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1.
Cell ; 187(8): 1936-1954.e24, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38490196

RESUMO

Microglia are brain-resident macrophages that shape neural circuit development and are implicated in neurodevelopmental diseases. Multiple microglial transcriptional states have been defined, but their functional significance is unclear. Here, we identify a type I interferon (IFN-I)-responsive microglial state in the developing somatosensory cortex (postnatal day 5) that is actively engulfing whole neurons. This population expands during cortical remodeling induced by partial whisker deprivation. Global or microglial-specific loss of the IFN-I receptor resulted in microglia with phagolysosomal dysfunction and an accumulation of neurons with nuclear DNA damage. IFN-I gain of function increased neuronal engulfment by microglia in both mouse and zebrafish and restricted the accumulation of DNA-damaged neurons. Finally, IFN-I deficiency resulted in excess cortical excitatory neurons and tactile hypersensitivity. These data define a role for neuron-engulfing microglia during a critical window of brain development and reveal homeostatic functions of a canonical antiviral signaling pathway in the brain.


Assuntos
Encéfalo , Interferon Tipo I , Microglia , Animais , Camundongos , Interferon Tipo I/metabolismo , Microglia/metabolismo , Neurônios/metabolismo , Peixe-Zebra , Encéfalo/citologia , Encéfalo/crescimento & desenvolvimento
2.
Ann Surg Oncol ; 29(13): 7964-7973, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36149608

RESUMO

INTRODUCTION: Patient-reported outcome measures (PROM) are used to assess value-based care. Little is known as to whether PROM response in breast cancer reflects the diverse patient population. The BREAST-Q, a validated measure of satisfaction and quality of life, and Recovery Tracker, a postoperative assessment tool, are PROM routinely delivered to all patients undergoing breast surgery at our institution. Here we determine whether response to PROM differs by age, race, language, or disease stage. METHODS: All patients who had a breast operation between January 2020 and July 2021 were requested to complete the BREAST-Q and Recovery Tracker. Non-responders did not complete the PROM at any timepoint; responders completed 1 or more. Primary outcomes included rates of non-response versus response overall. RESULTS: Of 6374 patients identified, 5653 (88.7%) responded to either PROM [4366/4751 (91.9%) BREAST-Q; 2746/3384 (81.1%) Recovery Tracker]. On univariate analysis, non-responders were older (60 years versus 55 years, p < 0.001) and more often non-English speaking (p < 0.001), Hispanic ethnicity (p = 0.031), and Black race (p < 0.001), versus responders. On multivariate analysis, non-responders were significantly more often Black race and non-English speaking (p < 0.001). Non-English speakers were significantly less responsive among all ethnicities and races except Black race. Although breast cancer stage did not reach significance for response, patients with malignant disease and those receiving neoadjuvant chemotherapy responded more often. CONCLUSIONS: Our findings demonstrate high patient engagement using 2 different PROM following breast surgery, but suggest that PROM results may not reflect the experience of the entire breast cancer population. Care process changes based solely on PROM should consider these findings to ensure that the views of the entire spectrum of patients with breast cancer are represented.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/cirurgia , Qualidade de Vida , Mastectomia , Terapia Neoadjuvante , Medidas de Resultados Relatados pelo Paciente
3.
Glia ; 68(7): 1445-1465, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034934

RESUMO

Brain injury activates complex inflammatory signals in dying neurons, surviving neurons, and glia. Here, we establish that inflammation regulates the regeneration of photoreceptors in the zebrafish retina and determine the cellular expression and function of the inflammatory protease, matrix metalloproteinase 9 (Mmp-9), during this regenerative neurogenesis. Following photoreceptor ablation, anti-inflammatory treatment suppresses the number of injury-induced progenitors and regenerated photoreceptors. Upon photoreceptor injury, mmp-9 is induced in Müller glia and Müller glia-derived photoreceptor progenitors. Deleting mmp-9 results in over production of injury-induced progenitors and regenerated photoreceptors, but over time the absence of Mmp-9 compromises the survival of the regenerated cones. At all time-points studied, the levels of tnf-α are significantly elevated in mutant retinas. Anti-inflammatory treatment in mutants rescues the defects in cone survival. These data provide a link between injury-induced inflammation in the vertebrate CNS, Mmp-9 function during neuronal regeneration and the requirement of Mmp-9 for the survival of regenerated cones.


Assuntos
Inflamação/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Regeneração Nervosa/fisiologia , Regeneração/fisiologia , Animais , Animais Geneticamente Modificados , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Neuroglia/metabolismo , Retina/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Células-Tronco/fisiologia , Peixe-Zebra
4.
BMC Genomics ; 20(1): 554, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277573

RESUMO

BACKGROUND: Citrus are among the most important crops in the world. However, there are many diseases that affect Citrus caused by different pathogens. Citrus also hosts many symbiotic microorganisms in a relationship that may be advantageous for both organisms. The fungi Phyllosticta citricarpa, responsible for citrus black spot, and Phyllosticta capitalensis, an endophytic species, are examples of closely related species with different behavior in citrus. Both species are always biologically associated and are morphologically very similar, and comparing their genomes could help understanding the different lifestyles. In this study, a comparison was carried to identify genetic differences that could help us to understand the biology of P. citricarpa and P. capitalensis. RESULTS: Drafts genomes were assembled with sizes close to 33 Mb for both fungi, carrying 15,206 and 14,797 coding sequences for P. citricarpa and P. capitalensis, respectively. Even though the functional categories of these coding sequences is similar, enrichment analysis showed that the pathogenic species presents growth and development genes that may be necessary for the pathogenicity of P. citricarpa. On the other hand, family expansion analyses showed the plasticity of the genome of these species. Particular families are expanded in the genome of an ancestor of P. capitalensis and a recent expansion can also be detected among this species. Additionally, evolution could be driven by environmental cues in P. citricarpa. CONCLUSIONS: This work demonstrated genomic differences between P. citricarpa and P. capitalensis. Although the idea that these differences could explain the different lifestyles of these fungi, we were not able to confirm this hypothesis. Genome evolution seems to be of real importance among the Phyllosticta isolates and it is leading to different biological characteristics of these species.


Assuntos
Ascomicetos/genética , Ascomicetos/patogenicidade , Citrus/microbiologia , Genoma de Planta , Filogenia , Endófitos/genética , Enzimas/genética , Enzimas/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Genômica , Interações Hospedeiro-Patógeno/genética , Doenças das Plantas/microbiologia
5.
J Exp Biol ; 222(Pt 20)2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31492818

RESUMO

Holometabolous insects have been able to radiate to vast ecological niches as adults through the evolution of adult-specific structures such as wings, antennae and eyes. These structures arise from imaginal discs that show regenerative capacity when damaged. During imaginal disc regeneration, development has been shown to be delayed in the fruit fly Drosophila melanogaster, but how conserved the delay-inducing mechanisms are across holometabolous insects has not been assessed. The goal of this research was to develop the hornworm Manduca sexta as an alternative model organism to study such damage-induced mechanisms, with the advantage of a larger hemolymph volume enabling access to the hormonal responses to imaginal disc damage. Upon whole-body X-ray exposure, we noted that the imaginal discs were selectively damaged, as assessed by TUNEL and Acridine Orange stains. Moreover, development was delayed, predominantly at the pupal-to-adult transition, with a concomitant delay in the prepupal ecdysteroid peak. The delays to eclosion were dose dependent, with some ability for repair of damaged tissues. We noted a shift in critical weight, as assessed by the point at which starvation no longer impacted developmental timing, without a change in growth rate, which was uncoupled from juvenile hormone clearance in the body. The developmental profile was different from that of D. melanogaster, which suggests species differences may exist in the mechanisms delaying development.


Assuntos
Discos Imaginais/patologia , Manduca/crescimento & desenvolvimento , Nicotiana/parasitologia , Animais , Peso Corporal/efeitos da radiação , Ecdisteroides/metabolismo , Cabeça , Discos Imaginais/efeitos da radiação , Hormônios Juvenis/metabolismo , Estágios do Ciclo de Vida/efeitos da radiação , Manduca/efeitos da radiação , Modelos Biológicos , Fatores de Tempo , Raios X
7.
BMC Genomics ; 17(1): 623, 2016 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-27515968

RESUMO

BACKGROUND: Leucine-rich repeat receptor-like kinases (LRR-RLKs) represent the largest subfamily of plant RLKs. The functions of most LRR-RLKs have remained undiscovered, and a few that have been experimentally characterized have been shown to have important roles in growth and development as well as in defense responses. Although RLK subfamilies have been previously studied in many plants, no comprehensive study has been performed on this gene family in Citrus species, which have high economic importance and are frequent targets for emerging pathogens. In this study, we performed in silico analysis to identify and classify LRR-RLK homologues in the predicted proteomes of Citrus clementina (clementine) and Citrus sinensis (sweet orange). In addition, we used large-scale phylogenetic approaches to elucidate the evolutionary relationships of the LRR-RLKs and further narrowed the analysis to the LRR-XII group, which contains several previously described cell surface immune receptors. RESULTS: We built integrative protein signature databases for Citrus clementina and Citrus sinensis using all predicted protein sequences obtained from whole genomes. A total of 300 and 297 proteins were identified as LRR-RLKs in C. clementina and C. sinensis, respectively. Maximum-likelihood phylogenetic trees were estimated using Arabidopsis LRR-RLK as a template and they allowed us to classify Citrus LRR-RLKs into 16 groups. The LRR-XII group showed a remarkable expansion, containing approximately 150 paralogs encoded in each Citrus genome. Phylogenetic analysis also demonstrated the existence of two distinct LRR-XII clades, each one constituted mainly by RD and non-RD kinases. We identified 68 orthologous pairs from the C. clementina and C. sinensis LRR-XII genes. In addition, among the paralogs, we identified a subset of 78 and 62 clustered genes probably derived from tandem duplication events in the genomes of C. clementina and C. sinensis, respectively. CONCLUSIONS: This work provided the first comprehensive evolutionary analysis of the LRR-RLKs in Citrus. A large expansion of LRR-XII in Citrus genomes suggests that it might play a key role in adaptive responses in host-pathogen co-evolution, related to the perennial life cycle and domestication of the citrus crop species.


Assuntos
Citrus/genética , Evolução Molecular , Genoma de Planta , Proteínas de Plantas/genética , Proteínas Serina-Treonina Quinases/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Cromossomos de Plantas/metabolismo , Citrus/metabolismo , Família Multigênica , Filogenia , Proteínas de Plantas/classificação , Proteínas de Plantas/metabolismo , Proteínas Serina-Treonina Quinases/classificação , Proteínas Serina-Treonina Quinases/metabolismo
8.
Environ Technol ; 44(8): 1135-1144, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34704545

RESUMO

Phosphorus is a crucial resource for the agricultural industry, but its limited supply requires recovery from waste materials before it is lost and leads to eutrophication. Dairy manure is rich with phosphorus, and the growth and consolidation within the dairy industry has led to dairy manure management becoming a significant concern. Hydrothermal carbonization (HTC) and membrane distillation (MD) were investigated as an alternative to treat dairy manure and recover nutrients, specifically phosphorus and nitrogen. HTC is a thermal treatment process that converts organic matter into a hydrochar analogous to a low-grade coal, and MD is a thermally-driven separation process that can utilize low-grade waste heat from HTC, thus the two processes are synergetic. A byproduct of the HTC process is the aqueous product (HAP) that contains the water-soluble nutrients and organic components of dairy manure. In this work, the efficacy of MD to concentrate the nutrients in the presence of dissolved organic carbon was assessed. Samples included synthetic nutrient-rich streams as well as HAP produced at HTC temperatures ranging from 200 °C to 260 °C. In each case, the nutrients were successfully concentrated in the feed loop with rejections >99%. Dissolved carbon was found to foul the MD membrane at levels proportional to its hydrophobicity, with little fouling observed for glucose and substantial fouling observed for HAP solutions created at higher temperatures.


Assuntos
Destilação , Esterco , Nutrientes , Água , Temperatura , Carbono , Fósforo
9.
Cancer Med ; 12(7): 8063-8072, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36737878

RESUMO

BACKGROUND: Data on the clinical value of second opinions in oncology are limited. We examined diagnostic and treatment changes resulting from second opinions and the expected impact on morbidity and prognosis. METHODS: This retrospective cohort study included patients presenting in 2018 to a high-volume cancer center for second opinions about newly diagnosed colorectal, head and neck, lung, and myeloma cancers or abnormal results. Two sub-specialty physicians from each cancer type reviewed 30 medical records (120 total) using a process and detailed data collection guide meant to mitigate institutional bias. The primary outcome measure was the rate of treatment changes that were "clinically meaningful", i.e., expected to impact morbidity and/or prognosis. Among those with treatment changes, another outcome measure was the rate of clinically meaningful diagnostic changes that led to treatment change. RESULTS: Of 120 cases, forty-two had clinically meaningful changes in treatment with positive expected outcomes (7 colorectal, 17 head and neck, 11 lung, 7 myeloma; 23-57%). Two patients had negative expected outcomes from having sought a second opinion, with worse short-term morbidity and unchanged long-term morbidity and prognosis. All those with positive expected outcomes had improved expected morbidity (short- and/or long-term); 11 (0-23%) also had improved expected prognosis. Nine involved a shift from treatment to observation; 21 involved eliminating or reducing the extent of surgery, compared to 6 adding surgery or increasing its extent. Of the 42 with treatment changes, 13 were due to clinically meaningful diagnostic changes (1 colorectal, 5 head and neck, 3 lung, 4 myeloma; 3%-17%) . CONCLUSIONS: Second-opinion consultations sometimes add clinical value by improving expected prognoses; more often, they offer treatment de-escalations, with corresponding reductions in expected short- and/or long-term morbidity. Future research could identify subgroups of patients most likely to benefit from second opinions.


Assuntos
Neoplasias Colorretais , Mieloma Múltiplo , Humanos , Estudos Retrospectivos , Prognóstico , Encaminhamento e Consulta
10.
bioRxiv ; 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37609307

RESUMO

Following acute retinal damage, zebrafish possess the ability to regenerate all neuronal subtypes. This regeneration requires Müller glia (MG) to reprogram and divide asymmetrically to produce a multipotent Müller glia-derived neuronal progenitor cell (MGPC). This raises three key questions. First, does loss of different retinal cell subtypes induce unique MG regeneration responses? Second, do MG reprogram to a developmental retinal progenitor cell state? And finally, to what extent does regeneration recapitulate retinal development? We examined these questions by performing single-nuclear and single-cell RNA-Seq and ATAC-Seq in both developing and regenerating retinas. While MG reprogram to a state similar to late-stage retinal progenitors in developing retinas, there are transcriptional differences between reprogrammed MG/MGPCs and late progenitors, as well as reprogrammed MG in outer and inner retinal damage models. Validation of candidate genes confirmed that loss of different subtypes induces differences in transcription factor gene expression and regeneration outcomes. This work identifies major differences between gene regulatory networks activated following the selective loss of different subtypes of retina neurons, as well as between retinal regeneration and development.

11.
Res Sq ; 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37790324

RESUMO

Following acute retinal damage, zebrafish possess the ability to regenerate all neuronal subtypes. This regeneration requires Müller glia (MG) to reprogram and divide asymmetrically to produce a multipotent Müller glia-derived neuronal progenitor cell (MGPC). This raises three key questions. First, does loss of different retinal cell subtypes induce unique MG regeneration responses? Second, do MG reprogram to a developmental retinal progenitor cell state? And finally, to what extent does regeneration recapitulate retinal development? We examined these questions by performing single-nuclear and single-cell RNA-Seq and ATAC-Seq in both developing and regenerating retinas. While MG reprogram to a state similar to late-stage retinal progenitors in developing retinas, there are transcriptional differences between reprogrammed MG/MGPCs and late progenitors, as well as reprogrammed MG in outer and inner retinal damage models. Validation of candidate genes confirmed that loss of different subtypes induces differences in transcription factor gene expression and regeneration outcomes. This work identifies major differences between gene regulatory networks activated following the selective loss of different subtypes of retina neurons, as well as between retinal regeneration and development.

12.
Nat Commun ; 14(1): 8477, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38123561

RESUMO

Following acute retinal damage, zebrafish possess the ability to regenerate all neuronal subtypes through Müller glia (MG) reprogramming and asymmetric cell division that produces a multipotent Müller glia-derived neuronal progenitor cell (MGPC). This raises three key questions. First, do MG reprogram to a developmental retinal progenitor cell (RPC) state? Second, to what extent does regeneration recapitulate retinal development? And finally, does loss of different retinal cell subtypes induce unique MG regeneration responses? We examined these questions by performing single-nuclear and single-cell RNA-Seq and ATAC-Seq in both developing and regenerating retinas. Here we show that injury induces MG to reprogram to a state similar to late-stage RPCs. However, there are major transcriptional differences between MGPCs and RPCs, as well as major transcriptional differences between activated MG and MGPCs when different retinal cell subtypes are damaged. Validation of candidate genes confirmed that loss of different subtypes induces differences in transcription factor gene expression and regeneration outcomes.


Assuntos
Redes Reguladoras de Genes , Peixe-Zebra , Animais , Peixe-Zebra/genética , Retina/metabolismo , Neurogênese/genética , Neuroglia/metabolismo , Proliferação de Células/fisiologia , Células Ependimogliais/metabolismo
13.
bioRxiv ; 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35233577

RESUMO

Microglia are brain resident phagocytes that can engulf synaptic components and extracellular matrix as well as whole neurons. However, whether there are unique molecular mechanisms that regulate these distinct phagocytic states is unknown. Here we define a molecularly distinct microglial subset whose function is to engulf neurons in the developing brain. We transcriptomically identified a cluster of Type I interferon (IFN-I) responsive microglia that expanded 20-fold in the postnatal day 5 somatosensory cortex after partial whisker deprivation, a stressor that accelerates neural circuit remodeling. In situ, IFN-I responsive microglia were highly phagocytic and actively engulfed whole neurons. Conditional deletion of IFN-I signaling (Ifnar1fl/fl) in microglia but not neurons resulted in dysmorphic microglia with stalled phagocytosis and an accumulation of neurons with double strand DNA breaks, a marker of cell stress. Conversely, exogenous IFN-I was sufficient to drive neuronal engulfment by microglia and restrict the accumulation of damaged neurons. IFN-I deficient mice had excess excitatory neurons in the developing somatosensory cortex as well as tactile hypersensitivity to whisker stimulation. These data define a molecular mechanism through which microglia engulf neurons during a critical window of brain development. More broadly, they reveal key homeostatic roles of a canonical antiviral signaling pathway in brain development.

14.
JAMA Netw Open ; 5(3): e221078, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35244701

RESUMO

IMPORTANCE: Electronic patient-reported outcomes (ePROs) may have the potential to improve cancer care delivery by enhancing patient quality of life, reducing acute care visits, and extending overall survival. However, the optimal cadence of ePRO assessments is unknown. OBJECTIVE: To determine patient response preferences and the clinical value associated with a daily cadence for ePROs for patients receiving antineoplastic treatment. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study of adult patients undergoing antineoplastic treatment assessed a remote monitoring program using ePROs that was developed to manage cancer therapy-related symptoms. ePRO data submitted between October 16, 2018 to February 29, 2020, from a single regional site within the Memorial Sloan Kettering Cancer Center network were included. Data were analyzed from April 2020 to January 2022. EXPOSURE: While undergoing active treatment, patients received a daily ePRO assessment that, based on patient responses, generated yellow (moderate) or red (severe) symptom alerts that were sent to clinicians. MAIN OUTCOMES AND MEASURES: The main outcomes assessed included patient response rate, symptom alert frequency, and an analysis of the clinical value of daily ePROs. RESULTS: A total of 217 patients (median [range] age, 66 [31-92] years; 103 [47.5%] women and 114 [52.5%] men) initiating antineoplastic therapy at high risk for symptoms were monitored for a median (range) of 91 (2-369) days. Most patients had thoracic (59 patients [27.2%]), head and neck (48 patients [22.1%]), or gastrointestinal (43 patients [19.8%]) malignant neoplasms. Of 14 603 unique symptom assessments completed, 7349 (50.3%) generated red or yellow symptom alerts. Symptoms commonly generating alerts included pain (665 assessments [23.0%]) and functional status (465 assessments [16.1%]). Most assessments (8438 assessments [57.8%]) were completed at home during regular clinic hours (ie, 9 am-5 pm), with higher response rates on weekdays (58.4%; 95% CI, 57.5%-59.5%) than on weekend days (51.3%; 95% CI, 49.5%-53.1%). Importantly, 284 of 630 unique red alerts (45.1%) surfaced without a prior yellow alert for the same symptom within the prior 7 days; symptom severity fluctuated over the course of a week, and symptom assessments generating a red alert were followed by an acute care visit within 7 days 8.7% of the time compared with 2.9% for assessments without a red alert. CONCLUSIONS AND RELEVANCE: These findings suggest that daily ePRO assessments were associated with increased insight into symptom management in patients undergoing antineoplastic treatment and symptom alerts were associated with risk of acute care.


Assuntos
Antineoplásicos , Neoplasias , Adulto , Idoso , Antineoplásicos/efeitos adversos , Feminino , Humanos , Masculino , Neoplasias/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Avaliação de Sintomas
15.
Gene ; 828: 146476, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35413393

RESUMO

Energy cane is a dedicated crop to high biomass production and selected during Saccharum breeding programs to fit specific industrial needs for 2G bioethanol production. Internode elongation is one of the most important characteristics in Saccharum hybrids due to its relationship with crop yield. In this study, we selected the third internode elongation of the energy cane. To characterize this process, we divided the internode into five sections and performed a detailed transcriptome analysis (RNA-Seq) and cell wall characterization. The histological analyses revealed a remarkable gradient that spans from cell division and protoxylem lignification to the internode maturation and complete vascular bundle lignification. RNA-Seq analysis revealed more than 11,000 differentially expressed genes between the sections internal. Gene ontology analyzes showed enriched categories in each section, as well as the most expressed genes in each section, presented different biological processes. We found that the internode elongation and division zones have a large number of unique genes. Evaluated the specific profile of genes related to primary and secondary cell wall formation, cellulose synthesis, hemicellulose, lignin, and growth-related genes. For each section these genes presented different profiles along the internode in elongation in energy cane. The results of this study provide an overview of the regulation of gene expression of an internode elongation in energy cane. Gene expression analysis revealed promising candidates for transcriptional regulation of energy cane lignification and evidence key genes for the regulation of internode development, which can serve as a basis for understanding the molecular regulatory mechanisms that support the growth and development of plants in the Saccahrum complex.


Assuntos
Saccharum , Biomassa , Bengala , Regulação da Expressão Gênica de Plantas , Lignina , Melhoramento Vegetal , Saccharum/genética , Saccharum/metabolismo
16.
JCO Oncol Pract ; 18(12): e1935-e1942, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36265089

RESUMO

PURPOSE: Traditional oncology care models have not effectively identified and managed at-risk patients to prevent acute care. A next step is to harness advances in technology to enable patients to report symptoms any time, enabling digital hovering-intensive symptom monitoring and management. Our objective was to evaluate a digital platform that identifies and remotely monitors high-risk patients initiating antineoplastic therapy with the goal of preventing acute care visits. METHODS: This was a single-institution matched cohort quality improvement study conducted at a National Cancer Institute-designated cancer center between January 1, 2019, and March 31, 2020. Eligible patients were those initiating intravenous antineoplastic therapy who were identified as high risk for seeking acute care. Enrolled patients' symptoms were monitored using a digital platform. A dedicated team of clinicians managed reported symptoms. The primary outcomes of emergency department visits and hospitalizations within 6 months of treatment initiation were analyzed using cumulative incidence analyses with a competing risk of death. RESULTS: Eighty-one patients from the intervention arm were matched by stage and disease with contemporaneous high-risk control patients. The matched cohort had similar baseline characteristics. The cumulative incidence of an emergency department visit for the intervention cohort was 0.27 (95% CI, 0.17 to 0.37) at six months compared with 0.47 (95% CI, 0.36 to 0.58) in the control (P = .01) and of an inpatient admission was 0.23 (95% CI, 0.14 to 0.33) in the intervention cohort versus 0.41 (95% CI, 0.30 to 0.51) in the control (P = .02). CONCLUSION: The narrow employment of technology solutions to complex care delivery challenges in oncology can improve outcomes and innovate care. This program was a first step in using a digital platform and a remote team to improve symptom care for high-risk patients.


Assuntos
Antineoplásicos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Cuidados Paliativos , Hospitalização , Serviço Hospitalar de Emergência , Estudos de Coortes
17.
Nat Commun ; 12(1): 5916, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625548

RESUMO

Microglia are brain resident macrophages that play vital roles in central nervous system (CNS) development, homeostasis, and pathology. Microglia both remodel synapses and engulf apoptotic cell corpses during development, but whether unique molecular programs regulate these distinct phagocytic functions is unknown. Here we identify a molecularly distinct microglial subset in the synapse rich regions of the zebrafish (Danio rerio) brain. We found that ramified microglia increased in synaptic regions of the midbrain and hindbrain between 7 and 28 days post fertilization. In contrast, microglia in the optic tectum were ameboid and clustered around neurogenic zones. Using single-cell mRNA sequencing combined with metadata from regional bulk sequencing, we identified synaptic-region associated microglia (SAMs) that were highly enriched in the hindbrain and expressed multiple candidate synapse modulating genes, including genes in the complement pathway. In contrast, neurogenic associated microglia (NAMs) were enriched in the optic tectum, had active cathepsin activity, and preferentially engulfed neuronal corpses. These data reveal that molecularly distinct phagocytic programs mediate synaptic remodeling and cell engulfment, and establish the zebrafish hindbrain as a model for investigating microglial-synapse interactions.


Assuntos
Mesencéfalo/citologia , Microglia/citologia , Neurogênese/genética , Rombencéfalo/citologia , Colículos Superiores/citologia , Transcriptoma , Proteínas de Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Antígenos de Diferenciação de Linfócitos B/genética , Antígenos de Diferenciação de Linfócitos B/imunologia , Catepsina B/genética , Catepsina B/imunologia , Regulação da Expressão Gênica no Desenvolvimento , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Mesencéfalo/crescimento & desenvolvimento , Mesencéfalo/imunologia , Microglia/imunologia , Neurogênese/imunologia , Neurônios/citologia , Neurônios/imunologia , Fagocitose , Rombencéfalo/crescimento & desenvolvimento , Rombencéfalo/imunologia , Análise de Célula Única , Colículos Superiores/crescimento & desenvolvimento , Colículos Superiores/imunologia , Sinapses/imunologia , Sinapses/metabolismo , Sinapses/ultraestrutura , Peixe-Zebra , Proteínas de Peixe-Zebra/imunologia
18.
Spec Care Dentist ; 41(1): 66-77, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33215733

RESUMO

AIM: To determine the scientific evidence regarding the condition of periodontal diseases (PDs) as risk factors of coronary artery diseases. MATERIALS AND METHODS: A scoping review was performed through the selection of articles from online databases (Medline via PubMed, LILACS, and Cochrane CENTRAL), using a search algorithm and eligibility criteria for data extraction and data synthesis of included papers. Four hundred forty-one studies from online databases and 1364 from reference lists were initially identified, and 34 articles were selected for inclusion. Articles had to be published between 2015 and 2020 and had to associate PDs to coronary arterial diseases. All studies comprised a sample of 446443 participants. Favorable opinions totaled 70.59%, and the cross-sectional observational study design was more frequently found (32.35%). Biochemical outcomes were showed more frequently, such as inflammatory biomarkers (58.82%). Despite a large advantage for favorable opinions, a statistically significant result was not found when extracted data were combined with studies opinions. CONCLUSION: The evidence was classified as level II-3, hence, still distant from the best ranks and can therefore be considered as unclear. Moreover, studies with the higher potential to generate evidence showed a high risk of bias.


Assuntos
Doença da Artéria Coronariana , Doenças Periodontais , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Humanos , Doenças Periodontais/complicações , Doenças Periodontais/epidemiologia , Fatores de Risco
19.
Plant Physiol Biochem ; 167: 504-516, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34425395

RESUMO

Commercial cultivation of sugarcane is usually carried out by planting culm segments (sett) carrying buds in their internodes. However, this is an inefficient practice due to high sprouting irregularity. In this work, we inspect the first stages of the physiological preparation of the culm for sprouting, trying to identify compounds that actively participate in this process. We compared, during the first 48 h, the metabolic profile of sugarcane against energy cane, a cultivar known to have higher sprouting speed and consistency. In fact, during this short period it was possible to observe that energy cane already had a higher physiological activity than sugarcane, with significant changes in the catabolism of amino acids, increased levels of reducing sugars, lipids and metabolic activity in the phenylpropanoid pathway. On the other hand, sugarcane samples had just begun their activity during this same period, with an increase in the level of glutamate as the most significant change, which may be linked to the strategy of these cultivars to develop their roots before leaves, opposite of what is seen for energy cane. These results contribute to the development of strategies for increasing the efficiency of sprouting in sugarcane.


Assuntos
Saccharum , Bengala , Grão Comestível , Folhas de Planta
20.
JCO Oncol Pract ; 16(10): e1050-e1059, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32468925

RESUMO

PURPOSE: Early detection and management of symptoms in patients with cancer improves outcomes. However, the optimal approach to symptom monitoring and management is unknown. InSight Care is a mobile health intervention that captures symptom data and facilitates patient-provider communication to mitigate symptom escalation. PATIENTS AND METHODS: Patients initiating antineoplastic treatment at a Memorial Sloan Kettering regional location were eligible. Technology supporting the program included the following: a predictive model that identified patient risk for a potentially preventable acute care visit; a secure patient portal enabling communication, televisits, and daily delivery of patient symptom assessments; alerts for concerning symptoms; and a symptom-trending application. The main outcomes of the pilot were feasibility and acceptability evaluated through enrollment and response rates and symptom alerts, and perceived value evaluated on the basis of qualitative patient and provider interviews. RESULTS: The pilot program enrolled 100 high-risk patients with solid tumors and lymphoma (29% of new treatment starts v goal of 25%). Over 6 months of follow-up, the daily symptom assessment response rate was 56% (the goal was 50%), and 93% of patients generated a severe symptom alert. Patients and providers perceived value in the program, and archetypes were developed for program improvement. Enrolled patients were less likely to use acute care than were other high-risk patients. CONCLUSION: InSight Care was feasible and holds the potential to improve patient care and decrease facility-based care. Future work should focus on optimizing the cadence of patient assessments, the workforce supporting remote symptom management, and the return of symptom data to patients and clinical teams.


Assuntos
Neoplasias , Administração dos Cuidados ao Paciente , Telemedicina , Humanos , Linfoma/terapia , Neoplasias/terapia , Projetos Piloto , Avaliação de Sintomas
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