RESUMO
Over the last decade, the global population of refugees and other migrants in need of international protection (MNP) has more than doubled. Despite their rapid growth, panel data collection among MNP remains rare, leaving scholars with few data sources to draw on to understand dynamic changes in their social, economic, legal, or health circumstances. With that paucity in mind, we developed and piloted the Encuesta de Refugiados: Experiencias Sociales y Salud (ERESS), a weekly panel survey conducted with MNP living in Costa Rica. To our knowledge, this panel constitutes one of the first weekly surveys with MNP anywhere in the world. Here, we describe the overall study design, sample recruitment and retention, and key descriptive findings. We show that retaining demographically and socioeconomically diverse MNP in intensive panel surveys is possible and that doing so reveals valuable insights into dynamic changes in their incorporation, family dynamics, and health and wellbeing. By offering a summary of our field experiences and central methodological findings, we highlight the potential benefits and challenges of collecting intensive panel data with MNP, as scholars increasingly seek to understand their pre- and post-migration trajectories and relationships between the two.
Assuntos
Refugiados , Migrantes , Humanos , Costa Rica/epidemiologia , Dinâmica PopulacionalRESUMO
OBJECTIVE: The aim of this study is to demonstrate 3-dimensional (3D) acoustic wave sparsely activated localization microscopy (AWSALM) of microvascular flow in vivo using phase change contrast agents (PCCAs). MATERIALS AND METHODS: Three-dimensional AWSALM using acoustically activable PCCAs was evaluated on a crossed tube microflow phantom, the kidney of New Zealand White rabbits, and the brain of C57BL/6J mice through intact skull. A mixture of C 3 F 8 and C 4 F 10 low-boiling-point fluorocarbon gas was used to generate PCCAs with an appropriate activation pressure. A multiplexed 8-MHz matrix array connected to a 256-channel ultrasound research platform was used for transmitting activation and imaging ultrasound pulses and recording echoes. The in vitro and in vivo echo data were subsequently beamformed and processed using a set of customized algorithms for generating 3D super-resolution ultrasound images through localizing and tracking activated contrast agents. RESULTS: With 3D AWSALM, the acoustic activation of PCCAs can be controlled both spatially and temporally, enabling contrast on demand and capable of revealing 3D microvascular connectivity. The spatial resolution of the 3D AWSALM images measured using Fourier shell correlation is 64 µm, presenting a 9-time improvement compared with the point spread function and 1.5 times compared with half the wavelength. Compared with the microbubble-based approach, more signals were localized in the microvasculature at similar concentrations while retaining sparsity and longer tracks in larger vessels. Transcranial imaging was demonstrated as a proof of principle of PCCA activation in the mouse brain with 3D AWSALM. CONCLUSIONS: Three-dimensional AWSALM generates volumetric ultrasound super-resolution microvascular images in vivo with spatiotemporal selectivity and enhanced microvascular penetration.
Assuntos
Meios de Contraste , Microscopia , Camundongos , Animais , Coelhos , Camundongos Endogâmicos C57BL , Som , Acústica , Ultrassonografia/métodos , MicrobolhasRESUMO
RATIONALE: Restoration of blood flow after out-of-hospital cardiac arrest (OHCA) is associated with inflammation that causes cellular injury. The extent of this reperfusion injury (RI) is associated with the duration of ischemia and adequacy of resuscitation. Remote ischemic conditioning (RIC) consists of repeated application of non-lethal ischemia then reperfusion to a limb distal to the heart by inflating a blood pressure (BP) cuff. Trials in animal models in cardiac arrest and in humans with acute infarction show RIC reduces RI. OBJECTIVE: We sought to demonstrate the feasibility and safety of RIC in patients resuscitated from OHCA and transported to hospital. METHODS: This study was conducted under exception from informed consent (EFIC) for emergency research. Eligible subjects were randomized with masked allocation to control (standard care) versus intervention (standard care and RIC). Included were adults with non-traumatic OHCA. The primary outcome was attrition, the proportion of patients enrolled and not on allocated therapy for the study duration. Key secondary outcomes were survival to discharge, neurologic status at discharge, hospital-free survival, and adverse events. Results were summarized descriptively as recommended for pilot studies. RESULTS: N = 30 patients were enrolled (n = 14 control, n = 16 intervention). Mean age of enrolled patients was 52.5 ± 16.2 years. Eight (27%) were female gender and 7 (23%) had a shockable first recorded rhythm. 100% of enrolled patients completed their allocated study intervention (i.e., 0% attrition). The RIC group had 7 (44%) survival to discharge and median Rankin score of 6 (IQR 1, 6) at discharge as compared to the standard care group which had 6 (43%) survival to discharge and median Rankin score of 6 (IQR 1.5, 6) at discharge. A single patient (6%) in the intervention group had transient occlusion of their upper extremity intravenous line, which immediately resolved on repositioning of the blood pressure cuff. CONCLUSION: Application of RIC to patients resuscitated from CA and transported to an ED is feasible and safe. An adequately powered trial is required to assess whether RIC is effective at decreasing morbidity and mortality after CA.
Assuntos
Isquemia , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Resultado do Tratamento , Estudos de Viabilidade , Ressuscitação , Parada Cardíaca Extra-Hospitalar/terapiaRESUMO
BACKGROUND: Disparities in birth outcomes continue to exist in the United States, particularly for low-income, publicly insured women. Doula support has been shown to be a cost-effective intervention in predominantly middle-to-upper income White populations, and across all publicly insured women at the state level. This analysis extends previous studies by providing an estimate of benefits that incorporates variations in averted outcomes by race and ethnicity in the context of one region in Texas. The objectives of this study were to determine (1) whether the financial value of benefits provided by doula support exceeds the costs of delivering it; (2) whether the cost-benefit ratio differs by race and ethnicity; and (3) how different doula reimbursement levels affect the cost-benefit results with respect to pregnant people covered by Medicaid in central Texas. METHODS: We conducted a forward-looking cost-benefit analysis using secondary data carried out over a short-term time horizon taking a public payer perspective. We focused on a narrow set of health outcomes (preterm delivery and cesarean delivery) that was relatively straightforward to monetize. The current, usual care state was used as the comparison condition. RESULTS: Providing pregnant people covered by Texas Medicaid with access to doulas during their pregnancies was cost-beneficial (benefit-to-cost ratio: 1.15) in the base model, and 65.7% of the time in probabilistic sensitivity analyses covering a feasible range of parameters. The intervention is most cost-beneficial for Black women. Reimbursing doulas at $869 per client or more yielded costs that were greater than benefits, holding other parameters constant. CONCLUSIONS: Expanding Medicaid pregnancy-related coverage to include doula services would be cost-beneficial and improve health equity in Texas.
Assuntos
Doulas , Medicaid , Gravidez , Recém-Nascido , Estados Unidos , Feminino , Humanos , Análise Custo-Benefício , Texas , CesáreaRESUMO
INTRODUCTION: A qualitative picture of the health care experiences prior to pregnancy can inform patient-centered strategies to optimize preconception health. This study describes health care utilization and experiences and how health care costs were covered in the year prior to pregnancy in a population of primarily Hispanic women with low income. METHODS: Pregnant participants were recruited from 5 Federally Qualified Health Center clinics. Semistructured interviews included questions about health care in the year prior to pregnancy. Transcripts were analyzed using a thematic approach that integrated deductive and inductive analysis. RESULTS: Most participants self-identified as Hispanic. Just under half were US citizens. All but one were Medicaid or Children's Health Insurance Program Perinatal coverage insurance during pregnancy and relied on a variety of strategies to cover prepregnancy health care costs. Almost all received health care during the year prior to pregnancy. Fewer than half reported an annual preventive visit. Health care needs that led to care-seeking included a prior pregnancy, chronic depression, contraception, workplace injury, a persistent rash, screening and treatment for sexually transmitted infection, breast pain, stomach pain (leading to gallbladder removal), and kidney infection. The ways in which study participants covered the costs of health care ranged in terms of sources and complexity. Although some participants described stable health care coverage, most reported changes throughout the year as they pieced together various health care coverage programs and out-of-pocket payments. When participants did seek health care prior to their current pregnancy, most described the experience in positive terms and focused on health care provider communication quality. Respect of patient autonomy was highly valued. DISCUSSION: Women with pregnancy-related health care coverage accessed care for a wide range of health care needs prior to pregnancy. Health care providers may consider strategies to respectfully introduce preconception care into any visit by an individual who could become pregnant.
Assuntos
Hispânico ou Latino , Seguro Saúde , Feminino , Humanos , Gravidez , Acessibilidade aos Serviços de Saúde , Cobertura do Seguro , Medicaid , Cuidado Pré-Concepcional , Estados UnidosRESUMO
BACKGROUND: Morbidity and mortality rates related to methamphetamine are on the rise. Simultaneously, social-distancing guidelines were issued in March 2020 to decrease transmission of COVID-19. The aim of this study was to explore concerns regarding methamphetamine use during the COVID-19 pandemic and subsequent harm reduction strategies with patients who use methamphetamine to inform emergency department (ED)-based harm reduction approaches. METHODS: A mixed-methods study of adults residing in Washington with high-risk methamphetamine use and a recent ED visit from April-September 2020 was performed. Participants completed a survey and a semi-structured interview on perceptions and experiences of COVID-19. Descriptive statistics were used for survey responses. Interview transcripts were analyzed and guided by modified grounded theory using an iterative approach to refine the guide and codebook. Interviews were independently coded by 2 investigators and discussed until consensus. RESULTS: Twenty-five participants completed the survey; 20 participants were interviewed (45% recently used heroin, 40% unstably housed). Thirty-five percent was worried about COVID-19 infection. Three themes emerged from the interviews: (1) increase in meth use, (2) interplay of meth obtention and COVID-19, and (3) interactions with healthcare and social services. CONCLUSIONS: People who use methamphetamine noted an increase in use along with the social distancing guidelines put in place for COVID-19 and employed a variety of harm reduction profiles when obtaining methamphetamine. Also, the pandemic brought difficulties in accessing care and amplified mistrust in healthcare instructions and public health messages. Based on these qualitative interviews, further work should consider aligning methamphetamine and COVID-19 harm reduction messages and working with trusted community resources to improve harm reduction strategies for methamphetamine use and COVID-19. IRB: Informed Consent by the University of Washington Human Subjects Division (approval number, STUDY00009277).
RESUMO
Focused ultrasound and microbubbles can non-invasively and locally deliver therapeutics and imaging agents across the blood-brain barrier. Uniform treatment and minimal adverse bioeffects are critical to achieve reliable doses and enable safe routine use of this technique. Towards these aims, we have previously designed a rapid short-pulse ultrasound sequence and used it to deliver a 3 kDa model agent to mouse brains. We observed a homogeneous distribution in delivery and blood-brain barrier closing within 10 min. However, many therapeutics and imaging agents are larger than 3 kDa, such as antibody fragments and antisense oligonucleotides. Here, we evaluate the feasibility of using rapid short-pulses to deliver higher-molecular-weight model agents. 3, 10 and 70 kDa dextrans were successfully delivered to mouse brains, with decreasing doses and more heterogeneous distributions with increasing agent size. Minimal extravasation of endogenous albumin (66.5 kDa) was observed, while immunoglobulin (~ 150 kDa) and PEGylated liposomes (97.9 nm) were not detected. This study indicates that rapid short-pulses are versatile and, at an acoustic pressure of 0.35 MPa, can deliver therapeutics and imaging agents of sizes up to a hydrodynamic diameter between 8 nm (70 kDa dextran) and 11 nm (immunoglobulin). Increasing the acoustic pressure can extend the use of rapid short-pulses to deliver agents beyond this threshold, with little compromise on safety. This study demonstrates the potential for deliveries of higher-molecular-weight therapeutics and imaging agents using rapid short-pulses.
Assuntos
Sistemas de Liberação de Medicamentos , Microbolhas , Camundongos , Animais , Sistemas de Liberação de Medicamentos/métodos , Camundongos Endogâmicos C57BL , Encéfalo/diagnóstico por imagem , Barreira HematoencefálicaRESUMO
INTRODUCTION: Methamphetamine use is on the rise with increasing emergency department (ED) visits, behavioral health crises, and deaths associated with use and overdose. Emergency clinicians describe methamphetamine use as a significant problem with high resource utilization and violence against staff, but little is known about the patient's perspective. In this study our objective was to identify the motivations for initiation and continued methamphetamine use among people who use methamphetamine and their experiences in the ED to guide future ED-based approaches. METHODS: This was a qualitative study of adults residing in the state of Washington in 2020, who used methamphetamine in the prior 30 days, met criteria for moderate- to high-risk use, reported recently receiving care in the ED, and had phone access. Twenty individuals were recruited to complete a brief survey and semi-structured interview, which was recorded and transcribed prior to being coded. Modified grounded theory guided the analysis, and the interview guide and codebook were iteratively refined. Three investigators coded the interviews until consensus was reached. Data was collected until thematic saturation. RESULTS: Participants described a shifting line that separates the positive attributes from the negative consequences of using methamphetamine. Many initially used methamphetamine to enhance social interactions, combat boredom, and escape difficult circumstances by numbing the senses. However, continued use regularly led to isolation, ED visits for the medical and psychological sequelae of methamphetamine use, and engagement in increasingly risky behaviors. Because of their overwhelmingly frustrating experiences in the past, interviewees anticipated difficult interactions with healthcare clinicians, leading to combativeness in the ED, avoidance of the ED at all costs, and downstream medical complications. Participants desired a non-judgmental conversation and linkage to outpatient social resources and addiction treatment. CONCLUSION: Methamphetamine use can lead patients to seek care in the ED, where they often feel stigmatized and are provided little assistance. Emergency clinicians should acknowledge addiction as a chronic condition, address acute medical and psychiatric symptoms adequately, and provide positive connections to addiction and medical resources. Future work should incorporate the perspectives of people who use methamphetamine into ED-based programs and interventions.
Assuntos
Metanfetamina , Adulto , Humanos , Metanfetamina/efeitos adversos , Motivação , Serviço Hospitalar de Emergência , Pesquisa Qualitativa , ViolênciaRESUMO
Successful manual synthesis of the TD2.2 peptide acting as a blood-brain barrier shuttle was achieved. TD2.2 was successfully synthesised by sequential condensation of four protected peptide fragments on solid-phase settings, after several unsuccessful attempts using the stepwise approach. These fragments were chosen to minimise the number of demanding amino acids (in terms of coupling, Fmoc removal) in each fragment that are expected to hamper the overall synthetic process. Thus, the hydrophobic amino acids as well as Arg(Pbf) were strategically spread over multiple fragments rather than having them congested in one fragment. This study shows how a peptide that shows big challenges in the synthesis using the common stepwise elongation methodology can be synthesised with an acceptable purity. It also emphasises that choosing the right fragment with certain amino acid constituents is key for a successful synthesis. It is worth highlighting that lower amounts of reagents were required to synthesise the final peptide with an identical purity to that obtained by the automatic synthesiser.
Assuntos
Barreira Hematoencefálica , Peptídeos , Peptídeos/química , Fragmentos de Peptídeos/química , Aminoácidos/química , Técnicas de Síntese em Fase SólidaRESUMO
Delivering quality primary health care requires reliable energy access. In rural health facilities, electricity is often unreliable or absent. Low energy access has a gendered impact, affecting the ability of mothers to experience safe childbirth, for which basic lighting and sterilization are essential. Moreover, low energy access acts as a barrier to attract and retain female medical staff, who constitute women-predominated nursing and midwifery cadres that are critical for providing care to women. Using quantitative facility-level data, we explore the intersection of energy, health care, and gender in Haiti, Senegal, and the Democratic Republic of the Congo.
Assuntos
Atenção à Saúde , Instalações de Saúde , Feminino , Humanos , Haiti , Senegal , República Democrática do CongoRESUMO
Transcranial focused ultrasound (FUS) has the unique ability to target regions of the brain with high spatial precision, in a minimally invasive manner. Neuromodulation studies have shown that FUS can excite or inhibit neuronal activity, demonstrating its tremendous potential to improve the outcome of neurological diseases. Recent evidence has also shed light on the emerging promise that FUS has, with and without the use of intravenously injected microbubbles, in modulating the blood-brain barrier and the immune cells of the brain. As the resident immune cells of the central nervous system, microglia are at the forefront of the brain's maintenance and immune defense. Notably, microglia are highly dynamic and continuously survey the brain parenchyma by extending and retracting their processes. This surveillance activity aids microglia in performing key physiological functions required for brain activity and plasticity. In response to stressors, microglia rapidly alter their cellular and molecular profile to help facilitate a return to homeostasis. While the underlying mechanisms by which both FUS and FUS + microbubbles modify microglial structure and function remain largely unknown, several studies in adult mice have reported changes in the expression of the microglia/macrophage marker ionized calcium binding adaptor molecule 1, and in their phagocytosis, notably of protein aggregates, such as amyloid beta. In this review, we discuss the demonstrated and putative biological effects of FUS and FUS + microbubbles in modulating microglial activities, with an emphasis on the key cellular and molecular changes observed in vitro and in vivo across models of brain health and disease. Understanding how this innovative technology can modulate microglia paves the way for future therapeutic strategies aimed to promote beneficial physiological microglial roles, and prevent or treat maladaptive responses.
RESUMO
Background Cardiogenic shock (CS) is critical end-organ hypoperfusion due to reduced cardiac output. Early therapy, such as vasoactive agents or the initiation of mechanical circulatory support (MCS), requires early diagnosis and is associated with better outcomes. A novel ultrasound platform (GE Healthcare, Milwaukee, WI) has semi-automated imaging software (SAIS), which could simplify the point-of-care ultrasound (POCUS) diagnosis of CS. We assessed the feasibility of using POCUS with SAIS in patients in shock, determined the ability of SAIS to identify the subset of patients with CS, and described the process and outcome of care of patients with vs. without CS after presenting to Emergency Department (ED) with hypotension. Methods This prospective case-control study was conducted at an urban ED. Physicians with prior POCUS education received one hour of training with the study device. The qualitative ejection fraction was determined by visual assessment. SAIS measurements of hemodynamics were made with the study device and included left ventricle outflow tract velocity time integral (LVOT VTI), inferior vena cava collapsibility or distensibility indices, and pulmonary B-line assessment. ED patients with a systolic blood pressure ≤ 90 mmHg or need for a vasopressor initiation in the ED were enrolled. The diagnosis of CS was determined by a medical record review. All data were summarized descriptively. Results Twenty-nine cases underwent POCUS, and 87 controls did not. Baseline characteristics, process, and outcome of care were similar between groups. Seventy-nine percent (79%) of cases had a complete POCUS with SAIS. Of these, 55% had reduced LVOT VTI, 38% had IVC collapsibility <50%, and 48% of cases had a B-line pattern consistent with pulmonary edema. The mean LVOT VTI for cases with CS was 9.4± 5.4 cm; the mean LVOT VTI for cases without CS was 15.2 ± 6.0 cm. Among patients who did not undergo POCUS, 31 (36%) had a formal echocardiogram, and eight (9%) had a final diagnosis of cardiogenic shock during hospitalization. Conclusion Physicians with one hour of platform-specific training were able to implement POCUS with SAIS among patients who present with shock. POCUS with SAIS may aid in the early recognition of CS.
RESUMO
Glioblastoma (GBM) is an aggressive malignant primary brain tumor with limited therapeutic options. We show that the angiotensin II (AngII) type 2 receptor (AT2R) is a therapeutic target for GBM and that AngII, endogenously produced in GBM cells, promotes proliferation through AT2R. We repurposed EMA401, an AT2R antagonist originally developed as a peripherally restricted analgesic, for GBM and showed that it inhibits the proliferation of AT2R-expressing GBM spheroids and blocks their invasiveness and angiogenic capacity. The crystal structure of AT2R bound to EMA401 was determined and revealed the receptor to be in an active-like conformation with helix-VIII blocking G-protein or ß-arrestin recruitment. The architecture and interactions of EMA401 in AT2R differ drastically from complexes of AT2R with other relevant compounds. To enhance central nervous system (CNS) penetration of EMA401, we exploited the crystal structure to design an angiopep-2-tethered EMA401 derivative, A3E. A3E exhibited enhanced CNS penetration, leading to reduced tumor volume, inhibition of proliferation, and increased levels of apoptosis in an orthotopic xenograft model of GBM.
Assuntos
Bloqueadores do Receptor Tipo 2 de Angiotensina II , Compostos Benzidrílicos , Neoplasias Encefálicas , Reposicionamento de Medicamentos , Glioblastoma , Isoquinolinas , Receptor Tipo 2 de Angiotensina , Analgésicos/farmacologia , Angiotensina II/química , Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 2 de Angiotensina II/uso terapêutico , Apoptose , Compostos Benzidrílicos/química , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Humanos , Isoquinolinas/química , Isoquinolinas/farmacologia , Isoquinolinas/uso terapêutico , Conformação Proteica em alfa-Hélice , Receptor Tipo 2 de Angiotensina/química , Receptor Tipo 2 de Angiotensina/metabolismo , Carga Tumoral/efeitos dos fármacosRESUMO
INTRODUCTION: Opioid use disorder (OUD) and related comorbid conditions are highly prevalent among patients presenting to emergency department (ED) settings. Research has developed few comprehensive disease management strategies for at-risk patients presenting to the ED that both decrease illicit opioid use and improve initiation and retention in medication treatment for OUD (MOUD). METHODS: The research team conducted a pilot pragmatic clinical trial that randomized 40 patients presenting to a single ED to a collaborative care intervention (n = 20) versus usual care control (n = 20) conditions. Interviewers blinded to patient intervention and control group status followed-up with participants at 1, 3, and 6 months after presentation to the ED. The 3-month Emergency Department Longitudinal Integrated Care (ED-LINC) collaborative care intervention for patients at risk for OUD included: 1) a Brief Negotiated Interview at bedside, 2) overdose education and facilitation of MOUD, 3) longitudinal proactive care management, 4) utilization of the statewide health information exchange platform for 24/7 tracking of recurrent ED utilization, and 5) weekly caseload supervision that incorporated measurement-based care treatment assessment with stepped-up care for patients with recalcitrant symptoms. RESULTS: Overall, the ED-LINC intervention was feasibly delivered and acceptable to patients. The pilot study achieved >80% follow-up rates at 1, 3, and 6 months. In adjusted longitudinal mixed model regression analyses, no statistically significant differences existed in days of opioid use over the past 30 days for ED-LINC intervention patients when compared to patients receiving usual care (incidence-rate ratio (IRR) 1.50, 95% CI 0.54-4.16). The unadjusted mean number of days of illicit opioid use decreased at the 1-month and 3-month follow-up time points for both groups. ED-LINC intervention patients had increased rates of MOUD initiation compared to control patients (50% versus 30%); intervention versus control comparisons did not achieve statistical significance, although power to detect significant differences in the pilot was limited. CONCLUSIONS: The ED-LINC intervention for patients with OUD can be feasibly implemented and warrants testing in larger scale, adequately powered randomized pragmatic clinical trial investigations. CLINICALTRIALS: gov NCT03699085.
Assuntos
Prestação Integrada de Cuidados de Saúde , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Serviço Hospitalar de Emergência , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Projetos PilotoRESUMO
Liposomes are clinically used drug carriers designed to improve the delivery of drugs to specific tissues while minimising systemic distribution. However, liposomes are unable to cross the blood-brain barrier (BBB) and enter the brain, mostly due to their large size (ca. 100 nm). A noninvasive and localised method of delivering liposomes across the BBB is to intravenously inject microbubbles and apply long pulses of ultrasound (pulse length: >1 ms) to a targeted brain region. Recently, we have shown that applying rapid short pulses (RaSP) (pulse length: 5 µs) can deliver drugs with an improved efficacy and safety profile. However, this was tested with a relatively smaller 3-kDa molecule (dextran). In this study, we examine whether RaSP can deliver liposomes to the murine brain in vivo. Fluorescent DiD-PEGylated liposomes were synthesized and injected intravenously alongside microbubbles. The left hippocampus of mice was then sonicated with either a RaSP sequence (5 µs at 1.25 kHz in groups of 10 ms at 0.5 Hz) or a long pulse sequence (10 ms at 0.5 Hz), with each pulse having a 1-MHz centre frequency (0.35 and 0.53 MPa). The delivery and distribution of the fluorescently-labelled liposomes were assessed by fluorescence imaging of the brain sections. The safety profile of the sonicated brains was assessed by histological staining. RaSP was shown to locally deliver liposomes across the BBB at 0.53 MPa with a more diffused and safer profile compared to the long pulse ultrasound sequence. Cellular uptake of liposomes was observed in neurons and microglia, while no uptake within astrocytes was observed in both RaSP and long pulse-treated brains. This study shows that RaSP allows a targeted and safe delivery of liposomal drugs into the murine brain with potential to deliver drugs into neuronal and glial targets.
Assuntos
Lipossomos , Microbolhas , Animais , Barreira Hematoencefálica , Encéfalo/diagnóstico por imagem , Sistemas de Liberação de Medicamentos/métodos , CamundongosRESUMO
One of the key hallmarks of Alzheimer's disease is the aggregation of the amyloid-ß peptide to form fibrils. Consequently, there has been great interest in studying molecules that can disrupt amyloid-ß aggregation. While a handful of molecules have been shown to inhibit amyloid-ß aggregation in vitro, there remains a lack of in vivo data reported due to their inability to cross the blood-brain barrier. Here, we investigate a series of new metal complexes for their ability to inhibit amyloid-ß aggregation in vitro. We demonstrate that octahedral cobalt complexes with polyaromatic ligands have high inhibitory activity thanks to their dual binding mode involving π-π stacking and metal coordination to amyloid-ß (confirmed via a range of spectroscopic and biophysical techniques). In addition to their high activity, these complexes are not cytotoxic to human neuroblastoma cells. Finally, we report for the first time that these metal complexes can be safely delivered across the blood-brain barrier to specific locations in the brains of mice using focused ultrasound.
RESUMO
STUDY OBJECTIVE: Opioid use disorder (OUD) is on the rise nationwide with increasing emergency department (ED) visits and deaths secondary to overdose. Although previous research has shown that patients who are started on buprenorphine in the ED have increased engagement in addiction treatment, access to on-demand medications for OUD is still limited, in part because of the need for linkages to outpatient care. The objective of this study is to describe emergency and outpatient providers' perception of local barriers to transitions of care for ED-initiated buprenorphine patients. METHODS: Purposive sampling was used to recruit key stakeholders, identified as physicians, addiction specialists, and hospital administrators, from 10 EDs and 11 outpatient clinics in King County, Washington. Twenty-one interviews were recorded and transcribed and then coded using an integrated deductive and inductive content analysis approach by 2 team members to verify accuracy of the analysis. Interview guides and coding were informed by the Consolidated Framework for Implementation Research (CFIR), which provides a structure of domains and constructs associated with effective implementation of evidence-based practice. RESULTS: From the 21 interviews with emergency and outpatient providers, this study identified 4 barriers to transitions of care for ED-initiated buprenorphine patients: scope of practice, prescribing capacity, referral incoordination, and loss to follow-up. CONCLUSION: Next steps for implementation of this intervention in a community setting include establishing a standard of care for treatment and referral for ED patients with OUD, increasing buprenorphine prescribing capacity, creating a central repository for streamlined referrals and follow-up, and supporting low-barrier scheduling and navigation services.
RESUMO
Female labor force participation is important for women, children, and societies, but also may have unintended impacts including an increased risk of intimate partner violence (IPV). IPV is a global health, human rights, and development problem with far-reaching economic and societal consequences. Mexico has a very high prevalence of IPV: 43.9% of Mexican women have reported experiencing IPV at the hands of their current partner. The literature on women's economic participation reveals mixed evidence on whether women's employment is associated with higher levels of IPV or whether it is protective against IPV. As the effect of women's work operates differently across contexts, we aim to estimate the effect of women's employment on their risk of experiencing IPV in rural and urban Mexico. Utilizing the nationally representative 2016 Mexican National Survey on the Dynamics of Household Relationships (ENDIREH), we employ propensity score matching (PSM) to address the potential selection bias between women who are employed and/or receiving a cash transfer with women who are not. We additionally implement inverse probability weighted regression adjustment (IPWRA) to explore this relationship and compare the results with the PSM findings. Three different measures of women's economic participation are analyzed: whether they had engaged in any productive work outside of the home in the past year, whether they received conditional cash transfers through Mexico's Prospera program, and whether they received Prospera and worked. Given the high levels of IPV in Mexico and the greater levels of economic participation borne of an increased number of women in the workforce, our results have important potential implications for targeting support to survivors of violence who receive cash transfers and undertake employment in both urban and rural areas.
Assuntos
Violência por Parceiro Íntimo , Criança , Estudos Transversais , Emprego , Feminino , Humanos , México/epidemiologia , Prevalência , Fatores de RiscoRESUMO
Passive acoustic mapping (PAM) is an algorithm that reconstructs the location of acoustic sources using an array of receivers. This technique can monitor therapeutic ultrasound procedures to confirm the spatial distribution and amount of microbubble activity induced. Current PAM algorithms have an excellent lateral resolution but have a poor axial resolution, making it difficult to distinguish acoustic sources within the ultrasound beams. With recent studies demonstrating that short-length and low-pressure pulses-acoustic wavelets-have the therapeutic function, we hypothesized that the axial resolution could be improved with a quasi-pulse-echo approach and that the resolution improvement would depend on the wavelet's pulse length. This article describes an algorithm that resolves acoustic sources axially using time of flight and laterally using delay-and-sum beamforming, which we named axial temporal position PAM (ATP-PAM). The algorithm accommodates a rapid short pulse (RaSP) sequence that can safely deliver drugs across the blood-brain barrier. We developed our algorithm with simulations (k-wave) and in vitro experiments for one-, two-, and five-cycle pulses, comparing our resolution against that of two current PAM algorithms. We then tested ATP-PAM in vivo and evaluated whether the reconstructed acoustic sources mapped to drug delivery within the brain. In simulations and in vitro, ATP-PAM had an improved resolution for all pulse lengths tested. In vivo, experiments in mice indicated that ATP-PAM could be used to target and monitor drug delivery into the brain. With acoustic wavelets and time of flight, ATP-PAM can locate acoustic sources with a vastly improved spatial resolution.