Transmission potential of human schistosomes can be driven by resource competition among snail intermediate hosts.

Predicting and disrupting transmission of human parasites from wildlife hosts or vectors remains challenging because ecological interactions can influence their epidemiological traits. Human schistosomes, parasitic flatworms that cycle between freshwater snails and humans, typify this challenge. Human exposure risk, given water contact, is driven by the production of free-living cercariae by snail populations. Conventional epidemiological models and management focus on the density of infected snails under the assumption that all snails are equally infectious. However, individual-level experiments contradict this assumption, showing increased production of schistosome cercariae with greater access to food resources. We built bioenergetics theory to predict how resource competition among snails drives the temporal dynamics of transmission potential to humans and tested these predictions with experimental epidemics and demonstrated consistency with field observations. This resource-explicit approach predicted an intense pulse of transmission potential when snail populations grow from low densities, i.e., when per capita access to resources is greatest, due to the resource-dependence of cercarial production. The experiment confirmed this prediction, identifying a strong effect of infected host size and the biomass of competitors on per capita cercarial production. A field survey of 109 waterbodies also found that per capita cercarial production decreased as competitor biomass increased. Further quantification of snail densities, sizes, cercarial production, and resources in diverse transmission sites is needed to assess the epidemiological importance of resource competition and support snail-based disruption of schistosome transmission. More broadly, this work illustrates how resource competition can sever the correspondence between infectious host density and transmission potential.

Interventions can shift the thermal optimum for parasitic disease transmission.

Temperature constrains the transmission of many pathogens. Interventions that target temperature-sensitive life stages, such as vector control measures that kill intermediate hosts, could shift the thermal optimum of transmission, thereby altering seasonal disease dynamics and rendering interventions less effective at certain times of the year and with global climate change. To test these hypotheses, we integrated an epidemiological model of schistosomiasis with empirically determined temperature-dependent traits of the human parasite Schistosoma mansoni and its intermediate snail host (Biomphalaria spp.). We show that transmission risk peaks at 21.7 °C (Topt ), and simulated interventions targeting snails and free-living parasite larvae increased Topt by up to 1.3 °C because intervention-related mortality overrode thermal constraints on transmission. This Topt shift suggests that snail control is more effective at lower temperatures, and global climate change will increase schistosomiasis risk in regions that move closer to Topt Considering regional transmission phenologies and timing of interventions when local conditions approach Topt will maximize human health outcomes.

Risk Factors for Mortality Among Children Younger Than Age 5 Years With Severe Diarrhea in Low- and Middle-income Countries: Findings From the World Health Organization-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks.

BACKGROUND: Diarrhea is the second leading cause of death in children younger than 5 years of age globally. The burden of diarrheal mortality is concentrated in low-resource settings. Little is known about the risk factors for childhood death from diarrheal disease in low- and middle-income countries. METHODS: Data from the World Health Organization (WHO)-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks, which are composed of active, sentinel, hospital-based surveillance sites, were analyzed to assess mortality in children <5 years of age who were hospitalized with diarrhea between 2008 and 2018. Case fatality risks were calculated, and multivariable logistic regression was performed to identify risk factors for mortality. RESULTS: This analysis comprises 234 781 cases, including 1219 deaths, across 57 countries. The overall case fatality risk was found to be 0.5%. Risk factors for death in the multivariable analysis included younger age (for <6 months compared with older ages, odds ratio [OR] = 3.54; 95% confidence interval [CI], 2.81-4.50), female sex (OR = 1.18; 95% CI, 1.06-1.81), presenting with persistent diarrhea (OR = 1.91; 95% CI, 1.01-3.25), no vomiting (OR = 1.13; 95% CI, .98-1.30), severe dehydration (OR = 3.79; 95% CI, 3.01-4.83), and being negative for rotavirus on an enzyme-linked immunosorbent assay test (OR = 2.29; 95% CI, 1.92-2.74). Cases from the African Region had the highest odds of death compared with other WHO regions (OR = 130.62 comparing the African Region with the European Region; 95% CI, 55.72-422.73), whereas cases from the European Region had the lowest odds of death. CONCLUSIONS: Our findings support known risk factors for childhood diarrheal mortality and highlight the need for interventions to address dehydration and rotavirus-negative diarrheal infections.

Experimental water hyacinth invasion and destructive management increase human schistosome transmission potential.

Invasive species cause environmental degradation, decrease biodiversity, and alter ecosystem function. Invasions can also drive changes in vector-borne and zoonotic diseases by altering important traits of wildlife hosts or disease vectors. Managing invasive species can restore biodiversity and ecosystem function, but it may have cascading effects on hosts, parasites, and human risk of infection. Water hyacinth, Eichhornia crassipes, is an extremely detrimental invader in many sites of human schistosome transmission, especially in Lake Victoria, where hyacinth is correlated with high snail abundance and hotspots of human schistosome infection. Hyacinth is often managed via removal or in situ destruction, but the effects of these strategies on snail intermediate hosts and schistosomes are not known. We evaluated the effects of water hyacinth invasion and these management strategies on the dynamics of human schistosomes, Schistosoma mansoni, and snails, Biomphalaria glabrata, in experimental mesocosms over 17 weeks. We hypothesized that hyacinth, which is inedible to snails, would affect snail growth, reproduction, and cercariae production through the balance of its competitive effects on edible algae and its production of edible detritus. We predicted that destruction would create a pulse of edible detrital resources, thereby increasing snail growth, reproduction, and parasite production. Conversely, we predicted that removal would have small or negligible effects on snails and schistosomes, because it would alleviate competition on edible algae without generating a resource pulse. We found that hyacinth invasion suppressed algae, changed the timing of peak snail abundance, and increased total production of human-infectious cercariae ~6-fold relative to uninvaded controls. Hyacinth management had complex effects on algae, snails, and schistosomes. Removal increased algal growth and snail abundance (but not biomass), and slightly reduced schistosome production. In contrast, destruction increased snail biomass (but not abundance), indicating increases in body size. Destruction caused the greatest schistosome production (10-fold more than the control), consistent with evidence that larger snails with greater access to food are most infectious. Our results highlight the dynamic effects of invasion and management on a globally impactful human parasite and its intermediate host. Ultimately, preventing or removing hyacinth invasions would simultaneously benefit human and environmental health outcomes.

Central line-associated Rhizobium radiobacter bloodstream infection in two allogeneic hematopoietic cell transplant recipients.

INTRODUCTION: Rhizobium radiobacter is a gram-negative, opportunistic phytopathogen that rarely causes human infections. We report two cases of Rhizobium radiobacter central line-associated bloodstream infection (CLABSI) in allogeneic hematopoietic cell transplantation (alloHCT) recipients. We review previous reports and common microbiological characteristics associated with this organism. CASE REPORTS: Two adult males developed R. radiobacter CLABSIs at day +81 and day +77 post-alloHCT. Patient one was asymptomatic on presentation while patient two was febrile. One patient had a polymicrobial infection, which has not been previously described. The presence of high-level ceftazidime resistance in both patients suggests third-generation cephalosporin resistance may be more common than previously recognized. MANAGEMENT AND OUTCOME: For both patients, microbiologic clearance was achieved through peripherally inserted central catheter removal and initiation of intravenous cefepime. Antibiotic therapy was narrowed to oral levofloxacin for a total 14-day course from the time of first negative blood culture. There has been no subsequent recurrence of R. radiobacter infection at 12 and 5 months of follow-up for patients one and two, respectively. DISCUSSION: These two cases add to the scant literature characterizing R. radiobacter infection following alloHCT. Immunosuppressive agents for graft-versus-host disease prophylaxis may have predisposed these patients to R. radiobacter infection. Our reports, and previously reported cases, suggest R. radiobacter exhibits low virulence, mild symptom burden, and does not confer a high mortality risk. In the alloHCT setting, further accumulation of cases is needed to aid in understanding clinical features and characteristics of R. radiobacter infection.

Do you know the Wooly Bully? Testing era-based knowledge to verify participant age online.

People in online studies sometimes misrepresent themselves. Regardless of their motive for doing so, participant misrepresentation threatens the validity of research. Here, we propose and evaluate a way to verify the age of online respondents: a test of era-based knowledge. Across six studies (N = 1543), participants of various ages completed an age verification instrument. The instrument assessed familiarity with cultural phenomena (e.g., songs and TV shows) from decades past and present. We consistently found that our instrument discriminated between people of different ages. In Studies 1a and 1b, self-reported age correlated strongly with performance on the instrument (mean r = .8). In Study 2, the instrument reliably detected imposters who we knew were misrepresenting their age. For impostors, self-reported age did not correlate with performance on the instrument (r = .077). Finally, in Studies 3a, 3b, and 3c, the instrument remained robust with African Americans, people from low educational backgrounds, and recent immigrants to the United States. Thus, our instrument shows promise for verifying the age of online respondents, and, as we discuss, our approach of assessing "insider knowledge" holds great promise for verifying other identities within online studies.

Snail juvenile growth rate as a rapid predictor of the transmission potential of parasitizing human schistosomes.

Host and parasite traits that are sensitive to environmental perturbations merit special attention in the mitigation of diseases. While life table experiments allow a practical evaluation of variability of these traits with environmental change, they are cost and resource intensive. Here, we use a model snail host-trematode parasite system to test the efficacy of an expeditious alternative. Rapidly changing host traits (such as juvenile growth rate) can be used as effective predictors of parasite transmission potential across a range of environmental factors. This approach can be applied to anticipate epidemiological changes under diverse environmental scenarios.

Resource fluctuations inhibit the reproduction and virulence of the human parasite Schistosoma mansoni in its snail intermediate host.

Resource availability can powerfully influence host-parasite interactions. However, we currently lack a mechanistic framework to predict how resource fluctuations alter individual infection dynamics. We address this gap with experiments manipulating resource supply and starvation for a human parasite, Schistosoma mansoni, and its snail intermediate host to test a hypothesis derived from mechanistic energy budget theory: resource fluctuations should reduce schistosome reproduction and virulence by inhibiting parasite ingestion of host biomass. Low resource supply caused hosts to remain small, reproduce less and produce fewer human-infectious cercariae. Periodic starvation also inhibited cercarial production and prevented infection-induced castration. The periodic starvation experiment also revealed substantial differences in fit between two bioenergetic model variants, which differ in their representation of host starvation. Simulations using the best-fit parameters of the winning model suggest that schistosome performance substantially declines with resource fluctuations with periods greater than 7 days. These experiments strengthen mechanistic theory, which can be readily scaled up to the population level to understand key feedbacks between resources, host population dynamics, parasitism and control interventions. Integrating resources with other environmental drivers of disease in an explicit bioenergetic framework could ultimately yield mechanistic predictions for many disease systems.

Identification of clam plasma proteins that bind its pathogen Quahog Parasite Unknown.

The hard clam (Mercenaria mercenaria) is among the most economically-important marine species along the east coast of the United States, representing the first marine resource in several Northeastern states. The species is rather resilient to infections and the only important disease of hard clams results from an infection caused by Quahog Parasite Unknown (QPX), a protistan parasite that can lead to significant mortality events in wild and aquacultured clam stocks. Though the presence of QPX disease has been documented since the 1960s, little information is available on cellular and molecular interactions between the parasite and the host. This study examined the interactions between the clam immune system and QPX cells. First, the effect of clam plasma on the binding of hemocytes to parasite cells was evaluated. Second, clam plasma proteins that bind QPX cells were identified through proteomic (LC-MS/MS) analyses. Finally, the effect of prior clam exposure to QPX on the abundance of QPX-reactive proteins in the plasma was evaluated. Results showed that plasma factors enhance the attachment of hemocytes to QPX. Among the proteins that specifically bind to QPX cells, several lectins were identified, as well as complement component proteins and proteolytic enzymes. Furthermore, results showed that some of these lectins and complement-related proteins are inducible as their abundance significantly increased following QPX challenge. These results shed light on plasma proteins involved in the recognition and binding of parasite cells and provide molecular targets for future investigations of factors involved in clam resistance to the disease, and ultimately for the selection of resistant clam stocks.

Ectopic POU5F1 in the male germ lineage disrupts differentiation and spermatogenesis in mice.

Expression levels of the pluripotency determinant, POU5F1, are tightly regulated to ensure appropriate differentiation during early embryogenesis. POU5F1 is also present in the spermatogonial stem cell/progenitor cell population in mice and it is downregulated as spermatogenesis progresses. To test if POU5F1 downregulation is required for SSCs to differentiate, we produced transgenic mice that ubiquitously express POU5F1 in Cre-expressing lineages. Using a Vasa-Cre driver to produce ectopic POU5F1 in all postnatal germ cells, we found that POU5F1 downregulation was necessary for spermatogonial expansion during the first wave of spermatogenesis and for the production of differentiated spermatogonia capable of undergoing meiosis. In contrast, undifferentiated spermatogonia were maintained throughout adulthood, consistent with a normal presence of POU5F1 in these cells. The results suggest that POU5F1 downregulation in differentiating spermatogonia is a necessary step for the progression of spermatogenesis. Further, the creation of a transgenic mouse model for conditional ectopic expression of POU5F1 may be a useful resource for studies of POU5F1 in other cell lineages, during tumorogenesis and cell fate reprogramming.

Hot-Melt Extrusion-Based Dexamethasone-PLGA Implants: Physicochemical, Physicomechanical, and Surface Morphological Properties and In Vitro Release Corrected for Drug Degradation.

Developing bioequivalent (BE) generic products of complex dosage forms like intravitreal implants (IVIs) of corticosteroids such as dexamethasone prepared using hot-melt extrusion (HME), based on biodegradable poly (lactide-co-glycolide) (PLGA) polymers, can be challenging. A better understanding of the relationship between the physicochemical and physicomechanical properties of IVIs and their effect on drug release and ocular bioavailability is crucial to develop novel BE approaches. It is possible that the key physicochemical and physicomechanical properties of IVIs such as drug properties, implant surface roughness, mechanical strength and toughness, and implant erosion could vary for different compositions, resulting in changes in drug release. Therefore, this study investigated the hypothesis that biodegradable ophthalmic dexamethasone-loaded implants with 20% drug and 80% PLGA polymer(s) prepared using single-pass hot-melt extrusion (HME) differ in physicochemical and/or physicomechanical properties and drug release depending on their PLGA polymer composition. Acid end-capped PLGA was mixed with an ester end-capped PLGA to make three formulations: HME-1, HME-2, and HME-3, containing 100%, 80%, and 60% w/w of the acid end-capped PLGA. Further, this study compared the drug release between independent batches of each composition. In vitro release tests (IVRTs) indicated that HME-1 implants can be readily distinguished by their release profiles from HME-2 and HME-3, with the release being similar for HME-2 and HME-3. In the early stages, drug release generally correlated well with polymer composition and implant properties, with the release increasing with PLGA acid content (for day-1 release, R2 = 0.80) and/or elevated surface roughness (for day-1 and day-14 release, R2 ≥ 0.82). Further, implant mechanical strength and toughness correlated inversely with PLGA acid content and day-1 drug release. Drug release from independent batches was similar for each composition. The findings of this project could be helpful for developing generic PLGA polymer-based ocular implant products.

Stimulation of perforant path fibers induces LTP concurrently in amygdala and hippocampus in awake freely behaving rats.

Long-term potentiation (LTP) which has long been considered a cellular model for learning and memory is defined as a lasting enhancement in synaptic transmission efficacy. This cellular mechanism has been demonstrated reliably in the hippocampus and the amygdala-two limbic structures implicated in learning and memory. Earlier studies reported on the ability of cortical stimulation of the entorhinal cortex to induce LTP simultaneously in the two sites. However, to retain a stable baseline of comparison with the majority of the LTP literature, it is important to investigate the ability of fiber stimulation such as perforant path activation to induce LTP concurrently in both structures. Therefore, in this paper we report on concurrent LTP in the basolateral amygdala (BLA) and the dentate gyrus (DG) subfield of the hippocampus induced by theta burst stimulation of perforant path fibers in freely behaving Sprague-Dawley rats. Our results indicate that while perforant path-evoked potentials in both sites exhibit similar triphasic waveforms, the latency and amplitude of BLA responses were significantly shorter and smaller than those of DG. In addition, we observed no significant differences in either the peak level or the duration of LTP between DG and BLA.

People See Political Opponents as More Stupid Than Evil.

Affective polarization is a rising threat to political discourse and democracy. Public figures have expressed that "conservatives think liberals are stupid, and liberals think conservatives are evil." However, four studies (N = 1,660)-including a representative sample-reveal evidence that both sides view political opponents as more unintelligent than immoral. Perceiving the other side as "more stupid than evil" occurs both in general judgments (Studies 1, 3, and 4) and regarding specific issues (Study 2). Study 4 also examines "meta-perceptions" of how Democrats and Republicans disparage one another, revealing that people correctly perceive that both Democrats and Republicans see each other as more unintelligent than immoral, although they exaggerate the extent of this negativity. These studies clarify the way everyday partisans view each other, an important step in designing effective interventions to reduce political animosity.

Uterine Rupture Secondary to Pyomyoma, Leading to Intra-Abdominal Abscesses following an Uncomplicated Vaginal Delivery.

Background: Pyomyomas are an infrequent complication of uterine fibroids and, in extremely rare cases, the cause of spontaneous uterine rupture. A few documented cases were managed conservatively with oral antibiotics and CT-guided drainage or myomectomy with fertility preserved. However, treatment more frequently involves IV antibiotics and a hysterectomy. Case Description. A 31-year-old G2P0111 PPD 7 presented with intra-abdominal abscesses of unknown source. She was treated with broad-spectrum antibiotics, image-guided percutaneous (IR) drainage of the largest abscess, and surgical exploration with debridement. During surgery, she was diagnosed with spontaneous uterine rupture. The uterine defect was successfully repaired, and she was able to be successfully managed with fertility-sparing treatment. The patient ultimately did not require a hysterectomy. The final pathology was consistent with pyomyoma. Conclusion: In a majority of cases, pyomyoma treatment requires a hysterectomy, and fertility is unable to be preserved. However, conservative management with IV antibiotics, IR drainage, and surgical debridement could be a fertility-preserving approach to the treatment of pyomyomas.

Did people really drink bleach to prevent COVID-19? A guide for protecting survey data against problematic respondents.

Survey respondents who are non-attentive, respond randomly, or misrepresent who they are can impact the outcomes of surveys. Prior findings reported by the CDC have suggested that people engaged in highly dangerous cleaning practices during the COVID-19 pandemic, including ingesting household cleaners such as bleach. In our attempts to replicate the CDC's results, we found that 100% of reported ingestion of household cleaners are made by problematic respondents. Once inattentive, acquiescent, and careless respondents are removed from the sample, we find no evidence that people ingested cleaning products to prevent a COVID-19 infection. These findings have important implications for public health and medical survey research, as well as for best practices for avoiding problematic respondents in all survey research conducted online.

Effectiveness of COVID-19 mRNA Vaccines in Preventing COVID-19-Associated Outpatient Visits and Hospitalizations Among American Indian and Alaska Native Persons, January-November 2021: A Test-Negative Case-Control Analysis Using Surveillance Data.

Background: Despite the disproportionate morbidity and mortality experienced by American Indian and Alaska Native (AI/AN) persons during the coronavirus disease 2019 (COVID-19) pandemic, few studies have reported vaccine effectiveness (VE) estimates among these communities. Methods: We conducted a test-negative case-control analysis among AI/AN persons aged ≥12 years presenting for care from January 1, 2021, through November 30, 2021, to evaluate the effectiveness of mRNA COVID-19 vaccines against COVID-19-associated outpatient visits and hospitalizations. Cases and controls were patients with ≥1 symptom consistent with COVID-19-like illness; cases were defined as those test-positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and controls were defined as those test-negative for SARS-CoV-2. We used unconditional multivariable logistic regression to estimate VE, defined as 1 minus the adjusted odds ratio for vaccination among cases vs controls. Results: The analysis included 207 cases and 267 test-negative controls. Forty-four percent of cases and 78% of controls received 2 doses of either BNT162b2 or mRNA-1273 vaccine. VE point estimates for 2 doses of mRNA vaccine were higher for hospitalized participants (94.6%; 95% CI, 88.0-97.6) than outpatient participants (86.5%; 95% CI, 63.0-95.0), but confidence intervals overlapped. Conclusions: Among AI/AN persons, mRNA COVID-19 vaccines were highly effective in preventing COVID-associated outpatient visits and hospitalizations. Maintaining high vaccine coverage, including booster doses, will reduce the burden of disease in this population.

Deconstructing moral character judgments.

People often make judgments of others' moral character - an inferred moral essence that presumably predicts moral behavior. We first define moral character and explore why people make character judgments before outlining three key elements that drive character judgments: behavior (good vs. bad, norm violations, and deliberation), mind (intentions, explanations, capacities), and identity (appearance, social groups, and warmth). We also provide taxonomy of moral character that goes beyond simply good vs. evil. Drawing from the theory of dyadic morality, we outline a two-dimensional triangular space of character judgments (valence and strength/agency), with three key corners - heroes, villains, and victims. Varieties of perceived moral character include saints and demons, strivers/sinners and opportunists, the nonmoral, virtuous, and culpable victims, and pure victims.

Divergent effects of invasive macrophytes on population dynamics of a snail intermediate host of Schistosoma Mansoni.

Vectors and intermediate hosts of globally impactful human parasites are sensitive to changes in the ecological communities in which they are embedded. Sites of endemic transmission of human schistosome can also be invaded by nonnative species, especially aquatic plants (macrophytes). We tested the effects on macrophyte invasions on experiment snail and schistosome populations created in 100 L mesocosm tanks. We established macrophyte-free mesocosms and those containing one of four widespread macrophyte species that are inedible to snails (duckweed, hornwort, water lettuce, or water hyacinth) and then tracked edible resources (periphyton algae) and the abundance, reproduction, and infection of snail intermediate hosts for 16 weeks. We predicted that the three floating macrophytes would reduce periphyton, thereby reducing snail reproduction, abundance, and infections. In contrast, we predicted that hornwort, which is submerged and provides substrate for periphyton growth, would increase snail reproduction and abundance. As predicted, all floating macrophytes decreased periphyton, but only water hyacinth significantly decreased snail reproduction and abundance. Snail abundance increased significantly only with water lettuce. We hypothesize that this unanticipated increase in snails occurred because water lettuce produced abundant and/or high quality detritus, subsidizing snails despite low periphyton availability. Unfortunately, we detected too few infections to analyze. Aquatic macrophytes exert strong species-specific effects on snail populations. Therefore, efforts to manage invasive plants in endemic sites should evaluate changes in resources, snails, and transmission potential. We recommend caution with management efforts that produce large amounts of detritus, which might stimulate snail populations and therefore risk of human exposure.

Interventions to reduce partisan animosity.

Rising partisan animosity is associated with a reduction in support for democracy and an increase in support for political violence. Here we provide a multi-level review of interventions designed to reduce partisan animosity, which we define as negative thoughts, feelings and behaviours towards a political outgroup. We introduce the TRI framework to capture three levels of intervention-thoughts (correcting misconceptions and highlighting commonalities), relationships (building dialogue skills and fostering positive contact) and institutions (changing public discourse and transforming political structures)-and connect these levels by highlighting the importance of motivation and mobilization. Our review encompasses both interventions conducted as part of academic research projects and real-world interventions led by practitioners in non-profit organizations. We also explore the challenges of durability and scalability, examine self-fulfilling polarization and interventions that backfire, and discuss future directions for reducing partisan animosity.

Size-asymmetric competition among snails disrupts production of human-infectious Schistosoma mansoni cercariae.

Parasites can harm hosts and influence populations, communities, and ecosystems. However, parasites are reciprocally affected by population- and community-level dynamics. Understanding feedbacks between infection dynamics and larger-scale epidemiological and ecological processes could improve predictions and reveal novel control methods. We evaluated how exploitative resource competition among hosts, a fundamental aspect of population biology, influences within-host infection dynamics of the widespread human parasite Schistosoma mansoni in its intermediate host, Biomphalaria glabrata. We added size-dependent consumption of shared resources to a parameterized bioenergetics model to predict a priori the growth, parasite production, and survival of an infected focal host coexisting with an uninfected conspecific competitor in an experiment that varied competitor size. The model quantitatively anticipated that competitors disrupt growth and parasite production and that these effects increase with competitor size. Fitting the model to these data improved its match to host survivorship. Thus, resource competition alters infection dynamics, there are strong size asymmetries in these effects, and size-asymmetric resource competition effects on infection dynamics can be accurately predicted by bioenergetics theory. More broadly, this framework can assess parasite transmission and control in other contexts, such as in resource competitive host communities, or in response to eutrophication, food supplementation, or culling.