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Recently exposed reservoir sediments, prone to colonization by invasive species, provide novel settings to test hypotheses related to soil conditions and propagule supply as potential drivers of plant assembly in disturbed ecosystems. We used a dam removal site in southwestern Wisconsin to examine the relationship between the physiochemical properties of dewatered sediments, seeding density, and plant community assembly. The plant communities from five seed densities (1000, 500, 250, 125, and 0 seed m−2) were annually assessed over four years. We hypothesized (1) that the native aboveground biomass and the proportion of native to invasive (non-seeded species) aboveground biomass would increase with the seeding density and (2) that the diversity of seeded native species would increase with a higher seeding density. We found evidence that sowing at least 500 seeds m−2 of prairie species increased their abundance, establishment, and plot diversity compared to non-seeded plants that persisted four years after seeding (p < 0.05). The seeding density treatments led to the assembly of two distinct communities: “native” and “invasive”. The “native” community, assembled in plots seeded with at least 500 seeds m−2, had a greater aboveground biomass and diversity (i.e., richness) of seeded plants compared to plots with lower seed densities, and its productivity was positively related to this richness. In the “weedy” community, the diversity of invasive species had no relationship to their aboveground biomass, likely because these species share similar traits (i.e., redundancy) and may have performed similar functions within the plant community. These findings suggest that the seeding density interacted with the disturbed soil resources to increase the diversity and productivity of seeded native species and may serve as a positive feedback mechanism for the establishment of native communities in dewatered sediments.

Abstract Heartworm disease, caused by Dirofilaria immitis, remains a significant threat to canines and felines. The development of parasites resistant to macrocyclic lactones (ML) has created a significant challenge to the control of the infection. The goal of this study was to determine if mice lacking a functional immune response would be susceptible to D. immitis. Immunodeficient NSG mice were susceptible to the infection, sustaining parasites for at least 15 weeks, with infective third-stage larvae molting and developing into the late fourth-stage larvae. Proteomic analysis of host responses to the infection revealed a complex pattern of changes after infection, with at least some of the responses directed at reducing immune control mechanisms that remain in NSG mice. NSG mice were infected with isolates of D. immitis that were either susceptible or resistant to MLs, as a population. The susceptible isolate was killed by ivermectin whereas the resistant isolate had improved survivability, while both isolates were affected by moxidectin. It was concluded that D. immitis survives in NSG mice for at least 15 weeks. NSG mice provide an ideal model for monitoring host responses to the infection and for testing parasites in vivo for susceptibility to direct chemotherapeutic activity of new agents.

Abstract Background Globally, governments put in place measures to curb the spread of COVID-19. Information on the effects of these measures on the urban poor is limited. This study aimed to explore the lived experiences of the urban poor in Kenya in the context of government’s COVID-19 response measures and its impact on the human right to food. Methods A qualitative study was conducted in two informal settlements in Nairobi between January and March 2021. Analysis draws on eight focus group discussions, eight in-depth interviews, 12 key informant interviews, two photovoice sessions and three digital storytelling sessions. Phenomenology was applied to understand an individual’s lived experiences with the human right to food during COVID − 19. Thematic analysis was performed using NVIVO software. Results The human right to food was affected in various ways. Many people lost their livelihoods, affecting affordability of food, due to response measures such as social distancing, curfew, and lockdown. The food supply chain was disrupted causing limited availability and access to affordable, safe, adequate, and nutritious food. Consequently, hunger and an increased consumption of low-quality food was reported. Social protection measures were instituted. However, these were inadequate and marred by irregularities. Some households resorted to scavenging food from dumpsites, skipping meals, sex-work, urban-rural migration and depending on food donations to survive. On the positive side, some households resorted to progressive measures such as urban farming and food sharing in the community. Generally, the response measures could have been more sensitive to the human rights of the urban poor. Conclusions The government’s COVID-19 restrictive measures exacerbated the already existing vulnerability of the urban poor to food insecurity and violated their human right to food. Future response measures should be executed in ways that respect the human right to food and protect marginalized people from resultant vulnerabilities.

Background Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. Methods and findings In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. Conclusion We present a first comprehensive molecular characterization of differences between two ARDS etiologies–COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions. Author summary Acute respiratory distress syndrome (ARDS) is a critical condition of the lung that can arise after severe infections, traumatic injury, or inhalation of toxins. Patients with ARDS are in a complex disease state and at risk of multiple clinical complications, such as thrombosis, lung fibrosis, acute kidney injury, and increased mortality. Currently, there are substantial challenges in the treatment of ARDS due to the high heterogeneity of this condition across patients. Our study compared metabolomic and proteomic changes induced by two different causes of ARDS—COVID-19 infection and bacterial sepsis. We used blood samples of patients from each ARDS group for molecular profiling and identified several hundred molecules from various biological processes differing between the two groups. Based on these results, we made several new propositions: (1) A role of arginine metabolism in long-term sequelae of ARDS. (2) The potential use of JAK-STAT pathway inhibitors for bacterial sepsis-induced ARDS. (3) ARDS-associated mitochondrial dysfunction as a reason for poor prognosis of acute kidney injury that occurred during ARDS. (4) A synergy between prothrombotic processes as a potential reason for hypercoagulation in ARDS. We hypothesize that combination therapy targeting two or more of these prothrombotic processes may ameliorate hypercoagulation.

Dirofilaria immitis, also known as heartworm, is a major parasitic threat for dogs and cats around the world. Because of its impact on the health and welfare of companion animals, heartworm disease is of huge veterinary and economic importance especially in North America, Europe, Asia and Australia. Within the animal health market many different heartworm preventive products are available, all of which contain active components of the same drug class, the macrocyclic lactones. In addition to compliance issues, such as under-dosing or irregular treatment intervals, the occurrence of drug-resistant heartworms within the populations in the Mississippi River areas adds to the failure of preventive treatments. The objective of this review is to provide an overview of the disease, summarize the current disease control measures and highlight potential new avenues and best practices for treatment and prevention.

Chronic airway diseases including asthma and COPD are prevalent and high-burden conditions with the majority of patients successfully managed in the primary care setting. However, for some patients with more complex disease such as difficult-to-treat or severe asthma, or complex COPD, tertiary care is required. This review provides an overview of the successful tertiary care multidisciplinary respiratory service that operates in Newcastle, New South Wales, Australia, which has been integrated into the tertiary care outpatient clinics for almost three decades. The service is multifaceted in terms of the clinical care it provides; it includes an “Inpatient Service”, “Asthma Management Service”, “Difficult Airways Clinic”, “Drug Administration Clinic”, “Rapid Access Clinic” and “Pulmonary Rehabilitation”, and has an integrated research programme. The core of the multidisciplinary approach to airway diseases is a person-centred model of care, the “Treatable Traits” approach. The staffing of this service comprises consultant physicians, respiratory advanced trainees, respiratory scientists, physiotherapists, speech pathologists, nurse specialists and a nurse consultant. Patients that present to this service undergo an initial assessment and clinical review by team members, synthesis of relevant data, and development of a diagnosis and management plan. Based on this clinical review, specific interventions are determined according to the traits identified. Over time the service has evolved to accommodate the increasing numbers of patients requiring access to the Difficult Airways Clinic assessment and therapies. This has been facilitated by partnering with the Centres of Excellence in Severe Asthma and Treatable Traits to develop educational and practice management tools.

Abstract Patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (PH) are at increased risk when undergoing anesthesia and major surgery. Data on outcomes for elective orthopedic surgery in patients with PH are limited. A patient pathway was established to provide access to elective lower limb arthroplasty. This included assessment of orthopedic needs, fitness for anesthesia, preoperative optimization, and intra‐ and postoperative management. Patient data were retrospectively retrieved using patient's hospital records. Between 2012 and 2020, 29 operations (21 total hip replacements [THRs], 7 total knee replacements [TKRs], 1 total hip revision) were performed in 25 patients (mean age: 67 years). Perioperatively, 72% were treated with low‐dose intravenous prostanoid. All had arterial lines, and central access and perioperative lithium dilution cardiac output monitoring was used in 86% of cases. Four patients underwent GA, 21 spinal anesthesia, and 4 CSE anesthesia. Supplemental nerve blocks were performed in all patients undergoing general, and 12 of 21 undergoing spinal anesthesia. All were managed in high dependency postoperatively. Hospital length of stay and complication rates were higher than reported in non‐PH patients. Perioperative complications included hypotension requiring vasopressors (n = 10), blood transfusion (n = 7), nonorthopedic infection (n = 4), and decompensated right heart failure (n = 1). There was no associated mortality. All implants were functioning well at 6 weeks and subsequent follow‐up. EmPHasis‐10 quality of score decreased by 5.5 (±2.1) (p = 0.04). A dedicated multiprofessional pathway can be used to safely select and manage patients with PH through elective lower limb arthroplasty.

Nematode parasites undermine human health and global food security. The frontline anthelmintic portfolio used to treat parasitic nematodes is threatened by the escalation of anthelmintic resistance, resulting in a demand for new drug targets for parasite control. Nematode neuropeptide signalling pathways represent an attractive source of novel drug targets which currently remain unexploited. The complexity of the nematode neuropeptidergic system challenges the discovery of new targets for parasite control, however recent advances in parasite ‘omics’ offers an opportunity for the in silico identification and prioritization of targets to seed anthelmintic discovery pipelines. In this study we employed Hidden Markov Model-based searches to identify ~1059 Caenorhabditis elegans neuropeptide G-protein coupled receptor (Ce-NP-GPCR) encoding gene homologs in the predicted protein datasets of 10 key parasitic nematodes that span several phylogenetic clades and lifestyles. We show that, whilst parasitic nematodes possess a reduced complement of Ce-NP-GPCRs, several receptors are broadly conserved across nematode species. To prioritize the most appealing parasitic nematode NP-GPCR anthelmintic targets, we developed a novel in silico nematode parasite drug target prioritization pipeline that incorporates pan-phylum NP-GPCR conservation, C. elegans-derived reverse genetics phenotype, and parasite life-stage specific expression datasets. Several NP-GPCRs emerge as the most attractive anthelmintic targets for broad spectrum nematode parasite control. Our analyses have also identified the most appropriate targets for species- and life stage- directed chemotherapies; in this context we have identified several NP-GPCRs with macrofilaricidal potential. These data focus functional validation efforts towards the most appealing NP-GPCR targets and, in addition, the prioritization strategy employed here provides a blueprint for parasitic nematode target selection beyond NP-GPCRs.

We implemented an in-person survey of parents/guardians concerning COVID-19 vaccine for a predominantly African-American Medicaid pediatric patient population between the ages of 6–59 months at a Children’s Hospital General Pediatric Clinic in Norfolk, VA. Vaccine hesitancy was predominantly based on concerns surrounding safety and overall need for the vaccine.

Abstract Background Cell-free plasma mitochondrial DNA (mtDNA) levels are associated with endothelial dysfunction and differential outcomes in critical illness. A substantial alteration in metabolic homeostasis is commonly observed in severe critical illness. We hypothesized that metabolic profiles significantly differ between critically ill patients relative to their level of plasma mtDNA. Methods We performed a metabolomic study with biorepository plasma samples collected from 73 adults with systemic inflammatory response syndrome or sepsis at a single academic medical center. Patients were treated in a 20-bed medical ICU between 2008 and 2010. To identify key metabolites and metabolic pathways related to plasma NADH dehydrogenase 1 (ND1) mtDNA levels in critical illness, we first generated metabolomic data using gas and liquid chromatography-mass spectroscopy. We performed fold change analysis and volcano plot visualization based on false discovery rate-adjusted p values to evaluate the distribution of individual metabolite concentrations relative to ND1 mtDNA levels. We followed this by performing orthogonal partial least squares discriminant analysis to identify individual metabolites that discriminated ND1 mtDNA groups. We then interrogated the entire metabolomic profile using pathway overrepresentation analysis to identify groups of metabolite pathways that were different relative to ND1 mtDNA levels. Results Metabolomic profiles significantly differed in critically ill patients with ND1 mtDNA levels ≥ 3200 copies/μl plasma relative to those with an ND1 mtDNA level

Abstract Monoclonal antibodies directed against interleukin (IL)‐5, such as mepolizumab and benralizumab, are an effective and established treatment for severe eosinophilic asthma. Here, we present a patient with eosinophilic asthma with a partial clinical response to mepolizumab initially, as measured by these biomarkers, who when investigated was found to have refractory airway eosinophilia. Escalation of the mepolizumab dose led to further but still only partial response. A treatment trial with benralizumab was more successful and led to suppression of airway eosinophilia. We review the literature, focusing on eosinophil biology at the tissues and the different mechanisms of action of the two agents.

Unexpected questing activity of ticks was noted during the winter months of January and February in the Central Midwestern states of Kansas, Missouri, Oklahoma, and Arkansas. From nine geographically distinct locations, four species of ticks were collected using the flagging method, of which the lone star tick, Amblyomma americanum, was most abundant, followed by the American dog tick, Dermacentor variabilis, the Gulf coast tick, Amblyomma maculatum, and the Black legged tick, Ixodes scapularis. More A. americanum nymphs were caught questing than male or female adults. The winter activity of these medically important ticks in this region poses concern for public health and offers an insight into future tick activity in light of ongoing climate change. More studies on the seasonality of these tick species, and how different climate parameters affect their seasonal activity in this region are warranted and would be expected to benefit for both human and veterinary medicine.

Climate extreme events exert disproportionate impacts on ecosystems and humankind. Focusing on univariate statistics to estimate the harm from compound extreme events usually falls short in communicating the real risk. Here, the co-occurrence of hot, dry, and windy events (HDWs) in the central United States was analyzed over the period 1949–2018. Results demonstrate south-west Kansas and north Texas as locations where HDWs are more frequent. The combination of drought and a heatwave in 1980 and 2011, increased the likelihood of HDWs. Use of copula enables the study of the co-occurrence of multiple extremes. The copula approach identified a greater risk of HDWs compared with traditional empirical analysis. The dependence structure between the temperature, humidity, and wind variables showed no effect on the co-occurrence frequency of HDWs in the warm-season (May through September). Results suggest an increase in the risk of HDWs in spite of the historical wind speed drop across the majority of Great Plains. Multivariate perspectives are necessary for a more informed assessment of compound extremes risk and for improved design of adaption strategies.

Background: State parties to human rights conventions and declarations are often faced with the seemingly contradictory problem of having an obligation to protect people from harmful practices while also having an obligation to enable access to culturally appropriate effective healing. As people increasingly migrate across the globe, previous distinctions between ‘traditional’ and ‘complementary and alternative medicine’ practices are being transcended. There are connections across transnational healing pathways that link local, national, and global movements of people and knowledge. Objective: This paper contributes to the development of the concept and practice of the right to health in all its forms, exploring the right to traditional, complementary, and alternative health (R2TCAH) across different contexts. Design: The paper draws on four settings – England, South Africa, Kenya, and Jordan – and is based on key informant interviews and a literature review undertaken in 2010, and updated in 2013. The paper begins by reviewing the international legal context for the right to health. It then considers legal and professional regulations from the global north and south. Results: Additional research is needed to establish the legal basis, compare regulatory frameworks, and explore patient and provider perspectives of regulation. This leads to being able to make recommendations on how to balance protection from harm and the obligation to ensure culturally appropriate services. Such an exploration must also challenge Western theories of human rights. Key concepts, such as individual harm, consent, and respect of the autonomy of the individual already established and recognised in international health law, could be adopted in the development of a template for future comparative research. Conclusions: Exploration of the normative content of the right to health in all its forms will contribute to supporting traditional, complementary, and alternative health service users and providers in terms of access to information, non-discrimination, clarification of state obligations, and accountability.

The basics of climate must be understood to have a climate literate populace. Understanding climatic change is a wicked problem. This work identifies three foundational content challenges to climate and climate change education, discusses them thoroughly, and offers graphics and conceptual models to address this content in the classroom. The three concepts covered are: 1) conflation between weather and climate, 2) understanding the differences among spatial and temporal scales of climate, and 3) distinguishing between natural climate variability and human-driven climatic change. The goal of this work is to offer science-based pathways for teaching important concepts in climate change education.