Synthesis and in vitro characteristics of biogenic-derived hydroxyapatite for bone remodeling applications.

The inorganic component of bone matrix, hydroxyapatite (HAp) (with formula Ca10(PO4)6(OH)2), can be obtained from inexpensive waste resources that serve as excellent calcium precursors. In the present study, HAp nano-powder was synthesized from eggshells (ES) and crab shells (CS) by wet chemical precipitation method. Also, a hybrid sample was considered which is a mixture of HAp nano-powder synthesized from eggshells (25%) and crab shells (75%) (EC). The presence of phosphate, carbonate, and hydroxyl groups in the synthesized powder was confirmed through FTIR analysis. The phase composition was determined using XRD, and elemental analysis revealed a Ca/P ratio ranging from 1.5 to 1.8, confirming the HAp nature of the nano-powder, which ranged in size from 73 to 375 nm. Importantly, preliminary in vitro tests were conducted using mouse preosteoblast cell line MC3T3-E1 to evaluate the cytotoxic effects of the synthesized HAp. The results indicated excellent biocompatibility. Moreover, sample EC exhibited a significantly higher proliferation on days 3, 6, 9, and 12. EC demonstrated promising antimicrobial properties by exhibiting a significantly higher inhibitory effect against the bacteria Streptococcus mutans and Escherichia coli, and the fungi Candida albicans and Aspergillus niger. Additionally, EC displayed notable antioxidant activity, with IC50 values of 271.543 µg/ml and 407.764 µg/ml in DPPH and H2O2 assays, respectively. Furthermore, it showed strong anti-inflammatory properties, with a dose-dependent inhibition against protein denaturation. Given these findings, the synthesized HAp holds promise as a potential bone filler and could be beneficial for bone remodeling applications.

Nuclear roles for non-lamin intermediate filament proteins.

The nuclear-localized lamins have long been thought to be the only intermediate filaments (IFs) with an impact on the architecture, properties, and functions of the nucleus. Recent studies, however, uncovered significant roles for IFs other than lamins (here referred to as "non-lamin IFs") in regulating key properties of the nucleus in various cell types and biological settings. In the cytoplasm, IFs often occur in the perinuclear space where they contribute to local stiffness and impact the shape and/or the integrity of the nucleus, particularly in cells under stress. In addition, selective non-lamin IF proteins can occur inside the nucleus where they partake in fundamental processes including nuclear architecture and chromatin organization, regulation of gene expression, cell cycle progression, and the repair of DNA damage. This text reviews the evidence supporting a role for non-lamin IF proteins in regulating various properties of the nucleus and highlights opportunities for further study.

Comparison of an ID NOW COVID-19 Assay Used at the Point of Care to Laboratory-Based Nucleic Acid Amplification Tests.

The emergence of a novel coronavirus, namely, SARS-CoV-2, necessitated the use of rapid, accurate diagnostics to quickly diagnose COVID-19. This need has increased with the emergence of new variants and continued waves of COVID-19 cases. The ID NOW COVID-19 assay is a rapid nucleic acid amplification test (NAAT) that is used by hospitals, urgent care facilities, medical clinics, and public health laboratories for rapid molecular SARS-CoV-2 testing at the point of care. The District of Columbia Department of Forensic Sciences Public Health Laboratory Division (DC DFS PHL) implemented ID NOW COVID-19 testing in nontraditional laboratory settings, including a mobile testing unit, health clinic, and emergency department, to assist with rapid identification and isolation for populations at high risk of SARS-CoV-2 transmission in the District of Columbia. The DC DFS PHL provided these nontraditional laboratories with safety risk assessment, assay training, competency assessment, and quality control monitoring as parts of a comprehensive quality management system (QMS). We assessed the accuracy of the ID NOW COVID-19 assay when operated in the context of these trainings and systems. This was done by comparing results from 9,518 paired tests, and strong agreement (κ = 0.88, OPA = 98.3%) was found between the ID NOW COVID-19 assay and laboratory-based NAATs. These findings indicate that the ID NOW COVID-19 assay can be used to detect SARS-CoV-2 in nontraditional laboratory settings when used within the context of a comprehensive QMS.

MODE: Multiply modulated frame technique, excitation and coherence transfer.

The study of modulated pulse (MODE pulse) approach for the application in NMR has been in the literature for over a decade. Although the method's purpose was initially to decouple the spins, its application can be extended to broadband excitation, inversion and coherence transfer between spins (TOCSY). In this paper, the experimental validation of the TOCSY experiment with the help of MODE pulse and how the coupling constant varies over different frames are shown. We demonstrate that the TOCSY with a higher MODE pulse will result in less coherence transfer even with the same RF-power, and a lower MODE pulse will require a larger RF-amplitude to achieve TOCSY over the same bandwidth. We also present a quantitative analysis of the error due to fast oscillating terms that can be neglected, giving the required results.

An improved algorithm for design of broadband excitation, inversion, and mixing pulse sequences by iterative optimization of phases: TOPS-2.

This paper presents an improved iterative algorithm (TOPS-2) for the design of broadband inversion, excitation and coherent transfer mixing sequence (TOCSY) pulses. The evolution of the Bloch vector is presented as a sequence of small constant flip angle pulses with varying phases and constant amplitude. This paper describes an improved algorithm for iterative optimization of piece-wise constant phases as we incorporate the quadratic terms in the propagators. In our iterative optimization we obtain a closed-form expression for each phase, and these phases are optimized sequentially using the new improved algorithm. This paper compares the simulation results of the TOPS vs TOPS-2 and shows that TOPS-2 perform better. Experimental validation of excitation and inversion TOPS-2 pulse sequence is performed with .5% H2O in 99.5% D2O, and experimental validation of TOPS-2 mixing (TOCSY) pulse sequence is done with 0.1% of Ethylbenzene (EB) in CDCl3 solvent.

Morpho-functional characterization of the submucosal glands at the nasopharyngeal end of the auditory tube in humans.

BACKGROUND: The auditory tube (AT), an osteocartilaginous channel, connects the nasopharynx to the middle ear cavity. At the nasopharyngeal opening of the AT, there are dense collections of submucosal glands. In a recent article, Valstar et al. proposed these nasopharyngeal tubal glands conglomerate as salivary glands, which starkly contrasts with their previously known anatomy for being a component of the respiratory tract. This study examines the contesting views regarding the taxonomical categorization of the nasopharyngeal tubal glands. MATERIALS AND METHODS: The AT glands in context were examined in human cadavers grossly, and microscopically using routine and special (Hematoxylin and Eosin [H&E] and Periodic acid-Schiff [PAS] respectively), as well as immunohistochemical (for alpha-SMA and salivary amylase) staining methods and compared with the major and minor salivary glands and the submucosal glands in the trachea. Further, a biochemical analysis was performed to detect the presence of salivary amylase in the oral and nasopharyngeal secretions of the four living human subjects, representing major salivary glands and tubal glands, respectively. RESULTS: The submucosal seromucous glands with a surface lining of respiratory epithelium were observed at the nasopharyngeal end of AT. The cells in the tubal glands showed cytoplasmic positivity for alpha-SMA, which indicated the presence of the myoepithelial cells; however, this expression was significantly lower than in the seromucous submucosal glands within the trachea. Salivary alpha-amylase was undetectable in the cadaveric tissue samples. Moreover, the amylase level in the nasopharyngeal swabs was negligible compared to the oral swabs. CONCLUSION: The anatomical location along the respiratory tract, the presence of respiratory epithelium in the overlying mucosa, their morpho-functional resemblance to the seromucous glands in the trachea, and the absence of salivary amylase strongly indicate that the tubal glands are taxonomically different from the salivary glands. Given the available evidence, their existing recognition as a part of the respiratory tract and an integral component of the AT seems more appropriate.

Regeneration or Repair? The Role of Alveolar Epithelial Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis (IPF).

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease (ILD) with unknown etiology in which gradual fibrotic scarring of the lungs leads to usual interstitial pneumonia (UIP) and, ultimately, to death. IPF affects three million people worldwide, and the only currently available treatments include the antifibrotic drugs nintedanib and pirfenidone, which effectively reduce fibrosis progression are, unfortunately, not effective in curing the disease. In recent years, the paradigm of IPF pathogenesis has shifted from a fibroblast-driven disease to an epithelium-driven disease, wherein, upon recurrent microinjuries, dysfunctional alveolar type II epithelial cells (ATII) are not only unable to sustain physiological lung regeneration but also promote aberrant epithelial-mesenchymal crosstalk. This creates a drift towards fibrosis rather than regeneration. In the context of this review article, we discuss the most relevant mechanisms involved in IPF pathogenesis with a specific focus on the role of dysfunctional ATII cells in promoting disease progression. In particular, we summarize the main causes of ATII cell dysfunction, such as aging, environmental factors, and genetic determinants. Next, we describe the known mechanisms of physiological lung regeneration by drawing a parallel between embryonic lung development and the known pathways involved in ATII-driven alveolar re-epithelization after injury. Finally, we review the most relevant interventional clinical trials performed in the last 20 years with the aim of underlining the urgency of developing new therapies against IPF that are not only aimed at reducing disease progression by hampering ECM deposition but also boost the physiological processes of ATII-driven alveolar regeneration.

CCR4+ monocytic myeloid-derived suppressor cells are associated with the increased epithelial-mesenchymal transition in pancreatic adenocarcinoma patients.

Among all the cancer-related deaths globally, pancreatic ductal adenocarcinoma (PDAC) accounts for the seventh leading cause of mortality. A dysregulated immune system disrupts anti-tumor immunity by abnormal accumulation of myeloid-derived suppressor cells (MDSCs), but the underlying mechanisms are still inconclusive. To gain new insights into the role of MDSCs in tumor settings, we aimed to determine the mechanism of expansion of various subsets of MDSCs in PDAC patients and their role in promoting invasiveness. We assessed the load of MDSCs, chemokines responsible for the recruitment of MDSCs in PDAC patients by flow cytometry. We investigated the chemokine profile of tumor tissue using qRT-PCR and the status of epithelial-mesenchymal transition (EMT) related markers E-Cadherin, N-Cadherin, Snail, and ZEB1 by qRT-PCR and immunohistochemistry. We found a higher frequency of tumor infiltrated MDSCs in PDAC patients. Chemokine ligands CCL2 and the receptor CCR4 were markedly elevated in the PDAC tumor, while CCR4+ monocytic MDSCs (M-MDSCs) were found significantly elevated in peripheral blood and tumor tissue. In tumor tissue, expression of E-Cadherin was significantly reduced, while N-Cadherin, Snail, and ZEB1 were markedly raised. The frequency of CCR4+ M-MDSCs significantly correlated with the expression of mesenchymal transition markers N-Cadherin, Snail, and ZEB1. Collectively, these results suggest that the CCL2-CCR4 axis plays a crucial role in driving the recruitment of M-MDSCs, which is associated with increased invasiveness in PDAC. This study sheds light on the expansion mechanism of MDSCs, which can serve as a crucial target of future anti-cancer strategies to inhibit tumor cell invasiveness.

Senescent chondrogenic progenitor cells derived from articular cartilage of knee osteoarthritis patients contributes to senescence-associated secretory phenotype via release of IL-6 and IL-8.

OBJECTIVES: Despite the presence of chondrogenic progenitor cells (CPCs) in knee osteoarthritis patients they are unable to repair the damaged cartilage. This study aimed to evaluate the oxidative stress, cellular senescence, and senescence-associated secretory phenotype (SASP) in the CPCs derived from osteoarthritic cartilage and compare with the CPCs of healthy articular cartilage. METHODS: Isolated CPCs were characterized based on phenotypic expression of stem cell markers, clonogenicity, and tri-lineage differentiation assay. Production of ROS was measured using DCFDA assay. Cellular senescence in CPCs was assessed by senescence-associated beta-galactosidase assay and expression of senescence markers at the gene level using real-time PCR. Morphological features associated with senescent OA-CPCs were studied using scanning electron microscopy. To study SASP, the production of inflammatory cytokines was assessed in the culture supernatant using a flow-cytometer based cytometric bead array. RESULTS: OA-CPCs exhibited elevated ROS levels along with a relatively high percentage of senescent cells compared to non-OA CPCs, and a positive correlation exists between ROS production and senescence. The morphological assessment of senescent CPCs revealed increased cell size and multiple nuclei in senescent OA-CPCs. These results were further validated by elevated expression of senescence genes p16, p21, and p53. Additionally, culture supernatant of senescent OA-CPCs expressed IL-6 and IL-8 cytokines indicative of SASP. CONCLUSIONS: Despite exhibiting similar expression of stem cell markers and clonogenicity, CPCs undergo oxidative stress in diseased knee joint leading to increased production of intracellular ROS in chondrogenic progenitor cells that support cellular senescence. Further, senescence in OA-CPCs is mediated via the release of pro-inflammatory cytokines, IL-6 and IL-8.

Evaluation of probiotic properties of Lysinibacillus macroides under in vitro conditions and culture of Cyprinus carpio on growth parameters.

Cyprinus carpio is an important freshwater fish in aquaculture. It was used for the isolation of potential probiotic strain for aquaculture applications. The most dominant strain was isolated on MRS agar from the gastrointestinal (GI) of C. carpio and identified as Lysinibacillus macroides using molecular marker 16S rRNA gene. Various probiotic properties such as acid and bile tolerance and antibiotic susceptibility were analysed under in vitro conditions. Further, formulate pelletized feed using probiotic (L. macroides) in different concentrations (2, 4, 6 and 8%). Rearing of C. carpio was carried out 45 days and fed with formulated feed. The highest length (5.14 ± 0.07 cm) and weight (3.56 ± 0.07 g) of C. carpio fingerlings was recorded in the 8% LM probiotic pelletized feed, while in fingerlings fed with control showed lower in the length (3.02 ± 0.13 cm) and the weight (0.92 ± 0.04 g) on the 45th day of the experiment. Both percentage of weight gain (PWG) and specific growth rate (SGR) were significantly increased (P < 0.05) of C. carpio fingerlings fed with probiotic feed compared to control feed. Hence, the use of probiotic bacteria could be an encouraging alternative feed for future endeavours in the field of aquaculture. In conclusion, L. macroides can serve as probiotic for sustainable, competitive and promising beneficial bacteria to aquaculture industry.

A role for keratin 17 during DNA damage response and tumor initiation.

High levels of the intermediate filament protein keratin 17 (K17) are associated with poor prognoses for several human carcinomas. Studies in mouse models have shown that K17 expression is positively associated with growth, survival, and inflammation in skin and that lack of K17 delays onset of tumorigenesis. K17 occurs in the nucleus of human and mouse tumor keratinocytes where it impacts chromatin architecture, gene expression, and cell proliferation. We report here that K17 is induced following DNA damage and promotes keratinocyte survival. The presence of nuclear K17 is required at an early stage of the double-stranded break (DSB) arm of the DNA damage and repair (DDR) cascade, consistent with its ability to associate with key DDR effectors, including γ-H2A.X, 53BP1, and DNA-PKcs. Mice lacking K17 or with attenuated K17 nuclear import showed curtailed initiation in a two-step skin carcinogenesis paradigm. The impact of nuclear-localized K17 on DDR and cell survival provides a basis for the link between K17 induction and poor clinical outcomes for several human carcinomas.

Myeloid-derived suppressor cells: Bridging the gap between inflammation and pancreatic adenocarcinoma.

Pancreatic cancer has been identified as one of the deadliest malignancies because it remains asymptomatic and usually presents in the advanced stage. Tumour immune evasion is a well-known mechanism of tumorigenesis in various forms of human malignancies. Chronic inflammation via complex networking of various inflammatory cytokines in the local tissue microenvironment dysregulates the immune system and support tumour development. Pro-inflammatory mediators present in the tumour microenvironment increase the tumour burden by causing immune suppression through the generation of myeloid-derived suppressor cells (MDSCs) and T regulatory cells. These cells, along-with myofibroblasts, create a highly immunosuppressive and resistant tumour microenvironment and are thus considered as one of the culprits for the failure of anti-cancer chemotherapies in pancreatic adenocarcinoma patients. Targeting these MDSCs using various combinatorial approaches might have the potential for abrogating the resistance and suppressive nature of the pancreatic tumour microenvironment. Therefore, there is more curiosity in studying the crosstalk of MDSCs with other immune cells during pathological conditions and the underlying mechanisms of immunosuppression in the current scenario. In this article, the possible role of MDSCs in inflammation-mediated tumour progression of pancreatic adenocarcinoma has been discussed.

Bone Mineral Density: Clinical Relevance and Quantitative Assessment.

Bone mineral density (BMD) measurement by dual-energy x-ray absorptiometry (DXA) is an internationally accepted standard-of-care screening tool used to assess fragility-fracture risk. Society guidelines have recommended which populations may benefit from DXA screening and the use of the fracture risk assessment tool (FRAX) to guide decisions regarding pharmacologic treatment for osteoporosis. According to the U.S. National Osteoporosis Foundation guidelines, postmenopausal women and men at least 50 y old with osteopenic BMD warrant pharmacologic treatment if they have a FRAX-calculated 10-y probability of at least 3% for hip fracture or at least 20% for major osteoporotic fracture. Patients with osteoporosis defined by a clinical event, namely a fragility fracture, or with an osteoporotic BMD should also be treated. Patients who are treated for osteoporosis should be monitored regularly to track expected gains in BMD by serial DXA scans. With some drug therapies, BMD targets can be reached whereby further improvements in BMD are not associated with further reductions in fracture risk. Although reaching this target might suggest a stopping point for therapy, the reversibility of most treatments for osteoporosis, except for the bisphosphonates, has dampened enthusiasm for this approach. In the case of denosumab, it is now apparent that stopping therapy at any point can lead to an increase in multiple-fracture risk. For patients who do not respond to antiosteoporosis pharmacologic therapy with an improvement in BMD, or who have an incident fragility fracture on therapy, secondary causes of osteoporosis or non-compliance with medical therapy should be considered.

IL-6 is associated with expansion of myeloid-derived suppressor cells and enhanced immunosuppression in pancreatic adenocarcinoma patients.

Chronic inflammation favours the expansion of myeloid-derived suppressor cells (MDSCs) by secreting pro-inflammatory mediators. The role of MDSCs in mediating immunosuppression in pancreatic adenocarcinoma and in defining a premalignant route from chronic pancreatitis remains unclear. We aimed to study the immunosuppressive potential of all subsets of MDSCs and their correlation with inflammatory cytokines in pancreatic adenocarcinoma and chronic pancreatitis. Relative frequencies of MDSCs, immunosuppressive markers arginase-1 (ARG-1), programmed death-ligand 1 (PD-L1), reactive oxygen species (ROS) and cytokines in circulation and surgically resected local pancreatic tissue of chronic pancreatitis and pancreatic adenocarcinoma patients were analysed by multicolour flow cytometry and cytokine bead array, respectively. Levels of cytokines involved in MDSCs activation were analysed by ELISA, and the immunosuppressive nature of MDSCs was confirmed by T-cell suppression assay. Frequencies of circulating MDSCs and ARG-1, PD-L1, and ROS were significantly higher in pancreatic adenocarcinoma than healthy controls and showed a significant positive correlation with MDSCs burden in cancer tissue. Serum levels of cytokines IL-6, IL-8 and IL-10 were significantly elevated in pancreatic adenocarcinoma. IL-6 serum levels showed a significant positive correlation with frequencies of circulating MDSCs in pancreatic adenocarcinoma patients, and MDSCs mediated suppression of T-cell proliferation in vitro was associated with elevated IL-6 levels in the cell culture medium. Collectively, our results suggest that IL-6 plays a crucial role in the expansion of MDSCs and activating their immunosuppressive nature in pancreatic adenocarcinoma. The relative frequency of MDSCs in circulation can be used as a potential diagnostic biomarker for pancreatic cancer.

Keratin 17 regulates nuclear morphology and chromatin organization.

Keratin 17 (KRT17; K17), a non-lamin intermediate filament protein, was recently found to occur in the nucleus. We report here on K17-dependent differences in nuclear morphology, chromatin organization, and cell proliferation. Human tumor keratinocyte cell lines lacking K17 exhibit flatter nuclei relative to normal. Re-expression of wild-type K17, but not a mutant form lacking an intact nuclear localization signal (NLS), rescues nuclear morphology in KRT17-null cells. Analyses of primary cultures of skin keratinocytes from a mouse strain expressing K17 with a mutated NLS corroborated these findings. Proteomics screens identified K17-interacting nuclear proteins with known roles in gene expression, chromatin organization and RNA processing. Key histone modifications and LAP2ß (an isoform encoded by TMPO) localization within the nucleus are altered in the absence of K17, correlating with decreased cell proliferation and suppression of GLI1 target genes. Nuclear K17 thus impacts nuclear morphology with an associated impact on chromatin organization, gene expression, and proliferation in epithelial cells.This article has an associated First Person interview with the first author of the paper.

Nuclear Medicine Advanced Associates: Physician Extenders in Nuclear Medicine-Now Is the Time.

From its inception in 2008 until 2020, the nuclear medicine advanced associate (NMAA) has evolved into a valuable member of the imaging team. Data show that NMAAs perform key services including supervision, interpretation, protocoling of adjunct studies, and management, freeing nuclear medicine physicians to concentrate on more complicated and time-intensive responsibilities. Additionally, the profession has gained ground by becoming recognized by the Nuclear Medicine Technology Certification Board (NMTCB), with the advent of a formal NMAA certification examination and recognition guidelines for institutions interested in establishing NMAA educational programs. Actions are under way for the creation of new NMAA programs with pathways to enhance and expand student recruitment. A special task force has been established by the Society of Nuclear Medicine and Molecular Imaging Advanced Associate Council to raise awareness of the advantages of the physician extender within the practice setting. Practicing NMAAs perform duties that are beyond the scope of nuclear medicine technologists.

Antidiabetic potential of Andrographis echioides Nees. leaf extract on high fat diet-fed C57BL/6J diabetic mice.

The present study validates the antidiabetic potential of Andrographis echioides leaf extract (AeLE) on high fat diet-fed diabetic C57BL/6J mice. The male C57BL/6J mouse (age 6-8 weeks) were divided into 2 groups (lean control group and diabetic group). The lean control group (6 animals) was fed with standard diet pellets. The diabetic group animals (24 animals) were made diabetic by feeding a high-fat diet for 12 weeks. This group was then further divided into 4 groups of 6 animals each and treated orally (for 28 days) with vehicle (0.5%carboxymethyl cellulose), metformin 100mg/kg body weight and 2 different concentrations of test drug viz., 100mg/kg and 200mg/kg body weight. The results show a significant reduction in blood glucose and other biochemical parameters. After 28 days, the metformin and AeLE (200 mg/kg b.w) treated animals had an average serum glucose value of 129.69±1.97 mg/dl and 109.6±3.92 mg/dl, respectively. Also, the liver markers were positively affected by AeLE. In conclusion, A. echioides leaf extract was found to reduce hyperglycemia and significantly improve the biochemical profile of the mice.

Prospective evaluation of oral premalignant lesions using a multimodal imaging system: a pilot study.

BACKGROUND: Multimodal optical imaging, incorporating reflectance and fluorescence modalities, is a promising tool to detect oral premalignant lesions in real-time. METHODS: Images were acquired from 171 sites in 66 patient visits for clinical evaluation of oral lesions. An automated algorithm was used to classify lesions as high- or low-risk for neoplasia. Biopsies were acquired at clinically indicated sites and those classified as high-risk by imaging, at the surgeon's discretion. RESULTS: Twenty sites were biopsied based on clinical examination or imaging. Of these, 12 were indicated clinically and by imaging; 58% were moderate dysplasia or worse. Four biopsies were indicated by imaging evaluation only; 75% were moderate dysplasia or worse. Finally, four biopsies were indicated by clinical evaluation only; 75% were moderate dysplasia or worse. CONCLUSION: Multimodal imaging identified more cases of high-grade dysplasia than clinical evaluation, and can improve detection of high grade precancer in patients with oral lesions.

Chronic inflammation during osteoarthritis is associated with an increased expression of CD161 during advanced stage.

Increasing evidence suggests a role of inflammation during the pathogenesis of osteoarthritis (OA). The local and systemic inflammation was studied in 33 patients of different KL grades, grade2 (n = 11), grade3 (n = 6) and grade4 (n = 16). The levels of cytokines, adipokines and matrix metalloproteinases (MMPs) were measured in serum and synovial fluid (SF) by flow cytometry and ELISA, respectively. The frequency of T cells and CD161 expression was measured by flow cytometry. The levels of IL-1ß, IL-6 and IL-10 were significantly higher in sera and SF of patients with OA as compared to healthy control's serum. Higher levels of MMP9 and leptin and lower levels of adiponectin were observed in SF as compared to serum. The MMP9 in SF and MMP13 levels in serum and SF decreased in KL grade 4 cases. In these patients, higher levels of leptin and lower levels of adiponectin were observed in SF versus patients of lower grades. There was increased infiltration of CD8+ T cells in SF of OA cases with decreased frequency in grade 4 cases. The expression of CD161 on T cells was significantly higher in SF than peripheral blood with significant upregulation in grade 4 patients. The CD161 expression had significant positive correlation with IL-17 in the serum of patients. The ROC curves of CD161 expression significantly distinguished grade 2 and grade 4 patients. Collectively, an elevated CD161 expression on T cells in circulation and synovial compartment clearly distinguished lower and higher grade patients warranting studies to assess its role as a contributing factor towards OA progression.

Development of an integrated multimodal optical imaging system with real-time image analysis for the evaluation of oral premalignant lesions.

Oral premalignant lesions (OPLs), such as leukoplakia, are at risk of malignant transformation to oral cancer. Clinicians can elect to biopsy OPLs and assess them for dysplasia, a marker of increased risk. However, it is challenging to decide which OPLs need a biopsy and to select a biopsy site. We developed a multimodal optical imaging system (MMIS) that fully integrates the acquisition, display, and analysis of macroscopic white-light (WL), autofluorescence (AF), and high-resolution microendoscopy (HRME) images to noninvasively evaluate OPLs. WL and AF images identify suspicious regions with high sensitivity, which are explored at higher resolution with the HRME to improve specificity. Key features include a heat map that delineates suspicious regions according to AF images, and real-time image analysis algorithms that predict pathologic diagnosis at imaged sites. Representative examples from ongoing studies of the MMIS demonstrate its ability to identify high-grade dysplasia in OPLs that are not clinically suspicious, and to avoid unnecessary biopsies of benign OPLs that are clinically suspicious. The MMIS successfully integrates optical imaging approaches (WL, AF, and HRME) at multiple scales for the noninvasive evaluation of OPLs.