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1.
PLoS One ; 19(3): e0291158, 2024.
Article in English | MEDLINE | ID: mdl-38489299

ABSTRACT

Fluorescence-based assays provide sensitive and adaptable methods for point of care testing, environmental monitoring, studies of protein abundance and activity, and a wide variety of additional applications. Currently, their utility in remote and low-resource environments is limited by the need for technically complicated or expensive instruments to read out fluorescence signal. Here we describe the Genes in Space Fluorescence Viewer (GiS Viewer), a portable, durable viewer for rapid molecular assay readout that can be used to visualize fluorescence in the red and green ranges. The GiS Viewer can be used to visualize any assay run in standard PCR tubes and contains a heating element. Results are visible by eye or can be imaged with a smartphone or tablet for downstream quantification. We demonstrate the capabilities of the GiS Viewer using two case studies-detection of SARS-CoV-2 RNA using RT-LAMP and quantification of drug-induced changes in gene expression via qRT-PCR on Earth and aboard the International Space Station. We show that the GiS Viewer provides a reliable method to visualize fluorescence in space without the need to return samples to Earth and can further be used to assess the results of RT-LAMP and qRT-PCR assays on Earth.


Subject(s)
COVID-19 , Humans , SARS-CoV-2/genetics , RNA, Viral/genetics , Molecular Diagnostic Techniques/methods , Point-of-Care Testing , Nucleic Acid Amplification Techniques/methods , Biological Assay , Sensitivity and Specificity
2.
ACS Synth Biol ; 13(3): 942-950, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38442491

ABSTRACT

Cell-free protein synthesis (CFPS) is a rapidly maturing in vitro gene expression platform that can be used to transcribe and translate nucleic acids at the point of need, enabling on-demand synthesis of peptide-based vaccines and biotherapeutics as well as the development of diagnostic tests for environmental contaminants and infectious agents. Unlike traditional cell-based systems, CFPS platforms do not require the maintenance of living cells and can be deployed with minimal equipment; therefore, they hold promise for applications in low-resource contexts, including spaceflight. Here, we evaluate the performance of the cell-free platform BioBits aboard the International Space Station by expressing RNA-based aptamers and fluorescent proteins that can serve as biological indicators. We validate two classes of biological sensors that detect either the small-molecule DFHBI or a specific RNA sequence. Upon detection of their respective analytes, both biological sensors produce fluorescent readouts that are visually confirmed using a hand-held fluorescence viewer and imaged for quantitative analysis. Our findings provide insights into the kinetics of cell-free transcription and translation in a microgravity environment and reveal that both biosensors perform robustly in space. Our findings lay the groundwork for portable, low-cost applications ranging from point-of-care health monitoring to on-demand detection of environmental hazards in low-resource communities both on Earth and beyond.


Subject(s)
Biosensing Techniques , Space Flight , Proteins , Biosensing Techniques/methods , Point-of-Care Systems , Cell-Free System
3.
Gynecol Oncol ; 184: 160-167, 2024 May.
Article in English | MEDLINE | ID: mdl-38320467

ABSTRACT

INTRODUCTION: Telemedicine rapidly increased with the COVID-19 pandemic and could reduce cancer care disparities. Our objective was to evaluate sociodemographic (race, insurance), patient, health system, and cancer factors associated with telemedicine use in gynecologic cancers. METHODS: We conducted a retrospective cohort study of patients with endometrial cancer and epithelial ovarian cancer with at least one visit from March 2020 to October 2021, using a real-world electronic health record-derived database, representing approximately 800 sites in US academic (14%) and community practices (86%). We used multivariable Poisson regression modeling to analyze the association of ever using telemedicine with patient, sociodemographic, health system, and cancer factors. RESULTS: Of 3950 patients with ovarian cancer, 1119 (28.3%) had at least one telemedicine visit. Of 2510 patients with endometrial cancer, 720 (28.7%) had at least one telemedicine visit. At community cancer practices, patients who identified as Black were less likely to have a telemedicine visit than patients who identified as white in both ovarian and endometrial cancer (Ovarian: RR 0.62, 95% CI 0.42-0.9; Endometrial: RR 0.56, 95% CI 0.38-0.83). Patients in the Southeast, Midwest, West, and Puerto Rico were less likely to have telemedicine visits than patients in the Northeast. Uninsured patients were less likely, and patients with Medicare were more likely, to have one or more telemedicine visit than patients with private insurance. CONCLUSIONS: In this national cohort study, <30% of patients ever used telemedicine, and significant racial and regional disparities existed in utilization. Telemedicine expansion efforts should include programs to improve equity in access to telemedicine.


Subject(s)
Healthcare Disparities , Telemedicine , Humans , Female , Telemedicine/statistics & numerical data , Retrospective Studies , Middle Aged , Healthcare Disparities/statistics & numerical data , Aged , United States , Endometrial Neoplasms/therapy , COVID-19/epidemiology , Carcinoma, Ovarian Epithelial/therapy , Adult , Ovarian Neoplasms/therapy
4.
Gynecol Oncol ; 177: 103-108, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37659265

ABSTRACT

OBJECTIVE: Prior to the COVID-19 pandemic, telehealth visits and remote clinical trial operations (such as local collection of laboratory tests or imaging studies) were underutilized in gynecologic oncology clinical trials. Current literature on these operational changes provides anecdotal experience and expert opinion with few studies describing patient-level safety data. We aimed to evaluate the safety and feasibility of telehealth and remote clinical trial operations during the COVID-19 Pandemic. METHODS: Gynecologic oncology patients enrolled and actively receiving treatment on a clinical trial at a single, academic institution during the designated pre-Telehealth and Telehealth periods were identified. Patients with at least 1 provider or research coordinator telehealth visit were included. Patient demographics, health system encounters, adverse events, and protocol deviations were collected. Pairwise comparisons were performed between the pre-Telehealth and Telehealth period with each patient serving as their own control. RESULTS: Thirty-one patients met inclusion criteria. Virtual provider visits and off-site laboratory testing increased during the Telehealth period. Delays in provider visits, imaging, and laboratory testing did not differ between time periods. Total and minor protocol deviations increased in incidence during the Telehealth period and were due to documentation of telehealth and deferment of non-therapeutic testing. Major protocol deviations, emergency department visits, admissions, and severe adverse events were of low incidence and did not differ between time periods. CONCLUSIONS: Telehealth and remote clinical trial operations appeared safe and did not compromise clinical trial protocols in a small, single institutional study. Larger scale evaluations of such trial adaptations should be performed to determine continued utility following the Pandemic.

5.
Ann Am Thorac Soc ; 20(12): 1743-1751, 2023 12.
Article in English | MEDLINE | ID: mdl-37769182

ABSTRACT

Rationale: Being overweight or obese is common among patients with chronic obstructive pulmonary disease (COPD), but whether interventions targeted at weight loss improve functional impairments is unknown. Objectives: INSIGHT (Intervention Study in Overweight Patients with COPD) tested whether a pragmatic low-intensity lifestyle intervention would lead to better physical functional status among overweight or obese participants with COPD. Methods: The trial was a 12-month, multicenter, patient-level pragmatic clinical trial. Participants were recruited from April 2017 to August 2019 from 38 sites across the United States and randomized to receive usual care or usual care plus lifestyle intervention. The intervention was a self-directed video program delivering the Diabetes Prevention Program's Group Lifestyle Balance curriculum. Results: The primary outcome was 6-minute-walk test distance at 12 months. Priority secondary outcomes were postwalk modified Borg dyspnea at 12 months and weight at 12 months. Participants (N = 684; mean age, 67.0 ± 8.0 yr [standard deviation]; 41.2% female) on average were obese (body mass index, 33.0 ± 4.6 kg/m2) with moderate COPD (forced expiratory volume in 1 second % predicted, 58.1 ± 15.7%). At 12 months, participants randomized to the intervention arm walked farther (adjusted difference, 42.3 ft [95% confidence interval (CI), 7.9-76.7 ft]; P = 0.02), had less dyspnea at the end of the 6-minute-walk test (adjusted difference, -0.36 [95% CI, -0.63 to -0.09]; P = 0.008), and had greater weight loss (adjusted difference, -1.34 kg [95% CI, -2.33 to -0.34 kg]; P = 0.008) than control participants. The intervention did not improve the odds of achieving clinically meaningful thresholds of walk distance (98.4 ft) or dyspnea (1 unit) but did achieve meaningful thresholds of weight loss (3% and 5%). Conclusions: Among participants with COPD who were overweight or obese, a self-guided low-intensity video-based lifestyle intervention led to modest weight loss but did not lead to clinically important improvements in physical functional status and dyspnea. Clinical trial registered with www.clinicaltrials.gov (NCT02634268).


Subject(s)
Overweight , Pulmonary Disease, Chronic Obstructive , Humans , Female , Middle Aged , Aged , Male , Overweight/complications , Overweight/therapy , Quality of Life , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/therapy , Life Style , Dyspnea/etiology , Dyspnea/therapy , Obesity/complications , Obesity/therapy , Weight Loss
6.
JAMA ; 328(22): 2230-2241, 2022 12 13.
Article in English | MEDLINE | ID: mdl-36511927

ABSTRACT

Importance: The effectiveness of remotely delivered, self-directed, weight loss programs in routine clinical practice is largely unknown. Objective: To test whether a self-directed, remotely administered behavioral lifestyle intervention improves weight and self-reported general health status compared with usual care. Design, Setting, and Participants: In this randomized clinical trial, 511 adults with a body mass index (BMI) of 30 or more and less than 45 (based on electronic health record [EHR] weight and height), were enrolled from 30 Veterans Health Administration (VHA) sites between February 15, 2018, and December 18, 2018 (final follow-up February 18, 2021). Interventions: Participants were randomly assigned to the intervention group (n = 254) or the control group (n = 257). Both received usual care. Participants randomized to the intervention received Diabetes Prevention Program-based self-directed videos, handouts, and coaching messages via an online platform or US mail for 12 months. Main Outcomes and Measures: Coprimary outcomes were weight measured in primary care and recorded in the EHR and self-reported general health status using the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) physical component score (PCS; higher scores are better [range, 0-100]) at the 12-month follow-up. The between-group minimal clinically important differences are 3 kg for weight and 5 points for the SF-12 PCS. Linear mixed models used weights and SF-12 PCS measured at either time point, with participants analyzed according to randomization assignment. Statistical significance for each coprimary outcome was based on a 2-sided α level of .025. Results: Among 511 participants randomized (mean age, 57.4 [SD, 13.9] years; 231 female [45%]), 429 (84.0%) had EHR-based weights and 410 (80.2%) had SF-12 PCS data at 12 months. The unadjusted mean weight at 12 months declined from 102.7 kg to 99.8 kg in the intervention group compared with 101.9 kg to 101.0 kg in the control group (adjusted between-group mean difference, -1.93 [97.5% CI, -3.24 to -0.61]; P = .001). At 12 months, the unadjusted mean SF-12 PCS scores declined from 44.8 to 44.3 among intervention participants compared with 44.5 to 43.2 among control participants (adjusted between-group mean difference, intervention minus control, 0.69 [97.5% CI, -1.11 to 2.49]; P = .39). Cardiovascular events represented the highest percentage of serious adverse events, accounting for 25% of events in the intervention group and 35% in the control group. Conclusions and Relevance: Among adults with obesity, a remotely delivered self-directed, behavioral lifestyle intervention, compared with usual care, resulted in statistically significantly greater weight loss at 12 months, although the difference was not clinically important. There was no significant difference in self-reported general physical health status at 12 months. Trial Registration: ClinicalTrials.gov Identifier: NCT03260140.


Subject(s)
Behavior Therapy , Obesity , Weight Reduction Programs , Adult , Female , Humans , Middle Aged , Behavior Therapy/methods , Health Status , Obesity/diagnosis , Obesity/therapy , Weight Loss , Weight Reduction Programs/methods , Body Weight , Telemedicine/methods , Self Care , Healthy Lifestyle , Male , Aged
7.
Front Psychiatry ; 13: 924672, 2022.
Article in English | MEDLINE | ID: mdl-35800016

ABSTRACT

Background: Over the past two decades, the United States has experienced a dramatic increase in the rate of injection drug use, injection associated infections, and overdose mortality. A hospital-based program for treating opioid use disorder in people who inject drugs presenting with invasive infections was initiated at an academic tertiary care center in 2020. The goal of this program was to improve care outcomes, enhance patient experiences, and facilitate transition from the hospital to longer term addiction care. The purpose of this study was to interview two cohorts of patients, those admitted before vs. after initiation of this program, to understand the program's impact on care from the patient's perspective and explore ways in which the program could be improved. Methods: Thirty patients admitted to the hospital with infectious complications of injection drug use were interviewed using a semi-structured format. Interviews were transcribed and coded. Emergent themes were reported. Limited descriptive statistics were reported based on chart review. Results: Thirty interviews were completed; 16 participants were part of the program (admitted after program implementation) while 14 were not participants (admitted prior to implementation). Common themes associated with hospitalization included inadequate pain control, access to medications for opioid use disorder (MOUD), loss of freedom, stigma from healthcare personnel, and benefits of having an interprofessional team. Participants in the program were more likely to report adequate pain control and access to MOUD and many cited benefits from receiving care from an interprofessional team. Conclusions: Patients with opioid use disorder admitted with injection related infections reported improved experiences when receiving care from an interprofessional team focused on their addiction. However, perceived stigma from healthcare personnel and loss of freedom related to hospitalization were continued barriers to care before and after implementation of this program.

8.
Open Forum Infect Dis ; 9(7): ofac264, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35854986

ABSTRACT

Background: Online resources and social media have become increasingly ubiquitous in medical education. Little is known about the need for educational resources aimed at infectious disease (ID) fellows. Methods: We conducted an educational needs assessment through a survey that aimed to describe ID fellows' current use of online and social media tools, assess the value of online learning, and identify the educational content preferred by ID fellows. We subsequently convened focus groups with ID fellows to explore how digital tools contribute to fellow learning. Results: A total of 110 ID fellows responded to the survey. Over half were second-year fellows (61, 55%). Although many respondents were satisfied with the educational resources provided by their fellowship program (70, 64%), the majority were interested in an online collaborative educational resource (97, 88%). Twitter was the most popular social media platform for education and the most valued online resource for learning. Focus groups identified several themes regarding social medial learning: broadened community, low barrier to learning, technology-enhanced learning, and limitations of current tools. Overall, the focus groups suggest that fellows value social media and online learning. Conclusions: ID fellows are currently using online and social media resources, which they view as valuable educational tools. Fellowship programs should consider these resources as complementary to traditional teaching and as a means to augment ID fellow education.

9.
BMC Pregnancy Childbirth ; 22(1): 197, 2022 Mar 11.
Article in English | MEDLINE | ID: mdl-35277129

ABSTRACT

BACKGROUND: Abusive and disrespectful treatment of women during childbirth is a critical global issue that threatens women's sexual rights and reproductive rights and access to quality maternal care. This phenomenon has been documented in Colombia. However, little emphasis has been placed on identifying the drivers of and potential interventions against disrespect and abuse against particularly vulnerable populations in the country, including internally displaced indigenous women. METHODS: This report is a sub-analysis of a larger project. Semi-structured interviews were conducted with indigenous (Embera) women with childbirth experience (n = 10), maternal healthcare workers (n = 6), and community stakeholders (n = 5) in Medellín, Colombia. Qualitative analysis techniques, consisting of inductive and deductive approaches, were used to identify and characterize the drivers of disrespect and abuse against indigenous women during childbirth and points for intervention. Existing frameworks were adapted to thematically organize drivers and potential solutions into four interrelated subsystems: individual and community factors, clinician factors, facility factors, and national health system factors. RESULTS: Participants highlighted disrespect and abuse as stemming from (within the individual and community level) its normalization, lack of autonomy and empowerment among indigenous women, lacking antenatal care, (within the clinician level) prejudice, linguistic or cultural barriers to communication, lack of understanding of indigenous culture, medical culture and training, burnout and demoralization, (within the facility level) inadequate infrastructure, space, and human resources, and (within the national systems level) lack of clear policies and the devaluing of respectful maternity care. They called for interventions specific to these drivers, grounded in dignity and respect for indigenous culture. CONCLUSION: This paper expands upon the growing literature on global mistreatment during childbirth by highlighting drivers of mistreatment and identifying points for intervention in a previously unstudied population. Our data show that indigenous women are especially vulnerable to mistreatment due to cultural and linguistic barriers and prejudice. Broad and meaningful action is urgently needed to realize these women's rights to respectful maternity care. Interventions must be multifaceted and locally specific, taking into account the needs and wants of the women they serve.


RESUMEN: CONTEXTO: El trato abusivo recibido por mujeres durante el parto es un problema mundial que amenaza los derechos de las mujeres y el acceso a una atención materna de calidad. Este fenómeno ha sido documentado en Colombia, pero poco énfasis se ha hecho en poblaciones vulnerables, como las mujeres indígenas desplazadas. METODOLOGíA: Se presentan resultados derivados de un proyecto macro. Se realizaron entrevistas con mujeres indígenas Emberas que tuvieron experiencia de parto en Medellín (n = 10), profesionales de salud (n = 6) y líderes comunitarios (n = 5). Se utilizaron técnicas de análisis cualitativo de enfoques inductivos y deductivos, para identificar aspectos que generan el maltrato contra las mujeres indígenas durante el parto y posibles intervenciones para evitar su ocurrencia. Los modelos teóricos existentes se adaptaron para organizar temáticamente los generadores del maltrato y soluciones en cuatro subsistemas: factores individuales y comunitarios, factores clínicos, factores relacionados a los hospitales y factores asociados al sistema nacional. RESULTADOS: Los participantes destacaron como factores a nivel individual y comunitario la normalización de tratos irrespetuosos y abusivos de parte de los profesionales de salud con las mujeres indígenas, así como su falta de autonomía y empoderamiento. A nivel clínico, se identificó la falta de atención prenatal, barreras para la comunicación, falta de comprensión de la cultura indígena, la cultura y formación médica, la desmoralización de los médicos. Sobre los servicios de salud, se encontraron infraestructuras, espacios y recursos humanos inadecuados. En el nivel del sistema, se identifican la falta de políticas y poca valoración de la atención respetuosa. Los participantes señalaron la importancia de realizar intervenciones sobre estos generadores, basados en la dignidad y el respeto por la cultura indígena. CONCLUSIONES: Este artículo amplía la creciente literatura global sobre el maltrato dirigido a las maternas durante el parto y muestra que las mujeres indígenas son especialmente vulnerables debido a las barreras y prejuicios culturales y lingüísticos. Se necesitan urgentemente acciones amplias para hacer realidad los derechos de las mujeres frente a la atención materna respetuosa. Las intervenciones deben ser multifacéticas y específicas a nivel local, teniendo en cuenta las necesidades y deseos de las mujeres a las que sirven.


Subject(s)
Maternal Health Services , Attitude of Health Personnel , Colombia , Delivery, Obstetric/methods , Female , Humans , Parturition , Pregnancy , Professional-Patient Relations , Quality of Health Care
10.
J Addict Med ; 16(2): e133-e136, 2022.
Article in English | MEDLINE | ID: mdl-33840774

ABSTRACT

OBJECTIVES: To identify the barriers to accessing health care and social services faced by people who inject drugs (PWID) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This report is a sub-analysis of a larger qualitative study. Semi-structured interviews were conducted with PWID admitted to an academic medical center from 2017 to 2020 for an invasive injection-related infection. Standard qualitative analysis techniques, consisting of both inductive and deductive approaches, were used to identify and characterize the effects of COVID-19 on participants. RESULTS: Among the 30 PWID interview participants, 14 reported barriers to accessing health and addiction services due to COVID-19. As facilities decreased appointment availability or transitioned to telemedicine, PWID reported being unable to access services. Social distancing led to isolation or loneliness during hospital stays and in the community. Recovery meetings and support groups, critical to addiction recovery, were particularly affected. Other participants reported that uncertainty and fear of contracting the virus generated changes in behavior that led them to avoid seeking services. CONCLUSIONS: COVID-19 has disrupted health systems and social services, leading PWID to experience unprecedented barriers to accessing and maintaining health and addiction services in both inpatient and outpatient settings. Opioid use disorder management must be understood as a holistic process, and a multidisciplinary approach to ensuring comprehensive care, even in the midst of this pandemic, is needed.


Subject(s)
COVID-19 , Opioid-Related Disorders , Substance Abuse, Intravenous , Health Services Accessibility , Humans , Pandemics , Substance Abuse, Intravenous/epidemiology
11.
Elife ; 102021 07 20.
Article in English | MEDLINE | ID: mdl-34282722

ABSTRACT

Background: Polyamine levels are intricately controlled by biosynthetic, catabolic enzymes and antizymes. The complexity suggests that minute alterations in levels lead to profound abnormalities. We described the therapeutic course for a rare syndrome diagnosed by whole exome sequencing caused by gain-of-function variants in the C-terminus of ornithine decarboxylase (ODC), characterized by neurological deficits and alopecia. Methods: N-acetylputrescine levels with other metabolites were measured using ultra-performance liquid chromatography paired with mass spectrometry and Z-scores established against a reference cohort of 866 children. Results: From previous studies and metabolic profiles, eflornithine was identified as potentially beneficial with therapy initiated on FDA approval. Eflornithine normalized polyamine levels without disrupting other pathways. She demonstrated remarkable improvement in both neurological symptoms and cortical architecture. She gained fine motor skills with the capacity to feed herself and sit with support. Conclusions: This work highlights the strategy of repurposing drugs to treat a rare disease. Funding: No external funding was received for this work.


Subject(s)
Dicarboxylic Acid Transporters/genetics , Drug Repositioning , Eflornithine/pharmacology , Eflornithine/therapeutic use , Gain of Function Mutation/genetics , Mitochondrial Membrane Transport Proteins/genetics , Alopecia , Child, Preschool , Dicarboxylic Acid Transporters/chemistry , Genetic Variation , Humans , Mitochondrial Membrane Transport Proteins/chemistry , Ornithine Decarboxylase/genetics , Polyamines , Putrescine/analogs & derivatives , Rare Diseases/drug therapy , Rare Diseases/genetics , Exome Sequencing
12.
Am J Emerg Med ; 49: 117-123, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34102456

ABSTRACT

BACKGROUND: Emergency departments (EDs) play an essential role in the timely initiation of HIV post-exposure prophylaxis (PEP) for sexual assault victims. METHODS: Retrospective analysis of sexual assault victims evaluated and offered HIV PEP in an urban academic ED between January 1, 2005 and January 1, 2018. Data on demographics, comorbidities, nature of sexual assault, initial ED care, subsequent healthcare utilization within 28 days of initial ED visit, and evidence of seroconversion within 6 months of the initial ED visit were obtained. Predictors of subsequent ED visit and follow-up in the infectious diseases clinic were evaluated using logistic regression analysis. RESULTS: Four hundred twenty-three ED visits met criteria for inclusion in this study. Median age at ED presentation was 25 years (IQR 21-34 years), with the majority of victims being female (95.5%), Black (63.4%), unemployed (66.3%) and uninsured (53.9%); psychiatric comorbidities (38.8%) and substance abuse (23.6%) were common. About 87% of the patients accepted HIV PEP (368 of 423 ED visits). Age (OR 0.97, 95% CI 0.94-0.99, p = 0.025) and sexual assault involving >1 assailant (OR 0.48, 95% CI 0.26-0.88, p = 0.018) were associated with lower likelihood of HIV PEP acceptance. Ten patients (2.7%) followed up with the infectious disease clinic within 28 days of starting HIV PEP; 70 patients (19%) returned to the ED for care during the same time period. Psychiatric comorbidity (OR 2.48, 95% CI 1.43-4.30, p = 0.001) and anal penetration (OR 2.02, 95% CI 1.10-3.70, p = 0.024) were associated with greater likelihood of repeat ED visit; female gender (OR 0.30, 95% CI 0.11-0.85, p = 0.023) was associated with lower likelihood of repeat visit. Completion of HIV PEP was documented for 14 (3.3%) individuals. CONCLUSIONS: While ED patient acceptance of HIV PEP after sexual assault was high, infectious disease clinic follow-up and documented completion of PEP remained low. Innovative care models bridging EDs to outpatient clinics and community support services are needed to optimize transitions of care for sexual assault victims, including those receiving HIV PEP.


Subject(s)
HIV Infections/prevention & control , Post-Exposure Prophylaxis/methods , Sex Offenses , Adult , Anti-HIV Agents/therapeutic use , Emergency Service, Hospital/organization & administration , Female , HIV Infections/drug therapy , Humans , Logistic Models , Male , Retrospective Studies
13.
PLoS One ; 16(6): e0253403, 2021.
Article in English | MEDLINE | ID: mdl-34191829

ABSTRACT

As we explore beyond Earth, astronauts may be at risk for harmful DNA damage caused by ionizing radiation. Double-strand breaks are a type of DNA damage that can be repaired by two major cellular pathways: non-homologous end joining, during which insertions or deletions may be added at the break site, and homologous recombination, in which the DNA sequence often remains unchanged. Previous work suggests that space conditions may impact the choice of DNA repair pathway, potentially compounding the risks of increased radiation exposure during space travel. However, our understanding of this problem has been limited by technical and safety concerns, which have prevented integral study of the DNA repair process in space. The CRISPR/Cas9 gene editing system offers a model for the safe and targeted generation of double-strand breaks in eukaryotes. Here we describe a CRISPR-based assay for DNA break induction and assessment of double-strand break repair pathway choice entirely in space. As necessary steps in this process, we describe the first successful genetic transformation and CRISPR/Cas9 genome editing in space. These milestones represent a significant expansion of the molecular biology toolkit onboard the International Space Station.


Subject(s)
CRISPR-Cas Systems/genetics , Cosmic Radiation/adverse effects , DNA Breaks, Double-Stranded/radiation effects , DNA Repair/radiation effects , Occupational Exposure/adverse effects , Astronauts , DNA, Fungal/genetics , DNA, Fungal/radiation effects , Gene Editing , Humans , Mutagenesis , Mutation , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/radiation effects , Saccharomyces cerevisiae Proteins/genetics , Spacecraft
14.
Salud Colect ; 17: e3727, 2021 11 23.
Article in Spanish | MEDLINE | ID: mdl-35896323

ABSTRACT

This study aims to understand the experiences of obstetric violence experienced by Embera women during childbirth at healthcare facilities in the city of Medellin, Colombia. Employing a qualitative, ethnographic approach, semi-structured interviews were conducted with nine indigenous Embera women between February and March of 2020. The data indicate these women, members of the largest indigenous community in Medellín, experience similar forms of obstetric violence to non-indigenous women, which might be explained by the authoritarian medical habitus and a health system that prioritizes market forces. However, the data also reveal that indigenous women experience a specific form of this phenomenon: a lack of respect or cultural sensitivity, stemming from the process of colonialism to which indigenous peoples have been subjected. This dynamic continues to be expressed during delivery in healthcare childbirth settings via ignorance and disregard for indigenous ancestral knowledge, which can be understood as microaggressions that occur frequently but are difficult to identify.


El objetivo de este estudio es comprender las experiencias frente a la violencia obstétrica que vivieron las mujeres emberas durante la atención del parto en servicios de salud de la ciudad de Medellín, Colombia. A través de un abordaje cualitativo de tipo etnográfico, con entrevistas semiestructuradas realizadas a nueve mujeres indígenas emberas entre febrero y marzo de 2020, se identificó que estas mujeres, representantes del grupo más grande de los pueblos indígenas en Medellín, experimentan formas de violencia obstétrica similares a las vividas por mujeres occidentalizadas, que pueden ser explicadas por el habitus médico autoritario, y por un sistema de salud que privilegia las lógicas del mercado. Sin embargo, esta investigación amplía la comprensión de la violencia obstétrica al identificar que las mujeres indígenas experimentan otra forma particular de este fenómeno: la falta de respeto o sensibilidad cultural, lo cual deviene del proceso de colonialidad vivido por los pueblos originarios, y que hoy en día se expresa en el contexto de la atención al parto, bajo formas como el desconocimiento y desprecio de los saberes ancestrales que las mujeres de las comunidades indígenas aún conservan y que podemos comprender como microagresiones comunes y ambiguas.


Subject(s)
Ethnicity , Parturition , Anthropology, Cultural , Colombia , Female , Humans , Pregnancy , Qualitative Research , Violence
15.
Salud colect ; 17: 3727-3727, 2021. tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1377288

ABSTRACT

RESUMEN El objetivo de este estudio es comprender las experiencias frente a la violencia obstétrica que vivieron las mujeres emberas durante la atención del parto en servicios de salud de la ciudad de Medellín, Colombia. A través de un abordaje cualitativo de tipo etnográfico, con entrevistas semiestructuradas realizadas a nueve mujeres indígenas emberas entre febrero y marzo de 2020, se identificó que estas mujeres, representantes del grupo más grande de los pueblos indígenas en Medellín, experimentan formas de violencia obstétrica similares a las vividas por mujeres occidentalizadas, que pueden ser explicadas por el habitus médico autoritario, y por un sistema de salud que privilegia las lógicas del mercado. Sin embargo, esta investigación amplía la comprensión de la violencia obstétrica al identificar que las mujeres indígenas experimentan otra forma particular de este fenómeno: la falta de respeto o sensibilidad cultural, lo cual deviene del proceso de colonialidad vivido por los pueblos originarios, y que hoy en día se expresa en el contexto de la atención al parto, bajo formas como el desconocimiento y desprecio de los saberes ancestrales que las mujeres de las comunidades indígenas aún conservan y que podemos comprender como microagresiones comunes y ambiguas.


ABSTRACT This study aims to understand the experiences of obstetric violence experienced by Embera women during childbirth at healthcare facilities in the city of Medellin, Colombia. Employing a qualitative, ethnographic approach, semi-structured interviews were conducted with nine indigenous Embera women between February and March of 2020. The data indicate these women, members of the largest indigenous community in Medellín, experience similar forms of obstetric violence to non-indigenous women, which might be explained by the authoritarian medical habitus and a health system that prioritizes market forces. However, the data also reveal that indigenous women experience a specific form of this phenomenon: a lack of respect or cultural sensitivity, stemming from the process of colonialism to which indigenous peoples have been subjected. This dynamic continues to be expressed during delivery in healthcare childbirth settings via ignorance and disregard for indigenous ancestral knowledge, which can be understood as microaggressions that occur frequently but are difficult to identify.

16.
FASEB Bioadv ; 2(3): 160-165, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32161905

ABSTRACT

Human spaceflight endeavors present an opportunity to expand our presence beyond Earth. To this end, it is crucial to understand and diagnose effects of long-term space travel on the human body. Developing tools for targeted, on-site detection of specific DNA sequences will allow us to establish research and diagnostics platforms that will benefit space programs. We describe a simple DNA diagnostic method that utilizes colorimetric loop-mediated isothermal amplification (LAMP) to enable detection of a repetitive telomeric DNA sequence in as little as 30 minutes. A proof of concept assay for this method was carried out using existing hardware on the International Space Station and the results were read instantly by an astronaut through a simple color change of the reaction mixture. LAMP offers a novel platform for on-orbit DNA-based diagnostics that can be deployed on the International Space Station and to the broader benefit of space programs.

17.
PLoS One ; 13(10): e0205852, 2018.
Article in English | MEDLINE | ID: mdl-30379894

ABSTRACT

The distance and duration of human spaceflight missions is set to markedly increase over the coming decade as we prepare to send astronauts to Mars. However, the health impact of long-term exposure to cosmic radiation and microgravity is not fully understood. In order to identify the molecular mechanisms underpinning the effects of space travel on human health, we must develop the capacity to monitor changes in gene expression and DNA integrity in space. Here, we report successful implementation of three molecular biology procedures on board the International Space Station (ISS) using a miniaturized thermal cycler system and C. elegans as a model organism: first, DNA extraction-the initial step for any type of DNA analysis; second, reverse transcription of RNA to generate complementary DNA (cDNA); and third, the subsequent semi-quantitative PCR amplification of cDNA to analyze gene expression changes in space. These molecular procedures represent a significant expansion of the budding molecular biology capabilities of the ISS and will permit more complex analyses of space-induced genetic changes during spaceflight missions aboard the ISS and beyond.


Subject(s)
Caenorhabditis elegans/genetics , DNA, Helminth/genetics , Electrophoresis, Agar Gel/instrumentation , Gene Expression , RNA, Helminth/genetics , Reverse Transcriptase Polymerase Chain Reaction/instrumentation , Animals , Astronauts , Caenorhabditis elegans/radiation effects , Cosmic Radiation/adverse effects , DNA, Helminth/isolation & purification , Electrophoresis, Agar Gel/methods , Humans , RNA, Helminth/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction/methods , Space Flight , Weightlessness
18.
J Acoust Soc Am ; 141(5): 2989, 2017 05.
Article in English | MEDLINE | ID: mdl-28599520

ABSTRACT

Speakers have been shown to alter their speech to resemble that of their conversational partner. Do speakers converge with their interlocutor's baseline, or does convergence stem from conversational properties that similarly affect both parties? Using the Switchboard corpus, this paper shows evidence for speakers' convergence in speech rate to the other party's baseline, not only to conversation-specific properties. Study 1 shows that the method for calculating speech rate used in this paper is powerful enough to replicate established findings. Study 2 demonstrates that speakers are mostly affected by their own behavior in other contexts, but that they also converge to their interlocutor's baseline, established using the interlocutor's behavior in other contexts. Study 2 also shows that speakers change their speech rate in response to the interlocutor's characteristics: speakers speak more slowly with older speakers regardless of the interlocutor's speech rate, and male speakers speak faster with other male speakers.


Subject(s)
Imitative Behavior , Speech Acoustics , Speech Perception , Verbal Behavior , Voice Quality , Age Factors , Female , Humans , Male , Sex Factors , Speech Production Measurement , Time Factors
19.
Pediatr Crit Care Med ; 15(7): e306-13, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24977687

ABSTRACT

OBJECTIVE: To describe packed RBC utilization patterns in trauma patients admitted to a PICU and study associated outcomes while controlling for severity. DESIGN: Retrospective cohort study. SETTING: The PICU of a tertiary care children's hospital. PATIENTS: All pediatric trauma patients admitted to Helen DeVos Children's Hospital PICU between June 2007 and July 2010, either directly from the emergency department or transferred from another institution. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 389 trauma patients, 107 patients (27.5%) transferred to the PICU were transfused with blood products. Of these transfusions, 81 were packed RBC transfusions and 26 were other blood products. Only 73 of the packed RBC transfusions had a documented time of transfusion: 17 (23.3%) were transfused prior to PICU admission, seven (9.5%) both before and after PICU, and 49 (67.1%) only after PICU admission. After adjusting for injury severity score, transfused patients had higher odds of needing mechanical ventilation (odds ratios, 9.2; 95% CI, 3.6-23.3) and higher risk of mortality (odds ratios, 8.6; 95% CI, 2.6-28.6), when compared with nontransfused patients. Mean age of packed RBC was 19.6 ± 9.3 days (mean ± SD). The impact of age of packed RBCs on mortality was examined as a categorical variable at 14, 21, and 28 days. Packed RBCs more than 28 days old (14/61 patients) were associated with longer lengths of stay (13 ± 12 vs 7 ± 6; p < 0.03), lower discharge Glasgow Coma Scale score (9 ± 6 vs 13 ± 4; p< 0.03), and more mortality (43% vs 13%; p < 0.02) when compared with blood less than 28 days old. CONCLUSIONS: In pediatric trauma patients, transfusion of packed RBC and use of older RBC units are associated with higher risk of adverse outcomes independent of injury severity.


Subject(s)
Critical Care , Erythrocyte Transfusion , Wounds and Injuries/therapy , Adolescent , Age Factors , Child , Child, Preschool , Female , Humans , Injury Severity Score , Length of Stay , Male , Respiration, Artificial , Retrospective Studies , Treatment Outcome
20.
BMC Plant Biol ; 13: 185, 2013 Nov 20.
Article in English | MEDLINE | ID: mdl-24256402

ABSTRACT

BACKGROUND: Epigenetic regulation is necessary for maintaining gene expression patterns in multicellular organisms. The Polycomb Group (PcG) proteins form several complexes with important and deeply conserved epigenetic functions in both the plant and animal kingdoms. One such complex, the Polycomb Repressive Complex 2 (PRC2), is critical to many developmental processes in plants including the regulation of major developmental transitions. In addition, PRC2 restricts the expression domain of various transcription factor families in Arabidopsis, including the class I KNOX genes and several of the ABCE class MADS box genes. While the functions of these transcription factors are known to be deeply conserved, whether or not their regulation by PRC2 is similarly conserved remains an open question. RESULTS: Here we use virus-induced gene silencing (VIGS) to characterize the function of the PRC2 complex in lateral organ development of Aquilegia x coerulea 'Origami', a member of the lower eudicot order Ranunculales. Leaves with PRC2 down-regulation displayed a range of phenotypes including ruffled or curled laminae, additional lobing, and an increased frequency of higher order branching. Sepals and petals were also affected, being narrowed, distorted, or, in the case of the sepals, exhibiting partial homeotic transformation. Many of the petal limbs also had a particularly intense yellow coloration due to an accumulation of carotenoid pigments. We show that the A. x coerulea floral MADS box genes AGAMOUS1 (AqAG1), APETALA3-3 (AqAP3-3) and SEPALLATA3 (AqSEP3) are up-regulated in many tissues, while expression of the class I KNOX genes and several candidate genes involved in carotenoid production or degradation are largely unaffected. CONCLUSIONS: PRC2 targeting of several floral MADS box genes may be conserved in dicots, but other known targets do not appear to be. In the case of the type I KNOX genes, this may reflect a regulatory shift associated with the evolution of compound leaves.


Subject(s)
Aquilegia/growth & development , Aquilegia/metabolism , Conserved Sequence , Crosses, Genetic , Organogenesis , Polycomb Repressive Complex 2/metabolism , Aquilegia/genetics , Down-Regulation/genetics , Flowers/anatomy & histology , Flowers/genetics , Gene Expression Regulation, Plant , Gene Silencing , Genetic Association Studies , Organogenesis/genetics , Phenotype , Plant Leaves/genetics , Plant Proteins/metabolism , Plant Viruses/physiology , Polycomb Repressive Complex 2/genetics
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