Environmental drivers of the occurrence and abundance of the Irukandji jellyfish (Carukia barnesi).

Understanding the links between species and their environment is critical for species management. This is particularly true for organisms of medical and/or economic significance. The 'Irukandji' jellyfish (Carukia barnesi) is well known for its small size, cryptic nature, and highly venomous sting. Being the namesake of the Irukandji syndrome, contact with this marine stinger often leads to hospitalization and can be fatal. Consequently, the annual occurrence of this organism is believed to cost the Australian government an estimated $AUD3 billion annually in medical costs and losses for tourism. Despite its economic importance the logistical difficulties related to surveying C.barnesi in situ has led to a paucity of knowledge regarding its ecology and significantly impeded management strategies to date. In this study, we use six years of direct C. barnesi capture data to explore patterns pertaining to the annual occurrence and abundance of this species in the nearshore waters of the Cairns coast. We provide novel insights into trends in medusae aggregations and size distribution and primarily focus on the potential role of environmental drivers for annual C. barnesi occurrence patterns. Using a two-part hurdle model, eight environmental parameters were investigated over four time periods for associations with records of medusa presence and abundance. Final models showed a small amount of variation in medusa presence and abundance patterns could be accounted for by long-term trends pertaining to rainfall and wind direction. However, the assessed environmental parameters could not explain high annual variation or site location effects. Ultimately best-fit models had very low statistical inference power explaining between 16 and 20% of the variance in the data, leaving approximately 80% of all variation in medusa presence and abundance unexplained.

Faster disease progression in Parkinson's disease with type 2 diabetes is not associated with increased α-synuclein, tau, amyloid-ß or vascular pathology.

AIMS: Growing evidence suggests a shared pathogenesis between Parkinson's disease and diabetes although the underlying mechanisms remain unknown. The aim of this study was to evaluate the effect of type 2 diabetes on Parkinson's disease progression and to correlate neuropathological findings to elucidate pathogenic mechanisms. METHODS: In this cohort study, medical records were retrospectively reviewed of cases with pathologically confirmed Parkinson's disease with and without pre-existing type 2 diabetes. Time to disability milestones (recurrent falls, wheelchair dependence, dementia and care home placement) and survival were compared to assess disease progression and their risk estimated using Cox hazard regression models. Correlation with pathological data was performed, including quantification of α-synuclein in key brain regions and staging of vascular, Lewy and Alzheimer's pathologies. RESULTS: Patients with PD and diabetes (male 76%; age at death 78.6 ± 6.2 years) developed earlier falls (p < 0.001), wheelchair dependence (p = 0.004), dementia (p < 0.001), care home admission (p < 0.001) and had reduced survival (p < 0.001). Predating diabetes was independently associated with a two to three-fold increase in the risk of disability and death. Neuropathological assessment did not show any differences in global or regional vascular pathology, α-synuclein load in key brain areas, staging of Lewy pathology or Alzheimer's disease pathology. CONCLUSIONS: Pre-existing type 2 diabetes contributes to faster disease progression and reduced survival in Parkinson's disease which is not driven by increased vascular, Lewy or Alzheimer's pathologies. Additional non-specific neurodegeneration related to chronic brain insulin resistance may be involved.

Bay watch: Using unmanned aerial vehicles (UAV's) to survey the box jellyfish Chironex fleckeri.

Biological investigations on free ranging marine species are regarded as challenging throughout the scientific community. This is particularly true for 'logistically difficult species' where their cryptic natures, low abundance, patchy distributions and difficult and/or dangerous sampling environments, make traditional surveys near impossible. What results is a lack of ecological knowledge on such marine species. However, advances in UAV technology holds potential for overcoming these logistical difficulties and filling this knowledge gap. Our research focused on one such logistically difficult species, the Australian box Jellyfish (Chironex fleckeri), and we investigated the capacity of consumer grade UAV technology to detect this, highly venomous, target species in the inshore waters of Northern Queensland Australia. At two sites in the Weipa area, we utilized video analysis, visual count comparisons with a netted animal tally, and evaluated the role of associated environmental conditions, such as wind speed, water visibility and cloud cover on jellyfish detection rates. In total fifteen, 70 meter transects were completed between two sites, with 107 individuals captured. Drone success varied between the two sites with a significant difference between field and post-field (laboratory) counts. Animal size and cloud cover also had significant effects on detection rates with an increase in cloud cover and animal size enhancing detection probability. This study provides evidence to suggest drone surveys overcome obstacles that traditional surveys can't, with respect to species deemed logistically difficult and open scope for further ecological investigations on such species.

Microglial burden, activation and dystrophy patterns in frontotemporal lobar degeneration.

BACKGROUND: Microglial dysfunction is implicated in frontotemporal lobar degeneration (FTLD). Although studies have reported excessive microglial activation or senescence (dystrophy) in Alzheimer's disease (AD), few have explored this in FTLD. We examined regional patterns of microglial burden, activation and dystrophy in sporadic and genetic FTLD, sporadic AD and controls. METHODS: Immunohistochemistry was performed in frontal and temporal grey and white matter from 50 pathologically confirmed FTLD cases (31 sporadic, 19 genetic: 20 FTLD-tau, 26 FTLD-TDP, four FTLD-FUS), five AD cases and five controls, using markers to detect phagocytic (CD68-positive) and antigen-presenting (CR3/43-positive) microglia, and microglia in general (Iba1-positive). Microglial burden and activation (morphology) were assessed quantitatively for each microglial phenotype. Iba1-positive microglia were assessed semi-quantitatively for dystrophy severity and qualitatively for rod-shaped and hypertrophic morphology. Microglia were compared in each region between FTLD, AD and controls, and between different pathological subtypes of FTLD, including its main subtypes (FTLD-tau, FTLD-TDP, FTLD-FUS), and subtypes of FTLD-tau, FTLD-TDP and genetic FTLD. Microglia were also compared between grey and white matter within each lobe for each group. RESULTS: There was a higher burden of phagocytic and antigen-presenting microglia in FTLD and AD cases than controls, but activation was often not increased. Burden was generally higher in white matter than grey matter, but activation was greater in grey matter. However, microglia varied regionally according to FTLD subtype and disease mechanism. Dystrophy was more severe in FTLD and AD than controls, and more severe in white than grey matter, but this also varied regionally and was particularly extensive in FTLD due to progranulin (GRN) mutations. Presence of rod-shaped and hypertrophic microglia also varied by FTLD subtype. CONCLUSIONS: This study demonstrates regionally variable microglial involvement in FTLD and links this to underlying disease mechanisms. This supports investigation of microglial dysfunction in disease models and consideration of anti-senescence therapies in clinical trials.

Pathological correlates of white matter hyperintensities in a case of progranulin mutation associated frontotemporal dementia.

White matter hyperintensities (WMH) are often seen on MRI brain scans in frontotemporal dementia (FTD) due to progranulin (GRN) mutations, but their pathological correlates are unknown. We examined the histological changes underlying WMH in a patient with GRN mutation associated behavioral variant FTD. In vivo and cadaveric MRI showed progressive, asymmetric frontotemporal and parietal atrophy, and asymmetrical WMH predominantly affecting frontal mid-zones. We first performed segmentation and localization analyses of WMH present on cadaveric MRI FLAIR images, then selected five different brain regions directly matched to differing severities of WMH for histological analysis. We used immunohistochemistry to assess vascular pathology, degree of spongiosis, neuronal and axonal loss, TDP-43, demyelination and astrogliosis, and microglial burden and morphology. Brain regions with significant WMH displayed severe cortical and white matter pathology, and prominent white matter microglial activation and microglial dystrophy, but only mild axonal loss and minimal vascular pathology. Our study suggests that WMH in GRN mutation carriers are not secondary to vascular pathology. Whilst cortical pathology induced axonal degeneration could contribute to white matter damage, individuals with GRN mutations could develop selective white matter vulnerability and myelin loss due to chronic, regional microglial dysfunction arising from GRN haploinsufficiency.

Immunohistochemical and Molecular Investigations Show Alteration in the Inflammatory Profile of Multiple System Atrophy Brain.

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease characterized by aggregation of α-synuclein in oligodendrocytes to form glial cytoplasmic inclusions. According to the distribution of neurodegeneration, MSA is subtyped as striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA), or as combination of these 2 (mixed MSA). In the current study, we aimed to investigate regional microglial populations and gene expression in the 3 different MSA subtypes. Microscopy with microglial marker Iba-1 combined with either proinflammatory marker CD68 or anti-inflammatory marker Arginase-1 was analyzed in control, SND, and OPCA cases (n = 5) using paraffin embedded sections. Western immunoblotting and cytokine array were used to determine protein expression in MSA and control brain regions. Gene expression was investigated using the NanoString nCounter Human Inflammation panel v2 mRNA Expression Assay. Analysis of neuropathological subtypes of MSA demonstrated a significant increase in microglia in the substantia nigra of OPCA cases. There was no difference in the microglial activation state in any region. Cytokine expression in MSA was comparable with controls. Decreased expression of CX3CL1 precursor protein and significantly greater CX3CR1 protein was found in MSA. NanoString analysis revealed the >2-fold greater expression of ARG1, MASP1, NOX4, PTGDR2, and C6 in MSA.

A Histologic Study of the Circadian System in Parkinson Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy.

Importance: Circadian dysfunction may be associated with the symptoms and neurodegeneration in Parkinson disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP), although the underlying neuroanatomical site of disruption and pathophysiological mechanisms are not fully understood. Objective: To perform a neuropathological analysis of disease-specific inclusions in the key structures of the circadian system in patients with PD, MSA, and PSP. Design, Setting, and Participants: This investigation was a brain bank case-control study assessing neuropathological inclusions in the suprachiasmatic nucleus (SCN) of the hypothalamus and pineal gland in healthy controls, PD (Lewy pathology), MSA (glial cytoplasmic inclusions), and PSP (tau inclusions). The study analyzed 12 healthy control, 28 PD, 11 MSA, and 21 PSP samples from consecutive brain donations (July 1, 2010, to June 30, 2016) to the Queen Square Brain Bank for Neurological Disorders and the Parkinson's UK Brain Bank, London, United Kingdom. Cases were excluded if neither SCN nor pineal tissue was available. Main Outcomes and Measures: Disease-specific neuropathological changes were graded using a standard semiquantitative scoring system (absent, mild, moderate, severe, or very severe) and compared between groups. Results: Because of limited tissue availability, the following total samples were examined in a semiquantitative histologic analysis: 5 SCNs and 7 pineal glands in the control group (6 male; median age at death, 83.8 years; interquartile range [IQR], 78.2-88.0 years), 13 SCNs and 17 pineal glands in the PD group (22 male; median age at death, 78.8 years; IQR, 75.5-83.8 years), 5 SCNs and 6 pineal glands in the MSA group (7 male; median age at death, 69.5 years; IQR, 61.6-77.7 years), and 5 SCNs and 19 pineal glands in the PSP group (13 male; median age at death, 74.3 years; IQR, 69.7-81.1 years). No neuropathological changes were found in either the SCN or pineal gland in healthy controls or MSA cases. Nine PD cases had Lewy pathology in the SCN, and only 2 PD cases had Lewy pathology in the pineal gland. All PSP cases showed inclusions in the SCN, but no PSP cases had pathology in the pineal gland. Conclusions and Relevance: Disease-related neuropathological changes were found in the SCN but not in the pineal gland in PD and PSP, while both structures were preserved in MSA, reflecting different pathophysiological mechanisms that may have important therapeutic implications.

Rethinking the treatment of chronic fatigue syndrome-a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT.

BACKGROUND: The PACE trial was a well-powered randomised trial designed to examine the efficacy of graded exercise therapy (GET) and cognitive behavioural therapy (CBT) for chronic fatigue syndrome. Reports concluded that both treatments were moderately effective, each leading to recovery in over a fifth of patients. However, the reported analyses did not consistently follow the procedures set out in the published protocol, and it is unclear whether the conclusions are fully justified by the evidence. METHODS: Here, we present results based on the original protocol-specified procedures. Data from a recent Freedom of Information request enabled us to closely approximate these procedures. We also evaluate the conclusions from the trial as a whole. RESULTS: On the original protocol-specified primary outcome measure - overall improvement rates - there was a significant effect of treatment group. However, the groups receiving CBT or GET did not significantly outperform the Control group after correcting for the number of comparisons specified in the trial protocol. Also, rates of recovery were consistently low and not significantly different across treatment groups. Finally, on secondary measures, significant effects were almost entirely confined to self-report measures. These effects did not endure beyond two years. CONCLUSIONS: These findings raise serious concerns about the robustness of the claims made about the efficacy of CBT and GET. The modest treatment effects obtained on self-report measures in the PACE trial do not exceed what could be reasonably accounted for by participant reporting biases.

Thermal and Osmotic Tolerance of 'Irukandji' Polyps: Cubozoa; Carukia barnesi.

This research explores the thermal and osmotic tolerance of the polyp stage of the Irukandji jellyfish Carukia barnesi, which provides new insights into potential polyp habitat suitability. The research also targets temperature, salinity, feeding frequency, and combinations thereof, as cues for synchronous medusae production. Primary findings revealed 100% survivorship in osmotic treatments between 19 and 46‰, with the highest proliferation at 26‰. As salinity levels of 26‰ do not occur within the waters of the Great Barrier Reef or Coral Sea, we conclude that the polyp stage of C. barnesi is probably found in estuarine environments, where these lower salinity conditions commonly occur, in comparison to the medusa stage, which is oceanic. Population stability was achieved at temperatures between 18 and 31°C, with an optimum temperature of 22.9°C. We surmise that C. barnesi polyps may be restricted to warmer estuarine areas where water temperatures do not drop below 18°C. Asexual reproduction was also positively correlated with feeding frequency. Temperature, salinity, feeding frequency, and combinations thereof did not induce medusae production, suggesting that this species may use a different cue, possibly photoperiod, to initiate medusae production.

Early Life History of the 'Irukandji' Jellyfish Carukia barnesi.

Adult medusae of Carukia barnesi were collected near Double Island, North Queensland Australia. From 73 specimens, 8 males and 15 females spawned under laboratory conditions. These gametes were artificially mixed which resulted in fertilized eggs. Post fertilization, most eggs developed to an encapsulated planula stage and then paused for between six days and six months prior to hatching as ciliated planulae. The paused stage planulae were negatively buoyant and adhered to substrate. The first planula was produced six days post fertilization, lacked larval ocelli, remained stationary, or moved very slowly for two days prior to metamorphosis into primary polyps. Mature polyps reproduced through asexual reproduction via lateral budding producing ciliated swimming polyps, which in turn settled and developed into secondary polyps. Medusae production for this species was in the form of monodisc strobilation, which left behind polyps able to continue asexual reproduction.

Prey Capture Ecology of the Cubozoan Carukia barnesi.

Adult Carukia barnesi medusae feed predominantly on larval fish; however, their mode of prey capture seems more complex than previously described. Our findings revealed that during light conditions, this species extends its tentacles and 'twitches' them frequently. This highlights the lure-like nematocyst clusters in the water column, which actively attract larval fish that are consequently stung and consumed. This fishing behavior was not observed during dark conditions, presumably to reduce energy expenditure when they are not luring visually oriented prey. We found that larger medusae have longer tentacles; however, the spacing between the nematocyst clusters is not dependent on size, suggesting that the spacing of the nematocyst clusters is important for prey capture. Additionally, larger specimens twitch their tentacles more frequently than small specimens, which correlate with their recent ontogenetic prey shift from plankton to larval fish. These results indicate that adult medusae of C. barnesi are not opportunistically grazing in the water column, but instead utilize sophisticated prey capture techniques to specifically target larval fish.

COMPARISON OF SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY SCAN PATTERNS AND CLINICAL REVIEW STRATEGIES IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To compare various spectral domain optical coherence tomography scan patterns and review strategies to identify an optimal imaging workflow for neovascular age-related macular degeneration. METHODS: A retrospective consecutive case series was performed in eyes after anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration with concurrent spectral domain optical coherence tomography imaging (Zeiss Cirrus), including horizontal/vertical five-line rasters, and macular cube analysis. For each scan pattern, a single report was independently reviewed in a masked fashion within the clinical image review software, whereas the cube was reviewed line-by-line in the reader software for the presence of fluid. RESULTS: One hundred and fifty-six reports and 39 cube scans of 39 patients were included. Among all spectral domain optical coherence tomography scans, 64% (25/39) had definitive fluid and 95% (37/39) had possible fluid. Sensitivities for definite fluid detection for horizontal, combined horizontal/vertical, and horizontal/vertical/map reviews were 68%, 76%, and 88%, respectively. When assessing for possible fluid, sensitivities for the detection for horizontal, combined horizontal/vertical, and horizontal/vertical/map reviews were 76%, 92%, and 97%, respectively. Line-by-line review of the cube scan had a sensitivity for definite and possible fluid detection of 96% and 86%, respectively. CONCLUSION: Optimizing both clinical accuracy and workflow are important factors in managing neovascular age-related macular degeneration. A zero-tolerance strategy with vertical/horizontal raster scans and thickness maps was comparable with line-by-line review of the cube to detect possible fluid.

Bevacizumab therapy and multimodal ultrawide-field imaging in immunogammopathy maculopathy secondary to Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia (WM) is associated with retinal findings of hyperviscosity, such as venous dilation, and findings of immunogammopathy maculopathy, such as serous macular detachment. This report describes a case of bilateral serous macular detachment with intraretinal schisis-like fluid in a patient with WM. Enhanced depth imaging optical coherence tomography revealed a thickened choroid with hyperreflective accumulations in the retinal pigment epithelium layer. Ultrawide-field fundus autofluorescence demonstrated a central area of hyperautofluorescence corresponding to the area of serous macular detachment. Ultrawide-field fluorescein angiography was characteristically silent. Intravitreal bevacizumab therapy resulted in significant reduction in intraretinal fluid but minimal change in subretinal fluid. Long-term follow-up demonstrated alterations in retinal architecture and improved serous detachments.

Retinal morphology of patients with achromatopsia during early childhood: implications for gene therapy.

IMPORTANCE: While older children and adults with achromatopsia have been studied, less is known of young children with achromatopsia. OBJECTIVES: To characterize the macular and foveal architecture of patients with achromatopsia during early childhood with handheld spectral-domain optical coherence tomographic imaging and to make phenotype-genotype correlations. DESIGN, SETTING, AND PARTICIPANTS: Comparative case series of 9 patients with achromatopsia and 9 age-matched control participants at a tertiary ophthalmology referral center. MAIN OUTCOMES AND MEASURES: Patients underwent complete ocular examination, full-field electroretinography, handheld spectral-domain optical coherence tomographic imaging, and screening for genetic mutations. RESULTS: The mean (SD) age of the patients with achromatopsia was 4.2 (2.4) years, and the mean (SD) age of the control participants was 4.0 (2.1) years. Cone-driven responses to photopic single-flash or 30-Hz stimuli were nonrecordable in 7 patients and severely attenuated in 2. Rod-driven responses to dim scotopic single-flash stimuli were normal in 7 patients and mildly subnormal in 2. Six patients (67%) had foveal ellipsoid zone disruption, of which 1 had a hyporeflective zone. Four patients (44%) had foveal hypoplasia. The average total retinal thicknesses of the macula and fovea in the patients with achromatopsia were 14% and 17% thinner than in the control participants (P < .001 and P = .001), which was mostly due to the outer retina that was 18% and 26% thinner than in control participants (both P < .001), respectively. Genetic testing revealed a common homozygous mutation in CNGB3 in 5 patients with complete achromatopsia and heterozygous mutations in CNGA3 in 2 patients with incomplete achromatopsia. The youngest and worst-affected patient harbored compound heterozygous mutations in CNGB3 and a single mutation in CNGA3. CONCLUSIONS AND RELEVANCE: In early childhood, there is a spectrum of foveal pathology that is milder than reported in older individuals with achromatopsia, which suggests the need for early therapeutic intervention. Neither age alone nor genotype alone predicts the degree of photoreceptor loss or preservation. Thus, in anticipation of future gene therapy trials in humans, we propose that handheld spectral-domain optical coherence tomography is an important tool for the early assessment and stratification of macular architecture in young children with achromatopsia.

Seasonality in polyps of a tropical cubozoan: A latina nr mordens.

A latina nr mordens have been located in large predictable spawning aggregations near Osprey Reef in the Coral Sea eight to ten days after a full moon; however, polyps have never been located in-situ. The polyp stage contributes to the abundance of medusae through asexual reproduction and metamorphosis, and may influence the periodicity of medusae by metamorphosis of the polyp. To elucidate the relationship between medusae periodicity and polyp ecology, polyps were exposed to thermal and osmotic treatments in order to determine the theoretical environmental limits to their distribution. Maximum fecundity occurred in thermal treatments of 21 to 25ºC and the theoretical minimum thermal requirement for population stability was approximately 17ºC. Polyps were also exposed to five feeding regimes and fecundity was found to be positively correlated with feeding frequency. Thermal and osmotic variations did not induce metamorphosis in this species, however, reduced food did. The implications of asexual reproduction and cues for metamorphosis in relation to population dynamics of this species are discussed.