32 research outputs found

    Identifying genetic variants underlying medication-induced osteonecrosis of the jaw in cancer and osteoporosis: a case control study

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    Background Bisphosphonate-induced osteonecrosis of the jaw (BRONJ) presents with a typical pattern of jaw necrosis in patients who have been prescribed bisphosphonates (BPs) and other antiangiogenetic drugs to treat osteoporosis or bone-related complications of cancer. Methods This study divided 38 patients with BRONJ into two groups according to the prescribing causes: cancer (n = 13) and osteoporosis (n = 25), and underwent whole exome sequencing and compared them with normal controls (n = 90). To identify candidate genes and variants, we conducted three analyses: a traditional genetic model, gene-wise variant score burden, and rare-variant analysis methods. Results The stop-gain mutation (rs117889746) of the PZP gene in the BRONJ cancer group was significantly identified in the additive trend model analysis. In the cancer group, ARIDS, HEBP1, LTBP1, and PLVAP were identified as candidate genes. In the osteoporosis group, VEGFA, DFFA, and FAM193A genes showed a significant association. No significant genes were identified in the rare-variant analysis pipeline. Biologically accountable functions related to BRONJ occurrence-angiogenesis-related signaling (VEGFA and PLVAP genes), TGF-β signaling (LTBP1 and PZP genes), heme toxicity (HEBP1) and osteoblast maturation (ARIDS)-were shown in candidate genes. Conclusion This study showed that the candidate causative genes contributing to the development of BRONJ differ according to the BP dose and background disease.This work was supported by the Education and Research Encouragement Fund of Seoul National University Hospital and the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF2018R1D1A1A02086109). There are no conficts of interest to declare

    More Than Smell—COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis

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    Correction: Chemical Senses, Volume 46, 2021, bjab050, https://doi.org/10.1093/chemse/bjab050 Published: 08 December 2021Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change +/- 100) revealed a mean reduction of smell (-79.7 +/- 28.7, mean +/- standard deviation), taste (-69.0 +/- 32.6), and chemesthetic (-37.3 +/- 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis.The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.Peer reviewe

    Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms

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    In a preregistered, cross-sectional study we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC=0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4<10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable

    Human taste detection of glucose oligomers with low degree of polymerization

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    <div><p>Studies have reported that some animals, including humans, can taste mixtures of glucose oligomers (i.e., maltooligosaccharides, MOS) and that their detection is independent of the known T1R2/T1R3 sweet taste receptor. In an effort to understand potential mechanisms underlying the taste perception of glucose oligomers in humans, this study was designed to investigate: 1) the variability of taste sensitivity to MOS with low degree-of-polymerization (DP), and 2) the potential role of hT1R2/T1R3 in the MOS taste detection. To address these objectives, a series of food grade, narrow-DP-range MOS were first prepared (DP 3, 3–4, 5–6, and 6–7) by fractionating disperse saccharide mixtures. Subjects were then asked to discriminate these MOS stimuli as well as glucose (DP 1) and maltose (DP 2) from blanks after the stimuli were swabbed on the tongue. All stimuli were presented at 75 mM with and without a sweet taste inhibitor (lactisole). An α-glucosidase inhibitor (acarbose) was added to all test stimuli to prevent oral digestion of glucose oligomers. Results showed that all six stimuli were detected with similar discriminability in normal tasting conditions. When the sweet receptor was inhibited, DP 1, 2, and 3 were not discriminated from blanks. In contrast, three higher-DP paired MOS stimuli (DP 3–4, 5–6, and 6–7) were discriminated from blanks at a similar degree. Overall, these results support the presence of a sweet-independent taste perception mechanism that is stimulated by MOS greater than three units.</p></div

    Representative chromatograms from HPLC-ELSD depicting saccharide character of the four samples (A, DP 3; B, DP 3–4, C: DP 5–6, and D: DP 6–7) produced through column chromatography.

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    <p>Representative chromatograms from HPLC-ELSD depicting saccharide character of the four samples (A, DP 3; B, DP 3–4, C: DP 5–6, and D: DP 6–7) produced through column chromatography.</p

    Chemical characterization of four MOS samples prepared for psychophysical testing.

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    <p>Chemical characterization of four MOS samples prepared for psychophysical testing.</p

    Proportion correct<sup>a</sup> and discriminability (<i>d’</i> value)<sup>b</sup> of target stimuli in the absence and presence of lactisole.

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    <p>Proportion correct<sup>a</sup> and discriminability (<i>d’</i> value)<sup>b</sup> of target stimuli in the absence and presence of lactisole.</p

    Nonconjugated Anionic Polyelectrolyte as an Interfacial Layer for the Organic Optoelectronic Devices

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    A nonconjugated anionic polyelectrolyte, poly­(sodium 4-styrene­sulfonate) (PSS-Na), was applied to the optoelectronic devices as an interfacial layer (IFL) at the semiconducting layer/cathode interface. The ultraviolet photoelectron spectroscopy and the Kelvin probe microscopy studies support the formation of a favorable interface dipole at the organic/​cathode interface. For polymer light-emitting diodes (PLEDs), the maximum luminance efficiency (LE<sub>max</sub>) and the turn-on voltage (<i>V</i><sub>on</sub>) of the device with a layer of PSS-Na spin-coated from the concentration of 0.5 mg/mL were 3.00 cd/A and 5.5 V, which are dramatically improved than those of the device without an IFL (LE<sub>max</sub> = 0.316 cd/A, <i>V</i><sub>on</sub> = 9.5 V). This suggests that the PSS-Na film at the emissive layer/cathode interface improves the electron injection ability. As for polymer solar cells (PSCs), the power conversion efficiency (PCE) of the device with a layer of PSS-Na spin-coated from the concentration of 0.5 mg/mL was 2.83%, which is a 16% increase compared to that of the PSC without PSS-Na. The PCE improvement is mainly due to the enhancement of the short-circuit current (12% increase). The results support that the electron collection and transporting increase by the introduction of the PSS-Na film at the photoactive layer/cathode interface. The improvement of the efficiency of the PLED and PSC is due to the reduction of the Schottky barrier by the formation of a favorable interface as well as the better Ohmic contact at the cathode interface
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