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1.
J Aerosol Med Pulm Drug Deliv ; 36(5): 235-245, 2023 10.
Article in English | MEDLINE | ID: mdl-37262184

ABSTRACT

Background: Significant evidence suggests that SARS-CoV-2 can be transmitted via respiratory aerosols, which are known to vary as a function of respiratory activity. Most animal models examine disease presentation following inhalation of small-particle aerosols similar to those generated during quiet breathing or speaking. However, despite evidence that particle size can influence dose-infectivity relationships and disease presentation for other microorganisms, no studies have examined the infectivity of SARS-CoV-2 contained in larger particle aerosols similar to those produced during coughing, singing, or talking. Therefore, the aim of the present study was to assess the influence of aerodynamic diameter on the infectivity and virulence of aerosols containing SARS-CoV-2 in a hamster model of inhalational COVID-19. Methods: Dose-response relationships were assessed for two different aerosol particle size distributions, with mass median aerodynamic diameters (MMADs) of 1.3 and 5.2 µm in groups of Syrian hamsters exposed to aerosols containing SARS-CoV-2. Results: Disease was characterized by viral shedding in oropharyngeal swabs, increased respiratory rate, decreased activity, and decreased weight gain. Aerosol particle size significantly influenced the median doses to induce seroconversion and viral shedding, with both increasing ∼30-fold when the MMAD was increased. In addition, disease presentation was dose-dependent, with seroconversion and viral shedding occurring at lower doses than symptomatic disease characterized by increased respiratory rate and decreased activity. Conclusions: These results suggest that aerosol particle size may be an important factor influencing the risk of COVID-19 transmission and needs to be considered when developing animal models of disease. This result agrees with numerous previous studies with other microorganisms and animal species, suggesting that it would be generally translatable across different species. However, it should be noted that the absolute magnitude of the observed shifts in the median doses obtained with the specific particle sizes utilized herein may not be directly applicable to other species.


Subject(s)
COVID-19 , Animals , Cricetinae , Mesocricetus , Administration, Inhalation , Particle Size , SARS-CoV-2 , Respiratory Aerosols and Droplets , Patient Acuity
2.
Comp Med ; 67(4): 330-334, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28830579

ABSTRACT

Relaxin is a 6-kDa peptide in the insulin superfamily of hormones. In addition to its effects on reproductive and musculoskeletal ligaments, relaxin has demonstrated beneficial effects on cardiac, renal, and vascular systems in preclinical models. The mouse intrapubic ligament ex vivo bioassay is the current standard for measuring in vivo relaxin bioactivity. However, this bioassay necessitates euthanasia and dissection of large cohorts to measure the intrapubic ligament at specified time points. We hypothesized that µCT imaging could be used to reduce the number of animals necessary for the intrapubic ligament bioassay by enabling a single animal to be followed longitudinally throughout the study rather than euthanizing different cohorts at established time points. Female CD1 mice were used to compare µCT imaging with the current standard. Both protocols revealed significant differences in intrapubic ligament length, with the µCT data having greater power when corrected for baseline imaging. From these data, we concluded that using µCT to measure the intrapubic ligament in mice primed with estrogen and dosed with relaxin is a viable refinement and will allow the use of fewer animals in longitudinal studies and provide more robust data, because animals can serve as their own controls.


Subject(s)
Biological Assay/methods , Ligaments/drug effects , Ligaments/diagnostic imaging , Relaxin/administration & dosage , X-Ray Microtomography , Administration, Intravenous , Animals , Estradiol/administration & dosage , Female , Infusion Pumps, Implantable , Infusions, Subcutaneous , Injections, Subcutaneous , Mice , Predictive Value of Tests , Time Factors
3.
Sci Justice ; 55(2): 131-8, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25753999

ABSTRACT

Forensic anthropologists are generally able to identify skeletal materials (bone and tooth) using gross anatomical features; however, highly fragmented or taphonomically altered materials may be problematic to identify. Several chemical analysis techniques have been shown to be reliable laboratory methods that can be used to determine if questionable fragments are osseous, dental, or non-skeletal in nature. The purpose of this review is to provide a detailed background of chemical analysis techniques focusing on elemental compositions that have been assessed for use in differentiating osseous, dental, and non-skeletal materials. More recently, chemical analysis studies have also focused on using the elemental composition of osseous/dental materials to evaluate species and provide individual discrimination, but have generally been successful only in small, closed groups, limiting their use forensically. Despite significant advances incorporating a variety of instruments, including handheld devices, further research is necessary to address issues in standardization, error rates, and sample size/diversity.


Subject(s)
Bone and Bones/chemistry , Dental Enamel/chemistry , Trace Elements/analysis , Animals , Cremation , Forensic Anthropology , Humans , Microscopy , Species Specificity , Spectrometry, X-Ray Emission , Spectroscopy, Near-Infrared , Spectrum Analysis, Raman
4.
J Forensic Sci ; 60(2): 382-90, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25620077

ABSTRACT

One of the tasks of a forensic anthropologist is to sort human bone fragments from other materials, which can be difficult when dealing with highly fragmented and taphonomically modified material. The purpose of this research is to develop a method using handheld X-ray fluorescence (HHXRF) spectrometry to distinguish human and nonhuman bone/teeth from nonbone materials of similar chemical composition using multivariate statistical analyses. The sample materials were derived primarily from previous studies: human bone and teeth, nonhuman bone, nonbiological materials, nonbone biological materials, and taphonomically modified materials. The testing included two phases, testing both the reliability of the instrument and the accuracy of the technique. The results indicate that osseous and dental tissue can be distinguished from nonbone material of similar chemical composition with a high degree of accuracy (94%). While it was not possible to discriminate rock apatite and synthetic hydroxyapatite from bone/teeth, this technique successfully discriminated ivory and octocoral.


Subject(s)
Bone and Bones , Spectrometry, X-Ray Emission , Tooth , Animals , Calcium/analysis , Forensic Anthropology/methods , Humans , Phosphorus/analysis , Principal Component Analysis , Species Specificity
5.
Mol Genet Metab ; 109(4): 345-53, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23800641

ABSTRACT

Liver transplantation appears to be quite beneficial for treatment of maple syrup urine disease (MSUD, an inherited disorder of branched chain amino acid metabolism); however, there is a limited availability of donor livers worldwide and the first year costs of liver transplants are quite high. Recent studies have suggested that intact adipose tissue, already widely used in reconstructive surgery, may have an underappreciated high capacity for branched chain amino acid (BCAA) metabolism. Here we examined the potential for adipose tissue transplant to lower circulating BCAAs in two models of defective BCAA metabolism, BCATm and PP2Cm [branched chain keto acid dehydrogenase complex (BCKDC) phosphatase] knockout (KO) mice. After 1-2g fat transplant, BCATm and PP2Cm KO mice gained or maintained body weight 3weeks after surgery and consumed similar or more food/BCAAs the week before phlebotomy. Transplant of fat into the abdominal cavity led to a sterile inflammatory response and nonviable transplanted tissue. However when 1-2g of fat was transplanted subcutaneously into the back, either as small (0.1-0.3g) or finely minced pieces introduced with an 18-ga. needle, plasma BCAAs decreased compared to Sham operated mice. In two studies on BCATm KO mice and one study on PP2Cm KO mice, fat transplant led to 52-81% reductions in plasma BCAAs compared to baseline plasma BCAA concentrations of untreated WT type siblings. In PP2Cm KO mice, individual BCAAs in plasma were also significantly reduced by fat transplant, as were the alloisoleucine/Phe ratios. Therefore, subcutaneous fat transplantation may have merit as an adjunct to dietary treatment of MSUD. Additional studies are needed to further refine this approach.


Subject(s)
Adipose Tissue/transplantation , Maple Syrup Urine Disease/metabolism , Maple Syrup Urine Disease/therapy , Transaminases/metabolism , 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)/blood , 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)/genetics , 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)/metabolism , 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)/therapeutic use , Adipose Tissue/metabolism , Amino Acid Metabolism, Inborn Errors/blood , Amino Acid Metabolism, Inborn Errors/genetics , Amino Acid Metabolism, Inborn Errors/therapy , Animals , Maple Syrup Urine Disease/blood , Maple Syrup Urine Disease/genetics , Mice , Mice, Knockout , Transaminases/blood , Transaminases/genetics , Transaminases/therapeutic use
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