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AbstractBabesiosis, caused by protozoan parasites of the genus Babesia, is an emerging tick-borne disease of significance for both human and animal health. Babesia parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of new Babesia species underscores the ongoing risk of zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental changes. One such pathogen, Babesia MO1, previously implicated in severe cases of human babesiosis in the United States, was initially considered a subspecies of B. divergens, the predominant agent of human babesiosis in Europe. Here we report comparative multiomics analyses of B. divergens and B. MO1 that offer insight into their biology and evolution. Our analysis shows that despite their highly similar genomic sequences, substantial genetic and genomic divergence occurred throughout their evolution resulting in major differences in gene functions, expression and regulation, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for B. MO1, B. divergens, and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.
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Pathogens such as Plasmodium, Babesia, and Theileria invade and multiply within host red blood cells, leading to the pathological consequences of malaria, babesiosis, and theileriosis. Establishing continuous in vitro culture systems and suitable animal models is crucial for studying these pathogens. This review spotlights the Babesia duncani in culture-in mouse (ICIM) model as a promising resource for advancing research on the biology, pathogenicity, and virulence of intraerythrocytic parasites. The model offers practical benefits, encompassing well-defined culture conditions, ease of manipulation, and a well-annotated genome. Moreover, B. duncani serves as a surrogate system for drug discovery, facilitating the evaluation of new antiparasitic drugs in vitro and in animals, elucidating their modes of action, and uncovering potential resistance mechanisms. The B. duncani ICIM model thus emerges as a multifaceted tool with profound implications, promising advancements in our understanding of parasitic biology and shaping the development of future therapies.
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Babesia , Babesiose , Modelos Animais de Doenças , Eritrócitos , Animais , Babesia/efeitos dos fármacos , Babesia/genética , Eritrócitos/parasitologia , Camundongos , Babesiose/tratamento farmacológico , Babesiose/parasitologia , Antiparasitários/uso terapêutico , Antiparasitários/farmacologia , Humanos , VirulênciaRESUMO
Background: Point-of-care ultrasound (POCUS) is a valuable tool that assists in diagnosis and management of patients in the emergency department (ED) while being cost-efficient and without the use of ionizing radiation. To discern the opinions and perceptions of ED staff about POCUS applications and barriers, we conducted a cross-sectional survey of employees of 12 EDs in North Texas. Methods: Participants completed a 20-item online survey about POCUS with questions pertaining to four domains: (1) employee and training information, (2) perceived benefits, (3) common applications, and (4) barriers to use. Out of 805 eligible ED employees, 103 completed the survey (16.1% response rate). Results: The results indicated a generally positive perception of POCUS among all employee types. Physician had significant exposure and training of POCUS than non-physician group ( p < 0.001). Physicians tend to find cardiac assessments more useful for clinical management than non-physicians (47% vs. 23%, p = 0.01), while non-physicians find soft tissue/abscess assessments more useful (27% vs. 9%, p = 0.01). Conclusion: The most significant barriers to POCUS use were time constraints for physicians and a lack of training for non-physician employees. Our study provides valuable insights into the perceptions of multiple ED professionals, serving as a foundation for promoting POCUS use in the ED.
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Evolutionary constraints greatly favor compact genomes that efficiently encode proteins. However, several eukaryotic organisms, including apicomplexan parasites such as Toxoplasma gondii, Plasmodium falciparum and Babesia duncani, the causative agents of toxoplasmosis, malaria and babesiosis, respectively, encode very large proteins, exceeding 20 times their average protein size. Although these large proteins represent <1% of the total protein pool and are generally expressed at low levels, their persistence throughout evolution raises important questions about their functions and possible evolutionary pressures to maintain them. In this study, we examined the trends in gene and protein size, function and expression patterns within seven apicomplexan pathogens. Our analysis revealed that certain large proteins in apicomplexan parasites harbor domains potentially important for functions such as antigenic variation, erythrocyte invasion and immune evasion. However, these domains are not limited to or strictly conserved within large proteins. While some of these proteins are predicted to engage in conventional metabolic pathways within these parasites, others fulfill specialized functions for pathogen-host interactions, nutrient acquisition and overall survival.
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Quality care in healthcare is a multifaceted concept that encompasses the execution of effective medical treatments and the patient's overall experience. It involves a multitude of factors, including effectiveness, safety, timeliness, equity, and patient centeredness, which are important in shaping the healthcare landscape. This cross-sectional study used the data from the Health Information National Trends Survey 6 (HINTS 6), which collects data on various aspects of health communication and information-seeking behaviors, to investigate the factors associated with quality care among White and Hispanic populations. All adults who participated in HINTS 6 and visited healthcare service at least once in the past 12 months were included in this study. Multivariable logistic regression was used to determine the association between quality care and delay or discriminated care with the adjustment of all other sociodemographic variables. We analyzed a total of 3611 participants. Poor social determinants of health (SDOHs) (OR 0.61, CI 0.43-0.88, p = 0.008), delayed needed medical care (OR 0.34, CI 0.26-0.43, p < 0.001), and discriminated care (OR 0.29, CI 0.15-0.54, p < 0.001) were all negatively associated with optimal quality care. Negative SDOHs could also be positively associated with delayed care and discriminated care.
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Babesiosis, caused by protozoan parasites of the genus Babesia , is an emerging tick-borne disease of significance for both human and animal health. Babesia parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of various Babesia species underscores the ongoing risk of new zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental shifts impacting the distribution and transmission dynamics of parasites, their vectors, and reservoir hosts. One such species, Babesia MO1, previously implicated in severe cases of human babesiosis in the midwestern United States, was initially considered closely related to B. divergens , the predominant agent of human babesiosis in Europe. Yet, uncertainties persist regarding whether these pathogens represent distinct variants of the same species or are entirely separate species. We show that although both B. MO1 and B. divergens share similar genome sizes, comprising three nuclear chromosomes, one linear mitochondrial chromosome, and one circular apicoplast chromosome, major differences exist in terms of genomic sequence divergence, gene functions, transcription profiles, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for B. MO1, B. divergens , and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.
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Airway management is a common and critical procedure in acute settings, such as the Emergency Department (ED) or Intensive Care Unit (ICU) of hospitals. Many of the traditional physical examination methods have limitations in airway assessment. Point-of-care ultrasound (POCUS) has emerged as a promising tool for airway management due to its familiarity, accessibility, safety, and non-invasive nature. It can assist physicians in identifying relevant anatomy of the upper airway with objective measurements of airway parameters, and it can guide airway interventions with dynamic real-time images. To date, ultrasound has been considered highly accurate for assessment of the difficult airway, confirmation of proper endotracheal intubation, prediction of post-extubation laryngeal edema, and preparation for cricothyrotomy by identifying the cricothyroid membrane. This review aims to provide a comprehensive overview of the key evidence on the use of ultrasound in airway management. Databases including PubMed and Embase were systematically searched. A search strategy using a combination of the term "ultrasound" combined with several search terms, i.e., "probe", "anatomy", "difficult airway", "endotracheal intubation", "laryngeal edema", and "cricothyrotomy" was performed. In conclusion, POCUS is a valuable tool with multiple applications ranging from pre- and post-intubation management. Clinicians should consider using POCUS in conjunction with traditional exam techniques to manage the airway more efficiently in the acute setting.
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Babesiosis is a malaria-like disease in humans and animals that is caused by Babesia species, which are tick-transmitted apicomplexan pathogens. Babesia duncani causes severe to lethal infection in humans, but despite the risk that this parasite poses as an emerging pathogen, little is known about its biology, metabolic requirements or pathogenesis. Unlike other apicomplexan parasites that infect red blood cells, B. duncani can be continuously cultured in vitro in human erythrocytes and can infect mice resulting in fulminant babesiosis and death. We report comprehensive, detailed molecular, genomic, transcriptomic and epigenetic analyses to gain insights into the biology of B. duncani. We completed the assembly, 3D structure and annotation of its nuclear genome, and analysed its transcriptomic and epigenetics profiles during its asexual life cycle stages in human erythrocytes. We used RNA-seq data to produce an atlas of parasite metabolism during its intraerythrocytic life cycle. Characterization of the B. duncani genome, epigenome and transcriptome identified classes of candidate virulence factors, antigens for diagnosis of active infection and several attractive drug targets. Furthermore, metabolic reconstitutions from genome annotation and in vitro efficacy studies identified antifolates, pyrimethamine and WR-99210 as potent inhibitors of B. duncani to establish a pipeline of small molecules that could be developed as effective therapies for the treatment of human babesiosis.
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Babesia , Babesiose , Carrapatos , Animais , Humanos , Camundongos , Babesia/genética , Babesiose/tratamento farmacológico , Multiômica , Eritrócitos/parasitologiaRESUMO
Background: The coronavirus disease 2019 (COVID-19) outbreak is an international public health emergency. Early identification of COVID-19 patients with false-negative RT-PCR tests is paramount in the ED to prevent both nosocomial and community transmission. This study aimed to compare clinical characteristics of repeat emergency department (ED) visits among coronavirus disease 2019 (COVID-19) patients with initial false-negative reverse transcriptase-polymerase chain reaction (RT-PCR)-based COVID-19 test. Methods: This is a retrospective, multi-center, cohort study conducted at 12 hospitals affiliated with Baylor Scott & White Health system. Patients visiting the EDs of these hospitals between June and August 2020 were screened. Patients tested negative for viral RNA by quantitative RT-PCR in the first ED visit and positive in the second ED visit were included. The primary outcome was the comparison of clinical characteristics between two consecutive ED visits including the clinical symptoms, triage vital signs, laboratory, and chest X-ray (CXR) results. Results: A total of 88 confirmed COVID-19 patients with initial false-negative RT-PCR COVID-19 test in the ED were included in the final analyses. The mean duration of symptoms in the second ED visit was significantly higher (3.6 ± 0.4 vs. 2.6 ± 0.3 days, p = 0.020). In the first ED visit, lymphocytopenia (35.2%), fever (32.6%), nausea (29.5%), and dyspnea (27.9%) are the most common signs of COVID-19 infection during the window period. There were significant increases in the rate of hypoxia (13.6% vs. 4.6%, p = 0.005), abnormal infiltrate on CXR (59.7% vs. 25.9%, p < 0.001), and aspartate aminotransferase (AST) elevation (26.1% vs. 9.1%, p < 0.001) in the second ED visit. Conclusions: Early COVID-19 testing (less than 3 days of symptom duration) could be associated with a false-negative result. In this window period, lymphocytopenia, fever, nausea, and dyspnea are the most common early signs that can potentially be clinical hints for COVID-19 diagnosis.
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Atrial fibrillation (AF) is a growing public health concern, the impact of which is frequently underestimated. It has a profound effect on the quality of life (QoL) which appears to be disproportionately lower in female patients compared to men. We aim to explore the factors contributing to sex-related disparities in the QoL of AF patients by conducting a systematic review using the PubMed electronic search database. We used the following combination of medical subject heading (MeSH) parameters: "atrial fibrillation" and "sex" and "quality of life" with specific inclusion and exclusion criteria. We identified 13 relevant studies published between 2010 and 2020 for our review. These studies evaluated sex-related differences in QoL scores, symptom burden, and AF-related complications originating across different continents in Asia, Europe, and North America. We found that female patients reported a reduced QoL as compared to men and they were more likely to be older with multiple co-morbidities at presentation. Women also reported more frequent and severe symptoms, potentially explained by the greater prevalence of anxiety and depression and thus enhancing symptom perception. Moreover, they were less likely to be managed by anti-arrhythmic medications and invasive rhythm control strategies such as catheter ablation. Female patients with AF experienced more severe strokes, but no sex disparities were found in AF-related cognitive decline. We determined that the more prominent contributory factors towards a lowered QoL in female AF patients appear to be secondary to a higher burden and perception of symptoms as well as under-utilization of invasive treatment modalities. However, further studies are warranted to confirm these findings.