Neurosurgical experience of managing optic pathway gliomas

Background: Optic pathway gliomas (OPGs), also known as visual pathway gliomas, are debilitating tumors that account for 3–5% of all pediatric brain tumors. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of these tumors results in visual loss and blindness, endocrine and hypothalamic dysfunction, hydrocephalus, and premature death. Their involvement of the visual pathways and proximity to other eloquent brain structures typically precludes complete resection or optimal radiation dosing without incurring significant neurological injury. There are various surgical interventions that can be performed in relation to these lesions including biopsy, cerebrospinal fluid diversion, and partial or radical resection, but their role is a source of debate. This study catalogues our surgical experience and patient outcomes in order to support decision-making in this challenging pathology. Methods: A retrospective review of all cases of OPGs treated in a single center from July 1990 to July 2020. Data was collected on patient demographics, radiographic findings, pathology, and management including surgical interventions. Outcome data included survival, visual function, endocrine, and hypothalamic dysfunction. Results: One hundred twenty-one patients with OPG were identified, and 50 of these patients underwent a total of 104 surgical procedures. These included biopsy (31), subtotal or gross total resection (20 operations in 17 patients), cyst drainage (17), Ommaya reservoir insertion (9), or cerebrospinal fluid diversion (27). During the study period, there was 6% overall mortality, 18% hypothalamic dysfunction, 20% endocrine dysfunction, and 42% had some cognitive dysfunction. At diagnosis 75% of patients had good or moderate visual function in at least one eye, and overall, this improved to 83% at the end of the study period. In comparison the worst eye had good or moderate visual function in 56%, and this reduced to 53%. Baseline and final visual function were poorer in patients who had a surgical resection, but improvements in vision were still found—particularly in the best eye. Discussion/conclusion: OPG are debilitating childhood tumor that have lifelong consequences in terms of visual function and endocrinopathies/hypothalamic dysfunction; this can result in substantial patient morbidity. Decisions regarding management and the role of surgery in this condition are challenging and include cerebrospinal fluid diversion, biopsy, and in highly select cases cystic decompression or surgical resection. In this paper, we review our own experience, outcomes, and surgical philosophy

Surveillance imaging of grade 1 astrocytomas in children: can duration and frequency of follow-up imaging and the use of contrast agents be reduced?

Purpose: The optimum strategy for the surveillance of low-grade gliomas in children has not been established, and there is concern about the use of gadolinium-based contrast agents (GBCAs), particularly in children, due to their deposition in the brain. The number of surveillance scans and the use of GBCAs in surveillance of low-risk tumours should ideally be limited. We aimed to investigate the consistency and utility of our surveillance imaging and also determine to what extent the use of GBCAs contributed to decisions to escalate treatment in children with grade 1 astrocytomas. / Methods: This was a retrospective single-centre study at a tertiary paediatric hospital. All children with a new diagnosis of a non-syndromic World Health Organization (WHO) grade 1 astrocytoma between 2007 and 2013 were included, with surveillance imaging up to December 2018 included in analysis. The intervals of surveillance imaging were recorded, and imaging and electronic health records were examined for decisions related to treatment escalation. / Results: Eighty-eight patients had 690 surveillance scans in the study period. Thirty-one patients had recurrence or progression leading to treatment escalation, 30 of whom were identified on surveillance imaging. The use of GBCAs did not appear to contribute to multidisciplinary team (MDT) decisions in the majority of cases. / Conclusion: Surveillance imaging could be reduced in number and duration for completely resected cerebellar tumours. MDT decisions were rarely made on the basis of post-contrast imaging, and GBCA administration could therefore potentially be restricted in the setting of surveillance of grade 1 astrocytomas in children

The ITGAV rs3738919 variant and susceptibility to rheumatoid arthritis in four Caucasian sample sets

INTRODUCTION: Angiogenesis is an important process in the development of destructive synovial pannus in rheumatoid arthritis (RA). The ITGAV +gene encodes a cell cycle-associated antigen, integrin alphanubeta 3, which plays a role in RA angiogenesis. Previously, two independent studies identified an association between the major allele of the ITGAV single-nucleotide polymorphism (SNP) rs3738919 and RA. We therefore tested this association in an independent study using New Zealand (NZ) and Oxford (UK) RA case control samples. METHODS: We compared genotype frequencies in 740 NZ Caucasian RA patients and 553 controls genotyped for rs3738919, using a polymerase chain reaction-restriction fragment length polymorphism assay. A TaqMan genotyping SNP assay was used to type 713 Caucasian RA patients and 515 control samples from Oxford for the rs3738919 variant. Association of rs3738919 with RA was tested in these two sample sets using the chi-square goodness-of-fit test. The Mantel-Haenszel test was used to perform a meta-analysis, combining the genetic results from four independent Caucasian case control cohorts, consisting of 3,527 cases and 4,126 controls. Haplotype analysis was also performed using SNPs rs3911238, rs10174098 and rs3738919 in the Wellcome Trust Case Control Consortium, NZ and Oxford case control samples. RESULTS: We found no evidence for association between ITGAV and RA in either the NZ or Oxford sample set (odds ratio [OR] = 0.88, P(allelic) = 0.11 and OR = 1.18, P(allelic) = 0.07, respectively). Inclusion of these data in a meta-analysis (random effects) of four independent cohorts (3,527 cases and 4,126 controls) weakens support for the hypothesis that rs3738919 plays a role in the development of RA (OR(combined) = 0.92, 95% confidence interval 0.80 to 1.07; P = 0.29). No consistent haplotype associations were evident. CONCLUSIONS: Association of ITGAV SNP rs7378919 with RA was not replicated in NZ or Oxford case control sample sets. Meta-analysis of these and previously published data lends limited support for a role for the ITGAV in RA in Caucasians of European ancestry

Operation Wallacea - Cusuco National Park, Honduras 2016 & 2017 : end of season report

This end of season report is submitted as a review of the summer 2016-2017 seasons and the research activities of the Operation Wallacea research teams in Cusuco National Park over the course of the two summers. This report contains a summary of the methodologies and surveys employed, in addition to the data collected during that time, and a complete analysis of that data as part of this complete report. A more detailed analysis of the herpetofauana dataset, coving the period 2007-2017, is provided, as this information was absent from more recent reports

Amplification of Inflammation by Lubricin Deficiency Implicated in Incident, Erosive Gout Independent of Hyperuricemia

Objective In gout, hyperuricemia promotes urate crystal deposition that stimulates the NLRP3 inflammasome and IL-1β-mediated arthritis. Incident gout without background hyperuricemia is rarely reported. To identify hyperuricemia-independent mechanisms driving gout incidence and progression, we characterized erosive urate crystalline inflammatory arthritis meeting ACR/EULAR gout classification criteria in a normouricemic young adult female. Methods Whole genome sequencing, quantitative proteomics, whole blood RNA-seq, and IL-1β-induced murine knee synovitis characterized proband candidate genes, biomarkers, and pathogenic mechanisms. Results Lubricin was attenuated in proband serum, associated with elevated acute phase reactants and inflammatory whole blood transcripts and transcriptional pathways. The proband had predicted damaging gene variants of NLRP3 and of Inter-Alpha-Trypsin Inhibitor Heavy Chain 3, an inhibitor of lubricin-degrading Cathepsin G. Proband serum protein interactome network changes supported enhanced lubricin degradation, with Cathepsin G activity increased relative to its inhibitors SERPINB6 and Thrombospondin1. TLR2 activation suppressed cultured human synovial fibroblast lubricin mRNA and release (p\u3c0.01). Lubricin blunted urate crystal precipitation, and IL-1β induction of xanthine oxidase and urate in cultured macrophages (p\u3c0.001). In lubricin-deficient mice, IL-1β knee injection increased xanthine oxidase positive synovial resident M1 macrophages (p\u3c0.05). Conclusion We linked normouricemic erosive gout to attenuated lubricin, with impaired control of Cathepsin G activity, compounded by deleterious NLRP3 variants. Lubricin suppressed monosodium urate crystallization, and blunted IL-1β-induced increases in macrophage xanthine oxidase and urate. Collective activities of articular lubricin that could limit incident and erosive gouty arthritis independently of hyperuricemia are subject to disruption by inflammation, activated Cathepsin G, and synovial fibroblast TLR2 signaling

Using Africa’s protected area network to estimate the global population of a threatened and declining species: a case study of the critically endangered White-headed Vulture Trigonoceps occipitalis

The White-headed Vulture Trigonoceps occipitalis (WhV) is uncommon and largely restricted to protected areas across its range in sub-Saharan Africa. We used the World Database on Protected Areas to identify protected areas (PAs) likely to contain White-headed Vultures. Vulture occurrence on road transects in Southern, East, and West Africa was adjusted to nests per km2 using data from areas with known numbers of nests and corresponding road transect data. Nest density was used to calculate the number of WhV nests within identified PAs and from there extrapolated to estimate the global population. Across a fragmented range, 400 PAs are estimated to contain 1893 WhV nests. Eastern Africa is estimated to contain 721 nests, Central Africa 548 nests, Southern Africa 468 nests, and West Africa 156 nests. Including immature and nonbreeding birds, and accounting for data deficient PAs, the estimated global population is 5475 - 5493 birds. The identified distribution highlights are alarming: over 78% (n = 313) of identified PAs contain fewer than five nests. A further 17% (n = 68) of PAs contain 5 - 20 nests and 4% (n = 14) of identified PAs are estimated to contain >20 nests. Just 1% (n = 5) of PAs are estimated to contain >40 nests; none is located in West Africa. Whilst ranging behavior of WhVs is currently unknown, 35% of PAs large enough to hold >20 nests are isolated by more than 100 km from other PAs. Spatially discrete and unpredictable mortality events such as poisoning pose major threats to small localized vulture populations and will accelerate ongoing local extinctions. Apart from reducing the threat of poisoning events, conservation actions promoting linkages between protected areas should be pursued. Identifying potential areas for assisted re-establishment via translocation offers the potential to expand the range of this species and alleviate risk

The Oxytocin Receptor Gene (OXTR) Variant rs53576 Is Not Related to Emotional Traits or States in Young Adults

Background: To understand the genetic underpinnings of emotion, researchers have studied genetic variants in the oxytocin system, a hormone and neurotransmitter important to socio-emotional functioning. The oxytocin receptor gene (OXTR) variant rs53576 has been associated with emotional traits such as positive affect and related constructs such as optimism and self-esteem. Individuals carrying the A allele (AG and AA genotypes) of rs53576 have been found to score lower in these traits when compared to GG homozygotes, although not always. Given recent mixed evidence regarding this polymorphism, replication of these associations is critical.Methods: Using a cross-sectional design, the present study tested the association between rs53576 and a wide variety of emotional traits and states in a sample of 611 young adults ages 18 – 25 of various ethnicities (European, Asian, Māori/Pacific Islander, other). Participants completed standard trait measures of positive and negative affect, depressive symptoms, life engagement, psychological well-being, optimism, and self-esteem. They also completed state measures of positive and negative affect and life engagement for 13-days using Internet daily diaries.Results: Controlling for ethnicity and gender, variation at the OXTR variant rs53576 obtained from blood samples was not related to any of the emotional traits or states. This null finding occurred despite measuring emotions in “near to real time” using daily diaries and having sufficient power to detect a medium effect size difference between homozygous genotype groups.Conclusion: These findings suggest that variation at the rs53576 locus may not be as involved in emotional differences as initial studies suggested

Macaque models of human infectious disease.

Macaques have served as models for more than 70 human infectious diseases of diverse etiologies, including a multitude of agents-bacteria, viruses, fungi, parasites, prions. The remarkable diversity of human infectious diseases that have been modeled in the macaque includes global, childhood, and tropical diseases as well as newly emergent, sexually transmitted, oncogenic, degenerative neurologic, potential bioterrorism, and miscellaneous other diseases. Historically, macaques played a major role in establishing the etiology of yellow fever, polio, and prion diseases. With rare exceptions (Chagas disease, bartonellosis), all of the infectious diseases in this review are of Old World origin. Perhaps most surprising is the large number of tropical (16), newly emergent (7), and bioterrorism diseases (9) that have been modeled in macaques. Many of these human diseases (e.g., AIDS, hepatitis E, bartonellosis) are a consequence of zoonotic infection. However, infectious agents of certain diseases, including measles and tuberculosis, can sometimes go both ways, and thus several human pathogens are threats to nonhuman primates including macaques. Through experimental studies in macaques, researchers have gained insight into pathogenic mechanisms and novel treatment and vaccine approaches for many human infectious diseases, most notably acquired immunodeficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV). Other infectious agents for which macaques have been a uniquely valuable resource for biomedical research, and particularly vaccinology, include influenza virus, paramyxoviruses, flaviviruses, arenaviruses, hepatitis E virus, papillomavirus, smallpox virus, Mycobacteria, Bacillus anthracis, Helicobacter pylori, Yersinia pestis, and Plasmodium species. This review summarizes the extensive past and present research on macaque models of human infectious disease

A review of the ecological value of Cusuco National Park an urgent call forconservation action in a highly threatened Mesoamerican cloud forest

Cloud forests are amongst the most biologically unique, yet threatened, ecosystems in Mesoamerica. We summarize the ecological value and conservation status of a well-studied cloud forest site: Cusuco National Park (CNP), a 23,440 ha protected area in the Merendón mountains, northwest Honduras. We show CNP to have exceptional biodiversity; of 966 taxa identified to a species-level to date, 362 (37.5%) are Mesoamerican endemics, 67 are red-listed by the IUCN, and at least 49 are micro-endemics known only from the Merendón range. CNP also provides key ecosystem services including provision of drinking water and downstream flood mitigation, as well as carbon sequestration, with an estimated stock of 3.5 million megagrams of carbon in 2000. Despite its ecological importance, CNP faces multiple environmental threats and associated stresses, including deforestation (1,759 ha since 2000 equating to 7% of total forest area), poaching (7% loss of mammal relative abundance per year), amphibian declines due to chytridiomycosis (70% of species threatened or near-threatened), and climate change (a mean 2.6 °C increase in temperature and 112 mm decrease in rainfall by 2100). Despite conservation actions, including community ranger patrols, captive-breeding programmes, and ecotourism initiatives, environmental degradation of CNP continues. Further action is urgently required, including reinforcement and expansion of ranger programmes, greater stakeholder engagement, community education programmes, development of alternative livelihood projects, and legislative enforcement and prosecution. Without a thorough and rapid response to understand and mitigate illegal activities, the extirpation and extinction of species and the loss of vital ecosystem services are inevitable in the coming decades