Bridging the gap in rural healthcare

Rural areas ; Rural development

Investigation of catalytic combustion of impurities in air Final report, 24 Mar. - 28 Dec. 1966

Catalytic coil to oxidize carbon monoxide, hydrogen, and methane present as impurities in ai

Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy

The goal of breast-conserving surgery is to completely remove all of the cancer. Currently, no intraoperative tools can microscopically analyze the entire lumpectomy specimen, which results in 20 to 60% of patients undergoing second surgeries to achieve clear margins. To address this critical need, we have laid the foundation for the development of a device that could allow accurate intraoperative margin assessment. We demonstrate that by taking advantage of the intrinsic optical contrast of breast tissue, photoacoustic microscopy (PAM) can achieve multilayered histology-like imaging of the tissue surface. The high correlation of the PAM images to the conventional histologic images allows rapid computations of diagnostic features such as nuclear size and packing density, potentially identifying small clusters of cancer cells. Because PAM does not require tissue processing or staining, it can be performed promptly and intraoperatively, enabling immediate directed re-excision and reducing the number of second surgeries

Inhibition of CaMKK2 reverses age-associated decline in bone mass

Decline in bone formation is a major contributing factor to the loss of bone mass associated with aging. We previously showed that the genetic ablation of the tissue-restricted and multifunctional Ca(2+)/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) stimulates trabecular bone mass accrual, mainly by promoting anabolic pathways and inhibiting catabolic pathways of bone remodeling. In this study, we investigated whether inhibition of this kinase using its selective cell-permeable inhibitor STO-609 will stimulate bone formation in 32 week old male WT mice and reverse age-associated of decline in bone volume and strength. Tri-weekly intraperitoneal injections of saline or STO-609 (10 μM) were performed for six weeks followed by metabolic labeling with calcein and alizarin red. New bone formation was assessed by dynamic histomorphometry whereas micro-computed tomography was employed to measure trabecular bone volume, microarchitecture and femoral mid-shaft geometry. Cortical and trabecular bone biomechanical properties were assessed using three-point bending and punch compression methods respectively. Our results reveal that as they progress from 12 to 32 weeks of age, WT mice sustain a significant decline in trabecular bone volume, microarchitecture and strength as well as cortical bone strength. However, treatment of the 32 week old WT mice with STO-609 stimulated apposition of new bone and completely reversed the age-associated decrease in bone volume, quality, as well as trabecular and cortical bone strength. We also observed that regardless of age, male Camkk2(-/-) mice possessed significantly elevated trabecular bone volume, microarchitecture and compressive strength as well as cortical bone strength compared to age-matched WT mice, implying that the chronic loss of this kinase attenuates age-associated decline in bone mass. Further, whereas STO-609 treatment and/or the absence of CaMKK2 significantly enhanced the femoral mid-shaft geometry, the mid-shaft cortical wall thickness and material bending stress remained similar among the cohorts, implying that regardless of treatment, the material properties of the bone remain similar. Thus, our cumulative results provide evidence for the pharmacological inhibition of CaMKK2 as a bone anabolic strategy in combating age-associated osteoporosis

Photoacoustic microscopy enables multilayered histological imaging of human breast cancer without staining

In 2016, an estimated ~250,000 new cases of invasive and non-invasive breast cancer were diagnosed in US women. About 60–75% of these cases were treated with breast conserving surgery (BCS) as the initial therapy. To reduce the local recurrence rate, the goal of BCS is to excise the tumor with a rim of normal surrounding tissue, so that no cancer cells remain at the cut margin, while preserving as much normal breast tissue as possible. Therefore, patients with remaining cancer cells at the cut margin commonly require a second surgical procedure to obtain clear margins. Different approaches have been used to decrease the positive margin rate to avoid re-excision. However, these techniques are variously ineffective in reducing the re-operative rate, difficult to master by surgeons, or time-consuming for large specimens. Thus, 20-60% of patients undergoing BCS still require second surgeries due to positive surgical margins. The ideal tool for margin assessment would provide the same information as histological analysis, without the need for processing specimens. To achieve this goal, we have developed and refined label-free photoacoustic microscopy (PAM) for breast specimens. Exploiting the intrinsic optical contrast of tissue, ultraviolet (UV) laser illumination can highlight cell nuclei, thus providing the same contrast as hematoxylin labeling used in conventional histology and measuring features related to the histological landscape without the need for labels. We demonstrate that our UV-PAM system can provide label-free, high-resolution, and histology-like imaging of fixed, unprocessed breast tissue

Mandibular and Neural Crest Cell Deficits Seen in TsDn65 Down Syndrome Mouse Model Rescued By Green Tea Polyphenol, EGCG

poster abstractDown Syndrome (DS) is caused by trisomy of the human chromosome 21 (Hsa21) and occurs in ~1 of every 700 births. DS is distinguished by over 80 phenotypic abnormalities including skeletal deficits and craniofacial phenotypes characterized by a flattened skull, slanted eyes, and a smaller mandible. To study these abnormalities, we utilize the Ts65Dn DS mouse model containing a triplication of approximately half of the gene homologues found on Hsa21 and mirrors the skeletal and mandibular phenotypes observed in DS. In Ts65Dn mice, the origin of the mandibular deficits were traced to a reduction in size of the 1st branchial arch (BA1), the developmental precursor to the mandible, occurring at embryonic day 9.5 (E9.5). At E9.5, we observe a lack of proliferation and migration of neural crest cells (NCC) from the neural tube (NT) into the BA1, causing a reduced BA1. We hypothesize that an overexpression of Dyrk1a, a Hsa21 homologue, contributes to the mandibular deficit seen in E9.5 Ts65Dn embryos. We propose that EGCG, a green tea polyphenol, will inhibit DYRK1a activity, rescuing the BA1 deficit. To test our hypothesis, Ts65Dn mothers were treated with EGCG from E0-E9.5 and sacrificed to retrieve the E9.5 embryos. Our results from unbiased stereological assessments show that E0-E9.5 EGCG in vivo treatment has the potential to increase NCC number, BA1 volume, and embryo volume of trisomic embryos. This data provide preclinical testing for a potential therapy of DS craniofacial disorders, which may extend to treating bone deficits in DS and osteoporosis