Longitudinal brain volumetrics in glioma survivors.

OBJECTIVE: Radiation therapy (RT) is used selectively for patients with low-grade glioma (LGG) given the concerns for potential cognitive effects in survivors, but prior cognitive outcome studies among LGG survivors have had inconsistent findings. Translational studies that characterize changes in brain anatomy and physiology after treatment of LGG may help to both contextualize cognitive findings and improve the overall understanding of radiation effects in normal brain tissue. This study aimed to investigate the hypothesis that patients with LGG who are treated with RT will experience greater brain volume loss than those who do not receive RT. METHODS: This retrospective longitudinal study included all patients with WHO grade 2 glioma who received posttreatment surveillance MRI at the University of Alabama at Birmingham. Volumetric analysis of contralateral cortical white matter (WM), cortical gray matter (GM), and hippocampus was performed on all posttreatment T1-weighted MRI sequences using the SynthSeg script. The effect of clinical and treatment variables on brain volumes was assessed using two-level hierarchical linear models. RESULTS: The final study cohort consisted of 105 patients with 1974 time points analyzed. The median length of imaging follow-up was 4.6 years (range 0.36-18.9 years), and the median number of time points analyzed per patient was 12 (range 2-40). Resection was performed in 79 (75.2%) patients, RT was administered to 61 (58.1%) patients, and chemotherapy was administered to 66 (62.9%) patients. Age at diagnosis (ß = -0.06, p < 0.001) and use of RT (ß = -1.12, p = 0.002) were associated with the slope of the contralateral cortical GM volume model (i.e., change in GM over time). Age at diagnosis (ß = -0.08, p < 0.001), midline involvement (ß = 1.31, p = 0.006), and use of RT (ß = -1.45, p = 0.001) were associated with slope of the contralateral cortical WM volume model. Age (ß = -0.0027, p = 0.001), tumor resection (ß = -0.069, p < 0.001), use of chemotherapy (ß = -0.0597, p = 0.003), and use of RT (ß = -0.0589, p < 0.001) were associated with the slope of the contralateral hippocampus volume model. CONCLUSIONS: This study demonstrated volume loss in contralateral brain structures among LGG survivors, and patients who received RT experienced greater volume loss than those who did not. The results of this study may help to provide context for cognitive outcome research in LGG survivors and inform the design of future strategies to preserve cognition.

System Action Learning: Reorientating Practice for System Change in Preventive Health.

It is now widely accepted that many of the problems we face in public health are complex, from chronic disease to COVID-19. To grapple with such complexity, researchers have turned to both complexity science and systems thinking to better understand the problems and their context. Less work, however, has focused on the nature of complex solutions, or intervention design, when tackling complex problems. This paper explores the nature of system intervention design through case illustrations of system action learning from a large systems level chronic disease prevention study in Australia. The research team worked with community partners in the design and implementation of a process of system action learning designed to reflect on existing initiatives and to reorient practice towards responses informed by system level insights and action. We were able to observe and document changes in the mental models and actions of practitioners and in doing so shine a light on what may be possible once we turn our attention to the nature and practice of system interventions.

"I want to feel young again": experiences and perspectives of young people who inject drugs living with hepatitis C in Vancouver, Canada.

OBJECTIVES: People who inject drugs (PWID) are disproportionately impacted by hepatitis C virus (HCV). Despite the availability and efficacy of direct-acting antiviral (DAA) HCV therapies, treatment rates remain low among PWID. Among PWID, those who are young (under age 30) experience high rates of HCV and also face distinct barriers to care. The objective of this study is to identify facilitators and barriers to navigating various facets of the HCV cascade of care, including DAA treatment access, among young PWID. METHODS: We draw on data from in-depth, semi-structured interviews conducted between May and November 2019 with a sample of 11 young, street-involved PWID who have lived experience of HCV and who live in Metro Vancouver, Canada. Informed by a social constructivist epistemology, data were thematically analyzed using an equity-oriented theoretical framework. RESULTS: Our analysis yielded two key themes. First, participants described facilitators to HCV care access, including individual factors (e.g., desire to be cured, knowledge of side effects) and healthcare and socio-contextual factors (e.g., peer supports, supportive youth-specific services). Second, participants described a contrasting set of barriers to HCV care access, including concerns over treatment side effects and (in)eligibility, complex healthcare system navigation, substance use- and housing-related stigma, and clinician gatekeeping of DAAs. CONCLUSION: Findings from this study underscore the need for HCV-related knowledge-building efforts among young PWID and clinicians. Also needed are structural policy interventions to facilitate access to DAAs, including anti-stigma efforts, access to safe housing, and the scale-up of low-barrier youth-specific services and decentralized HCV care.

RéSUMé: OBJECTIFS: Les personnes qui font usage de drogues par injection (PUDI) sont démesurément touchées par le virus de l'hépatite C (VHC). Malgré la disponibilité et l'efficacité potentielle des traitements antiviraux à action directe (AAD) contre le VHC, les taux de traitement demeurent faibles chez les PUDI. Les jeunes PUDI (moins de 30 ans) présentent des taux élevés de VHC tout en faisant face à des obstacles distincts pour se faire soigner. Notre étude vise à cerner les éléments qui favorisent ou qui entravent la négociation des divers aspects de la cascade des soins du VHC, dont l'accès aux traitements par AAD, chez les jeunes PUDI. MéTHODE: Nos données proviennent d'entretiens semi-directifs approfondis menés entre mai et novembre 2019 auprès d'un échantillon de 11 jeunes PUDI de la rue ayant une expérience vécue du VHC et vivant dans le District régional du Grand Vancouver, au Canada. Éclairées par une épistémologie constructiviste sociale, les données ont été analysées thématiquement à l'aide d'un cadre théorique orienté sur l'équité. RéSULTATS: Deux grands thèmes se sont dégagés de notre analyse. Premièrement, les participants ont décrit les éléments qui favorisent l'accès aux soins du VHC, dont les facteurs individuels (p. ex. le désir de guérir, la connaissance des effets secondaires) et les facteurs socio-contextuels et liés aux soins de santé (p. ex. l'entraide des pairs, les services de soutien pour les jeunes). Deuxièmement, les participants ont décrit un ensemble opposé d'obstacles à l'accès aux soins du VHC, dont les craintes par rapport aux effets secondaires des traitements et à l'(in)admissibilité aux traitements, le parcours complexe du système de soins de santé, la stigmatisation associée à l'usage de substances et au logement, ainsi que la protection de l'accès aux AAD par les cliniciens. CONCLUSION: Les constatations de l'étude confirment la nécessité de renforcer les connaissances sur le VHC, tant chez les jeunes PUDI que chez les cliniciens. Sont aussi nécessaires des interventions stratégiques structurelles pour faciliter l'accès aux AAD, dont la lutte contre la stigmatisation, la sécurité du logement, l'augmentation des services jeunesse « à bas seuil ¼ et la décentralisation des soins du VHC.

Characterization of Brucella abortus S19 as a challenge strain for use in a mouse model of brucellosis.

The objective of this project was to conduct a feasibility study to determine whether the Brucella abortus S19 vaccine infects and persists in mice and determine whether S19 can be used as a challenge strain for vaccine trial studies. Groups of BALB/c mice were inoculated (intraperitoneally, subcutaneously, intranasally) and euthanized to determine colonization titers in the spleens and lungs. This study showed that S19 does infect and persist in the tissues of mice for 8 weeks and demonstrates that S19 can be used, safely and economically under BSL2 containment, as the challenge strain for future trials to evaluate vaccine efficacy.

Will peer-based interventions improve hepatitis C virus treatment uptake among young people who inject drugs?

People who inject drugs (PWID) are disproportionately affected by hepatitis C virus (HCV) and have low rates of direct-acting antiviral (DAA) treatment uptake, despite universal coverage of the medication in most Canadian settings. Investigation into peer-based interventions as a means of improving treatment uptake has yielded promising results in adult PWID populations. In this commentary, we discuss the benefits and considerations of integrating peer-based interventions into HCV care for adolescent and young adult PWID living with HCV. Given that young PWID experience high transmission rates and account for most new infections, improving strategies for youth engagement with DAA treatment is critical. We describe how peer-based interventions can feature the unique importance of peer relationships in this period of life and provide a low-barrier way of delivering health promotion messages. In particular, we discuss the ability of peer-based interventions to reshape the narrative of HCV care in young PWID peer networks by empowering youth to share experiences and knowledge with others. We conclude by addressing knowledge gaps in the literature which must be filled in order to strengthen the impact of peer-based interventions on treatment uptake rates among young PWID.

RéSUMé: Les personnes qui font usage de drogues par injection (PUDI) sont démesurément touchées par le virus de l'hépatite C (VHC) et présentent de faibles taux de recours aux traitements antiviraux à action directe (AAD), pourtant couverts par la plupart des régimes d'assurance-médicaments au Canada. Une enquête sur l'intervention par les pairs comme moyen d'améliorer le recours aux traitements a donné des résultats prometteurs dans des populations de PUDI adultes. Dans notre commentaire, nous expliquons les avantages d'intégrer l'intervention par les pairs dans les soins des adolescents et des jeunes adultes vivant avec le VHC qui font usage de drogues par injection, ainsi que les éléments à considérer. Comme les jeunes PUDI affichent des taux de transmission élevés et sont responsables de la plupart des nouveaux cas d'infection, il est essentiel d'améliorer les stratégies de recours aux traitements par AAD chez les jeunes. Nous expliquons que l'intervention par les pairs mise sur l'importance unique des égaux durant cette période de la vie et constitue un moyen « à bas seuil ¼ de faire passer les messages de promotion de la santé. En particulier, nous expliquons que l'intervention par les pairs peut transformer le discours sur les soins du VHC dans les réseaux d'entraide de jeunes PUDI en donnant à ces jeunes le pouvoir de partager leur expérience et leurs connaissances avec d'autres. En conclusion, nous abordons les lacunes à combler dans la littérature scientifique pour renforcer l'impact de l'intervention par les pairs sur les taux de recours aux traitements chez les jeunes PUDI.

Oral acute toxicity and impact of neonicotinoids on Apis mellifera L. and Scaptotrigona postica Latreille (Hymenoptera: Apidae).

Wild and managed bees are essential for crop pollination and food production. However, the widespread use of insecticides such as neonicotinoids may affect the survival, development, behavior, and maintenance of bee colonies. Therefore, in this study we evaluated the impacts of three neonicotinoid insecticides on the survival and walking abilities of the Africanized honeybee A. mellifera and stingless bee S. postica. A. mellifera was more susceptible than S. postica to all neonicotinoids tested. The median lethal concentrations LC50 values estimated for acetamiprid, imidacloprid, and thiacloprid were 189.62, 22.78, and 142.31 ng µL-1 of diet for A. mellifera, and 475.94, 89.11, and 218.21 ng µL-1 of diet for S. postica, respectively. All tested neonicotinoids affected the speed, distance traveled, duration and frequency of resting, and continuous mobility of both bee species. The results showed that in spite of the different susceptibility to compounds with cyano and nitro radicals, the behavioral variables showed different levels of commitment according to the molecule insecticide and bee species. These results contribute not only to the understanding of the effects of neonicotinoid insecticides on A. mellifera and S. postica, but also to help in the development of protocols that aim to reduce the impact of these insecticides in Neotropical environments.

Characterization of mule deerpox virus in Florida white-tailed deer fawns expands the known host and geographic range of this emerging pathogen.

Infections caused by mule deerpox virus (MDPV) have been sporadically reported in North American cervids. White-tailed deer (Odocoileus virginianus) fawns from a farm located in South Central Florida presented with ulcerative and crusting lesions on the coronary band as well as the mucocutaneous tissues of the head. Evaluation of the crusted skin lesions was undertaken using microscopic pathology and molecular techniques. A crusted skin sample was processed for virus isolation in four mammalian cell lines. The resulting isolate was characterized by negative staining electron microscopy and deep sequencing. Histopathologic evaluation of the skin lesions from the fawns revealed a hyperplastic and proliferative epidermis with ballooning degeneration of epidermal and follicular keratinocytes with intracytoplasmic eosinophilic inclusions. Electron microscopy of cell culture supernatant demonstrated numerous large brick-shaped particles typical of most poxviruses. Polymerase chain reaction assays followed by Sanger sequencing revealed a poxvirus gene sequence nearly identical to that of previous strains of MDPV. The full genome was recovered by deep sequencing and genetic analyses supported the Florida white-tailed deer isolate (MDPV-F) as a strain of MDPV. Herein, we report the first genome sequence of MDPV from a farmed white-tailed deer fawn in the South Central Florida, expanding the number of locations and geographic range in which MDPV has been identified.

Complete genome sequence of a novel sea otterpox virus.

Members of the Poxviridae family are large, double-stranded DNA viruses that replicate in the cytoplasm of their host cells. The subfamily Chordopoxvirinae contains viruses that infect a wide range of vertebrates including marine mammals within the Balaenidae, Delphinidae, Mustelidae, Odobenidae, Otariidae, Phocidae, and Phocoenidae families. Recently, a novel poxvirus was found in a northern sea otter pup (Enhydra lutris kenyoni) that stranded in Alaska in 2009. The phylogenetic relationships of marine mammal poxviruses are not well established because of the lack of complete genome sequences. The current study sequenced the entire sea otterpox virus Enhydra lutris kenyoni (SOPV-ELK) genome using an Illumina MiSeq sequencer. The SOPV-ELK genome is the smallest poxvirus genome known at 127,879 bp, is 68.7% A+T content, is predicted to encode 132 proteins, and has 2546 bp inverted terminal repeats at each end. Genetic and phylogenetic analyses based on the concatenated amino acid sequences of 7 chorodopoxvirus core genes revealed the SOPV-ELK is 52.5-74.1% divergent from other known chordopoxviruses and is most similar to pteropoxvirus from Australia (PTPV-Aus). SOPV-ELK represents a new chordopoxvirus species and may belong to a novel genus. SOPV-ELK encodes eight unique genes. While the function of six predicted genes remains unknown, two genes appear to function as novel immune-modulators. SOPV-ELK-003 appears to encode a novel interleukin-18 binding protein (IL-18 BP), based on limited sequence and structural similarity to other poxviral IL-18 BPs. SOPV-ELK-035 appears to encode a novel tumor necrosis factor receptor-like (TNFR) protein that may be associated with the depression of the host's antiviral response. Additionally, SOPV-ELK-036 encodes a tumor necrosis factor-like apoptosis-inducing ligand (TRAIL) protein that has previously only been found in PTPV-Aus. The SOPV-ELK genome is the first mustelid poxvirus and only the second poxvirus from a marine mammal to be fully sequenced. Sequencing of the SOPV-ELK genome is an important step in unraveling the position of marine mammal poxviruses within the larger Poxviridae phylogenetic tree and provides the necessary sequence to develop molecular tools for future diagnostics and epidemiological studies.

Genome Sequence of an Alphaherpesvirus from a Beluga Whale (Delphinapterus leucas).

Beluga whale alphaherpesvirus 1 was isolated from a blowhole swab taken from a juvenile beluga whale. The genome is 144,144 bp in size and contains 86 putative genes. The virus groups phylogenetically with members of the genus Varicellovirus in subfamily Alphaherpesvirinae and is the first alphaherpesvirus sequenced from a marine mammal.

Genome Sequence of a Gammaherpesvirus from a Common Bottlenose Dolphin (Tursiops truncatus).

A herpesvirus genome was sequenced directly from a biopsy specimen of a rectal lesion from a female common bottlenose dolphin. This genome sequence comprises a unique region (161,235 bp) flanked by multiple copies of a terminal repeat (4,431 bp) and contains 72 putative genes. The virus was named common bottlenose dolphin gammaherpesvirus 1.

Initial characterization of novel beaked whale morbillivirus in Hawaiian cetaceans.

Cetacean morbillivirus (CeMV) is a causative factor in epizootics that have resulted in thousands of deaths throughout the Atlantic and Mediterranean since 1987, but less is known of its presence and significance in the Pacific. The first case of CeMV reported in Hawai'i was in a Longman's beaked whale that stranded in 2010. The initial CeMV sequence from this individual indicated the possibility of a novel strain. To address this, archived samples from cetaceans that stranded in Hawai'i between 1997 and 2014 were screened for CeMV. The beaked whale morbillivirus (BWMV) was detected in 15 individuals representing 12 different species (24% of Code 1 and 2 stranded cetaceans). The earliest detected case was a humpback whale that stranded in 1998. Sequence comparisons of a 2.2 kb sequence spanning the phosphoprotein (P) and nucleocapsid (N) genes strongly suggest that the BWMV represents a novel strain of CeMV present in Hawai'i and the Central Pacific. In contrast to recently reported isolates from Brazil and Australia that may represent a distinct clade, BWMV appears to be more closely related to known strains of CeMV (dolphin morbillivirus; porpoise morbillivirus; and pilot whale morbillivirus). Detection rates with repeat sampling of positive lymph nodes were between 2 and 61%, illustrating the extreme heterogeneity that can occur in affected tissues. Taken together, these results suggest that BWMV may be common and established in Hawaiian cetacean populations. BWMV will be important for understanding CeMV and health threats in the relatively understudied cetaceans of the Pacific.

Coinfection and vertical transmission of Brucella and Morbillivirus in a neonatal sperm whale (Physeter macrocephalus) in Hawaii, USA.

The viral genus Morbillivirus and the bacterial genus Brucella have emerged as important groups of pathogens that are known to affect cetacean health on a global scale, but neither pathogen has previously been reported from endangered sperm whales (Physeter macrocephalus). A female neonate sperm whale stranded alive and died near Laie on the island of Oahu, Hawaii, US, in May of 2011. Congestion of the cerebrum and enlarged lymph nodes were noted on the gross necropsy. Microscopic findings included lymphoid depletion, chronic meningitis, and pneumonia, suggesting an in utero infection. Cerebrum, lung, umbilicus, and select lymph nodes (tracheobronchial and mediastinal) were positive for Brucella by PCR. Brucella sp. was also cultured from the cerebrum and from mediastinal and tracheobronchial lymph nodes. Twelve different tissues were screened for Morbillivirus by reverse-transcriptase (RT)-PCR and select tissues by immunohistochemistry, but only the tracheobronchial lymph node and spleen were positive by RT-PCR. Pathologic findings observed were likely a result of Brucella, but Morbillivirus may have played a key role in immune suppression of the mother and calf. The in utero infection in this individual strongly supports vertical transmission of both pathogens.

Failure of selective termination and dexamethasone rescue therapy to arrest HELLP syndrome in a midtrimester triplet gestation with one triploid fetus.

We present a case of a patient with a triplet pregnancy at 22 weeks with one triploid fetus (69XXX) who developed severe preeclampsia that did not reverse with dexamethasone rescue therapy and selective termination. With multiple gestations on the rise and the early diagnosis of abnormal pregnancies being accomplished through ultrasound, serum markers, and invasive procedures, the question remains if there is a point in gestation before which selective termination of an abnormal fetus would allow the pregnancy to continue without preeclampsia developing or progressing. Appropriate counseling as to the maternal risk in cases of trisomy 13 or triploidy is essential as early in pregnancy as possible.