Vaccines targeting the complex pre-erythrocytic stage of Plasmodium parasites may benefit from the inclusion of multiple antigens. However, discerning protective effects can be difficult because newer candidates may not be as protective as leading antigens like the circumsporozoite protein (CSP) in the conventional pre-clinical mouse model. We developed a modified mouse model challenge strategy that maximizes the contribution of T cells induced by novel candidate antigens at the sporozoite challenge time point and used this approach to test Plasmodium P36 and P52 vaccine candidates alone and in concert with non-protective doses of CSP.
View Article and Find Full Text PDFVaccines targeting the complex pre-erythrocytic stage of parasites may benefit from inclusion of multiple antigens. However, discerning protective effects can be difficult because newer candidates may not be as protective as leading antigens like the circumsporozoite protein (CSP) in the conventional pre-clinical mouse model. We developed a modified mouse model challenge strategy that maximizes the contribution of T cells induced by novel candidate antigens at the sporozoite challenge time point and used this approach to test P36 and P52 vaccine candidates alone and in concert with non-protective doses of CSP.
View Article and Find Full Text PDFRadiation-attenuated sporozoite (RAS) vaccines can completely prevent blood stage Plasmodium infection by inducing liver-resident memory CD8 T cells to target parasites in the liver. Such T cells can be induced by 'Prime-and-trap' vaccination, which here combines DNA priming against the P. yoelii circumsporozoite protein (CSP) with a subsequent intravenous (IV) dose of liver-homing RAS to "trap" the activated and expanding T cells in the liver.
View Article and Find Full Text PDFMalaria is caused by parasites and was responsible for over 247 million infections and 619,000 deaths in 2021. Radiation-attenuated sporozoite (RAS) vaccines can completely prevent blood stage infection by inducing protective liver-resident memory CD8 T cells. Such T cells can be induced by 'prime-and-trap' vaccination, which here combines DNA priming against the circumsporozoite protein (CSP) with a subsequent intravenous (IV) dose of liver-homing RAS to "trap" the activated and expanding T cells in the liver.
View Article and Find Full Text PDFMalaria-causing parasites have a complex life cycle and present numerous antigen targets that may contribute to protective immune responses. The currently recommended vaccine-RTS,S-functions by targeting the Plasmodium falciparum circumsporozoite protein (CSP), which is the most abundant surface protein of the sporozoite form responsible for initiating infection of the human host. Despite showing only moderate efficacy, RTS,S has established a strong foundation for the development of next-generation subunit vaccines.
View Article and Find Full Text PDFBiomedical personnel can become contaminated with nonhazardous reagents used in the laboratory. We describe molecular studies performed on nasal secretions collected longitudinally from asymptomatic laboratory coworkers to determine if they were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) circulating in the community or with SARS-CoV-2 DNA from a plasmid vector. Participants enrolled in a prospective study of incident SARS-CoV-2 infection had nasal swabs collected aseptically by study staff at enrollment, followed by weekly self-collection of anterior nasal swabs.
View Article and Find Full Text PDFBlocking Plasmodium, the causative agent of malaria, at the asymptomatic pre-erythrocytic stage would abrogate disease pathology and prevent transmission. However, the lack of well-defined features within vaccine-elicited antibody responses that correlate with protection represents a major roadblock to improving on current generation vaccines. We vaccinated mice (BALB/cJ and C57BL/6J) with Py circumsporozoite protein (CSP), the major surface antigen on the sporozoite, and evaluated vaccine-elicited humoral immunity and identified immunological factors associated with protection after mosquito bite challenge.
View Article and Find Full Text PDFVaccine-induced sterilizing protection from infection by Plasmodium parasites, the pathogens that cause malaria, will be essential in the fight against malaria as it would prevent both malaria-related disease and transmission. Stopping the relatively small number of parasites injected by the mosquito before they can migrate from the skin to the liver is an attractive means to this goal. Antibody-eliciting vaccines have been used to pursue this objective by targeting the major parasite surface protein present during this stage, the circumsporozoite protein (CSP).
View Article and Find Full Text PDFEndocrinol Diabetes Metab Case Rep
February 2022
Summary: Multiple endocrine neoplasia type 1 NM_001370259.2(MEN1):c.466G>C(p.
View Article and Find Full Text PDFBackground: Coronavirus disease 2019 (COVID-19) is associated with endothelial activation and coagulopathy, which may be related to pre-existing or infection-induced pro-thrombotic autoantibodies such as those targeting angiotensin II type I receptor (AT1R-Ab).
Methods: We compared prevalence and levels of AT1R-Ab in COVID-19 cases with mild or severe disease to age and sex matched negative controls utilizing multivariate logistic and quantile regression adjusted for comorbidities including hypertension, diabetes, and heart disease.
Results: There were trends toward increased prevalence (50% vs.
Both subunit and attenuated whole-sporozoite vaccination strategies against Plasmodium infection have shown promising initial results in malaria-naive westerners but less efficacy in malaria-exposed individuals in endemic areas. Here, we demonstrate proof of concept by using a rodent malaria model in which non-neutralizing antibodies (nNAbs) can directly interfere with protective anti-circumsporozoite protein (CSP) humoral responses. We characterize a monoclonal antibody, RAM1, against Plasmodium yoelii sporozoite major surface antigen CSP.
View Article and Find Full Text PDFThis is a brief report of the etiology of infectious diseases in a pediatric emergency department. Our cohort study of 4647 children demonstrated rhinovirus as the most common etiology in a pediatric emergency department (23%) and intensive care (48%). The population-based incidence of rhinovirus-related visits was 1796/100,000/yr in children <5 years.
View Article and Find Full Text PDFLatent forms of Plasmodium vivax, called hypnozoites, cause malaria relapses from the liver into the bloodstream and are a major obstacle to malaria eradication. To experimentally assess the impact of a partially protective pre-erythrocytic vaccine on reducing Plasmodium vivax relapses, we developed a liver-humanized mouse model that allows monitoring of relapses directly in the blood. We passively infused these mice with a suboptimal dose of an antibody that targets the circumsporozoite protein prior to challenge with P.
View Article and Find Full Text PDFThe fate of protective immunity following mild severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection remains ill defined. Here, we characterize antibody responses in a cohort of participants recovered from mild SARS-CoV-2 infection with follow-up to 6 months. We measure immunoglobulin A (IgA), IgM, and IgG binding and avidity to viral antigens and assess neutralizing antibody responses over time.
View Article and Find Full Text PDFPurpose: The Sino-Nasal Outcome Test-22 (SNOT-22) is the most commonly used disease-specific quality of life questionnaire in rhinology. The purpose of this prospective study was to translate and validate SNOT-22 into Finnish.
Methods: The validation process followed the guidelines proposed for cross-cultural adaptation of health-related measures of quality of life.
J Speech Lang Hear Res
August 2017
Purpose: The aim of this study was to investigate developmental and noise-induced changes in central auditory processing indexed by event-related potentials in typically developing children.
Method: P1, N2, and N4 responses as well as mismatch negativities (MMNs) were recorded for standard syllables and consonants, frequency, intensity, vowel, and vowel duration changes in silent and noisy conditions in the same 14 children at the ages of 2 and 4 years.
Results: The P1 and N2 latencies decreased and the N2, N4, and MMN amplitudes increased with development of the children.
Objective: To evaluate visual acuity (VA) and visual fields (VF) quantitatively before and after endoscopic transsphenoidal surgery (ETS), with special attention to prognostic factors such as the pituitary adenoma (PA) suprasellar extension (SSE), volume and the patients' age.
Methods: Medical records of 47 patients with PA undergoing ETS were evaluated. VA, VF, preoperative visual impairment score (VISpre) and postoperative visual impairment score (VISpost) were determined.
Objective: Narrow band imaging (NBI) improves diagnosis of laryngopharyngeal cancer, but most reported NBI studies are from experienced centers. Feasibility reports on use at everyday outpatient departments are needed.
Study Design: Researcher-initiated, prospective, multicenter.
Background: A large group of young children are exposed to repetitive middle ear infections but the effects of the fluctuating hearing sensations on immature central auditory system are not fully understood. The present study investigated the consequences of early childhood recurrent acute otitis media (RAOM) on involuntary auditory attention switching.
Methods: By utilizing auditory event-related potentials, neural mechanisms of involuntary attention were studied in 22-26 month-old children (N = 18) who had had an early childhood RAOM and healthy controls (N = 19).
Objectives: To investigate at the age of 2 years the effects of childhood recurrent acute otitis media (RAOM) on central auditory processing by using cortical event-related potentials elicited by syllable stimuli.
Design: During a 1-year period, 22- to 26-month-old children fulfilling the criteria for tympanostomy tube insertion in Oulu University Hospital, Oulu, Finland, were recruited to the RAOM group (N = 20). The control group (N = 19) was matched by age, sex, and mother's educational level.
Context. The literature concerning the health-related quality of life (HRQoL) of patients with surgically treated PA is controversial. Objective.
View Article and Find Full Text PDFContext: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively.
Objective: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas.
J Clin Endocrinol Metab
September 2010
Context: Data on the incidence of pituitary adenomas (PAs) are scant and outdated. A population-based regional cohort with thorough case identification was used to evaluate the incidence of clinically detected PAs in the era of magnetic resonance imaging.
Objective: The objective of the study was to describe the age- and sex-specific incidence of all PA subgroups, with data on incidentally found PAs, pituitary apoplexies, and time trends.
A method to assess nasal airflow resistance is presented that provides a continuous resistance value and applies a novel minimally obtrusive measurement technique. Instead of calculating the resistance once for each breathing cycle conventionally, it is calculated for each signal sample at any sampling frequency. The continuous pressure recording is produced with a nasopharyngeal catheter inserted 8 cm deep along the floor of the other nasal cavity and the flow recording is produced with respiratory effort bands.
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