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The proliferation of Distributed Energy Resources (DERs) is paving the way for new energy-efficient services that aim to make end-users more active. According to the literature, these services will be managed by a central figure, aggregators. This paper proposes several business models to accommodate them in the electric power industry. Several potential alternatives are identified from the study of different design elements, such as the control strategy, architecture, and signals that need to be exchanged. These alternatives are then tested by analyzing pairwise relationships between all the actors involved (Aggregator-Prosumers, Aggregator-DSO, and Aggregator-TSO). Every business model is first explained individually, including how contracts would operate, in order to determine their advantages and drawbacks. Finally, a comparison of all the alternatives is put forward together with an overview of the main initiatives that have already been implemented.
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Perioperative medication management is a complex topic. Physicians working in the perioperative space are frequently called upon to make decisions regarding continuing or stopping certain medications. For patients with psychiatric disorders, the overwhelming recommendation is to continue therapy with heightened awareness of anesthesiologists regarding potential side effects or medication interactions.
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BACKGROUND: There is an increasing need to promote diversity, equity, and inclusion (DEI) in all aspects of academic medicine, including through continuing medical education. Although professional medical organizations' annual meetings play an instrumental role in continuing medical education for physicians, there are no studies describing DEI content in the annual meeting programming of professional medical organizations, including the Academy of Consultation-Liaison Psychiatry (ACLP), the primary professional organization for consultation-liaison psychiatrists. OBJECTIVE: To examine the ACLP annual meeting titles using Content Analysis. METHODS: We examined the publicly available ACLP annual meeting content titles on the ACLP website from 2010 to 2021. National DEI leaders from ACLP's DEI subcommittee iteratively generated keywords that covered a broad scope of DEI-related themes. Each annual meeting's content was independently coded by 2 members of the DEI subcommittee with discrepancies adjudicated by 2 additional members. Descriptive statistics were used to characterize the content of the annual meeting. RESULTS: Of the 2615 annual meeting titles from 2010 to 2021 that were analyzed, 2531 were not coded to have DEI themes. Three percent (n = 84) of titles were coded to have a DEI theme as follows: Culture/diversity (n = 20, 24%), bias/disparities (n = 17, 20%), race/racism (n = 17, 20%), social justice (n = 12, 14%), gender/sexism (n = 10, 12%), and LGBTQ+ (n = 8, 10%). The frequency of DEI titles each year ranged from 1% (2010, 2018) to 17% (2021) with an increase in DEI content in 2021 (n = 24, 17%). CONCLUSIONS: Although professional medical organizations like the ACLP are poised to leverage their continuing medical education platforms embedded in annual meeting programming to train consultation-liaison psychiatrists on DEI topics, our findings suggest more work is needed to develop and promote DEI-focused educational programming for their annual meetings.
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Recycling of membrane proteins enables the reuse of receptors, ion channels and transporters. A key component of the recycling machinery is the endosomal sorting complex for promoting exit 1 (ESCPE-1), which rescues transmembrane proteins from the endolysosomal pathway for transport to the trans-Golgi network and the plasma membrane. This rescue entails the formation of recycling tubules through ESCPE-1 recruitment, cargo capture, coat assembly and membrane sculpting by mechanisms that remain largely unknown. Herein, we show that ESCPE-1 has a single-layer coat organization and suggest how synergistic interactions between ESCPE-1 protomers, phosphoinositides and cargo molecules result in a global arrangement of amphipathic helices to drive tubule formation. Our results thus define a key process of tubule-based endosomal sorting.
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Proteínas Portadoras , Endosomas , Endosomas/metabolismo , Transporte de Proteínas , Proteínas Portadoras/metabolismo , Proteínas de la Membrana/metabolismo , Membrana Celular/metabolismoRESUMEN
OBJECTIVE: Electroconvulsive therapy (ECT) devices are classified as class II (moderate risk) for the treatment of depressive disorders and catatonia in patients aged 13 and older, but it is unknown how often the treatment is utilized by child and adolescent patients. The aim of this study was to examine the demographics of child and adolescent hospitalizations involving ECT, the medical and psychiatric comorbidities of these hospitalizations, and the overall number of treatments administered per hospitalization. METHOD: The 2019 Kids' Inpatient Database, a national sample of pediatric discharges from 3998 acute care hospitals, was analyzed for hospitalizations involving patients aged 19 and younger receiving ECT based on inpatient procedural codes. RESULTS: 315 (95% confidence interval 275 to 354) discharges among child and adolescent patients, or 0.03% of youth hospitalizations, involved the administration of ECT in the KID in 2019. Hospitalizations in the Northeast, those involving patients residing in ZIP codes in the top income quartile, and those for commercially insured patients had higher odds of ECT administration. Primary discharge diagnoses among ECT recipients were major depressive disorder (143; 46.4%), schizophrenia and other psychotic disorders (71; 23.1%) and bipolar disorder (59; 19.2%). In total 153 (48.6%) of ECT recipients had a coded diagnosis of suicidal ideation. Hospitalizations involved a median of 2 (IQR 1 to 5) ECT treatments before discharge. CONCLUSIONS: ECT is rarely utilized in the inpatient treatment of child and adolescent patients, but is most often administered to patients with mood and psychotic disorders. Commercial insurance and higher income were associated with higher odds of ECT administration, suggesting that access to care may be limited.
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Trastorno Depresivo Mayor , Terapia Electroconvulsiva , Trastornos Psicóticos , Humanos , Niño , Adolescente , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/terapia , Hospitales Generales , Pacientes InternosRESUMEN
Neuroendocrine neoplasms (NENs) are mutationally quiet (low number of mutations/Mb), and epigenetic mechanisms drive their development and progression. We aimed at comprehensively characterising the microRNA (miRNA) profile of NENs, and exploring downstream targets and their epigenetic modulation. In total, 84 cancer-related miRNAs were analysed in 85 NEN samples from lung and gastroenteropancreatic (GEP) origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N = 63) and methylomics (N = 30) were performed to predict miRNA target genes, signalling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas cohorts and in NEN cell lines. We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5-year survival of 80%, 66% and 36%). Expression of the eight-miRNA gene signature correlated with 71 target genes involved in PI3K-Akt and TNFα-NF-kB signalling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. In brief, we identified an 8-miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patients.
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Neoplasias Intestinales , MicroARNs , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , MicroARNs/genética , Pronóstico , Epigénesis Genética , Fosfatidilinositol 3-Quinasas/metabolismo , Tumores Neuroendocrinos/genética , Neoplasias Pancreáticas/genética , Neoplasias Intestinales/genética , Neoplasias Gástricas/genéticaRESUMEN
PROBLEM: Violence in Chicago has been persistently high in low-income communities of color. Recent attention has focused on how structural inequities weaken protective factors that help keep communities healthy and safe. Spikes in community violence seen in Chicago since the COVID-19 pandemic further expose the lack of social service, health care, economic, and political safety nets in low-income communities and the apparent dearth of faith in those systems. APPROACH: The authors contend that a comprehensive, collaborative approach to violence prevention that prioritizes treatment and community partnerships is needed to address social determinants of health and structural characteristics that often provide the context for interpersonal violence. One strategy to address decreasing faith in systems like hospitals is foregrounding frontline paraprofessional prevention workers who possess cultural capital based on their experiences navigating interpersonal and structural violence. Hospital-based violence intervention programs help professionalize these prevention workers by providing a framework for patient-centered crisis intervention and assertive case management. The authors describe how the Violence Recovery Program (VRP), a multidisciplinary hospital-based violence intervention model, leverages the cultural capital of credible messengers to use teachable moments to promote trauma-informed care to violently injured patients, assess their immediate risk for reinjury and retaliation, and connect them to wrap-around services to help aid comprehensive recovery. OUTCOMES: Violence recovery specialists have engaged over 6,000 victims of violence since the program's launch in 2018. Three-quarters of patients expressed social determinants of health needs. Over the past year, specialists have connected over one-third of engaged patients to mental health referrals and community-based social services. NEXT STEPS: High violence rates in Chicago limited case management opportunities in the emergency room. In fall 2022, the VRP began to establish collaborative agreements with community-based street outreach programs and medical-legal partnerships to address structural determinants of health.
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COVID-19 , Pandemias , Humanos , Relaciones Médico-Paciente , Violencia/prevención & control , HospitalesRESUMEN
Delirium, a common neuropsychiatric syndrome among hospitalized patients, has been associated with significant morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). Although delirium is often reversible with prompt diagnosis and appropriate management, timely screening of hospitalized patients, including HSCT recipients at risk for delirium, is lacking. The association between delirium symptoms and healthcare utilization among HSCT recipients is also limited. We conducted a retrospective analysis of 502 hospitalized patients admitted for allogeneic or autologous HSCT at 2 tertiary care hospitals between April 2016 and April 2021. We used Natural Language Processing (NLP) to identify patients with delirium symptoms, as defined by an NLP-assisted chart review of the electronic health record (EHR). We used multivariable regression models to examine the associations between delirium symptoms, clinical outcomes, and healthcare utilization, adjusting for patient-, disease-, and transplantation-related factors. Overall, 44.4% (124 of 279) of patients undergoing allogeneic HSCT and 39.0% (87 of 223) of those undergoing autologous HSCT were identified as having delirium symptoms during their index hospitalization. Two-thirds (139 of 211) of the patients with delirium symptoms were prescribed treatment with antipsychotic medications. Among allogeneic HSCT recipients, delirium symptoms were associated with longer hospital length of stay (ß = 7.960; P < .001), fewer days alive and out of the hospital (ß = -23.669; P < .001), and more intensive care unit admissions (odds ratio, 2.854; P = .002). In autologous HSCT recipients, delirium symptoms were associated with longer hospital length of stay (ß = 2.204; P < .001). NLP-assisted EHR review is a feasible approach to identifying hospitalized patients, including HSCT recipients at risk for delirium. Because delirium symptoms are negatively associated with health care utilization during and after HSCT, our findings underscore the need to efficiently identify patients hospitalized for HSCT who are at risk of delirium to improve their outcomes. © 2023 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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Delirio , Trasplante de Células Madre Hematopoyéticas , Humanos , Estudios Retrospectivos , Hospitalización , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Aceptación de la Atención de Salud , Delirio/diagnóstico , Delirio/epidemiología , Delirio/etiologíaRESUMEN
BACKGROUND: Sisal wool condition is a skin disease affecting Merino sheep in the Argentine Patagonia region. Corynebacterium spp. isolates have previously been isolated from skin swabs from lesions, while specific identification of the bacteria involved has not been reported. HYPOTHESIS/OBJECTIVES: The aim of this work was to characterize the bacterial agent isolated from sisal wool lesions and to develop a diagnostic method for field surveillance. MATERIALS AND METHODS: Molecular identification of a collection of 72 isolates obtained previously was performed using PCR and 16S rRNA and rpoB sequencing. A field survey was carried out on two farms in the Río Negro province of Argentine Patagonia. Swab samples from sheep with and without skin lesions were collected and analysed by PCR and culture. RESULTS: Isolates analysed were confirmed by sequencing as Corynebacterium bovis. Using a PCR test without culture step, all field samples from affected sheep were positive for C. bovis; samples from the healthy skin from the same animals or clinically healthy sheep all were negative. CONCLUSIONS AND CLINICAL RELEVANCE: Sisal wool skin disease was associated with C. bovis infection based on culture and PCR methods; the latter may be useful for helping to pursue a disease control strategy.
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Infecciones por Corynebacterium , Enfermedades de las Ovejas , Enfermedades de la Piel , Ovinos/genética , Animales , Lana , Infecciones por Corynebacterium/diagnóstico , Infecciones por Corynebacterium/veterinaria , Infecciones por Corynebacterium/microbiología , ARN Ribosómico 16S/genética , Enfermedades de las Ovejas/diagnóstico , Corynebacterium/genética , Enfermedades de la Piel/veterinariaRESUMEN
One of the main intoxications to livestock in the Patagonia region of Argentina is the tremorgenic disease "Mal de Huecú", attributed to the consumption of the native grasses Poa huecu and/or Festuca argentina. In this report, five outbreaks of spontaneous intoxications were investigated. Several indole-diterpene alkaloids were identified in Poa huecu and Festuca argentina including the known tremorgen terpendole C and are likely the cause of "Mal de Huecú" disease.
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Diterpenos , Festuca , Micotoxinas , Humanos , Alcaloides Indólicos , Poaceae , Síndrome , Temblor/inducido químicamenteRESUMEN
OBJECTIVE: Catatonia is a neuropsychiatric disorder that can occur in the setting of many illnesses, but the frequency of catatonia diagnosis among hospitalized patients is poorly characterized. This study reports the occurrence of catatonia diagnosis among acute care hospital discharges in the United States and the cooccurring diagnoses of these patients. METHOD: The National Inpatient Sample, an all-payors database of acute care hospital discharges, was queried for patients older than 18 discharged with a diagnosis of catatonia in 2019. RESULTS: 13,630 encounters among the 30,080,038 adult hospitalizations in the NIS during the study year included a diagnosis of catatonia. Total hospital charges for these admissions were $1.15 billion, with 215,165 cumulative hospital days. In this sample, approximately 60% of admissions had a primary psychiatric discharge diagnosis, while 40% had a primary neurologic or medical discharge diagnosis. Procedures were performed in 36.7% of hospitalizations involving catatonia, of which electroconvulsive therapy was most common. CONCLUSIONS: Catatonia is a rare but costly discharge diagnosis among patients in acute care hospitals. It occurs across the age spectrum and is associated with a range of medical and psychiatric comorbidities. Further research is needed to better characterize the occurrence of catatonia and its optimal treatment.
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Catatonia , Adulto , Catatonia/diagnóstico , Catatonia/epidemiología , Catatonia/terapia , Hospitalización , Hospitales , Humanos , Pacientes Internos , Alta del Paciente , Estados Unidos/epidemiologíaRESUMEN
Objective: Catatonia is a neuropsychiatric condition occurring across the age spectrum and associated with great morbidity and mortality. While prospective cohorts have investigated catatonia incidence among psychiatric patients, no studies have comprehensively explored the incidence of catatonia in general hospitals. We examine the incidence of catatonia diagnosis, demographics of catatonia patients, comorbidities, and inpatient procedures utilized among pediatric patients hospitalized with catatonia in the United States. Methods: The Kids' Inpatient Database, a national all-payors sample of pediatric hospitalizations in general hospitals, was examined for the year 2019. Hospitalizations with a discharge diagnosis of catatonia were included in the analysis. Hospitalizations with catatonia as the primary discharge diagnosis were compared to hospitalizations with catatonia as a secondary discharge diagnosis. Results: A total of 900 (95% CI: 850-949) pediatric discharges (291 with catatonia as a primary diagnosis, 609 with catatonia as a secondary diagnosis) occurred during the study year. Mean age was 15.6 ± 2.6 years, and 9.9% were under age 13. Comorbidities were common among patients with catatonia, with psychotic disorders (165; 18.3%), major depressive disorder (69; 7.7%), bipolar disorder (39; 4.3%) and substance-related disorders (20; 2.2%) as the most common primary diagnoses. There was significant comorbidity with neurologic illness, developmental disorders, autism spectrum disorder, and inflammatory conditions. In total 390 catatonia discharges (43.3%) included at least one procedure during admission. Conclusions: catatonia is rarely diagnosed in pediatric patients in general hospitals but is associated with significant and severe psychiatric and medical comorbidities. Further research is needed into the optimal diagnosis, workup, and treatment of catatonia in pediatric patients.
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Catatonia , Terapia Electroconvulsiva , Adolescente , Benzodiazepinas , Humanos , Resultado del TratamientoRESUMEN
Small-Cell Lung Cancer (SCLC) is an aggressive neuroendocrine malignancy with a poor prognosis. Here, we focus on the neuroendocrine SCLC subtypes, SCLC-A and SCLC-N, whose transcription addiction was driven by ASCL1 and NEUROD1 transcription factors which target E-box motifs to activate up to 40% of total genes, the promoters of which are maintained in a steadily open chromatin environment according to ATAC and H3K27Ac signatures. This leverage is used by the marine agent lurbinectedin, which preferentially targets the CpG islands located downstream of the transcription start site, thus arresting elongating RNAPII and promoting its degradation. This abrogates the expression of ASCL1 and NEUROD1 and of their dependent genes, such as BCL2, INSM1, MYC, and AURKA, which are responsible for relevant SCLC tumorigenic properties such as inhibition of apoptosis and cell survival, as well as for a part of its neuroendocrine features. In summary, we show how the transcription addiction of these cells becomes their Achilles's heel, and how this is effectively exploited by lurbinectedin as a novel SCLC therapeutic endeavor.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Carbolinas , Compuestos Heterocíclicos de 4 o más Anillos , Neoplasias Pulmonares , Proteínas Represoras , Carcinoma Pulmonar de Células Pequeñas , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Carbolinas/farmacología , Línea Celular Tumoral , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Regiones Promotoras Genéticas/efectos de los fármacos , Proteínas Represoras/metabolismo , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/metabolismoRESUMEN
Extravasation of monocytes into tissue and to the site of injury is a fundamental immunological process, which requires rapid responses via post translational modifications (PTM) of proteins. Protein arginine methyltransferase 7 (PRMT7) is an epigenetic factor that has the capacity to mono-methylate histones on arginine residues. Here we show that in chronic obstructive pulmonary disease (COPD) patients, PRMT7 expression is elevated in the lung tissue and localized to the macrophages. In mouse models of COPD, lung fibrosis and skin injury, reduced expression of PRMT7 associates with decreased recruitment of monocytes to the site of injury and hence less severe symptoms. Mechanistically, activation of NF-κB/RelA in monocytes induces PRMT7 transcription and consequential mono-methylation of histones at the regulatory elements of RAP1A, which leads to increased transcription of this gene that is responsible for adhesion and migration of monocytes. Persistent monocyte-derived macrophage accumulation leads to ALOX5 over-expression and accumulation of its metabolite LTB4, which triggers expression of ACSL4 a ferroptosis promoting gene in lung epithelial cells. Conclusively, inhibition of arginine mono-methylation might offer targeted intervention in monocyte-driven inflammatory conditions that lead to extensive tissue damage if left untreated.
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Proteína-Arginina N-Metiltransferasas , Enfermedad Pulmonar Obstructiva Crónica , Animales , Arginina/metabolismo , Histonas/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular , Ratones , Monocitos/metabolismo , Proteína-Arginina N-Metiltransferasas/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/genéticaRESUMEN
Over the last decade, the increasing interest in long non-coding RNAs (lncRNAs) has led to the discovery of these transcripts in multiple organisms. LncRNAs tend to be specifically, and often lowly, expressed in certain tissues, cell types and biological contexts. Although lncRNAs participate in the regulation of a wide variety of biological processes, including development and disease, most of their functions and mechanisms of action remain unknown. Poor conservation of the DNA sequences encoding for these transcripts makes the identification of lncRNAs orthologues among different species very challenging, especially between evolutionarily distant species such as flies and humans or mice. However, the functions of lncRNAs are unexpectedly preserved among different species supporting the idea that conservation occurs beyond DNA sequences and reinforcing the potential of characterising lncRNAs in animal models. In this review, we describe the features and roles of lncRNAs in the fruit fly Drosophila melanogaster, focusing on genomic and functional comparisons with human and mouse lncRNAs. We also discuss the current state of advances and limitations in the study of lncRNA conservation and future perspectives.
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ARN Largo no Codificante , Animales , Secuencia de Bases , Drosophila melanogaster/genética , Genoma , Genómica , Humanos , Ratones , ARN Largo no Codificante/genéticaRESUMEN
It is well known that several of the swainsonine-containing plant species found widespread around the world have a negative economic impact in each country. In Argentina, most of the information on the poisonous plant species that produce α-mannosidosis is published in Spanish and thus not available to most English-speaking researchers interested in toxic plants. Therefore, the aim of this review is to summarize the information about swainsonine-containing plants in Argentina, which are extensively distributed throughout different ecoregions of the country. To date, five species from three genera have been shown to induce α-mannosidosis in livestock in Argentina: Ipomoea carnea subsp. fistulosa, Ipomoea hieronymi subsp. calchaquina (Convolvulaceae), Astragalus garbancillo, Astragalus pehuenches (Fabaceae), and Sida rodrigoi (Malvaceae). These species contain the indolizidine alkaloid swainsonine, which inhibits the lysosomal enzyme α-mannosidase and consequently affects glycoprotein metabolism, resulting in partially metabolized sugars. The prolonged consumption of these poisonous plants produces progressive weight loss and clinical signs related to a nervous disorder, characterized by tremors of head and neck, abnormalities of gait, difficulty in standing, ataxia and wide-based stance. Histological lesions are mainly characterized by vacuolation of different cells, especially neurons of the central nervous system. The main animal model used to study α-mannosidosis is the guinea pig because, when experimentally poisoned, it exhibits many of the characteristics of naturally intoxicated livestock.
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Intoxicación por Plantas , alfa-Manosidosis , Animales , Argentina , Cobayas , Intoxicación por Plantas/veterinaria , Plantas Tóxicas , RumiantesRESUMEN
Eukaryotic genomes are packaged into high-order chromatin structures organized in discrete territories inside the cell nucleus, which is surrounded by the nuclear envelope acting as a barrier. This chromatin organization is complex and dynamic and, thus, determining the spatial and temporal distribution and folding of chromosomes within the nucleus is critical for understanding the role of chromatin topology in genome function. Primarily focusing on the regulation of gene expression, we review here how the genome of Drosophila melanogaster is organized into the cell nucleus, from small scale histone-DNA interactions to chromosome and lamina interactions in the nuclear space.