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Evidence suggests that reductions in healthcare utilization, including forgone care, during the COVID-19 pandemic may be contributing towards excess morbidity and mortality. The objective of this study was to describe individual and community-level correlates of forgone care during the COVID-19 pandemic. We conducted a cross-sectional, secondary data analysis of participants (n = 2,003) who reported needing healthcare in two population-representative surveys conducted in Baltimore, MD in 2021 and 2021-2022. Abstracted data included the experience of forgone care, socio-demographic data, comorbidities, financial strain, and community of residence. Participant's community of residence were linked with data acquired from the Baltimore Neighborhood Indicators Alliance relevant to healthcare access and utilization, including walkability and internet access, among others. The data were analyzed using weighted random effects logistic regression. Individual-level factors found to be associated with increased odds for forgone care included individuals age 35-49 (compared to 18-34), female sex, experiencing housing insecurity during the pandemic, and the presence of functional limitations and mental illness. Black/African American individuals were found to have reduced odds of forgone care, compared to any other race. No community-level factors were significant in the multilevel analyses. Moving forward, it will be critical that health systems identify ways to address any barriers to care that populations might be experiencing, such as the use of mobile health services or telemedicine platforms. Additionally, public health emergency preparedness planning efforts must account for the unique needs of communities during future crises, to ensure that their health needs can continue to be met. Finally, additional research is needed to better understand how healthcare access and utilization practices have changed during versus before the pandemic., Competing Interests: S. Mehta receives material support from Abbott Diagnostics. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors do not have any other conflicts of interest to disclose, (Copyright: © 2024 Meyer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Parasites causing malaria need to migrate in order to penetrate tissue barriers and enter host cells. Here we show that the actin filament-binding protein coronin regulates gliding motility in Plasmodium berghei sporozoites, the highly motile forms of a rodent malaria-causing parasite transmitted by mosquitoes. Parasites lacking coronin show motility defects that impair colonization of the mosquito salivary glands but not migration in the skin, yet result in decreased transmission efficiency. In non-motile sporozoites low calcium concentrations mediate actin-independent coronin localization to the periphery. Engagement of extracellular ligands triggers an intracellular calcium release followed by the actin-dependent relocalization of coronin to the rear and initiation of motility. Mutational analysis and imaging suggest that coronin organizes actin filaments for productive motility. Using coronin-mCherry as a marker for the presence of actin filaments we found that protein kinase A contributes to actin filament disassembly. We finally speculate that calcium and cAMP-mediated signaling regulate a switch from rapid parasite motility to host cell invasion by differentially influencing actin dynamics.

It is poorly understood how progressive brain swelling in experimental cerebral malaria (ECM) evolves in space and over time, and whether mechanisms of inflammation or microvascular sequestration/obstruction dominate the underlying pathophysiology. We therefore monitored in the Plasmodium berghei ANKA-C57BL/6 murine ECM model, disease manifestation and progression clinically, assessed by the Rapid-Murine-Coma-and-Behavioral-Scale (RMCBS), and by high-resolution in vivo MRI, including sensitive assessment of early blood-brain-barrier-disruption (BBBD), brain edema and microvascular pathology. For histological correlation HE and immunohistochemical staining for microglia and neuroblasts were obtained. Our results demonstrate that BBBD and edema initiated in the olfactory bulb (OB) and spread along the rostral-migratory-stream (RMS) to the subventricular zone of the lateral ventricles, the dorsal-migratory-stream (DMS), and finally to the external capsule (EC) and brainstem (BS). Before clinical symptoms (mean RMCBS = 18.5±1) became evident, a slight, non-significant increase of quantitative T2 and ADC values was observed in OB+RMS. With clinical manifestation (mean RMCBS = 14.2±0.4), T2 and ADC values significantly increased along the OB+RMS (p = 0.049/p = 0.01). Severe ECM (mean RMCBS = 5±2.9) was defined by further spread into more posterior and deeper brain structures until reaching the BS (significant T2 elevation in DMS+EC+BS (p = 0.034)). Quantitative automated histological analyses confirmed microglial activation in areas of BBBD and edema. Activated microglia were closely associated with the RMS and neuroblasts within the RMS were severely misaligned with respect to their physiological linear migration pattern. Microvascular pathology and ischemic brain injury occurred only secondarily, after vasogenic edema formation and were both associated less with clinical severity and the temporal course of ECM. Altogether, we identified a distinct spatiotemporal pattern of microglial activation in ECM involving primarily the OB+RMS axis, a distinct pathway utilized by neuroblasts and immune cells. Our data suggest significant crosstalk between these two cell populations to be operative in deeper brain infiltration and further imply that the manifestation and progression of cerebral malaria may depend on brain areas otherwise serving neurogenesis.

Parents may adapt their offspring sex ratio in response to their own phenotype and environmental conditions. The most significant causes for adaptive sex-ratio variation might express themselves as different distributions of fitness components between sexes along a given variable. Several causes for differential sex allocation in raptors with reversed sexual size dimorphism have been suggested. We search for correlates of fledgling sex in an extensive dataset on common buzzards Buteo buteo, a long-lived bird of prey. Larger female offspring could be more resource-demanding and starvation-prone and thus the costly sex. Prominent factors such as brood size and laying date did not predict nestling sex. Nonetheless, lifetime sex ratio (LSR, potentially indicative of individual sex allocation constraints) and overall nestling sex were explained by territory quality with more females being produced in better territories. Additionally, parental plumage morphs and the interaction of morph and prey abundance tended to explain LSR and nestling sex, indicating local adaptation of sex allocation However, in a limited census of nestling mortality, not females but males tended to die more frequently in prey-rich years. Also, although females could have potentially longer reproductive careers, a subset of our data encompassing full individual life histories showed that longevity and lifetime reproductive success were similarly distributed between the sexes. Thus, a basis for adaptive sex allocation in this population remains elusive. Overall, in common buzzards most major determinants of reproductive success appeared to have no effect on sex ratio but sex allocation may be adapted to local conditions in morph-specific patterns.

Sterile protection against malaria infection can be achieved by the inoculation of intact sporozoites while treating concomitantly with the 4-aminoquinoline chloroquine. We present an analysis of protective immunity elicited by successive immunization with Plasmodium berghei sporozoites under chemoprophylaxis. Immunization resulted in a protective, stage-specific immune response. Protection appeared to be mediated by CD8(+) T cells and was abrogated upon their specific depletion. Adoptive transfer of splenocytes rendered recipient animals resistant to sporozoite infection, but not to blood-stage challenge. Immunization with sporozoites under chemoprophylaxis results in robust immunity, and the presence of blood-stage infection at sporozoite immunization had no downregulating effect on the protective immune response.

Objectives: In general, assessment tools for stigma in mental disorders such as attention deficit hyperactivity disorder (ADHD) are lacking. Moreover, misbeliefs and misconceptions about ADHD are common, in particular with regard to the adult form of ADHD. The aim of the present study was to develop a questionnaire measuring stigma in adults with ADHD and to demonstrate its sensitivity., Methods: A questionnaire initially containing 64 items associated with stigma in adults with ADHD was developed. A total number of 1261 respondents were included in the analyses. The psychometric properties were investigated on a sample of 1033 participants. The sensitivity of the questionnaire was explored on 228 participants consisting of teachers, physicians and control participants., Results: Thirty-seven items were extracted due to exploratory factor analysis (EFA) and the internal consistency of items. Confirmatory factor analysis (CFA) revealed good psychometric properties of a 6-factor structure. Teachers and physicians differed significantly in their stigmatizing attitudes from control participants., Conclusions: The present data shed light on various dimensions of stigma in adult ADHD. Reliability and Social Functioning, Malingering and Misuse of Medication, Ability to Take Responsibility, Norm-violating and Externalizing Behavior, Consequences of Diagnostic Disclosure and Etiology represent critical aspects associated with stigmatization.

Human populations are rarely exposed to one pathogen alone. Particularly in high incidence regions such as sub-Saharan Africa, concurrent infections with more than one pathogen represent a widely underappreciated public health problem. Two of the world's most notorious killers, malaria and tuberculosis, are co-endemic in impoverished populations in the tropics. However, interactions between both infections in a co-infected individual have not been studied in detail. Both pathogens have a major impact on the lung as the prime target organ for aerogenic Mycobacterium tuberculosis and the site for one of the main complications in severe malaria, malaria-associated acute respiratory distress syndrome (MA-ARDS). In order to study the ramifications caused by both infections within the same host we established an experimental mouse model of co-infection between Mycobacterium tuberculosis and Plasmodium berghei NK65, a recently described model for MA-ARDS. Our study provides evidence that malaria-induced immune responses impair host resistance to Mycobacterium tuberculosis. Using the natural routes of infection, we observed that co-infection exacerbated chronic tuberculosis while rendering mice less refractory to Plasmodium. Co-infected animals presented with enhanced inflammatory immune responses as reflected by exacerbated leukocyte infiltrates, tissue pathology and hypercytokinemia accompanied by altered T-cell responses. Our results--demonstrating striking changes in the immune regulation by co-infection with Plasmodium and Mycobacterium--are highly relevant for the medical management of both infections in humans.