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1.
Article in English | MEDLINE | ID: mdl-32110775

ABSTRACT

Preeclampsia leads to increased risk of morbidity and mortality for both mother and fetus. Most previous studies have largely neglected mechanical compression of the left renal vein by the gravid uterus as a potential mechanism. In this study, we first used a murine model to investigate the pathophysiology of left renal vein constriction. The results indicate that prolonged renal vein stenosis after 14 days can cause renal necrosis and an increase in blood pressure (BP) of roughly 30 mmHg. The second part of this study aimed to automate a diagnostic tool, known as the supine pressor test (SPT), to enable pregnant women to assess their preeclampsia development risk. A positive SPT has been previously defined as an increase of at least 20 mmHg in diastolic BP when switching between left lateral recumbent and supine positions. The results from this study established a baseline BP increase between the two body positions in nonpregnant women and demonstrated the feasibility of an autonomous SPT in pregnant women. Our results demonstrate that there is a baseline increase in BP of roughly 10-14 mmHg and that pregnant women can autonomously perform the SPT. Overall, this work in both rodents and humans suggests that (1) stenosis of the left renal vein in mice leads to elevation in BP and acute renal failure, (2) nonpregnant women experience a baseline increase in BP when they shift from left lateral recumbent to supine position, and (3) the SPT can be automated and used autonomously.

2.
Vaccine ; 34(41): 4857-4865, 2016 09 22.
Article in English | MEDLINE | ID: mdl-27595442

ABSTRACT

The targeting of vaccine antigens to antigen presenting cells (APC), such as dendritic cells (DCs), is a promising strategy for boosting vaccine immunogenicity and, in turn, protective and/or therapeutic efficacy. However, in vivo systems are needed to evaluate the potential of this approach for testing human vaccines. To this end, we examined human CD8(+) T-cell expansion to novel DC-targeting vaccines in vitro and in vivo in humanized mice. Vaccines incorporating the influenza matrix protein-1 (FluM1) antigen fused to human specific antibodies targeting different DC receptors, including DEC-205, DCIR, Dectin-1, and CD40, elicited human CD8(+) T-cell responses, as defined by the magnitude of specific CD8(+) T-cells to the targeted antigen. In vitro we observed differences in response to the different vaccines, particularly between the weakly immunogenic DEC-205-targeted and more strongly immunogenic CD40-targeted vaccines, consistent with previous studies. However, in humanized mice adoptively transferred (AT) with mature human T cells (HM-T), vaccines that performed weakly in vitro (i.e., DEC-205, DCIR, and Dectin-1) gave stronger responses in vivo, some resembling those of the strongly immunogenic CD40-targeted vaccine. These results demonstrate the utility of the humanized mouse model as a platform for studies of human vaccines.


Subject(s)
Adoptive Transfer , Antibodies, Monoclonal/immunology , CD8-Positive T-Lymphocytes/immunology , Dendritic Cells/immunology , Influenza Vaccines/immunology , Viral Matrix Proteins/immunology , Animals , Antigen Presentation , Antigens, CD/immunology , CD40 Antigens/immunology , Cross-Priming , Epitopes/immunology , Humans , Immunity, Cellular , Lectins, C-Type/immunology , Mice , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Minor Histocompatibility Antigens/immunology , Receptors, Cell Surface/immunology , Recombinant Fusion Proteins/immunology
3.
Int J Adolesc Med Health ; 30(1)2016 Apr 18.
Article in English | MEDLINE | ID: mdl-27089402

ABSTRACT

BACKGROUND: Normal fear is an adaptive response to a real or imagined threat. Fears occur in children and adolescents at varying levels while they negotiate different developmental phases. OBJECTIVE: The present study aimed at assessing the types of fears in children and adolescents between the ages of 11 and 19 years. Age and gender based differences in these fears were also studied. MATERIALS AND METHODS: The study sample consisted of 2010 adolescents from an urban setting between the ages of 11 and 19 who filled in a proforma questionnaire for socio-demographic details and also filled in the Fear Survey Schedule for Children-Revised (FSSC-R). Statistical analysis of the data was done along with the use of descriptive statistics. RESULTS: The prevalence of fears among adolescents was found to be 85.17% in the total sample. Girls reported a significantly greater number of fears (p<0.0001) and greater levels of fear (p<0.0001) than boys. Age however, did not affect the number of fears reported. Girls scored significantly higher on all the subscales of the FSSC-R. 'Failing a test' emerged as the most common fear expressed by the sample. Girls expressed a greater fear for snakes and earthquakes than boys. CONCLUSION: Girls expressed fears to a greater extent than boys and adolescents demonstrated a high level of fears in general. There is a need for further studies in this direction to elucidate the nature of fears in this population.

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