The use of platelet-rich plasma in treatment of olfactory dysfunction: A pilot study.

BackgroundOlfactory dysfunction is a prevalent problem with a significant impact on quality of life and increased mortality. Limited effective therapies exist. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects. This novel pilot study evaluated the role of PRP on olfactory neuroregeneration in patients with hyposmia.MethodsSeven patients who had olfactory loss greater than 6 months in duration, no evidence of sinonasal inflammatory disease, and no improvement with olfactory training and budesonide topical rinses were enrolled in this preliminary study. Patients received a single intranasal injection of PRP into the mucosa of the olfactory cleft. The Sniffin' Sticks olfactory test consisting of threshold, discrimination, and identification measurements (TDI) was administered at the beginning of the study and at 1 and 3 months.ResultsAll patients reported a subjective improvement of their smell shortly after injection but then stabilized. At 3-month post-treatment, two patients with functional anosmia (TDI < 16) did not improve significantly. Five patients with hyposmia (TDI > 16 but <30) showed an improvement with 60% achieving normosmia (TDI > 30) at 3-month follow-up. On average, patients with baseline TDI > 16 improved by 5.85 points with the most significant improvement in the threshold subcomponent. There were no adverse outcomes from intranasal PRP injections.ConclusionPRP appears safe for use in the treatment of olfactory loss, and preliminary data suggest possible efficacy, especially for those with moderate yet persistent loss. Further studies will help determine optimal frequency and duration of use.Level of evidence 2

Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms.

BackgroundRapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of coronavirus disease 2019 (COVID-19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID-19 may help facilitate screening and early isolation of cases.MethodsA single-institution, cross-sectional study evaluating patient-reported symptoms with a focus on smell and taste was conducted using an internet-based platform on adult subjects who underwent testing for COVID-19. Logistic regression was employed to identify symptoms associated with COVID-19 positivity.ResultsA total of 1480 patients with influenza-like symptoms underwent COVID-19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID-19-positive patients and 203 of 1378 (15%) COVID-19-negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID-19-negative patients (p < 0.001). Smell and taste impairment were independently and strongly associated with COVID-19 positivity (anosmia: adjusted odds ratio [aOR] 10.9; 95% CI, 5.08-23.5; ageusia: aOR 10.2; 95% CI, 4.74-22.1), whereas sore throat was associated with COVID-19 negativity (aOR 0.23; 95% CI, 0.11-0.50). Of patients who reported COVID-19-associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness.ConclusionIn ambulatory individuals with influenza-like symptoms, chemosensory dysfunction was strongly associated with COVID-19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease-related symptoms

Neural Indices of Vowel Discrimination in Monolingual and Bilingual Infants and Children

Objectives: To examine maturation of neural discriminative responses to an English vowel contrast from infancy to 4 years of age and to determine how biological factors (age and sex) and an experiential factor (amount of Spanish versus English input) modulate neural discrimination of speech. Design: Event-related potential (ERP) mismatch responses (MMRs) were used as indices of discrimination of the American English vowels [ε] versus [I] in infants and children between 3 months and 47 months of age. A total of 168 longitudinal and cross-sectional data sets were collected from 98 children (Bilingual Spanish–English: 47 male and 31 female sessions; Monolingual English: 48 male and 42 female sessions). Language exposure and other language measures were collected. ERP responses were examined in an early time window (160 to 360 msec, early MMR [eMMR]) and late time window (400 to 600 msec, late MMR). Results: The eMMR became more negative with increasing age. Language experience and sex also influenced the amplitude of the eMMR. Specifically, bilingual children, especially bilingual females, showed more negative eMMR compared with monolingual children and with males. However, the subset of bilingual children with more exposure to English than Spanish compared with those with more exposure to Spanish than English (as reported by caretakers) showed similar amplitude of the eMMR to their monolingual peers. Age was the only factor that influenced the amplitude of the late MMR. More negative late MMR was observed in older children with no difference found between bilingual and monolingual groups. Conclusions: Consistent with previous studies, our findings revealed that biological factors (age and sex) and language experience modulated the amplitude of the eMMR in young children. The early negative MMR is likely to be the mismatch negativity found in older children and adults. In contrast, the late MMR amplitude was influenced only by age and may be equivalent to the Nc in infants and to the late negativity observed in some auditory passive oddball designs

Structures of CD6 and Its Ligand CD166 Give Insight into Their Interaction

SummaryCD6 is a transmembrane protein with an extracellular region containing three scavenger receptor cysteine rich (SRCR) domains. The membrane proximal domain of CD6 binds the N-terminal immunoglobulin superfamily (IgSF) domain of another cell surface receptor, CD166, which also engages in homophilic interactions. CD6 expression is mainly restricted to T cells, and the interaction between CD6 and CD166 regulates T-cell activation. We have solved the X-ray crystal structures of the three SRCR domains of CD6 and two N-terminal domains of CD166. This first structure of consecutive SRCR domains reveals a nonlinear organization. We characterized the binding sites on CD6 and CD166 and showed that a SNP in CD6 causes glycosylation that hinders the CD6/CD166 interaction. Native mass spectrometry analysis showed that there is competition between the heterophilic and homophilic interactions. These data give insight into how interactions of consecutive SRCR domains are perturbed by SNPs and potential therapeutic reagents

Spitzer Photometry of WISE-Selected Brown Dwarf and Hyper-Luminous Infrared Galaxy Candidates

We present Spitzer 3.6 and 4.5 $\mu$m photometry and positions for a sample of 1510 brown dwarf candidates identified by the WISE all-sky survey. Of these, 166 have been spectroscopically classified as objects with spectral types M(1), L(7), T(146), and Y(12); Sixteen other objects are non-(sub)stellar in nature. The remainder are most likely distant L and T dwarfs lacking spectroscopic verification, other Y dwarf candidates still awaiting follow-up, and assorted other objects whose Spitzer photometry reveals them to be background sources. We present a catalog of Spitzer photometry for all astrophysical sources identified in these fields and use this catalog to identify 7 fainter (4.5 $\mu$m $\sim$ 17.0 mag) brown dwarf candidates, which are possibly wide-field companions to the original WISE sources. To test this hypothesis, we use a sample of 919 Spitzer observations around WISE-selected high-redshift hyper-luminous infrared galaxy (HyLIRG) candidates. For this control sample we find another 6 brown dwarf candidates, suggesting that the 7 companion candidates are not physically associated. In fact, only one of these 7 Spitzer brown dwarf candidates has a photometric distance estimate consistent with being a companion to the WISE brown dwarf candidate. Other than this there is no evidence for any widely separated ($>$ 20 AU) ultra-cool binaries. As an adjunct to this paper, we make available a source catalog of $\sim$ 7.33 $\times 10^5$ objects detected in all of these Spitzer follow-up fields for use by the astronomical community. The complete catalog includes the Spitzer 3.6 and 4.5 $\mu$m photometry, along with positionally matched $B$ and $R$ photometry from USNO-B; $J$, $H$, and $K_s$ photometry from 2MASS; and $W1$, $W2$, $W3$, and $W4$ photometry from the WISE all-sky catalog

Lack of asthma and rhinitis control in general practitioner-managed patients prescribed fixed-dose combination therapy in Australia

Peer reviewedPublisher PD

ART adherence changes among patients in community substance use treatment: a preliminary analysis from MACH14

Abstract Background Opiate substitution treatment has been associated with better adherence to lifesaving antiretroviral medications, but the impact of other substance abuse treatment on adherence is unknown. Findings In this study, 215 patients who had been in adherence-focused research studies provided electronically-measured adherence data and a measure of whether the patient had recently been in substance abuse treatment. Recent engagement in substance abuse treatment was independently associated with significantly higher adherence, after covarying for recent substance use and other factors potentially affecting adherence. Conclusions The findings suggest that substance abuse treatment is associated with better adherence. Potential mechanisms by which substance abuse treatment improves adherence, such as more stability or more future-orientation, require further study

High-resolution deconstruction of evolution induced by chemotherapy treatments in breast cancer xenografts.

The processes by which tumors evolve are essential to the efficacy of treatment, but quantitative understanding of intratumoral dynamics has been limited. Although intratumoral heterogeneity is common, quantification of evolution is difficult from clinical samples because treatment replicates cannot be performed and because matched serial samples are infrequently available. To circumvent these problems we derived and assayed large sets of human triple-negative breast cancer xenografts and cell cultures from two patients, including 86 xenografts from cyclophosphamide, doxorubicin, cisplatin, docetaxel, or vehicle treatment cohorts as well as 45 related cell cultures. We assayed these samples via exome-seq and/or high-resolution droplet digital PCR, allowing us to distinguish complex therapy-induced selection and drift processes among endogenous cancer subclones with cellularity uncertaint

ART adherence changes among patients in community substance use treatment: a preliminary analysis from MACH14

Background: Opiate substitution treatment has been associated with better adherence to lifesaving antiretroviral medications, but the impact of other substance abuse treatment on adherence is unknown. Findings: In this study, 215 patients who had been in adherence-focused research studies provided electronically-measured adherence data and a measure of whether the patient had recently been in substance abuse treatment. Recent engagement in substance abuse treatment was independently associated with significantly higher adherence, after covarying for recent substance use and other factors potentially affecting adherence. Conclusions: The findings suggest that substance abuse treatment is associated with better adherence. Potential mechanisms by which substance abuse treatment improves adherence, such as more stability or more future-orientation, require further study