models of demyelinating sphingolipidoses, we demonstrate that altered lipid metabolism changes the abundance of specific plasma membrane proteins. These altered membrane proteins have known roles in cell adhesion and signaling, with several implicated in neurological diseases. The cell surface abundance of the adhesion molecule neurofascin (NFASC), a protein critical for the maintenance of myelin-axon contacts, changes following disruption to sphingolipid metabolism. This provides a direct molecular link between altered lipid abundance and myelin stability. We show that the NFASC isoform NF155, but not NF186, interacts directly and specifically with the sphingolipid sulfatide via multiple binding sites and that this interaction requires the full-length extracellular domain of NF155. We demonstrate that NF155 adopts an S-shaped conformation and preferentially binds sulfatide-containing membranes in cis, with important implications for protein arrangement in the tight axon-myelin space. Our work links glycosphingolipid imbalances to disturbance of membrane protein abundance and demonstrates how this may be driven by direct protein-lipid interactions, providing a mechanistic framework to understand the pathogenesis of galactosphingolipidoses.
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Doenças Desmielinizantes , Sulfoglicoesfingolipídeos , Humanos , Glicoesfingolipídeos/metabolismo , Proteínas de Transporte/metabolismo , Fatores de Crescimento Neural/metabolismo , Bainha de Mielina/metabolismo , Moléculas de Adesão Celular/metabolismo , Doenças Desmielinizantes/patologiaRESUMO
Mechanophores are molecular motifs that respond to mechanical perturbance with targeted chemical reactions toward desirable changes in material properties. A large variety of mechanophores have been investigated, with applications focusing on functional materials, such as strain/stress sensors, nanolithography, and self-healing polymers, among others. The responses of engineered mechanophores, such as light emittance, change in fluorescence, and generation of free radicals (FRs), have potential for bioimaging and therapy. However, the biomedical applications of mechanophores are not well explored. Herein, we report an in vitro demonstration of an FR-generating mechanophore embedded in biocompatible hydrogels for noninvasive cancer therapy. Controlled by high-intensity focused ultrasound (HIFU), a clinically proven therapeutic technique, mechanophores were activated with spatiotemporal precision to generate FRs that converted to reactive oxygen species (ROS) to effectively kill tumor cells. The mechanophore hydrogels exhibited no cytotoxicity under physiological conditions. Upon activation with HIFU sonication, the therapeutic efficacies in killing in vitro murine melanoma and breast cancer tumor cells were comparable with lethal doses of H2O2 This process demonstrated the potential for mechanophore-integrated HIFU combination as a noninvasive cancer treatment platform, named "mechanochemical dynamic therapy" (MDT). MDT has two distinct advantages over other noninvasive cancer treatments, such as photodynamic therapy (PDT) and sonodynamic therapy (SDT). 1) MDT is ultrasound based, with larger penetration depth than PDT. 2) MDT does not rely on sonosensitizers or the acoustic cavitation effect, both of which are necessary for SDT. Taking advantage of the strengths of mechanophores and HIFU, MDT can provide noninvasive treatments for diverse cancer types.
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Fenômenos Biomecânicos , Biopolímeros/química , Hidrogéis/química , Ondas Ultrassônicas , Animais , Compostos Azo/química , Humanos , Hidrogéis/síntese química , Melanoma Experimental , Camundongos , Neoplasias/terapia , Polietilenoglicóis/química , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Termodinâmica , Terapia por Ultrassom/métodosRESUMO
The low-temperature modification of ß-Ag2Se has proven to be useful as a near-room-temperature thermoelectric material. Over the past years, research has been devoted to interstitial, vacancy, and substitutional doping into the parent ß-Ag2Se structure, aiming at tuning the material's charge and heat transport properties to enhance thermoelectric performance. The transformation of ß-Ag2Se into α-Ag2Se at â¼134 °C and the low solubility of dopants are the main obstacles for the doping approach. Herein, we report a facile, safe, scalable, and cost-effective benchtop approach to successfully produce metal-doped ß-Ag2Se. The doped materials display a remarkable enhancement of thermoelectric performance with a record-high peak zT of 1.30 at 120 °C and an average zT of â¼1.15 in the 25-120 °C range for 0.2 at. % Zn-doped Ag2Se. The enhancement in zT is attributed to point defects created by Zn doping into Ag vacancies/interstitials, which enhances the scattering of phonons and tunes the charge carrier properties, leading to the significant suppression of thermal conductivity. The simplicity of the synthetic method developed herein and the high performance of the final products provide an avenue to produce high-quality Ag2Se-based thermoelectric materials.
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Multi-omics approaches have been successfully applied to investigate pregnancy and health outcomes at a molecular and genetic level in several studies. As omics technologies advance, research areas are open to study further. Here we discuss overall trends and examples of successfully using omics technologies and techniques (e.g., genomics, proteomics, metabolomics, and metagenomics) to investigate the molecular epidemiology of pregnancy. In addition, we outline omics applications and study characteristics of pregnancy for understanding fundamental biology, causal health, and physiological relationships, risk and prediction modeling, diagnostics, and correlations.
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Genômica , Proteômica , Humanos , Gravidez , Feminino , Epidemiologia Molecular , Genômica/métodos , Proteômica/métodos , Metabolômica/métodos , MetagenômicaRESUMO
OBJECTIVES: This study evaluated the scale-up of a remote monitoring (RM) service, capturing monthly Rheumatoid Arthritis Impact of Disease scores and patient-generated text messages, for patients with rheumatoid arthritis (RA; in remission or with low disease activity) attending routine outpatient clinics across six hospitals. We explored patients and staff experiences and implementation outcomes. METHODS: A pragmatic, mixed methods approach was used, with active patient involvement throughout. We undertook a rapid review, analysed service-level data, and conducted a patient survey and patient and staff interviews, informed by the Capability, Opportunity, Motivation, Behaviour (COM-B) and Exploration, Preparation, Implementation, Sustainment (EPIS) theoretical frameworks. RESULTS: The review included 37 articles, covering themes of patient and clinician acceptability, engagement, feasibility and clinical impact. Service-level data (n = 202) showed high levels of patient engagement with the service. The patient survey (n = 155) showed patients felt the service was easy to use, had confidence in it and felt it improved access to care. Patient interview (n = 22) findings mirrored those of the survey. Motivating factors included increased responsiveness and ease of contact with clinical teams. Views from staff interviews (n = 16) were more mixed. Some implementation barriers were specific to roll-out sites. Prioritisation of staff needs was emphasised. CONCLUSION: Patients were positive about the service and engagement was high. Staff views and engagement were more mixed. Results suggest that equal levels of patient and staff engagement are required for sustainability. These findings further our understanding of the implementation challenges to scaling RM interventions for patients with RA in routine care settings.
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The COVID-19 pandemic has resulted in the rapid development of a range of vaccines against SARS-CoV-2. Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare but life-threatening complication of primarily adenoviral-based vaccines associated with the presence of antibodies to a PF4/polyanion neoepitope and measured by using enzyme-linked immunosorbent assays. Presented are serial anti-PF4/polyanion antibody, platelet, and D-dimer measurements in a large cohort of patients and their relation to relapse. Overall, 51% of patients using the Stago assay had persistently positive anti-PF4/polyanion levels 100 days' postdiagnosis, whereas 94% of patients monitored by using the Immucor assay remain positive. The median duration of positivity of the PF4 assay is 87 days, with 72% of patients remaining positive after a median follow-up of 105 days. The use of plasma exchange seemed to reduce anti-PF4/polyanion levels and increase platelet counts in the acute setting more rapidly than other therapies. The rate of relapse in this study was 12.6%, with all relapsed cases exhibiting persistently positive PF4 antibodies and falling platelet counts. Only one patient had extension of their thrombosis. Overall, despite the persistence of PF4 antibodies in 72% of patients, the rate of relapse was low and did not seem to result in recrudescence of the aggressive clinical picture seen at index presentation. Monitoring of these patients in the UK cohort is ongoing and will aid in definition of the natural history of this novel condition.
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COVID-19 , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Trombose , Vacinas , Anticorpos/efeitos adversos , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Heparina/efeitos adversos , Humanos , Pandemias , Fator Plaquetário 4 , Recidiva , SARS-CoV-2 , Trombocitopenia/induzido quimicamente , Trombocitopenia/complicações , Vacinas/efeitos adversosRESUMO
INTRODUCTION: The SARS-CoV-2 (COVID-19) pandemic has strained healthcare systems and presented unique challenges for children requiring cancer care, particularly in low- and middle-income countries. This study aimed to assess the impact of the COVID-19 pandemic on access to cancer care for children and adolescents in Northern Tanzania. METHODS: In this cross-sectional study, we assessed the demographic and clinical characteristics of 547 pediatric and adolescent cancer patients (ages 0-19 years old) between 2016 and 2022 using the population-based Kilimanjaro Cancer Registry (KCR). We categorized data into pre-COVID-19 (2016-2019) and COVID-19 (2020-2022) eras, and performed descriptive analyses of diagnostic, treatment, and demographic information. A secondary analysis was conducted on a subset of 167 patients with stage of diagnosis at presentation. RESULTS: Overall admissions nearly doubled during the pandemic (n = 190 versus 357). The variety of diagnoses attended at KCMC increased during the pandemic, with only five groups of diseases reported in 2016 to twelve groups of diseases in 2021. Most patients were diagnosed at a late stage (stage III or IV) across eras, with the proportion of under-five years old patients increasing late-diagnoses from 29.4% (before the pandemic), 52.8% (during the pandemic), when compared to the overall cohort. Around 95% of children in this age category reported late-stage diagnosis during the pandemic. Six out of the twelve cancer site groups also reported an increase in late-stage diagnosis. During the pandemic, the proportion of children receiving surgery increased from 15.8 to 30.8% (p < 0.001). CONCLUSION: Childhood and adolescent cancer care changed in Northern Tanzania during the COVID-19 pandemic, with increased late-stage diagnoses presentations among younger patients and the increased use of surgical therapies in the context of a growing practice. Understanding the impact of the COVID-19 pandemic on pediatric and adolescent cancer care can help us better adapt healthcare systems and interventions to the emerging needs of children and adolescents with cancer in the midst of a health crisis.
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COVID-19 , Neoplasias , Adolescente , Humanos , Criança , Recém-Nascido , Lactente , Pré-Escolar , Adulto Jovem , Adulto , COVID-19/epidemiologia , Estudos Transversais , Pandemias , SARS-CoV-2 , Tanzânia/epidemiologia , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapiaRESUMO
Individuals with mood disorders are predisposed to metabolic dysfunction, while those with metabolic dysregulation such as diabetes and obesity experience more severe depressive symptoms. Both metabolic dysfunction and mood disorders are independently associated with cognitive deficits. Therefore, given their close association, this study aimed to explore the association between metabolic dysfunction in individuals with mood disorders in relation to cognitive outcomes. A comprehensive search comprised of these three domains was carried out; a random-effects meta-analysis pooling mean cognitive outcomes was conducted (PROSPERO ID: CRD42022295765). Sixty-three studies were included in this review; 26 were synthesized in a quantitative meta-analysis. Comorbid metabolic dysregulation was associated with significantly lower global cognition among individuals with mood disorders. These trends were significant within each mood disorder subgroup, including major depressive disorder, bipolar disorder, and self-report depression/depressive symptoms. Type 2 diabetes was associated with the lowest cognitive performance in individuals with mood disorders, followed by peripheral insulin resistance, body mass index ⩾25 kg/m2, and metabolic syndrome. Significant reduction in scores was also observed among individual cognitive domains (in descending order) of working memory, attention, executive function, processing speed, verbal memory, and visual memory. These findings demonstrate the detrimental effects of comorbid metabolic dysfunction in individuals with mood disorders. Further research is required to understand the underlying mechanisms connecting mood disorders, metabolism, and cognition.
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Transtorno Depressivo Maior , Diabetes Mellitus Tipo 2 , Humanos , Transtornos do Humor/epidemiologia , Transtornos do Humor/complicações , Transtorno Depressivo Maior/psicologia , Testes Neuropsicológicos , Cognição , Memória de Curto PrazoRESUMO
The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.
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Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/terapia , Melanoma/diagnóstico , Melanoma/patologia , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Estadiamento de Neoplasias , Oncologia/normas , Oncologia/métodosRESUMO
Receptor for advanced glycation endproducts (RAGE) and toll-like receptor 4 (TLR4) are pattern-recognition receptors that bind to molecular patterns associated with pathogens, stress, and cellular damage. Diffusion plays an important role in receptor functionality in the cell membrane. However, there has been no prior investigation of the reciprocal effect of RAGE and TLR4 diffusion properties in the presence and absence of each receptor. This study reports how RAGE and TLR4 affect the mobility of each other in the human embryonic kidney (HEK) 293 cell membrane. Diffusion properties were measured using single-particle tracking (SPT) with quantum dots (QDs) that are selectively attached to RAGE or TLR4. The Brownian diffusion coefficients of RAGE and TLR4 are affected by the presence of the other receptor, leading to similar diffusion coefficients when both receptors coexist in the cell. When TLR4 is present, the average Brownian diffusion coefficient of RAGE increases by 40%, while the presence of RAGE decreases the average Brownian diffusion coefficient of TLR4 by 32%. Diffusion in confined membrane domains is not altered by the presence of the other receptor. The mobility of the cell membrane lipid remains constant whether one or both receptors are present. Overall, this work shows that the presence of each receptor can affect a subset of diffusion properties of the other receptor without affecting the mobility of the membrane.
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Membrana Celular , Receptor para Produtos Finais de Glicação Avançada , Receptor 4 Toll-Like , Humanos , Receptor 4 Toll-Like/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Células HEK293 , Membrana Celular/metabolismo , DifusãoRESUMO
PURPOSE OF REVIEW: Cardiogenic shock (CS) is a devasting complicating of acute myocardial infarction (AMI), associated with significant mortality. Prior studies have reported sex differences in the presentation, management and outcomes of patients with AMI and CS. These differences are likely due to a variety of factors influencing therapeutic decision-making and impacting survival. This review highlights the more contemporary studies exploring differences in women and men with AMI-CS, providing a critical perspective towards understanding the factors that might lead to these differences and outlining potential opportunities to reduce disparities in treatment and improve survival for women with AMI-CS. RECENT FINDINGS: Recent reports demonstrate that women with AMI-CS are older than men and have more cardiovascular comorbidities. When examining an unselected population of patients with AMI-CS, women receive less aggressive treatment compared to men and have poorer outcomes. However, when examining a selected population of patients with AMI-CS treated with mechanical circulatory support (MCS) and/or admitted to centers that implement CS protocols to manage AMI-CS, these sex-based differences in outcomes are largely mitigated. SUMMARY: Standardizing protocols for the diagnosis and treatment of patients with AMI-CS, with an emphasis on early revascularization and appropriate invasive therapies, can improve outcomes in women and narrow the gender gap.
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Infarto do Miocárdio , Choque Cardiogênico , Humanos , Choque Cardiogênico/terapia , Choque Cardiogênico/etiologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Feminino , Masculino , Fatores Sexuais , Disparidades em Assistência à Saúde , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , ComorbidadeRESUMO
Gaps in the United States Environmental Protection Agency (US EPA) Lead and Copper Rule (LCR) leave some consumers and their pets vulnerable to high cuprosolvency in drinking water. This study seeks to help proactive utilities who wish to mitigate cuprosolvency problems through the addition of orthophosphate corrosion inhibitors. The minimum doses of orthophosphate necessary to achieve acceptable cuprosolvency in relatively new copper pipe were estimated as a function of alkalinity via linear regressions for the 90th, 95th, and 100th percentile copper tube segments (R2 > 0.98, n = 4). Orthophosphate was very effective at reducing cuprosolvency in the short term but, in some cases, resulted in higher long-term copper concentrations than the corresponding condition without orthophosphate. Alternatives to predicting "long-term" results for copper tubes using simpler bench tests starting with fresh Cu(OH)2 solids showed promise but would require further vetting to overcome limitations such as maintaining water chemistry and orthophosphate residuals and to ensure comparability to results using copper tube.
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Água Potável , Poluentes Químicos da Água , Estados Unidos , Cobre/análise , Fosfatos , Abastecimento de Água , CorrosãoRESUMO
Pityriasis rosea is an acute, self-limited exanthem that typically occurs in adolescence and young adulthood, classically featuring ovoid erythematous and scaly lesions on the trunk and proximal extremities. While its cause is not definitively known, the classic form of pityriasis rosea may result from the reactivation of latent human herpesvirus (HHV) infections (HHV-6 and HHV-7). Interestingly, drug eruptions that clinically and/or histopathologically resemble pityriasis rosea have also been reported. These pityriasis rosea-like drug eruptions tend to occur at an older age and have a shorter duration than the classic type. As there are different management paradigms, the distinction between classic pityriasis rosea and the mimicking drug eruption is important to recognize. Herein, we report a case of a pityriasis rosea-like drug eruption that occurred in association with imatinib mesylate treatment for chronic myeloid leukemia. We also review the clinicopathologic features of reported cases of pityriasis rosea-like drug eruption, including those due to imatinib. While the clinical morphology of the cutaneous drug-related eruption mimics the lesions seen in classic pityriasis rosea, the presence of unique histopathologic findings, including necrotic keratinocytes, interface dermatitis, and eosinophils, may aid in distinction.
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Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with a high propensity for local invasion and recurrence. Although it is a rare event, the occurrence of multiple tumors in a single patient raises a diagnostic dilemma, as metastatic disease should be differentiated from multiple primary malignant events. In more than 90% of DFSP, a pathogenic t(17;22) translocation leads to the expression of COL1A1::PDGFB fusion transcripts. Karyotype analysis, fluorescence in situ hybridization, and RT-PCR can be useful ancillary studies in detecting this characteristic rearrangement, and sequencing of the fusion transcript can be used to support a clonal origin in metastatic and multifocal disease. However, previous reports have demonstrated variable sensitivity of these assays, in part due to the high sequence variability of the COL1A1::PDGFB fusion. Here, we report a patient who developed two distinct DFSP tumors over the course of 7 years. Chromosomal microarray analysis identified distinctive genomic alterations in the two tumors, supporting the occurrence of multiple primary malignant events.
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Dermatofibrossarcoma , Proteínas de Fusão Oncogênica , Neoplasias Cutâneas , Humanos , Masculino , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 22/genética , Cadeia alfa 1 do Colágeno Tipo I , Dermatofibrossarcoma/genética , Dermatofibrossarcoma/patologia , Dermatofibrossarcoma/diagnóstico , Hibridização in Situ Fluorescente/métodos , Análise em Microsséries/métodos , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Proteínas de Fusão Oncogênica/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Translocação Genética , Pessoa de Meia-IdadeRESUMO
Pyrrole-containing natural products form a large group of structurally diverse compounds that occur in both terrestrial and marine organisms. In the present study the formation of trideuteromethylated artifacts of pyrrole-containing natural products was investigated, focusing on the discorhabdins. Three deuterated discorhabdins, 1, 3, and 5, were identified to be isolation procedure artifacts caused by the presence of DMSO-d6 during NMR sample preparation and handling. Three additional semisynthetic derivatives, 7-9, were made during the investigation of the mechanism of formation, which was shown to be driven by trideuteromethyl radicals in the presence of water, methanol, TFA, and traces of iron in the deuterated solvent. Generation of trideuteromethylated artifacts was also confirmed for other classes of pyrrole-containing metabolites, namely, makaluvamines, tambjamines, and dibromotryptamines, which had also been dissolved in DMSO-d6 during the structure elucidation process. Semisynthetic discorhabdins were assessed for antiproliferative activity against a panel of human tumor cell lines, and 14-trideuteromethyldiscorhabdin L (3) averaged low micromolar potency.
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Produtos Biológicos , Dimetil Sulfóxido , Humanos , Dimetil Sulfóxido/química , Pirróis/química , Produtos Biológicos/farmacologia , Artefatos , Solventes/químicaRESUMO
A high throughput screen performed to identify catalytic inhibitors of the oncogenic fusion form of cAMP-dependent protein kinase A catalytic subunit alpha (J-PKAcα) found an individual fraction from an organic extract of the marine soft coral Acrozoanthus australiae as active. Bioassay-guided isolation led to the identification of a 2-amino adenine alkaloid acroamine A (1), the first secondary metabolite discovered from this genus and previously reported as a synthetic product. As a naturally occurring protein kinase inhibitor, to unambiguously assign its chemical structure using modern spectroscopic and spectrometric techniques, five N-methylated derivatives acroamines A1-A5 (2-6) were semisynthesized. Three additional brominated congeners A6-A8 (7-9) were also semisynthesized to investigate the structure-activity relationship of the nine compounds as J-PKAcα inhibitors. Compounds 1-9 were tested for J-PKAcα and wild-type PKA inhibitory activities, which were observed exclusively in acroamine A (1) and its brominated analogs (7-9) achieving moderate potency (IC50 2-50 µM) while none of the N-methylated analogs exhibited kinase inhibition.
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Alcaloides , Antozoários , Proteínas Quinases Dependentes de AMP Cíclico , Animais , Antozoários/química , Estrutura Molecular , Alcaloides/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Relação Estrutura-Atividade , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Adenina/farmacologia , Adenina/análogos & derivados , Adenina/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Domínio CatalíticoRESUMO
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (1) and E2 (2), were isolated from a Penicillium fungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of 1 and 2 were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey's reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable 1 and 2 underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2 in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7 and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2 to 7 and 8 was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.
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Dicetopiperazinas , Penicillium , Penicillium/química , Dicetopiperazinas/farmacologia , Dicetopiperazinas/química , Estrutura Molecular , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Prior research has identified traumatic experiences and substance use as risk factors for adolescent engagement in sexual risk-taking; however, these studies have relied upon subthreshold or non-dually diagnosed samples. The present study examined differences in sexual risk behaviors between adolescents with a substance use disorder (SUD) and co-occurring posttraumatic stress disorder (PTSD) versus those with an SUD and another co-occurring psychiatric disorder. Participants were 269 adolescents who met the clinical screening criteria for an SUD and at least one psychiatric disorder. Bivariate comparisons and generalized linear models were used to compare sexual risk behaviors in participants with co-occurring PTSD (30.0%) and those with a different psychiatric disorder (70.0%). Participants with co-occurring PTSD were twice as likely to have multiple sex partners during the same period compared to those without PTSD, odds ratio (OR) = 2.35, p = .012. They also reported, on average, over twice the incidence rate of unprotected sexual encounters, incidence rate ratio (IRR) = 2.06, p = .034, and a 51.0% higher incidence of sexual risk behaviors, IRR = 1.51, p = .008, than participants without co-occurring PTSD. The results suggest dually diagnosed adolescents with co-occurring PTSD are more likely to engage in sexual risk behaviors than those with a different co-occurring disorder, placing them at higher risk for adverse health effects, such as sexually transmitted infections and unplanned pregnancies. As such, this population is likely to benefit from targeted trauma-informed sexual health education programs focused on sexual risk reduction.
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INTRODUCTION: An unprecedented shortage of infant formula occurred in the United States (U.S.) in 2022 and posed widespread challenges to infant feeding nationwide. The purpose of this study is to investigate mothers' experiences during the 2022 infant formula shortage and its perceived impacts on infants' diet and health. METHODS: Mothers (n = 45) of infants under 8 months old from Washington D.C. were invited to participate in a virtual study meeting during the summer of 2022. Mothers completed surveys regarding their demographics, infants' anthropometrics, infant feeding practices, information they have received about infant feeding, and knowledge about infant feeding practices. They then participated in a qualitative interview about their experiences during the infant formula shortage. RESULTS: Overarching themes were: the shortage (1) had adverse impacts on mothers' mental and emotional health; (2) had significant financial and intangible costs; (3) led to changes in infant feeding practices; (4) social and family networks were helpful in navigating the shortage; and (5) mothers felt fortunate to have resources to breastfeed and/or obtain formula. DISCUSSION: The infant formula shortage adversely impacted mothers' mental and emotional health, and was costly, in terms of financial and intangible costs. Findings demonstrate the need to develop clinical and policy approaches to support mothers in feeding their infants and provide education about safe infant feeding practices.