Monitoring of blood glucose is an invasive, painful and costly practice in diabetes. Consequently, the search for a more cost-effective (reagent-free), non-invasive and specific diabetes monitoring method is of great interest. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used in diagnosis of several diseases, however, applications in the monitoring of diabetic treatment are just beginning to emerge. Here, we used ATR-FTIR spectroscopy to evaluate saliva of non-diabetic (ND), diabetic (D) and insulin-treated diabetic (D+I) rats to identify potential salivary biomarkers related to glucose monitoring. The spectrum of saliva of ND, D and D+I rats displayed several unique vibrational modes and from these, two vibrational modes were pre-validated as potential diagnostic biomarkers by ROC curve analysis with significant correlation with glycemia. Compared to the ND and D+I rats, classification of D rats was achieved with a sensitivity of 100%, and an average specificity of 93.33% and 100% using bands 1452 cm-1 and 836 cm-1 , respectively. Moreover, 1452 cm-1 and 836 cm-1 spectral bands proved to be robust spectral biomarkers and highly correlated with glycemia (R 2 of 0.801 and 0.788, P < 0.01, respectively). Both PCA-LDA and HCA classifications achieved an accuracy of 95.2%. Spectral salivary biomarkers discovered using univariate and multivariate analysis may provide a novel robust alternative for diabetes monitoring using a non-invasive and green technology.

Background: Coronavirus disease 2019 (COVID-19) is a global health problem, which is challenging healthcare worldwide. In this critical review, we discussed the advantages and limitations in the implementation of salivary diagnostic platforms of COVID-19. The diagnostic test of COVID-19 by invasive nasopharyngeal collection is uncomfortable for patients and requires specialized training of healthcare professionals in order to obtain an appropriate collection of samples. Additionally, these professionals are in close contact with infected patients or suspected cases of COVID-19, leading to an increased contamination risk for frontline healthcare workers. Although there is a colossal demand for novel diagnostic platforms with non-invasive and self-collection samples of COVID-19, the implementation of the salivary platforms has not been implemented for extensive scale testing. Up to date, several cross-section and clinical trial studies published in the last 12 months support the potential of detecting SARS-CoV-2 RNA in saliva as a biomarker for COVID-19, providing a self-collection, non-invasive, safe, and comfortable procedure. Therefore, the salivary diagnosis is suitable to protect healthcare professionals and other frontline workers and may encourage patients to get tested due to its advantages over the current invasive methods. The detection of SARS-CoV-2 in saliva was substantial also in patients with a negative nasopharyngeal swab, indicating the presence of false negative results. Furthermore, we expect that salivary diagnostic devices for COVID-19 will continue to be used with austerity without excluding traditional gold standard specimens to detect SARS-CoV-2.

Zika virus (ZIKV) diagnosis is currently performed through an invasive, painful, and costly procedure using molecular biology. Consequently, the search for a non-invasive, more cost-effective, reagent-free, and sustainable method for ZIKV diagnosis is of great relevance. It is critical to prepare a global strategy for the next ZIKV outbreak given its devastating consequences, particularly in pregnant women. Attenuated total reflection–Fourier transform infrared (ATR-FTIR) spectroscopy has been used to discriminate systemic diseases using saliva; however, the salivary diagnostic application in viral diseases is unknown. To test this hypothesis, we intradermally challenged interferon-gamma gene knockout C57/BL6 mice with ZIKV (50 µL,105 FFU, n = 7) or vehicle (50 µL, n = 8). Saliva samples were collected on day three (due to the peak of viremia) and the spleen was also harvested. Changes in the salivary spectral profile were analyzed by Student’s t test (p < 0.05), multivariate analysis, and the diagnostic capacity by ROC curve. ZIKV infection was confirmed by real-time PCR of the spleen sample. The infrared spectroscopy coupled with univariate analysis suggested the vibrational mode at 1547 cm−1 as a potential candidate to discriminate ZIKV and control salivary samples. Three PCs explained 93.2% of the cumulative variance in PCA analysis and the spectrochemical analysis with LDA achieved an accuracy of 93.3%, with a specificity of 87.5% and sensitivity of 100%. The PCA-SVM analysis showed 100% discrimination between both classes. Our results suggest that ATR-FTIR applied to saliva might have high accuracy in ZIKV diagnosis with potential as a non-invasive and cost-effective diagnostic tool.

Abstract The aim of this study was to evaluate the effect of acute sepsis in the periodontal ligament, alveolar and furcation bone in absence of periodontitis induction through histological and immunohistochemical analyses. A septic rat model was established by cecal ligation and puncture (CLP). Twelve rats were randomly divided into CLP (n=6) and Sham (n=6) groups. The animals were euthanized at 24 h and hemimandibles were submitted to histomorfometric (bone matrix, collagenous fibers, fibroblasts, osteocytes, inflammatory cells, and blood vessels) and immunohistochemical (BMP-2/4, RANKL and osteocalcin) evaluation in alveolar bone, furcation bone and periodontal ligament. Our results demonstrated that histomorphometric parameters were similar in alveolar bone, furcation bone and periodontal ligament of Sham and CLP rats. Regarding to immunohistochemical analyses, the number of BMP-2/4 and RANKL immunolabeled cells was also similar in both groups. Furthermore, it was detected a reduction in the osteocalcin immunolabeled cells in periodontal ligaments of CLP compared to Sham rats (p=0.0014). In conclusion, the acute sepsis induction resulted in reduced number of osteocalcin labelled cells in periodontal ligament region. Moreover, no significant histological differences were observed in the periodontium of rats under acute sepsis. Considering the role of osteocalcin in bone remodeling, the study contributes to revealing the importance of careful periodontal evaluation in the presence of sepsis.

Cyclo-Gly-Pro (CGP) attenuates nociception, however its effects on salivary glands remain unclear. In this study, we investigated the acute effects of CGP on salivary flow and composition, and on the submandibular gland composition, compared with morphine. Besides, we characterized the effects of naloxone (a non-selective opioid receptor antagonist) on CGPand morphine-induced salivary and glandular alterations in mice. After that, in silico analyses were performed to predict the interaction between CGP and opioid receptors. Morphine and CGP significantly reduced salivary flow and total protein concentration of saliva and naloxone restored them to the physiological levels. Morphine and CGP also reduced several infrared vibrational modes (Amide I, 1687-1594cm-1 ; Amide II, 1594-1494cm-1 ; CH 2 /CH 3 , 1488-1433cm-1 ; C = O, 1432-1365cm-1 ; PO 2 asymmetric, 1290-1185cm-1 ; PO 2 symmetric, 1135-999cm-1) and naloxone reverted these alterations. The in silico docking analysis demonstrated the interaction of polar contacts between the CGP and opioid receptor Cys219 residue. Altogether, we showed that salivary hypofunction and glandular changes elicited by CGP may occur through opioid receptor suggesting that the blockage of opioid receptors in superior cervical and submandibular ganglions may be a possible strategy to restore salivary secretion while maintaining antinociceptive action due its effects on the central nervous system.

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34Monitoring of blood glucose is an invasive, painful and costly practice in diabetes. 35 Consequently, the search for a more cost-effective (reagent-free), non-invasive and 36 specific diabetes monitoring method is of great interest. Attenuated total reflectance 37 Fourier transform infrared (ATR-FTIR) spectroscopy has been used in diagnosis of 38 several diseases, however, applications in the monitoring of diabetic treatment are just 39 beginning to emerge. Here, we used ATR-FTIR spectroscopy to evaluate saliva of non-40 diabetic (ND), diabetic (D) and diabetic 6U-treated of insulin (D6U) rats to identify 41 potential salivary biomarkers related to glucose monitoring. The spectrum of saliva of 42 ND, D and D6U rats displayed several unique vibrational modes and from these, two 43 vibrational modes were pre-validated as potential diagnostic biomarkers by ROC curve 44 analysis with significant correlation with glycemia. Compared to the ND and D6U rats, 45 classification of D rats was achieved with a sensitivity of 100%, and an average specificity 46 of 93.33% and 100% using bands 1452 cm -1 and 836 cm -1 , respectively. Moreover, 1452 47 cm -1 and 836 cm -1 spectral bands proved to be robust spectral biomarkers and highly 48 correlated with glycemia (R 2 of 0.801 and 0.788, P < 0.01, respectively). Both PCA-LDA 49 and HCA classifications achieved an accuracy of 95.2%. Spectral salivary biomarkers 50 discovered using univariate and multivariate analysis may provide a novel robust 51 alternative for diabetes monitoring using a non-invasive and green technology. 52 53 54 55 56 57 58 59 60 61 62 63 64 65 67 Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia 68 which results from insufficient secretion and/or reduced insulin action in peripheral 69 tissues (Rolo e Palmeira, 2006; Ashcroft e Rorsman, 2012). According to the 70 International Diabetes Federation (IDF), there are an estimated 425 million adults with 71 diabetes worldwide, these include 212 million whom are estimated undiagnosed (IDF, 72 2017). Frequent monitoring of diabetes is essential for improved glucose control and to 73 delay clinical complications related with diabetes. Besides, the early screening of DM is 74 paramount to reduce the complications of this metabolic disorder worldwide (Uspstf, 75 2008). Despite being relatively invasive and painful, blood analysis per glucometer is 76 currently feasible for screening, monitoring and diagnosing diabetes by needle finger 77 punctures (Dowlaty et al., 2013; Mascarenhas et al., 2014). The constant need of piercing 78 the fingers several times daily by most patients is inconvenient and may lead to the 79 development of finger calluses and difficulty in obtaining blood samples (Dowlaty et al., 80 2013). 81 Saliva reflects several physiological functions of the body (Desai e Mathews, 82 2014; Javaid et al., 2016). In this way, salivary biomarkers might be an attractive 83 alternative to blood for early detection, and for monitoring systemic diseases (Hu et al., 84 2007). Among...