Resources, key traits and the size of fungal epidemics in Daphnia populations

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111939/1/jane12363.pd

Habitat, predators, and hosts regulate disease in Daphnia through direct and indirect pathways

Community ecology can link habitat to disease via interactions among habitat, focal hosts, other hosts, their parasites, and predators. However, complicated food web interactions (i.e., trophic interactions among predators and their impacts on host density and diversity) often obscure the important pathways regulating disease. Here, we disentangle community drivers in a case study of planktonic disease, using a two‐step approach. In step one, we tested univariate field patterns linking community interactions directly to two disease metrics. Density of focal hosts (Daphnia dentifera) was related to density but not prevalence of fungal (Metschnikowia bicuspidata) infections. Both disease metrics appeared to be driven by selective predators that cull infected hosts (fish, e.g., Lepomis macrochirus), sloppy predators that spread parasites while feeding (midges, Chaoborus punctipennis), and spore predators that reduce contact between focal hosts and parasites (other zooplankton, especially small‐bodied Ceriodaphnia sp.). Host diversity also negatively correlated with disease, suggesting a dilution effect. However, several of these univariate patterns were initially misleading, due to confounding ecological links among habitat, predators, host density, and host diversity. In step two, path models uncovered and explained these misleading patterns, and grounded them in habitat structure (refuge size). First, rather than directly reducing infection prevalence, fish predation drove disease indirectly through changes in density of midges and frequency of small spore predators (which became more frequent in lakes with small refuges). Second, small spore predators drove the two disease metrics through fundamentally different pathways: they directly reduced infection prevalence, but indirectly reduced density of infected hosts by lowering density of focal hosts (likely via competition). Third, the univariate diversity–disease pattern (signaling a dilution effect) merely reflected the confounding direct effects of these small spore predators. Diversity per se had no effect on disease, after accounting for the links between small spore predators, diversity, and infection prevalence. In turn, these small spore predators were regulated by both size‐selective fish predation and refuge size. Thus, path models not only explain each of these surprising results, but also trace their origins back to habitat structure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134436/1/ecm1222_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134436/2/ecm1222-sup-0001-AppendixS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134436/3/ecm1222.pd

Differential gene expression in the insect vector Anasa tristis in response to symbiont colonization but not infection with a vectored phytopathogen

Many insects selectively associate with specific microbes in long-term, symbiotic relationships. Maintaining these associations can be vital for the insect hosts’ development, but insects must also contend with potential coinfections from other microbes in the environment. Fending off microbial threats while maintaining mutualistic microbes has resulted in many insects developing specialized symbiotic organs to house beneficial microbes. Though locally concentrated in these organs, symbiont establishment can have global consequences for the insect, including influence over the success of coinfecting microbes in colonizing the insect host. We use a transcriptomic approach to examine how the mutualistic symbiosis between the agricultural pest Anasa tristis and bacteria in the genus Caballeronia affects insect gene expression locally within the symbiotic organs and in the insect host at large. We simultaneously determine whether Caballeronia colonization impacts insect host responses to infection with the plant pathogen Serratia marcescens, which it vectors to plants. We found that no significant differential gene expression was elicited by infection with S. marcescens. This was a surprising finding given previous work indicating that symbiotic A. tristis clear S. marcescens infection rapidly compared to aposymbiotic individuals. Our results indicate that symbiotic and nonsymbiotic tissues in A. tristis differ greatly in their gene expression, particularly following successful symbiont colonization. We found evidence for local downregulation of host immunity and upregulation of cell communication within the symbiotic organs, functions which can facilitate the success of the A. tristis-Caballeronia symbiosis

Improved Systemic Saturation After Ventricular Assist Device Implantation in a Patient With Decompensated Dextro-transposition of the Great Arteries After the Fontan Procedure

We report the successful implantation of a HeartMate II left ventricular assist device after a failed Fontan procedure in a patient with dextro-transposition of the great arteries. The patient had developed significant intrapulmonary arteriovenous shunting. Despite the theoretical risk of worsening intrapulmonary shunting due to the decrease in systemic vascular resistance after device implantation, our patient did well. He was discharged from the hospital in stable condition and had better oxygen saturation than before the device was implanted. To our knowledge, ours is the 2nd report of the use of a ventricular assist device after the failure of a Fontan procedure, and the first report concerning the effect of ventricular assist device implantation on intrapulmonary shunting

Disease-driven Reduction in Human Mobility Influences Human-Mosquito Contacts and Dengue Transmission Dynamics

Heterogeneous exposure to mosquitoes determines an individual’s contribution to vector-borne pathogen transmission. Particularly for dengue virus (DENV), there is a major difficulty in quantifying human-vector contacts due to the unknown coupled effect of key heterogeneities. To test the hypothesis that the reduction of human out-of-home mobility due to dengue illness will significantly influence population-level dynamics and the structure of DENV transmission chains, we extended an existing modeling framework to include social structure, disease-driven mobility reductions, and heterogeneous transmissibility from different infectious groups. Compared to a baseline model, naïve to human pre-symptomatic infectiousness and disease-driven mobility changes, a model including both parameters predicted an increase of 37% in the probability of a DENV outbreak occurring; a model including mobility change alone predicted a 15.5% increase compared to the baseline model. At the individual level, models including mobility change led to a reduction of the importance of out-of-home onward transmission (R, the fraction of secondary cases predicted to be generated by an individual) by symptomatic individuals (up to -62%) at the expense of an increase in the relevance of their home (up to +40%). An individual’s positive contribution to R could be predicted by a GAM including a non-linear interaction between an individual’s biting suitability and the number of mosquitoes in their home (\u3e10 mosquitoes and 0.6 individual attractiveness significantly increased R). We conclude that the complex fabric of social relationships and differential behavioral response to dengue illness cause the fraction of symptomatic DENV infections to concentrate transmission in specific locations, whereas asymptomatic carriers (including individuals in their pre-symptomatic period) move the virus throughout the landscape. Our findings point to the difficulty of focusing vector control interventions reactively on the home of symptomatic individuals, as this approach will fail to contain virus propagation by visitors to their house and asymptomatic carriers

Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: An international study

\ua9 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.Background and purpose: Spinal muscular atrophy (SMA) is a rare and progressive neuromuscular disorder with varying severity levels. The aim of the study was to calculate minimal clinically important difference (MCID), minimal detectable change (MDC), and values for the Hammersmith Functional Motor Scale Expanded (HFMSE) in an untreated international SMA cohort. Methods: The study employed two distinct methods. MDC was calculated using distribution-based approaches to consider standard error of measurement and effect size change in a population of 321 patients (176 SMA II and 145 SMA III), allowing for stratification based on age and function. MCID was assessed using anchor-based methods (receiver operating characteristic [ROC] curve analysis and standard error) on 76 patients (52 SMA II and 24 SMA III) for whom the 12-month HFMSE could be anchored to a caregiver-reported clinical perception questionnaire. Results: With both approaches, SMA type II and type III patients had different profiles. The MCID, using ROC analysis, identified optimal cutoff points of −2 for type II and −4 for type III patients, whereas using the standard error we found the optimal cutoff points to be 1.5 for improvement and −3.2 for deterioration. Furthermore, distribution-based methods uncovered varying values across age and functional status subgroups within each SMA type. Conclusions: These results emphasize that the interpretation of a single MCID or MDC value obtained in large cohorts with different functional status needs to be made with caution, especially when these may be used to assess possible responses to new therapies

Different trajectories in upper limb and gross motor function in spinal muscular atrophy

INTRODUCTION: The Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM) have been widely used in natural history studies and clinical trials. Our aim was to establish how the scales relate to each other at different age points in spinal muscular atrophy (SMA) type 2 and 3, and to describe their coherence over 12 mo. METHODS: The study was performed by cross-sectional and longitudinal reanalysis of previously published natural history data. The longitudinal analysis of the 12-mo changes also included the analysis of concordance between scales with changes grouped as stable (±2 points), improved (>+2) or declined (>−2). RESULTS: Three hundred sixty-four patients were included in the cross-sectional analysis, showing different trends in score and point of slope change for the two scales. For type 2, the point of slope change was 4.1 y for the HFMSE and 5.8 for the RULM, while for type 3, it was 6 y for the HFMSE and 7.3 for the RULM. One-hundred-twenty-one patients had at least two assessments at 12 mo. Full concordance was found in 57.3% of the assessments, and in 40.4% one scale remained stable and the other changed. Each scale appeared to be more sensitive to specific age or functional subgroups. DISCUSSION: The two scales, when used in combination, may increase the sensitivity to detect clinically meaningful changes in motor function in patients with SMA types 2 and 3

Global change drivers and the risk of infectious disease

Anthropogenic change is contributing to the rise in emerging infectious diseases, but it remains unclear which global change drivers most increase disease and under what contexts. We amassed a dataset from the literature that includes 1,832 observations of infectious disease responses to global change drivers across 1,202 host-parasite combinations. We found that biodiversity loss, climate change, and introduced species were associated with increases in disease-related endpoints or harm (i.e., enemy release for introduced species), whereas urbanization was associated with decreases in disease endpoints. Natural biodiversity gradients, deforestation, forest fragmentation, and most classes of chemical contaminants had non-significant effects on these endpoints. Overall, these results were consistent across human and non-human diseases. Context-dependent effects of the global change drivers on disease were common and are discussed. These findings will help better target disease management and surveillance efforts towards global change drivers that increase disease.One-Sentence SummaryHere we quantify which global change drivers increase infectious diseases the most to better target global disease management and surveillance efforts

Disease Trajectories in the Revised Hammersmith Scale in a Cohort of Untreated Patients with Spinal Muscular Atrophy types 2 and 3

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterised by progressive motor function decline. Motor function is assessed using several functional outcome measures including the Revised Hammersmith Scale (RHS). Objective: In this study, we present longitudinal trajectories for the RHS in an international cohort of 149 untreated paediatric SMA 2 and 3 patients (across 531 assessments collected between March 2015 and July 2019). Methods: We contextualise these trajectories using both the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM). At baseline, this cohort included 50% females and 15% of patients had undergone spinal fusion surgery. Patient trajectories were modelled using a natural cubic spline with age, sex, and random effects for each patient. Results: RHS and HFMSE scores show similar trends over time in this cohort not receiving disease modifying therapies. The results confirm the strong correlation between the RHS and RULM previously observed in SMA types 2 and 3a. Scoliosis surgery is associated with a reduction of 3 points in the RHS, 4.5 points in the HFMSE for the SMA 2 population, and a reduction of 11.8 points in the RHS, and 13.4 points in the HFMSE for the SMA 3a populations. When comparing the RHS and RULM, there is a lower correlation in the type 3a\u27s than the type 2 patients. In the SMA 2 population, there is no significant difference between the sexes in either the RHS or HFMSE trajectories. There is no significant difference in the RULM trajectory in the SMA 2 or 3a participants by sex. Conclusions: This study demonstrates that the RHS could be used in conjunction with other functional measures such as the RULM to holistically detect SMA disease progression. This will assist with fully understanding changes that occur with treatments, further defining trajectories and therapy outcomes

Clinical variability in spinal muscular atrophy type III

Objective: We report natural history data in a large cohort of 199 patients with spinal muscular atrophy (SMA) type III assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim of the study was to establish the annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, SMN2 copy number, and functional status. Methods: HFMSE longitudinal changes were assessed using piecewise linear mixed‐effects models. The dependency in the data due to repeated measures was accounted for by a random intercept per individual and an unstructured covariance R matrix was used as correlation structure. An additional descriptive analysis was performed for 123 patients, for a total of 375 12‐month assessments. Results: A break point at age 7 years was set for the whole cohort and for SMA IIIA and IIIB. Age, SMA type, and ambulatory status were significantly associated with changes in mean HFMSE score, whereas gender and SMN2 copy number were not. The increase in response before the break point of age 7 years is significant only for SMA IIIA (β = 1.79, p < 0.0001). After the break point, the change in the rate of HFMSE score significantly decrease for both SMA IIIA (β = −1.15, p < 0.0001) and IIIB (β = −0.69, p = 0.002). Interpretation: Our findings contribute to the understanding of the natural history of SMA type III and will be helpful in the interpretation of the real‐world data of patients treated with commercially available drugs. ANN NEUROL 2020;88:1109–111