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Vesicular glutamate transporters (VGLUTs) were long thought to be specific markers of glutamatergic excitatory transmission. The discovery, two decades ago, of the atypical VGLUT3 has thoroughly modified this oversimplified view. VGLUT3 is strategically expressed in discrete populations of glutamatergic, cholinergic, serotonergic, and even GABAergic neurons. Recent reports show the subtle, but critical, implications of VGLUT3-dependent glutamate co-transmission and its roles in the regulation of diverse brain functions and dysfunctions. Progress in the neuropharmacology of VGLUT3 could lead to decisive breakthroughs in the treatment of Parkinson's disease (PD), addiction, eating disorders, anxiety, presbycusis, or pain. This review summarizes recent findings on VGLUT3 and its vesicular underpinnings as well as on possible ways to target this atypical transporter for future therapeutic strategies.For years, a discussion has persevered on the benefits and drawbacks of antibody discovery using animal immunization versus in vitro selection from non-animal-derived recombinant repertoires using display technologies. While it has been argued that using recombinant display libraries can reduce animal consumption, we hold that the number of animals used in immunization campaigns is dwarfed by the number sacrificed during preclinical studies. Thus, improving quality control of antibodies before entering in vivo studies will have a larger impact on animal consumption. Both animal immunization and recombinant repertoires present unique advantages for discovering antibodies that are fit for purpose. Furthermore, we anticipate that machine learning will play a significant role within discovery workflows, refining current antibody discovery practices.

To describe the social network characteristics of pregnant women with opioid use disorder (OUD) and explore how changes in social relationships during pregnancy may influence substance use behaviors.

Between 2017 and 2018, we conducted an exploratory pilot study among 50 pregnant women with OUD. Participants completed a detailed social network inventory to describe the behaviors (e.g. substance-using), social support characteristics (e.g. financial, emotional, informational) and roles (e.g. family member, friend) of network members. The primary outcome was a self-reported decrease in substance use during pregnancy. Pearson correlations were used to test for associations between covariates reflecting different aspects of participants' social networks and decreased substance use during pregnancy.

Most participants (84.0 %) decreased substance use during pregnancy and stated that pregnancy motivated them to engage in treatment (94.0 %). Participants had a median of 8 (IQR 4-18) network members with differing proportions of those who did and did not use substances. Pregnancy prompted participants to significantly increase contact with (26.4 % vs. 5.0 %), have increased support from (35.7 % vs. 7.5 %), and a have a feeling of increased closeness with (26.1 % vs. 3.3 %) network members who did not use substances. However, decreased substance use during pregnancy was most strongly (negatively) associated with the proportion of network members who used substances and provided informational support (r=-0.25, p = 0.08) and a feeling of closeness (r=-0.26, p = 0.08).

Our findings indicate that pregnancy has a profound influence on women's substance use behaviors and that changes in social relationships due to pregnancy may influence substance use.

Our findings indicate that pregnancy has a profound influence on women's substance use behaviors and that changes in social relationships due to pregnancy may influence substance use.

Management of chronic pain is an essential aspect of HIV primary care. Previous literature in the general population has elucidated racial disparities in the evaluation and treatment of pain. This study examined racial/ethnic differences in patient satisfaction and barriers to pain management among a cohort of PWH receiving LTOT.

Patient-reported survey and EMR data were compared between non-white (n = 135; 81.3 %) and white (n = 31; 18.7 %) patients in a cohort of 166 PWH receiving LTOT in two clinics in Atlanta and Boston. Quantile and linear regression were used to evaluate the association between race and pain management outcomes 1) satisfaction with pain management (0-10) and 2) patient-related barriers to pain management, including patient perceptions of pain medications, fatalism, and communication about pain. Models were adjusted for sex, age, clinical site, and baseline general health.

Non-white participants were noted to receive chronic opioids for a shorter mean duration of time than white participants (6.0 versus 11.0 years, p < 0.001) and lower mean morphine equivalent daily dose (MEDD) than white participants (28.1 versus 66.9 mg, p < 0.001). In adjusted analyses, there was no significant difference in satisfaction with pain management among non-white and white participants (p = 0.101). There was no significant difference in barriers to pain management in unadjusted (p = 0.335) nor adjusted models (p = 0.397).

While non-white PWH were noted to have received lower doses of chronic opioids and for shorter duration than white PWH, satisfaction with pain management was similar. Patient-related barriers to pain management were similar among non-white and white PWH.

While non-white PWH were noted to have received lower doses of chronic opioids and for shorter duration than white PWH, satisfaction with pain management was similar. Patient-related barriers to pain management were similar among non-white and white PWH.

Women with histories of opioid misuse face drug-related stigma, which can be amplified during pregnancy. While women are often blamed for their drug use and urged to change, the social contexts that create and reinforce stigma are largely unchallenged. Drawing on a multidimensional model of stigma, we examine how stigma manifested across women's pregnancy journeys to shape access and quality of care.

We triangulate in-depth interviews with 28 women with histories of opioid misuse who were pregnant or recently gave birth and 18 healthcare providers in Ohio. Thematic analysis examined how stigma operates across contexts of care.

Providers represented physicians, nurses, social workers, counselors, and healthcare administrators. Among 28 women, average age was 30 (range 22-41) and 79 % were White. Most women used prenatal medication-assisted treatment (MAT), including Suboxone (n = 19) or methadone (n = 8), and 15 were pregnant. Evidence of stigma emerged across healthcare contexts. selleck chemicals Structural stigma encoded barriers to care in insurance practices and punitive drug treatment, while enacted stigma manifested as mistreatment and judgment from providers. Unpredictability of an infant diagnosis of neonatal abstinence syndrome (NAS), even when women were "doing everything right" by using MAT, perpetuated anticipated stigma from fear of loss of custody and internalized stigma among women who felt guilty about the diagnosis. Providers recognized the harmful effects of these stigmas and many actively addressed it.

We recommend harm reduction approaches to address the multiplicity of stigmas that women navigate in opioid misuse and pregnancy to improve healthcare experiences.

We recommend harm reduction approaches to address the multiplicity of stigmas that women navigate in opioid misuse and pregnancy to improve healthcare experiences.American Indian communities in Minnesota have been disproportionately impacted by the opioid use disorder (OUD) epidemic, which tribal communities have taken numerous steps to address. The Cascade of Care is a public health framework for measuring population-level OUD risk, treatment engagement, treatment retention, and recovery outcomes, which can help communities monitor the impact of responses to the OUD epidemic and identify where treatment- and recovery-related barriers and facilitators may exist. However, no studies have quantified the Cascade of Care stages within tribal communities and the extent to which these stages can be quantified using existing data sources is unknown. We utilized data from the Minnesota Drug and Alcohol Abuse Normative Evaluation System (DAANES) to quantify OUD Cascade of Care stages for an American Indian tribal nation in Minnesota and for the entire state. DAANES data indicated 269 individuals in the tribal community received treatment for opioid-related problems in 2018. Among them, an estimated 65-99 % initiated medications for OUD and an estimated 13-41 % were retained in treatment for at least 180 days. Existing state-level data can provide information about Cascade of Care stages for American Indian communities, particularly with regard to treatment admission, initiation of medications for OUD, and treatment retention. Additional data sources are needed to measure population-level OUD risk, recovery, and cultural and contextual factors that may impact treatment and recovery.Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by cells of the immune system, predominantly Th17 lymphocytes and γδ lymphocytes. In this paper, we review the role of IL-17A in the pathogenesis of hypertension and target organ damage. Studies in mice have shown that IL-17A increases blood pressure, probably by acting on multiple levels. Furthermore, IL-17A plasma concentrations are already elevated in patients with mild or moderate hypertension. Preclinical studies on arterial hypertension have detected IL-17A-producing cells in target organs such as the heart, vessels and kidneys. Patients with hypertensive nephrosclerosis show kidney infiltration by Th17 lymphocytes and γδ lymphocytes that express IL-17A. In addition, in experimental models of hypertension, blocking IL-17A by genetic strategies, or using neutralising antibodies, lowers blood pressure by acting on the vascular wall and tubule sodium transport and reduces damage to target organs. As a whole, the data presented in this review suggest that IL-17A participates in the regulation of blood pressure and in the genesis and maintenance of arterial hypertension, and may constitute a therapeutic target in the future.Compared to cerebral ischaemia, the frequency of spinal cord ischaemia is rare. Spinal infarcts lead to various types of neurological deficits, usually consisting of an abrupt and complete tetra- or paraplegia. Magnetic resonance imaging is the most valuable tool to show the infarct and to rule out other causes of acute spinal cord syndromes., such as myelitis or acute compressions. Nowadays, in western countries, most spinal cord infarcts are due to aortic diseases (atherosclerosis, aneurysm, dissection) or are of iatrogenic origin (mainly aortic surgery and interventional radiology), while other causes are rare. There is no specific treatment, besides prevention of complications, treatment of the underlying cause and rehabilitation.

Abducens nerve palsy (ANP) is the most common oculomotor palsy. This study aimed to evaluate the efficacy of medial rectus recession with lateral rectus plication in patients with unilateral acquired ANP and to describe the etiologies of this condition.

Thirty-one patients were included in this retrospective single-center study conducted between 2000 and 2019 at the university research hospital in Tours. The following data were collected before and after surgery diplopia, oculomotor deviations, ocular motility, and head posturing.

The mean age was 55.9±18.9 years and the mean postoperative follow-up was 11±4 months. Postoperatively, the patients had significant reduction in diplopia in primary position (P<0.001), in abduction of the affected eye (P<0.001) and in distance and near horizontal deviations (P<0.001). Abduction of the affected eye was significantly improved (P<0.001), but reduction in head posturing was insignificant (P=0.27). The etiologies were as follows trauma (8 patients, 26%), neoplasm (6 patients, 16%), stroke-related (5 patients, 16%), compressive (5 patients, 16%), undetermined (5 patients, 16%) and inflammatory (2 patients, 6%).