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Hassalstrongylus dollfusi (Díaz-Ungría, 1963) Durette-Desset, 1971 was described in a wild house mouse, Mus musculus, from Venezuela and, since then, has never been reported again in the type host or in any other host. In this work, specimens assignable to H. dollfusi were found at 10 localities in Northeast Argentina, in five species of sigmodontine rodents. The nematodes were attributed to H. dollfusi based on diagnostic characters such as: synlophe with 22–31 subequal ridges; in males, hypertrophy of right ray 4 of the male bursa, thickening of the dorsal ray and bases of rays 8, distal tip of the spicules bent and spoon shaped; and, in females, presence of subventral postvulvar alae supported by hypertrophied struts. The new host recorded are: Oligoryzomys fornesi, O. flavescens, O. nigripes, Holochilus chacarius and Akodon azarae. The parasite showed a strong preference for host species of Oligoryzomys, which appear to act as primary hosts. The parasite could be present, parasitizing different species of Oligoryzomys, in a geographic area from the type locality in Venezuela southward to north Corrientes in Argentina. It has not been reported from populations of Oligoryzomys spp. of the Argentinean and Brazilian Atlantic Forest, nor south of 28° S, which may be explained by constraints in the environmental conditions required by the free-living stages of the parasite. This study provides the first identification and redescription of H. dollfusi in southern South America, from autochthonous hosts, six decades after its description.

A lot of attention has been given to multihop wireless networks lately, but further research—in particular, through experimentation—is needed. This attention has motivated an increase in the number of 802.11-based deployments, both indoor and outdoor. These testbeds, which require a significant amount of resources during both deployment and maintenance, are used to run measurements in order to analyze and understand the limitation and differences between analytical or simulation-based figures and the results from real-life experimentation. This paper makes two major contributions: (i) first, we describe a novel wireless multihop testbed, which we name FloorNet, that is deployed and operated under the false floor of a lab in our Computer Science building. This false floor provides a strong physical protection that prevents disconnections or misplacements, as well as radio shielding (to some extent) thanks to the false floor panels—this later feature is assessed through experimentation; (ii) second, by running exhaustive and controlled experiments we are able to analyze the performance limits of commercial off-the-shelf hardware, as well as to derive practical design criteria for the deployment and configuration of mesh networks. These results both provide valuable insights of wireless multihop performance and prove that FloorNet constitutes a valuable asset to research on wireless mesh networks.

Latino/a/x sexual minority men (SMM) and transgender women remain disproportionately impacted by HIV, with higher HIV incidence and lower uptake of pre-exposure prophylaxis (PrEP) than their non-Hispanic White peers. Disparities in PrEP uptake among Latino/a/x populations have been found to be due to structural, social, and personal barriers. Social marketing interventions have been shown to effectively address barriers and increase PrEP uptake in other populations, and thus offer potential as a tool to increase PrEP uptake for Latino/a/x populations. The PrEPárate campaign was developed through community based participatory research and ran from April to September 2022 in Cook County, Illinois. We conducted a mixed methods evaluation through surveys (N = 515) and semi-structured interviews with survey participants and community partners (N = 14). We examined cross-sectional associations of campaign exposure with PrEP awareness and uptake in adjusted multivariable regression models. We used rapid qualitative methods to analyze interviews and assess implementation outcomes following the RE-AIM framework. The campaign reached over 118,000 people on social media, with additional reach over public transit and local events. PrEPárate exposure was associated with increased PrEP awareness (aOR = 5.23; 95% CI [2.58, 10.63]) and PrEP uptake (aOR = 1.69; 95% CI [1.09, 2.62]). Survey respondents expressed that the campaign name, visuals, ambassadors, and distribution were effective in engaging the target audience. Community partners felt the campaign was implemented with fidelity to the original vision and identified future directions for PrEPárate. Social marketing campaigns, anchored in community engagement, may be an effective strategy to increase PrEP awareness and uptake among underserved Latino/a/x populations., Competing Interests: Declarations. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Young men who have sex with men and young transgender women (YMSM-YTW) use online spaces to meet sexual partners with increasing regularity, and research shows that experiences of racism online mimics the real world., Objective: We analyzed differences by race and ethnicity in web-based and mobile apps used to meet sexual partners as reported by Chicago-based YMSM-YTW in 2016-2017., Methods: A racially and ethnically diverse sample of 643 YMSM-YTW aged 16-29 years were asked to name websites or mobile apps used to seek a sexual partner in the prior 6 months, as well as provide information about sexual partnerships from the same period. We used logistic regression to assess the adjusted association of race and ethnicity with (1) use of any website or mobile apps to find a sexual partner, (2) use of a "social network" to find a sexual partner compared to websites or mobile apps predominantly used for dating or hookups, (3) use of specific websites or mobile apps, and (4) reporting successfully meeting a sexual partner online among website or mobile app users., Results: While most YMSM-YTW (454/643, 70.6%) used websites or mobile apps to find sexual partners, we found that Black non-Hispanic YMSM-YTW were significantly less likely to report doing so (comparing White non-Hispanic to Black non-Hispanic: adjusted odds ratio [aOR] 1.74, 95% CI 1.10-2.76). Black non-Hispanic YMSM-YTW were more likely to have used a social network site to find a sexual partner (comparing White non-Hispanic to Black non-Hispanic: aOR 0.20, 95% CI 0.11-0.37), though this was only reported by one-third (149/454, 32.8%) of all app-using participants. Individual apps used varied by race and ethnicity, with Grindr, Tinder, and Scruff being more common among White non-Hispanic YMSM-YTW (93/123, 75.6%; 72/123, 58.5%; and 30/123, 24.4%, respectively) than among Black non-Hispanic YMSM-YTW (65/178, 36.5%; 25/178, 14%; and 4/178, 2.2%, respectively) and Jack'd and Facebook being more common among Black non-Hispanic YMSM-YTW (105/178, 59% and 64/178, 36%, respectively) than among White non-Hispanic YMSM-YTW (6/123, 4.9% and 8/123, 6.5%, respectively). Finally, we found that while half (230/454, 50.7%) of YMSM-YTW app users reported successfully meeting a new sexual partner on an app, Black non-Hispanic YMSM-YTW app users were less likely to have done so than White non-Hispanic app users (comparing White non-Hispanic to Black non-Hispanic: aOR 2.46, 95% CI 1.50-4.05)., Conclusions: We found that Black non-Hispanic YMSM-YTW engaged with websites or mobile apps and found sexual partners systematically differently than White non-Hispanic YMSM-YTW. Our findings give a deeper understanding of how racial and ethnic sexual mixing patterns arise and have implications for the spread of sexually transmitted infections among Chicago's YMSM-YTW., (© Kathryn Risher, Patrick Janulis, Elizabeth McConnell, Darnell Motley, Pedro Alonso Serrano, Joel D Jackson, Alonzo Brown, Meghan Williams, Daniel Mendez, Gregory Phillips II, Joshua Melville, Michelle Birkett. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org).)

In this work, iron hexacyanoferrate (FeHCF-Prussian blue) particles have been grown onto a reduced graphene oxide substrate through a pulsed electrodeposition process. Thus, the prepared FeHCF electrode exhibits a specific volumetric capacitance of 88 F cm -3 (specific areal capacitance of 26.6 mF cm -2 ) and high cycling stability with a capacitance retention of 93.7% over 10,000 galvanostatic charge-discharge cycles in a 1 M KCl electrolyte. Furthermore, two identical FeHCF electrodes were paired up in order to construct a symmetrical supercapacitor, which delivers a wide potential window of 2 V in a 1 M KCl electrolyte and demonstrates a large energy density of 27.5 mWh cm -3 at a high power density of 330 W cm -3 .

Background: Latino, Latina, and Latinx (Latino/a/x) individuals remain disproportionately impacted by HIV, particularly sexual minority men and transgender women. Pre-exposure prophylaxis (PrEP) is an effective means of biomedical HIV prevention, but awareness and uptake remain low among marginalized Latino/a/x populations. Social marketing campaigns have demonstrated promise in promoting PrEP in other populations but are poorly studied in Latino/a/x sexual minority men and transgender women., Objective: This study aims to (1) adapt and pilot a PrEP social marketing campaign tailored to Latino/a/x populations with a focus on sexual minority men and transgender women through community-based participatory research (CBPR) and (2) evaluate the reach and ad performance of the adapted PrEP social marketing campaign., Methods: We used the ADAPT-ITT (assessment, decision, adaptation, production, topical experts-integration, training, and testing) framework for adapting evidence-based interventions for new settings or populations. This paper presents how each phase of the ADAPT-ITT framework was applied via CBPR to create the PrEPárate ("Be PrEPared") campaign. Key community engagement strategies included shared ownership with community partners, focus groups to guide content, crowdsourcing to name the campaign, design by local Latino/a/x artists, and featuring local influencers as the faces of PrEPárate. We evaluated campaign reach and advertisement performance using social media platform metrics (paid and organic reach, impressions, unique clicks, and click-through rates [CTR]) and website use statistics from Google Analytics., Results: The PrEPárate campaign ran in Cook County, Illinois, from April to September 2022. The campaign reached over 118,750 people on social media (55,750 on Facebook and Instagram [Meta Platforms Inc] and 63,000 on TikTok [ByteDance Ltd]). The Meta ads performed over the industry benchmark with ads featuring local transgender women (2% CTR) and cisgender sexual minority men (1.4% CTR). Of the different Grindr (Grindr Inc) ad formats piloted, the interstitial Grindr ads were the highest performing (1183/55,479, 2.13% CTR). YouTube (Google) ads were low performing at 0.11% (153/138,337) CTR and were stopped prematurely, given limits on sexual education-related content. In the first year, there were 5006 visitors to the website., Conclusions: Adaptation of an existing evidence-based intervention served as an effective method for developing a PrEP social marketing campaign for Latino/a/x audiences. CBPR and strong community partnerships were essential to tailor materials and provide avenues to systematically address barriers to PrEP access. Social marketing is a promising strategy to promote PrEP among underserved Latino/a/x populations., (©Harita S Shah, Pedro Alonso Serrano, Gregory Phillips II. Originally published in JMIR Formative Research (https://formative.jmir.org), 17.07.2024.)

The spread of the monkeypox virus (mpox) in 2022 primarily within the sexual networks of men who have sex with men (MSM) triggered a potentially stigmatizing public health response in the USA. Despite mpox being primarily spread through skin-to-skin contact, most messaging has promoted abstinence and/or reduction in sexual risk behaviors. More research is needed on decreases in sexual risk behaviors among sexual and gender minority (SGM) youth and young adults (YYA) related to the most recent mpox epidemic and whether there are factors associated with these decreases in sexual risk behavior. Participants within an ongoing cohort study of SGM YYA who reside in Illinois were offered the opportunity to participate in an mpox survey between September 10th and September 20th, 2022. Analyses looked at demographic factors associated with sexual activity since the start of the outbreak, as well as associations with two sexual risk reduction factors. Survey participation was 68.7% (322/469). Three-quarters of participants (82.6%) reported sexual activity since June 1st. Most sexually active participants (83.5%) adopted at least one sexual risk reduction behavior due to mpox. Black and Latinx individuals were less likely to be sexually active but more likely to report risk reduction behaviors (31.3% and 22.6%, respectively). Participants who received the mpox vaccine were more likely to report sexual activity. SGM YYA in Illinois reported that their sexual behaviors were impacted by the mpox outbreak. However, associations between vaccination and sexual behavior demonstrate that those who are vaccinated do adopt protective methods despite not decreasing sexual activity. Therefore, sex-positive communications and harm reduction messaging may be more appropriate as opposed to abstinence-only prevention, which can further stigmatize an already marginalized group., (© 2023. Society for Prevention Research.)

Nearly two-thirds of patients with Alzheimer's are women. Identifying therapeutics specific for women is critical to lowering their elevated risk for developing this major cause of adult dementia. Moreover, targeting epigenetic processes that regulate multiple cellular pathways is advantageous given Alzheimer's multifactorial nature. Histone acetylation is an epigenetic process heavily involved in memory consolidation. Its disruption is linked to Alzheimer's. Through our computational studies, we predicted that the investigational drug RG2833 (N-[6-(2-aminoanilino)-6-oxohexyl]-4-methylbenzamide) has repurposing potential for Alzheimer's. RG2833 is a histone deacetylase HDAC1/3 inhibitor that is orally bioavailable and permeates the blood-brain-barrier. We investigated the RG2833 therapeutic potential in TgF344-AD rats, which are a model of Alzheimer's that exhibits age-dependent progression, thus mimicking this aspect of Alzheimer's patients that is difficult to establish in animal models. We investigated the RG2833 effects on cognitive performance, gene expression, and AD-like pathology in 11-month TgF344-AD female and male rats. A total of 89 rats were used: wild type n = 45 (17 females, 28 males), and TgF344-AD n = 44 (24 females, 20 males)] across multiple cohorts. No obvious toxicity was detected in the TgF344-AD rats up to 6 months of RG2833-treatment starting at 5 months of age administering the drug in rodent chow at ∼30mg/kg of body weight. We started treatment early in the course of pathology when therapeutic intervention is predicted to be more effective than in later stages of the disease. The drug-treatment significantly mitigated hippocampal-dependent spatial memory deficits in 11-month TgF344-AD females but not in males, compared to wild type littermates. This female sex-specific drug effect has not been previously reported. RG2833-treatment failed to ameliorate amyloid beta accumulation and microgliosis in female and male TgF344-AD rats. However, RNAseq analysis of hippocampal tissue from TgF344-AD rats showed that drug-treatment in females upregulated the expression of immediate early genes, such as Arc, Egr1 and c-Fos, and other genes involved in synaptic plasticity and memory consolidation. Remarkably, out of 17,168 genes analyzed for each sex, no significant changes in gene expression were detected in males at P < 0.05, false discovery rate < 0.05, and fold-change ≥ 1.5. Our data suggest that histone modifying therapeutics such as RG2833 improve cognitive behavior by modulating the expression of immediate early, neuroprotective and synaptic plasticity genes. Our preclinical study supports that RG2833 has therapeutic potential specifically for female Alzheimer's patients. RG2833 evaluations using other AD-related models is necessary to confirm our findings.

Objective: Prior epidemic literature suggests that the rapid proliferation of Monkeypox (Mpox) within the United States may trigger severe stress reactions that increase the risk of developing secondary traumatic stress among young adults most at risk of exposure. The present exploratory study aimed to investigate the degree to which proximity to Mpox (i.e. knowing people who acquired Mpox), was associated with symptoms of secondary traumatization., Method: An online survey was administered to 253 participants enrolled in Keeping it LITE, a prospective U.S. cohort study of ethnically diverse, sexually active, sexual and gender minority persons ages 19-39 in September 2022. A multiple linear regression was used to examine the association between proximity to Mpox and secondary traumatic stress (STS) symptoms., Results: Study findings demonstrated that Mpox morbidity was low (1%); however, 37% of participants reported knowing at least one person diagnosed with Mpox. For most individuals, this person was a friend (28%). 16% of participants were found to have at least one indicator of Mpox-related STS. Results of our multiple linear regression demonstrated a positive association between an individual's indirect exposure to Mpox via their interpersonal relationships and STS symptoms., Conclusions: Findings suggest that the more adults' interpersonal relationships are saturated with people who have acquired Mpox, the more likely they are to develop symptoms of secondary traumatization. These findings provide tentative initial evidence that secondary exposure to Mpox via one's social network may undermine adults' mental health even after the conclusion of the outbreak.

Stimulant-use disorders can present with long-term cognitive and mental health deficits. Little is known about the underlying molecular mechanisms perpetuating sex differences in cognitive and behavioral deficits in preclinical models of addiction to stimulants such as methamphetamine (MA). The current study investigated the neurochemical shifts underlying sex disparities in MA-induced working memory deficits and an addictive phenotype following abstinence from chronic MA abuse. We used our previously reported mouse model of voluntary oral methamphetamine administration (VOMA) consisting of an acquisition phase (days 1-14) characterized by escalating doses of MA and a binge phase (days 14-28) characterized by static doses. Female VOMA mice exhibited sustained MA consumption during the binge phase, demonstrating sex-specific vulnerabilities to the maintenance of MA addiction. The 8-arm radial maze was used to test spatial working memory performance following abstinence from VOMA. Results indicate working memory deficits correlated to higher MA consumption in females only. Hippocampal and accumbal tissue were collected and analyzed by immunoblotting. Female VOMA mice had decreased GluA1, but not GluA2, in the hippocampus, which may perpetuate synaptic destabilization and working memory deficits. Female-specific increases in GluA1 and p-GSK3 β expression in accumbal tissue suggest vulnerability toward abstinence-induced drug craving and heightened downstream neurotoxicity. Our study reveals female-specific neurochemical shifts in hippocampal and accumbal AMPA receptor signaling following abstinence from chronic MA consumption that may perpetuate female susceptibility to MA-induced cognitive deficits. These data demonstrate a novel molecular pathway that would exacerbate memory deficits and perpetuate an addictive phenotype in female populations following MA abuse., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

This study examined experiences of healthcare inaccessibility and lesbian, gay, bisexual, transgender, queer, plus (LGBTQ+) discrimination among sexual and gender minority youth at elevated risk for HIV in the United States. Participants for this cross-sectional survey study ( N  = 3330) were cisgender men, transgender men and women, and nonbinary individuals ages 18-34 recruited for a larger study examining HIV risk behavior between December 2017 and December 2019. Results indicated that 41.1% of participants had at least one lifetime experience of LGBTQ + healthcare discrimination, and 44.1% reported past 6-month experiences of discrimination or problems accessing healthcare. Transgender men and women were more likely than cisgender men and nonbinary participants to report experiences of discrimination, and transgender men were more likely to report problems accessing healthcare. A majority of participants (72.8%) reported that their most recent healthcare provider was aware of their sexual or gender identity. These results indicate a high prevalence of structural barriers in healthcare access for sexual and gender minority youth at elevated risk for HIV, including finical and logistical barriers as well as anticipated and experienced discrimination. We discuss these findings and highlight the importance of easily accessible and culturally competent care for this community.

Introduction: The 2022 global outbreak of Monkeypox virus (Mpox), which has primarily spread through the sexual networks of sexual and gender minority (SGM) individuals, has introduced new public health challenges. While an efficacious Mpox vaccine is in active circulation, few Mpox vaccine studies have examined its uptake among SGM groups. The aims of this study were to investigate (a) the prevalence of Mpox vaccine uptake among SGM and (b) the contextual, Mpox-disease specific, and Mpox-vaccine specific factors associated with Mpox vaccine among SGM., Methods: We conducted a cross-sectional survey in Illinois, USA in September 2022; 320 young SGM completed self-administered questionnaires. Multinomial logistic regression was used to assess the contextual, Mpox-disease specific, and Mpox-vaccine specific factors associated with Mpox vaccine uptake. Adjusted Odds Ratios (aORs) and 95 % Confidence Intervals (CI) are reported., Results: Approximately 50 % of the SGM participants included in this study had received at least their first dose of the Mpox vaccine. Multinomial regression analysis showed that individuals who had recently experienced food insecurity, had higher degrees of fear of social rejection due to Mpox acquisition, and were more Mpox-vaccine hesitant were more likely to be unvaccinated. Conversely, knowing people who have contracted Mpox, having higher formal educational attainment, having higher degrees of Mpox-related internalized heterosexism, and being more concerned about one's safety regarding Mpox morbidity were more likely to be double-dosers., Conclusion: Approximately 50 % of the SGMs included in this study received at least their first dose of the Mpox vaccine; however, only one-quarter of participants completed the recommended 2-dose Mpox regimen. Our findings indicate that socioeconomic stability, fear of social rejection due to disease acquisition, and Mpox-specific vaccine hesitancy may be important structural targets to consider when developing vaccine-uptake prevention and intervention strategies tailored to the needs of sexual and gender minorities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study sought to analyze prevalence and correlates of online racialized sexual discrimination (RSD), or sexualized discriminatory treatment, in the context of sexualized encounters, among cisgender men and transgender individuals who have sex with men at risk for HIV. Data were collected as part of a baseline survey from a large national sample ( N = 2,166). Among participants of color ( N = 1,042), 84.9% had experienced RSD in the past 6 months, and transgender participants experienced similar levels of RSD as cisgender men. Experience of RSD was associated with older age and more frequent experiences of general discrimination, but not with geographic location, mental health symptoms, sexual risk behavior, or internalized homonegativity. These findings confirm that RSD is highly prevalent among sexual and gender minority individuals of color who have sex with men. Implications and areas for future research are discussed.

Alzheimer's disease is a multifactorial disease that exhibits cognitive deficits, neuronal loss, amyloid plaques, neurofibrillary tangles and neuroinflammation in the brain. Hence, a multi-target drug would improve treatment efficacy. We applied a new multi-scale predictive modelling framework that integrates machine learning with biophysics and systems pharmacology to screen drugs for Alzheimer's disease using patients' tissue samples. Our predictive modelling framework identified ibudilast as a drug with repurposing potential to treat Alzheimer's disease. Ibudilast is a multi-target drug, as it is a phosphodiesterase inhibitor and toll-like receptor 4 (TLR4) antagonist. In addition, we predict that ibudilast inhibits off-target kinases (e.g. IRAK1 and GSG2). In Japan and other Asian countries, ibudilast is approved for treating asthma and stroke due to its anti-inflammatory potential. Based on these previous studies and on our predictions, we tested for the first time the efficacy of ibudilast in Fisher transgenic 344-AD rats. This transgenic rat model is unique as it exhibits hippocampal-dependent spatial learning and memory deficits and Alzheimer's disease pathology, including hippocampal amyloid plaques, tau paired-helical filaments, neuronal loss and microgliosis, in a progressive age-dependent manner that mimics the pathology observed in Alzheimer's disease patients. Following long-term treatment with ibudilast, transgenic rats were evaluated at 11 months of age for spatial memory performance and Alzheimer's disease pathology. We demonstrate that ibudilast-treatment of transgenic rats mitigated hippocampal-dependent spatial memory deficits, as well as hippocampal (hilar subregion) amyloid plaque and tau paired-helical filament load, and microgliosis compared to untreated transgenic rat. Neuronal density analysed across all hippocampal regions was similar in ibudilast-treated transgenic compared to untreated transgenic rats. Interestingly, RNA sequencing analysis of hippocampal tissue showed that ibudilast-treatment affects gene expression levels of the TLR and ubiquitin-proteasome pathways differentially in male and female transgenic rats. Based on the TLR4 signalling pathway, our RNA sequencing data suggest that ibudilast-treatment inhibits IRAK1 activity by increasing expression of its negative regulator IRAK3, and/or by altering TRAF6 and other TLR-related ubiquitin ligase and conjugase levels. Our results support that ibudilast can serve as a repurposed drug that targets multiple pathways including TLR signalling and the ubiquitin/proteasome pathway to reduce cognitive deficits and pathology relevant to Alzheimer's disease., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The objective of this analysis was to describe individual and structural-level factors associated with pre-exposure prophylaxis (PrEP) use among a sample of sexual and gender minorities (SGM) at risk for HIV recruited using limited interaction strategies. SGM (N = 3330), ages 15-34, without HIV enrolled in a nationwide limited interaction cohort study from 2017 to 2020. A baseline cross-sectional single-survey design examined individual and structural-level correlates of PrEP lifetime use and current use using logistic regression. PrEP lifetime use and current use were reported by 31.2% and 23.9%, respectively, of SGM with PrEP data (n = 3077). PrEP use outcomes (lifetime or current use) in cisgender MSM were associated with being over age 18, Black or other race, Hispanic/Latina/x/o ethnicity, being gay, being out to one's healthcare provider, having health insurance, being a college graduate, and having a greater number of PrEP peers. PrEP use outcomes (lifetime use or current use) in transgender/non-binary participants were associated with being over age 24, being Latinx, being transgender vs. non-binary, being assigned male at birth, being out to their healthcare provider, living in the western or northeastern United States, and having more peers on PrEP. More work is needed to address lower PrEP uptake in SGM under 18 and those whose sex risk may be more dynamic (e.g., non-binary, pansexual/queer, and bisexual SGM) and such strategies should consider utilizing peers to provide information and ameliorate structural barriers., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We investigated the relevance of the prostaglandin D2 pathway in Alzheimer's disease, because prostaglandin D2 is a major prostaglandin in the brain. Thus, its contribution to Alzheimer's disease merits attention, given the known impact of the prostaglandin E2 pathway in Alzheimer's disease. We used the TgF344-AD transgenic rat model because it exhibits age-dependent and progressive Alzheimer's disease pathology. Prostaglandin D2 levels in hippocampi of TgF344-AD and wild-type littermates were significantly higher than prostaglandin E2. Prostaglandin D2 signals through DP1 and DP2 receptors. Microglial DP1 receptors were more abundant and neuronal DP2 receptors were fewer in TgF344-AD than in wild-type rats. Expression of the major brain prostaglandin D2 synthase (lipocalin-type PGDS) was the highest among 33 genes involved in the prostaglandin D2 and prostaglandin E2 pathways. We treated a subset of rats (wild-type and TgF344-AD males) with timapiprant, a potent highly selective DP2 antagonist in development for allergic inflammation treatment. Timapiprant significantly mitigated Alzheimer's disease pathology and cognitive deficits in TgF344-AD males. Thus, selective DP2 antagonists have potential as therapeutics to treat Alzheimer's disease., (© 2022 Wallace et al.)

Social interaction deficits seen in psychiatric disorders emerge in early-life and are most closely linked to aberrant neural circuit function. Due to technical limitations, we have limited understanding of how typical versus pathological social behavior circuits develop. Using a suite of invasive procedures in awake, behaving infant rats, including optogenetics, microdialysis, and microinfusions, we dissected the circuits controlling the gradual increase in social behavior deficits following two complementary procedures-naturalistic harsh maternal care and repeated shock alone or with an anesthetized mother. Whether the mother was the source of the adversity (naturalistic Scarcity-Adversity) or merely present during the adversity (repeated shock with mom), both conditions elevated basolateral amygdala (BLA) dopamine, which was necessary and sufficient in initiating social behavior pathology. This did not occur when pups experienced adversity alone. These data highlight the unique impact of social adversity as causal in producing mesolimbic dopamine circuit dysfunction and aberrant social behavior., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: HIV infection rates among sexual minority men and transgender individuals, particularly adolescents and young adults, remain elevated in the United States despite continued improvement in the HIV public health response. However, there remains a knowledge gap in understanding the barriers faced by this community in receiving HIV care and prevention resources. To address this, the Keeping it LITE study was conducted to assess HIV risk factors and barriers to preventive treatment in a large national cohort of young sexual minority men and transgender individuals at high risk of HIV infection., Objective: This study aims to evaluate the feasibility of enrolling a large remote cohort, challenges encountered in recruitment, and adjustments made to address these challenges., Methods: A large national cohort (n=3444) of young sexual minority men and transgender individuals were recruited. Participants were recruited via advertisements on social media; social apps for lesbian, gay, bisexual, transgender, and queer individuals; print advertising; and word-of-mouth. Before enrolling, participants verified their HIV status using an at-home HIV test or by providing their own testing documentation. Descriptive statistics were generated, and a series of logistic regressions were conducted to evaluate demographic differences between recruitment methods, HIV testing methods, and enrollment status., Results: The Keeping it LITE study was particularly successful in recruiting participants via social media, with over half of the participants recruited from advertisements on social media platforms such as Facebook, Instagram, and Snapchat. Participants were also recruited via word-of-mouth; lesbian, gay, bisexual, transgender, and queer apps (ie, Grindr, Scruff); and print advertisements, and participants recruited from these sources tended to be older and have a higher risk profile. The study was also successful in recruiting a large sample of transgender youth, particularly transgender men and nonbinary individuals. At-home HIV testing was acceptable and more heavily used by younger participants, although several barriers were encountered and overcome in the implementation of this testing. The study had more limited success in recruiting participants aged 13-17 years because of lower enrollment rates and barriers to advertising on social media platforms. The implications of these findings for the future development of HIV research and intervention protocols among sexual minorities and trans youth are discussed., Conclusions: The methods used in the Keeping it LITE study, particularly recruitment via social media, were found to be feasible and acceptable to participants., (©Neil Gleason, Pedro A Serrano, Alejandro Muñoz, Audrey French, Sybil Hosek. Originally published in JMIR Formative Research (https://formative.jmir.org), 26.11.2021.)

Background: Female populations exhibit vulnerabilities to psychostimulant addiction, as well as cognitive dysfunction following bouts of abuse., Aims: The goal for this study was to advance our understanding of the mechanisms that produce sex disparities in drug addiction., Methods: We used an animal model for voluntary oral methamphetamine administration (VOMA) and focused on male and female mice that consumed 7.6-8.2 mg/kg of methamphetamine (MA) per day during the last 18 days of the paradigm., Results: The VOMA-exposed female mice displayed increased locomotor activity in the drug-administration context compared to male mice, demonstrating sex-specific changes in contextual sensitization. During 2 weeks of forced abstinence, mice underwent further behavioral testing. We show that abstinence increased open-arm entries on the elevated plus maze in both sexes. There were no differences in immobility on the tail suspension test. In a hippocampal-dependent radial arm maze task, VOMA-treated female mice, but not male mice, showed working memory deficits. Hippocampal tissue was collected and analyzed using Western blotting. VOMA-exposed female mice exhibited increased kappa opioid receptor (κOR) expression in the hippocampus compared to male mice, suggesting a vulnerability toward abstinence-induced dysphoria. Female VOMA mice also exhibited a decrease in the memory protein marker, protein kinase M zeta (PKMζ), in the hippocampus., Conclusions: Our study reveals sex-specific effects following abstinence from chronic MA consumption on hippocampal κOR and PKMζ expression, suggesting that these neural changes in female mice may underlie spatial memory deficits and identify an increased susceptibility to dysregulated neural mechanisms. These data validate VOMA as a model sensitive to sex differences in behavior and hippocampal neurochemistry following chronic MA exposure.

Objective: In 2019, US advocates reported misleading language regarding the safety of TDF/FTC (Truvada) used by lawsuit advertisements against Gilead Sciences. We sought to ascertain the reach and effects of the advertisements on preexposure prophylaxis (PrEP) opinions and decisions in a cohort of youth and young adults at-risk for HIV., Design: An online survey was administered to participants enrolled in Keeping it LITE, a prospective US cohort study of ethnically diverse, sexually active, cisgender and transgender persons ages 13-37., Methods: Quantitative data were analyzed using descriptive and inferential analysis in SAS, and qualitative data via thematic analysis., Results: Survey response rate was 51.3% (n = 1485). Mean age at baseline was 24. Previous PrEP use was reported by 43% of respondents and 32.7% reported PrEP use in the past 6 months. Almost half (48.7%) were aware of the lawsuit. Most of these participants (81.3%) reported the advertisements did not impact their PrEP use, but 13.2% decided to not to begin a Truvada-based PrEP regimen and 5.5% decided to stop taking Truvada due to the advertisements claims. Predictors of changing PrEP behavior were lower education and no previous PrEP use. The qualitative analysis revealed the advertisements increased skepticism about safety and benefit of Truvada PrEP and led to greater distrust of the pharmaceutical industry., Conclusion: The advertisements reached a large, diverse US audience. Disturbingly, 18.7% of PrEP candidates who were aware of the lawsuit attributed not initiating or cessation of a Truvada-based PrEP regimen to exposure to the Truvada lawsuit advertisements.

This work described a bioinspired soft robotic finger with variable bending length to conform objects with different sizes by means of selectively varying the structural stiffness of its segments. The basic design is a shape memory alloy-based soft actuator with embedded stiffness-varying structures serving as modifiable endoskeletons. The stiffness-varying structure is composed of shape memory polymer (SMP) embedded with Nichrome (Ni-Cr) wires as heating elements. Joule heating of SMP through Ni-Cr wire inducing its phase change from the glassy state to the rubbery state enables the actuator structure change from the stiff state ( E  = 125.65 MPa) to the compliant state ( E  = 3.33 MPa). The Ni-Cr wire was designed with multiple solder tabs to enable the SMP that can be heated segmentally leading to the stiffness reduction of desired segments of finger to obtain different bendable lengths. A finger with three segments was fabricated, and its deformation and actuation force were measured based on different bendable lengths. A gripper was then assembled using two identical fingers where the angle between them can be manually adjusted. The angles for the two fingers with specific bending length were determined to enable them to form a closed configuration when maximum bending is reached. The grasping force of the gripper was then measured, and it was used to grip different objects. Results show that the performance of the gripper in gripping the size and weight of the object was markedly improved compared with the gripper that cannot vary its gripping length.

Background: Inflammation in the brain is mediated by the cyclooxygenase pathway, which leads to the production of prostaglandins. Prostaglandin (PG) D2, the most abundant PG in the brain, increases under pathological conditions and is spontaneously metabolized to PGJ2. PGJ2 is highly neurotoxic, with the potential to transition neuroinflammation into a chronic state and contribute to neurodegeneration as seen in many neurological diseases. Conversely, PACAP27 is a lipophilic peptide that raises intracellular cAMP and is an anti-inflammatory agent. The aim of our study was to investigate the therapeutic potential of PACAP27 to counter the behavioral and neurotoxic effects of PGJ2 observed in aged subjects., Methods: PGJ2 was injected bilaterally into the hippocampal CA1 region of 53-week-old and 12-week-old C57BL/6N male mice, once per week over 3 weeks (three total infusions) and included co-infusions of PACAP27 within respective treatment groups. Our behavioral assessments looked at spatial learning and memory performance on the 8-arm radial maze, followed by histological analyses of fixed hippocampal tissue using Fluoro-Jade C and fluorescent immunohistochemistry focused on IBA-1 microglia., Results: Aged mice treated with PGJ2 exhibited spatial learning and long-term memory deficits, as well as neurodegeneration in CA3 pyramidal neurons. Aged mice that received co-infusions of PACAP27 exhibited remediated learning and memory performance and decreased neurodegeneration in CA3 pyramidal neurons. Moreover, microglial activation in the CA3 region was also reduced in aged mice cotreated with PACAP27., Conclusions: Our data show that PGJ2 can produce a retrograde spread of damage not observed in PGJ2-treated young mice, leading to age-dependent neurodegeneration of hippocampal neurons producing learning and memory deficits. PACAP27 can remediate the behavioral and neurodegenerative effects that PGJ2 produces in aged subjects. Targeting specific neurotoxic prostaglandins, such as PGJ2, offers great promise as a new therapeutic strategy downstream of cyclooxygenases, to combat the neuronal deficits induced by chronic inflammation., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Pre-exposure prophylaxis (PrEP) for the prevention of HIV infection among young men who have sex with men is a critical part of the HIV prevention landscape in the US. Given the unique challenges and resources of young MSM negotiating safer sex practices, including PrEP, counseling and supportive discussions to optimize both PrEP use and sexual health protection more generally may facilitate reaching HIV prevention goals. Within the context of a large, open-label PrEP study (ATN110/113), support for sexual health promotion and PrEP use was provided through use of integrated Next Step Counseling (iNSC) as part of study visits. We detail iNSC and, using session documentation collected throughout this study, we characterize iNSC implementation and the content generated from these discussions. We detail features of iNSC, training of counselors and the implementation of iNSC in a multi-site PrEP study with young MSM in the US. Case report forms completed by iNSC counselors at study visits at weeks 4, 8, 12, 24, 36, and 48 were evaluated. Implementation of each intervention step for each discussion is summarized at and across timepoints, as well as features of specific steps (e.g., kinds of facilitators and barriers). Implementation differences by group (e.g., race/ethnicity, age) were examined. iNSC case report forms from 1000 sessions involving 178 unique participants ages 15-22 from sessions conducted between 2013 and 2015 were reviewed. High fidelity to iNSC steps in terms of inclusion in sessions was reported; 98-100% of sessions included critical steps for sexual health protection discussions and 96-98% for PrEP use discussions. The vast majority of sessions appeared to flow in line with iNSC's emphasis on exploration and open discussion prior to considering specific needs and related strategies. Nearly three-quarters of sessions noted 'commitment to staying negative' as a motivator towards sexual health protection (more commonly reported by those identifying as White), while 'assuming partner is negative' was the most common challenge (less common for the older cohort), and 'having access' to a sexual health protection tool or strategy (besides PrEP) was the most common "need" (more common for those identifying as White or Latino). Carrying dose(s) to have them on-hand when needed was the most common PrEP adherence facilitator, drug and alcohol use was the most common challenge noted, and access to a dose when needed was the most common "need" (more common for participants self-identified as White). iNSC was implemented consistently throughout ATN110/113, and patient-centered discussions about sexual health protection and PrEP-use appeared feasible to incorporate into clinical care visits.

Child development research highlights caregiver regulation of infant physiology and behavior as a key feature of early life attachment, although mechanisms for maternal control of infant neural circuits remain elusive. Here we explored the neurobiology of maternal regulation of infant fear using neural network and molecular levels of analysis in a rodent model. Previous research has shown maternal suppression of amygdala-dependent fear learning during a sensitive period. Here we characterize changes in neural networks engaged during maternal regulation and the transition to infant self-regulation. Metabolic mapping of 2-deoxyglucose uptake during odor-shock conditioning in postnatal day (PN)14 rat pups showed that maternal presence blocked fear learning, disengaged mesolimbic circuitry, basolateral amygdala (BLA), and plasticity-related AMPA receptor subunit trafficking. At PN18, when maternal presence only socially buffers threat learning (similar to social modulation in adults), maternal presence failed to disengage the mesolimbic dopaminergic system, and failed to disengage both the BLA and plasticity-related AMPA receptor subunit trafficking. Further, maternal presence failed to block threat learning at PN14 pups following abuse, and mesolimbic dopamine engagement and AMPA were not significantly altered by maternal presence-analogous to compromised maternal regulation of children in abusive relationships. Our results highlight three key features of maternal regulation: (1) maternal presence blocks fear learning and amygdala plasticity through age-dependent suppression of amygdala AMPA receptor subunit trafficking, (2) maternal presence suppresses engagement of brain regions within the mesolimbic dopamine circuit, and (3) early-life abuse compromises network and molecular biomarkers of maternal regulation, suggesting reduced social scaffolding of the brain.

Background: Young men who have sex with men (YMSM) in the United States have among the highest incidence of HIV and sexually transmitted infection (STI) and the lowest uptake of HIV and STI testing and pre-exposure prophylaxis (PrEP). Nearly universal mobile phone ownership among youth provides an opportunity to leverage mobile health apps to increase HIV/STI testing and PrEP uptake among YMSM., Objective: The goals of this project are to develop and refine LYNX, a novel mobile app to support linkage to HIV/STIs testing and PrEP services among YMSM in the United States, and to evaluate the acceptability and feasibility of LYNX in a pilot randomized controlled trial (RCT)., Methods: This research protocol will be conducted in 3 phases: an iterative development phase with a series of 3 focus groups among 20 YMSM to refine the LYNX app; an open technical pilot among 15 YMSM to optimize usability of the app; and then a 6-month pilot RCT among 60 HIV-uninfected YMSM at risk for HIV acquisition. Developed using the Information, Motivation, and Behavioral skills theoretical model, the LYNX app includes an electronic diary to track sexual behaviors (information), a personalized risk score to promote accurate risk perception (information/motivation), testing reminders (motivation/behavioral skills), and access to home-based HIV/STI testing options and geospatial-based HIV/STI testing care sites (behavioral skills). Feasibility and acceptability will be assessed through app analytics of usage patterns and acceptability scales administered via computer-assisted self-interview at 3 and 6 months. We will also evaluate preliminary efficacy by comparing the proportion of YMSM who test at least once during the 6-month pilot and the proportion who successfully link to a PrEP provider in the intervention versus control groups., Results: Formative work is currently underway. The LYNX pilot RCT will begin enrollment in October 2018, with study results available in 2019., Conclusions: The LYNX app is one of the first mobile apps designed to increase HIV/STI testing and PrEP uptake among YMSM. As low-perceived risk is a barrier to HIV/STI testing and PrEP use among youth, the personalized risk assessment and interactive sexual diary in LYNX could assist YMSM in better understanding their HIV risk and providing motivation to test for HIV/STIs and initiate PrEP. Coupled with community-based recruitment, this novel mobile app has great potential to reach and engage YMSM not currently involved in care and increase rates of HIV/STI testing and PrEP uptake in this vulnerable population., Trial Registration: ClinicalTrials.gov NCT03177512; https://clinicaltrials.gov/ct2/show/NCT03177512 (Archived by WebCite at http://www.webcitation.org/73c917wAw)., International Registered Report Identifier (irrid): PRR1-10.2196/10659., (©Albert Liu, Kenneth Coleman, Kelly Bojan, Pedro Alonso Serrano, Temitope Oyedele, Amayvis Garcia, Elizabeth Enriquez-Bruce, Patricia Emmanuel, Jeb Jones, Patrick Sullivan, Lisa Hightow-Weidman, Susan Buchbinder, Hyman Scott. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 25.01.2019.)

It is well known that young organisms do not maintain memories as long as adults, but the mechanisms for this ontogenetic difference are undetermined. Previous work has revealed that the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAr) subunits are trafficked into the synaptic membrane following memory retrieval in adults. Additionally, phosphorylated PSD-95-pS295 promotes AMPAr stabilization at the synapse. We investigated these plasticity related proteins as potential mediators in the differential contextual stress memory retrieval capabilities observed between adult and juvenile rats. Rats were assigned to either pedestal stress (1 h) or no stress control (home cage). Each animal was placed alone in an open field for 5 min at the base of a 6 × 6 sq inch pedestal (4ft high). Stress subjects were then placed on this pedestal for 1hr and control subjects were placed in their home cage following initial exploration. Each animal was returned to the open field for 5 min either 1d or 7d following initial exposure. Freezing postures were quantified during the memory retrieval test. The 1d test shows adult (P90) and juvenile (P26) stressed rats increase their freezing time compared to controls. However, the 7d memory retrieval test shows P90 stress rats but not P26 stress rats freeze while in the fear context. Twenty minutes after the memory retrieval test, hippocampi and amygdala were micro-dissected and prepared for western blot analysis. Our results show that 1d fear memory retrieval induced an upregulation of PSD-95 and pS295 in the adult amygdala but not in the juvenile. However, the juvenile animals upregulated PKMζ, PI3K and GluA2/3, GluA1-S845 in the dorsal hippocampus (DH), but the adults did not. Following the 7d memory retrieval test, adults upregulated GluA2 in the amygdala but not the juveniles. In the DH, adults increased PSD-95 and pS295 but not the juveniles. The adults appear to preferentially increase amygdala-driven processing at 1d and increase DH-driven context specific processing at 7d. These data identify molecular processes that may underlie the reduced fear-memory retrieval capability of juveniles. Together these data provide a potential molecular target that could be beneficial in treatment of anxiety disorders and PTSD.

Although infants learn and remember, they rapidly forget, a phenomenon known as infantile amnesia. While myriad mechanisms impact this rapid forgetting, the molecular events supporting memory maintenance have yet to be explored. To explore memory mechanisms across development, we used amygdala-dependent odor-shock conditioning and focused on mechanisms important in adult memory, the AMPA receptor subunits GluA1/2 and upstream protein kinases important for trafficking AMPAR, protein kinase M zeta (PKMζ) and iota/lambda (PKCι/λ). We use odor-shock conditioning in infant rats because it is late-developing (postnatal day, PN10) and can be modulated by corticosterone during a sensitive period in early life. Our results show that memory-related molecules did not change in pups too young to learn threat (PN8) but were activated in pups old enough to learn (PN12), with increased PKMζ-PKCι/λ and GluA2 similar to that observed in adult memory, but with an uncharacteristic decrease in GluA1. This molecular signature and behavioral avoidance of the conditioned odor was recapitulated in PN8 pups injected with CORT before conditioning to precociously induce learning. Blocking learning via CORT inhibition in older pups (PN12) blocked the expression of these molecules. PN16 pups showed a more adult-like molecular cascade of increased PKMζ-PKCι/λ and GluA1-2. Finally, at all ages, zeta inhibitory peptide (ZIP) infusions into the amygdala 24 hr after conditioning blocked memory. Together, these results identify unique features of memory processes across early development: AMPAR subunits GluA1/2 and PKC isoform expression are differentially used, which may contribute to mechanisms of early life forgetting.

Methamphetamine (MA) is an addictive drug with neurotoxic effects on the brain producing cognitive impairment and increasing the risk for neurodegenerative disease. Research has focused largely on examining the neurochemical and behavioral deficits induced by injecting relatively high doses of MA [30 mg/kg of body weight (bw)] identifying the upper limits of MA-induced neurotoxicity. Accordingly, we have developed an appetitive mouse model of voluntary oral MA administration (VOMA) based on the consumption of a palatable sweetened oatmeal mash containing a known amount of MA. This VOMA model is useful for determining the lower limits necessary to produce neurotoxicity in the short-term and long-term as it progresses over time. We show that mice consumed on average 1.743 mg/kg bw/hour during 3 hours, and an average of 5.23 mg/kg bw/day over 28 consecutive days on a VOMA schedule. Since this consumption rate is much lower than the neurotoxic doses typically injected, we assessed the effects of long-term chronic VOMA on both spatial memory performance and on the levels of neurotoxicity in the hippocampus. Following 28 days of VOMA, mice exhibited a significant deficit in short-term spatial working memory and spatial reference learning on the radial 8-arm maze (RAM) compared to controls. This was accompanied by a significant decrease in memory markers protein kinase Mzeta (PKMζ), calcium impermeable AMPA receptor subunit GluA2, and the post-synaptic density 95 (PSD-95) protein in the hippocampus. Compared to controls, the VOMA paradigm also induced decreases in hippocampal levels of dopamine transporter (DAT) and tyrosine hydroxylase (TH), as well as increases in dopamine 1 receptor (D1R), glial fibrillary acidic protein (GFAP) and cyclooxygenase-2 (COX-2), with a decrease in prostaglandins E2 (PGE2) and D2 (PGD2). These results demonstrate that chronic VOMA reaching 146 mg/kg bw/28d induces significant hippocampal neurotoxicity. Future studies will evaluate the progression of this neurotoxic state.

Background: Stress is a prevailing risk factor for mood-related illnesses, wherein women represent the majority of those affected by major depression. Despite the growing literature suggesting that affective disorders can arise after a traumatic event is vicariously experienced, this relationship remains understudied in female subjects at the preclinical level. Thus, the objective of the current investigation was to examine whether exposure to emotional and/or psychological stress (ES) mediates depression-related outcomes in female mice., Methods: Female C57BL/6 mice (8 weeks old, null parity) vicariously experienced the defeat bout of a male conspecific, by a male CD1 aggressor, for 10 consecutive days. Twenty-four hours after the last stress exposure, female mice were tested in the social interaction, sucrose preference, tail suspension, or elevated plus maze tests. Furthermore, we examined whether ketamine and chlordiazepoxide, pharmacological agents used to treat mood-related disorders in the clinical population, would reverse the ES-induced social dysfunction., Results: When compared with control mice, female mice exposed to ES displayed decreased social behavior and preference for sucrose, along with increased immobility in the tail suspension test. Also, they displayed higher levels of blood serum corticosterone, as well as decreased body weight. Lastly, the ES-induced avoidance-like phenotype was ameliorated by both ketamine and chlordiazepoxide., Conclusions: Our data indicate that female mice exposed to ES display a behavioral and physiologic profile that mimics symptoms of depression in the clinical population. As such, this experimental model may be adopted to examine vicarious stress-induced mood-related disorders, as well as pharmacological antidepressant response, in a sex-specific manner., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Hippocampal dendritic spine density rapidly increases following estradiol (E 2 ) treatment, but the types of spines and trafficking of synaptic markers have received little investigation. We assessed rapid effects of E 2 over time on the density of four spine types (stubby, filopodial, long thin, and mushroom) and trafficking of AMPA receptor subunit GluA2 and PSD95 on tertiary, apical dendrites in CA1. Castrated male rats received 20 μg kg -1 of E 2 or vehicle and were sacrificed 30 or 120 min later. Images of Golgi-Cox impregnated and PSD95/GluA2 stained dendrites were captured under the confocal microscope and quantified with IMARIS-XT. Stubby and filopodial spine densities did not change following treatment. Long-thin spines significantly decreased at 30 min while mushroom spines significantly increased at 120 min. GluA2, PSD95, and GluA2/PSD95 colocalization levels in stubby or long thin spines did not change, but filopodial spines had significantly reduced GluA2 levels at 30 min. Mushroom spines showed significantly increased levels for GluA2, PSD95 and GluA2/PSD95 colocalization at 120 min. Because GluA2 is important for memory consolidation, current results present novel data suggesting that trafficking of GluA2 to mushroom spines provides one mechanism contributing to estradiol's ability to enhance learning and memory by the PI3 signaling pathway., (© 2017 Wiley Periodicals, Inc.)

Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by which stress affects the amygdala and amygdala-dependent fear memories remain unclear. Here we review the literature on the enhancing effects of acute and chronic stress on the acquisition and/or consolidation of a fear memory, as measured by auditory Pavlovian fear conditioning, and discuss potential mechanisms by which these changes occur in the amygdala. We hypothesize that stress-mediated activation of glucocorticoid receptors (GR) and norepinephrine release within the amygdala leads to the mobilization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors to the synapse, which underlies stress-induced increases in fear memory. We discuss the implications of this hypothesis for evaluating the effects of stress on extinction and for developing treatments for anxiety disorders. Understanding how stress-induced changes in glucocorticoid and norepinephrine signaling might converge to affect emotional learning by increasing the trafficking of AMPA receptors and enhancing amygdala excitability is a promising area for future research.

One emerging avenue for the exploration of adolescents' sexual orientation identity development is the Internet, since it allows for varying degrees of anonymity and exploration. The purpose of this phenomenological study was to examine the role of the Internet in facilitating the sexual orientation identity development process of gay and bisexual male adolescents. Qualitative interviews were conducted with an ethnically diverse sample of 63 gay/bisexual male adolescents (ages 15-23). Participants reported using a range of Internet applications as they explored and came to accept their sexual orientation identity, with the intended purpose and degree of anonymity desired determining which applications were used. Youth reported that the Internet provided a range of functions with regard to the exploration and acceptance of their sexual orientation identity, including (1) increasing self-awareness of sexual orientation identity, (2) learning about gay/bisexual community life, (3) communicating with other gay/bisexual people, (4) meeting other gay/bisexual people, (5) finding comfort and acceptance with sexual orientation, and (6) facilitating the coming out process. Future research and practice may explore the Internet as a platform for promoting the healthy development of gay and bisexual male adolescents by providing a developmentally and culturally appropriate venue for the exploration and subsequent commitment to an integrated sexual orientation identity., (© The Author(s) 2015.)

Social stress, including bullying during adolescence, is a risk factor for common psychopathologies such as depression. To investigate the neural mechanisms associated with juvenile social stress-induced mood-related endophenotypes, we examined the behavioral, morphological, and biochemical effects of the social defeat stress model of depression on hippocampal dendritic spines within the CA1 stratum radiatum. Adolescent (postnatal day 35) male C57BL/6 mice were subjected to defeat episodes for 10 consecutive days. Twenty-four h later, separate groups of mice were tested on the social interaction and tail suspension tests. Hippocampi were then dissected and Western blots were conducted to quantify protein levels for various markers important for synaptic plasticity including protein kinase M zeta (PKMζ), protein kinase C zeta (PKCζ), the dopamine-1 (D1) receptor, tyrosine hydroxylase (TH), and the dopamine transporter (DAT). Furthermore, we examined the presence of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor subunit GluA2 as well as colocalization with the post-synaptic density 95 (PSD95) protein, within different spine subtypes (filopodia, stubby, long-thin, mushroom) using an immunohistochemistry and Golgi-Cox staining technique. The results revealed that social defeat induced a depression-like behavioral profile, as inferred from decreased social interaction levels, increased immobility on the tail suspension test, and decreases in body weight. Whole hippocampal immunoblots revealed decreases in GluA2, with a concomitant increase in DAT and TH levels in the stressed group. Spine morphology analyses further showed that defeated mice displayed a significant decrease in stubby spines, and an increase in long-thin spines within the CA1 stratum radiatum. Further evaluation of GluA2/PSD95 containing-spines demonstrated a decrease of these markers within long-thin and mushroom spine types. Together, these results indicate that juvenile social stress induces GluA2- and dopamine-associated dysregulation in the hippocampus - a neurobiological mechanism potentially underlying the development of mood-related syndromes as a consequence of adolescent bullying.

Environmental enrichment (EE) housing paradigms have long been shown beneficial for brain function involving neural growth and activity, learning and memory capacity, and for developing stress resiliency. The expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA2, which is important for synaptic plasticity and memory, is increased with corticosterone (CORT), undermining synaptic plasticity and memory. Thus, we determined the effect of EE and stress on modulating GluA2 expression in Sprague-Dawley male rats. Several markers were evaluated which include: plasma CORT, the glucocorticoid receptor (GR), GluA2, and the atypical protein kinase M zeta (PKMζ). For 1 week standard-(ST) or EE-housed animals were treated with one of the following four conditions: (1) no stress; (2) acute stress (forced swim test, FST; on day 7); (3) chronic restraint stress (6 h/day for 7 days); and (4) chronic + acute stress (restraint stress 6 h/day for 7 days + FST on day 7). Hippocampi were collected on day 7. Our results show that EE animals had reduced time immobile on the FST across all conditions. After chronic + acute stress EE animals showed increased GR levels with no change in synaptic GluA2/PKMζ. ST-housed animals showed the reverse pattern with decreased GR levels and a significant increase in synaptic GluA2/PKMζ. These results suggest that EE produces an adaptive response to chronic stress allowing for increased GR levels, which lowers neuronal excitability reducing GluA2/PKMζ trafficking. We discuss this EE adaptive response to stress as a potential underlying mechanism that is protective for retaining synaptic plasticity and memory function.

Methamphetamine (MA) is a toxic, addictive drug shown to modulate learning and memory, yet the neural mechanisms are not fully understood. We investigated the effects of 2 weekly injections of MA (30 mg/kg) on working memory using the radial 8-arm maze (RAM) across 5 weeks in adolescent-age mice. MA-treated mice show a significant improvement in working memory performance 1 week following the first MA injection compared to saline-injected controls. Following 5 weeks of MA abstinence mice were re-trained on a reference and working memory version of the RAM to assess cognitive flexibility. MA-treated mice show significantly more working memory errors without effects on reference memory performance. The hippocampus and dorsal striatum were assessed for expression of glutamate receptors subunits, GluA2 and GluN2B; dopamine markers, dopamine 1 receptor (D1), dopamine transporter (DAT) and tyrosine hydroxylase (TH); and memory markers, protein kinase M zeta (PKMζ) and protein kinase C zeta (PKCζ). Within the hippocampus, PKMζ and GluA2 are both significantly reduced after MA supporting the poor memory performance. Additionally, a significant increase in GluN2B and decrease in D1 identifies dysregulated synaptic function. In the striatum, MA treatment increased cytosolic DAT and TH levels associated with dopamine hyperfunction. MA treatment significantly reduced GluN2B while increasing both PKMζ and PKCζ within the striatum. We discuss the potential role of PKMζ/PKCζ in modulating dopamine and glutamate receptors after MA treatment. These results identify potential underlying mechanisms for working memory deficits induced by MA.

It is well established that male rats have an advantage in acquiring place-learning strategies, allowing them to learn spatial tasks more readily than female rats. However many of these differences have been examined solely during acquisition or in 24h memory retention. Here, we investigated whether sex differences exist in remote long-term memory, lasting 30d after training, and whether there are differences in the expression pattern of molecular markers associated with long-term memory maintenance. Specifically, we analyzed the expression of protein kinase M zeta (PKMζ) and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA2. To adequately evaluate memory retention, we used a robust training protocol to attenuate sex differences in acquisition and found differential effects in memory retention 1d and 30d after training. Female cohorts tested for memory retention 1d after 60 training trials outperformed males by making significantly fewer reference memory errors at test. In contrast, male cohorts tested 30d after 60 training trials outperformed females of the same condition, making fewer reference memory errors and achieving significantly higher retention test scores. Furthermore, given 60 training trials, females tested 30d later showed significantly worse memory compared to females tested 1d later, while males tested 30d later did not differ from males tested 1d later. Together these data suggest that with robust training males do no retain spatial information as well as females do 24h post-training but maintain this spatial information for longer. Males also showed a significant increase in synaptic PKMζ expression and a positive correlation with retention test scores, while females did not. Interestingly, both sexes showed a positive correlation between retention test scores and synaptic GluA2 expression. Furthermore, the increased expression of synaptic PKMζ, associated with male memory but not with female memory, identifies another potential sex-mediated difference in memory processing.

GluA2-containing AMPA receptors and their association with protein kinase M zeta (PKMζ) and post-synaptic density-95 (PSD-95) are important for learning, memory and synaptic plasticity processes. Here we investigated these synaptic markers in the context of an acute 1h platform stress, which can disrupt spatial memory retrieval for a short-term memory on the object placement task and long-term memory retrieval on a well-learned radial arm maze task. Acute stress increased serum corticosterone and elevated the expression of synaptic PKMζ while decreasing synaptic GluA2. Using co-immunoprecipitation, we found that this stressor promotes the clustering of GluA2, PKMζ and PSD-95, which is consistent with effects reported from overexpression of PKMζ in cell culture. Because PKMζ overexpression has also been shown to induce spine maturation in culture, we examined how stress impacts synaptic markers within changing spines across various hippocampal subfields. To achieve this, we employed a new technique combining Golgi staining and immmunohistochemistry to perform 3D reconstruction of tertiary dendrites, which can be analyzed for differences in spine types and the colocalization of synaptic markers within these spines. In CA1, stress increased the densities of long-thin and mushroom spines and the colocalization of GluA2/PSD-95 within these spines. Conversely, in CA3, stress decreased the densities of filopodia and stubby spines, with a concomitant reduction in the colocalization of GluA2/PSD-95 within these spines. In the outer molecular layer (OML) of the dentate gyrus (DG), stress increased both stubby and long-thin spines, together with greater GluA2/PSD-95 colocalization. These data reflect the rapid effects of stress on inducing morphological changes within specific hippocampal subfields, highlighting a potential mechanism by which stress can modulate memory consolidation and retrieval.

Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within a single task. Thus, we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM) with a sequence of four baited and four unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test 2 weeks after training. Multiple training trials not only provide robust training, but also test the subjects' ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing 2 weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI.

On the heels of several trials demonstrating the efficacy of pre-exposure prophylaxis (PrEP) and the recent approval by the FDA of the supplemental indication for Truvada as PrEP, researchers, advocates, and community providers are calling for the investigation of implementation strategies that combine behavioral interventions with biomedical prevention. This paper describes the modification and integration of an evidence-based group-level intervention into a small PrEP pilot trial with young men who have sex with men (YMSM). The behavioral intervention as well as ongoing risk reduction counseling sessions were found to be highly acceptable among a sample of racially diverse YMSM.

We introduce a technique to generate arbitrary nondiffracting beams. Using a genetic algorithm that uses a Gaussian weight function merged with spatial spectrum engineering techniques, we show that it is possible to obtain the angular spectrum representation of arbitrary light patterns, thus demonstrating their nondiffracting properties.

Prenatal exposure to opiates, which is invariably followed by postnatal withdrawal, can affect cognitive performance. To further characterize these effects, we examined radial 8-arm maze performance and expression of brain derived neurotrophic factor (BDNF) in male rats prenatally exposed to the opiate l-alpha-acetylmethadol (LAAM). Female rats received 1.0 mg/kg/day LAAM or water via daily oral gavage for 28 days prior to breeding, during breeding, and throughout pregnancy. Pups were fostered to non-treated lactating dams at birth and underwent neonatal opiate withdrawal. At 5-6 months, prenatal water- and LAAM-exposed males (n=6 each; non-littermates) received radial arm maze training consisting of ten trials a day for five days and three retention trials on day six. Rats prenatally exposed to LAAM had poorer maze performance, decreased percent correct responding and more reference and working memory errors than prenatal water-treated controls. However, they were able to acquire the task by the end of training. There were no differences between the groups on retention 24 h after testing. Following retention testing, hippocampi were removed and protein extracted from cytosol and synaptic fractions. Western blots were used to measure levels of mature and precursor BDNF protein, as well as the BDNF receptor TrkB. BDNF precursor protein was significantly decreased in the synaptic fraction of trained prenatal LAAM-treated rats compared to prenatal water-treated trained controls. No effects were found for the full-length or truncated TrkB receptor. In untrained rats, prenatal treatment did not affect any of the measures. These data suggest that prenatal opiate exposure and/or postnatal withdrawal compromise expression of proteins involved in the neural plasticity underlying learning.

Protein kinase M zeta (PKM zeta) is a newly described form of PKC that is necessary and sufficient for the maintenance of hippocampal long term potentiation (LTP) and the persistence of memory in Drosophila. PKM zeta is the independent catalytic domain of the atypical PKC zeta isoform and produces long term effects at synapses because it is persistently active, lacking autoinhibition from the regulatory domain of PKC zeta. PKM has been thought of as a proteolytic fragment of PKC. Here we report that brain PKM zeta is a new PKC isoform, synthesized from a PKM zeta mRNA encoding a PKC zeta catalytic domain without a regulatory domain. Multiple zeta-specific antisera show that PKM zeta is expressed in rat forebrain as the major form of zeta in the near absence of full-length PKC zeta. A PKC zeta knockout mouse, in which the regulatory domain was disrupted and catalytic domain spared, still expresses brain PKM zeta, indicating that this form of PKM is not a PKC zeta proteolytic fragment. Furthermore, the distribution of brain PKM zeta does not correlate with PKC zeta mRNA but instead with an alternate zeta RNA transcript thought incapable of producing protein. In vitro translation of this RNA, however, generates PKM zeta of the same molecular weight as that in brain. Metabolic labeling of hippocampal slices shows increased de novo synthesis of PKM zeta in LTP. Because PKM zeta is a kinase synthesized in an autonomously active form and is necessary and sufficient for maintaining LTP, it serves as an example of a link coupling gene expression directly to synaptic plasticity.

Pyogenic liver abscess in patients with Crohn's disease is not common, but the mortality has been reported to be high if diagnosis and treatment is delayed. Intra-abdominal abscesses, fistulous disease, and steroid therapy have all been reported to be important predisposing factors in the pathogenesis of this entity. We present a patient with Crohn's disease in whom multiple abscesses were encountered in the right lobe of the liver. The diagnosis of liver abscess was established by abdominal computed tomography and the patient was treated by percutaneous catheter drainage. Awareness of this rare complication is important because diagnosis is difficult to make and a high index of suspicion is required. Once suspected, aggressive diagnostic workup and treatment is indicated. Most patients with liver abscess can be successfully managed by percutaneous catheter drainage combined with antibiotic therapy if it is diagnosed before extensive necrosis has occurred.

The aim of this study was to evaluate the results of the Gilbert repair for primary treatment of indirect inguinal hernias performed as day cases. From September 1996 to September 1998, 145 patients who were admitted for ambulatory surgery underwent Gilbert tension-free repair for treatment of unilateral inguinal hernia. Sex, age, the American Society of Anaesthesiologists (ASA) preoperative assessment score, type of anaesthesia, operating time, postoperative recovery, postoperative pain, morbidity, mortality, recurrence, return to work and the normal daily activities were assessed. The mean follow-up was 21 months (range 12-36). Gilbert's classification, type 2 and 3 hernias were the most common. Spinal anaesthesia was used in 73% of patients. Mortality was zero. Four patients developed postoperative haematomas, two urinary retention, three seromas, and two wound infections. During the follow-up period, only two recurrences of hernia were noted (1.4%). In conclusion, these data show that Gilbert repair is a safe operation, which is simple to learn. It can be performed on an outpatient basis, with a low complication rate, a low level of pain and a short recovery period. Although it seems to have a low risk of recurrence, a long-term follow-up is needed.