Frailty and Early Mortality following Intracerebral Hemorrhage.

INTRODUCTION: Prognostication in spontaneous intracerebral hemorrhage (ICH) is vital for effective clinical decision-making but can be challenging. Frailty - the loss of physiological reserve to withstand stressor events - is a risk factor for poor outcomes after ischemic stroke, yet its role in ICH remains poorly understood. This study investigates whether frailty is independently associated with 28-day mortality following ICH. METHODS: A validated pre-stroke frailty index (FI) was measured for individuals presenting with ICH, yielding a FI of 0-1. The relationship between 28-day mortality and FI was assessed using multivariable logistic regression adjusting for age, neurosurgical intervention, National Institutes of Health Stroke Scale (NIHSS), Glasgow Coma Score (GCS), and ICH volume. RESULTS: Forty (34.5%) of 116 individuals with ICH died within 28 days. Frailty was independently associated with 28-day mortality, with each 0.1 increase in FI independently associated with an adjusted odds ratio of death of 1.09 (95% CI: 1.01-1.18). ICH volume was also independently associated with mortality (aOR 1.04, 95% CI: 1.02-1.06 per 10 mL increase). In contrast, age and neurosurgical intervention were not independently associated with mortality in our cohort. CONCLUSION: Higher pre-stroke frailty is independently associated with early mortality following spontaneous ICH, indicating the potential of frailty evaluation to inform prognostication and clinical decision-making.

18F-NaF uptake on vascular PET imaging in symptomatic versus asymptomatic atherosclerotic disease: A meta-analysis.

INTRODUCTION: 18F-sodium fluoride (NaF) positron-emission tomography (PET) is increasingly being used to measure microcalcification in atherosclerotic disease in vivo. Correlations have been drawn between sodium fluoride uptake and the presence of high-risk plaque features, as well as its association with clinical atherosclerotic sequelae. The aim of this study was to perform a meta-analysis of NaF uptake on PET imaging and its relation to symptomatic and asymptomatic disease. METHODS: A systematic review was performed according to PRISMA guidelines, via searching the Ovid MEDLINE, Ovid Embase, Cochrane Library, PubMed, Scopus, and Web of Science Core Collection databases up to May 2024. The search strategy included the terms 'NaF', 'PET', and 'plaque', and all studies with data regarding the degree of microcalcification, as measured by 18F-NaF uptake in symptomatic and asymptomatic atherosclerotic plaques, were included. Analysis involved calculating mean differences between uptake values and comparison using a random-effects model. RESULTS: A total of 16 articles, involving 423 participants, were included in the meta-analysis (10 carotid artery studies, five coronary artery studies, and one in peripheral vascular disease). Comparing 18F-NaF uptake in symptomatic versus asymptomatic atherosclerotic plaques, a mean difference of 0.43 (95% CI 0.29 to 0.57; p < 0.0001, I2 = 65%) was noted in studies comparing symptomatic and asymptomatic plaques in the same participant, with a significant difference in effect based on arterial territory studied (χ2 = 12.68, p = 0.0018). In studies of participants with and without symptomatic disease, there was no significant difference between symptomatic and asymptomatic plaques (mean difference 0.27, 95% CI -0.26 to 0.80, p = 0.28, I2 = 85%). CONCLUSIONS: PET imaging using 18F-NaF can detect differences in microcalcification between symptomatic and asymptomatic atherosclerotic plaques within, but not between, individuals, and thus, is a marker of symptomatic disease. The standardization of 18F-NaF PET imaging protocols, and its future use as a risk stratification tool or outcome measure, requires further study. (PROSPERO Registration ID: CRD42023451363).

Host ecology and biogeography drive parasite community composition in Atlantic killifishes.

Understanding the mechanisms of parasite community assembly can be confounded by phylogenetic distance among host species. Addressing this requires focusing on parasite communities within closely related taxa. Thus, we took a macroecological approach to examining parasite community structure within Killifish species in the genus Fundulus to disentangle the effects of host phylogeny and ecological variables. We constructed a database of parasite communities within Fundulus species from 15 published and unpublished surveys covering the Atlantic coast of the US and Canada. The database was expanded by sampling sites in underrepresented provinces and states, totaling 10 Fundulus species from 57 unique geographic sites. Univariate analysis of observed parasite species richness among Fundulus populations in the dataset found that latitude, climate type, and salinity were the dominant factors determining parasite species richness. Multivariate analysis found that host species and landscape type were the most important factors in determining the similarity of parasite assemblages. Unexpectedly, parasite species richness decreased in low latitudes, and host phylogenetic distance was not found to be a significant factor in the similarity of parasite communities. These results indicate that commonly reported large-scale drivers of parasite community structure, such as latitude and phylogeny, could have diminished significance at the host genus level relative to host ecology, biogeography, and local landscape factors.

Mysterious microsporidians: springtime outbreaks of disease in Daphnia communities in shallow pond ecosystems.

Parasites can play key roles in ecosystems, especially when they infect common hosts that play important ecological roles. Daphnia are critical grazers in many lentic freshwater ecosystems and typically reach peak densities in early spring. Daphnia have also become prominent model host organisms for the field of disease ecology, although most well-studied parasites infect them in summer or fall. Here, we report field patterns of virulent microsporidian parasites that consistently infect Daphnia in springtime, in a set of seven shallow ponds in Georgia, USA, sampled every 3-4 weeks for 18 months. We detected two distinct parasite taxa, closely matching sequences of Pseudoberwaldia daphniae and Conglomerata obtusa, both infecting all three resident species of Daphnia: D. ambigua, D. laevis, and D. parvula. To our knowledge, neither parasite has been previously reported in any of these host species or anywhere in North America. Infection prevalence peaked consistently in February-May, but the severity of these outbreaks differed substantially among ponds. Moreover, host species differed markedly in terms of their maximum infection prevalence (5% [D. parvula] to 72% [D. laevis]), mean reduction of fecundity when infected (70.6% [D. ambigua] to 99.8% [D. laevis]), mean spore yield (62,000 [D. parvula] to 377,000 [D. laevis] per host), and likelihood of being infected by each parasite. The timing and severity of the outbreaks suggests that these parasites could be impactful members of these shallow freshwater ecosystems, and that the strength of their effects is likely to hinge on the composition of ponds' zooplankton communities.

Management of carotid atherosclerosis in stroke.

Internal carotid artery atherosclerosis is a major risk factor for stroke, accounting for 15-20% of ischaemic strokes. Revascularisation procedures-either carotid endarterectomy or carotid artery stenting-can reduce the risk of stroke for those with significant (>50%) luminal stenosis but particularly for those with more severe (70-99%) stenosis. However, advances in medical pharmacotherapy have implications for the relative benefit from surgery for symptomatic carotid atherosclerosis, as well as our approach to asymptomatic disease. This review considers the evidence underpinning the current medical and surgical management of symptomatic carotid atherosclerosis, the importance of factors beyond the degree of luminal stenosis, and developments in therapeutic strategies. We also discuss the importance of non-stenotic but high-risk carotid atherosclerotic plaques on the cause of stroke, and their implications for clinical practice.

Trial of Dexamethasone for Chronic Subdural Hematoma.

BACKGROUND: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied. METHODS: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death). RESULTS: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group. CONCLUSIONS: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.).

Within-host and external environments differentially shape ß-diversity across parasite life stages.

Uncovering drivers of community assembly is a key aspect of learning how biological communities function. Drivers of community similarity can be especially useful in this task as they affect assemblage-level changes that lead to differences in species diversity between habitats. Concepts of ß-diversity originally developed for use in free-living communities have been widely applied to parasite communities to gain insight into how infection risk changes with local conditions by comparing parasite communities across abiotic and biotic gradients. Factors shaping ß-diversity in communities of immature parasites, such as larvae, are largely unknown. This is a key knowledge gap as larvae are frequently the infective life-stage and understanding variation in these larval communities is thus key for disease prevention. Our goal was to uncover links between ß-diversity of parasite communities at different life stages; therefore, we used gastrointestinal nematodes infecting African buffalo in Kruger National Park, South Africa, to investigate within-host and extra-host drivers of adult and larval parasite community similarity. We employed a cross-sectional approach using PERMANOVA that examined each worm community at a single time point to assess independent drivers of ß-diversity in larvae and adults as well as a longitudinal approach with path analysis where adult and larval communities from the same host were compared to better link drivers of ß-diversity between these two life stages. Using the cross-sectional approach, we generally found that intrinsic, within-host traits had significant effects on ß-diversity of adult nematode communities, while extrinsic, extra-host variables had significant effects on ß-diversity of larval nematode communities. However, the longitudinal approach provided evidence that intrinsic, within-host factors affected the larval community indirectly via the adult community. Our results provide key data for the comparison of community-level processes where adult and immature stages inhabit vastly different habitats (i.e. within-host vs. abiotic environment). In the context of parasitism, this helps elucidate host infection risk via larval stages and the drivers that shape persistence of adult parasite assemblages, both of which are useful for predicting and preventing infectious disease.

What underlies the difference between self-reported health and disability after stroke? A qualitative study in the UK.

BACKGROUND: Levels of self-reported health do not always correlate with levels of physical disability in stroke survivors. We aimed to explore what underlies the difference between subjective self-reported health and objectively measured disability among stroke survivors. METHODS: Face to face semi-structured interviews were conducted with stroke survivors recruited from a stroke clinic or rehabilitation ward in the UK. Fifteen stroke survivors purposively sampled from the clinic who had discordant self-rated health and levels of disability i.e. reported health as 'excellent' or 'good' despite significant physical disability (eight), or as 'fair' or 'poor' despite minimal disability (seven) were compared to each other, and to a control group of 13 stroke survivors with concordant self-rated health and disability levels. Interviews were conducted 4 to 6 months after stroke and data analysed using the constant comparative method informed by Albrecht and Devlieger's concept of 'disability paradox'. RESULTS: Individuals with 'excellent' or 'good' self-rated health reported a sense of self-reliance and control over their bodies, focussed on their physical rehabilitation and lifestyle changes and reported few bodily and post-stroke symptoms regardless of level of disability. They also frequently described a positive affect and optimism towards recovery. Some, especially those with 'good' self-rated health and significant disability also found meaning from their stroke, reporting a spiritual outlook including practicing daily gratitude and acceptance of limitations. Individuals with minimal disability reporting 'fair' or 'poor' self-rated health on the other hand frequently referred to their post-stroke physical symptoms and comorbidities and indicated anxiety about future recovery. These differences in psychological outlook clustered with differences in perception of relational and social context including support offered by family and healthcare professionals. CONCLUSIONS: The disability paradox may be illuminated by patterns of individual attributes and relational dynamics observed among stroke survivors. Harnessing these wider understandings can inform new models of post-stroke care for evaluation.

Life in the margins: host-parasite relationships in ecological edges.

Transitional zones, such as edge habitat, are key landscapes for investigating biodiversity. "Soft edges" are permeable corridors that hosts can cross, while "hard edges" are impermeable borders that hosts cannot pass. Although pathogen transmission in the context of edges is vital to species conservation, drivers of host-parasite relationships in ecological edges remain poorly understood. Thus, we defined a framework for testing hypotheses of host-parasite interactions in hard and soft edges by (1) characterizing hard and soft edges from both the host and parasite perspectives, (2) predicting the types of parasites that would be successful in each type of edge, and (3) applying our framework to species invasion fronts as an example of host-parasite relationships in a soft edge. Generally, we posited that parasites in soft edges are more likely to be negatively affected by habitat fragmentation than their hosts because they occupy higher trophic levels but parasite transmission would benefit from increased host connectivity. Parasites along hard edges, however, are at higher risk of local extinction due to host population perturbations with limited opportunity for parasite recolonization. We then used these characteristics to predict functional traits that would lead to parasite success along soft and hard edges. Finally, we applied our framework to invasive species fronts to highlight predictions regarding host connectivity and parasite traits in soft edges. We anticipate that our work will promote a more complete discussion of habitat connectivity using a common framework and stimulate empirical research into host-parasite relationships within ecological edges and transitional zones.

Colonization of a novel host by fleas: changes in egg production and egg size.

We studied the success of fleas, Synosternus cleopatrae and Xenopsylla ramesis, in switching to a novel host by establishing experimental lines maintained on different hosts for 18 generations. Fleas fed on principal (P-line) or novel hosts, either sympatric with (S-line) or allopatric to (A-line) a flea and its principal host, then we assessed their reproductive performance via the number and size of eggs. We compared reproductive performance between hosts within a line and between lines within a host asking: (a) whether fleas adapt to a novel host species after multiple generations; (b) if yes, whether the pattern of adaptation differs between novel host species sympatric with or allopatric to a flea and its principal host; and (c) adaptation to a novel host is accompanied with a loss of success in exploitation of an original host. Fleas from the S- and A-lines increased their egg production on a novel host (except X. ramesis from the S-line). S. cleopatrae from the S-line but not the A-line increased egg size on a novel host, whereas X. ramesis from the A-line but not the S-line produced larger eggs from a novel host. We found no indication of a loss of reproductive performance on the original host while adapting to a novel host. We conclude that fleas are able to switch rapidly to a new host with the pattern of a switch to either sympatric or an allopatric host depending on the identities of both flea and host species.

CREB transcription in the medial prefrontal cortex regulates the formation of long-term associative recognition memory.

The medial prefrontal cortex (mPFC) is known to be critical for specific forms of long-term recognition memory, however the cellular mechanisms in the mPFC that underpin memory maintenance have not been well characterized. This study examined the importance of phosphorylation of cAMP responsive element binding protein (CREB) in the mPFC for different forms of long-term recognition memory in the rat. Adenoviral transduction of the mPFC with a dominant-negative inhibitor of CREB impaired object-in-place memory following a 6 or 24 h retention delay, but no impairment was observed following delays of 5 min or 3 h. Long-term object temporal order memory and spatial temporal order memory was also impaired. In contrast, there were no impairments in novel object recognition or object location memory. These results establish, for the first time, the importance of CREB phosphorylation within the mPFC for memory of associative and temporal information crucial to recognition.

Efficacy of spoken word comprehension therapy in patients with chronic aphasia: a cross-over randomised controlled trial with structural imaging.

OBJECTIVE: The efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, 'Listen-In', and examined the relation between brain structure and therapy response. METHODS: A cross-over randomised repeated measures trial with five testing time points (12-week intervals), conducted at the university or participants' homes, captured baseline (T1), therapy (T2-T4) and maintenance (T5) effects. Participants with chronic poststroke aphasia and spoken language comprehension impairments completed consecutive Listen-In and standard care blocks (both 12 weeks with order randomised). Repeated measures analyses of variance compared change in spoken language comprehension on two co-primary outcomes over therapy versus standard care. Three structural MRI scans (T2-T4) for each participant (subgroup, n=25) were analysed using cross-sectional and longitudinal voxel-based morphometry. RESULTS: Thirty-five participants completed, on average, 85 hours (IQR=70-100) of Listen-In (therapy first, n=18). The first study-specific co-primary outcome (Auditory Comprehension Test (ACT)) showed large and significant improvements for trained spoken words over therapy versus standard care (11%, Cohen's d=1.12). Gains were largely maintained at 12 and 24 weeks. There were no therapy effects on the second standardised co-primary outcome (Comprehensive Aphasia Test: Spoken Words and Sentences). Change on ACT trained words was associated with volume of pretherapy right hemisphere white matter and post-therapy grey matter tissue density changes in bilateral temporal lobes. CONCLUSIONS: Individuals with chronic aphasia can improve their spoken word comprehension many years after stroke. Results contribute to hemispheric debates implicating the right hemisphere in therapy-driven language recovery. Listen-In will soon be available on GooglePlay. TRIAL REGISTRATION NUMBER: NCT02540889.

Feeding performance on a novel host: no adaptation over generations and differential patterns in two flea species.

To model the colonization of a novel host by fleas, Synosternus cleopatrae and Xenopsylla ramesis, we established experimental lines maintained for 15 generations on a principal or a novel host (either co-occurring with a flea or not). We compared the blood meal size and the energy expended for digestion by fleas from the 15th generation of each line on these hosts between hosts within a line and between lines within a host asking (a) whether fleas adapt to a novel host (increased blood consumption/decreased energy expended for digestion); (b) if yes, whether this adaptation leads to the loss of ability to exploit an original host, and (c) whether the success of adaptation to a novel host depends on its ecological co-occurrence with a flea. The blood consumption and digestion energetics of fleas fed on the principal host differed from those on other hosts. The effect of the principal host on feeding performance differed between fleas, with S. cleopatrae consuming less blood and expending more energy for digestion on the principal than on any other host, whereas the opposite was true for X. ramesis. No changes in feeding performance on a novel host over generations were found. We propose several explanations for the lack of adaptation to a novel host over time. We explain the poor performance of S. cleopatrae on its principal host via its immune response mounting pattern. We argue that the principal host of a parasite is not necessarily the host on which the parasite demonstrates the best performance.

Flea infestation, social contact, and stress in a gregarious rodent species: minimizing the potential parasitic costs of group-living.

Both parasitism and social contact are common sources of stress that many gregarious species encounter in nature. Upon encountering such stressors, individuals secrete glucocorticoids and although short-term elevation of glucocorticoids is adaptive, long-term increases are correlated with higher mortality and deleterious reproductive effects. Here, we used an experimental host-parasite system, social rodents Acomys cahirinus and their characteristic fleas Parapulex chephrenis, in a fully-crossed design to test the effects of social contact and parasitism on stress during pregnancy. By analysing faecal glucocorticoid metabolites, we found that social hierarchy did not have a significant effect on glucocorticoid concentration. Rather, solitary females had significantly higher glucocorticoid levels than females housed in pairs. We found a significant interaction between the stressors of parasitism and social contact with solitary, uninfested females having the highest faecal glucocorticoid metabolite levels suggesting that both social contact and infestation mitigate allostatic load in pregnant rodents. Therefore, the increased risk of infestation that accompanies group-living could be outweighed by positive aspects of social contact within A. cahirinus colonies in nature.

Clinical frailty independently predicts early mortality after ischaemic stroke.

BACKGROUND: Clinical frailty is an important syndrome for clinical care and research, independently predicting mortality and rates of institutionalisation in a range of medical conditions. However, there has been little research into the role of frailty in stroke. OBJECTIVE: This study investigates the effect of frailty on 28-day mortality following ischaemic stroke and outcomes following stroke thrombolysis. METHODS: Frailty was measured using the Clinical Frailty Scale (CFS) for all ischaemic stroke admissions aged ≥75 years. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS). 28-day mortality and clinical outcomes were collected retrospectively. Analysis included both dichotomised measures of frailty (non-frail: CFS 1-4, frail: 5-8) and CFS as a continuous ordinal scale. RESULTS: In 433 individuals with ischaemic stroke, 28-day mortality was higher in frail versus non-frail individuals (39 (16.7%) versus 10 (5%), P < 0.01). On multivariable analysis, a one-point increase in CFS was independently associated with 28-day mortality (OR 1.03 (1.01-1.05)). In 63 thrombolysed individuals, median NIHSS reduced significantly in non-frail individuals (12.5 (interquartile range (IQR) 9.25) to 5 (IQR 10.5), P < 0.01) but not in frail individuals (15 (IQR 11.5) to 16 (IQR 16.5), P = 0.23). On multivariable analysis, a one-point increase in CFS was independently associated with a one-point reduction in post-thrombolysis NIHSS improvement (coefficient 1.07, P = 0.03). CONCLUSION: Clinical frailty is independently associated with 28-day mortality after ischaemic stroke and appears independently associated with attenuated improvement in NIHSS following stroke thrombolysis. Further research is needed to elucidate the underlying mechanisms and how frailty may be utilised in clinical decision-making.

A Critical Role for the Nucleus Reuniens in Long-Term, But Not Short-Term Associative Recognition Memory Formation.

Recognition memory for single items requires the perirhinal cortex (PRH), whereas recognition of an item and its associated location requires a functional interaction among the PRH, hippocampus (HPC), and medial prefrontal cortex (mPFC). Although the precise mechanisms through which these interactions are effected are unknown, the nucleus reuniens (NRe) has bidirectional connections with each regions and thus may play a role in recognition memory. Here we investigated, in male rats, whether specific manipulations of NRe function affected performance of recognition memory for single items, object location, or object-in-place associations. Permanent lesions in the NRe significantly impaired long-term, but not short-term, object-in-place associative recognition memory, whereas single item recognition memory and object location memory were unaffected. Temporary inactivation of the NRe during distinct phases of the object-in-place task revealed its importance in both the encoding and retrieval stages of long-term associative recognition memory. Infusions of specific receptor antagonists showed that encoding was dependent on muscarinic and nicotinic cholinergic neurotransmission, whereas NMDA receptor neurotransmission was not required. Finally, we found that long-term object-in-place memory required protein synthesis within the NRe. These data reveal a specific role for the NRe in long-term associative recognition memory through its interactions with the HPC and mPFC, but not the PRH. The delay-dependent involvement of the NRe suggests that it is not a simple relay station between brain regions, but, rather, during high mnemonic demand, facilitates interactions between the mPFC and HPC, a process that requires both cholinergic neurotransmission and protein synthesis.SIGNIFICANCE STATEMENT Recognizing an object and its associated location, which is fundamental to our everyday memory, requires specific hippocampal-cortical interactions, potentially facilitated by the nucleus reuniens (NRe) of the thalamus. However, the role of the NRe itself in associative recognition memory is unknown. Here, we reveal the crucial role of the NRe in encoding and retrieval of long-term object-in-place memory, but not for remembrance of an individual object or individual location and such involvement is cholinergic receptor and protein synthesis dependent. This is the first demonstration that the NRe is a key node within an associative recognition memory network and is not just a simple relay for information within the network. Rather, we argue, the NRe actively modulates information processing during long-term associative memory formation.

Relationships between selective neuronal loss and microglial activation after ischaemic stroke in man.

Modern ischaemic stroke management involves intravenous thrombolysis followed by mechanical thrombectomy, which allows markedly higher rates of recanalization and penumbral salvage than thrombolysis alone. However, <50% of treated patients eventually enjoy independent life. It is therefore important to identify complementary therapeutic targets. In rodent models, the salvaged penumbra is consistently affected by selective neuronal loss, which may hinder recovery by interfering with plastic processes, as well as by microglial activation, which may exacerbate neuronal death. However, whether the salvaged penumbra in man is similarly affected is still unclear. Here we determined whether these two processes affect the non-infarcted penumbra in man and, if so, whether they are inter-related. We prospectively recruited patients with (i) acute middle-cerebral artery stroke; (ii) penumbra present on CT perfusion obtained <4.5 h of stroke onset; and (iii) early neurological recovery as a marker of penumbral salvage. PET with 11C-flumazenil and 11C-PK11195, as well as MRI to map the final infarct, were obtained at predefined follow-up times. The presence of selective neuronal loss and microglial activation was determined voxel-wise within the MRI normal-appearing ipsilateral non-infarcted zone and surviving penumbra masks, and their inter-relationship was assessed both across and within patients. Dilated infarct contours were consistently excluded to control for partial volume effects. Across the 16 recruited patients, there was reduced 11C-flumazenil and increased 11C-PK11195 binding in the whole ipsilateral non-infarcted zone (P = 0.04 and 0.02, respectively). Within the non-infarcted penumbra, 11C-flumazenil was also reduced (P = 0.001), but without clear increase in 11C-PK11195 (P = 0.18). There was no significant correlation between 11C-flumazenil and 11C-PK11195 in either compartment. This mechanistic study provides direct evidence for the presence of both neuronal loss and microglial activation in the ipsilateral non-infarcted zone. Further, we demonstrate the presence of neuronal loss affecting the surviving penumbra, with no or only mild microglial activation, and no significant relationship between these two processes. Thus, microglial activation may not contribute to penumbral neuronal loss in man, and its presence in the ipsilateral hemisphere may merely reflect secondary remote degeneration. Selective neuronal loss in the surviving penumbra may represent a novel therapeutic target as an adjunct to penumbral salvage to further improve functional outcome. However, microglial activation may not stand as the primary therapeutic approach. Protecting the penumbra by acutely improving perfusion and oxygenation in conjunction with thrombectomy for example, may be a better approach. 11C-flumazenil PET would be useful to monitor the effects of such therapies.

Species and site contributions to ß-diversity in fleas parasitic on the Palearctic small mammals: ecology, geography and host species composition matter the most.

The ß-diversity of fleas parasitic on small mammals in 45 regions of the Palearctic was partitioned into species [species contributions to ß-diversity (SCBD)] and site ( = assemblage) contributions [local contributions to ß-diversity (LCBD)]. We asked what are the factors affecting SCBD and LCBD and tested whether (a) variation in ecological, morphological, life history and geographic traits of fleas can predict SCBD and (b) variation in flea and host community metrics, off-host environmental factors, host species composition of flea assemblages can predict LCBD. We used spatial variables to describe geographic distribution of flea assemblages with various LCBD values. SCBD significantly increased with an increase in abundance and a decrease in phylogenetic host specificity of a flea as well as with size and latitude of its geographic range, but was not associated with any morphological/life history trait. LCBD of flea assemblages did not depend on either flea or host species richness or environmental predictors, but was significantly affected by compositional uniqueness ( = LCBD) of regional host assemblages and variables describing their species composition. In addition, variation in LCBD was also explained by broad-to-moderate-scale spatial variables. We conclude that SCBD of fleas could be predicted via their ecological and geographic traits, whereas LCBD of their assemblages could be predicted via host composition.