RESUMEN
Chromatin plays an essential role in the nuclear mechanical response and determining nuclear shape, which maintain nuclear compartmentalization and function. However, major genomic functions, such as transcription activity, might also impact cell nuclear shape via blebbing and rupture through their effects on chromatin structure and dynamics. To test this idea, we inhibited transcription with several RNA polymerase II inhibitors in wild-type cells and perturbed cells that presented increased nuclear blebbing. Transcription inhibition suppressed nuclear blebbing for several cell types, nuclear perturbations and transcription inhibitors. Furthermore, transcription inhibition suppressed nuclear bleb formation, bleb stabilization and bleb-based nuclear ruptures. Interestingly, transcription inhibition did not alter the histone H3 lysine 9 (H3K9) modification state, nuclear rigidity, and actin compression and contraction, which typically control nuclear blebbing. Polymer simulations suggested that RNA polymerase II motor activity within chromatin could drive chromatin motions that deform the nuclear periphery. Our data provide evidence that transcription inhibition suppresses nuclear blebbing and rupture, in a manner separate and distinct from chromatin rigidity.
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Cromatina , ARN Polimerasa II , ARN Polimerasa II/metabolismo , Cromatina/metabolismo , Núcleo Celular/metabolismo , Transcripción Genética , Actinas/metabolismoRESUMEN
BACKGROUND: Accurate prevalence estimates of drug use and its harms are important to characterize burden and develop interventions to reduce negative health outcomes and disparities. Lack of a sampling frame for marginalized/stigmatized populations, including persons who use drugs (PWUD) in rural settings, makes this challenging. Respondent-driven sampling (RDS) is frequently used to recruit PWUD. However, the validity of RDS-generated population-level prevalence estimates relies on assumptions that should be evaluated. METHODS: RDS was used to recruit PWUD across seven Rural Opioid Initiative studies between 2018-2020. To evaluate RDS assumptions, we computed recruitment homophily and design effects, generated convergence and bottleneck plots, and tested for recruitment and degree differences. We compared sample proportions with three RDS-adjusted estimators (two variations of RDS-I and RDS-II) for five variables of interest (past 30-day use of heroin, fentanyl, and methamphetamine; past 6-month homelessness; and being positive for hepatitis C virus (HCV) antibody) using linear regression with robust confidence intervals. We compared regression estimates for the associations between HCV positive antibody status and (a) heroin use, (b) fentanyl use, and (c) age using RDS-1 and RDS-II probability weights and no weights using logistic and modified Poisson regression and random-effects meta-analyses. RESULTS: Among 2,842 PWUD, median age was 34 years and 43% were female. Most participants (54%) reported opioids as their drug of choice, however regional differences were present (e.g., methamphetamine range: 4-52%). Many recruitment chains were not long enough to achieve sample equilibrium. Recruitment homophily was present for some variables. Differences with respect to recruitment and degree varied across studies. Prevalence estimates varied only slightly with different RDS weighting approaches, most confidence intervals overlapped. Variations in measures of association varied little based on weighting approach. CONCLUSIONS: RDS was a useful recruitment tool for PWUD in rural settings. However, several violations of key RDS assumptions were observed which slightly impacts estimation of proportion although not associations.
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Población Rural , Humanos , Población Rural/estadística & datos numéricos , Femenino , Masculino , Adulto , Trastornos Relacionados con Opioides/epidemiología , Persona de Mediana Edad , Prevalencia , Consumidores de Drogas/estadística & datos numéricos , Muestreo , Trastornos Relacionados con Sustancias/epidemiología , Selección de PacienteRESUMEN
People who nonmedically use drugs (PWUD) face intricate social issues that suppress self-actualization, communal integration, and overall health and wellness. "Strengths-based" approaches, an under-used pedagogy and practice in addiction medicine, underscore the significance of identifying and recognizing the inherent and acquired skills, attributes, and capacities of PWUD. A strengths-based approach engenders client affirmation and improves their capacity to reduce drug use-related harms by leveraging existing capabilities. Exploring this paradigm, we conducted and analyzed interviews with 46 PWUD who were clients at syringe services programs in New York City and rural southern Illinois, two areas with elevated rates of opioid-related morbidity and mortality, to assess respondents' perceived strengths. We located two primary thematic modalities in which strengths-based ethos is expressed: individuals (1) being and advocate and resource for harm reduction knowledge and practices and (2) engaging in acts of continuous self-actualization. These dynamics demonstrate PWUD strengths populating and manifesting in complex ways that both affirm and challenge humanist and biomedical notions of individual agency, as PWUD refract enacted, anticipated, and perceived stigmas. In conclusion, programs that blend evidence-based, systems-level interventions on drug use stigma and disenfranchisement with meso and micro-level strengths-based interventions that affirm and leverage personal identity, decision-making capacity, and endemic knowledge may help disrupt health promotion cleavages among PWUD.
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Consumidores de Drogas , Trastornos Relacionados con Sustancias , Humanos , Analgésicos Opioides/uso terapéutico , Trastornos Relacionados con Sustancias/epidemiología , Actitud , Reducción del DañoRESUMEN
BACKGROUND: Research conducted in urban areas has highlighted the impact of housing instability on people who inject drugs (PWID), revealing that it exacerbates vulnerability to drug-related harms and impedes syringe service program (SSP) use. However, few studies have explored the effects of houselessness on SSP use among rural PWID. This study examines the relationship between houselessness and SSP utilization among PWID in eight rural areas across 10 states. METHODS: PWID were recruited using respondent-driven sampling for a cross-sectional survey that queried self-reported drug use and SSP utilization in the prior 30 days, houselessness in the prior 6 months and sociodemographic characteristics. Using binomial logistic regression, we examined the relationship between experiencing houselessness and any SSP use. To assess the relationship between houselessness and the frequency of SSP use, we conducted multinomial logistic regression analyses among participants reporting any past 30-day SSP use. RESULTS: Among 2394 rural PWID, 56.5% had experienced houselessness in the prior 6 months, and 43.5% reported past 30-day SSP use. PWID who had experienced houselessness were more likely to report using an SSP compared to their housed counterparts (adjusted odds ratio [aOR] = 1.24 [95% confidence intervals [CI] 1.01, 1.52]). Among those who had used an SSP at least once (n = 972), those who experienced houselessness were just as likely to report SSP use two (aOR = 0.90 [95% CI 0.60, 1.36]) and three times (aOR = 1.18 [95% CI 0.77, 1.98]) compared to once. However, they were less likely to visit an SSP four or more times compared to once in the prior 30 days (aOR = 0.59 [95% CI 0.40, 0.85]). CONCLUSION: This study provides evidence that rural PWID who experience houselessness utilize SSPs at similar or higher rates as their housed counterparts. However, housing instability may pose barriers to more frequent SSP use. These findings are significant as people who experience houselessness are at increased risk for drug-related harms and encounter additional challenges when attempting to access SSPs.
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Consumidores de Drogas , Infecciones por VIH , Abuso de Sustancias por Vía Intravenosa , Humanos , Abuso de Sustancias por Vía Intravenosa/epidemiología , Programas de Intercambio de Agujas , Estudios Transversales , Recolección de DatosRESUMEN
BACKGROUND: Chronic health conditions associated with long-term drug use may pose additional risks to people who use drugs (PWUD) when coupled with COVID-19 infection. Despite this, PWUD, especially those living in rural areas, may be less likely to seek out health services. Previous research has highlighted the increased disease burden of COVID-19 among PWUD. Our manuscript supplements this literature by exploring unique attitudes of PWUD living in rural areas toward the pandemic, COVID-19 vaccination, and the role of harm reduction (HR) organizations in raising health awareness among PWUD. METHODS: Semi-structured interviews were conducted with 20 PWUD living in rural southern Illinois. Audio recordings were professionally transcribed. A preliminary codebook was created based on interview domains. Two trained coders conducted iterative coding of the transcripts, and new codes were added through line-by-line coding and thematic grouping. RESULTS: Twenty participants (45% female, mean age of 38) completed interviews between June and November 2021. Participants reported negative impacts of the pandemic on mental health, financial wellbeing, and drug quality. However, the health impacts of COVID-19 were often described as less concerning than its impacts on these other aspects of life. Many expressed doubt in the severity of COVID-19 infection. Among the 16 unvaccinated participants who reported receiving most of their information from the internet or word of mouth, uncertainty about vaccine contents and distrust of healthcare and government institutions engendered wariness of the vaccination. Distrust of healthcare providers was related to past stigmatization and judgement, but did not extend to the local HR organization, which was unanimously endorsed as a positive institution. Among participants who did not access services directly from the HR organization, secondary distribution of HR supplies by other PWUD was a universally cited form of health maintenance. Participants expressed interest in low-threshold healthcare, including COVID-19 vaccination, should it be offered in the local HR organization's office and mobile units. CONCLUSION: COVID-19 and related public health measures have affected this community in numerous ways. Integrating healthcare services into harm reduction infrastructures and mobilizing secondary distributors of supplies may promote greater engagement with vaccination programs and other healthcare services. TRIAL NUMBER: NCT04427202.
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COVID-19 , Reducción del Daño , Adulto , Femenino , Humanos , Masculino , Vacunas contra la COVID-19 , Atención a la Salud , PandemiasRESUMEN
Community-acquired coinfection in coronavirus disease 2019 (COVID-19) is not well defined. Current literature describes coinfection in 0-40% of COVID-19 patients. In this retrospective report, coinfection was identified in 3.7% of patients and 41% of patients admitted to intensive care (Pâ <â .005). Despite infrequent coinfection, antibiotics were used in 69% of patients.
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COVID-19 , Coinfección , Coinfección/epidemiología , Hospitalización , Humanos , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: Empiric antibiotics for community acquired bacterial pneumonia (CABP) are often prescribed to patients with COVID-19, despite a low reported incidence of co-infections. Stewardship interventions targeted at facilitating appropriate antibiotic prescribing for CABP among COVID-19 patients are needed. We developed a guideline for antibiotic initiation and discontinuation for CABP in COVID-19 patients. The purpose of this study was to assess the impact of this intervention on the duration of empiric CABP antibiotic therapy among patients with COVID-19. METHODS: This was a single-center, retrospective, quasi-experimental study of adult patients admitted between 3/1/2020 to 4/25/2020 with COVID-19 pneumonia, who were initiated on empiric CABP antibiotics. Patients were excluded if they were initiated on antibiotics > 48 h following admission or if another source of infection was identified. The primary outcome was the duration of antibiotic therapy (DOT) prior to the guideline (March 1 to March27, 2020) and after guideline implementation (March 28 to April 25, 2020). We also evaluated the clinical outcomes (mortality, readmissions, length of stay) among those initiated on empiric CABP antibiotics. RESULTS: A total of 506 patients with COVID-19 were evaluated, 102 pre-intervention and 404 post-intervention. Prior to the intervention, 74.5% (n = 76) of patients with COVID-19 received empiric antibiotics compared to only 42% of patients post-intervention (n = 170), p < 0.001. The median DOT in the post-intervention group was 1.3 days shorter (p < 0.001) than the pre-intervention group, and antibiotics directed at atypical bacteria DOT was reduced by 2.8 days (p < 0.001). More patients in the post-intervention group were initiated on antibiotics based on criteria consistent with our guideline (68% versus 87%, p = 0.001). There were no differences between groups in terms of clinical outcomes. CONCLUSION: Following the implementation of a guideline outlining recommendations for initiating and discontinuing antibiotics for CABP among COVID-19 inpatients, we observed a reduction in antibiotic prescribing and DOT. The guideline also resulted in a significant increase in the rate of guideline-congruent empiric antibiotic initiation.
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Antibacterianos/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Adulto , Programas de Optimización del Uso de los Antimicrobianos , Coinfección/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Hospitalización , Humanos , Pacientes Internos , Neumonía Bacteriana/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Estudios RetrospectivosRESUMEN
RATIONALE & OBJECTIVE: Contaminated water and other fluids are increasingly recognized to be associated with health care-associated infections. We investigated an outbreak of Gram-negative bloodstream infections at 3 outpatient hemodialysis facilities. STUDY DESIGN: Matched case-control investigations. SETTING & PARTICIPANTS: Patients who received hemodialysis at Facility A, B, or C from July 2015 to November 2016. EXPOSURES: Infection control practices, sources of water, dialyzer reuse, injection medication handling, dialysis circuit priming, water and dialysate test findings, environmental reservoirs such as wall boxes, vascular access care practices, pulsed-field gel electrophoresis, and whole-genome sequencing of bacterial isolates. OUTCOMES: Cases were defined by a positive blood culture for any Gram-negative bacteria drawn July 1, 2015 to November 30, 2016 from a patient who had received hemodialysis at Facility A, B, or C. ANALYTICAL APPROACH: Exposures in cases and controls were compared using matched univariate conditional logistic regression. RESULTS: 58 cases of Gram-negative bloodstream infection occurred; 48 (83%) required hospitalization. The predominant organisms were Serratia marcescens (n=21) and Pseudomonas aeruginosa (n=12). Compared with controls, cases had higher odds of using a central venous catheter for dialysis (matched odds ratio, 54.32; lower bound of the 95% CI, 12.19). Facility staff reported pooling and regurgitation of waste fluid at recessed wall boxes that house connections for dialysate components and the effluent drain within dialysis treatment stations. Environmental samples yielded S marcescens and P aeruginosa from wall boxes. S marcescens isolated from wall boxes and case-patients from the same facilities were closely related by pulsed-field gel electrophoresis and whole-genome sequencing. We identified opportunities for health care workers' hands to contaminate central venous catheters with contaminated fluid from the wall boxes. LIMITATIONS: Limited patient isolates for testing, on-site investigation occurred after peak of infections. CONCLUSIONS: This large outbreak was linked to wall boxes, a previously undescribed source of contaminated fluid and biofilms in the immediate patient care environment.
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Bacteriemia/epidemiología , Infección Hospitalaria/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/epidemiología , Diálisis Renal/efectos adversos , Anciano , Bacteriemia/microbiología , Femenino , Estudios de Seguimiento , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Asian American Pacific Islander (AAPI) sexual and gender minorities (SGM) face unique challenges in mental health and accessing high-quality health care. OBJECTIVE: The objective of this study was to identify barriers and facilitators for shared decision making (SDM) between AAPI SGM and providers, especially surrounding mental health. RESEARCH DESIGN: Interviews, focus groups, and surveys. SUBJECTS: AAPI SGM interviewees in Chicago (n=20) and San Francisco (n=20). Two focus groups (n=10) in San Francisco. MEASURES: Participants were asked open-ended questions about their health care experiences and how their identities impacted these encounters. Follow-up probes explored SDM and mental health. Participants were also surveyed about attitudes towards SGM disclosure and preferences about providers. Transcripts were analyzed for themes and a conceptual model was developed. RESULTS: Our conceptual model elucidates the patient, provider, and encounter-centered factors that feed into SDM for AAPI SGM. Some participants shared the stigma of SGM identities and mental health in their AAPI families. Their AAPI and SGM identities were intertwined in affecting mental health. Some providers inappropriately controlled the visibility of the patient's identities, ignoring or overemphasizing them. Participants varied on whether they preferred a provider of the same race, and how prominently their AAPI and/or SGM identities affected SDM. CONCLUSIONS: Providers should understand identity-specific challenges for AAPI SGM to engage in SDM. Providers should self-educate about AAPI and SGM history and intracommunity heterogeneity before the encounter, create a safe environment conducive to patient disclosure of SGM identity, and ask questions about patient priorities for the visit, pronouns, and mental health.
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Asiático/psicología , Toma de Decisiones Conjunta , Nativos de Hawái y Otras Islas del Pacífico/psicología , Participación del Paciente/psicología , Minorías Sexuales y de Género/psicología , Femenino , Humanos , Entrevistas como Asunto , Masculino , Salud Mental , Estigma SocialRESUMEN
Opioid overprescribing is a major driver of the current opioid overdose epidemic. However, annual opioid prescribing in the USA dropped from 782 to 640 morphine milligram equivalents per capita between 2010 and 2015, while opioid overdose deaths increased by 63%. To better understand the role of prescription opioids and health care utilization prior to opioid-related overdose, we analyzed the death records of decedents who died of an opioid overdose in Illinois in 2016 and linked to any existing controlled substance monitoring program (CSMP) and emergency department (ED) or hospital discharge records. We found that of the 1893 opioid-related overdoses, 573 (30.2%) decedents had not filled an opioid analgesic prescription within the 6 years prior to death. Decedents without an opioid prescription were more likely to be black (33.3% vs 20.2%, p < .001), Hispanic (16.3% vs 8.8%, p < .001), and Chicago residents (46.8% vs 25.6%, p < .001) than decedents with at least one filled opioid prescription. Decedents who did not fill an opioid prescription were less likely to die of an overdose involving prescribed opioids (7.3% vs 19.5%, p < .001) and more likely to fatally overdose on heroin (63% vs 50.4%, p < .001) or fentanyl/fentanyl analogues (50.3% vs 41.8%, p = .001). Between 2012 and the time of death, decedents without an opioid prescription had fewer emergency department admissions (2.5 ± 4.2 vs 10.6 ± 15.8, p < .001), were less likely to receive an opioid use disorder diagnosis (41.3% vs 47.5%, p = .052), and were less likely to be prescribed buprenorphine for opioid use disorder treatment (3.3% vs 8.6%, p < .001). Public health interventions have often focused on opioid prescribing and the use of CSMPs as the core preventive measures to address the opioid crisis. We identified a subset of individuals in Illinois who may not be impacted by such interventions. Additional research is needed to understand what strategies may be successful among high-risk populations that have limited opioid analgesic prescription history and low health care utilization.
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Analgésicos Opioides/envenenamiento , Buprenorfina/uso terapéutico , Sobredosis de Droga/mortalidad , Fentanilo/envenenamiento , Heroína/envenenamiento , Trastornos Relacionados con Opioides/mortalidad , Aceptación de la Atención de Salud/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto , Negro o Afroamericano/estadística & datos numéricos , Chicago/epidemiología , Sobredosis de Droga/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/epidemiología , Salud Pública , Factores de RiesgoRESUMEN
Background: Prescription opioid use (POU) among young adults is increasing. This represents a major public health concern due to the increased risks of opioid use misuse and opioid-related overdose. Limited research has examined the POU among young black men who have sex with men (YBMSM), a diverse group experiencing continued increases in HIV incidence over the past decade. Objective: This study aims to examine the prevalence and both the individual and network characteristics of POU among YBMSM. Methods: Data were from a longitudinal cohort study of 16-29 year old YBMSM (N = 514) between 2013 and 2016 in Chicago. Bivariate and multivariable associations were estimated using general estimating equations (GEE). Results: Approximately 4.2% of YBMSM reported POU in the past 12 months with a cumulative incidence rate of 4.1% over the 18-month follow-up period. YBMSM having criminal justice involvements, experiencing violence, or using any illicit drug other than marijuana in the past 12 months were more likely to report POU in the past 12 months. The presence of a mother figure, however, was associated with a decreased risk of POU in the past 12 months, while engaging in condomless anal sex with their named sexual partners was associated with an increased risk of POU in the past 12 months. Conclusions: This is one of the first studies to describe POU among a population-based sample of YBMSM. The high incidence rate of POU among YBMSM is alarming, and it underscores the need for further analysis on POU among this key population.
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Negro o Afroamericano/psicología , Homosexualidad Masculina/estadística & datos numéricos , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Chicago/epidemiología , Estudios de Cohortes , Humanos , Estudios Longitudinales , Masculino , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Chronic infection with hepatitis C virus (HCV) genotype 2 or 3 can be treated with sofosbuvir without interferon. Because sofosbuvir is costly, its benefits should be compared with the additional resources used. OBJECTIVE: To estimate the cost-effectiveness of sofosbuvir-based treatments for HCV genotype 2 or 3 infection in the United States. DESIGN: Monte Carlo simulation, including deterministic and probabilistic sensitivity analyses. DATA SOURCES: Randomized trials, observational cohorts, and national health care spending surveys. TARGET POPULATION: 8 patient types defined by HCV genotype (2 vs. 3), treatment history (naive vs. experienced), and cirrhosis status (noncirrhotic vs. cirrhotic). TIME HORIZON: Lifetime. PERSPECTIVE: Payer. INTERVENTION: Sofosbuvir-based therapies, pegylated interferon-ribavirin, and no therapy. OUTCOME MEASURES: Discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: The ICER of sofosbuvir-based treatment was less than $100,000 per QALY in cirrhotic patients (genotype 2 or 3 and treatment-naive or treatment-experienced) and in treatment-experienced noncirrhotic patients but was greater than $200,000 per QALY in treatment-naive noncirrhotic patients. RESULTS OF SENSITIVITY ANALYSIS: The ICER of sofosbuvir-based therapy for treatment-naive noncirrhotic patients with genotype 2 or 3 infection was less than $100,000 per QALY when the cost of sofosbuvir was reduced by approximately 40% and 60%, respectively. In probabilistic sensitivity analyses, cost-effectiveness conclusions were robust to uncertainty in treatment efficacy. LIMITATION: The analysis did not consider possible benefits of preventing HCV transmission. CONCLUSION: Sofosbuvir provides good value for money for treatment-experienced patients with HCV genotype 2 or 3 infection and those with cirrhosis. At their current cost, sofosbuvir-based regimens for treatment-naive noncirrhotic patients exceed willingness-to-pay thresholds commonly cited in the United States. PRIMARY FUNDING SOURCE: National Institute on Drug Abuse and National Institute of Allergy and Infectious Diseases.
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Antivirales/economía , Antivirales/uso terapéutico , Análisis Costo-Beneficio , Hepatitis C Crónica/tratamiento farmacológico , Uridina Monofosfato/análogos & derivados , Progresión de la Enfermedad , Genotipo , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/genética , Humanos , Interferón-alfa/economía , Interferón-alfa/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/etiología , Cadenas de Markov , Método de Montecarlo , Años de Vida Ajustados por Calidad de Vida , Ribavirina/economía , Ribavirina/uso terapéutico , Sofosbuvir , Estados Unidos , Uridina Monofosfato/economía , Uridina Monofosfato/uso terapéuticoRESUMEN
Lamin intermediate filaments form a peripheral meshwork to support nuclear shape and function. Knockout of the LMNA gene that encodes for both lamin A and C results in an abnormally shaped nucleus. To determine the relative contribution of lamin A and C to nuclear shape, we measured nuclear blebbing and circular deviation in separate lamin A and lamin C knockdown and LMNA-/- stable cells. Lamin A knockdown increased nuclear blebbing while loss of lamin A, C, or both increased circular deviation. Overall, loss of lamin A, lamin C or both lamin A/C affect nuclear shape differentially.
RESUMEN
The nucleus must maintain stiffness to protect the shape and integrity of the nucleus to ensure proper function. Defects in nuclear stiffness caused from chromatin and lamin perturbations produce abnormal nuclear shapes common in aging, heart disease, and cancer. Loss of nuclear shape via protrusions called blebs leads to nuclear rupture that is well-established to cause nuclear dysfunction, including DNA damage. However, it remains unknown how increased DNA damage affects nuclear stiffness, shape, and ruptures, which could create a negative feedback loop. To determine if increased DNA damage alters nuclear physical properties, we treated MEF cells with DNA damage drugs cisplatin and bleomycin. DNA damage drugs caused increased nuclear blebbing and rupture in interphase nuclei within a few hours and independent of mitosis. Micromanipulation force measurements reveal that DNA damage decreased chromatin-based nuclear mechanics but did not change lamin-based strain stiffening at long extensions relative to wild type. Immunofluorescence measurements of DNA damage treatments reveal the mechanism is an ATM-dependent decrease in heterochromatin leading to nuclear weaken, blebbing, and rupture which can be rescued upon ATM inhibition treatment. Thus, DNA damage drugs cause ATM-dependent heterochromatin loss resulting in nuclear softening, blebbing, and rupture.
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Introduction: To expand access to naloxone, the state of Illinois implemented a standing order allowing registered pharmacies to dispense the drug without an individual prescription. To participate under the standing order, pharmacies were required to opt in through a formal registration process. In our study we aimed to evaluate the availability and price of naloxone at registered pharmacies. Methods: This was a prospective, de-identified, cross-sectional telephone survey. Trained interviewers posed as potential customers and used a standardized script to determine the availability of naloxone between February-December, 2019. The primary outcome was defined as a pharmacy indicating it carried naloxone, currently had naloxone in stock, and was able to dispense it without an individual prescription. Results: Of 948 registered pharmacies, 886 (93.5%) were successfully contacted. Of those, 792 (83.4%) carried naloxone, 659 (74.4%) had naloxone in stock, and 472 (53.3%) allowed purchase without a prescription. Naloxone nasal spray (86.4%) was the formulation most commonly stocked. Chain pharmacies were more likely to carry naloxone (adjusted odds ratio [aOR] 3.16, 95% confidence interval [CI] 1.97-5.01, P < 0.01) and have naloxone in stock (aOR 2.72, 95% CI 1.76-4.20, P < 0.01), but no more likely to dispense it without a prescription. Pharmacies in higher population areas (aOR 0.99, 95% CI 0.99-0.99, P < 0.05) and rural areas adjacent to metropolitan areas (aOR 0.5, 95% CI 025-0.98, P < 0.05) were less likely to have naloxone available without a prescription. Associations of naloxone availability based on other urbanicity designations, overdose count, and overdose rate were not significant. Conclusion: Among pharmacies in Illinois that formally registered to dispense naloxone without a prescription, the availability of naloxone remains limited. Additional interventions may be needed to maximize the potential impact of a statewide standing order.
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Naloxona , Antagonistas de Narcóticos , Farmacias , Naloxona/provisión & distribución , Naloxona/uso terapéutico , Humanos , Estudios Transversales , Estudios Prospectivos , Illinois , Antagonistas de Narcóticos/provisión & distribución , Antagonistas de Narcóticos/uso terapéutico , Farmacias/estadística & datos numéricos , Órdenes Permanentes , Accesibilidad a los Servicios de Salud , Masculino , Femenino , Sobredosis de Droga/tratamiento farmacológicoRESUMEN
[This corrects the article DOI: 10.1016/j.pmedr.2023.102496.].
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The nucleus is a mechanically stable compartment of the cell that contains the genome and performs many essential functions. Nuclear mechanical components chromatin and lamins maintain nuclear shape, compartmentalization, and function by resisting antagonistic actin contraction and confinement. Studies have yet to compare chromatin and lamins perturbations side-by-side as well as modulated actin contraction while holding confinement constant. To accomplish this, we used nuclear localization signal green fluorescent protein to measure nuclear shape and rupture in live cells with chromatin and lamin perturbations. We then modulated actin contraction while maintaining actin confinement measured by nuclear height. Wild type, chromatin decompaction, and lamin B1 null present bleb-based nuclear deformations and ruptures dependent on actin contraction and independent of actin confinement. Actin contraction inhibition by Y27632 decreased nuclear blebbing and ruptures while activation by CN03 increased rupture frequency. Lamin A/C null results in overall abnormal shape also reliant on actin contraction, but similar blebs and ruptures as wild type. Increased DNA damage is caused by nuclear blebbing or abnormal shape which can be relieved by inhibition of actin contraction which rescues nuclear shape and decreases DNA damage levels in all perturbations. Thus, actin contraction drives nuclear blebbing, bleb-based ruptures, and abnormal shape independent of changes in actin confinement.
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Actinas , Cromatina , Actinas/metabolismo , Cromatina/metabolismo , Lamina Tipo A/metabolismo , Núcleo Celular/metabolismoRESUMEN
ISSUES: To date, there has been no synthesis of research addressing the scale and nuances of the opioid epidemic in racial/ethnic minority populations in the United States that considers the independent and joint impacts of dynamics such as structural disadvantage, provider bias, health literacy, cultural norms and various other risk factors. APPROACH: Using the "risk environment" framework, we conducted a scoping review on PubMed, Embase and Google Scholar of peer-reviewed literature and governmental reports published between January 2000 and February 2024 on the nature and scale of opioid use, opioid prescribing patterns, and fatal overdoses among racial/ethnic minorities in the United States, while also examining macro, meso and individual-level risk factors. KEY FINDINGS: Results from this review illuminate a growing, but fragmented, literature lacking standardisation in racial/ethnic classification and case reporting, specifically in regards to Indigenous and Asian subpopulations. This literature broadly illustrates racial/ethnic minorities' increasing nonmedical use of opioids, heightened burdens of fatal overdoses, specifically in relation to polydrug use and synthetic opioids, with notable elevations among Black/Latino subgroups, in addition uneven opioid prescribing patterns. Moreover, the literature implicates a variety of unique risk environments corresponding to dynamics such as residential segregation, provider bias, overpolicing, acculturative stress, patient distrust, and limited access to mental health care services and drug treatment resources, including medications for opioid use disorder. IMPLICATIONS: There has been a lack of rigorous, targeted study on racial/ethnic minorities who use opioids, but evidence highlights burgeoning increases in usage, especially polydrug/synthetic opioid use, and disparities in prescriptions and fatal overdose risk-phenomena tied to multi-level forms of entrenched disenfranchisement. CONCLUSION: There is a need for further research on the complex, overlapping risk environments of racial/ethnic minorities who use opioids, including deeper inclusion of Indigenous and Asian individuals, and efforts to generate greater methodological synergies in population classification and reporting guidelines.
Asunto(s)
Analgésicos Opioides , Sobredosis de Droga , Minorías Étnicas y Raciales , Trastornos Relacionados con Opioides , Humanos , Estados Unidos/epidemiología , Analgésicos Opioides/envenenamiento , Sobredosis de Droga/etnología , Sobredosis de Droga/mortalidad , Trastornos Relacionados con Opioides/etnología , Trastornos Relacionados con Opioides/mortalidad , Factores de RiesgoRESUMEN
The objective of this study was to understand barriers to healthcare and social service utilization among older adults residing in rural areas who use drugs. A cross-sectional survey of persons who use opioids or inject drugs in rural counties with high overdose rates across ten states was conducted. For this analysis, participants were restricted to only the 375 individuals aged 50 and older. They were asked about barriers to utilizing healthcare and social services. Multivariate analyses were conducted. The most common barriers were a lack of transportation and a fear of stigma. The average number of barriers was 2.53. Those who were either uninsured or homeless endorsed 37% more barriers. For every five-year increase in age, the number of barriers reduced by 15%. Efforts to reduce these barriers may include expanding eligibility for transportation and housing services and leveraging trusted community members to broker linkages to providers to overcome stigma.
RESUMEN
This study seeks to understand the general adult population's knowledge, attitudes, and stigma towards methamphetamine use and people with a history of methamphetamine use utilizing a cross-sectional national survey. We analyzed data from a cross-sectional survey drawn from AmeriSpeak®, a probability-based ongoing panel of over 35,000 households representative of the U.S. household population. We developed a 10-item social stigma scale, and estimated a multivariable generalized linear regression model for public stigma towards methamphetamine use as our dependent variable and a series of covariates. Six adjusted independent variables were noted to be significantly associated with higher stigma towards methamphetamine use: older age, higher household income, married status, Republican party affiliation, no history of methamphetamine use, and higher racism score. Sex assigned at birth, race (with Black as reference category), education level, and history of arrest or incarceration showed no statistical significance in stigma scores. In a separate regression model limited to people with a history of methamphetamine use (n = 727), notably White respondents had lower stigma compared to Black respondents. Our large population-based survey identified several factors associated with higher stigma towards those who use methamphetamines, including higher racist attitudes which was associated with a higher stigma score and higher internalized stigma amongst Black respondents with a history of methamphetamine use. Given the scope of methamphetamine use in the U.S., addressing stigma, in particular in regard to race, may impact the nation's public health efforts to reduce methamphetamine-associated adverse outcomes.