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An ongoing study of mother-to-child human herpes virus-8 (HHV-8) transmission in Zambian women (n = 3160) allowed us to examine the association of medical injections with HIV serostatus while simultaneously accounting for other factors known to be correlated with HIV prevalence. Multi-method data collection included structured interviews, medical record abstraction, clinical examinations, and biological measures. Medically administered intramuscular or intravenous injections in the past five years (but not blood transfusions) were overwhelmingly correlated with HIV prevalence, exceeding the contribution of sexual behaviours in a multivariable logistic regression. Statistically significant associations with HIV also were found for some demographic variables, sexual behaviours, alcohol use, and sexually transmitted diseases (STD). The results confirmed that iatrogenic needle exposure, sexual behaviour, demographic factors, substance use, and STD history are all implicated in Zambian women's HIV+ status. However, the disproportionate association of medical injection history with HIV highlights the need to investigate further and prospectively the role of health-care injection in sub-Saharan Africa's HIV epidemic. [ABSTRACT FROM AUTHOR]

BACKGROUND: The seroprevalence of Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) in sub-Saharan Africa suggests that multiple routes of transmission exist. In the present study, we examined 2 possible routes of mother-to-child transmission, through breast milk and saliva, during the first 6 months after delivery. METHODS: The prevalence of HHV-8 DNA in the breast-milk cells (n=75), milk supernatant (n=56), colostrum (n=2), and saliva cells (n=65) of HHV-8-seropositive mothers who recently gave birth was examined. Polymerase chain reaction analysis was performed for the detection of HHV-8 in cross-sectional samples isolated at 2, 4, and 6 months after delivery. RESULTS: None of the 75 breast-milk samples but 2 of the colostrum samples that were analyzed contained HHV-8 DNA at a limit of detection of approximately 1 HHV-8 copy/10(4) cellular genomes, whereas Epstein-Barr virus DNA and HIV-1 DNA were detected in 16 and 22 samples, respectively. Analysis of 65 saliva cell samples, which were obtained from mothers who also provided milk samples, revealed that 19 of the samples had detectable HHV-8 DNA. Viral DNA was found at all time points, but the presence of viral DNA in saliva was independent of maternal HIV-1 serostatus (chi 2=0.33; P=.57). CONCLUSIONS: Our findings demonstrate the lack of HHV-8 DNA in the breast milk of seropositive mothers, and they suggest that contact with breast milk is not a likely source of horizontal transmission of virus to infants in sub-Saharan Africa. Copyright © 2004 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Given that learners do not always predict their future memory performance accurately, there is a need to better understand how metamemory accuracy can be improved. Prior research suggests that one way to improve is practice-participants tend to become better at predicting their future memory performance over the course of multi-trial learning experiments. However, it is currently unclear whether such improvements result from participants having practised making metamemory judgements or whether comparable improvements occur even in their absence. This issue was investigated in three multi-trial, cued recall experiments wherein participants either did or did not receive practice making judgements of learning. Metamemory accuracy increased across study blocks but did so equally for the two groups. These results indicate that increased metamemory accuracy with practice is not due to participants having practised explicit metamemory monitoring but instead due to other factors associated with multi-trial learning such as retrieval practice and the availability of prior test performance as a metamemory cue., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Despite a high prevalence of injection drug use (IDU) in Puerto Rico, little is known about how it affects neuropsychological functioning in this population. Investigations of intra-individual variability (IIV) have alluded to its utility as a potential indicator of neural decline. The purpose of this study was to characterize IIV among Hispanic residents of Puerto Rico who engage in IDU. Injectors and non-injectors completed the Neuropsí Atención y Memoria battery. Measures of IIV were calculated for the overall test battery (OTB), the three battery indices, and three domains of attention, memory, and executive functioning. The injector group showed significantly greater IIV than the non-injector group on all measures (OTB, indices, and individual domains). Additionally, injectors showed significantly higher IIV in the domain of executive functioning compared to other cognitive domains and battery indices. In contrast, non-injectors did not show any significant within-group differences on any IIV measures. The higher performance variability observed in the IDU group suggests a negative influence of IDU on cognition, with executive functioning being more susceptible to these effects. These findings support the need for continued investigations into the clinical application of IIV for diagnostic and prognostic purposes in the Hispanic IDU population.

Although previous studies have suggested that subtype B HIV-1 proviruses in the brain are associated with physiological changes and immune activation accompanied with microgliosis and astrogliosis, and indicated that both HIV-1 subtype variation and geographical location might influence the neuropathogenicity of HIV-1 in the brain. The natural course of neuropathogenesis of the most widespread subtype C HIV-1 has not been adequately investigated, especially for people living with HIV (PLWH) in sub-Saharan Africa. To characterize the natural neuropathology of subtype C HIV-1, postmortem frontal lobe and basal ganglia tissues were collected from nine ART-naïve individuals who died of late-stage AIDS with subtype C HIV-1 infection, and eight uninfected deceased individuals as controls. Histological staining was performed on all brain tissues to assess brain pathologies. Immunohistochemistry (IHC) against CD4, p24, Iba-1, GFAP, and CD8 in all brain tissues was conducted to evaluate potential viral production and immune activation. Histological results showed mild perivascular cuffs of lymphocytes only in a minority of the infected individuals. Viral capsid p24 protein was only detected in circulating immune cells of one infected individual, suggesting a lack of productive HIV-1 infection of the brain even at the late-stage of AIDS. Notably, similar levels of Iba-1 or GFAP between HIV + and HIV- brain tissues indicated a lack of microgliosis and astrogliosis, respectively. Similar levels of CD8 + cytotoxic T lymphocyte (CTL) infiltration between HIV + and HIV- brain tissues indicated CTL were not likely to be involved within subtype C HIV-1 infected participants of this cohort. Results from this subtype C HIV-1 study suggest that there is a lack of productive infection and limited neuropathogenesis by subtype C HIV-1 even at late-stage disease, which is in contrast to what was reported for subtype B HIV-1 by other investigators., (© 2024. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

Background: Human immunodeficiency virus 1 (HIV-1) tissue reservoirs remain the main obstacle against an HIV cure. Limited information exists regarding cannabis's effects on HIV-1 infections in vivo, and the impact of cannabis use on HIV-1 parenchymal tissue reservoirs is unexplored., Methods: To investigate whether cannabis use alters HIV-1 tissue reservoirs, we systematically collected 21 postmortem brain and peripheral tissues from 20 men with subtype C HIV-1 and with suppressed viral load enrolled in Zambia, 10 of whom tested positive for cannabis use. The tissue distribution and copies of subtype C HIV-1 LTR, gag, env DNA and RNA, and the relative mRNA levels of cytokines IL-1β, IL-6, IL-10, and TGF-β1 were quantified using PCR-based approaches. Utilizing generalized linear mixed models we compared persons with HIV-1 and suppressed viral load, with and without cannabis use., Results: The odds of tissues harboring HIV-1 DNA and the viral DNA copies in those tissues were significantly lower in persons using cannabis. Moreover, the transcription levels of proinflammatory cytokines IL-1β and IL-6 in lymphoid tissues of persons using cannabis were also significantly lower., Conclusions: Our findings suggested that cannabis use is associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs in men with suppressed viral load., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Seasonal coronaviruses (HCoVs) are known to contribute to cross-reactive antibody (Ab) responses against SARS-CoV-2. While these responses are predictable due to the high homology between SARS-CoV-2 and other CoVs, the impact of these responses on susceptibility to SARS-CoV-2 infection in cancer patients is unclear. To investigate the influence of prior HCoV infection on anti-SARS-CoV-2 Ab responses among COVID-19 asymptomatic individuals with cancer and controls without cancers, we utilized the VirScan technology in which phage immunoprecipitation and sequencing (PhIP-seq) of longitudinal plasma samples was performed to investigate high-resolution (i.e., epitope level) humoral CoV responses. Despite testing positive for anti-SARS-CoV-2 Ab in the plasma, a majority of the participants were asymptomatic for COVID-19 with no prior history of COVID-19 diagnosis. Although the magnitudes of the anti-SARS-CoV-2 Ab responses were lower in individuals with Kaposi sarcoma (KS) compared to non-KS cancer individuals and those without cancer, the HCoV Ab repertoire was similar between individuals with and without cancer independent of age, sex, HIV status, and chemotherapy. The magnitudes of the anti-spike HCoV responses showed a strong positive association with those of the anti-SARS-CoV-2 spike in cancer patients, and only a weak association in non-cancer patients, suggesting that prior infection with HCoVs might play a role in limiting SARS-CoV-2 infection and COVID-19 disease severity.

Protein-level immunodominance patterns against Kaposi sarcoma-associated herpesvirus (KSHV), the aetiologic agent of Kaposi sarcoma (KS), have been revealed from serological probing of whole protein arrays, however, the epitopes that underlie these patterns have not been defined. We recently demonstrated the utility of phage display in high-resolution linear epitope mapping of the KSHV latency-associated nuclear antigen (LANA/ORF73). Here, a VirScan phage immunoprecipitation and sequencing approach, employing a library of 1,988 KSHV proteome-derived peptides, was used to quantify the breadth and magnitude of responses of 59 sub-Saharan African KS patients and 22 KSHV-infected asymptomatic individuals (ASY), and ultimately to support an application of machine-learning-based predictive modeling using the peptide-level responses. Comparing anti-KSHV antibody repertoire revealed that magnitude, not breadth, increased in KS. The most targeted epitopes in both KS and ASY were in the immunodominant proteins, notably, K8.129-56 and ORF65140-168, in addition to LANA. Finally, using unbiased machine-learning-based predictive models, reactivity to a subset of 25 discriminative peptides was demonstrated to successfully classify KS patients from asymptomatic individuals. Our study provides the highest resolution mapping of antigenicity across the entire KSHV proteome to date, which is vital to discern mechanisms of viral pathogenesis, to define prognostic biomarkers, and to design effective vaccine and therapeutic strategies. Future studies will investigate the diagnostic, prognostic, and therapeutic potential of the 25 discriminative peptides., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bennett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pancreatic Ductal Adenocarcinoma (PDAC) is projected to become the 2nd leading cause of cancer-related deaths in the United States. Limitations in early detection and treatment barriers contribute to the lack of substantial success in the treatment of this challenging-to-treat malignancy. Desmoplasia is the hallmark of PDAC microenvironment that creates a physical and immunologic barrier. Stromal support cells and immunomodulatory cells face aberrant signaling by pancreatic cancer cells that shifts the complex balance of proper repair mechanisms into a state of dysregulation. The product of this dysregulation is the desmoplastic environment that encases the malignant cells leading to a dense, hypoxic environment that promotes further tumorigenesis, provides innate systemic resistance, and suppresses anti-tumor immune invasion. This desmoplastic environment combined with the immunoregulatory events that allow it to persist serve as the primary focus of this review. The physical barrier and immune counterbalance in the tumor microenvironment (TME) make PDAC an immunologically cold tumor. To convert PDAC into an immunologically hot tumor, tumor microenvironment could be considered alongside the tumor cells. We discuss the complex network of microenvironment molecular and cellular composition and explore how they can be targeted to overcome immuno-therapeutic challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hartupee, Nagalo, Chabu, Tesfay, Coleman-Barnett, West and Moaven.)

Pancreatic cancers are the third leading cause of cancer-related death in the USA and outcomes remain poor despite improvements in imaging and treatment paradigms. Currently, computed tomography (CT) and magnetic resonance imaging (MRI) are frequently utilized for staging and restaging of these malignancies, but positron emission tomography (PET)/CT can play a role in troubleshooting and improve whole-body staging. PET/MRI is a novel imaging modality that allows for simultaneous acquisition of PET and MRI images, leading to improved image quality and potential increased sensitivity. Early studies suggest that PET/MRI may play a larger role in pancreatic cancer imaging in future. This manuscript will briefly discuss current imaging approaches to pancreatic cancer and outline existing evidence and published data supporting the use of PET/MRI for pancreatic cancers., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Research has found substantial negative effects of divided attention (DA) during encoding but less substantial effects when attention is divided during retrieval, an asymmetry which has been interpreted as indicating that different control processes or forms of attention are involved in encoding and retrieval (e.g., Chun & Johnson, 2011; Craik, Govoni, Naveh-Benjamin, & Anderson, 1996; Long, Kuhl, & Chun, 2018). The extant evidence, however, is not strong support for qualitative differences and might simply indicate differential sensitivity. The present experiments document a stronger, double dissociation by focusing on the Attentional Boost Effect (ABE) - a phenomenon in which the detection of targets in a secondary task enhances encoding of co-occurring stimuli. The dual-task interaction account proposes that the classical negative effects produced by dual-task interference are offset by a transient increase in externally-directed attention brought about by target detection. Since externally-directed attention is less valuable for retrieval processes, the ABE should result in a net negative effect when applied in the test phase because the dual-task interference would no longer be offset by the externally-directed boost occurring during target trials. Experiments 1, 2 and 4 confirmed the predictions by showing that test words paired with target stimuli were recognized significantly worse than test words paired with distractor stimuli. In contrast, Experiments 3 and 4 replicated the usual positive effects of the ABE with respect to encoding. We discuss these findings in light of recent theoretical proposals suggesting that encoding and retrieval processes are subserved by different forms of attention (external [perceptual] vs. internal [reflective]). Implications for the Transfer-Appropriate-Processing view of memory are also illustrated., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. Indeed, KSHV infection of primary human endothelial cell cultures, even at high levels, is rarely associated with long-term culture, transformation, or growth deregulation, yet infection in vivo is sustained for life. Investigations of immune mediators that distinguish KSHV infection, KSHV/HIV co-infection, and symptomatic KS disease have yet to reveal consistent correlates of protection against or progression to KS. In addition to viral infection, it is plausible that pathogenesis also requires an immunological and metabolic environment permissive to the abnormal endothelial cell growth evident in KS tumors. In this study, we explored whether plasma metabolomes could differentiate asymptomatic KSHV-infected individuals with or without HIV co-infection and symptomatic KS from each other., Methods: To investigate how metabolic changes may correlate with co-infections and tumorigenesis, plasma samples derived from KSHV seropositive sub-Saharan African subjects in three groups, (A) asymptomatic (lacking neoplastic disease) with KSHV infection only, (B) asymptomatic co-infected with KSHV and HIV, and (C) symptomatic with clinically diagnosed KS, were subjected to analysis of lipid and polar metabolite profiles RESULTS: Polar and nonpolar plasma metabolic differentials were evident in both comparisons. Integration of the metabolic findings with our previously reported KS transcriptomics data suggests dysregulation of amino acid/urea cycle and purine metabolic pathways, in concert with viral infection in KS disease progression., Conclusions: This study is, to our knowledge, the first to report human plasma metabolic differentials between in vivo KSHV infection and co-infection with HIV, as well as differentials between co-infection and epidemic KS., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Radiology has recognized the need to increase the diversity of its workforce for decades; however, women and people of color remain disproportionately underrepresented. A welcoming and inclusive environment is essential to physician recruitment and retention, but disruptive behavior in the workplace can be a barrier to achieving this goal. Disruptive behavior can be overt or subtle, can be intentional or inadvertent, and can occur in different settings throughout a radiologist's career, including during patient care, among colleagues, from department leadership, and even from professional societies. The purpose of this article is to provide an overview of where a radiologist may encounter disruptive behaviors, the impact that such behaviors can have on the physician's and practice's well-being, and tips for how to address and mitigate these behaviors in the future.

Antiretroviral therapy has been effective in suppressing HIV viral load and enabling people living with HIV to experience longer, more conventional lives. However, as people living with HIV are living longer, they are developing aging-related diseases prematurely and are more susceptible to comorbidities that have been linked to chronic inflammation. Coincident with HIV infection and aging, drug abuse has also been independently associated with gut dysbiosis, microbial translocation, and inflammation. Here, we hypothesized that injection drug use would exacerbate HIV-induced immune activation and inflammation, thereby intensifying immune dysfunction. We recruited 50 individuals not using injection drugs (36/50 HIV+) and 47 people who inject drugs (PWID, 12/47 HIV+). All but 3 of the HIV+ subjects were on antiretroviral therapy. Plasma immune profiles were characterized by immunoproteomics, and cellular immunophenotypes were assessed using mass cytometry. The immune profiles of HIV+/PWID-, HIV-/PWID+, and HIV+/PWID+ were each significantly different from controls; however, few differences between these groups were detected, and only 3 inflammatory mediators and 2 immune cell populations demonstrated a combinatorial effect of injection drug use and HIV infection. In conclusion, a comprehensive analysis of inflammatory mediators and cell immunophenotypes revealed remarkably similar patterns of immune dysfunction in HIV-infected individuals and in people who inject drugs with and without HIV-1 infection., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Yes-associated protein-1 (YAP-1) is a Hippo system transcription factor, which serves as an oncogene in squamous cell carcinoma, and several solid tumors when the Hippo pathway is dysregulated. Yet, the activity of YAP-1 in ocular surface squamous neoplasia (OSSN) has not been determined. Here, we investigate the relationship between YAP-1 overexpression and OSSN. Using a cross-sectional study design, we recruited 227 OSSN patients from the University Teaching Hospitals in Lusaka, Zambia. Immunohistochemistry was used to assess YAP-1 protein overexpression in tumor tissue relative to surrounding benign squamous epithelium. OSSN patient samples (preinvasive, n = 62, 27% and invasive, n = 165, 73%) were studied. One hundred forty-nine invasive tumors contained adjacent preinvasive tissue, bringing the total number of preinvasive lesions examined to 211 (62 + 149). There was adjacent benign squamous epithelium in 50.2% (114/227) of OSSN samples. Nuclear YAP- 1 was significantly overexpressed in preinvasive (Fisher's (F): p <.0001, Monte Carlo (MC): p <.0001) and invasive (F: p <.0001, MC: p <.0001) OSSN in comparison to adjacent benign squamous epithelium when analyzed for basal keratinocyte positive count, staining intensity, expression pattern, and Immunostaining intensity-distribution index. YAP-1 expression did not differ between preinvasive and invasive OSSN (p >.05), keratinizing and non- keratinizing cancer (p >.05), or between T1/T2 and T3/T4 stages in invasive tumors (p >.05). However, grade 2 and 3 tumors had significantly stronger nucleus YAP-1 overexpression intensity than grade 1 tumors (F: p = .0078, MC: p = .0489). By immunohistochemistry, we identified significant overexpression (upregulation of YAP-1 protein expression) in preinvasive and invasive OSSN lesions compared to neighboring benign squamous epithelium. YAP-1 expression was significantly higher in poorly and moderately differentiated invasive squamous cancer than in well-differentiated carcinomas. Overexpression of YAP-1 within the margin of preinvasive and invasive OSSN, but not in the neighboring normal epithelium, indicates that it plays a role in the development and progression of OSSN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Julius, Siyumbwa, Maate, Moonga, Kang, Kaile, West, Wood and Angeletti.)

Kaposi's Sarcoma (KS) is a heterogenous, multifocal vascular malignancy caused by the human herpesvirus 8 (HHV8), also known as Kaposi's Sarcoma-Associated Herpesvirus (KSHV). Here, we show that KS lesions express iNOS/NOS2 broadly throughout KS lesions, with enrichment in LANA positive spindle cells. The iNOS byproduct 3-nitrotyrosine is also enriched in LANA positive tumor cells and colocalizes with a fraction of LANA-nuclear bodies. We show that iNOS is highly expressed in the L1T3/mSLK tumor model of KS. iNOS expression correlated with KSHV lytic cycle gene expression, which was elevated in late-stage tumors (>4 weeks) but to a lesser degree in early stage (1 week) xenografts. Further, we show that L1T3/mSLK tumor growth is sensitive to an inhibitor of nitric oxide, L-NMMA. L-NMMA treatment reduced KSHV gene expression and perturbed cellular gene pathways relating to oxidative phosphorylation and mitochondrial dysfunction. These finding suggest that iNOS is expressed in KSHV infected endothelial-transformed tumor cells in KS, that iNOS expression depends on tumor microenvironment stress conditions, and that iNOS enzymatic activity contributes to KS tumor growth., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paul M. Lieberman is a founder and advisor to Vironika, LLC., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Tissue changes and the enlargement of the prostate, whether benign or malignant, are among the most common groups of diseases that affect men and can have significant impacts on length and quality of life. The prevalence of benign prostatic hyperplasia (BPH) increases significantly with age and affects nearly all men as they grow older. Other than skin cancers, prostate cancer is the most common cancer among men in the United States. Imaging is an essential component in the diagnosis and management of these conditions. Multiple modalities are available for prostate imaging, including several novel imaging modalities that have changed the landscape of prostate imaging in recent years. This review will cover the data relating to commonly used standard-of-care prostate imaging modalities, advances in newer technologies, and newer standards that impact prostate gland imaging.

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection against SARS-CoV-2 and its emerging variants with varying degrees of efficacy. Amino acid changes, primarily in the receptor-binding domain (RBD), result in selection for viral infectivity, disease severity, and immune evasion. Therefore, many studies have centered around neutralizing antibodies that target the RBD and their generation achieved through infection or vaccination. Here, we conducted a unique longitudinal study, analyzing the effects of a three-dose mRNA vaccine regimen exclusively using the monovalent BNT162b2 (Pfizer/BioNTech) vaccine, systematically administered to nine previously uninfected (naïve) individuals. We compare changes in humoral antibody responses across the entire SARS-CoV-2 spike glycoprotein (S) using a high-throughput phage display technique (VirScan). Our data demonstrate that two doses of vaccination alone can achieve the broadest and highest magnitudes of anti-S response. Moreover, we present evidence of novel highly boosted non-RBD epitopes that strongly correlate with neutralization and recapitulate independent findings. These vaccine-boosted epitopes could facilitate multi-valent vaccine development and drug discovery.

HIV-associated epidemic Kaposi sarcoma (EpKS) remains one of the most prevalent cancers in sub-Saharan Africa despite the widespread uptake of anti-retroviral therapy and HIV-1 suppression. In an effort to define potential therapeutic targets against KS tumors, we analyzed previously published KS bulk tumor transcriptomics to identify cell surface biomarkers. In addition to upregulated gene expression (>6-fold) in the EpKS tumor microenvironment, biomarkers were selected for correlation with KSHV latency-associated nuclear antigen (LANA) expression. The cell surface glycoprotein genes identified were KDR, FLT4, ADAM12, UNC5A, ZP2, and OX40, as well as the endothelial lineage determinants Prox-1 and CD34. Each protein was evaluated for its expression and co-localization with KSHV LANA using multi-color immunofluorescence in KS tissues, KSHV-infected L1T2 cells, uninfected TIVE cells, and murine L1T2 tumor xenografts. Five surface glycoproteins (KDR, FLT4, UNC5A, ADAM12, and CD34) were associated with LANA-positive cells but were also detected in uninfected cells in the KS microenvironment. In vitro L1T2 cultures showed evidence of only FLT4, KDR, and UNC5A, whereas mouse L1T2 xenografts recapitulated human KS cell surface expression profiles, with the exception of CD34 and Prox-1. In KS tumors, most LANA-positive cells co-expressed markers of vascular as well as lymphatic endothelial lineages, suggesting KS-associated dedifferentiation to a more mesenchymal/progenitor phenotype.

The humoral antibody response against Kaposi sarcoma-associated herpesvirus (KSHV) in infected individuals has been characterized demonstrating the latency-associated nuclear antigen (LANA) as the most antigenic KSHV protein. Despite the antigenicity of the protein, specific LANA epitopes have not been systematically characterized. Here, we utilized a bacteriophage T7 library, which displays 56-amino acid KSHV LANA peptides with 28-amino acid overlap (VirScan), to define those epitopes in LANA targeted by antibodies from a cohort of 62 sub-Saharan African Kaposi sarcoma (KS) patients and 22 KSHV-infected asymptomatic controls. Intra- and inter-patient breadth and magnitude of the anti-LANA responses were quantified at the peptide and amino acid levels. From these data, we derived a detailed epitope annotation of the entire LANA protein, with a high-resolution focus on the N- and C-termini. Overall, the central repeat region was highly antigenic, but the responses to this region could not be confidently mapped due to its high variability. The highly conserved N-terminus was targeted with low breadth and magnitude. In a minority of individuals, antibodies specific to the nuclear localization sequence and a portion of the proline-rich regions of the N-terminus were evident. In contrast, the first half of the conserved C-terminal domain was consistently targeted with high magnitude. Unfortunately, this region was not included in LANA partial C-terminal crystal structures, however, it was predicted to adopt predominantly random-coil structure. Coupled with functional and secondary structure domain predictions, VirScan revealed fine resolution epitope mapping of the N- and C-terminal domains of LANA that is consistent with previous antigenicity studies and may prove useful to correlate KSHV humoral immunity with pathogenesis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Bennett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Memory retrieval affects subsequent memory in ways both positive (e.g., the testing effect) and negative (e.g., retrieval-induced forgetting, RIF). The changes to memory that retrieval produces can be thought of as the encoding consequences of retrieval, examined here with respect to attention. In three experiments, participants first studied category-example word pairs, and then practiced retrieval for half the pairs from one-third of the categories (the R + items) and restudied half the pairs from a different third of the categories (the S + items), while the final third of the categories were in the nonpracticed control condition (the Np items). This was followed in turn by a final test over all categories and examples, including the unpracticed examples from the retrieval-practice and restudied categories (the R- and S- items, respectively). The middle phase (of retrieval practice and restudy) was conducted under full attention (FA) or under divided attention (DA) in which participants also performed a distracting secondary task. DA had little effect on final recall in the retrieval practice (R +) condition but significantly reduced final recall of the restudied (S +) items, producing a net increase in the testing effect relative to the FA condition. RIF (measured as the difference between the R- and Np items) was substantial in the FA condition but was eliminated by DA. This occurred because the final recall of R- items significantly increased in the DA compared to FA condition, a highly unusual result in which distraction actually improved an aspect of memory performance. In sum, DA during retrieval practice dissociated the positive and negative effects of retrieval on subsequent memory, increasing the positive effect, embodied by the testing effect, but decreasing the negative effect, embodied by RIF. The theoretical implications are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Subtype B HIV-1 reservoirs have been intensively investigated, but reservoirs in other subtypes and how they respond to antiretroviral therapy (ART) is substantially less established. To characterize subtype C HIV-1 reservoirs, we implemented postmortem frozen, as well as formalin fixed paraffin embedded (FFPE) tissue sampling of central nervous system (CNS) and peripheral tissues. HIV-1 LTR, gag, envelope (env) DNA and RNA was quantified using genomic DNA and RNA extracted from frozen tissues. RNAscope was used to localize subtype C HIV-1 DNA and RNA in FFPE tissue. Despite uniform viral load suppression in our cohort, PCR results showed that subtype C HIV-1 proviral copies vary both in magnitude and tissue distribution, with detection primarily in secondary lymphoid tissues. Interestingly, the appendix harbored proviruses in all subjects. Unlike subtype B, subtype C provirus was rarely detectable in the CNS, and there was no detectable HIV-1 RNA. HIV-1 RNA was detected in peripheral lymphoid tissues of 6 out of 8 ART-suppressed cases. In addition to active HIV-1 expression in lymphoid tissues, RNAscope revealed HIV RNA detection in CD4-expressing cells in the appendix, suggesting that this tissue was a previously unreported potential treatment-resistant reservoir for subtype C HIV-1.

Background: Respondent Driven Sampling (RDS) is an effective sampling strategy to recruit hard-to-reach populations but the impact of the COVID-19 pandemic on the use of this strategy in the collection of data involving human subjects, particularly among marginalized and vulnerable populations, is not known. Based on an ongoing study using RDS to recruit and study the interactions between HIV infection, injection drug use, and the microbiome in Puerto Rico, this paper explores the effectiveness of RDS during the pandemic and provided potential strategies that could improve recruitment and data collection., Results: RDS was employed to evaluate its effectiveness in recruiting a group of people who inject drugs (PWID) and controls ( N = 127) into a study in the midst of the COVID-19 pandemic. The participants were distributed among three subsets: 15 were HIV+ and PWID, 58 were HIV- PWID, and 54 were HIV+ and not PWID., Findings: Results show that recruitment through peer networks using RDS was possible across all sub-groups. Yet, while those in the HIV+ PWID sub-group managed to recruit from other-sub groups of HIV- PWID and HIV+, this occurred at a lower frequency., Conclusion: Despite the barriers introduced by COVID-19, it is clear that even in this environment, RDS continues to play a powerful role in recruiting hard-to-reach populations. Yet, more attention should be paid at how future pandemics, natural disasters, and other big events might affect RDS recruitment of vulnerable and hard-to-reach populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abadie, Habecker, Carrasco, Chiou, Fernando, Bennett, Valentin-Acevedo, Dombrowski, West and Wood.)

Oligometastatic prostate cancer has traditionally been defined in the literature as a limited number of metastatic lesions (either to soft tissue or bone), typically based on findings seen on CT, MRI, and skeletal scintigraphy. Although definitions have varied among research studies, many important clinical trials have documented effective treatments and prognostication in patients with oligometastatic prostate cancer. In current clinical practice, prostate-specific membrane antigen (PSMA)-PET/CT is increasingly utilized for the initial staging of high-risk patients and, in many cases, detecting metastases that would have otherwise been undetected with conventional staging imaging. Thus, patients with presumed localized and/or oligometastatic prostate cancer undergo stage migration based on more novel molecular imaging. As a result, it is challenging to apply the data from the era before widespread PET utilization to current clinical practice and to relate current trials using PSMA-PET/CT for disease detection to older studies using conventional staging imaging alone. This manuscript aims to review the definition of oligometastatic prostate cancer, summarize important studies utilizing both PSMA-PET/CT and conventional anatomic imaging, discuss the concept of stage migration, and discuss current problems and challenges with the current definition of oligometastatic disease.

Molecular imaging of prostate cancer continues to grow, with recent inclusion of several positron emission tomography (PET) radiotracers into the recent National Comprehensive Cancer Network guidelines and the US Food and Drug Administration approval of prostate-specific membrane antigen (PSMA)-targeted radiotracers. While much of the work for many of these radiotracers is focused on systemic staging and restaging in both newly diagnosed high-risk prostate cancer and biochemically recurrent disease patients, the potential role of molecular imaging for the detection of localized prostate cancer has not yet been fully established. The primary aim of this article will be to present the potential role for molecular imaging in the detection of localized prostate cancer and discuss potential advantages and disadvantages to utilization of both PET/computed tomography (CT) and PET/magnetic resonance imaging (MRI) for this clinical indication of use., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Soroush Rais-Bahrami – consultant, Blue Earth Diagnostics Samuel Galgano – research support, Blue Earth Diagnostics and research support, Novartis., (© The Author(s), 2022.)

Background: The etiopathogenesis of ocular surface squamous neoplasia (OSSN) is not fully understood. We assessed the frequency of oncogenic viruses in OSSN by immunohistochemistry (IHC) and polymerase chain reaction (PCR) for human papillomavirus (HPV), Epstein-Barr virus (EBV), Merkel cell polyomavirus (MCPyV), Kaposi sarcoma virus, and adenovirus. Cases from Zambia were prospectively enrolled using a cross-sectional study design between November 2017 and March 2020., Methods: Demographic and clinical data [age, sex, HIV status, antiretroviral therapy (ART) history, CD4 count, plasma viral load] and tumor biopsies were collected from 243 consenting patients. Tumor samples were bisected, and half was used for DNA isolation, while the other half was formalin fixed and paraffin embedded (FFPE) for histopathology analysis. The expressions of latent EBV nuclear antigen 1 (EBNA1), CDKN2A/p16INK4A (p16), and MCPyV large T-antigen (LT) were tested by IHC. Multiplex PCR was used to detect 16 HPV genotypes and four other DNA tumor viruses [Kaposi's sarcoma-associated herpesvirus (KSHV), EBV, MCPyV, and adenovirus]. Relationships between HIV status, viral DNA and protein expression, and tumor grades were determined by statistical analysis., Results: OSSN tumors from patients were 29.6% preinvasive and 70.4% invasive. Patients presented with unilateral tumors that were 70.4% late stage (T3/T4). OSSN patients were HIV positive (72.8%). IHC on 243 FFPE biopsies resulted in the detection of EBNA1 (EBV), p16 high-risk HPV (HR-HPV), and MCPyV LT expression in 89.0%, 4.9%, and 0.0%, respectively. EBNA1 was expressed in all grades of preinvasive [cornea-conjunctiva intraepithelial neoplasia (CIN)1, 100%; CIN2, 85.7%; CIN3, 95.8%; and carcinoma in situ (CIS), 83.8%] and in invasive (89.2%) OSSN. PCR on 178 samples detected EBV, HR-HPV, and MCPyV in 80.3%, 9.0%, and 13.5% of tumors, respectively. EBV was detected in all grades of preinvasive and invasive OSSN. EBV detection was associated with high HIV viral loads (p = 0.022). HR-HPV was detected in 0.0% CIN1, 0.0% CIN2, 5.6% CIN3, 13.0% CIS, and 7.0% invasive OSSN., Conclusions: Our findings of EBV DNA and EBNA1 protein in all the grades of preinvasive and especially invasive OSSN are consistent with a potential causal role for EBV in OSSN. A role of HPV in OSSN was not clearly established in this study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Julius, Siyumbwa, Moonga, Maate, Kaile, Haynatski, Minhas, Snow, Peterson, Gihozo, Streeter, Kaur, Evans, Gonzalez, Samwel, Kang, West, Wood and Angeletti.)

Although relatively rare in the United States, penile squamous cell carcinoma is encountered worldwide at a higher rate. Initial diagnosis is often made on clinical exam, as almost all of these lesions are externally visible and amenable to biopsy. In distinction to other types of malignancies, penile cancer relies heavily on clinical nodal staging of the inguinal lymph node chains. As with all cancers, imaging plays a role in the initial staging, restaging, and surveillance of these patients. The aim of this manuscript is to highlight the applications, advantages, and limitations of different imaging modalities in the evaluation of penile cancer, including ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography.

Infection with HIV-1 remains uncurable due to reservoirs of latently infected cells. Any potential cure for HIV will require a mechanism to identify and target these cells in vivo. We created a panel of Jurkat cell lines latently infected with the HIV DuoFlo virus to identify candidate biomarkers of latency. SWATH mass spectrometry was used to compare the membrane proteomes of one of the cell lines to parental Jurkat cells. Several candidate proteins with significantly altered expression were identified. The differential expression of several candidates was validated in multiple latently infected cell lines. Three factors (LAG-3, CD147,CD231) were altered across numerous cell lines, but the expression of most candidate biomarkers was variable. These results confirm that phenotypic differences in latently infected cells exists and identify additional novel biomarkers. The variable expression of biomarkers across different cell clones suggests universal antigen-based detection of latently infected cells may require a multiplex approach., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Research has demonstrated that people remember emotional information better than neutral information. However, such research has almost exclusively defined emotion in terms of valence and arousal. Discrete emotions may affect memory above and beyond such dimensions, with recent research indicating that disgusting information is better remembered than frightening information. We initially sought to determine whether participants are sensitive to the effects of discrete emotions when predicting their future memory performance. Participants in Experiment 1 were more confident in their memory for emotional (both frightening and disgusting) images relative to neutral images, but confidence did not differ between frightening and disgusting images. However, because we did not replicate the mnemonic advantage of disgust, subsequent experiments were concerned with testing the replicability of this effect. Because metamemorial judgments sometimes eliminate memory effects, participants in Experiment 2 did not make such judgments. Even so, the effect did not replicate. The disgust advantage was ultimately replicated in Experiment 3, where participants completed a secondary task at encoding. The disgust advantage is replicable but appears less robust than previously recognised. A single-paper meta-analysis indicated that the effect is more likely under divided attention, perhaps because the mechanisms which mediate disgust-memory are relatively automatic.

Kaposi's sarcoma (KS) is an AIDS-defining malignancy that can improve or worsen with antiretroviral therapy (ART). We aimed at identifying clinical, HIV-related, and sociodemographic factors associated with either progression or nonprogression (regression or stable disease) of ART-treated HIV-associated KS in patients with limited cutaneous disease. We conducted a prospective cohort study of ART-treated HIV-associated KS cases. Clinical, HIV-related, and sociodemographic variables were collected at baseline, and patients were followed up to determine treatment outcomes. Cox regression, linear mixed effects model, and Spearman's rank correlation were used for analysis. Half (50%) of the study participants had KS regression or stable disease, whereas the other half (50%) had disease progression during the treatment and follow-up period. Among the data analyzed, presence of KS nodules at baseline (hazard ratio = 5.47; 95% confidence interval = 1.32-22.65; p  = .02) was an independent predictor of poor treatment outcome. Progressors and nonprogressors were indistinguishable in the changes they experienced in the HIV plasma viral load and CD4 counts as a result of ART. Even when cutaneous presentation is limited, the presence of nodular morphotype KS lesions should be considered an indicator for combined ART plus chemotherapy. Temporal trends in CD4 counts and HIV viral loads did not correlate with treatment outcome in ART-treated HIV-associated KS.

Background: Neutralizing-antibody (nAb) is the major focus of most ongoing COVID-19 vaccine trials. However, nAb response against SARS-CoV-2, when present, decays rapidly. Given the myriad roles of antibodies in immune responses, it is possible that antibodies could also mediate protection against SARS-CoV-2 via effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), which we sought to explore here., Methods: Plasma of 3 uninfected controls and 20 subjects exposed to, or recovering from, SARS-CoV-2 infection were collected from U.S. and sub-Saharan Africa. Immunofluorescence assay was used to detect the presence of SARS-CoV-2 specific IgG antibodies in the plasma samples. SARS-CoV-2 specific neutralizing capability of these plasmas was assessed with SARS-CoV-2 spike pseudotyped virus. ADCC activity was assessed with a calcein release assay., Results: SARS-CoV-2 specific IgG antibodies were detected in all COVID-19 subjects studied. All but three COVID-19 subjects contained nAb at high potency (>80% neutralization). Plasma from 19/20 of COVID-19 subjects also demonstrated strong ADCC activity against SARS-CoV-2 spike glycoprotein, including two individuals without nAb against SARS-CoV-2., Conclusion: Both neutralizing and non-neutralizing COVID-19 plasmas can mediate ADCC. Our findings argue that evaluation of potential vaccines against SARS-CoV-2 should include investigation of the magnitude and durability of ADCC, in addition to nAb., Competing Interests: The authors have declared that no competing interests exist.

Aim: This study aimed to characterize the clinical and pathologic presentation of ocular surface tumors (OSTs) and to more precisely differentiate the grades of ocular surface squamous neoplasia (OSSN) and benign lesions among Zambians., Methods: Two-hundred sixty-five Zambian patients presenting with ocular surface growths, suspicious for OSSN, were recruited between November 2017 and November 2019 to a cross-sectional study to investigate their lesions. Sociodemographic data were collected, HIV infection status and vision tests were performed, and lesions were measured and documented. Lesions >2 mm in diameter were excised and sent for pathology analysis. In addition to the biopsies, tears, blood, and buccal swabs were collected. CD4+ T-cell counts were measured by flow cytometry. Lesions were classified according to the WHO guidelines. χ 2 and bivariate correlations were used to analyze variable associations and strengths with phi/Cramer's V and correlation coefficients, respectively. Binary logistics was used to adjust for covariance., Results: In this study, 68.3% of the participants were found to be HIV positive. The most frequent diagnoses were invasive OSSN (45.3%), preinvasive OSSN (29.1%), and pterygium (22.6%). Invasive OSSN comprised keratinizing squamous cell carcinoma (SCC) (87.5%), basaloid SCC (3.3%), and spindle cell carcinoma (3.3%). Unusual carcinomas, not described previously, included hybrid SCC (5.0%) and acantholytic SCC (0.8%). Invasive OSSN had advanced tumor (T3/T4) staging (93.3%) at diagnosis. Lymphadenopathy was rare (2.3%), and metastasis was absent. Patients were mostly female (59.2%). Median age was 36 (interquartile ranges 33-41) years (ranges 18-81). Patients with invasive OSSN were more likely to present with pain ( p = 0.007), redness ( p = 0.034), excessive tearing ( p = 0.0001), discharge ( p = 0.011), bleeding ( p = 0.007), reduced vision ( p = 0.0001), fungating lesion ( p = 0.001), and blindness ( p = 0.005); location at temporal limbus ( p = 0.0001), inferior limbus ( p = 0.0001), or circumlimbal ( p = 0.001); and extension to cornea ( p = 0.006) and forniceal palpebral conjunctiva ( p = 0.001). Invasive OSSN was associated with any smoking habit and alcohol consumption ( p = 0.04 and 0.03, respectively). HIV positivity was strongly associated with OSSN (74.6% OSSN vs. 49.3% benign lesions; p = 0.0001; phi: 0.237 [ p = 0.0001])., Conclusion: OSTs are very common in Zambia and are strongly associated with HIV coinfection. Patients with OSSN were more likely to be HIV positive than those with pterygia. Despite the commonality of OSTs in sub-Saharan Africa, these cancers have historically been poorly characterized., Competing Interests: The authors have no competing interests., (Copyright © 2021 by S. Karger AG, Basel.)

Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA., Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by immunofluorescence assay against the spike and nucleocapsid proteins of all known human coronaviruses (HCoVs)., Results: The prevalence of SARS-CoV-2 serological cross-reactivity was significantly higher in samples from SSA compared with the USA. Most of these cross-reactive samples cross-recognized the SARS-CoV-2 nucleocapsid protein and the spike proteins of other HCoVs. Nucleocapsid proteins from HCoV-NL63 and HCoV-229E were detected in most samples, thereby implicating prior exposure to these two HCoVs as the likely source of cross-reactive antibodies against SARS-CoV-2., Conclusion: The low incidences of SARS-CoV-2 infection and disease in SSA appear to be correlated with the pre-pandemic serological cross-recognition of HCoVs, which are substantially more prevalent in SSA than the USA., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Although the immune response is likely to play a pivotal role in controlling Kaposi sarcoma (KS)-associated herpesvirus (KSHV) and preventing disease development, the exact factors responsible for that control remain ill defined. T cell responses are weak and variable, and neutralizing Abs are more frequently detected in individuals with KS. This suggests a potential role for nonneutralizing Abs, which to date have been largely uninvestigated. Ab-dependent cell cytotoxicity (ADCC) is a common effector function for nonneutralizing Abs and is known to play a protective role in other herpesvirus infections; yet, ADCC has never been investigated in the context of KSHV infection. In this study, we provide, to our knowledge, the first evidence that anti-KSHV Abs are capable of mediating ADCC responses against infected human cells undergoing lytic reactivation. ADCC activity significantly higher than seronegative controls was detected in 24 of 68 KSHV-seropositive individuals tested. However, ADCC responses were not associated with KS development or progression. ADCC activity was also found to be independent of HIV status, sex, age, KSHV Ab titer, and KSHV-neutralizing activity. Nevertheless, additional investigations into effector cell function between KS and asymptomatic individuals are needed to determine whether ADCC has a role in preventing KS., (Copyright © 2020 by The American Association of Immunologists, Inc.)

While mother-to-child transmission is believed to play in important role in early childhood infection with Kaposi sarcoma-associated herpesvirus (KSHV), the maternal immune response remains largely uncharacterized. This study aimed to characterize the longitudinal humoral response to KSHV in a cohort of HIV-infected Zambian mothers without KS and identify potential factors that may influence transmission. In total, 86/124 (69.4%) mothers were found to be KSHV seropositive. Longitudinal KSHV titers were fairly stable over time, although seroreversion was still common. Of the total 124 mothers, 81 had at least 1 child KSHV seroconvert during the 2 years analyzed, while the remaining 43 mothers had KSHV-seronegative children. Mothers of KSHV-negative children had higher geometric mean titers than mothers of KSHV-positive children; however, there was no difference in the presence of neutralizing antibodies. This suggests that a strong anti-KSHV immune response, and potentially nonneutralizing antibodies, may reduce transmission., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective(s): To elucidate relationships in antiretroviral resistance between HIV-1-infected mother-infant pairs by defining the resistance profiles in the mothers and infants and quantifying drug resistance prevalence in the pairs post-Option B+ implementation., Design: Collection of dried blood spots from mother-infant pairs during routine HIV-1 screens in Lusaka, Zambia from 2015 to 2018., Methods: DNA was extracted from the dried blood spots, the HIV-1 pol region was amplified, and the purified proviral DNA was sequenced using Sanger sequencing. Drug resistance mutations (DRM) were identified in sequenced DNA using the Stanford HIVdb (https://hivdb.stanford.edu/)., Results: DRM were detected in 45% (44/97) of samples, and these samples were found to harbor resistance to at least two antiretrovirals. The prevalence of nonnucleoside reverse transcriptase inhibitor resistance was significantly higher than that of other antiretroviral classes. DRM were detected disproportionately in infants (67%; 33/49) compared with mothers (23%; 11/48), but the magnitude of resistance did not differ when resistance was detected. The disparity in drug resistance profiles was reinforced in pairwise comparison of resistance profiles in mother-infant pairs., Conclusion: While Option B+ is effective in reducing mother-to-child transmission, in cases where this regimen fails, high-level nonnucleoside reverse transcriptase inhibitor resistance is frequently detected in infants. This underscores the importance of pretreatment drug resistance screening in both mothers and infants and emphasizes the necessary change to protease inhibitor-based and integrase inhibitor-based regimens for treatment of HIV-1-infected infants and mothers.

West, JT, Miller, WM, Jeon, S, and Ye, X. The effects of a preconditioning rolling session on subsequent eccentric exercise-induced muscle damage. J Strength Cond Res 34(8): 2112-2119, 2020-The aim of this study was to examine the effects of a preexercise unilateral quadriceps muscle rolling intervention on subsequent ipsilateral (IPSI) or contralateral (CTRA) knee extension eccentric exercise-induced muscle damage. Twenty-seven healthy volunteers (14 men) underwent an eccentric exercise protocol (6 sets of 10 repetitions with 75% of the maximal isometric strength) with a single-leg knee extension machine. Before the eccentric exercise, the subjects were randomly assigned to either (a) IPSI group: rolling the ipsilateral knee extensor muscles, (b) CTRA: rolling the contralateral muscles, or (c) Control: sitting for 6 minutes (same duration as the rolling intervention protocol) relaxed. The muscle soreness, passive knee extension range of motion, and knee extension isometric strength were measured before, immediately, 24 hours, and 48 hours after exercise. The magnitudes of the range of motion decrement were attenuated in both the IPSI (p = 0.031) and CTRA (p = 0.014) groups 24 hours after the eccentric exercise, when compared with the control. Isometric strength (p = 0.783) and muscle soreness (p = 0.586) responses were not significantly different among the 3 groups (time points and sexes merged). Additionally, women displayed an overall faster recovery than men in isometric strength (p = 0.001) and muscle soreness (p = 0.024), evidenced by the measurements at 48 hours after exercise. Our study suggests that unilateral quadriceps rolling intervention before high-intensity muscle-damaging exercise has a beneficial effect on maintaining range of motion in both the ipsilateral and contralateral muscles.

In sub-Saharan Africa, endemic Kaposi's sarcoma (EnKS) is still prevalent despite high incidence of epidemic Kaposi's sarcoma (EpKS) resulting from the on-going HIV-1 epidemic. While KSHV is clearly the etiologic agent of KS, the mechanisms underlying KS development are not fully understood. For example, HIV-1 co-infection and concomitant immune dysfunction have been associated with EpKS development. However, the direct or indirect role(s) of HIV-1, and therefore of immune suppression, in EpKS remains unclear. How, or whether, EpKS is mechanistically distinct from EnKS is unknown. Thus, the absence of HIV-1 co-infection in EnKS provides a unique control for investigating and deciphering whether HIV-1 plays a direct or indirect role in the EpKS tumor microenvironment. We hypothesized that HIV-1 co-infection would induce transcriptome changes that differentiate EpKS from EnKS, thereby defining the direct intra-tumor role of HIV-1 in KS. Comparison of ART-treated and -naïve patients would further define the impact of ART on the KS transcriptome. We utilized RNA-seq followed by multiparameter bioinformatics analysis to compare transcriptomes from KS lesions to uninvolved control skin. We provide the first transcriptomic comparison of EpKS versus EnKS, ART-treated vs-naïve EpKS and male vs female EpKS to define the roles of HIV-1 co-infection, the impact of ART, and gender on KS gene expression profiles. Our findings suggest that ART-use and gender have minimal impact on transcriptome profiles of KS lesions. Gene expression profiles strongly correlated between EpKS and EnKS patients (Spearman r = 0.83, p<10-10). A subset of genes involved in tumorigenesis and inflammation/immune responses showed higher magnitude, but not unique dysregulation in EnKS compared to EpKS. While gender and ART had no detectable contribution, the trend toward higher magnitude of gene dysregulation in EnKS coupled with the absence of HIV-1 transcripts in EpKS may suggest an indirect or systemic effect of HIV-1 to promote KS tumorigenesis., Competing Interests: The authors have declared that no competing interests exists.

The testing effect is 1 of several memory effects moderated by experimental design, such that the effect on free recall is larger in a mixed-list than pure-list design (Mulligan, Susser, & Smith, 2016). The current experiments assess hypotheses regarding why this pattern is found. Three extant accounts of design effects (Nguyen & McDaniel, 2015) are the item-order account, the retrieval-distinctiveness account, and the rehearsal-borrowing account. Three experiments contrasted these accounts, finding support for rehearsal borrowing but no evidence for the rehearsal-distinctiveness or item-order accounts. In addition, each experiment found that the testing effect was larger in the mixed-list than pure-list condition, attesting to the replicability of the design-moderation pattern for the testing effect. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Kaposi's sarcoma-associated herpes virus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS). The prognostic utility of KSHV and HIV-1 (human immunodeficiency virus) viremia as well as immunological parameters in clinical management of participants with KS is unclear. The objective of this study was to investigate viral and immunological parameters as predictors of KS treatment responses in participants with KS from sub-Saharan Africa (SSA). Plasma KSHV-DNA, HIV-1 viral load, total anti-KSHV antibody, KSHV-neutralizing antibody (nAb), cytokine/chemokine levels, and T-cell differentiation subsets were quantified before and after KS treatment in 13 participants with KS and in 13 KSHV-infected asymptomatic control individuals. One-way analysis of variance and the Mann-Whitney t-test were used to assess differences between groups where p -values <0.05 were considered significant. Subjects with patch and plaque KS lesions responded more favorably to treatment than those with nodular lesions. Pre-treatment and post-treatment levels of plasma KSHV-DNA, HIV-1 viral load, KSHV-Ab responses, cytokines, and T-cell populations did not predict the KS treatment response. Elevated KSHV-humoral and cytokine responses persisted in participants with KS despite a clinical KS response. While patch and plaque KS lesions were more common among treatment responders, none of the analyzed viral and immunological parameters distinguished responders from non-responders at baseline or after treatment.

Objective: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent for Kaposi's sarcoma (KS), one of the most common cancers in Tanzania. We have investigated KSHV prevalence and factors associated with KSHV infection in Tanzania., Methods: This is a cross-sectional study of voluntary blood-donors from Dar es Salaam, Tanzania. Plasma was screened for KSHV, HIV-1, HBV, HCV and Treponema pallidum (syphilis). Associations between KSHV sero-status and risk factors were analyzed. Odds ratios (OR) and 95% confidence intervals (CI) are reported to evaluate risk factors of KSHV infection. All tests were 2-tailed, and P-values <0.05 were considered statistically significant., Results: The overall KSHV seroprevalence was 56.9%. Significantly increased risk of KSHV infection was detected in persons from the Lake and Central Zones (OR=6.4, 95% CI=1.6-25.3, P=0.008 and OR=5.7, 95% CI=1.0-32.5, P=0.048 respectively). A trend toward increased risk of KSHV infection with HIV-1 co-infection was not significant (OR=2.8, 95% CI=1.0-8.0, P=0.06). Seroreactivity to T. pallidum was surprisingly high (14.9%)., Conclusion: The prevalence of KSHV infection and syphilis was high among Tanzanian blood-donors. The most common transfusion-transmissible infections did not associate with KSHV infection. Regions of focal KSHV infection need further investigation for underappreciated risk factors., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Tanzania faces one of the highest cervical cancer burdens in the world. Recent work has suggested that the bacterial family Mycoplasmataceae is associated with higher levels of human papillomavirus (HPV), human immunodeficiency virus (HIV), and pre-cancerous cervical lesions. Mycoplasmataceae infection in Tanzania is not well understood, especially when considering the differences between sexually transmitted species of Mycoplasmataceae . To establish the prevalence of common Mycoplasmataceae cervical infections and evaluate their relationship with risk factors for cervical cancer, 1160 Tanzanian women responded to an epidemiological questionnaire and were tested for HIV, HPV, cervical lesions, Mycoplasma genitalium , Mycoplasma hominis , Ureaplasma spp., and Lactobacillus iners . A subset of 134 women were used for 16s metagenomic sequencing of cervical DNA to establish the relative abundance of Mycoplasmataceae and Lactobacillus present. PCR detection of bacteria at the cervix found Ureaplasma spp. in 51.4% of women, M. hominis in 34%, M. genitalium in 2.3%, and L. iners in 75.6%. M. hominis and M. genitalium infection were significantly more prevalent among women with HPV and HIV. M. hominis prevalence was similar despite severity of cervical lesions; however, abundance of M. hominis increased significantly in women with cervical lesions. These results emphasize the importance of understanding the relationship between M. hominis and HPV-related cervical pathogenesis.

Despite the close association between Kaposi's sarcoma (KS) and immune dysfunction, it remains unclear whether tumor infiltrating immune cells (TIIC), by their absence, presence, or dysfunction, are mechanistically correlated with KS pathogenesis. Therefore, their potential capacity to serve as prognostic biomarkers of KS disease progression or control is unclear. Because epidemic-KS (EpKS) occurs with HIV-1 co-infection, it is particularly important to compare TIIC between EpKS and HIV-negative African endemic-KS (EnKS) to dissect the roles of HIV-1 and Kaposi Sarcoma-associated herpesvirus (KSHV) in KS pathogenesis. This cross-sectional study of 13 advanced KS (4 EnKS, 9 EpKS) patients and 3 healthy controls utilized single-color immunohistochemistry and dual-color immunofluorescence assays to characterize and quantify KSHV infected cells in relation to various TIIC in KS biopsies. Analysis of variance (ANOVA) and Mann-Whitney tests were used to assess differences between groups where P -values < 0.05 were considered significant. The abundance of KSHV infected cells was heterogeneous in KS biopsies. Despite the presence of T-cell chemoattractant chemokine CxCL-9 in biopsies, CD8 + T-cells were sparsely distributed in regions with evident KSHV infected cells but were readily detectable in regions devoid of KSHV infected cells ( P < 0.0001). CD68 + (M1) macrophages were evenly and diffusely distributed in KS biopsies, whereas, the majority of CD163 + (M2) macrophages were localized in regions devoid of KSHV infected cells ( P < 0.0001). Overall, the poor immune cell infiltration or co-localization in KS biopsies independent of HIV-1 co-infection suggests a fundamental tumor immune evasion mechanism that warrants further investigation., Competing Interests: CONFLICTS OF INTEREST The funders played no role in design of the study, the collection, analysis or interpretation of the data, the writing of the manuscript or the decision to submit the manuscript for publication. We declare that we have no conflict of interest.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), one of the most prevalent cancers of people living with HIV/AIDS in sub-Saharan Africa. The seroprevalence for KSHV is high in the region, and no prophylactic vaccine against the virus is available. In this study, we characterized the antigenic targets of KSHV-specific neutralizing antibodies (nAbs) in asymptomatic KSHV-infected individuals and KS patients with high nAbs titers. We quantified the extent to which various KSHV envelope glycoproteins (gB, ORF28, ORF68, gH, gL, gM, gN and gpK8.1) adsorbed/removed KSHV-specific nAbs from the plasma of infected individuals. Our study revealed that plasma from a majority of KSHV neutralizers recognizes multiple viral glycoproteins. Moreover, the breadth of nAbs responses against these viral glycoproteins varies among endemic KS, epidemic KS and asymptomatic KSHV-infected individuals. Importantly, among the KSHV glycoproteins, the gH/gL complex, but neither gH nor gL alone, showed the highest adsorption of KSHV-specific nAbs. This activity was detected in 80% of the KSHV-infected individuals regardless of their KS status. The findings suggest that the gH/gL complex is the predominant antigenic determinant of KSHV-specific nAbs. Therefore, gH/gL is a potential target for development of KSHV prophylactic vaccines.

Despite ongoing efforts, sub-Saharan Africa faces a higher cervical cancer burden than anywhere else in the world. Besides HPV infection, definitive factors of cervical cancer are still unclear. Particular states of the cervicovaginal microbiota and viral infections are associated with increased cervical cancer risk. Notably, HIV infection, which is prevalent in sub-Saharan Africa, greatly increases risk of cervicovaginal dysbiosis and cervical cancer. To better understand and address cervical cancer in sub-Saharan Africa, a better knowledge of the regional cervicovaginal microbiome is required This review establishes current knowledge of HPV, HIV, cervicovaginal infections, and the cervicovaginal microbiota in sub-Saharan Africa. Because population statistics are not available for the region, estimates are derived from smaller cohort studies. Microbiota associated with cervical inflammation have been found to be especially prevalent in sub-Saharan Africa, and to associate with increased cervical cancer risk. In addition to high prevalence and diversity of HIV and HPV, intracellular bacterial infections such as Chlamydia, Gonorrhea, and Mycoplasma hominis are much more common than in regions with a low burden of cervical cancer. This suggests the prevalence of cervical cancer in sub-Saharan Africa may be partially attributed to increased cervical inflammation resulting from higher likelihood of cervical infection and/or microbial dysbiosis., (Copyright © 2020 Klein, Kahesa, Mwaiselage, West, Wood and Angeletti.)

The majority of research on metamemory focuses on retrospective memory: memory for past events. Prospective memory, in contrast, refers to the process of remembering to carry out intentions in the future. Despite claims that metacognition is essential to prospective remembering, it is unclear whether the metamemorial effects that researchers have observed in studies of retrospective memory extend to prospective memory. In the present study, we tested whether the underconfidence with practice (UWP) effect, the finding that in multitrial learning situations, participants become relatively underconfident following retrieval practice, would generalize to a prospective memory paradigm. Participants memorized target-response word pairs and were told that during an upcoming lexical-decision task (the ongoing task), the targets would appear and, should they recognize any of these targets, they were to notify the experimenter and attempt to recall the associated response. Participants then predicted their ability to recognize each target and recall each response. Participants predicted their memory and completed the ongoing task three times. In Experiment 1, we observed preliminary evidence for UWP for the prospective component (recognizing the targets) but no UWP for the retrospective component (recalling the responses). However, after changing the way JOLs were elicited to be more consistent with past studies of UWP (i.e., cueing them with the target instead of the target-response word pair), we observed UWP for both prospective and retrospective memory in Experiments 2 and 3. The present results suggest that, as with retrospective memory, participants become relatively underconfident in their prospective memory following practice. (PsycINFO Database Record (c) 2019 APA, all rights reserved).