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OBJECTIVES: Migration is associated with increased risk of HIV infection in Africa, but evidence about non-HIV sexually transmitted infection (STI) burden among African migrants is limited. METHODS: We used data from the Sexually Transmitted Infection Prevalence Study, a cross-sectional population-based study of chlamydia, gonorrhoea, trichomoniasis, syphilis and herpes simplex virus type 2 prevalence in southern Uganda, to compare STI prevalence between adults aged 18 and 49 years with and without a recent history of migration. Migration status was determined using household census data, with a recent migration history defined as having moved into one's community of current residence within the last ~18 months. Unadjusted and adjusted modified Poisson regression models were used to compare individual STI prevalence risk by recent migration status with associations reported as adjusted prevalence risk ratios (adjPRRs) with 95% CIs. Adjusted models included participants' sex, age, community type, education, occupation and marital status. RESULTS: Among 1825 participants, 358 (19.6%) had a recent migration history. Overall, migrants exhibited a significantly higher combined prevalence of curable STIs (gonorrhoea, chlamydia, high-titre syphilis (rapid plasma regain ≥1:8) and trichomoniasis) as compared with long-term residents (34.4% vs 24.2%; adjPRR=1.23; 95% CI 1.03 to 1.47). Significant differences in curable STI prevalence by migration status were concentrated among persons living with HIV (49.4% prevalence in migrants vs 32.6% in long-term residents; adjPRR=1.42; 95% CI 1.10 to 1.85) and among women (38.8% in migrants vs 27.8% in long-term residents; adjPRR=1.26; 95% CI 1.01 to 1.58). High-titre syphilis prevalence was especially elevated among male migrants (11.2% in migrants vs 4.9% in long-term residents; adjPRR=1.82; 95% CI 1.06 to 3.13). CONCLUSIONS: The prevalence of non-HIV STIs is higher among migrants. Tailored outreach and service delivery approaches that address the needs of mobile populations are crucial for integrated HIV and STI epidemic control in Uganda to optimise resources and reduce transmission risks.
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OBJECTIVE: Voluntary medical male circumcision (MC) is a critical tool in combination HIV prevention programmes in Africa. Self-reported MC (SrMC) status is used in HIV epidemiological surveys to assess MC coverage but is subject to response bias with limited validation. This study evaluated the utility of SrMC status as a marker of MC as well as self-reported genital lesions for genital ulcer disease (GUD) among Ugandan men. METHODS: Male participants aged 18-49 years in the cross-sectional Sexually Transmitted Infection Prevalence study, conducted between May and October 2019, responded to a questionnaire capturing SrMC status and current genital ulcer symptoms followed by clinical assessment to verify MC and presence of GUD.Sensitivity, specificity, positive predictive value, negative predictive value and corresponding CIs (95% CI) for SrMC status and GUD were estimated. RESULTS: There were 853 male participants, of whom 470 (55.1%) self-reported being circumcised and 23 (2.7%) self-reported GUD (SrGUD). MC was clinically confirmed in 50.2% (n=428) of participants with sensitivity of SrMC status at 99% (95% CI: 98% to 100%) and specificity 89% (95% CI: 86% to 92%). Specificity of SrMC was lowest among persons living with HIV and viremic (>1000 copies/mL) at 72% (95% CI: 46% to 90%). 18 participants had clinically confirmed GUD, but only 12 SrGUD symptoms, corresponding to a sensitivity and specificity of 67% (95% CI: 41% to 87%) and 99% (95% CI: 98% to 99%), respectively. CONCLUSIONS: SrMC status is a robust proxy for clinically confirmed MC status and may reliably be used to assess MC coverage in this setting. Conversely, GUD symptoms were under-reported, which may impact effective syndromic management of sexually transmitted infections and warrants further examination.
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Background: Thirty-day hospital readmission measures quality of care, but there are limited data among people with HIV (PWH) and people without HIV (PWoH) in the era of universal recommendation for antiretroviral therapy. We descriptively compared 30-day all-cause, unplanned readmission risk between PWH and PWoH. Methods: A retrospective cohort study was conducted using the 2019 Nationwide Readmissions Database (2019/01/01-2019/12/31), an all-payer database that represents all US hospitalizations. Index (initial) admissions and readmissions were determined using US Centers for Medicare & Medicaid Services definitions. Crude and age-adjusted risk ratios (aRR) comparing the 30-day all-cause, unplanned readmission risk between PWH to PWoH were estimated using random effect logistic regressions and predicted marginal estimates. Survey weights were applied to all analyses. Findings: We included 24,338,782 index admissions from 18,240,176 individuals. The median age was 52(IQR = 40-60) years for PWH and 61(IQR = 38-74) years for PWoH. The readmission risk was 20.9% for PWH and 12.2% for PWoH (age-adjusted-RR:1.88 [95%CI = 1.84-1.92]). Stratified by age and sex, young female (age 18-29 and 30-39 years) PWH had a higher readmission risk than young female PWoH (aRR = 3.50 [95%CI = 3.11-3.88] and aRR = 4.00 [95%CI = 3.67-4.32], respectively). While the readmission risk increased with age among PWoH, the readmission risk was persistently high across all age groups among PWH. The readmission risk exceeded 30% for PWH admitted for hypertensive heart disease, heart failure, and chronic kidney disease. Interpretation: PWH have a disproportionately higher risk of readmission than PWoH, which is concerning given the aging profile of PWH. More efforts are needed to address readmissions among PWH. Funding: US National Institutes of Health.
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The primary obstacle to curing HIV-1 is a reservoir of CD4+ cells that contain stably integrated provirus. Previous studies characterizing the proviral landscape, which have been predominantly conducted in males in the United States and Europe living with HIV-1 subtype B, have revealed that most proviruses that persist during antiretroviral therapy (ART) are defective. In contrast, less is known about proviral landscapes in females with non-B subtypes, which represents the largest group of individuals living with HIV-1. Here, we analyze genomic DNA from resting CD4+ T-cells from 16 female and seven male Ugandans with HIV-1 receiving suppressive ART (n = 23). We perform near-full-length proviral sequencing at limiting dilution to examine the proviral genetic landscape, yielding 607 HIV-1 subtype A1, D, and recombinant proviral sequences (mean 26/person). We observe that intact genomes are relatively rare and clonal expansion occurs in both intact and defective genomes. Our modification of the primers and probes of the Intact Proviral DNA Assay (IPDA), developed for subtype B, rescues intact provirus detection in Ugandan samples for which the original IPDA fails. This work will facilitate research on HIV-1 persistence and cure strategies in Africa, where the burden of HIV-1 is heaviest.
Subject(s)
CD4-Positive T-Lymphocytes , Genome, Viral , HIV Infections , HIV-1 , Proviruses , Humans , HIV-1/genetics , HIV-1/drug effects , HIV-1/classification , Proviruses/genetics , HIV Infections/drug therapy , HIV Infections/virology , Male , Female , Genome, Viral/genetics , CD4-Positive T-Lymphocytes/virology , Adult , DNA, Viral/genetics , Uganda , Viral Load , Anti-HIV Agents/therapeutic useABSTRACT
Objectives: Public sharing of de-identified biomedical data promotes collaboration between researchers and accelerates the development of disease prevention and treatment strategies. However, open-access data sharing presents challenges to researchers who need to protect the privacy of study participants, ensure that data are used appropriately, and acknowledge the inputs of all involved researchers. This article presents an approach to data sharing which addresses the above challenges by using a publicly available dashboard with de-identified, aggregated participant data from a large HIV surveillance cohort. Materials and Methods: Data in this study originated from the Rakai Community Cohort Study (RCCS), which was integrated into a centralized data mart as part of a larger data management strategy for the Rakai Health Sciences Program in Uganda. These data were used to build a publicly available, protected health information (PHI)-secured visualization dashboard for general research use. Results: Using two unique case studies, we demonstrate the capability of the dashboard to generate the following hypotheses: firstly, that HIV prevention strategies ART and circumcision have differing levels of impact depending on the marital status of investigated communities; secondly, that ART is very successful in comparison to circumcision as an interventional strategy in certain communities. Discussion: The democratization of large-scale anonymized epidemiological data using public-facing dashboards has multiple benefits, including facilitated exploration of research data and increased reproducibility of research findings. Conclusion: By allowing the public to explore data in depth and form new hypotheses, public-facing dashboard platforms have significant potential to generate new relationships and collaborations and further scientific discovery and reproducibility.
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PURPOSE: The purpose of our study was to evaluate the association of baseline MRI Prostate Imaging Reporting and Data System (PI-RADS) score with biopsy reclassification in a multicenter active surveillance (AS) cohort. MATERIALS AND METHODS: We identified men in the Michigan Urological Surgery Improvement Collaborative registry (46 hospital-based/academic/private practice urology groups) with National Comprehensive Cancer Network (NCCN) low-risk and favorable intermediate-risk prostate cancer who underwent MRI within 6 months before or after initial biopsy and enrolled in AS from June 2016 to January 2021. The primary objective was to determine the association of baseline MRI PI-RADS score (≥4 lesion) with reclassification to high-grade prostate cancer (≥grade group 3) on surveillance biopsy. Multivariable Cox proportional hazards regression models were constructed and adjusted for pathologic, MRI, and clinical/biopsy factors, with landmark time of 6 months from diagnostic biopsy. We included an interaction term between PI-RADS score and NCCN group in the Cox model. RESULTS: A total of 1491 men were included with median age 64 years (IQR: 59-69) with median follow-up 11.0 months (IQR: 6.0-23.0) after landmark. Baseline PI-RADS ≥ 4 lesion was associated with an increased hazard of biopsy reclassification (HR: 2.3 [95% CI: 1.6-3.2], P < .001), along with grade group 2 vs 1 (HR: 2.5 [95% CI: 1.7-3.7], P < .001), and increasing age (per 10 years; HR: 1.8 [95% CI: 1.4-2.4], P < .001). The interaction between NCCN risk group with MRI findings was not significant (P = .7). CONCLUSIONS: In this multicenter cohort study of real-world data, baseline MRI PI-RADS score was significantly associated with early biopsy reclassification in men undergoing AS with NCCN low- or favorable intermediate-risk prostate cancer.
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BACKGROUND: Various strategies have been used to reduce pedicle screw loosening following lumbar instrumented fusion, but all strategies have limitations. In this prospective multicenter cohort study, outcomes of elderly patients with reduced bone density who underwent primary or revision fusion surgery using a novel technique of pedicle screw augmentation with demineralized bone fiber (DBF) anchors were evaluated. METHODS: This study included elderly patients (aged >65 years) with dual-energy x-ray absorptiometry-confirmed reduced bone density who required lumbar pedicle screw fixation and were treated with supplemental DBF allograft anchors during primary or revision surgery. The need for DBF anchors was determined by evaluating preoperative computed tomography (CT) scans (for revision surgery) and by the surgeons' tactile feedback intraoperatively during pedicle screw insertion and removal. After determining the pedicle screw void diameter with a sizing instrument, DBF anchors and pedicle screws of the same diameter were placed into the void. CT scans were obtained on postoperative day 2 to assess pedicle breach, pedicle fracture, or anchor material extrusion and at 6 and 12 months postoperatively to assess screw loosening. Thereafter, to minimize radiation exposure, CT scans were only performed for recurrence of pain. RESULTS: Twenty-three patients (79% women; mean age, 74 years) received 50 lumbosacral pedicle screws augmented with DBF anchors. Most surgeries (n = 18, 78%) were revisions, and most anchors were inserted into revision pedicle screw trajectories (n = 33, 66%). Day-2 CT scans revealed no pedicle breach/fracture or extrusion of anchor material. During a mean follow-up of 15 months (12-20 months), no screw loosening was detected, and no patient required pedicle screw revision surgery. There were no adverse events attributable to DBF allografts. CONCLUSIONS: DBF allograft anchors appear to be safe and effective for augmenting pedicle screws during revision surgeries in female elderly patients with reduced bone density. CLINICAL RELEVANCE: Clinically, DBF reduced the rate of pedicle screw loosening in patients with reduced bone density. A significant reduction in screw loosening can decrease the need for revision surgeries, which are costly and carry additional risks. Enhanced bone integration from the DBF may promote better healing and long-term stability.
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Introduction: To prioritize and tailor interventions for ending AIDS by 2030 in Africa, it is important to characterize the population groups in which HIV viraemia is concentrating. Methods: We analysed HIV testing and viral load data collected between 2013-2019 from the open, population-based Rakai Community Cohort Study (RCCS) in Uganda, to estimate HIV seroprevalence and population viral suppression over time by gender, one-year age bands and residence in inland and fishing communities. All estimates were standardized to the underlying source population using census data. We then assessed 95-95-95 targets in their ability to identify the populations in which viraemia concentrates. Results: Following the implementation of Universal Test and Treat, the proportion of individuals with viraemia decreased from 4.9% (4.6%-5.3%) in 2013 to 1.9% (1.7%-2.2%) in 2019 in inland communities and from 19.1% (18.0%-20.4%) in 2013 to 4.7% (4.0%-5.5%) in 2019 in fishing communities. Viraemia did not concentrate in the age and gender groups furthest from achieving 95-95-95 targets. Instead, in both inland and fishing communities, women aged 25-29 and men aged 30-34 were the 5-year age groups that contributed most to population-level viraemia in 2019, despite these groups being close to or had already achieved 95-95-95 targets. Conclusions: The 95-95-95 targets provide a useful benchmark for monitoring progress towards HIV epidemic control, but do not contextualize underlying population structures and so may direct interventions towards groups that represent a marginal fraction of the population with viraemia.
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Background: Syphilis diagnosis in the emergency department (ED) setting is often missed due to the lack of ED-specific testing strategies. We characterized ED patients with high-titer syphilis infections (HTSIs) with the goal of defining a screening strategy that most parsimoniously identifies undiagnosed, untreated syphilis infections. Methods: Unlinked, de-identified remnant serum samples from patients attending an urban ED, between 10 January and 9 February 2022, were tested using a three-tier testing algorithm, and sociodemographic variables were extracted from ED administrative database prior to testing. Patients who tested positive for treponemal antibodies in the first tier and positive at high titer (≥1:8) for nontreponemal antibodies in the second tier were classified as HTSI. Human immunodeficiency virus (HIV) status was determined with Bio-Rad enzyme-linked immunosorbent assay and confirmatory assays. Exact logistic regression and classification and regression tree (CART) analyses were performed to determine factors associated with HTSI and derive screening strategies. Results: Among 1951 unique patients tested, 23 (1.2% [95% confidence interval, .8%-1.8%]) had HTSI. Of those, 18 (78%) lacked a primary care physician, 5 (22%) were HIV positive, and 8 (35%) were women of reproductive age (18-49 years). CART analysis (area under the curve of 0.67) showed that using a screening strategy that measured syphilis antibodies in patients with HIV, without a primary care physician, and women of reproductive age would have identified most patients with HTSI (21/23 [91%]). Conclusions: We show a high prevalence of HTSI in an urban ED and propose a feasible, novel screening strategy to curtail community transmission and prevent long-term complications.
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Timing of HIV-1 reservoir formation is important for informing HIV cure efforts. It is unclear how much of the variability seen in dating reservoir formation is due to sampling and gene-specific differences. We used a Bayesian extension of root to tip regression (bayroot) to re-estimate formation date distributions in participants from Swedish and South African cohorts, and assessed the impact of variable timing, frequency, and depth of sampling on these estimates. Significant shifts in formation date distributions were only observed with use of faster-evolving genes, while timing, frequency, and depth of sampling had minor or no significant effect on estimates.
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Cell density, the ratio of cell mass to volume, is an indicator of molecular crowding and therefore a fundamental determinant of cell state and function. However, existing density measurements lack the precision or throughput to quantify subtle differences in cell states, particularly in primary samples. Here we present an approach for measuring the density of 30,000 single cells per hour with a precision of 0.03% (0.0003 g/mL) by integrating fluorescence exclusion microscopy with a suspended microchannel resonator. Applying this approach to human lymphocytes, we discovered that cell density and its variation decrease as cells transition from quiescence to a proliferative state, suggesting that the level of molecular crowding decreases and becomes more regulated upon entry into the cell cycle. Using a pancreatic cancer patient-derived xenograft model, we found that the ex vivo density response of primary tumor cells to drug treatment can predict in vivo tumor growth response. Our method reveals unexpected behavior in molecular crowding during cell state transitions and suggests density as a new biomarker for functional precision medicine.
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Sculpins (coastrange and slimy) and sticklebacks (ninespine and threespine) are widely distributed fishes cohabiting 2 south-central Alaskan lakes (Aleknagik and Iliamna), and all these species are parasitized by cryptic diphyllobothriidean cestodes in the genus Schistocephalus. The goal of this investigation was to test for host-specific parasitic relationships between sculpins and sticklebacks based upon morphological traits (segment counts) and sequence variation across the NADH1 gene. A total of 446 plerocercoids was examined. Large, significant differences in mean segment counts were found between cestodes in sculpin (mean = 112; standard deviation [s.d.] = 15) and stickleback (mean = 86; s.d. = 9) hosts within and between lakes. Nucleotide sequence divergence between parasites from sculpin and stickleback hosts was 20.5%, and Bayesian phylogenetic analysis recovered 2 well-supported clades of cestodes reflecting intermediate host family (i.e. sculpin, Cottidae vs stickleback, Gasterosteidae). Our findings point to the presence of a distinct lineage of cryptic Schistocephalus in sculpins from Aleknagik and Iliamna lakes that warrants further investigation to determine appropriate evolutionary and taxonomic recognition.
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Background: Empirical data on transportation access and HIV treatment outcomes in sub-Saharan Africa are rare. We assessed the association between household transport ownership and HIV viral suppression in rural Uganda. Methods: The study was conducted among people living with HIV aged 15-49 years using cross-sectional data from the Rakai Community Cohort Study (RCCS), collected from June 14, 2018, to November 6, 2020. Transport ownership was defined as household possession of a car, motorcycle, or bicycle. HIV viral suppression was defined as < 1000 HIV RNA copies/ml. Poisson regression with robust variance estimation identified unadjusted and adjusted prevalence ratios and 95% confidence intervals (CI) of HIV viral suppression by transport ownership. Results: The study included 3,060 persons aged 15-49 living with HIV. Overall HIV viral suppression was 86.5% and was higher among women compared to men (89.3% versus 81.6%; adjusted prevalence ratio: 1.14, 95% CI: 1.10, 1.18). A total of 874 participants (28.6%) resided in households that owned at least one means of transport. HIV viral suppression was 79.8% among men and 88.2% among women from households without any means of transport, compared to 85.4% among men and 92.4% among women from households with at least one means of transport. Adjusted prevalence ratios of HIV viral suppression were 1.11 (95% CI: 1.04, 1.18) for males and 1.06 (95% CI: 1.03, 1.10) for females from households owning at least one means of transport compared with those from households with none. Conclusion: There was increased HIV viral suppression among people living with HIV from households with transport means compared to those from households without transport means, suggesting transport may facilitate access to, and continued engagement with, HIV treatment services.
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HIV incidence has been declining in Africa with scale-up of HIV interventions. However, there is limited data on HIV evolutionary trends in African populations with waning epidemics. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a twenty-five-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from persons living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994 to 2018) and four hyperendemic Lake Victoria fishing communities (2011 to 2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was estimated using the Shannon diversity index and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Evolutionary dynamics were assessed among demographic and behavioral sub-groups, including by migration status. 9,931 HIV sequences were available from 4,999 PLHIV, including 3,060 and 1,939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (p<0.001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (p<0.001). The proportion of viruses classified as recombinants significantly increased by more than four-fold. Inter-subtype HIV diversity has generally increased. While p24 intra-subtype genetic diversity and divergence leveled off after 2014, diversity and divergence of gp41 increased through 2017. Inter- and intra-subtype viral diversity increased across all population sub-groups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics in declining African HIV epidemics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development.
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BACKGROUND: The principal barrier to an HIV cure is the presence of the latent viral reservoir (LVR), which has been understudied in African populations. From 2018 to 2019, Uganda instituted a nationwide rollout of ART consisting of Dolutegravir (DTG) with two NRTI, which replaced the previous regimen of one NNRTI and the same two NRTI. METHODS: Changes in the inducible replication-competent LVR (RC-LVR) of ART-suppressed Ugandans with HIV (n = 88) from 2015 to 2020 were examined using the quantitative viral outgrowth assay. Outgrowth viruses were examined for viral evolution. Changes in the RC-LVR were analyzed using three versions of a Bayesian model that estimated the decay rate over time as a single, linear rate (model A), or allowing for a change at time of DTG initiation (model B&C). FINDINGS: Model A estimated the slope of RC-LVR change as a non-significant positive increase, which was due to a temporary spike in the RC-LVR that occurred 0-12 months post-DTG initiation (p < 0.005). This was confirmed with models B and C; for instance, model B estimated a significant decay pre-DTG initiation with a half-life of 6.9 years, and an â¼1.7-fold increase in the size of the RC-LVR post-DTG initiation. There was no evidence of viral failure or consistent evolution in the cohort. INTERPRETATION: These data suggest that the change from NNRTI- to DTG-based ART is associated with a significant temporary increase in the circulating RC-LVR. FUNDING: Supported by the NIH (grant 1-UM1AI164565); Gilead HIV Cure Grants Program (90072171); Canadian Institutes of Health Research (PJT-155990); and Ontario Genomics-Canadian Statistical Sciences Institute.
Subject(s)
East African People , HIV Infections , HIV Integrase Inhibitors , HIV-1 , Humans , Anti-Retroviral Agents/therapeutic use , Bayes Theorem , CD4-Positive T-Lymphocytes , HIV Infections/drug therapy , HIV Integrase Inhibitors/pharmacology , HIV Integrase Inhibitors/therapeutic use , Viral Load , Virus LatencyABSTRACT
To date, an affordable, effective treatment for an HIV-1 cure remains only a concept with most "latency reversal" agents (LRAs) lacking specificity for the latent HIV-1 reservoir and failing in early clinical trials. We assessed HIV-1 latency reversal using a multivalent HIV-1-derived virus-like particle (HLP) to treat samples from 32 people living with HIV-1 (PLWH) in Uganda, US and Canada who initiated combined antiretroviral therapy (cART) during chronic infection. Even after 5-20 years on stable cART, HLP could target CD4+ T cells harbouring latent HIV-1 reservoir resulting in 100-fold more HIV-1 release into culture supernatant than by common recall antigens, and 1000-fold more than by chemotherapeutic LRAs. HLP induced release of a divergent and replication-competent HIV-1 population from PLWH on cART. These findings suggest HLP provides a targeted approach to reactivate the majority of latent HIV-1 proviruses among individuals infected with HIV-1.
Subject(s)
HIV Infections , HIV-1 , Humans , Virus Latency , CD4-Positive T-Lymphocytes , CanadaABSTRACT
Pacific salmon (Oncorhynchus spp.) hatch and feed in freshwater habitats, migrate to sea to mature, and return to spawn at natal sites. The final, riverine stages of the return migrations are mediated by chemical properties of the natal stream that they learned as juveniles. Like some other fish, salmon growth is asymptotic; they grow continuously throughout life toward a maximum size. The continued growth of the nervous system may be plastic in response to environmental variables. Due to the ecological, cultural, and economic importance of Pacific salmon, individuals are often reared in hatcheries and released into the wild as juveniles to supplement natural populations. However, hatchery-reared individuals display lower survivorship and may also stray (i.e., spawn in a non-natal stream) at higher rates than their wild counterparts. Hatchery environments may lack stimuli needed to promote normal development of the nervous system, thus leading to behavioral deficits and a higher incidence of straying. This study compared the peripheral olfactory system and brain organization of hatchery-reared and wild-origin sockeye salmon fry (Oncorhynchus nerka). Surface area of the olfactory rosette, diameter of the olfactory nerve, total brain size, and size of major brain regions were measured from histological sections and compared between wild and hatchery-origin individuals. Hatchery-origin fish had significantly larger optic tecta, and marginally insignificant, yet noteworthy trends, existed in the valvula cerebelli (hatchery > wild) and olfactory bulbs (hatchery < wild). We also found a putative difference in olfactory nerve diameter (dmin) (hatchery > wild), but the validity of this finding needs further analyses with higher resolution methods. Overall, these results provide insight into the potential effects of hatchery rearing on nervous system development in salmonids, and may explain behavioral deficits displayed by hatchery-origin individuals post-release.
Subject(s)
Brain , Salmon , Animals , Salmon/physiology , Salmon/growth & development , Salmon/anatomy & histology , Brain/physiology , Brain/growth & development , Environment , Aquaculture , FisheriesABSTRACT
Collision tumors are rare neoplasms displaying two distinct cell populations developing in juxtaposition to one another without areas of intermingling. There are currently no guidelines for the recommended treatment for such rare collision cases. We herein report a unique case of a 45-year-old female who presented with a left-sided palpable inguinal lymph node. A subsequent excisional biopsy yielded a diagnosis of collision lymphoma (CL) of nodular sclerosing Hodgkin lymphoma (HL) and germinal center diffuse large B-cell lymphoma (DLBCL). This case report highlights the challenges in managing CL and the potential efficacy of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab regimen (R-CHOP) and adjuvant radiation therapy (RT) in treating this rare condition. Our goal is to enrich the literature with our case on CL in an attempt to progress to a path of ultimately establishing a definitive treatment approach to CL of DLBCL and HL.
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INTRODUCTION: Population-level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale-up. METHODS: In 2015-2020, we measured VLS (<200 RNA copies/ml) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/ml) or high-level (≥1000 copies/ml) viraemia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e. visit-pairs; â¼18-month visit intervals) and classified as durable VLS (<200 copies/ml at both visits), new/renewed VLS (<200 copies/ml at follow-up only), viral rebound (<200 copies/ml at initial visit only) or persistent viraemia (≥200 copies/ml at both visits). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viraemia were also assessed using multivariable Poisson regression with generalized estimating equations. RESULTS: Overall, 3080 participants contributed 4604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n = 1083), 46.9% remained viraemic through follow-up, 91.3% of which was high-level viraemia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viraemia self-reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high-level viraemia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (vs. 40- to 49-year-olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21-3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10-1.74) and persons reporting hazardous alcohol use (adjRR = 1.09, 95% CI: 1.03-1.16). The prevalence of persistent high-level viraemia was highest among males <30 years (32.0%). CONCLUSIONS: Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high-level viraemia for ≥12 months and reported higher-risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control.