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1.
Int J Equity Health ; 23(1): 102, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778347

RESUMEN

BACKGROUND: While insurance is integral for accessing healthcare in the US, coverage alone may not ensure access, especially for those publicly insured. Access barriers for Medicaid-insured patients are rooted in social drivers of health, insurance complexities in the setting of managed care plans, and federal- and state-level policies. Elucidating barriers at the health system level may reveal opportunities for sustainable solutions. METHODS: To understand barriers to ambulatory care access for patients with Medi-Cal (California's Medicaid program) and identify improvement opportunities, we performed a qualitative study using semi-structured interviews of a referred sample of clinicians and administrative staff members experienced with clinical patient encounters and/or completion of referral processes for patients with Medi-Cal (n = 19) at a large academic medical center. The interview guide covered the four process steps to accessing care within the health system: (1) scheduling, (2) referral and authorization, (3) contracting, and (4) the clinical encounter. We transcribed and inductively coded the interviews, then organized themes across the four steps to identify perceptions of barriers to access and improvement opportunities for ambulatory care for patients with Medi-Cal. RESULTS: Clinicians and administrative staff members at a large academic medical center revealed barriers to ambulatory care access for Medi-Cal insured patients, including lack of awareness of system-level policy, complexities surrounding insurance contracting, limited resources for social support, and poor dissemination of information to patients. Particularly, interviews revealed how managed Medi-Cal impacts academic health systems through additional time and effort by frontline staff to facilitate patient access compared to fee-for-service Medi-Cal. Interviewees reported that this resulted in patient care delays, suboptimal care coordination, and care fragmentation. CONCLUSIONS: Our findings highlight gaps in system-level policy, inconsistencies in pursuing insurance authorizations, limited resources for scheduling and social work support, and poor dissemination of information to and between providers and patients, which limit access to care at an academic medical center for Medi-Cal insured patients. Many interviewees additionally shared the moral injury that they experienced as they witnessed patient care delays in the absence of system-level structures to address these barriers. Reform at the state, insurance organization, and institutional levels is necessary to form solutions within Medi-Cal innovation efforts.


Asunto(s)
Accesibilidad a los Servicios de Salud , Medicaid , Investigación Cualitativa , Humanos , Estados Unidos , California , Masculino , Femenino , Entrevistas como Asunto , Atención Ambulatoria
2.
BMC Health Serv Res ; 24(1): 1139, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334375

RESUMEN

BACKGROUND: Ambulatory access to academic medical centers (AMCs) for patients insured with Medi-Cal (i.e., Medicaid in California) is understudied, particularly among the 85% of beneficiaries enrolled in managed care plans. As more AMCs develop partnerships with these plans, data on patient experiences of access to care and quality are needed to guide patient-centered improvements in care delivery. METHODS: The authors conducted semi-structured, qualitative interviews with Medi-Cal-insured patients with initial visits at a large, urban AMC during 2022. Participant recruitment was informed by a database of ambulatory Medi-Cal encounters. The interview guide covered Medi-Cal enrollment, scheduling, and visit experience. Interviews were transcribed and inductively coded, then organized into themes across four domains: access, affordability, patient-provider interactions, and continuity. RESULTS: Twenty participant interviews were completed (55% female, 85% English speaking, 80% self-identified minority or "other" race, and 30% Hispanic or Latino) with primary and/or specialty care visits. Within the access domain, participants reported delays with Medi-Cal enrollment and access to specialist care or testing, though appointment scheduling was reported to be easy. Affordability concerns included out-of-pocket medical and parking costs, and missed income when patients or families skipped work to facilitate care coordination. Participants considered clear, bilateral communication with providers fundamental to positive patient-provider interactions. Some participants perceived discrimination by providers based on their insurance status. Participants valued continuity, but experienced frustration arising from frequent and unexpected health plan changes that disrupted care with their established AMC providers. CONCLUSIONS: The missions of AMCs typically focus on clinical care, education, research, and equity. However, reports from Medi-Cal insured patients receiving care at AMCs highlight their stress and confusion related to inconsistent provider access, uncompensated costs, variability in perceptions of quality, and fragmented care. Recommendations based upon patient-reported concerns suggest opportunities for AMC health system-level improvements that are compatible with AMC missions.


Asunto(s)
Centros Médicos Académicos , Atención Ambulatoria , Accesibilidad a los Servicios de Salud , Entrevistas como Asunto , Medicaid , Investigación Cualitativa , Humanos , Masculino , Femenino , Estados Unidos , Persona de Mediana Edad , Adulto , California
3.
Ann Vasc Surg ; 74: 158-164, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33548403

RESUMEN

BACKGROUND: There has been a dramatic rise in opioid-related deaths over the past decade. Most of the reduction strategies have focused on outpatient use; however, recent studies have demonstrated an association between inpatient opioid use and consumption following discharge across a variety of surgical procedures. The objective of this study is to evaluate the association of inpatient use of opioids as well as the consumption of opioids after discharge following endovascular aortic aneurysm repair (EVAR). METHODS: A prospectively maintained database was reviewed for cases between 2015 and 2018. Patients were included in the study if they underwent an elective EVAR, had an intensive care unit stay less than 1 day and total length of stay less than 3 days. Patients were contacted to participate in a survey of opioid use if they received a prescription at discharge. The primary outcome was percent of prescribed opioids consumed following discharge. Multivariate analyses were performed to determine predictors of receiving an opioid prescription. RESULTS: One hundred seventy-one patients were included in the analysis; 95% patients were white and 85% male. 59% of patients responded to the survey. Seventy-one (42%) received an opioid prescription at discharge. Patients that received a discharge prescription tended to be younger (71 vs. 75 years, P = 0.005) and more likely to have received opioids while in the hospital (79% vs. 45%, P < 0.001). Additionally, patients who received opioids at discharge received a significantly greater amount of milligram oral morphine equivalents (OME) while in the hospital (27.76 ± 38.91 vs. 10.05 ±29.43, P < 0.001). Multivariate analysis demonstrated age, estimated blood loss (EBL), and OME per day to be significant inpatient predictors of requiring an outpatient opioid prescription. Open femoral access (27%) was not a predictor of opioid prescription at discharge. A total of 1185 pills were prescribed (29.6 ± 2.06 per patient), but only 208 pills consumed (5.2 ± 1.27 per patient). Around 82% of total pills prescribed were not consumed. CONCLUSIONS: This study evaluates inpatient opioid use and postdischarge consumption following EVAR. These data identify key factors associated with receiving an opioid prescription at discharge and demonstrate that patients consume far fewer opioids than prescribed. These findings provide insight as to which patients may not require an outpatient prescription following EVAR, leading to potential practice-changing opioid reduction strategies.


Asunto(s)
Analgésicos Opioides/uso terapéutico , Aneurisma de la Aorta/cirugía , Utilización de Medicamentos/estadística & datos numéricos , Procedimientos Endovasculares , Dolor Postoperatorio/tratamiento farmacológico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Cuidados Posteriores , Anciano , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Masculino , Prescripciones/estadística & datos numéricos , Estudios Retrospectivos , Encuestas y Cuestionarios
4.
Ann Vasc Surg ; 72: 284-289, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33160058

RESUMEN

BACKGROUND: Opioid overprescription for acute postoperative pain is an inadvertent contributor to the opioid epidemic via pill diversion and misuse. In response, the surgical community advocates for evidence-based postoperative opioid prescribing guidelines. The objective of this study is to evaluate patient-reported opioid consumption after lower extremity bypass surgery. METHODS: We conducted a retrospective review of a prospectively maintained database of infrainguinal bypass operations from 2016 to 2019. For patients receiving an opioid prescription at discharge, a telephone survey was administered questioning the percentage of pills used. Exclusion criteria included chronic opioid use and reoperations or amputations within 30 days. The primary outcome was the difference in opioids prescribed versus opioids consumed. RESULTS: Forty-nine patients met inclusion criteria. Forty-one (84%) were prescribed opioids at discharge, and 27 (65.9%) completed the survey. The average age was 65.8 ± 7.7 years; 29.6% were women. Oxycodone immediate-release was most commonly prescribed (78%). On average, patients received 318 ± 156 morphine milligram equivalent. A total of 940 opioid pills were prescribed (36.0 ± 11.3 per patient), but only 37% were consumed. This difference resulted in 568 unused pills. CONCLUSIONS: This is the first study to specifically evaluate opioid use in a strictly lower extremity bypass population. Over 60% of pills were unused, which poses significant societal risk for misuse. Our findings contribute to knowledge of operation-specific opioid use, which may shape practice recommendations and reduce opioid overprescription after vascular surgery.


Asunto(s)
Analgésicos Opioides/uso terapéutico , Extremidad Inferior/irrigación sanguínea , Dolor Postoperatorio/tratamiento farmacológico , Alta del Paciente , Enfermedad Arterial Periférica/cirugía , Pautas de la Práctica en Medicina , Procedimientos Quirúrgicos Vasculares/efectos adversos , Anciano , Anciano de 80 o más Años , Analgésicos Opioides/efectos adversos , Bases de Datos Factuales , Prescripciones de Medicamentos , Utilización de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
5.
BMJ Open ; 14(2): e079825, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38365289

RESUMEN

OBJECTIVES: To examine changes in the 30-day surgical mortality rate after common surgical procedures during the COVID-19 pandemic and investigate whether its impact varies by urgency of surgery or patient race, ethnicity and socioeconomic status. DESIGN: We used a quasi-experimental event study design to examine the effect of the COVID-19 pandemic on surgical mortality rate, using patients who received the same procedure in the prepandemic years (2016-2019) as the control, adjusting for patient characteristics and hospital fixed effects (effectively comparing patients treated at the same hospital). We conducted stratified analyses by procedure urgency, patient race, ethnicity and socioeconomic status (dual-Medicaid status and median household income). SETTING: Acute care hospitals in the USA. PARTICIPANTS: Medicare fee-for-service beneficiaries aged 65-99 years who underwent one of 14 common surgical procedures from 1 January 2016 to 31 December 2020. MAIN OUTCOME MEASURES: 30-day postoperative mortality rate. RESULTS: Our sample included 3 620 689 patients. Surgical mortality was higher during the pandemic, with peak mortality observed in April 2020 (adjusted risk difference (aRD) +0.95 percentage points (pp); 95% CI +0.76 to +1.26 pp; p<0.001) and mortality remained elevated through 2020. The effect of the pandemic on mortality was larger for non-elective (vs elective) procedures (April 2020: aRD +0.44 pp (+0.16 to +0.72 pp); p=0.002 for elective; aRD +1.65 pp (+1.00, +2.30 pp); p<0.001 for non-elective). We found no evidence that the pandemic mortality varied by patients' race and ethnicity (p for interaction=0.29), or socioeconomic status (p for interaction=0.49). CONCLUSIONS: 30-day surgical mortality during the COVID-19 pandemic peaked in April 2020 and remained elevated until the end of the year. The influence of the pandemic on surgical mortality did not vary by patient race and ethnicity or socioeconomic status, indicating that once patients were able to access care and undergo surgery, surgical mortality was similar across groups.


Asunto(s)
COVID-19 , Etnicidad , Humanos , Anciano , Estados Unidos/epidemiología , Medicare , Pandemias , Clase Social
6.
Surgery ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39304449

RESUMEN

BACKGROUND: Patients with non-English language preference encounter language barriers across phases of surgical care. Patients with a non-English language preference represent 35% of California households and are disproportionately insured by Medicaid. To determine whether language predicts surgical outcomes, we investigated the association of patient non-English language preference with postoperative emergency department visits and readmissions among California Medicaid enrollees. METHODS: Our retrospective analysis of adult Medicaid enrollees undergoing 1 of 10 common inpatient operations using California hospital administrative data (2016-2019) modeled the association between non-English language preference and 30-day postoperative emergency department visits and readmissions using mixed effects logistic regression with hospital random intercept, adjusting for patient, operation, hospital, and community characteristics. Secondary analyses stratified by operation urgency and by insurance type in an all-payor cohort. RESULTS: Of 115,527 Medicaid enrollees, 17.2% had non-English language preference (n = 19,881), 66% were female (n = 73,653), and 40% were Hispanic/Latino (n = 45,541). Patients with non-English language preference experienced fewer postoperative emergency department visits (non-English language preference: 13.5%, English preference: 17.9%, P < .001) and readmissions (non-English language preference: 7.5%, English preference: 8.5%, P < .001), which persisted in adjusted models (adjusted odds ratio emergency department, 0.80, 95% confidence interval, 0.77-0.85; readmissions: adjusted odds ratio, 0.86, 95% confidence interval, 0.80-0.92). Non-English language preference was associated with fewer emergency department visits after elective (adjusted odds ratio, 0.80; 95% confidence interval, 0.73-0.88) and urgent/emergent surgery (adjusted odds ratio, 0.80; 95% confidence interval, 0.75-0.85) but not readmissions after elective surgery (adjusted odds ratio, 0.89; 95% confidence interval, 0.78-1.01). This pattern was only observed for Medicaid and not other insurance types. CONCLUSION: Patients with non-English language preference who receive Medicaid have fewer postoperative emergency department visits and readmissions, even after urgent surgery. Our findings suggest that patterns of health care seeking after surgery vary by patient language, and investigating explanatory mechanisms is needed.

7.
BMJ ; 380: e073290, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36858422

RESUMEN

OBJECTIVE: To assess inequities in mortality by race and sex for eight common surgical procedures (elective and non-elective) across specialties in the United States. DESIGN: Retrospective cohort study. SETTING: US, 2016-18. PARTICIPANTS: 1 868 036 Black and White Medicare beneficiaries aged 65-99 years undergoing one of eight common surgeries: repair of abdominal aortic aneurysm, appendectomy, cholecystectomy, colectomy, coronary artery bypass surgery, hip replacement, knee replacement, and lung resection. MAIN OUTCOME MEASURE: The main outcome measure was 30 day mortality, defined as death during hospital admission or within 30 days of the surgical procedure. RESULTS: Postoperative mortality overall was higher in Black men (1698 deaths, adjusted mortality rate 3.05%, 95% confidence interval 2.85% to 3.24%) compared with White men (21 833 deaths, 2.69%, 2.65% to 2.73%), White women (21 847 deaths, 2.38%, 2.35% to 2.41%), and Black women (1631 deaths, 2.18%, 2.04% to 2.31%), after adjusting for potential confounders. A similar pattern was found for elective surgeries, with Black men showing a higher adjusted mortality (393 deaths, 1.30%, 1.14% to 1.46%) compared with White men (5650 deaths, 0.85%, 0.83% to 0.88%), White women (4615 deaths, 0.82%, 0.80% to 0.84%), and Black women (359 deaths, 0.79%, 0.70% to 0.88%). This 0.45 percentage point difference implies that mortality after elective procedures was 50% higher in Black men compared with White men. For non-elective surgeries, however, mortality did not differ between Black men and White men (1305 deaths, 6.69%, 6.26% to 7.11%; and 16 183 deaths, 7.03%, 6.92% to 7.14%, respectively), although mortality was lower for White women and Black women (17 232 deaths, 6.12%, 6.02% to 6.21%; and 1272 deaths, 5.29%, 4.93% to 5.64%, respectively). These differences in mortality appeared within seven days after surgery and persisted for up to 60 days after surgery. CONCLUSIONS: Postoperative mortality overall was higher among Black men compared with White men, White women, and Black women. These findings highlight the need to understand better the unique challenges Black men who require surgery face.


Asunto(s)
Aneurisma de la Aorta Abdominal , Medicare , Anciano , Masculino , Estados Unidos , Humanos , Femenino , Estudios Retrospectivos , Apendicectomía , Resultado del Tratamiento
8.
J Am Coll Surg ; 237(2): 352-361, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37154441

RESUMEN

In response to concerns about healthcare access and long wait times within the Veterans Health Administration (VA), Congress passed the Choice Act of 2014 and the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act of 2018 to create a program for patients to receive care in non-VA sites of care, paid by VA. Questions remain about the quality of surgical care between these sites in specific and between VA and non-VA care in general. This review synthesizes recent evidence comparing surgical care between VA and non-VA delivered care across the domains of quality and safety, access, patient experience, and comparative cost/efficiency (2015 to 2021). Eighteen studies met the inclusion criteria. Of 13 studies reporting quality and safety outcomes, 11 reported that quality and safety of VA surgical care were as good as or better than non-VA sites of care. Six studies of access did not have a preponderance of evidence favoring care in either setting. One study of patient experience reported VA care as about equal to non-VA care. All 4 studies of cost/efficiency outcomes favored non-VA care. Based on limited data, these findings suggest that expanding eligibility for veterans to get care in the community may not provide benefits in terms of increasing access to surgical procedures, will not result in better quality, and may result in worse quality of care, but may reduce inpatient length of stay and perhaps cost less.


Asunto(s)
Accesibilidad a los Servicios de Salud , Hospitales de Veteranos , Humanos , Estados Unidos , United States Department of Veterans Affairs
9.
Syst Rev ; 12(1): 197, 2023 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-37838696

RESUMEN

BACKGROUND: Antiplatelet agents are central in the management of vascular disease. The use of dual antiplatelet therapy (DAPT) for the management of thromboembolic complications must be weighed against bleeding risk in the perioperative setting. This balance is critical in patients undergoing cardiac or non-cardiac surgery. The management of patients on DAPT for any indication (including stents) is not clear and there is limited evidence to guide decision-making. This review summarizes current evidence since 2015 regarding the occurrence of major adverse events associated with continuing, suspending, or varying DAPT in the perioperative period. METHODS: A research librarian searched PubMed and Cochrane from November 30, 2015 to May 17, 2022, for relevant terms regarding adult patients on DAPT for any reason undergoing surgery, with a perioperative variation in DAPT strategy. Outcomes of interest included the occurrence of major adverse cardiac events, major adverse limb events, all-cause death, major bleeding, and reoperation. We considered withdrawal or discontinuation of DAPT as stopping either aspirin or a P2Y12 inhibitor or both agents; continuation of DAPT indicates that both drugs were given in the specified timeframe. RESULTS: Eighteen observational studies met the inclusion criteria. No RCTs were identified, and no studies were judged to be at low risk of bias. Twelve studies reported on CABG. Withholding DAPT therapy for more than 2 days was associated with less blood loss and a slight trend favoring less transfusion and surgical re-exploration. Among five observational CABG studies, there were no statistically significant differences in patient death across DAPT management strategies. Few studies reported cardiac outcomes. The remaining studies, which were about procedures other than exclusively CABG, demonstrated mixed findings with respect to DAPT strategy, bleeding, and ischemic outcomes. CONCLUSION: The evidence base on the benefits and risks of different perioperative DAPT strategies for patients with stents is extremely limited. The strongest signal, which was still judged as low certainty evidence, is that suspension of DAPT for greater than 2 days prior to CABG surgery is associated with less bleeding, transfusions, and re-explorations. Different DAPT strategies' association with other outcomes of interest, such as MACE, remains uncertain. SYSTEMATIC REVIEW REGISTRATION: A preregistered protocol for this review can be found on the PROSPERO International Prospective Register of systematic reviews ( http://www.crd.york.ac.uk/PROSPERO/ ; registration number: CRD42022371032).


Asunto(s)
Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Adulto , Humanos , Aspirina/uso terapéutico , Hemorragia/inducido químicamente , Inhibidores de Agregación Plaquetaria/uso terapéutico , Stents , Revisiones Sistemáticas como Asunto
10.
Cell Rep ; 40(13): 111440, 2022 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-36170833

RESUMEN

Low dopamine D2 receptor (D2R) availability in the striatum can predispose for cocaine abuse; though how low striatal D2Rs facilitate cocaine reward is unclear. Overexpression of D2Rs in striatal neurons or activation of D2Rs by acute cocaine suppresses striatal Penk mRNA. Conversely, low D2Rs in D2-striatal neurons increases striatal Penk mRNA and enkephalin peptide tone, an endogenous mu-opioid agonist. In brain slices, met-enkephalin and inhibition of enkephalin catabolism suppresses intra-striatal GABA transmission. Pairing cocaine with intra-accumbens met-enkephalin during place conditioning facilitates acquisition of preference, while mu-opioid receptor antagonist blocks preference in wild-type mice. We propose that heightened striatal enkephalin potentiates cocaine reward by suppressing intra-striatal GABA to enhance striatal output. Surprisingly, a mu-opioid receptor antagonist does not block cocaine preference in mice with low striatal D2Rs, implicating other opioid receptors. The bidirectional regulation of enkephalin by D2R activity and cocaine offers insights into mechanisms underlying the vulnerability for cocaine abuse.


Asunto(s)
Trastornos Relacionados con Cocaína , Cocaína , Analgésicos Opioides/farmacología , Animales , Cocaína/farmacología , Trastornos Relacionados con Cocaína/metabolismo , Cuerpo Estriado/metabolismo , Encefalina Metionina/metabolismo , Encefalina Metionina/farmacología , Encefalinas/metabolismo , Encefalinas/farmacología , Ratones , Antagonistas de Narcóticos/metabolismo , Antagonistas de Narcóticos/farmacología , ARN Mensajero/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Recompensa , Ácido gamma-Aminobutírico/metabolismo
11.
Alcohol ; 67: 23-36, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29310048

RESUMEN

Alcohol operant self-administration paradigms are critical tools for studying the neural circuits implicated in both alcohol-seeking and consummatory behaviors and for understanding the neural basis underlying alcohol-use disorders. In this study, we investigate the predictive value of two operant models of oral alcohol self-administration in mice, one in which alcohol is delivered into a cup following nose-poke responses with no accurate measurement of consumed alcohol solution, and another paradigm that provides access to alcohol via a sipper tube following lever presses and where lick rate and consumed alcohol volume can be measured. The goal was to identify a paradigm where operant behaviors such as lever presses and nose pokes, as well as other tracked behavior such as licks and head entries, can be used to reliably predict blood alcohol concentration (BAC). All mice were first exposed to alcohol in the home cage using the "drinking in the dark" (DID) procedure for 3 weeks and then were trained in alcohol self-administration using either of the operant paradigms for several weeks. Even without sucrose fading or food pre-training, mice acquired alcohol self-administration with both paradigms. However, neither lever press nor nose-poke rates were good predictors of alcohol intake or BAC. Only the lick rate and consumed alcohol were consistently and significantly correlated with BAC. Using this paradigm that accurately measures alcohol intake, unsupervised cluster analysis revealed three groups of mice: high-drinking (43%), low-drinking (37%), and non-drinking mice (20%). High-drinking mice showed faster acquisition of operant responding and achieved higher BACs than low-drinking mice. Lick rate and volume consumed varied with the alcohol concentration made available only for high- and low-drinking mice, but not for non-drinking mice. In addition, high- and low-drinking mice showed similar patterns during extinction and significant cue-induced reinstatement of seeking. Only high-drinking mice showed insensitivity to quinine adulteration, indicating a willingness to drink alcohol despite pairing with aversive stimuli. Thus, this study shows that relying on active presses is not an accurate determination of drinking behavior in mice. Only paradigms that allow for accurate measurements of consumed alcohol and/or lick rate are valid models of operant alcohol self-administration, where compulsive-like drinking could be accurately determined based on changes in alcohol intake when paired with bitter-tasting stimuli.


Asunto(s)
Consumo de Bebidas Alcohólicas/psicología , Conducta Adictiva/psicología , Condicionamiento Operante/efectos de los fármacos , Etanol/administración & dosificación , Extinción Psicológica/efectos de los fármacos , Animales , Conducta Adictiva/diagnóstico , Condicionamiento Operante/fisiología , Relación Dosis-Respuesta a Droga , Extinción Psicológica/fisiología , Femenino , Predicción , Masculino , Ratones , Ratones Endogámicos C57BL , Autoadministración
12.
Physiol Rep ; 1(5): e00096, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24303168

RESUMEN

Fetal-neonatal iron deficiency induces adult learning impairments concomitant with changes in expression of key genes underlying hippocampal learning and memory in spite of neonatal iron replenishment. Notably, expression of brain-derived neurotrophic factor (BDNF), a gene critical for neuronal maturation and synaptic plasticity, is lowered both acutely and in adulthood following early-life iron deficiency. Although the mechanism behind its long-term downregulation remains unclear, epigenetic modification in BDNF, as seen in other models of early-life adversity, may play a role. Given that early iron deficiency occurs during critical periods in both hippocampal and gonadal development, we hypothesized that the iron-sufficient offspring (F2 IS) of formerly iron-deficient (F1 FID) rats would show a similar suppression of the BDNF gene as their parents. We compared hippocampal mRNA levels of BDNF and functionally related genes among F1 IS, F1 ID, and F2 IS male rats at postnatal day (P) 15 and P65 using RT-qPCR. As expected, the F1 ID group showed a downregulation of BDNF and associated genes acutely at P15 and chronically at P65. However, the F2 IS group showed an upregulation of these genes at P15, returning to control levels at P65. These results demonstrate that adverse effects of early iron deficiency on hippocampal gene expression observed in the F1 are not present in the F2 generation, suggesting differential effects of nutritionally induced epigenetic programing during the critical periods of hippocampal and gonadal development.

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