Optogenetic activation of visual thalamus generates artificial visual percepts.

The lateral geniculate nucleus (LGN), a retinotopic relay center where visual inputs from the retina are processed and relayed to the visual cortex, has been proposed as a potential target for artificial vision. At present, it is unknown whether optogenetic LGN stimulation is sufficient to elicit behaviorally relevant percepts, and the properties of LGN neural responses relevant for artificial vision have not been thoroughly characterized. Here, we demonstrate that tree shrews pretrained on a visual detection task can detect optogenetic LGN activation using an AAV2-CamKIIα-ChR2 construct and readily generalize from visual to optogenetic detection. Simultaneous recordings of LGN spiking activity and primary visual cortex (V1) local field potentials (LFPs) during optogenetic LGN stimulation show that LGN neurons reliably follow optogenetic stimulation at frequencies up to 60 Hz and uncovered a striking phase locking between the V1 LFP and the evoked spiking activity in LGN. These phase relationships were maintained over a broad range of LGN stimulation frequencies, up to 80 Hz, with spike field coherence values favoring higher frequencies, indicating the ability to relay temporally precise information to V1 using light activation of the LGN. Finally, V1 LFP responses showed sensitivity values to LGN optogenetic activation that were similar to the animal's behavioral performance. Taken together, our findings confirm the LGN as a potential target for visual prosthetics in a highly visual mammal closely related to primates.

Structural competency, Latin American social medicine, and collective health: Exploring shared lessons through the work of Jaime Breilh.

ABSTRACTStructural competency is a recent framework for understanding and addressing the structural drivers of disease. Latin American Social Medicine and Collective Health is a decades-long movement similarly concerned with the study and transformation of social structures to achieve health equity. In this paper, we put insights from Latin American Social Medicine and Collective Health into conversation with the developing structural competency framework. We focus specifically on insights from Jaime Breilh's new article summarising his theoretical work on medical ethics and rights in this special issue and his new book, Critical Epidemiology and the People's Health. This paper is comprised of three parts. Part 1 provides an introduction to the structural competency framework. Part 2 provides an overview of the Latin American Social Medicine and Collective Health movement, along with a summary of the social determination of health paradigm. Part 3 places insights from these works into conversation with structural competency and considers ways in which Latin American Social Medicine and Collective Health might inform the further development of structural competency, and potentially vice versa. The paper closes by calling for greater attention to Latin American Social Medicine and Collective Health among those committed to health equity within the anglophone world.

Thinking with and Against the Social Determinants of Health: The Latin American Social Medicine (Collective Health) Critique from Jaime Breilh.

The concept of the social determinants of health has become increasingly accepted and mainstream in anglophone public health over the past three decades. Moreover, it has been widely adopted into diverse geographic, sociocultural, and linguistic contexts. By recognizing the role of social conditions in influencing health inequalities, the concept challenges narrow behavioral and reductive biological understandings of health. Despite this, scholars and activists have critiqued the concept of the social determinants of health for being incomplete and even misrepresenting the true nature of health inequities. Arguably, these critiques have been most thoroughly developed among those working in the Latin American social medicine and collective health traditions who formulated the "social determination of health" paradigm and the concept of interculturality decades prior to the advent of the social determinants of health. We draw on Jaime Breilh's main works, with a focus on the recently published book, Critical Epidemiology and the People's Health, to (1) provide a broad overview of the social determination of health paradigm and its approach to interculturality and (2) clarify how these ideas and the broader collective health movement challenge assumptions within the social determinants of health concept.

Opioid Prescribing and Opioid Risk Mitigation Strategies in the Veterans Health Administration.

INTRODUCTION: The Veterans Health Administration (VHA) has taken a multifaceted approach to addressing opioid safety and promoting system-wide opioid stewardship. AIM: To provide a comprehensive evaluation of current opioid prescribing practices and implementation of risk mitigation strategies in VHA. SETTING: VHA is the largest integrated health care system in the United States. PROGRAM DESCRIPTION: VHA prescribing data in conjunction with implementation of opioid risk mitigation strategies are routinely tracked and reviewed by VHA's Pharmacy Benefits Management Services (including Academic Detailing Service) and the Pain Management Program Office. Additional data are derived from the Partnered Evidence-Based Policy Resource Center (PEPReC) and from a 2019 survey of interdisciplinary pain management teams at VHA facilities. Prescribing data are reported quarterly until first quarter fiscal year 2020 (Q1FY2020), ending December 31, 2019. PROGRAM EVALUATION: VHA opioid dispensing peaked in 2012 with 679,376 Veterans receiving an opioid prescription, and when including tramadol, in 2013 with 869,956 Veterans. Since 2012, the number of Veterans dispensed an opioid decreased 56% and co-prescribed opioid/benzodiazepine decreased 83%. Veterans with high-dose opioids (≥ 100 mg morphine equivalent daily dose) decreased 77%. In Q1FY2020, among Veterans on long-term opioid therapy (LTOT), 91.1% had written informed consent, 90.8% had a urine drug screen, and 89.0% had a prescription drug monitoring program query. Naloxone was issued to 217,469 Veterans and resulted in > 1,000 documented overdose reversals. In 2019, interdisciplinary pain management teams were fully designated at 68%, partially designated at 28%, and not available at 4% of 140 VA parent facilities. Fifty percent of Veterans on opioids at very high risk for overdose/suicide received interdisciplinary team reviews. IMPLICATIONS: VHA clinicians have greatly reduced their volume of opioid prescribing for pain management and expanded implementation of opioid risk mitigation strategies. IMPACTS: VHA's integrated health care system provides a model for opioid stewardship and interdisciplinary pain care.

Trends in naloxone prescriptions prescribed after implementation of a National Academic Detailing Service in the Veterans Health Administration: A preliminary analysis.

OBJECTIVES: To evaluate the effects of the U.S. Veterans Health Administration (VA) National Academic Detailing Service alongside the Opioid Overdose Education and Naloxone Distribution (OEND) program on naloxone prescriptions prescribed from October 2014 to September 2016. METHODS: A retrospective, repeated measures cohort study was conducted to evaluate the effectiveness of a real-world application of academic detailing (AD) alongside OEND on providers' outpatient naloxone prescribing from October 2014 to September 2016. Outcome was the number of naloxone prescriptions prescribed per month per provider. During the study period, VA providers were aware of OEND, but may not have been exposed to academic detailing. Therefore, providers were categorized as exposed when the first OEND-specific academic detailing session was provided during the study period. Generalized estimating equations were used to estimate the association between exposure to academic detailing and monthly naloxone prescriptions prescribed while taking into account the correlation within each provider. Incident rate ratios with 95% CIs were reported. RESULTS: Seven hundred fifty (22.6%) of 3313 providers received at least 1 OEND-specific academic detailing visit. At 1 year, the average number of naloxone prescriptions per month was 3-times greater in AD-exposed providers compared with AD-unexposed providers (95% CI 2.0-5.3); and at 2 years, the average number of naloxone prescriptions was 7-times greater (95% CI 3.0-17.9). Moreover, the average difference in naloxone prescribing from baseline to 2 years was 7.1% greater in AD-exposed providers compared with AD-unexposed providers (95% CI 2.0%-12.5%). CONCLUSIONS: This preliminary analysis provides the first evidence that academic detailing influenced naloxone prescribing rates in a large, integrated health care system at 1 and 2 years. In addition, AD-exposed providers had a higher average difference in naloxone prescribing rate compared with AD-unexposed providers after 2 years of follow-up.

Development and applications of the Veterans Health Administration's Stratification Tool for Opioid Risk Mitigation (STORM) to improve opioid safety and prevent overdose and suicide.

Concerns about opioid-related adverse events, including overdose, prompted the Veterans Health Administration (VHA) to launch an Opioid Safety Initiative and Overdose Education and Naloxone Distribution program. To mitigate risks associated with opioid prescribing, a holistic approach that takes into consideration both risk factors (e.g., dose, substance use disorders) and risk mitigation interventions (e.g., urine drug screening, psychosocial treatment) is needed. This article describes the Stratification Tool for Opioid Risk Mitigation (STORM), a tool developed in VHA that reflects this holistic approach and facilitates patient identification and monitoring. STORM prioritizes patients for review and intervention according to their modeled risk for overdose/suicide-related events and displays risk factors and risk mitigation interventions obtained from VHA electronic medical record (EMR)-data extracts. Patients' estimated risk is based on a predictive risk model developed using fiscal year 2010 (FY2010: 10/1/2009-9/30/2010) EMR-data extracts and mortality data among 1,135,601 VHA patients prescribed opioid analgesics to predict risk for an overdose/suicide-related event in FY2011 (2.1% experienced an event). Cross-validation was used to validate the model, with receiver operating characteristic curves for the training and test data sets performing well (>.80 area under the curve). The predictive risk model distinguished patients based on risk for overdose/suicide-related adverse events, allowing for identification of high-risk patients and enrichment of target populations of patients with greater safety concerns for proactive monitoring and application of risk mitigation interventions. Results suggest that clinical informatics can leverage EMR-extracted data to identify patients at-risk for overdose/suicide-related events and provide clinicians with actionable information to mitigate risk. (PsycINFO Database Record

Disruption of polycystin-L causes hippocampal and thalamocortical hyperexcitability.

Epilepsy or seizure disorder is among the least understood chronic medical conditions affecting over 65 million people worldwide. Here, we show that disruption of the polycystic kidney disease 2-like 1 (Pkd2l1 or Pkdl), encoding polycystin-L (PCL), a non-selective cation channel, increases neuronal excitability and the susceptibility to pentylenetetrazol-induced seizure in mice. PCL interacts with ß2-adrenergic receptor (ß2AR) and co-localizes with ß2AR on the primary cilia of neurons in the brain. Pkdl deficiency leads to the loss of ß2AR on neuronal cilia, which is accompanied with a remarkable reduction in cAMP levels in the central nervous system (CNS). The reduction of cAMP levels is associated with a reduction in the activation of cAMP response element-binding protein, but not the activation of Ca(2+)/calmodulin-dependent protein kinase II, Akt or mitogen-activated protein kinases. Our data, thus, indicate for the first time that a ciliary protein complex is required for the control of neuronal excitability in the CNS.

Considerations for using fluorescence polarization in the screening of G protein-coupled receptors.

Fluorescence polarization must be classified as a unique detection method relative to other intensity-based methods because both bound and unbound tracer is measured. Other fluorescence techniques require either physical removal of unbound tracer or a means for distinguishing only bound tracer. The presence of unbound tracer in the detection volume has profound consequences on how assay performance is gauged. The intent here is to provide tools for accurate assay performance assessment and to discuss some of the practical considerations necessary for understanding the advantages and limitations of the technology. An emphasis is placed on applications using G protein-coupled receptors.