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Climate change poses a significant threat to global agriculture, necessitating innovative solutions. Plant synthetic biology, particularly chloroplast engineering, holds promise as a viable approach to this challenge. Chloroplasts present a variety of advantageous traits for genetic engineering, but the development of genetic tools and genetic part characterization in these organelles is hindered by the lengthy time scales required to generate transplastomic organisms. To address these challenges, we have established a versatile protocol for generating highly active chloroplast-based cell-free gene expression (CFE) systems derived from a diverse range of plant species, including wheat (monocot), spinach, and poplar trees (dicots). We show that these systems work with conventionally used T7 RNA polymerase as well as the endogenous chloroplast polymerases, allowing for detailed characterization and prototyping of regulatory sequences at both transcription and translation levels. To demonstrate the platform for characterization of promoters and 5' and 3' untranslated regions (UTRs) in higher plant chloroplast gene expression, we analyze a collection of 23 5'UTRs, 10 3'UTRs, and 6 chloroplast promoters, assessed their expression in spinach and wheat extracts, and found consistency in expression patterns, suggesting cross-species compatibility. Looking forward, our chloroplast CFE systems open new avenues for plant synthetic biology, offering prototyping tools for both understanding gene expression and developing engineered plants, which could help meet the demands of a changing global climate.
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Plastid engineering offers the potential to carry multigene traits in plants; however, it requires reliable genetic parts to balance expression. The difficulty of chloroplast transformation and slow plant growth makes it challenging to build plants just to characterize genetic parts. To address these limitations, we developed a high-yield cell-free system from Nicotiana tabacum chloroplast extracts for prototyping genetic parts. Our cell-free system uses combined transcription and translation driven by T7 RNA polymerase and works with plasmid or linear template DNA. To develop our system, we optimized lysis, extract preparation procedures (e.g., runoff reaction, centrifugation, and dialysis), and the physiochemical reaction conditions. Our cell-free system can synthesize 34 ± 1 µg/mL luciferase in batch reactions and 60 ± 4 µg/mL in semicontinuous reactions. We apply our batch reaction system to test a library of 103 ribosome binding site (RBS) variants and rank them based on cell-free gene expression. We observe a 1300-fold dynamic range of luciferase expression when normalized by maximum mRNA expression, as assessed by the malachite green aptamer. We also find that the observed normalized gene expression in chloroplast extracts and the predictions made by the RBS Calculator are correlated. We anticipate that chloroplast cell-free systems will increase the speed and reliability of building genetic systems in plant chloroplasts for diverse applications.
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PURPOSE: To determine the safety and efficacy associated with drainage volumes greater than 1,500 mL in a single, unilateral thoracentesis without pleural manometry measurements. MATERIALS AND METHODS: This retrospective, single-institution study included 872 patients (18 years and older) who underwent ultrasound-guided thoracentesis. Patient and procedures data were collected including demographics, number of and laterality of thoracenteses, volume and consistency of fluid removed, and whether clinical or radiologic evidence of re-expansion pulmonary edema (REPE) developed within 24 h of thoracentesis. Fisher's exact test was used to test the significance of the relationship between volume of fluid removed and evidence of REPE. RESULTS: A total of 1376 thoracenteses were performed among the patients included in the study. The mean volume of fluid removed among all procedures was 901.1 mL (SD = 641.7 mL), with 194 (14.1%) procedures involving the removal of ≥ 1,500 mL of fluid. In total, six (0.7%) patients developed signs of REPE following thoracentesis, five of which were a first-time thoracentesis. No statistically significant difference in incidence of REPE was observed between those with ≥ 1,500 mL of fluid removed compared to those with < 1,500 mL of fluid removed (p-value = 0.599). CONCLUSIONS: Large-volume thoracentesis may safely improve patients' symptoms while preventing the need for repeat procedures.
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Edema Pulmonar , Toracocentesis , Ultrasonografía Intervencional , Humanos , Toracocentesis/métodos , Estudios Retrospectivos , Edema Pulmonar/epidemiología , Edema Pulmonar/diagnóstico por imagen , Edema Pulmonar/etiología , Femenino , Masculino , Anciano , Persona de Mediana Edad , Incidencia , Anciano de 80 o más Años , Drenaje/métodos , Adulto , Derrame Pleural/epidemiología , Derrame Pleural/diagnóstico por imagenRESUMEN
Purpose: Determine if there is a difference in adverse events (AE) between right or left hepatic percutaneous biliary drain placement (PTBD) in patients with biliary strictures. Materials & methods: This retrospective study included patients with benign or malignant biliary stricture treated with PTBD at a single institution from 7/28/2004-3/30/2021. 357 patients met inclusion criteria, 77 (21.6 %) had PTBD on the left and 280 (78.4 %) on the right. AEs associated with the initial drain placement or during subsequent intervention were collected and categorized. AEs that were grouped as periprocedural included: surgery, infection, hemorrhage, and drain failure. AEs in the postprocedural group included: chills, catheter displacement, cholangitis, biliary stones, drain malfunction, fever resolving without treatment, and pericatheter leakage. Surgery was considered a major AE and the remaining AEs were categorized as minor. Statistical analyses were performed using Logistic Regression Analysis and p-values less than 0.05 were considered statistically significant. Results: Overall, there was no statistically significant difference in AEs between right and left drains in the periprocedural and postprocedural period (p = 0.832, OR = 0.95 and p = 0.808, OR = 0.93 respectively). When analyzing minor AEs individually, only cholangitis occurred at a higher rate on the right side (p = 0.033, OR = 0.43). There was no statistical difference in the rate of major AEs in the periprocedural period between left and right drains (p = 0.311, OR = 1.37). Conclusion: Current literature is equivocal when comparing right versus left percutaneous biliary drains. This analysis describes no statistically significant difference in AEs between right and left hepatobiliary drains aside from slightly higher incidence of cholangitis for right sided drains.
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BACKGROUND: Appropriate staffing is essential to acute care delivery. Staffing ratio policy generates controversy. PURPOSE: This study examines perspectives on unit-level nurse-to-patient ratio policy in adult medical-surgical units. METHOD: Delphi methodology uses an invited diverse panel to analyze a policy's effects. Panelists completed iterative surveys about the impact they expect from unit-level ratio policy. FINDINGS: Panelists demonstrated moderate agreement that the proposed policy could increase staffing levels, decrease patient length of stay, and reduce nurse attrition. Other potential outcomes included reducing staffing in units above the minimum and increasing short-term costs. Panelists agreed that the policy could increase patient safety and nurse satisfaction and did not agree about the effect on long-term cost and innovation. Panelists also anticipated a mostly positive effect on patients and nurses. DISCUSSION: Policies that set unit-level nurse-to-patient ratios offer a potential strategy to improve medical-surgical staffing. Policy design should consider the range of expected outcomes.
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BACKGROUND: Candida auris (C auris) is a fungal pathogen that has the potential for environmental persistence leading to outbreaks in health care settings. There has been a worldwide surge in C auris outbreaks during the COVID-19 pandemic. In this report, we describe an outbreak of C auris, its control, patient outcomes, and lessons learned. METHODS: The outbreak occurred in a 600-bed adult academic tertiary care hospital. Contact tracing was initiated immediately after identification of the index case and surveillance testing for C auris was obtained from patients who were exposed to the index case. Infection prevention measures were closely followed. RESULTS: A total of 560 cultures were performed on 453 unique patients between August 2021 and December 2021. Of those, 31 cultures (5.5%) were positive for C auris; 27 (87.1%) were colonized with C auris, while 4 patients developed a clinical infection (12.9%). The secondary attack rate was 6.8% (31/453). The 30-day all-cause mortality rate for all patients who tested positive for C auris was 9.7%. DISCUSSION: C auris can cause protracted outbreaks that result in colonization and invasive infections. Multidisciplinary work to improve adherence to infection prevention measures as well as targeted admission screening are essential to limit outbreaks.
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COVID-19 , Candida auris , Candidiasis , Brotes de Enfermedades , SARS-CoV-2 , Centros de Atención Terciaria , Humanos , Centros de Atención Terciaria/estadística & datos numéricos , COVID-19/epidemiología , COVID-19/prevención & control , Masculino , Femenino , Persona de Mediana Edad , Anciano , Candidiasis/epidemiología , Candidiasis/microbiología , Candidiasis/prevención & control , Adulto , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Infección Hospitalaria/microbiología , Control de Infecciones/métodos , Trazado de Contacto , Anciano de 80 o más Años , Candidiasis InvasivaRESUMEN
PURPOSE: Closed-loop imaging programs (CLIPs) are designed to ensure that patients receive appropriate follow-up, but a review of incidental CT-detected breast findings in the setting of CLIPs has not been performed. METHODS: A retrospective review was conducted of CT reports at a single academic institution from July 1, 2020, to January 31, 2022, to identify reports with recommendations for breast imaging follow-up. Medical records were reviewed to evaluate patient adherence to follow-up, CLIP intervention, subsequent BI-RADS assessment, and diagnosis. Adherence was defined as diagnostic breast imaging performed within 6 months of the CT recommendation. RESULTS: Follow-up recommendations for breast imaging were included in CT report impressions for 311 patients. Almost half of patients (47.3% [147 of 311]) underwent follow-up breast imaging within 6 months, yielding breast cancer diagnoses in 12.9% (19 of 147) and a biopsy-proven positive predictive value of 65.5% (19 of 29). Most patients who returned for follow-up within 6 months did so without CLIP intervention. The majority of CT report impressions in the follow-up group (85.0% [125 of 147]) contained specific recommendations for "diagnostic breast imaging." For patients who did not receive follow-up, the CLIP team tracked all cases and intervened in 19.1% (28 of 147). The most common intervention was a phone call and/or fax to the primary care provider. Outpatient CT examination setting and specific recommendation for diagnostic breast imaging were significantly associated with higher follow-up adherence (P < .0001). CONCLUSIONS: Actionable CT-detected breast findings require follow-up diagnostic breast imaging because of a relevant cancer detection rate of 12.9%. Although many patients return for breast imaging without intervention, almost half of patients did not receive follow-up and may account for a significant number of missed cancer diagnoses. Specific CT recommendation verbiage is associated with higher follow-up adherence, which can be addressed across settings even without CLIPs.
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Neoplasias de la Mama , Tomografía Computarizada por Rayos X , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Estudios Retrospectivos , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Anciano , Adulto , Hallazgos Incidentales , Mamografía/métodos , Cooperación del Paciente , Anciano de 80 o más AñosRESUMEN
The short-beaked echidna is sexually monomorphic such that gender identification without veterinary intervention is challenging. The aim of this study was to evaluate and compare the most optimal noninvasive genetic source by extracting echidna genomic DNA (gDNA) from fecal scats, plucked hair, and quills to perform genetic sex testing using a range of molecular markers. Sex determination of 14 captive short-beaked echidnas was determined by amplifying isolated DNA from noninvasive samples, targeting two Y chromosome (male-specific) genes (mediator complex subunit 26 Y-gametologue [CRSPY] and anti-Müllerian hormone Y-gametologue [AMHY]), in addition to four confirmed sex-specific RADseq markers. Results of noninvasive samples were compared with blood samples and clinical records. Receiver operating characteristic curves were used to assess accuracy of sex determination of markers for each sample type. The gender of the echidnas was successfully identified on 75% of occasions using fecal samples, 90.6% occasions using hair, and 84.6% occasions with quills. Overall, the male-specific RADseq markers accurately identified the sex of echidnas with all sample types for 90% of animals; compared with 81.5% using CRSPY, and 82.0% using AMHY to identify sex. Collection of hair, quills, and feces provides a useful alternative to invasively collected samples, however, the accuracy of results depends on sample type and genetic marker selected. We found gender determination in the short-beaked echidna was most accurate using four male-specific RADseq markers on gDNA isolated from blood and hair. The noninvasive genetic sexing techniques documented here will inform and facilitate husbandry and genetic management of captive echidna populations.
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Tachyglossidae , Femenino , Animales , Masculino , Tachyglossidae/genética , Animales de Zoológico , ADN , Heces , BiomarcadoresRESUMEN
BACKGROUND: Peripherally inserted central catheters (PICCs) are the most common route of intravenous (I.V.) access for treatment of cystic fibrosis (CF) pulmonary exacerbations, but repeated PICC placement can result in upper extremity peripheral venous stenosis. Once peripheral stenosis develops, a non-cuffed tunneled central venous catheter (NcTCVC) is an alternative route for IV access. While these are regularly used at some CF centers, the safety and complication rate compared to PICCs in adults with CF has not been reported. This study aims to describe the safety of NcTCVCs in adults with CF. METHODS: A retrospective cohort study was performed at a CF Foundation accredited institution including adults with CF who received NcTCVCs in interventional radiology from 7/19/2007 to 3/09/2020. Complications analyzed included catheter related deep venous thrombosis (DVT), central line associated blood stream infection (CLABSI), and catheter related central venous stenosis. Complications were considered attributable if they occurred while the catheter was in place or within 30 days of catheter removal. RESULTS: During the study duration, 386 NcTCVCs were placed in 60 unique patients (55 % female) with a mean of 6.4 catheters per patient. Majority of NcTCVCs placed were 4 French (61.4 %). Average duration of indwelling NcTCVC was 16.2 days. No patients demonstrated catheter attributable symptomatic DVT. The incidence of DVT, CLABSI, and central venous stenosis was 0 (0 %), 4 (1 %), and 1 (0.3 %), respectively. CONCLUSIONS: Many adults with CF have required insertion of numerous PICCs for the treatment of recurrent pulmonary exacerbations. In those adults that develop PICC-associated peripheral vein stenosis precluding PICC placement, these results indicate NcTCVCs are a safe alternative.
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Cateterismo Venoso Central , Catéteres Venosos Centrales , Fibrosis Quística , Humanos , Fibrosis Quística/terapia , Fibrosis Quística/complicaciones , Femenino , Masculino , Estudios Retrospectivos , Adulto , Catéteres Venosos Centrales/efectos adversos , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodos , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/etiología , Adulto Joven , Persona de Mediana Edad , Catéteres de Permanencia/efectos adversos , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiologíaRESUMEN
BACKGROUND: Unintended pregnancy contributes to a high burden of maternal and fetal morbidity in the United States, and pregnancy intention screening offers a key strategy to improve preconception health and reproductive health equity. The One Key Question© is a pregnancy intention screening tool that asks a single question, "Would you like to become pregnant in the next year?" to all reproductive-age women. This study explored the perspectives of community health workers on using One Key Question in community-based settings. OBJECTIVES: This study aimed to identify barriers and facilitators to the use of the One Key Question pregnancy intention screening tool by community health workers who serve reproductive-age women in Salt Lake City, Utah. DESIGN: Using reproductive justice as a guiding conceptual framework, this study employed a qualitative descriptive design. Participants were asked to identify barriers and facilitators to the One Key Question, with open-ended discussion to explore community health workers' knowledge and perceptions about pregnancy intention screening. METHODS: We conducted focus groups with 43 community health workers in Salt Lake City, Utah, from December 2017 through January 2018. Participants were trained on the One Key Question algorithm and asked to identify barriers and facilitators to implementation. All focus groups occurred face-to-face in community settings and used a semi-structured facilitation guide developed by the study Principal Investigator with input from community partners. RESULTS: Pregnancy intention screening is perceived positively by community health workers. Barriers identified include traditional cultural beliefs about modesty and sex, lack of trust in health care providers, and female bias in the One Key Question algorithm. Facilitators include the simplicity of the One Key Question algorithm and the flexibility of One Key Question responses. CONCLUSION: One Key Question is an effective pregnancy intention screening tool in primary care settings but is limited in its capacity to reach those outside the health system. Community-based pregnancy intention screening offers an alternative avenue for implementation of One Key Question that could address many of these barriers and reduce disparities for underserved populations.
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Agentes Comunitarios de Salud , Intención , Embarazo , Femenino , Humanos , Estados Unidos , Atención PrenatalRESUMEN
Insufficient insulin secretion to meet metabolic demand results in diabetes. The intracellular flux of Ca2+ into ß-cells triggers insulin release. Since genetics strongly influences variation in islet secretory responses, we surveyed islet Ca2+ dynamics in eight genetically diverse mouse strains. We found high strain variation in response to four conditions: (1) 8 mM glucose; (2) 8 mM glucose plus amino acids; (3) 8 mM glucose, amino acids, plus 10 nM glucose-dependent insulinotropic polypeptide (GIP); and (4) 2 mM glucose. These stimuli interrogate ß-cell function, α- to ß-cell signaling, and incretin responses. We then correlated components of the Ca2+ waveforms to islet protein abundances in the same strains used for the Ca2+ measurements. To focus on proteins relevant to human islet function, we identified human orthologues of correlated mouse proteins that are proximal to glycemic-associated single-nucleotide polymorphisms in human genome-wide association studies. Several orthologues have previously been shown to regulate insulin secretion (e.g. ABCC8, PCSK1, and GCK), supporting our mouse-to-human integration as a discovery platform. By integrating these data, we nominate novel regulators of islet Ca2+ oscillations and insulin secretion with potential relevance for human islet function. We also provide a resource for identifying appropriate mouse strains in which to study these regulators.
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Islotes Pancreáticos , Ratones , Humanos , Animales , Islotes Pancreáticos/metabolismo , Estudio de Asociación del Genoma Completo , Insulina/metabolismo , Glucosa/metabolismo , Variación Genética , Aminoácidos/metabolismoRESUMEN
Background: While many studies have examined where and with whom autistic people live, very few have looked at autistic people's experience of moving home. Choosing where to live, and being able to move residence, could be important for autonomy, and we therefore undertook a systematic review to identify studies about autistic adults' experience of moving home. Methods: We entered search terms relevant to autism and moving home into six databases and Google Scholar. After screening the titles and abstracts, we identified a final set of articles and screened the full text. We then checked the reference lists for potentially relevant articles; then, we conducted a search for articles that cited our final set of articles. Three raters assessed each included article for methodological quality. Results: The search strategy identified a total of 311 articles (initial search, ancestry searching, articles from other sources). After deduplication, we screened a total of 165 articles for eligibility. A final set of seven articles was identified. Our narrative synthesis of the articles suggests that both autistic people and the relatives of autistic people think living independently is a source of positive personal development. However, autistic people reported that poor employment prospects impacted on their financial independence and hence independent living. Parents highlighted concerns about their offspring's personal care, safety, and the difficulty of navigating the housing system for those autistic people with co-occurring intellectual disability. Conclusions: Taken together, our review suggests that autistic people and those who care for them have a positive view of independent living and are aware of the barriers to achieving this. Our review highlights a gap in the understanding of autistic adults' experience of moving home. We briefly describe our ongoing research project [the "Moving (as an) Autistic Person" project] exploring autistic people's experiences of moving house.
Why is this topic important?: Many research studies find that autistic people do not live independentlymany autistic people live with their parents or in sheltered accommodation. As our knowledge about autistic people, and the diversity of their life experiences, increases, it is important to investigate a range of real-life transitions. So far, the transition to independent living has not been reviewed (specifically, the process of moving from one living place to another). What is the purpose of this article?: We reviewed published studies to try and find all the available studies that may have looked at the process of moving home for autistic people. What did the authors do?: We designed a search method to find all the articles that were relevant to this question. We searched six academic databases and used Google Scholar. What did you find about this topic?: We found that there were no studies which looked at the specific question of what autistic people experience when they move home. However, we did find some studies which looked at the benefits of living independently (with reports from autistic people and from the parents of autistic people). We also found one study which looked at the choices autistic people have in where, and with whom, they live. What do the authors recommend?: Based on the included studies, it does seem that autistic people may benefit from living independently. However, we do note that the issue of independent living cannot be examined without consideration of other factors, such as employment. Also, it is not universally the case that all autistic adults prefer, or will benefit from, living independently. How will these findings help autistic adults now or in the future?: We aim to use the findings of this review, alongside our ongoing mixed-methods study of autistic people's experiences, to design a tailored co-produced resource to help autistic people plan for moving home.
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Screen media use starts in early childhood, despite recommendations to limit use. This study explored low-income Mexican American mothers' and fathers' beliefs, parenting practices, and perceived contextual contributors related to toddler screen use. We conducted interviews with 32 low-income Mexican American parents. Transcripts of audio recordings were analyzed to identify themes. Parents perceived numerous benefits to screen use, including learning and enjoyment, as well as seeing it as a helpful tool for parents. Reported risks included harmful mental and physical effects and a risk of use being all-consuming. Parents managed screen use with a variety of practices, including giving close attention to content, monitoring duration, and engaging in co-use. They also used screens for behavior management and in specific situations, such as to prepare for sleep. Some differences in beliefs and parenting practices exist by screen device type. Parents also reported that contextual factors, such as weather and neighborhood safety, influenced screen use. This study extends the current literature regarding child screen use, with its focus on low-income Mexican American toddlers. The findings offer interventionists and providers insight into the management of screens in the lives of this population.
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Americanos Mexicanos , Responsabilidad Parental , Preescolar , Femenino , Humanos , Madres , Relaciones Padres-Hijo , Pobreza , Padre , MasculinoRESUMEN
INTRODUCTION: Type 2 diabetes is prevalent among US adults. Lifestyle interventions that modify health behaviours prevent or delay progression to diabetes among individuals at high risk. Despite the well-documented influence of individuals' social context on their health, evidence-based type 2 diabetes prevention interventions do not systematically incorporate participants' romantic partners. Involving partners of individuals at high risk for type 2 diabetes in primary prevention may improve engagement and outcomes of programmes. The randomised pilot trial protocol described in this manuscript will evaluate a couple-based lifestyle intervention to prevent type 2 diabetes. The objective of the trial is to describe the feasibility of the couple-based intervention and the study protocol to guide planning of a definitive randomised clinical trial (RCT). METHODS AND ANALYSIS: We used community-based participatory research principles to adapt an individual diabetes prevention curriculum for delivery to couples. This parallel two-arm pilot study will include 12 romantic couples in which at least one partner (ie, 'target individual') is at risk for type 2 diabetes. Couples will be randomised to either the 2021 version of the CDC's PreventT2 curriculum designed for delivery to individuals (six couples), or PreventT2 Together, the adapted couple-based curriculum (six couples). Participants and interventionists will be unblinded, but research nurses collecting data will be blinded to treatment allocation. Feasibility of the couple-based intervention and the study protocol will be assessed using both quantitative and qualitative measures. ETHICS AND DISSEMINATION: This study has been approved by the University of Utah IRB (#143079). Findings will be shared with researchers through publications and presentations. We will collaborate with community partners to determine the optimal strategy for communicating findings to community members. Results will inform a subsequent definitive RCT. TRIAL REGISTRATION NUMBER: NCT05695170.
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Diabetes Mellitus Tipo 2 , Estilo de Vida , Adulto , Humanos , Proyectos Piloto , Diabetes Mellitus Tipo 2/prevención & control , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE: Understanding parental experiences with managing their toddler's screen use is important to inform the design of interventions addressing early childhood screen use, yet current evidence is limited. To enhance our understanding of the context of toddler screen use, this study characterizes the screen-related discord and dismay parents experience in families with toddlers. DESIGN AND METHODS: In-depth interviews were conducted to explore everyday experiences with screen use among low-income Mexican American caregivers of toddlers (21 mothers, 10 fathers, 1 grandmother). Transcripts were content analyzed to identify prominent themes. RESULTS: Three themes were identified. Experiences of screen-related discord and dismay arose (1) between parent and child, (2) between parents, and (3) surfaced as parental internal dissonance about toddler screen use. Parent-child discord resulted from parental limit setting and child reactions to parental screen use, which often included tantrums. Parent-partner discord included patterns of agreeing to disagree and direct disagreement between partners. Parents also reported their own feelings of ambivalence and dismay as they struggled to reconcile their preferences against their toddler's actual screen use, while living in a screen-saturated world. CONCLUSIONS: Findings offer insight into types of screen-related discord and dismay low-income Mexican American parents experience as they attempt to manage their toddler's screen use. PRACTICE IMPLICATIONS: Although discord in families is normal, the screen-specific discord reported by participants warrants consideration in efforts promoting healthy screen use in families. Providers can tailor their counseling to consider the range of screen-related discord families of toddlers may experience.
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Americanos Mexicanos , Padres , Femenino , Humanos , Preescolar , Padres/psicología , Madres/psicología , Pobreza , Investigación Cualitativa , Responsabilidad ParentalRESUMEN
The short-tailed albatross (Phoebastria albatrus) is a threatened seabird whose present-day range encompasses much of the North Pacific. Within this species, there are two genetic clades (Clades 1 and 2) that have distinctive morphologies and foraging ecologies. Due to a global population collapse in the late 19th and early 20th centuries, the frequency of these clades among the short-tailed albatross population that historically foraged off British Columbia, Canada, is unclear. To document the species' historical genetic structure in British Columbia, we applied ancient DNA (aDNA) analysis to 51 archaeological short-tailed albatross specimens from the Yuquot site (Borden site number: DjSp-1) that span the past four millennia. We obtained a 141 bp cytochrome b sequence from 43 of the 51 (84.3%) analyzed specimens. Analyses of these sequences indicate 40 of the specimens belong to Clade 1, while 2 belong to Clade 2. We also identified a single specimen with a novel cytochrome b haplotype. Our results indicate that during the past four millennia most of the short-tailed albatrosses foraging near Yuquot belonged to Clade 1, while individuals from other lineages made more limited use of the area. Comparisons with the results of previous aDNA analyses of archaeological albatrosses from Japanese sites suggest the distribution of Clades 1 and 2 differed. While both albatross clades foraged extensively in the Northwest Pacific, Clade 1 albatrosses appear to have foraged along the west coast of Vancouver Island to a greater extent. Due to their differing distributions, these clades may be exposed to different threats.
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Patients with heart failure with preserved ejection fraction (HFpEF) have few pharmacologic therapies, and it is not known if supplementing with ubiquinol and/or d-ribose could improve outcomes. The overall objective of this study was to determine if ubiquinol and/or d-ribose would reduce the symptoms and improve cardiac performance in patients with HFpEF. This was a phase 2 randomized, double-blind, placebo-controlled trial of 216 patients with HFpEF who were ≥ 50 years old with a left ventricular ejection fraction (EF) ≥ 50%. A total of 4 study groups received various supplements over 12 weeks: Group 1 received placebo ubiquinol capsules and d-ribose powder, Group 2 received ubiquinol capsules (600 mg/d) and placebo d-ribose powder, Group 3 received placebo ubiquinol capsules with d-ribose powder (15 g/d), and Group 4 received ubiquinol capsules and d-ribose powder. There were 7 outcome measures for this study: Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score, level of vigor using a subscale from the Profile of Mood States, EF, the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (septal E/e' ratio), B-type natriuretic peptides, lactate/adenosine triphosphate ratio, and the 6-minute walk test. Treatment with ubiquinol and/or d-ribose significantly improved the KCCQ clinical summary score (17.30 to 25.82 points), vigor score (7.65 to 8.15 points), and EF (7.08% to 8.03%) and reduced B-type natriuretic peptides (-72.02 to -47.51) and lactate/adenosine triphosphate ratio (-4.32 to -3.35â¯×â¯10-4). There were no significant increases in the septal E/e' or the 6-minute walk test. In conclusion, ubiquinol and d-ribose reduced the symptoms of HFpEF and increased the EF. These findings support the use of these supplements in addition to standard therapeutic treatments for patients with HFpEF.
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Insuficiencia Cardíaca , Adenosina Trifosfato/farmacología , Adenosina Trifosfato/uso terapéutico , Cápsulas/farmacología , Cápsulas/uso terapéutico , Tolerancia al Ejercicio , Humanos , Lactatos/farmacología , Lactatos/uso terapéutico , Persona de Mediana Edad , Polvos/farmacología , Polvos/uso terapéutico , Ribosa/farmacología , Ribosa/uso terapéutico , Volumen Sistólico , Ubiquinona/análogos & derivados , Función Ventricular IzquierdaRESUMEN
Introduction: Cerebrospinal fluid (CSF) leaks occur when fluid seeps through a dural or skull base defect, typically in the nose or ear. CSF leaks commonly are identified and diagnosed by use of computed tomography (CT) and CT cisternogram. CT findings suggestive of a CSF leak include a skull-based bone defect along with opacification of the contiguous sinus. This study examined a series of CSF leaks on CT imaging to document imaging findings. Methods: A single-institution retrospective review of cases of CSF leak diagnosed by CT maxillofacial or CT cisternogram from January 1, 2008 to March 12, 2018 was performed. Patient demographics, history, imaging findings, and treatment were recorded. Results: Thirty-nine patients met the inclusion criteria for the study. The average age was 51, and a large majority were female (76.9%). Among the 25 patients in which it was reported, the mean size of skull base defect was 0.472 cm. Of the 39 total cases, 27 patients (69.2%) presented with sinus opacification on CT imaging. Conclusions: Radiologists should be aware of the possibility of notable sinus opacification observable on CT when investigating a potential CSF leak. Opacification may vary in both location and size depending on the nature and location of a CSF leak. Further research is needed to draw a correlation between sinus opacification seen on CT scan and the diagnosed origin of a CSF leak.
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Engineering regulatory parts for improved performance in genetic programs has played a pivotal role in the development of the synthetic biology cell programming toolbox. Here, we report the development of a novel high-throughput platform for regulatory part prototyping and analysis that leverages the advantages of engineered DNA libraries, cell-free protein synthesis (CFPS), high-throughput emulsion droplet microfluidics, standard flow sorting adapted to screen droplet reactions, and next-generation sequencing (NGS). With this integrated platform, we screened the activity of millions of genetic parts within hours, followed by NGS retrieval of the improved designs. This in vitro platform is particularly valuable for engineering regulatory parts of nonmodel organisms, where in vivo high-throughput screening methods are not readily available. The platform can be extended to multipart screening of complete genetic programs to optimize yield and stability.
Asunto(s)
Ensayos Analíticos de Alto Rendimiento , Microfluídica , Biblioteca de Genes , Microfluídica/métodos , Biosíntesis de Proteínas , Biología SintéticaRESUMEN
Multiple sclerosis (MS) is an auto-immune disease in which the body's immune system attacks the central nervous system. The demyelination of the nerve fibers can lead to physical, emotional, and cognitive impairments. We wanted to learn about challenges of living with the illness and how people deal with stress. 128 individuals with MS from Austria and the US participated in the qualitative interviews. We interviewed participants and coded their answers using inductive grounded theory. We asked three open-ended questions to inquire about life since being diagnosed with MS as well as about dealing with stress. Life shifts since diagnosis involved 'experiencing limitations' and could be categorized in 'emotional changes', 'changes with work', 'changes in social interaction', 'physical changes', 'changes in the medical context'. For dealing with stress active (strategies and activities) and passive coping strategies (avoid/ignore) were employed. General stress reactions were expressed in areas of emotional, physical and /or lifestyle. We recommend developing interventions in three core areas for the MS population: (1) dealing with life changes and significant experiences with MS, (2) focusing on the areas where life shifts took place, (3) focusing on active coping with stress and discussing consequences of passive coping strategies.