Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Resultados 1 - 20 de 1.560
Filtrar
Más filtros

Banco de datos
Tipo del documento
Publication year range
1.
CA Cancer J Clin ; 72(6): 570-593, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35653456

RESUMEN

Patients with advanced cancer generate 4 million visits annually to emergency departments (EDs) and other dedicated, high-acuity oncology urgent care centers. Because of both the increasing complexity of systemic treatments overall and the higher rates of active therapy in the geriatric population, many patients experiencing acute decompensations are frail and acutely ill. This article comprehensively reviews the spectrum of oncologic emergencies and urgencies typically encountered in acute care settings. Presentation, underlying etiology, and up-to-date clinical pathways are discussed. Criteria for either a safe discharge to home or a transition of care to the inpatient oncology hospitalist team are emphasized. This review extends beyond familiar conditions such as febrile neutropenia, hypercalcemia, tumor lysis syndrome, malignant spinal cord compression, mechanical bowel obstruction, and breakthrough pain crises to include a broader spectrum of topics encompassing the syndrome of inappropriate antidiuretic hormone secretion, venous thromboembolism and malignant effusions, as well as chemotherapy-induced mucositis, cardiomyopathy, nausea, vomiting, and diarrhea. Emergent and urgent complications associated with targeted therapeutics, including small molecules, naked and drug-conjugated monoclonal antibodies, as well as immune checkpoint inhibitors and chimeric antigen receptor T-cells, are summarized. Finally, strategies for facilitating same-day direct admission to hospice from the ED are discussed. This article not only can serve as a point-of-care reference for the ED physician but also can assist outpatient oncologists as well as inpatient hospitalists in coordinating care around the ED visit.


Asunto(s)
Hipercalcemia , Neoplasias , Anciano , Humanos , Urgencias Médicas , Oncología Médica , Neoplasias/complicaciones , Neoplasias/terapia , Náusea , Hipercalcemia/etiología
2.
Trends Genet ; 40(6): 511-525, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38641471

RESUMEN

Ribonucleases (RNases) play important roles in supporting canonical and non-canonical roles of tRNAs by catalyzing the cleavage of the tRNA phosphodiester backbone. Here, we highlight how recent advances in cryo-electron microscopy (cryo-EM), protein structure prediction, reconstitution experiments, tRNA sequencing, and other studies have revealed new insight into the nucleases that process tRNA. This represents a very diverse group of nucleases that utilize distinct mechanisms to recognize and cleave tRNA during different stages of a tRNA's life cycle including biogenesis, fragmentation, surveillance, and decay. In this review, we provide a synthesis of the structure, mechanism, regulation, and modes of tRNA recognition by tRNA nucleases, along with open questions for future investigation.


Asunto(s)
Microscopía por Crioelectrón , ARN de Transferencia , Ribonucleasas , ARN de Transferencia/genética , ARN de Transferencia/química , Ribonucleasas/genética , Ribonucleasas/química , Ribonucleasas/metabolismo , Humanos , Conformación de Ácido Nucleico
3.
Development ; 151(11)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38752427

RESUMEN

Bone morphogenic protein (BMP) signaling plays an essential and highly conserved role in embryo axial patterning in animal species. However, in mammalian embryos, which develop inside the mother, early development includes a preimplantation stage, which does not occur in externally developing embryos. During preimplantation, the epiblast is segregated from extra-embryonic lineages that enable implantation and development in utero. Yet, the requirement for BMP signaling is imprecisely defined in mouse early embryos. Here, we show that, in contrast to previous reports, BMP signaling (SMAD1/5/9 phosphorylation) is not detectable until implantation when it is detected in the primitive endoderm - an extra-embryonic lineage. Moreover, preimplantation development appears to be normal following deletion of maternal and zygotic Smad4, an essential effector of canonical BMP signaling. In fact, mice lacking maternal Smad4 are viable. Finally, we uncover a new requirement for zygotic Smad4 in epiblast scaling and cavitation immediately after implantation, via a mechanism involving FGFR/ERK attenuation. Altogether, our results demonstrate no role for BMP4/SMAD4 in the first lineage decisions during mouse development. Rather, multi-pathway signaling among embryonic and extra-embryonic cell types drives epiblast morphogenesis postimplantation.


Asunto(s)
Implantación del Embrión , Estratos Germinativos , Morfogénesis , Proteína Smad4 , Animales , Femenino , Ratones , Blastocisto/metabolismo , Blastocisto/citología , Proteína Morfogenética Ósea 4/metabolismo , Proteína Morfogenética Ósea 4/genética , Implantación del Embrión/genética , Embrión de Mamíferos/metabolismo , Desarrollo Embrionario/genética , Endodermo/metabolismo , Endodermo/embriología , Regulación del Desarrollo de la Expresión Génica , Estratos Germinativos/metabolismo , Ratones Noqueados , Morfogénesis/genética , Transducción de Señal , Proteína Smad4/metabolismo , Proteína Smad4/genética
4.
Cell ; 151(7): 1501-1512, 2012 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-23219485

RESUMEN

Macroautophagy is a bulk clearance mechanism in which the double-membraned phagophore grows and engulfs cytosolic material. In yeast, the phagophore nucleates from a cluster of 20-30 nm diameter Atg9-containing vesicles located at a multiprotein assembly known as the preautophagosomal structure (PAS). The crystal structure of a 2:2:2 complex of the earliest acting PAS proteins, Atg17, Atg29, and Atg31, was solved at 3.05 Å resolution. Atg17 is crescent shaped with a 10 nm radius of curvature. Dimerization of the Atg17-Atg31-Atg29 complex is critical for both PAS formation and autophagy, and each dimer contains two separate and complete crescents. Upon induction of autophagy, Atg17-Atg31-Atg29 assembles with Atg1 and Atg13, which in turn initiates the formation of the phagophore. The C-terminal EAT domain of Atg1 was shown to sense membrane curvature, dimerize, and tether lipid vesicles. These data suggest a structural mechanism for the organization of Atg9 vesicles into the early phagophore.


Asunto(s)
Proteínas Portadoras/química , Proteínas Fúngicas/química , Complejos Multiproteicos/química , Fagosomas/metabolismo , Saccharomycetales/química , Saccharomycetales/citología , Secuencia de Aminoácidos , Autofagia , Proteínas Relacionadas con la Autofagia , Proteínas Portadoras/metabolismo , Cristalografía por Rayos X , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Saccharomycetales/metabolismo , Alineación de Secuencia
5.
Nano Lett ; 24(40): 12361-12367, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39146017

RESUMEN

Electrodeposition is a versatile method for synthesizing nanostructured films, but controlling the morphology of films containing two or more elements requires a detailed understanding of the deposition process. We used liquid cell transmission electron microscopy to follow the electrodeposition of PtNi nanoparticle films on a carbon electrode during cyclic voltammetry. These in situ observations show that the film thickness increases with each cycle, and by the fourth cycle, branched and porous structures could be deposited. Synchrotron studies using in situ transmission X-ray microscopy further revealed that Ni was deposited in the oxide phase. Ex situ studies of bulk electrodeposited PtNi nanoparticle films indicated the number of cycles and the scanning rate were the most influential parameters, resulting in a different thickness, a different homogeneity, a different nanoparticle size, and a different surface structure, while the precursor concentration did not have a significant influence. By varying the potential range, we were able to obtain films with different elemental compositions.

6.
J Biol Chem ; 299(9): 105138, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37544645

RESUMEN

Through its role in intron cleavage, tRNA splicing endonuclease (TSEN) plays a critical function in the maturation of intron-containing pre-tRNAs. The catalytic mechanism and core requirement for this process is conserved between archaea and eukaryotes, but for decades, it has been known that eukaryotic TSENs have evolved additional modes of RNA recognition, which have remained poorly understood. Recent research identified new roles for eukaryotic TSEN, including processing or degradation of additional RNA substrates, and determined the first structures of pre-tRNA-bound human TSEN complexes. These recent discoveries have changed our understanding of how the eukaryotic TSEN targets and recognizes substrates. Here, we review these recent discoveries, their implications, and the new questions raised by these findings.


Asunto(s)
Endorribonucleasas , Eucariontes , Precursores del ARN , Empalme del ARN , ARN de Transferencia , Humanos , Intrones/genética , Conformación de Ácido Nucleico , Precursores del ARN/química , Precursores del ARN/metabolismo , ARN de Transferencia/química , ARN de Transferencia/metabolismo , Especificidad por Sustrato , Eucariontes/enzimología , Endorribonucleasas/química , Endorribonucleasas/metabolismo
7.
Ecol Lett ; 27(3): e14390, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38549267

RESUMEN

Chance pervades life. In turn, life histories are described by probabilities (e.g. survival and breeding) and averages across individuals (e.g. mean growth rate and age at maturity). In this study, we explored patterns of luck in lifetime outcomes by analysing structured population models for a wide array of plant and animal species. We calculated four response variables: variance and skewness in both lifespan and lifetime reproductive output (LRO), and partitioned them into contributions from different forms of luck. We examined relationships among response variables and a variety of life history traits. We found that variance in lifespan and variance in LRO were positively correlated across taxa, but that variance and skewness were negatively correlated for both lifespan and LRO. The most important life history trait was longevity, which shaped variance and skew in LRO through its effects on variance in lifespan. We found that luck in survival, growth, and fecundity all contributed to variance in LRO, but skew in LRO was overwhelmingly due to survival luck. Rapidly growing populations have larger variances in LRO and lifespan than shrinking populations. Our results indicate that luck-induced genetic drift may be most severe in recovering populations of species with long mature lifespan and high iteroparity.


Asunto(s)
Rasgos de la Historia de Vida , Reproducción , Humanos , Animales , Reproducción/genética , Fertilidad , Flujo Genético , Longevidad/fisiología
8.
Br J Haematol ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39082439

RESUMEN

Venetoclax (VEN) combined with hypomethylating agents (HMA) decitabine or azacitidine is used for adult acute myeloid leukaemia (AML), but its application in paediatric, adolescent and young adult (AYA) AML lacks prospective studies. We performed a retrospective chart review of paediatric and AYA AML patients treated with HMA + VEN at Cincinnati Children's Hospital Medical Centre. Twenty-seven patients received 30 HMA + VEN treatment courses for relapsed/refractory (R/R, n = 21) or newly diagnosed (n = 9) AML due to ineligibility for intensive chemotherapy. The R/R cohort had high-risk cytomolecular genetic alterations and prior extensive treatments, with 50% (n = 9) of relapse patients (n = 18) having undergone haematopoietic stem cell transplantation (HSCT). Venetoclax treatment using the 400 mg adult exposure-equivelant dosing (AED) had a median duration of 21 days (range 7-30 days). Grade 3-4 toxicities included neutropenia (90%), anaemia (64%), thrombocytopenia (64%) and febrile neutropenia (44%). The overall complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 73% (77% minimal residual disease [MRD] negativity <0.1%), with 60% undergoing HSCT. Among newly diagnosed patients (n = 9), 89% achieved CR/CRi (78% MRD negativity) and 78% proceeded to HSCT. The R/R cohort (n = 21) showed a 67% CR/CRi rate (71% MRD negativity), with 52% undergoing HSCT. These findings support the safety and efficacy of HMA + VEN in paediatric/AYA AML, indicating it as a viable option for patients unfit for intensive chemotherapy. Further studies are necessary to determine optimal venetoclax dosing, chemotherapy combinations and pharmacokinetics in this population.

9.
Am Nat ; 204(2): E11-E27, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39008843

RESUMEN

AbstractIn many species, a few individuals produce most of the next generation. How much of this reproductive skew is driven by variation among individuals in fixed traits, how much by external factors, and how much by random chance? And what does it take to have truly exceptional lifetime reproductive output (LRO)? In the past, we and others have partitioned the variance of LRO as a proxy for reproductive skew. Here we explain how to partition LRO skewness itself into contributions from fixed trait variation, four forms of "demographic luck" (birth state, fecundity luck, survival trajectory luck, and growth trajectory luck), and two kinds of "environmental luck" (birth environment and environment trajectory). Each of these is further partitioned into contributions at different ages. We also determine what we can infer about individuals with exceptional LRO. We find that reproductive skew is largely driven by random variation in lifespan, and exceptional LRO generally results from exceptional lifespan. Other kinds of luck frequently bring skewness down rather than increasing it. In populations where fecundity varies greatly with environmental conditions, getting a good year at the right time can be an alternate route to exceptional LRO, so that LRO is less predictive of lifespan.


Asunto(s)
Fertilidad , Longevidad , Reproducción , Animales , Modelos Biológicos , Ambiente
10.
Anal Chem ; 96(12): 4942-4951, 2024 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-38478960

RESUMEN

Bromochloro alkanes (BCAs) have been manufactured for use as flame retardants for decades, and preliminary environmental risk screening suggests they are likely to behave similarly to polychlorinated alkanes (PCAs), subclasses of which are restricted as Stockholm Convention Persistent Organic Pollutants (POPs). BCAs have rarely been studied in the environment, although some evidence suggests they may migrate from treated-consumer materials into indoor dust, resulting in human exposure via inadvertent ingestion. In this study, BCA-C14 mixture standards were synthesized and used to validate an analytical method. This method relies on chloride-enhanced liquid chromatography-electrospray ionization-Orbitrap-high resolution mass spectrometry (LC-ESI-Orbitrap-HRMS) and a novel CP-Seeker integration software package for homologue detection and integration. Dust sample preparation via ultrasonic extraction, acidified silica cleanup, and fractionation on neutral silica cartridges was found to be suitable for BCAs, with absolute recovery of individual homologues averaging 66 to 78% and coefficients of variation ≤10% in replicated spiking experiments (n = 3). In addition, a total of 59 indoor dust samples from six countries, including Australia (n = 10), Belgium (n = 10), Colombia (n = 10), Japan (n = 10), Thailand (n = 10), and the United States of America (n = 9), were analyzed for BCAs. BCAs were detected in seven samples from the U.S.A., with carbon chain lengths of C8, C10, C12, C14, C16, C18, C24 to C28, C30 and C31 observed overall, though not detected in samples from any other countries. Bromine numbers of detected homologues in the indoor dust samples ranged Br1-4 as well as Br7, while chlorine numbers ranged Cl2-11. BCA-C18 was the most frequently detected, observed in each of the U.S.A. samples, while the most prevalent degrees of halogenation were homologues of Br2 and Cl4-5. Broad estimations of BCA concentrations in the dust samples indicated that levels may approach those of other flame retardants in at least some instances. These findings suggest that development of quantification strategies and further investigation of environmental occurrence and health implications are needed.


Asunto(s)
Contaminación del Aire Interior , Retardadores de Llama , Humanos , Monitoreo del Ambiente , Organofosfatos/análisis , Polvo/análisis , Retardadores de Llama/análisis , Contaminación del Aire Interior/análisis , Halógenos , Dióxido de Silicio/análisis
11.
Development ; 148(13)2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34036333

RESUMEN

Fluorescent proteins and epitope tags can reveal protein localization in cells and animals, yet the large size of many tags hinders efficient genome targeting. Accordingly, many studies have relied on characterizing overexpressed proteins, which might not recapitulate endogenous protein activities. Here, we present two strategies for higher throughput production of endogenous protein reporters in mice, focusing on the blastocyst model of development. Our first strategy makes use of a split fluorescent protein, mNeonGreen2 (mNG2). Knock-in of a small portion of the mNG2 gene, in frame with gene coding regions of interest, was highly efficient in embryos, potentially obviating the need to establish mouse lines. When complemented by the larger portion of the mNG2 gene, fluorescence was reconstituted and endogenous protein localization faithfully reported in living embryos. Our second strategy achieves in-frame knock-in of a relatively small protein tag, which provides high efficiency and higher sensitivity protein reporting. Together, these two approaches provide complementary advantages and enable broad downstream applications.


Asunto(s)
Blastocisto/fisiología , Genoma , Animales , Sistemas CRISPR-Cas , Línea Celular , Técnica del Anticuerpo Fluorescente , Técnicas de Sustitución del Gen , Proteínas Fluorescentes Verdes/genética , Ratones , Factores de Transcripción
12.
J Pediatr ; 271: 114079, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38692562

RESUMEN

We sought to determine the prevalence of sexual health counseling in patients with Duchenne muscular dystrophy in a single-institution setting. Keywords related to sexual health and development concerns were documented at least once for 75% of patients across the duration of their care. Integration of sexual health discussions was facilitated by comprehensive multidisciplinary support, particularly with the inclusion of specialists in endocrinology and adolescent medicine.


Asunto(s)
Distrofia Muscular de Duchenne , Grupo de Atención al Paciente , Salud Sexual , Humanos , Distrofia Muscular de Duchenne/terapia , Adolescente , Masculino , Niño , Consejo
13.
Reproduction ; 168(5)2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39190001

RESUMEN

In brief: Animal studies are needed to inform clinical guidance on the effects of testosterone gender-affirming hormone therapy (T-GAHT) on fertility. This review summarizes current animal models of T-GAHT and identifies gaps in knowledge for future study. Abstract: Testosterone gender affirming hormone therapy (T-GAHT) is frequently used by transgender and gender-diverse individuals assigned female at birth to establish masculinizing characteristics. Although many seek parenthood, particularly as a gestational parent or through surrogacy, the current standard guidance of fertility counseling for individuals on testosterone (T) lacks clarity. At this time, individuals are typically recommended to undergo fertility preservation or stop treatment, associating T-therapy with a loss of fertility; however, there is an absence of consistent information regarding the true fertility potential for transgender and gender-diverse adults and adolescents. This review evaluates recent studies that utilize animal models of T-GAHT to relate to findings from clinical studies, with a more specific focus on fertility. Relevant literature based on murine models in post- and pre-pubertal populations has suggested reversibility of the impacts of T-GAHT, alone or following gonadotropin-releasing hormone agonist (GnRHa), on reproduction. These studies reported changes in clitoral area and ovarian morphology, including corpora lutea, follicle counts, and ovarian weights from T-treated mice. Future studies should aim to determine the impact of the duration of T-treatment and cessation on fertility outcomes, as well as establish animal models that are clinically representative of these outcomes with respect to gender diverse populations.


Asunto(s)
Salud Reproductiva , Personas Transgénero , Animales , Humanos , Femenino , Masculino , Testosterona/uso terapéutico , Testosterona/farmacología , Modelos Animales , Terapia de Reemplazo de Hormonas , Reproducción/efectos de los fármacos , Procedimientos de Reasignación de Sexo/métodos , Transexualidad/tratamiento farmacológico , Fertilidad/efectos de los fármacos
14.
Prev Med ; 179: 107828, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38110159

RESUMEN

OBJECTIVE: The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription. METHODS: We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days' supply and a refill prescription. RESULTS: Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days' supply) and headache (3-4 days' supply). CONCLUSIONS: Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined.


Asunto(s)
Dolor Musculoesquelético , Radiculopatía , Adulto , Humanos , Analgésicos Opioides/uso terapéutico , Estudios Retrospectivos , Pacientes Ambulatorios , Dolor Musculoesquelético/diagnóstico , Dolor Musculoesquelético/tratamiento farmacológico , Prescripciones , Cefalea , Pautas de la Práctica en Medicina , Dolor de Espalda
15.
Phys Chem Chem Phys ; 26(8): 6532-6539, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38323476

RESUMEN

We compute EOM-EA-CCSD and EOM-EA-CCSDT potential energy curves and one-electron properties of several anions at bond lengths close to where these states become unbound. We compare the anions of HCl and pyrrole, which are associated with s-wave scattering, with N2 and H2, which correspond to resonances. For HCl and pyrrole, we observe, on inclusion of diffuse basis functions, a pronounced bending effect in the anionic potential energy curves near the crossing points with their corresponding neutral molecules. Additionally, we observe that the Dyson orbital and second moment of the electron density become extremely large in this region; for HCl, the size of the latter becomes 5 orders of magnitude larger over a range of 5 pm. This behaviour is not observed in H2 or N2. Our work thus shows that bound state electronic-structure methods can distinguish between anions that turn into electronic resonances and those associated with s-wave scattering states.

16.
Prehosp Emerg Care ; 28(2): 390-397, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-36862061

RESUMEN

INTRODUCTION: The transition of Army Combat Medic Specialists (Military Occupational Specialty Code: 68W) from military to civilian emergency medical services (EMS) is challenging, and the pathway is not clearly defined. Our objective was to evaluate the current military requirements for 68W and how they compare to the 2019 EMS National Scope of Practice Model (SoPM) for the civilian emergency medical technician (EMT) and advanced emergency medical technician (AEMT). METHODS: This was a cross-sectional evaluation of the 68W skill floor as defined by the Soldier's Manual and Trainer's Guide Healthcare Specialist and Medical Education and Demonstration of Individual Competence in comparison to the 2019 SoPM, which categorizes EMS tasks into seven skill categories. Military training documents were reviewed and extracted for specific information on military scope of practice and task-specific training requirements. Descriptive statistics were calculated. RESULTS: Army 68Ws were noted to perform all (59/59) tasks that coincide with the EMT SoPM. Further, Army 68W practiced above scope in the following skill categories: airway/ventilation (3 tasks); medication administration route (7 tasks); medical director approved medication (6 tasks); intravenous initiation maintenance fluids (4 tasks); and miscellaneous (1 task). Army 68W perform 96% (74/77) of tasks aligned with the AEMT SoPM, excluding tracheobronchial suctioning of an intubated patient, end-tidal CO2 monitoring or waveform capnography, and inhaled nitrous oxide monitoring. Additionally, the 68W scope included six tasks that were above the SoPM for AEMT; airway/ventilation (2 tasks); medication administration route (2 tasks); and medical director approved medication (2 tasks). CONCLUSIONS: The scope of practice of U.S. Army 68W Combat Medics aligns well with the civilian 2019 Scope of Practice Model for EMTs and AEMTs. Based on the comparative scope of practice analysis, transitioning from Army 68W Combat Medic to civilian AEMT would require minimal additional training. This represents a promising potential workforce to assist with EMS workforce challenges. Although aligning the scope of practice is a promising first step, future research is needed to assess the relationship of Army 68Ws training with state licensure and certification equivalency to facilitate this transition.


Asunto(s)
Servicios Médicos de Urgencia , Auxiliares de Urgencia , Personal Militar , Humanos , Médicos de Combate , Estudios Transversales , Alcance de la Práctica , Certificación
17.
Nucleic Acids Res ; 50(14): 8290-8301, 2022 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-35801916

RESUMEN

Coronaviruses generate double-stranded (ds) RNA intermediates during viral replication that can activate host immune sensors. To evade activation of the host pattern recognition receptor MDA5, coronaviruses employ Nsp15, which is a uridine-specific endoribonuclease. Nsp15 is proposed to associate with the coronavirus replication-transcription complex within double-membrane vesicles to cleave these dsRNA intermediates. How Nsp15 recognizes and processes dsRNA is poorly understood because previous structural studies of Nsp15 have been limited to small single-stranded (ss) RNA substrates. Here we present cryo-EM structures of SARS-CoV-2 Nsp15 bound to a 52nt dsRNA. We observed that the Nsp15 hexamer forms a platform for engaging dsRNA across multiple protomers. The structures, along with site-directed mutagenesis and RNA cleavage assays revealed critical insight into dsRNA recognition and processing. To process dsRNA Nsp15 utilizes a base-flipping mechanism to properly orient the uridine within the active site for cleavage. Our findings show that Nsp15 is a distinctive endoribonuclease that can cleave both ss- and dsRNA effectively.


Asunto(s)
COVID-19 , Endorribonucleasas , Endorribonucleasas/metabolismo , Humanos , ARN Bicatenario/genética , SARS-CoV-2/genética , Uridina , Proteínas no Estructurales Virales/metabolismo
18.
Artículo en Inglés | MEDLINE | ID: mdl-38762048

RESUMEN

As climate change alters the hydric regime of many habitats, understanding the hydric physiology of animals becomes increasingly important. Plasma osmolality is a popular metric to assess an organism's hydration, but samples often need to be stored before being analyzed, under varying conditions and for different lengths of time. Previous studies on plasma storage conditions, and how they impact sample integrity, are minimal and have focused more on clinical applications than field studies. We studied the stability of osmolality values from wild rattlesnake plasma samples stored in commonly used plastic snap-cap tubes under different time (0, 2, 3, 7, 29 days) and temperature (refrigerated at 2 °C and frozen at -18 °C) treatments. We hypothesized that frozen samples would remain more stable (e.g., retain osmolality values more similar to baseline values) than refrigerated samples because freezing the plasma would reduce evaporation. We found that osmolality of samples increased over time at both temperatures, becoming significantly higher than baseline after 7 days. Contrary to our prediction, osmolality increased more in frozen samples than in refrigerated samples. We discuss possible reasons for our results, along with their implications. To obtain the most accurate plasma osmolality values, we recommend refrigerating plasma samples for as short a time as possible, 3 days or fewer, before analyzing them on an osmometer.


Asunto(s)
Temperatura , Concentración Osmolar , Animales , Factores de Tiempo , Plasma/química , Plasma/metabolismo , Recolección de Muestras de Sangre/métodos , Manejo de Especímenes/métodos , Congelación
19.
Am J Perinatol ; 41(9): 1113-1119, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38373709

RESUMEN

OBJECTIVE: This study aimed to compare sleep quality at 1 year postpartum following a hypertensive disorder of pregnancy (HDP) among individuals with persistent postpartum hypertension (HTN) compared with those with normal blood pressures (BPs). STUDY DESIGN: We combined data from the Heart Health 4 New Moms pilot randomized trial (n = 118) and the Pathways prospective cohort study (n = 36). Individuals with a singleton pregnancy complicated by gestational HTN or preeclampsia underwent a research study visit at a mean 48.7 ± 9.5 weeks postpartum with standardized BP measurement and assessment of subjective sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Persistent postpartum HTN was defined as Stage 1 HTN or greater (mean systolic BP ≥ 130 mm Hg or mean diastolic BP ≥ 80 mm Hg over three measurements at rest) or requiring antihypertensive medication. Statistical analysis was performed using univariate and multivariable logistic regression analyses. RESULTS: Of 154 individuals with an HDP included in the analysis, 84 (55%) were normotensive at 1 year postpartum and 70 (45%) had persistent postpartum HTN. Individuals with persistent postpartum HTN were more likely to be older, self-identify as Black race, have higher prepregnancy and 1-year postpartum body mass index (BMI), be multiparous, and deliver at an earlier gestational age. The mean global PSQI score was 8.7 ± 3.7, with 81% reporting poor sleep (PSQI > 5), and scores were higher among individuals who were persistently hypertensive (9.6 ± 3.5) compared with those who were normotensive at 1 year postpartum (7.9 ± 3.6), p < 0.01. Findings were unchanged in a multivariable model adjusting for age, self-reported race, prepregnancy BMI, and parity. CONCLUSION: Following an HDP, individuals reported poor sleep quality at 1 year postpartum. Individuals with persistent postpartum HTN reported lower sleep quality, suggesting that sleep behavior may be a target for intervention to improve maternal cardiovascular health following an HDP. KEY POINTS: · After an HDP, poor sleep quality was common at 1 year postpartum.. · Those with persistent postpartum HTN reported worse sleep quality at 1 year postpartum.. · Sleep behavior may be a target for intervention to improve maternal cardiovascular health..


Asunto(s)
Hipertensión Inducida en el Embarazo , Hipertensión , Periodo Posparto , Calidad del Sueño , Adulto , Femenino , Humanos , Embarazo , Adulto Joven , Presión Sanguínea , Índice de Masa Corporal , Modelos Logísticos , Proyectos Piloto , Preeclampsia , Estudios Prospectivos , Trastornos Puerperales
20.
Community Ment Health J ; 60(3): 620-625, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-37804403

RESUMEN

Federally funded medical and behavioral healthcare programs often have substantial evaluation outcome tracking and reporting requirements, which can become burdensome to program staff resulting in decreased buy-in, increased chance of staff burnout and turnover, and less rigorous and consistent data collection efforts. To address this issue, a novel data collection approach, "exception reporting," was implemented to supplement and support the required data collection for a federally funded Assertive Outpatient Treatment (AOT) program. This work details the process and outcomes related to exception reporting for this comprehensive behavioral health treatment program that serves justice involved clients with serious mental illness (SMI). Results indicate that exception reporting was easily integrated into clinician's normal workflows and resulted in a number of benefits. Specifically, results indicated that exception reporting decreased the data collection burden for program staff while allowing them to efficiently track program outcomes required by the funder. Additional research into which practice settings exception reporting can most easily be integrated into, and which client outcomes may be best tracked using this methodology, is indicated.


Asunto(s)
Atención a la Salud , Pacientes Ambulatorios , Humanos , Evaluación de Resultado en la Atención de Salud
SELECCIÓN DE REFERENCIAS
Detalles de la búsqueda