Microbiota, Gut Health, and Laryngopharyngeal Reflux Disease.

Recent advances in technology have allowed examination of microbial communities in efforts to classify microbiomes of "healthy" individuals. The gut and the oral cavity have been extensively researched but the upper airway (including the pharynx and larynx) has not received the same attention. This review details the emergence of microbiota as a field of interest and reviews existing evidence supporting a relationship between microbiome alterations and laryngopharyngeal reflux symptoms, as well as potential therapeutic interventions.

Accuracy and Interpretation of Transcutaneous Carbon Dioxide Monitoring in Critically Ill Children.

OBJECTIVES: Transcutaneous carbon dioxide (Tc co2 ) monitoring can noninvasively assess ventilation by estimating carbon dioxide ( CO2 ) levels in the blood. We aimed to evaluate the accuracy of Tc co2 monitoring in critically ill children by comparing it to the partial pressure of arterial carbon dioxide (Pa co2 ). In addition, we sought to determine the variation between Tc co2 and Pa co2 acceptable to clinicians to modify patient care and to determine which patient-level factors may affect the accuracy of Tc co2 measurements. DESIGN: Retrospective observational cohort study. SETTING: Single, quaternary care PICU from July 1, 2012, to August 1, 2020. PATIENTS: Included participants were admitted to the PICU and received noninvasive ventilation support (i.e., continuous or bilevel positive airway pressure), conventional mechanical ventilation, or high-frequency oscillatory or percussive ventilation with Tc co2 measurements obtained within 15 minutes of Pa co2 measurement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three thousand four hundred seven paired arterial blood gas and Tc co2 measurements were obtained from 264 patients. Bland-Altman analysis revealed a bias of -4.4 mm Hg (95% CI, -27 to 18.3 mm Hg) for Tc co2 levels against Pa co2 levels on the first measurement pair for each patient, which fell within the acceptable range of ±5 mm Hg stated by surveyed clinicians, albeit with wide limits of agreement. The sensitivity and specificity of Tc co2 to diagnose hypercarbia were 93% and 71%, respectively. Vasoactive-Infusion Score (VIS), age, and self-identified Black/African American race confounded the relationship between Tc co2 with Pa co2 but percent fluid overload, weight-for-age, probe location, and severity of illness were not significantly associated with Tc co2 accuracy. CONCLUSIONS: Tc co2 monitoring may be a useful adjunct to monitor ventilation in children with respiratory failure, but providers must be aware of the limitations to its accuracy.

Accuracy and Interpretation of Transcutaneous Carbon Dioxide Monitoring in Critically Ill Children.

OBJECTIVES: Transcutaneous carbon dioxide (Tcco2) monitoring can noninvasively assess ventilation by estimating carbon dioxide (CO2) levels in the blood. We aimed to evaluate the accuracy of Tcco2 monitoring in critically ill children by comparing it to the partial pressure of arterial carbon dioxide (Paco2). In addition, we sought to determine the variation between Tcco2 and Paco2 acceptable to clinicians to modify patient care and to determine which patient-level factors may affect the accuracy of Tcco2 measurements. DESIGN: Retrospective observational cohort study. SETTING: Single, quaternary care PICU from July 1, 2012, to August 1, 2020. PATIENTS: Included participants were admitted to the PICU and received noninvasive ventilation support (i.e., continuous or bilevel positive airway pressure), conventional mechanical ventilation, or high-frequency oscillatory or percussive ventilation with Tcco2 measurements obtained within 15 minutes of Paco2 measurement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three thousand four hundred seven paired arterial blood gas and Tcco2 measurements were obtained from 264 patients. Bland-Altman analysis revealed a bias of -4.4 mm Hg (95% CI, -27 to 18.3 mm Hg) for Tcco2 levels against Paco2 levels on the first measurement pair for each patient, which fell within the acceptable range of ±5 mm Hg stated by surveyed clinicians, albeit with wide limits of agreement. The sensitivity and specificity of Tcco2 to diagnose hypercarbia were 93% and 71%, respectively. Vasoactive-Infusion Score (VIS), age, and self-identified Black/African American race confounded the relationship between Tcco2 with Paco2 but percent fluid overload, weight-for-age, probe location, and severity of illness were not significantly associated with Tcco2 accuracy. CONCLUSIONS: Tcco2 monitoring may be a useful adjunct to monitor ventilation in children with respiratory failure, but providers must be aware of the limitations to its accuracy.

RECONSTITUTION OF THE CHORIOCAPILLARIS IN ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY.

PURPOSE: The purpose of this study was to describe findings derived from extensions of optical coherence tomography, including volume rendering and frame-averaged optical coherence tomography angiography (OCT-A), in a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE). METHODS: This is a case report of a patient with APMPPE imaged during the acute and convalescent stages. RESULTS: A 20-year-old man presented with an acute change in vision. He had multiple yellow-white placoid lesions at the level of the retinal pigment epithelium in the macula and nasal to the optic nerve in both eyes. Within 2 weeks, his visual acuity worsened to 20/80 and 20/400 in the right and left eyes, respectively. Spectral domain OCT showed focal defects in the ellipsoid and retinal pigment epithelium layers. Volume-rendering OCT-A showed inflammatory cells in the outer nuclear layer above the APMPPE lesion. Frame-averaged OCT-A revealed significant loss of capillary flow signal within capillary segments of the choriocapillaris. Ten weeks after presentation, there was resolution of the placoid changes, discontinuance of the inflammatory infiltrate in the outer nuclear layer, and significant reconstitution of flow in the choriocapillaris. The visual acuity was 20/20 in both eyes. CONCLUSION: Novel volume-rendered and frame-averaged OCT-A images in a patient with APMPPE allowed detection of inflammatory cell infiltrate in the outer nuclear layer and reversible capillary segment nonperfusion of associated APMPPE lesions. The findings suggest short-term insults to choriocapillaris function may be reversible and can be tracked with modern imaging techniques.

Stickler and Wagner Syndrome in African Americans.

BACKGROUND: Stickler (STL) and Wagner (WGN) syndromes are rare inherited vitreoretinopathies associated with retinal detachments (RD). There is a paucity of case reports describing these diseases in African American patients. METHODS: An IRB-approved, retrospective chart review of African American patients with genetically proven ocular-only STL or WGN was performed, and 6 patients were identified. RESULTS: Three patients had a COL2A1 mutation, two had a COL11A1 mutation, and one had a VCAN mutation. None had Pierre Robin facies. All were myopes with lattice degeneration and five had RD. Three underwent RD repair with vitrectomy (PPV), scleral buckle (SB), endolaser (EL), and silicone oil (SO). Two received laser retinopexy for localized RD and one received a prophylactic SB with 360° peripheral laser retinopexy. CONCLUSION: STL and WGN should be considered in myopic African American patients with lattice degeneration, giant retinal tears, abnormal vitreous, or spontaneous RD. Prophylactic laser treatment and aggressive surgical treatment of RD should be considered. [Ophthalmic Surg Lasers Imaging Retina 2023;54:97-101.].

Topical Dexamethasone as an Adjuvant to Mineralocorticoid Receptor Antagonists for the Treatment of Recalcitrant Central Serous Chorioretinopathy.

BACKGROUND AND OBJECTIVE: A previous report demonstrated efficacy of mineralocorticoid antagonist with adjuvant topical dexamethasone (MRA+DEX) in resolving subretinal fluid (SRF) in a chronic central serous chorioretinopathy (CSCR) patient. This pilot study investigates the use of MRA+DEX to treat recalcitrant, chronic CSCR patients. STUDY DESIGN: Retrospective review of chronic, recalcitrant CSCR patients unresponsive to MRA alone who were treated with MRA+DEX and followed for up to 3 months. Apical SRF thickness and visual acuity were measured. RESULTS: Ten eyes of eight chronic, recalcitrant patients were included with an average follow-up of 109 days. Mean percent reduction in apical fluid thickness at one month and at last follow-up after adding dexamethasone (DEX) was 33% and 52%, respectively. Five eyes (50%) achieved complete resolution of SRF. Three eyes (30%) showed partial response and two (20%) eyes had no response. There was no significant change in visual acuity. CONCLUSIONS: MRA+DEX decreased SRF in some recalcitrant, chronic CSCR patients. Large prospective studies are needed to evaluate the utility of MRA+DEX in these chronic CSCR patients. [Ophthalmic Surg Lasers Imaging Retina 2022;53:659-665.].

T1R2-mediated sweet sensing in a lizard.

Sugars are an important class of nutrients found in the flowers and fruits of angiosperms (flowering plants). Although T1R2-T1R3 has been identified as the mammalian sweet receptor, some birds rely on a repurposed T1R1-T1R3 savory receptor to sense sugars. Moreover, as the radiation of flowering plants occurred later than the last common ancestor of amniotes, sugar may not have been an important diet item for amniotes early in evolution, raising the question of whether T1R2-T1R3 is a universal sugar sensor or only a mammalian innovation. Here, using brief-access behavioral tests and functional characterization of taste receptors, we demonstrate that the nectar-taking Madagascar giant day gecko (Phelsuma grandis) can sense sugars through the T1R2-T1R3 receptor. These results reveal the existence of T1R2-based sweet taste in a non-avian reptile, which has important implications for our understanding of the evolutionary history of sugar detection in amniotes.

Transcutaneous auricular vagus nerve stimulation augments postprandial inhibition of ghrelin.

Vagus nerve stimulation (VNS) facilitates weight loss in animals and patients treated with VNS for depression or epilepsy. Likewise, chronic transcutaneous auricular VNS (taVNS) reduces weight gain and improves glucose tolerance in Zucker diabetic fatty rats. If these metabolic effects of taVNS observed in rats translate to humans is unknown. Therefore, the hypothesis of this study was that acute application of taVNS affects glucotropic and orexigenic hormones which could potentially facilitate weight loss and improve glucose tolerance if taVNS were applied chronically. In two single-blinded randomized cross-over protocols, blood glucose levels, plasma concentrations of insulin, C-peptide, glucagon, leptin, and ghrelin, together with heart rate variability and baroreceptor-heart rate reflex sensitivity were determined before and after taVNS (left ear, 10 Hz, 300 µs, 2.0-2.5 mA, 30 min) or sham-taVNS (electrode attached to ear with the stimulator turned off). In a first protocol, subjects (n = 16) were fasted throughout the protocol and in a second protocol, subjects (n = 10) received a high-calorie beverage (220 kCal) after the first blood sample, just before initiation of taVNS or sham-taVNS. No significant effects of taVNS on heart rate variability and baroreceptor-heart rate reflex sensitivity and only minor effects on glucotropic hormones were observed. However, in the second protocol taVNS significantly lowered postprandial plasma ghrelin levels (taVNS: -115.5 ± 28.3 pg/ml vs. sham-taVNS: -51.2 ± 30.6 pg/ml, p < 0.05). This finding provides a rationale for follow-up studies testing the hypothesis that chronic application of taVNS may reduce food intake through inhibition of ghrelin and, therefore, may indirectly improve glucose tolerance through weight loss.

Short-range contributions of local sources to ambient air.

Recent developments in aerobiology have enabled the investigation of airborne biomass with high temporal and taxonomic resolution. In this study, we assess the contributions of local sources to ambient air within a 160,000 m2 tropical avian park (AP). We sequenced and analyzed 120 air samples from seven locations situated 160 to 400 m apart, representing distinct microhabitats. Each microhabitat contained a characteristic air microbiome, defined by the abundance and richness of its airborne microbial community members, supported by both, PCoA and Random Forest analysis. Each outdoor microhabitat contained 1% to 18.6% location-specific taxa, while a core microbiome of 27.1% of the total taxa was shared. To identify and assess local sources, we compared the AP dataset with a DVE reference dataset from a location 2 km away, collected during a year-round sampling campaign. Intersection of data from the two sites demonstrated 61.6% of airborne species originated from local sources of the AP, 34.5% from ambient air background, and only 3.9% of species were specific to the DVE reference site. In-depth taxonomic analysis demonstrated association of bacteria-dominated air microbiomes with indoor spaces, while fungi-dominated airborne microbial biomass was predominant in outdoor settings with ample vegetation. The approach presented here demonstrates an ability to identify local source contributions against an ambient air background, despite the prevailing mixing of air masses caused by atmospheric turbulences.

Intravitreal dexamethasone insert in diabetic macular edema super-refractory to anti-vascular endothelial growth factor therapy.

BACKGROUND: Some patients with diabetic macular edema (DME) fail to completely respond to anti-vascular endothelial growth factor (VEGF) therapy. These patients have a high treatment burden in the absence of significant improvement. We investigate the role of intravitreal dexamethasone insert (IDI) in eyes with super-refractory DME. METHODS: A non-randomized interventional study was performed among eyes with super-refractory DME refractory to anti-VEGF therapy. Eyes were treated with IDI after failing clinical response to anti-VEGF, with a minimum of 15 prior. Failure to respond was defined as failure of vision to improve at least one line on Snellen Acuity chart, central subfield thickness (CST) greater than 320 µm, or failure of CST to improve by 10% or more. Eyes with glaucoma or prior uncontrolled steroid-responsive ocular hypertension were excluded. Patient outcomes were analyzed at weeks 6, 12, 24, and year 1. RESULTS: Six eyes of four patients were identified. All patients had failed aflibercept. The mean number of prior anti-VEGF injections was 34.5. Eyes received an average of 2.92 dexamethasone injections per person-year (PY) and required breakthrough anti-VEGF injection at 1.95/PY. Mean pre-treatment visual acuity was 0.475 LogMAR, improving to 0.342 at week 6, and 0.375 at 1 year. Mean CST pre-injection was 386.5 mm, improving to 315 mm at 1 year. No glaucoma developed. CONCLUSIONS: Intravitreal dexamethasone insert appears effective in eyes with super-refractory DME. IDI resulted in excellent anatomic improvement on SD-OCT as well as modest visual improvement. Injection burden was reduced in those who may otherwise receive years of monthly treatments.

Variation in predicted COVID-19 risk among lemurs and lorises.

The novel coronavirus SARS-CoV-2, which in humans leads to the disease COVID-19, has caused global disruption and more than 2 million fatalities since it first emerged in late 2019. As we write, infection rates are at their highest point globally and are rising extremely rapidly in some areas due to more infectious variants. The primary target of SARS-CoV-2 is the cellular receptor angiotensin-converting enzyme-2 (ACE2). Recent sequence analyses of the ACE2 gene predict that many nonhuman primates are also likely to be highly susceptible to infection. However, the anticipated risk is not equal across the Order. Furthermore, some taxonomic groups show high ACE2 amino acid conservation, while others exhibit high variability at this locus. As an example of the latter, analyses of strepsirrhine primate ACE2 sequences to date indicate large variation among lemurs and lorises compared to other primate clades despite low sampling effort. Here, we report ACE2 gene and protein sequences for 71 individual strepsirrhines, spanning 51 species and 19 genera. Our study reinforces previous results while finding additional variability in other strepsirrhine species, and suggests several clades of lemurs have high potential susceptibility to SARS-CoV-2 infection. Troublingly, some species, including the rare and endangered aye-aye (Daubentonia madagascariensis), as well as those in the genera Avahi and Propithecus, may be at high risk. Given that lemurs are endemic to Madagascar and among the primates at highest risk of extinction globally, further understanding of the potential threat of COVID-19 to their health should be a conservation priority. All feasible actions should be taken to limit their exposure to SARS-CoV-2.

Using historical genome-wide DNA to unravel the confused taxonomy in a songbird lineage that is extinct in the wild.

Urgent conservation action for terminally endangered species is sometimes hampered by taxonomic uncertainty, especially in illegally traded animals that are often cross-bred in captivity. To overcome these problems, we used a genomic approach to analyze historical DNA from museum samples across the Asian Pied Starling (Gracupica contra) complex in tropical Asia, a popular victim of the ongoing songbird crisis whose distinct Javan population ("Javan Pied Starling") is extinct in the wild and subject to admixture in captivity. Comparing genomic profiles across the entire distribution, we detected three deeply diverged lineages at the species level characterized by a lack of genomic intermediacy near areas of contact. Our study demonstrates that the use of historical DNA can be instrumental in delimiting species in situations of taxonomic uncertainty, especially when modern admixture may obfuscate species boundaries. Results of our research will enable conservationists to commence a dedicated ex situ breeding program for the Javan Pied Starling, and serve as a blueprint for similar conservation problems involving terminally endangered species subject to allelic infiltration from close congeners.

Human CD36hi monocytes induce Foxp3+ CD25+ T cells with regulatory functions from CD4 and CD8 subsets.

The fetal and neonatal immune systems are uniquely poised to generate tolerance to self, maternal and environmental antigens encountered in the womb and shortly after birth. However, the tolerogenic nature of fetal and neonatal immunity can be detrimental in the context of pathogens, leading to overwhelming bacterial infections or chronic viral infections. A variety of mechanisms contribute to fetal and neonatal tolerance, including a propensity to generate Foxp3+ regulatory T cells (Treg cells). However, the mechanism(s) of fetal Foxp3+ T-cell differentiation, the specific antigen-presenting cells required and factors that inhibit Treg generation after the neonatal period are poorly understood. Here, we demonstrate that a subset of CD14+ monocytes expressing the scavenger molecule, CD36, can generate CD4+ and CD8+ T cells that coexpress Foxp3 and T-bet from both umbilical cord blood. These Foxp3+ T-bet+ T cells potently suppress T-cell proliferation and ameliorate xenogeneic graft-versus-host disease. CD14+  CD36+ monocytes provide known Treg-inducing signals: membrane-bound transforming growth factor-beta and retinoic acid. Unexpectedly, adult peripheral blood monocytes are also capable of inducing Foxp3+ T cells from both cord blood and adult peripheral naïve T cells. The induction of Foxp3+ T cells in umbilical cord blood by monocytes was inhibited by the lymphoid fraction of adult peripheral blood cells. These studies highlight a novel immunoregulatory role of monocytes and suggest that antigen presentation by CD36hi monocytes may contribute to the peripheral development of Foxp3+ T-bet+ T cells with regulatory functions in both neonates and adults.

Variation in predicted COVID-19 risk among lemurs and lorises.

The novel coronavirus SARS-CoV-2, which in humans leads to the disease COVID-19, has caused global disruption and more than 1.5 million fatalities since it first emerged in late 2019. As we write, infection rates are currently at their highest point globally and are rising extremely rapidly in some areas due to more infectious variants. The primary viral target is the cellular receptor angiotensin-converting enzyme-2 (ACE2). Recent sequence analyses of the ACE2 gene predicts that many nonhuman primates are also likely to be highly susceptible to infection. However, the anticipated risk is not equal across the Order. Furthermore, some taxonomic groups show high ACE2 amino acid conservation, while others exhibit high variability at this locus. As an example of the latter, analyses of strepsirrhine primate ACE2 sequences to date indicate large variation among lemurs and lorises compared to other primate clades despite low sampling effort. Here, we report ACE2 gene and protein sequences for 71 individual strepsirrhines, spanning 51 species and 19 genera. Our study reinforces previous results and finds additional variability in other strepsirrhine species, and suggests several clades of lemurs have high potential susceptibility to SARS-CoV-2 infection. Troublingly, some species, including the rare and Endangered aye-aye (Daubentonia madagascariensis), as well as those in the genera Avahi and Propithecus, may be at high risk. Given that lemurs are endemic to Madagascar and among the primates at highest risk of extinction globally, further understanding of the potential threat of COVID-19 to their health should be a conservation priority. All feasible actions should be taken to limit their exposure to SARS-CoV-2.

The conservation value of admixed phenotypes in a critically endangered species complex.

In today's environmental crisis, conservationists are increasingly confronted with terminally endangered species whose last few surviving populations may be affected by allelic introgression from closely related species. Yet there is a worrying lack of evidence-based recommendations and solutions for this emerging problem. We analyzed genome-wide DNA markers and plumage variability in a critically endangered insular songbird, the Black-winged Myna (BWM, Acridotheres melanopterus). This species is highly threatened by the illegal wildlife trade, with its wild population numbering in the low hundreds, and its continued survival urgently depending on ex-situ breeding. Its three subspecies occur along a geographic gradient of melanism and are variably interpreted as three species. However, our integrative approach revealed that melanism poorly reflects the pattern of limited genomic differentiation across BWM subspecies. We also uncovered allelic introgression into the most melanistic subspecies, tertius, from the all-black congeneric Javan Myna (A. javanicus), which is native to the same islands. Based on our results, we recommend the establishment of three separate breeding programs to maintain subspecific traits that may confer local adaptation, but with the option of occasional cross-breeding between insurance populations in order to boost genetic diversity and increase overall viability prospects of each breeding program. Our results underscore the importance of evidence-based integrative approaches when determining appropriate conservation units. Given the rapid increase of terminally endangered organisms in need of ex-situ conservation, this study provides an important blueprint for similar programs dealing with phenotypically variable species.

Feeding cluster preferences in four genera of Lories and Lorikeets (Loriinae) that should be considered in the diet of nectarivorous psittacine species in captivity.

Lories and lorikeets are popular birds in the pet bird trade, captured from the wild and exported worldwide. Their captive propagation has not been so successful for many species due to health issues, low breeding success and reduced longevity. As a result, uptake from the wild is currently the only way to meet the market's demand. Field studies on Asian species of loris and lorikeets are limited; therefore, dietary recommendations are based on the well-studied Australian species such as the rainbow lorikeet (Trichoglossus moluccanus). We aimed to provide an ad libitum diet to diverse Loriinae species at Jurong Bird Park (Singapore) which allowed for them to select between a low and moderate protein diet to compare their nutrient and energy intake with other Loriinae species. We measured the following variables: daily dry matter (DM) intake, nectar-to-fruit energy intake ratio (NF ratio), metabolisable energy (ME), protein and non-protein energy (NPE)-to-protein energy (PE) ratio intake (all by kg metabolic body weight MBW, kg0.75 ) for 36 pairs over a 1-month period. A Kruskal-Wallis test revealed every genus had significantly different intakes of DM, NF ratio, NPE-to-PE ratio, ME and protein than each other. Post hoc Mann-Whitney U tests confirmed that the majority of variables were ingested in different amounts for each genus except for NF ratio, NPE/PE ratio which Lorius spp. are not different to Charmosyna sp. or Trichoglossus spp. and protein intake of Eos spp. does not differ from Trichoglossus spp. Our conclusion is that no species should be used as a model for a species from another genus of Loriinae; future studies should be species-specific for each genus to increase captive propagation success.

RETINAL VASCULAR PERFUSION DENSITY MAPPING USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN NORMALS AND DIABETIC RETINOPATHY PATIENTS.

PURPOSE: To describe a new method of retinal vascular perfusion density mapping using optical coherence tomography angiography and to compare current staging of diabetic retinopathy based on clinical features with a new grading scale based on perifoveal perfusion densities. METHODS: A retrospective review was performed on subjects with diabetic retinopathy and age-matched controls imaged with a spectral domain optical coherence tomography system (Optovue XR Avanti, Fremont, CA). Split-spectrum amplitude-decorrelation angiography (SSADA) generated optical coherence tomography angiograms of the superficial retinal capillaries, deep retinal capillaries, and choriocapillaris. Skeletonized optical coherence tomography angiograms were used to create color-coded perfusion maps and capillary perfusion density values for each image. Capillary perfusion density values were compared with clinical staging, and groups were compared using analysis of variance and Kruskal-Wallis analyses. RESULTS: Twenty-one control and 56 diabetic retinopathy eyes were imaged. Diabetic eyes were grouped according to clinical stage. Capillary perfusion density values from each microvascular layer were compared across all groups. Capillary perfusion density values were significantly lower in nearly all layers of all study groups compared with controls. Trend analysis showed a significant decrease in capillary perfusion density values as retinopathy progresses for most layers. CONCLUSION: Quantitative retinal vascular perfusion density mapping agreed closely with grading based on clinical features and may offer an objective method for monitoring disease progression in diabetic retinopathy.