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1.
Nature ; 626(7997): 45-57, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38297170

RESUMEN

The linear production and consumption of plastics today is unsustainable. It creates large amounts of unnecessary and mismanaged waste, pollution and carbon dioxide emissions, undermining global climate targets and the Sustainable Development Goals. This Perspective provides an integrated technological, economic and legal view on how to deliver a circular carbon and plastics economy that minimizes carbon dioxide emissions. Different pathways that maximize recirculation of carbon (dioxide) between plastics waste and feedstocks are outlined, including mechanical, chemical and biological recycling, and those involving the use of biomass and carbon dioxide. Four future scenarios are described, only one of which achieves sufficient greenhouse gas savings in line with global climate targets. Such a bold system change requires 50% reduction in future plastic demand, complete phase-out of fossil-derived plastics, 95% recycling rates of retrievable plastics and use of renewable energy. It is hard to overstate the challenge of achieving this goal. We therefore present a roadmap outlining the scale and timing of the economic and legal interventions that could possibly support this. Assessing the service lifespan and recoverability of plastic products, along with considerations of sufficiency and smart design, can moreover provide design principles to guide future manufacturing, use and disposal of plastics.


Asunto(s)
Contaminación Ambiental , Objetivos , Plásticos , Reciclaje , Desarrollo Sostenible , Biomasa , Dióxido de Carbono/análisis , Dióxido de Carbono/química , Dióxido de Carbono/metabolismo , Contaminación Ambiental/economía , Contaminación Ambiental/legislación & jurisprudencia , Contaminación Ambiental/prevención & control , Contaminación Ambiental/estadística & datos numéricos , Combustibles Fósiles , Calentamiento Global/prevención & control , Gases de Efecto Invernadero/análisis , Plásticos/síntesis química , Plásticos/economía , Plásticos/metabolismo , Plásticos/provisión & distribución , Reciclaje/economía , Reciclaje/legislación & jurisprudencia , Reciclaje/métodos , Reciclaje/tendencias , Energía Renovable , Desarrollo Sostenible/economía , Desarrollo Sostenible/legislación & jurisprudencia , Desarrollo Sostenible/tendencias , Tecnología/economía , Tecnología/legislación & jurisprudencia , Tecnología/métodos , Tecnología/tendencias
2.
J Med Virol ; 96(4): e29549, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38563352

RESUMEN

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population-based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan-Meier curves and log-rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98-1.10; log-rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19; 95% CI: 1.05-1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65; 95% CI: 0.16-2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94-1.1; aHR for 30-39 years: 1.05, 95% CI: 0.99-1.11; aHR for ≥40 years: 0.88, 95% CI: 0.67-1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk.


Asunto(s)
Infecciones por Papillomavirus , Embarazo , Femenino , Humanos , Recién Nacido , Adulto , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Estudios de Cohortes , Estudios Prospectivos , Investigación , Taiwán/epidemiología , Factores de Riesgo
3.
Am J Emerg Med ; 79: 116-121, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38422752

RESUMEN

IMPORTANCE: Medication nonadherence leads to worse health outcomes, increased healthcare service utilization, and increased overall healthcare costs. OBJECTIVE: To determine whether a discharge pharmacy located in the Emergency Department (ED) reduces ED revisits and hospitalizations. DESIGN: This is a cohort study where we extracted data from our electronic medical records with adult encounters between 12/2019-10/2021. For the purpose of this study, we defined a revisit to the ED as within 7 days and an admission within 30 days from prior initial ED visit. SETTING: The University of Chicago Medicine is an academic medical center located in Chicago's South Side. PARTICIPANTS: Between dates of 12/2019-11/2021, we had 78,660 adult distinct encounters. We created 5 different groups: no medications prescribed, ED discharge pharmacy only, e-prescriptions to outside pharmacies, combination of ED pharmacy and e-prescription sent elsewhere, and printed prescriptions with or without any e-prescriptions. EXPOSURE: Our ED pharmacy is located within the adult ED, serving only patients seen and discharged from the adult ED. MAIN OUTCOME(S) AND MEASURE(S): Our primary endpoint is to evaluate if prescribing and dispensing prescriptions from only our ED pharmacy is associated with decreased ED revisits within 7 days and reduced hospitalizations within 30 days of initial ED visit. RESULTS: When comparing patients who received prescriptions only from the ED discharge pharmacy, patients who received no prescriptions were 31.6% (P < 0.001) more likely to revisit our ED, and patients who received e-prescriptions sent to other pharmacies were 10.4% (P = 0.017) more likely to revisit. Patients who received e-prescriptions from other pharmacies were 29.2% (P < 0.001) more likely to be hospitalized and mixture of e-prescriptions were 59.5% (P < 0.001) more likely to be hospitalized compared to the ED pharmacy only group. CONCLUSIONS AND RELEVANCE: We believe having a pharmacy providing medications to patients being discharged from the ED reduces barriers like cost, transportation, and pharmacy access patients face trying to fill prescriptions at their local pharmacy. All of these reductions in barriers provides an easier and more convenient method for patients to obtain their medications at discharge from the ED, reducing the risk of a repeat ED visit and subsequent hospital admission.


Asunto(s)
Farmacias , Farmacia , Adulto , Humanos , Alta del Paciente , Estudios de Cohortes , Hospitalización , Servicio de Urgencia en Hospital
4.
J Health Commun ; 29(7): 440-449, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38832597

RESUMEN

Asian, Pacific Islander, African, and Caribbean communities in the U.S. are heavily impacted by chronic hepatitis B (HBV) and hepatocellular carcinoma (HCC). Educating these groups about the link between the two diseases is imperative to improve screening rates and health outcomes. This study aims to identify and incorporate preferred mediated communication methods into community-specific educational campaigns which emphasize the connection between the conditions, to promote uptake of prevention and management behaviors for HBV and HCC. Fifteen focus groups and two key informant interviews were conducted with Micronesian, Chinese, Hmong, Nigerian, Ghanaian, Vietnamese, Korean, Somali, Ethiopian, Filipino, Haitian, and Francophone West African communities. Data were analyzed using thematic coding and analysis. Findings demonstrate that all communities preferred materials be offered in both English and native languages and requested that materials highlight the connection between HBV and HCC. Delivery channel preferences and messaging themes varied by group. This study provides insight into community-specific preferences for learning about HBV and HCC. The findings can be used to design culturally and linguistically tailored, multi-platform, health education campaigns to facilitate improved HBV screening and vaccination rates and increase knowledge about HCC risk among highly impacted communities in the U.S.


Asunto(s)
Grupos Focales , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/prevención & control , Neoplasias Hepáticas/etnología , Femenino , Masculino , Comunicación en Salud/métodos , Adulto , Disparidades en el Estado de Salud , Persona de Mediana Edad , Carcinoma Hepatocelular/etnología , Carcinoma Hepatocelular/prevención & control , Estados Unidos , Hepatitis B/prevención & control , Hepatitis B/etnología , Hepatitis B Crónica/etnología , Hepatitis B Crónica/prevención & control , Competencia Cultural , Investigación Cualitativa , Etnicidad/estadística & datos numéricos , Etnicidad/psicología , Disparidades en Atención de Salud/etnología
5.
Int J Mol Sci ; 25(5)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38474302

RESUMEN

Our previous research studies have demonstrated the role of microRNA133b (miR133b) in healing the contused spinal cord when administered either intranasally or intravenously 24 h following an injury. While our data showed beneficial effects of exogenous miR133b delivered within hours of a spinal cord injury (SCI), the kinetics of endogenous miR133b levels in the contused spinal cord and rostral/caudal segments of the injury were not fully investigated. In this study, we examined the miR133b dysregulation in a mouse model of moderate unilateral contusion injury at the fifth cervical (C5) level. Between 30 min and 7 days post-injury, mice were euthanized and tissues were collected from different areas of the spinal cord, ipsilateral and contralateral prefrontal motor cortices, and off-targets such as lung and spleen. The endogenous level of miR133b was determined by RT-qPCR. We found that after SCI, (a) most changes in miR133b level were restricted to the injured area with very limited alterations in the rostral and caudal parts relative to the injury site, (b) acute changes in the endogenous levels were predominantly specific to the lesion site with delayed miR133b changes in the motor cortex, and (c) ipsilateral and contralateral hemispheres responded differently to unilateral SCI. Our results suggest that the therapeutic window for exogenous miR133b therapy begins earlier than 24 h post-injury and potentially lasts longer than 7 days.


Asunto(s)
Médula Cervical , Contusiones , MicroARNs , Traumatismos de la Médula Espinal , Animales , Ratones , Contusiones/metabolismo , Modelos Animales de Enfermedad , MicroARNs/metabolismo , MicroARNs/uso terapéutico , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/terapia , Médula Cervical/lesiones
6.
Pharmacogenet Genomics ; 33(2): 19-23, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36729768

RESUMEN

Pharmacogenomics is a crucial piece of personalized medicine. Preemptive pharmacogenomic testing is only used sparsely in the inpatient setting and there are few models to date for fostering the adoption of pharmacogenomic treatment in the inpatient setting. We created a multi-institutional project in Chicago to enable the translation of pharmacogenomics into inpatient practice. We are reporting our implementation process and barriers we encountered with solutions. This study, 'Implementation of Point-of-Care Pharmacogenomic Decision Support Accounting for Minority Disparities', sought to implement pharmacogenomics into inpatient practice at three sites: The University of Chicago, Northwestern Memorial Hospital, and the University of Illinois at Chicago. This study involved enrolling African American adult patients for preemptive genotyping across a panel of actionable germline variants predicting drug response or toxicity risk. We report our approach to implementation and the barriers we encountered engaging hospitalists and general medical providers in the inpatient pharmacogenomic intervention. Our strategies included: a streamlined delivery system for pharmacogenomic information, attendance at hospital medicine section meetings, use of physician and pharmacist champions, focus on hospitalists' care and optimizing system function to fit their workflow, hand-offs, and dealing with hospitalists turnover. Our work provides insights into strategies for the initial engagement of inpatient general medicine providers that we hope will benefit other institutions seeking to implement pharmacogenomics in the inpatient setting.


Asunto(s)
Pacientes Internos , Farmacogenética , Adulto , Humanos , Medicina de Precisión , Pruebas de Farmacogenómica , Farmacéuticos
7.
J Pediatr Gastroenterol Nutr ; 76(3): 385-389, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36728758

RESUMEN

OBJECTIVES: This study examines the sociodemographic differences between elective and nonelective admissions for failure to thrive (FTT). We investigate associations between admission type and hospital resource utilization, including length of stay and feeding tube placement. METHODS: We included children <2 years old with FTT in the nationwide Kids' Inpatient Database. We described differences between elective and nonelective admissions using Fisher exact and t tests. To assess associations of admission type and hospital resource utilization, we used negative binomial and logistic regression for length of stay and feeding tube placement, respectively. RESULTS: In this study of 45,920 admissions (37,224 nonelective vs 8696 elective), we found differences by race and ethnicity, income, and insurance type, among other factors. Compared to elective admissions, nonelective admissions had higher proportions of infants who were Black, Hispanic, and of lower-income. Nonelective admissions were associated with longer lengths of stay (incidence rate ratio 1.46; 95% CI: 1.37-1.55), independent of child age, sex, neighborhood income, insurance, admission day, chronic conditions, and location. Nonelective admissions were associated with lower odds of feeding tube placement compared to elective admissions (adjusted odds ratio 0.62; 0.56-0.68). In the stratified analyses, children of racial and ethnic minority groups admitted nonelectively versus electively had relatively higher odds of feeding tube placement, while White children had relatively lower odds of feeding tube placement. CONCLUSION: There are various sociodemographic differences between elective and nonelective FTT admissions. Future research is warranted to elucidate drivers of these differences, particularly those related to racial and ethnic disparities and structural racism.


Asunto(s)
Etnicidad , Insuficiencia de Crecimiento , Hospitalización , Niño , Preescolar , Humanos , Lactante , Insuficiencia de Crecimiento/epidemiología , Grupos Minoritarios
8.
Circ Res ; 127(9): e210-e231, 2020 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-32755283

RESUMEN

RATIONALE: Brain arteriovenous malformations (AVMs) are abnormal tangles of vessels where arteries and veins directly connect without intervening capillary nets, increasing the risk of intracerebral hemorrhage and stroke. Current treatments are highly invasive and often not feasible. Thus, effective noninvasive treatments are needed. We previously showed that AVM-brain endothelial cells (BECs) secreted higher VEGF (vascular endothelial growth factor) and lower TSP-1 (thrombospondin-1) levels than control BEC; and that microRNA-18a (miR-18a) normalized AVM-BEC function and phenotype, although its mechanism remained unclear. OBJECTIVE: To elucidate the mechanism of action and potential clinical application of miR-18a as an effective noninvasive treatment to selectively restore the phenotype and functionality of AVM vasculature. METHODS AND RESULTS: The molecular pathways affected by miR-18a in patient-derived BECs and AVM-BECs were determined by Western blot, RT-qPCR (quantitative reverse transcription polymerase chain reaction), ELISA, co-IP, immunostaining, knockdown and overexpression studies, flow cytometry, and luciferase reporter assays. miR-18a was shown to increase TSP-1 and decrease VEGF by reducing PAI-1 (plasminogen activator inhibitor-1/SERPINE1) levels. Furthermore, miR-18a decreased the expression of BMP4 (bone morphogenetic protein 4) and HIF-1α (hypoxia-inducible factor 1α), blocking the BMP4/ALK (activin-like kinase) 2/ALK1/ALK5 and Notch signaling pathways. As determined by Boyden chamber assays, miR-18a also reduced the abnormal AVM-BEC invasiveness, which correlated with a decrease in MMP2 (matrix metalloproteinase 2), MMP9, and ADAM10 (ADAM metallopeptidase domain 10) levels. In vivo pharmacokinetic studies showed that miR-18a reaches the brain following intravenous and intranasal administration. Intranasal co-delivery of miR-18a and NEO100, a good manufacturing practices-quality form of perillyl alcohol, improved the pharmacokinetic profile of miR-18a in the brain without affecting its pharmacological properties. Ultra-high-resolution computed tomography angiography and immunostaining studies in an Mgp-/- AVM mouse model showed that miR-18a decreased abnormal cerebral vasculature and restored the functionality of the bone marrow, lungs, spleen, and liver. CONCLUSIONS: miR-18a may have significant clinical value in preventing, reducing, and potentially reversing AVM.


Asunto(s)
Proteína Morfogenética Ósea 4/antagonistas & inhibidores , Células Endoteliales/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Malformaciones Arteriovenosas Intracraneales/terapia , MicroARNs/uso terapéutico , Trombospondina 1/metabolismo , Factores de Crecimiento Endotelial Vascular/metabolismo , Proteína ADAM10/metabolismo , Receptores de Activinas Tipo I/metabolismo , Receptores de Activinas Tipo II/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Humanos , Malformaciones Arteriovenosas Intracraneales/genética , Malformaciones Arteriovenosas Intracraneales/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Monoterpenos/administración & dosificación , Inhibidor 1 de Activador Plasminogénico/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo
9.
Eur Spine J ; 31(7): 1775-1783, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35147769

RESUMEN

PURPOSE: The aim of this study was to characterize if the use of surgical drains or length of drain placement following spine surgery increases the risk of post-operative infection. METHODS: Records of patients undergoing elective spinal surgery at a tertiary care center were collected between May 5, 2016 and August 16, 2018. Pre-operative baseline characteristics were recorded including patient's demographics and comorbidities. Intraoperative procedure information was documented related to procedure type, blood loss, and antibiotics used. Following surgery, patients were then further subdivided into two groups: patients who were discharged with a spinal surgical site drain and patients who did not receive a drain. Post-operative surgical variables included length of stay (LOS), drain length, number of antibiotics given, and type of post-operative infection. Univariate and multivariate statistical analysis was conducted. RESULTS: A total of 671 patients were included in the current study, 386 (57.5%) with and 285 (42.5%) without the drain. The overall infection rate was 5.7% with 6.22% among patients with the drain compared to 4.91% in patients without drain. The univariate analysis identified the following variables to be significantly associated with the infection: total number of surgical levels, spinal region, blood loss, redosing of antibiotics, length of stay, length of drain placement, and number of antibiotics (P < 0.05). However, the multivariate analysis none of the predictors was significant. CONCLUSIONS: The current study shows that the placement of drain does not increase rate of infection, irrespective of levels, length of surgery, or approach.


Asunto(s)
Drenaje , Infección de la Herida Quirúrgica , Antibacterianos/uso terapéutico , Drenaje/efectos adversos , Drenaje/métodos , Humanos , Tiempo de Internación , Región Lumbosacra , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología
10.
Sensors (Basel) ; 22(22)2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36433427

RESUMEN

This paper quantifies the coverage area of Low-Power Wide-Area Networks (LPWAN) for Packet Success Rates (PSR) above 85%, where acceptable Quality of Service (QoS) can be achieved. The network consists of battery-operated end-nodes (ENs) and multiple stationary gateways (GWs). We consider asynchronous communication that uses ALOHA-based random channel access. Each transmission from the ENs can be received by multiple GWs. Such spatial diversity results in favorable Signal-to-Noise ratios (SNR). The LoRa modulation is assumed and its specific features, such as IQ inversion, further contribute to decreasing the impact of interference. An increase in the GW density improves network performance, which allows support for a larger density of end-nodes as well as increasing the coverage area. Our simulation results show that a suburban area of up to 1.44 km2 can be covered with five GWs with up to fifty end-nodes with a PSR greater than 86%.


Asunto(s)
Comunicación , Suministros de Energía Eléctrica , Simulación por Computador , Serogrupo , Relación Señal-Ruido
11.
Health Promot Pract ; 23(1): 32-34, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34414804

RESUMEN

Research has documented the need for mental health services among refugee and immigrant youth. A joint collaboration on a community-based participatory research (CBPR) research project between a university, a local art and health collective, and an immigrant and refugee organization sought to identify and understand the mental health needs and strategies for immigrant youth in Philadelphia through youth discussion and engagement in a variety of art workshops. As a result of the COVID-19 pandemic, this CBPR research project was forced to make several programmatic changes, such as shifting to a virtual setting, that impacted project implementation and intended outcomes. These changes highlight valuable lessons and practical implications in pivoting a program during COVID-19 to continue working with marginalized communities with limited resources, including barriers to technology access, at a time when effectively addressing mental health for immigrant youth has become both more challenging and pressing.


Asunto(s)
COVID-19 , Emigrantes e Inmigrantes , Adolescente , Investigación Participativa Basada en la Comunidad , Humanos , Salud Mental , Pandemias , Philadelphia , SARS-CoV-2
12.
J Am Chem Soc ; 143(27): 10021-10040, 2021 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-34190553

RESUMEN

There is an ever-increasing demand for higher-performing polymeric materials counterbalanced by the need for sustainability throughout the life cycle. Copolymers comprising ester, carbonate, or ether linkages could fulfill some of this demand as their monomer-polymer chemistry is closer to equilibrium, facilitating (bio)degradation and recycling; many monomers are or could be sourced from renewables or waste. Here, an efficient and broadly applicable route to make such copolymers is discussed, a form of switchable polymerization catalysis which exploits a single catalyst, switched between different catalytic cycles, to prepare block sequence selective copolymers from monomer mixtures. This perspective presents the principles of this catalysis, catalyst design criteria, the selectivity and structural copolymer characterization tools, and the properties of the resulting copolymers. Uses as thermoplastic elastomers, toughened plastics, adhesives, and self-assembled nanostructures, and for programmed degradation, among others, are discussed. The state-of-the-art research into both catalysis and products, as well as future challenges and directions, are presented.

13.
J Neurosci Res ; 99(9): 2029-2045, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33969526

RESUMEN

CRISPR (clustered regularly interspaced short palindromic repeat)-based genetic screens offer unbiased and powerful tools for systematic and specific evaluation of phenotypes associated with specific target genes. CRISPR screens have been utilized heavily in vitro to identify functional coding and noncoding genes in a large number of cell types, including glioblastoma (GB), though no prior study has described the evaluation of CRISPR screening in GB in vivo. Here, we describe a protocol for targeting and transcriptionally repressing GB-specific long noncoding RNAs (lncRNAs) by CRISPR interference (CRISPRi) system in vivo, with tumor growth in the mouse cerebral cortex. Given the target-specific parameters of each individual screen, we list general steps involved in transducing guide RNA libraries into GB tumor lines, maintaining sufficient coverage, as well as cortically injecting and subsequently isolating transduced screen tumor cell populations for analysis. Finally, in order to demonstrate the use of this technique to discern an essential lncRNA, HOTAIR, from a nonessential lncRNA, we injected a 1:1 (HOTAIR:control nonessential lncRNA knockdown) mixture of fluorescently tagged U87 GB cells into the cortex of eight mice, evaluating selective depletion of HOTAIR-tagged cells at 2 weeks of growth. Fluorescently tagged populations were analyzed via flow cytometry for hiBFP (control knockdown) and green fluorescent protein (HOTAIR knockdown), revealing 17% (p = 0.007) decrease in fluorescence associated with HOTAIR knockdown relative to control. The described in vivo CRISPR screening methodology thus appears to be an effective option for identifying noncoding (and coding) genes affecting GB growth within the mouse cortex.


Asunto(s)
Neoplasias Encefálicas/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Glioblastoma/genética , ARN no Traducido/genética , Animales , Neoplasias Encefálicas/patología , Sistemas CRISPR-Cas/genética , Línea Celular Tumoral , Técnicas de Inactivación de Genes/métodos , Glioblastoma/patología , Células HEK293 , Humanos , Masculino , Ratones , Ratones Desnudos , Carga Tumoral/genética
14.
Reproduction ; 161(4): 399-409, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33539317

RESUMEN

Advanced maternal age is associated with a decline in fertility and oocyte quality. We used novel metabolic microsensors to assess effects of mare age on single oocyte and embryo metabolic function, which has not yet been similarly investigated in mammalian species. We hypothesized that equine maternal aging affects the metabolic function of oocytes and in vitro-produced early embryos, oocyte mitochondrial DNA (mtDNA) copy number, and relative abundance of metabolites involved in energy metabolism in oocytes and cumulus cells. Samples were collected from preovulatory follicles from young (≤14 years) and old (≥20 years) mares. Relative abundance of metabolites in metaphase II oocytes (MII) and their respective cumulus cells, detected by liquid and gas chromatography coupled to mass spectrometry, revealed that free fatty acids were less abundant in oocytes and more abundant in cumulus cells from old vs young mares. Quantification of aerobic and anaerobic metabolism, respectively measured as oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in a microchamber containing oxygen and pH microsensors, demonstrated reduced metabolic function and capacity in oocytes and day-2 embryos originating from oocytes of old when compared to young mares. In mature oocytes, mtDNA was quantified by real-time PCR and was not different between the age groups and not indicative of mitochondrial function. Significantly more sperm-injected oocytes from young than old mares resulted in blastocysts. Our results demonstrate a decline in oocyte and embryo metabolic activity that potentially contributes to the impaired developmental competence and fertility in aged females.


Asunto(s)
Células del Cúmulo/patología , Regulación del Desarrollo de la Expresión Génica , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Lípidos/análisis , Edad Materna , Mitocondrias/patología , Oocitos/patología , Oogénesis , Animales , Células del Cúmulo/metabolismo , ADN Mitocondrial/análisis , ADN Mitocondrial/genética , Femenino , Caballos , Mitocondrias/metabolismo , Oocitos/metabolismo , Consumo de Oxígeno
15.
Am J Nephrol ; 52(3): 250-260, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33827074

RESUMEN

INTRODUCTION: Use of certain antihypertensive medications has been an area of interest during the COVID-19 pandemic, and several hypotheses have been developed regarding the effects of renin-angiotensin system blockers as well as calcium channel blockers in those infected with COVID-19. We seek to determine the association between exposure to ACEI, ARB, and CCB and outcomes in those admitted to the hospital with COVID-19 infection. METHODS: This retrospective cohort study included 841 adult patients hospitalized with COVID-19 infection at the University of Chicago Medical Center between March 25 and June 22, 2020. Out of these 841, 453 patients had a personal history of hypertension. For the first part, we evaluated primary outcomes of in-hospital mortality and ICU admission in hospitalized COVID-19 patients based on their exposure to particular medications regardless of a personal history of hypertension and compared them with those who were not on these medications. For the second part, we evaluated the aforementioned outcomes in 453 patients with a personal history of hypertension based on their medication exposure. Secondary outcomes of length of stay, readmission rate, and new-onset dialysis requirement were also compared across the study groups. RESULTS: Out of 841 patients, 111 (13.19%) were on ACEI/ARB (median age: 66.1, SD 15.4; 52.25% females) and 730 (86.80%) were not on them (median age: 56.6, SD 20.3; 50.14% females), while 277 (32.93%) used CCB (median age: 64.6, SD 15.2; 57.04% females) and 564 (67.06%) did not use CCB (median age: 54.6, SD 21.2; 47.16% females). After adjusting for demographics and covariates, neither ACEI/ARB nor CCB exposure was associated with any effect on mortality, but ACEI/ARB exposure was associated with 42% reduction in risk of ICU admissions (OR 0.58, 95% CI [0.35, 0.95], p value 0.03). In addition, combined use of ACEI/ARB and CCB was associated with statistically significant (45%) reduction in ICU admission (OR 0.55, 95% CI [0.32, 0.94], p value 0.029). Out of 453 patients with a personal history of hypertension, 85 (18.76%) were taking ACEI/ARB (median age 65, SD 15.6; 56.47% females) and 368 (81.24%) were not on ACEI/ARB (median age 62.8, SD 16.4; 54.89% females), while 208 (45.92%) out of 453 were on CCB (median age 65; SD 14.8; 60.1% females) and 245 (54.08%) were not on CCB (median age 61.7, SD 17.3; 51.02% females). In the fully adjusted model in this group, ACEI use was associated with 71% reduction in in-house mortality (OR 0.29, 95% CI [0.09, 0.93], p value 0.03). DISCUSSION/CONCLUSION: Among all hospitalized patients with COVID-19 infection, exposure to ACEI/ARB, as well as combined exposure to ACEI/ARB and CCB, were associated with reduced incidence of ICU admissions. In those admitted patients who had a personal history of hypertension, there was a trend towards reduced in-hospital mortality in those exposed to ACEI.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , COVID-19/mortalidad , Bloqueadores de los Canales de Calcio/uso terapéutico , Hipertensión/tratamiento farmacológico , Anciano , COVID-19/complicaciones , COVID-19/etnología , Chicago/epidemiología , Femenino , Humanos , Hipertensión/complicaciones , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tratamiento Farmacológico de COVID-19
16.
Nature ; 526(7571): 118-21, 2015 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-26374997

RESUMEN

Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can affect nanoparticle effectiveness in complex, physiologically relevant systems. Despite the advances in bottom-up nanoengineering and surface chemistry, reductionist functionalization approaches remain inadequate in replicating the complex interfaces present in nature and cannot avoid exposure of foreign materials. Here we report on the preparation of polymeric nanoparticles enclosed in the plasma membrane of human platelets, which are a unique population of cellular fragments that adhere to a variety of disease-relevant substrates. The resulting nanoparticles possess a right-side-out unilamellar membrane coating functionalized with immunomodulatory and adhesion antigens associated with platelets. Compared to uncoated particles, the platelet membrane-cloaked nanoparticles have reduced cellular uptake by macrophage-like cells and lack particle-induced complement activation in autologous human plasma. The cloaked nanoparticles also display platelet-mimicking properties such as selective adhesion to damaged human and rodent vasculatures as well as enhanced binding to platelet-adhering pathogens. In an experimental rat model of coronary restenosis and a mouse model of systemic bacterial infection, docetaxel and vancomycin, respectively, show enhanced therapeutic efficacy when delivered by the platelet-mimetic nanoparticles. The multifaceted biointerfacing enabled by the platelet membrane cloaking method provides a new approach in developing functional nanoparticles for disease-targeted delivery.


Asunto(s)
Antibacterianos/administración & dosificación , Plaquetas/citología , Membrana Celular/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/administración & dosificación , Nanopartículas/química , Adhesividad Plaquetaria , Animales , Antibacterianos/farmacocinética , Vasos Sanguíneos/citología , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patología , Colágeno/química , Colágeno/inmunología , Activación de Complemento/inmunología , Reestenosis Coronaria/sangre , Reestenosis Coronaria/tratamiento farmacológico , Reestenosis Coronaria/metabolismo , Modelos Animales de Enfermedad , Docetaxel , Humanos , Macrófagos/inmunología , Masculino , Ratones , Polímeros/química , Ratas , Ratas Sprague-Dawley , Infecciones Estafilocócicas/sangre , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/citología , Staphylococcus aureus/metabolismo , Taxoides/administración & dosificación , Taxoides/farmacocinética , Liposomas Unilamelares/química , Vancomicina/administración & dosificación , Vancomicina/farmacocinética
17.
J Am Chem Soc ; 142(9): 4367-4378, 2020 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-32078313

RESUMEN

Carbon dioxide/epoxide copolymerization is an efficient way to add value to waste CO2 and to reduce pollution in polymer manufacturing. Using this process to make low molar mass polycarbonate polyols is a commercially relevant route to new thermosets and polyurethanes. In contrast, high molar mass polycarbonates, produced from CO2, generally under-deliver in terms of properties, and one of the most widely investigated, poly(cyclohexene carbonate), is limited by its low elongation at break and high brittleness. Here, a new catalytic polymerization process is reported that selectively and efficiently yields degradable ABA-block polymers, incorporating 6-23 wt % CO2. The polymers are synthesized using a new, highly active organometallic heterodinuclear Zn(II)/Mg(II) catalyst applied in a one-pot procedure together with biobased ε-decalactone, cyclohexene oxide, and carbon dioxide to make a series of poly(cyclohexene carbonate-b-decalactone-b-cyclohexene carbonate) [PCHC-PDL-PCHC]. The process is highly selective (CO2 selectivity >99% of theoretical value), allows for high monomer conversions (>90%), and yields polymers with predictable compositions, molar mass (from 38-71 kg mol-1), and forms dihydroxyl telechelic chains. These new materials improve upon the properties of poly(cyclohexene carbonate) and, specifically, they show good thermal stability (Td,5 ∼ 280 °C), high toughness (112 MJ m-3), and very high elongation at break (>900%). Materials properties are improved by precisely controlling both the quantity and location of carbon dioxide in the polymer chain. Preliminary studies show that polymers are stable in aqueous environments at room temperature over months, but they are rapidly degraded upon gentle heating in an acidic environment (60 °C, toluene, p-toluene sulfonic acid). The process is likely generally applicable to many other lactones, lactides, anhydrides, epoxides, and heterocumulenes and sets the scene for a host of new applications for CO2-derived polymers.

18.
Risk Anal ; 40(3): 608-623, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31691345

RESUMEN

Risk analysis standards are often employed to protect critical infrastructures, which are vital to a nation's security, economy, and safety of its citizens. We present an analysis framework for evaluating such standards and apply it to the J100-10 risk analysis standard for water and wastewater systems. In doing so, we identify gaps between practices recommended in the standard and the state of the art. While individual processes found within infrastructure risk analysis standards have been evaluated in the past, we present a foundational review and focus specifically on water systems. By highlighting both the conceptual shortcomings and practical limitations, we aim to prioritize the shortcomings needed to be addressed. Key findings from this study include (1) risk definitions fail to address notions of uncertainty, (2) the sole use of "worst reasonable case" assumptions can lead to mischaracterizations of risk, (3) analysis of risk and resilience at the threat-asset resolution ignores dependencies within the system, and (4) stakeholder values need to be assessed when balancing the tradeoffs between risk reduction and resilience enhancement.

19.
Vet Ophthalmol ; 23(4): 714-720, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32476246

RESUMEN

OBJECTIVE: To assess lens capsule opacity (LCO) following phacoemulsification in dogs receiving long-term topical ophthalmic flurbiprofen sodium 0.03%. ANIMAL STUDIED: Twenty-five client owned dogs undergoing phacoemulsification surgery for either diabetic or nondiabetic cataracts. METHODS: Prospective, randomized, masked clinical study assessing two groups of dogs for twelve months following phacoemulsification. All dogs underwent a complete eye examination and were photographed at each visit, beginning three weeks post-surgery, and repeated at 2, 3, 6, and 12 months post-surgery. Post-operative treatment protocols were similar for both groups, except that Group F received topical flurbiprofen once daily for 12 months and Group A received artificial tears once daily for 12 months. Digital photographs were analyzed for LCO using a subjective grading scale (0-4). The change in capsular opacities from 3 weeks to 12 months post-surgery was evaluated for each dog, and the groups were compared. RESULTS: There were 25 dogs evaluated post-phacoemulsification at each designated time point of the study. There were 12 dogs in Group A and 13 dogs in Group F. There was no significant statistical difference in LCO score between Groups A and F at baseline (3 weeks post-surgery), 6 months post-surgery, or 12 months post-surgery. Scores did not change significantly from baseline to 12 months within or between groups. CONCLUSIONS: Topical ophthalmic flurbiprofen sodium 0.03% solution applied once daily for 12 months following phacoemulsification does not appear to lead to a decrease in LCO formation as compared to artificial tears control.


Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Enfermedades de los Perros/cirugía , Flurbiprofeno/administración & dosificación , Soluciones Oftálmicas/administración & dosificación , Dolor Postoperatorio/veterinaria , Facoemulsificación/veterinaria , Animales , Perros , Femenino , Masculino , Dolor Postoperatorio/prevención & control , Estudios Prospectivos , Resultado del Tratamiento
20.
Vet Ophthalmol ; 23(4): 690-695, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32437053

RESUMEN

OBJECTIVE: Spontaneous eyeblink rate (SEBR) is inversely proportional to the level of attentional focus in humans. The objective of this study was to evaluate the effects of attentional focus on SEBR in horses. PROCEDURES: Twenty client-owned horses (2.5-23 years of age, five mares, 15 geldings) were evaluated. A GoPro HERO5 Session™ video recorder was attached to the halter and directed toward the eyes. Horses were acclimated for two hours before study commencement. Horses were filmed in five scenarios requiring different levels of attention: alone in a stall ("stall"), stall with an observer ("person"), standing in an arena ("stand"), walking in an arena ("walk"), and trotting in arena ("trot"). Each of the five scenarios was filmed for ten minutes. Video recordings were reviewed, and SEBR (incomplete, complete, and total blinks) was measured for both eyes in each scenario. RESULTS: The median (25%,75%) total SEBRs (blinks/min) were as follows: STALL: OD-16.6 (12.4, 24.3), OS-18.8 (11.5, 26.9); PERSON: OD-17.7 (14.6, 24.2), OS-17.4 (13.9, 24.4); STAND: OD-18.7 (15.1, 24.4), OS-19.4 (16.2, 24.7); WALK: OD-40.1 (34.1, 44.8), OS-40.6 (33.8, 44.7); and TROT: OD-39.7 (30.3, 44.6), OS-39.4 (28.6, 45.0). The total SEBRs at walk and trot were significantly greater than SEBR in stationary scenarios. CONCLUSIONS: Despite requiring increased levels of attentional focus, activities involving motion caused increased SEBR in horses. We hypothesize the need for additional tear distribution due to tear evaporation (associated with air movement over the corneas) prevailed over the level of attentional focus to increase the SEBR.


Asunto(s)
Atención , Parpadeo/fisiología , Caballos/fisiología , Movimiento , Lágrimas/fisiología , Animales , Femenino , Masculino , Grabación en Video
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