Environmental-mechanistic modelling of the impact of global change on human zoonotic disease emergence: A case study of Lassa fever

1. Human infectious diseases are a significant threat to global human health and economies (e.g., Ebola, SARs), with the majority of infectious diseases having an animal source (zoonotic). Despite their importance, the lack of a quantitative predictive framework hampers our understanding of how spill-overs of zoonotic infectious diseases into the human population will be impacted by global environmental stressors. 2. Here, we create an environmental-mechanistic model for understanding the impact of global change on the probability of zoonotic disease reservoir host-human spill-over events. As a case study, we focus on Lassa fever virus (LAS). We firstly quantify the spatial determinants of LAS outbreaks, including the phylogeographic distribution of its reservoir host Natal multimammate rat (Mastomys natalensis) (LAS host). Secondly, we use these determinants to inform our environmental-mechanistic model to estimate present day LAS spill-over events and the predicted impact of climate change, human population growth, and land use by 2070. 3. We find phylogeographic evidence to suggest that LAS is confined to only one clade of LAS host (Western clade Mastomys natalensis), and that the probability of its occurrence was a major determinant of the spatial variation in LAS historical outbreaks (69.8%), along with human population density (20.4%). Our estimates for present day LAS spill-over events from our environmental-mechanistic model were consistent with observed patterns, and we predict an increase in events per year by 2070 from 195,125 to 406,725 within the LAS endemic western African region. Of the component drivers, climate change and human population growth are predicted to have the largest effects by increasing landscape suitability for the host and human-host contact rates, while land use change has only a weak impact on the number of future events. 4. LAS spill-over events did not respond uniformly to global environmental stressors, and we suggest that understanding the impact of global change on zoonotic infectious disease emergence requires an understanding of how reservoir host species respond to environmental change. Our environmental-mechanistic modelling methodology provides a novel generalizable framework to understand the impact of global change on the spill-over of zoonotic diseases

Continuous-Flow Left Ventricular Assist Device Support in Patients with Ischemic Versus Nonischemic Cardiomyopathy.

To determine whether the cause of cardiomyopathy affects outcomes in patients who undergo continuous-flow left ventricular assist device support, we compared postimplant adverse events and survival between patients with ischemic and nonischemic cardiomyopathy. The inclusion criteria for the ischemic group were a history of myocardial infarction or revascularization (coronary artery bypass grafting or percutaneous coronary intervention), ≥75% stenosis of the left main or proximal left anterior descending coronary artery, or ≥75% stenosis of ≥2 epicardial vessels. From November 2003 through March 2016, 526 patients underwent device support: 256 (48.7%) in the ischemic group and 270 (51.3%) in the nonischemic group. The ischemic group was older (60.0 vs 50.0 yr), included more men than women (84.0% vs 72.6%), and had more comorbidities. More patients in the nonischemic group were able to have their devices explanted after left ventricular recovery (5.9% vs 2.0%; P=0.02). More patients in the ischemic group had gastrointestinal bleeding (31.2% vs 22.6%; P=0.03), particularly from arteriovenous malformations (20.7% vs 11.9%; P=0.006) and ulcers (16.4% vs 9.3%; P=0.01). Kaplan-Meier analysis revealed no difference in overall survival between groups (P=0.24). Older age, previous sternotomy, higher total bilirubin level, and concomitant procedures during device implantation independently predicted death (P ≤0.03), whereas cause of heart failure did not (P=0.08). Despite the similarity in overall survival between groups, ischemic cardiomyopathy was associated with more frequent gastrointestinal bleeding. This information may help guide the care of patients with ischemic cardiomyopathy who receive continuous-flow left ventricular assist device support

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

Assessing disease progression in spinal muscular atrophy, current gaps, and opportunities: a narrative review

\ua9 2025 The Author(s). Spinal Muscular Atrophy is a genetic disorder causing muscle atrophy and progressive weakness. People living with the condition can have a significant heterogenous phenotype ranging from arrest of motor development to mild impairment. Assessing disease severity has been done using a range of outcome measures that can be classified by body structure or function, by activities or by participation. Functional outcome measures can be generic measures, used to compare individuals or populations against general norms, or disease-specific measures designed to fit disease characteristics. Outcome measures assessing participation are primarily used to capture patients\u27 perceptions of health-related quality of life, daily activity abilities, caregiver burden, and the impact of physical symptoms like fatigue or pain. When assessing disease progression, often the focus on functional abilities has served as an overall indicator of change. With the appearance of disease modifying therapies and the need to evaluate the impact that they had in the course of the disease, new requirements for the existing assessments measure had appeared. The current available toolkit is able to capture a significant spectrum of both, natural history and effect of new treatments but the increased survival, changes in fatigue, bulbar function and others will benefit from further assessment

Clinical Predictors and Outcomes After Left Ventricular Assist Device Implantation and Tracheostomy

BACKGROUND: Postoperative respiratory failure is a major complication that affects up to 10% of patients who undergo cardiac surgery and has a high in-hospital mortality rate. Few studies have investigated whether patients who require tracheostomy for postoperative respiratory failure after continuous-flow left ventricular assist device (CF-LVAD) implantation have worse survival outcomes than patients who do not. OBJECTIVE: To identify risk factors for respiratory failure necessitating tracheostomy in CF-LVAD recipients and to compare survival outcomes between those who did and did not require tracheostomy. METHODS: Consecutive patients who underwent primary CF-LVAD placement at a single institution between August 1, 2002, and December 31, 2019, were retrospectively reviewed. Propensity score matching accounted for baseline differences between the tracheostomy and nontracheostomy groups. Multivariate logistic regression was used to identify tracheostomy risk factors and 90-day survival; Kaplan-Meier analysis was used to assess midterm survival. RESULTS: During the study period, 664 patients received a CF-LVAD; 106 (16.0%) underwent tracheostomy for respiratory failure. Propensity score matching produced 103 matched tracheostomy-nontracheostomy pairs. Patients who underwent tracheostomy were older (mean [SD] age, 57.9 [12.3] vs 54.6 [13.9] years; P = .02) and more likely to need preoperative mechanical circulatory support (61.3% vs 47.8%; P = .01) and preoperative intubation (27.4% vs 8.8%; P \u3c .001); serum creatinine was higher in the tracheostomy group (mean [SD], 1.7 [1.0] vs 1.4 [0.6] mg/dL; P \u3c .001), correlating with tracheostomy need (odds ratio, 1.76; 95% CI, 1.21-2.56; P = .003). Both before and after propensity matching, 30-day, 60-day, 90-day, and 1-year survival were worse in patients who underwent tracheostomy. Median follow-up was 0.8 years (range, 0.0-11.2 years). Three-year Kaplan-Meier survival was significantly worse for the tracheostomy group before (22.0% vs 61.0%; P \u3c .001) and after (22.4% vs 48.3%; P \u3c .001) matching. CONCLUSION: Given the substantially increased probability of death in patients who develop respiratory failure and need tracheostomy, those at high risk for respiratory failure should be carefully considered for CF-LVAD implantation. Comprehensive management to decrease respiratory failure before and after surgery is critical

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

Serial casting for contractures in SMA: consensus derived guidelines for treatment

Copyright \ua9 2025 Brown, Hoffman, Corbo-Galli, Kelley, Carry, Civitello, Coratti, DeSanctis, Duong, Driscoll, Flickinger, Glanzman, Jones, Maczek, Moat, Montes, Muni-Lofra, Nelson, Pasternak, Valle and Krosschell.Background: Individuals with Spinal Muscular Atrophy (SMA) often present with muscle contractures. Serial casting has been used in a variety of other peripheral nerve, muscle, and central nervous system disorders to improve knee and ankle range of motion limitations and functional performance in both ambulatory and non-ambulatory individuals. Objective: The goal of this study was to reach a consensus about the parameters, considerations and general guidelines that should inform practice when serial casting to improve flexibility in individuals with SMA. Methods: This international effort was conducted between August 2020 and May 2023. An expert panel of physical therapists was assembled with multiple panel meetings and a 2-round Delphi survey performed covering topics relevant to serial casting which included three domains: clinical appropriateness, program-based considerations and program adherence/feasibility. Consensus was reached for all items in the three topic areas using a validity index of >75%. Following completion of the Delphi survey, community insights from patients and caregivers were collected via semi-structured interview. Results: This study included the synthesis of meetings from the initial expert panel which produced a comprehensive survey for the different considerations when performing serial casting for an individual with SMA. The study also included the completion of a Delphi survey by 18 therapists in round 1 and 15 therapists in round 2 for a consensus on 296 items. Strong consensus was obtained in all three domains with 96.6% agreement for clinical appropriateness, 95.0% agreement for program-based considerations, and 96.9% for program adherence/feasibility. A guideline document was developed enumerating the specific items detailed in the survey. Community perspectives were utilized to support the results of the Delphi survey and to add insight into real-world experience. Conclusion: The serial casting guidelines developed upon collaborative discussions from the expert panel and from the Delphi survey consensus and semi-structured interviews, should be utilized when applying serial casts to patients with spinal muscular atrophy. Future endeavors should look to apply the guideline recommendations to determine casting efficacy for improving joint contracture and impact on function for those with SMA