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\"A new collection featuring the legendary 1980s Batman epics \"Ten Nights of the Beast\" and \"A Death in the Family\", never before collected! This new collection of 1980s Batman tales includes the legendary story \"A Death in the Family,\" in which the Joker ends up killing the secon Robin, Jason Todd. It all begins with the story \"Ten Nights of the Beast,\" which introduced the deadly post-Soviet villain known as the KGBeast. Following that, a series of stories concerning organized crime in the streets of Gotham City leads into \"A Death in the Family,\" in which Robin follows a trail to find his birth mother, who is in cahoots with the Joker.\"-- Provided by publisher.

Individuals differ in how they react to stress or trauma through different coping styles in which they may deal directly with a stressor by adopting approach coping styles or disengage with a stressor by utilizing avoidant coping styles. Avoidant coping styles have been linked to adverse outcomes including psychological distress, anxiety disorders, and post-traumatic stress disorder (PTSD). Recently, avoidance coping styles as measured by a subset of items on the Brief COPE were found to have a weak positive relationship with performance on a computer-based avatar task which is related to avoidant personality temperaments. This avatar task was developed as an alternative for paper and pencil self-report inventories for measuring avoidant tendencies based on possible response biases of avoidant individuals. In the current study, avoidance and approach coping styles as measured by the Brief Approach/Avoidance Coping Questionnaire (BACQ) were compared to avoidant coping as measured by the Brief COPE and performance on the avatar task. In addition to approach and avoidance coping, the BACQ also measures active avoidance coping (i.e., diversion) and passive avoidance coping (i.e., resignation and withdrawal). The relationships between approach and avoidance coping and performance on the avatar task were also analyzed with the outcome of perceived stress as measured by the Perceived Stress Scale (PSS). One hundred undergraduates voluntarily completed the BACQ, the Brief COPE, and the PSS. Participants also completed a computer-based task in which they guided an avatar through a series of social situations where they indicated how they would interact with or avoid interacting with strangers. Approach coping had a weak negative relationship to avoidance coping as measured by the BACQ and the Brief COPE. Performance on the avatar task had a moderate positive relationship with avoidance coping (diversion as well as resignation and withdrawal) as measured by the BACQ and a moderate negative relationship with approach coping as measured by the BACQ. A model including only approach, diversion, and resignation and withdrawal coping best predicted performance on the avatar task in a linear regression model. While resignation and withdrawal coping and diversion coping had moderate positive relationships to avatar task scores, only resignation and withdrawal had a strong positive relationship to perceived stress. A model than included only resignation and withdrawal coping best predicted perceived stress in a linear regression model. Overall, passive avoidant coping styles (i.e., resignation and withdrawal), but not active avoidant coping style (i.e., diversion), were related to perceived stress. These results support the continued study of multiple aspects of avoidant coping styles as well as the avatar task to increase our understanding of the maladaptive effects of excessive avoidance in the face of stress.

Current psychotherapies seek to reduce experiential avoidance (EA) which has also been put forth as a risk factor for anxiety disorders, depression, and post-traumatic stress disorder. EA is a potentially maladaptive self-regulatory tendency to avoid negative thoughts, feelings, memories, physical sensations, and other internal experiences. One unresolved issue with the most commonly used measures of EA, the Acceptance and Action Questionnaire-II (AAQ-II) which measures EA as a single factor and the Multidimensional Experiential Avoidance Questionnaire (MEAQ) which measures EA as six subdimensions, is what exactly is being measured. The AAQ-II appears to measure negative affect (NA), some aspects of avoidant coping, and psychological distress. In addition, the relationships of all the MEAQ subscales have not been thoroughly examined with these other constructs. In the current study, the relationships of AAQ-II and MEAQ scores with NA, avoidant coping styles, and perceived stress were examined. Two-hundred undergraduates (154 females and 46 males) completed the AAQ-II and MEAQ, the Distressed Type D Personality Scale (DS-14) which includes a measure of NA, the Brief COPE which measures coping styles, and the Perceived Stress Scale. Scores on the AAQ-II had moderate positive relationships with the MEAQ total score and all MEAQ subscales with the exception of distress endurance which had a moderate negative relationship. The AAQ-II had a stronger relationship with NA, avoidant coping, and perceived stress than did the MEAQ. All MEAQ subscales had a positive relationship to NA, avoidant coping, and perceived stress with the exception of distress endurance which had a negative relationship with these constructs. While the AAQ-II is limited as a unitary measure of EA the multiple dimensions of the MEAQ may involve an extraneous factor of distress endurance. Future work should examine the relationships of the MEAQ with NA, avoidant coping and perceived stress with clinical populations.

An estimated 34 million people are living with HIV worldwide (UNAIDS, 2012), with the number of infected persons rising every year. Increases in HIV prevalence have resulted not only from new infections, but also from increases in the survival of HIV-infected persons produced by effective anti-retroviral therapies. Augmentation of anti-viral immune responses may be able to further increase the survival of HIV-infected persons. One strategy to augment these responses is to reinvigorate exhausted anti-HIV immune cells present in chronically infected persons. The PD-1-PD-L1 pathway has been implicated in the exhaustion of virus-specific T cells during chronic HIV infection. Inhibition of PD-1 signaling using blocking anti-PD-1 antibodies has been shown to reduce simian immunodeficiency virus (SIV) loads in monkeys. We now show that PD-1 blockade can improve control of HIV replication in vivo in an animal model. BLT (Bone marrow-Liver-Thymus) humanized mice chronically infected with HIV-1 were treated with an anti-PD-1 antibody over a 10-day period. The PD-1 blockade resulted in a very significant 45-fold reduction in HIV viral loads in humanized mice with high CD8(+) T cell expression of PD-1, compared to controls at 4 weeks post-treatment. The anti-PD-1 antibody treatment also resulted in a significant increase in CD8(+) T cells. PD-1 blockade did not affect T cell expression of other inhibitory receptors co-expressed with PD-1, including CD244, CD160 and LAG-3, and did not appear to affect virus-specific humoral immune responses. These data demonstrate that inhibiting PD-1 signaling can reduce HIV viral loads in vivo in the humanized BLT mouse model, suggesting that blockade of the PD-1-PD-L1 pathway may have therapeutic potential in the treatment of patients already infected with the AIDS virus.

Although you might not think it, it's hard to catch HIV. Less than 1% of unprotected sexual exposures result in infection. What then leads to transmission? Carlson et al. determined the amino acid sequence of viruses infecting 137 Zambian heterosexual couples in which one partner infected the other (see the Perspective by Joseph and Swanstrom). The authors then used statistical modeling and found that transmitted viruses are typically the most evolutionarily fit. That is, compared to other viral variants in the infected person, the transmitted virus most closely matches the most common viral sequence found in the Zambian population. Science , this issue 10.1126/science.1254031 ; see also p. 136 An analysis of discordant couples reveals that transmitted HIV-1 viruses are typically the most evolutionarily fit. [Also see Perspective by Joseph and Swanstrom ] Heterosexual transmission of HIV-1 typically results in one genetic variant establishing systemic infection. We compared, for 137 linked transmission pairs, the amino acid sequences encoded by non-envelope genes of viruses in both partners and demonstrate a selection bias for transmission of residues that are predicted to confer increased in vivo fitness on viruses in the newly infected, immunologically naïve recipient. Although tempered by transmission risk factors, such as donor viral load, genital inflammation, and recipient gender, this selection bias provides an overall transmission advantage for viral quasispecies that are dominated by viruses with high in vivo fitness. Thus, preventative or therapeutic approaches that even marginally reduce viral fitness may lower the overall transmission rates and offer long-term benefits even upon successful transmission.

The only cure of HIV has been achieved in a small number of people who received a hematopoietic stem cell transplant (HSCT) comprising allogeneic cells carrying a rare, naturally occurring, homozygous deletion in the CCR5 gene. The rarity of the mutation and the significant morbidity and mortality of such allogeneic transplants precludes widespread adoption of this HIV cure. Here, we show the application of CRISPR/Cas9 to achieve >90% CCR5 editing in human, mobilized hematopoietic stem progenitor cells (HSPC), resulting in a transplant that undergoes normal hematopoiesis, produces CCR5 null T cells, and renders xenograft mice refractory to HIV infection. Titration studies transplanting decreasing frequencies of CCR5  edited HSPCs demonstrate that <90% CCR5 editing confers decreasing protective benefit that becomes negligible between 54% and 26%. Our study demonstrates the feasibility of using CRISPR/Cas9/RNP to produce an HSPC transplant with high frequency CCR5 editing that is refractory to HIV replication. These results raise the potential of using CRISPR/Cas9 to produce a curative autologous HSCT and bring us closer to the development of a cure for HIV infection. Mutations of CCR5 have been linked to improved outcome to HIV infection. Here the authors use CRISPR-Cas9 genome editing of CCR5 in mobilized hematopoietic stem progenitor cells and show protection in a murine xenograft HIV infection model.

Objective To characterize and address the opioid crisis disproportionately impacting rural U.S. regions. Methods The Rural Opioid Initiative (ROI) is a two-phase project to collect and harmonize quantitative and qualitative data and develop tailored interventions to address rural opioid use. The baseline quantitative survey data from people who use drugs (PWUD) characterizes the current opioid epidemic (2018–2020) in eight geographically diverse regions. Results Among 3,084 PWUD, 92% reported ever injecting drugs, 86% reported using opioids (most often heroin) and 74% reported using methamphetamine to get high in the past 30 days; 53% experienced homelessness in the prior 6 months; and 49% had ever overdosed. Syringe service program use varied by region and 53% had ever received an overdose kit or naloxone prescription. Less than half (48%) ever received medication for opioid use disorder (MOUD). Conclusions The ROI combines data across eight rural regions to better understand drug use including drivers and potential interventions in rural areas with limited resources. Baseline ROI data demonstrate extensive overlap between opioid and methamphetamine use, high homelessness rates, inadequate access to MOUD, and other unmet needs among PWUD in the rural U.S. By combining data across studies, the ROI provides much greater statistical power to address research questions and better understand the syndemic of infectious diseases and drug use in rural settings including unmet treatment needs.

Hepatitis C virus (HCV) remains a public health concern in the United States, particularly in rural communities where the opioid epidemic accelerates transmission among people who use drugs (PWUD). Despite this growing burden, the genetic features and transmission dynamics of HCV in these settings are poorly understood. We analyze 692 HCV antibody-positive specimens collected from rural communities in ten U.S. states using amplicon-based deep sequencing and the Global Hepatitis Outbreak and Surveillance Technology (GHOST) platform to reconstruct transmission networks. Among sequenced individuals, 29.5% are linked within clusters. Cluster structure varies by region from sparse networks in Ohio to dense clusters in New England and phylogenetic analyses show that some networks persist for over a decade, indicating sustained transmission. Nearly half of all clusters involve individuals connected through social recruitment, suggesting peer-referral strategies effectively identify transmission chains. Penalized regression retains only a few individual factors including younger age, peer or partner recruitment, illegal income, methamphetamine use, each with modest effects. These findings suggest that clustering is shaped primarily by social and structural contexts rather than individual characteristics and underscore the importance of integrating genomic surveillance with social-network insights to detect emerging HCV clusters and guide targeted interventions in underserved rural communities. This study explores the genetic structure of hepatitis C virus outbreaks in rural U.S communities affected by the opioid crisis. Analysis of intra-host viral populations from 692 participants reveals hidden transmission networks.

The continued spread of the HIV epidemic underscores the need to interrupt transmission. One attractive strategy is a topical vaginal microbicide. Sexual transmission of herpes simplex virus type 2 (HSV-2) in mice can be inhibited by intravaginal siRNA application. To overcome the challenges of knocking down gene expression in immune cells susceptible to HIV infection, we used chimeric RNAs composed of an aptamer fused to an siRNA for targeted gene knockdown in cells bearing an aptamer-binding receptor. Here, we showed that CD4 aptamer-siRNA chimeras (CD4-AsiCs) specifically suppress gene expression in CD4⁺ T cells and macrophages in vitro, in polarized cervicovaginal tissue explants, and in the female genital tract of humanized mice. CD4-AsiCs do not activate lymphocytes or stimulate innate immunity. CD4-AsiCs that knock down HIV genes and/or CCR5 inhibited HIV infection in vitro and in tissue explants. When applied intravaginally to humanized mice, CD4-AsiCs protected against HIV vaginal transmission. Thus, CD4-AsiCs could be used as the active ingredient of a microbicide to prevent HIV sexual transmission.