Smell and taste symptom-based predictive model for COVID-19 diagnosis.

BackgroundThe presentation of coronavirus 2019 (COVID-19) overlaps with common influenza symptoms. There is limited data on whether a specific symptom or collection of symptoms may be useful to predict test positivity.MethodsAn anonymous electronic survey was publicized through social media to query participants with COVID-19 testing. Respondents were questioned regarding 10 presenting symptoms, demographic information, comorbidities, and COVID-19 test results. Stepwise logistic regression was used to identify predictors for COVID-19 positivity. Selected classifiers were assessed for prediction performance using receiver operating characteristic (ROC) curve analysis.ResultsA total of 145 participants with positive COVID-19 testing and 157 with negative results were included. Participants had a mean age of 39 years, and 214 (72%) were female. Smell or taste change, fever, and body ache were associated with COVID-19 positivity, and shortness of breath and sore throat were associated with a negative test result (p < 0.05). A model using all 5 diagnostic symptoms had the highest accuracy with a predictive ability of 82% in discriminating between COVID-19 results. To maximize sensitivity and maintain fair diagnostic accuracy, a combination of 2 symptoms, change in sense of smell or taste and fever was found to have a sensitivity of 70% and overall discrimination accuracy of 75%.ConclusionSmell or taste change is a strong predictor for a COVID-19-positive test result. Using the presence of smell or taste change with fever, this parsimonious classifier correctly predicts 75% of COVID-19 test results. A larger cohort of respondents will be necessary to refine classifier performance

Corticostriatal functional connectivity of bothersome tinnitus in single-sided deafness

Subjective tinnitus is an auditory phantom perceptual disorder without an objective biomarker. Bothersome tinnitus in single-sided deafness (SSD) is particularly challenging to treat because the deaf ear can no longer be stimulated by acoustic means. We contrasted an SSD cohort with bothersome tinnitus (TIN; N = 15) against an SSD cohort with no or non-bothersome tinnitus (NO TIN; N = 15) using resting-state functional magnetic resonance imaging (fMRI). All study participants had normal hearing in one ear and severe or profound hearing loss in the other. We evaluated corticostriatal functional connectivity differences by placing seeds in the caudate nucleus and Heschl’s Gyrus (HG) of both hemispheres. The TIN cohort showed increased functional connectivity between the left caudate and left HG, and left and right HG and the left caudate. Within the TIN cohort, functional connectivity between the right caudate and cuneus was correlated with the Tinnitus Functional Index (TFI) relaxation subscale. And, functional connectivity between the right caudate and superior lateral occipital cortex, and the right caudate and anterior supramarginal gyrus were correlated with the TFI control subscale. These findings support a striatal gating model of tinnitus and suggest tinnitus biomarkers to monitor treatment response and to target specific brain areas for innovative neuromodulation therapies

Salivary glands regenerate after radiation injury through SOX2-mediated secretory cell replacement

Salivary gland acinar cells are routinely destroyed during radiation treatment for head and neck cancer that results in a lifetime of hyposalivation and co-morbidities. A potential regenerative strategy for replacing injured tissue is the reactivation of endogenous stem cells by targeted therapeutics. However, the identity of these cells, whether they are capable of regenerating the tissue, and the mechanisms by which they are regulated are unknown. Using in vivo and ex vivo models, in combination with genetic lineage tracing and human tissue, we discover a SOX2+ stem cell population essential to acinar cell maintenance that is capable of replenishing acini after radiation. Furthermore, we show that acinar cell replacement is nerve dependent and that addition of a muscarinic mimetic is sufficient to drive regeneration. Moreover, we show that SOX2 is diminished in irradiated human salivary gland, along with parasympathetic nerves, suggesting that tissue degeneration is due to loss of progenitors and their regulators. Thus, we establish a new paradigm that salivary glands can regenerate after genotoxic shock and do so through a SOX2 nerve-dependent mechanism

Tissue-specific calibration of extracellular matrix material properties by transforming growth factor-beta and Runx2 in bone is required for hearing

Publisher version: http://www.nature.com/embor/journal/v11/n10/full/embor2010135.htmlDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEPhysical cues, such as extracellular matrix stiffness, direct cell differentiation and support tissue-specific function. Perturbation of these cues underlies diverse pathologies, including osteoarthritis, cardiovascular disease and cancer. However, the molecular mechanisms that establish tissue-specific material properties and link them to healthy tissue function are unknown. We show that Runx2, a key lineage-specific transcription factor, regulates the material properties of bone matrix through the same transforming growth factor-beta (TGFbeta)-responsive pathway that controls osteoblast differentiation. Deregulated TGFbeta or Runx2 function compromises the distinctly hard cochlear bone matrix and causes hearing loss, as seen in human cleidocranial dysplasia. In Runx2(+/-) mice, inhibition of TGFbeta signalling rescues both the material properties of the defective matrix, and hearing. This study elucidates the unknown cause of hearing loss in cleidocranial dysplasia, and demonstrates that a molecular pathway controlling cell differentiation also defines material properties of extracellular matrix. Furthermore, our results suggest that the careful regulation of these properties is essential for healthy tissue functio

HIV-1 Nef Targets MHC-I and CD4 for Degradation Via a Final Common β-COP–Dependent Pathway in T Cells

To facilitate viral infection and spread, HIV-1 Nef disrupts the surface expression of the viral receptor (CD4) and molecules capable of presenting HIV antigens to the immune system (MHC-I). To accomplish this, Nef binds to the cytoplasmic tails of both molecules and then, by mechanisms that are not well understood, disrupts the trafficking of each molecule in different ways. Specifically, Nef promotes CD4 internalization after it has been transported to the cell surface, whereas Nef uses the clathrin adaptor, AP-1, to disrupt normal transport of MHC-I from the TGN to the cell surface. Despite these differences in initial intracellular trafficking, we demonstrate that MHC-I and CD4 are ultimately found in the same Rab7+ vesicles and are both targeted for degradation via the activity of the Nef-interacting protein, β-COP. Moreover, we demonstrate that Nef contains two separable β-COP binding sites. One site, an arginine (RXR) motif in the N-terminal α helical domain of Nef, is necessary for maximal MHC-I degradation. The second site, composed of a di-acidic motif located in the C-terminal loop domain of Nef, is needed for efficient CD4 degradation. The requirement for redundant motifs with distinct roles supports a model in which Nef exists in multiple conformational states that allow access to different motifs, depending upon which cellular target is bound by Nef

Cycle-averaged models of cardiovascular dynamics

Thesis (M.Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2002.Includes bibliographical references (p. 111).by Jolie L. Chang.M.Eng

Effectiveness and costs of sialendoscopy in pediatric patients with salivary gland disorders.

Objectives/hypothesisThis study aimed to characterize the common salivary gland disorders presenting in the pediatric population and to describe the diagnostic and therapeutic outcomes of sialendoscopy in this population.Study designRetrospective observational study in a tertiary care pediatric medical center.MethodsMedical records review of patients under 18 years of age who presented to pediatric otolaryngology with symptoms related to a salivary gland disorder from 2002 to 2014.ResultsFifty patients were identified with an average age of 7.5 years at presentation. Eighty percent (40/50) of cases were diagnosed with juvenile recurrent parotitis (JRP), and 15 underwent sialendoscopy. The other 10 (20%) patients presented with sialolithiasis. These patients had a higher average age at presentation (12.4 vs. 6.3 years), and the majority were successfully removed with sialendoscopic techniques. Juvenile recurrent parotitis patients who underwent sialendoscopy had significantly higher costs of care during the period of observation compared to those who did not have a procedure, without a statistically significant difference in outcomes.ConclusionsSialendoscopy is an effective tool for stone retrieval in pediatric sialolithiasis. Juvenile recurrent parotitis patients who underwent sialendoscopy had outcomes similar to those selected for conservative therapy, calling into question whether the substantially higher care costs can be justified. Further prospective studies addressing cost-effectiveness will help define the role of sialendoscopy in JRP.Level of evidence4

Effectiveness and costs of sialendoscopy in pediatric patients with salivary gland disorders.

Objectives/hypothesisThis study aimed to characterize the common salivary gland disorders presenting in the pediatric population and to describe the diagnostic and therapeutic outcomes of sialendoscopy in this population.Study designRetrospective observational study in a tertiary care pediatric medical center.MethodsMedical records review of patients under 18 years of age who presented to pediatric otolaryngology with symptoms related to a salivary gland disorder from 2002 to 2014.ResultsFifty patients were identified with an average age of 7.5 years at presentation. Eighty percent (40/50) of cases were diagnosed with juvenile recurrent parotitis (JRP), and 15 underwent sialendoscopy. The other 10 (20%) patients presented with sialolithiasis. These patients had a higher average age at presentation (12.4 vs. 6.3 years), and the majority were successfully removed with sialendoscopic techniques. Juvenile recurrent parotitis patients who underwent sialendoscopy had significantly higher costs of care during the period of observation compared to those who did not have a procedure, without a statistically significant difference in outcomes.ConclusionsSialendoscopy is an effective tool for stone retrieval in pediatric sialolithiasis. Juvenile recurrent parotitis patients who underwent sialendoscopy had outcomes similar to those selected for conservative therapy, calling into question whether the substantially higher care costs can be justified. Further prospective studies addressing cost-effectiveness will help define the role of sialendoscopy in JRP.Level of evidence4