Online Physician-Patient Interaction and Patient Satisfaction: Empirical Study of the Internet Hospital Service.

BACKGROUND: In China, a form of online health service called the internet hospital became a prominent means of patient care when face-to-face visits were not possible during the COVID-19 pandemic to minimize transmission of the SARS-CoV-2 virus. Patients' internet hospital experiences largely depend on online physician-patient interaction. Yet, little is known about how physicians can improve patient satisfaction by using specific communication strategies online. OBJECTIVE: This study aimed to identify specific communication strategies to help physicians deliver better quality internet hospital services. We also outline recommendations for hospitals to operate internet hospital platforms more effectively. METHODS: A longitudinal data set was collected from an internet hospital platform operated by a top hospital in China. By extracting communication patterns from approximately 20,000 records of online health care services and by controlling the features of service requests, we tested the impacts of response load, more detailed style, and emotional comfort on patient satisfaction. We further explored the effects of these communication patterns in different service contexts. RESULTS: Physicians with a low response load, a more detailed style, and expressions of emotional comfort received more positive patient feedback. Response load did not affect patient satisfaction with free online health service, whereas a more detailed style and emotional comfort enhanced satisfaction with free service. Response load significantly reduced patient satisfaction with paid online health service, while a more detailed style had no effect. Compared with free service, emotional comfort more strongly promoted patient satisfaction with paid service. CONCLUSIONS: The communication strategies identified can help physicians provide patients with a better internet hospital experience. These strategies require hospitals to schedule each physician's online service period more appropriately. In addition, tailoring the strategies to service situations can facilitate more targeted and effective internet hospital service for patients.

Function of bidirectional sensitivity in the otolith organs established by transcription factor Emx2.

Otolith organs of the inner ear are innervated by two parallel afferent projections to the brainstem and cerebellum. These innervations were proposed to segregate across the line of polarity reversal (LPR) within each otolith organ, which divides the organ into two regions of hair cells (HC) with opposite stereociliary orientation. The relationship and functional significance of these anatomical features are not known. Here, we show regional expression of Emx2 in otolith organs, which establishes LPR, mediates the neuronal segregation across LPR and constitutes the bidirectional sensitivity function. Conditional knockout (cKO) of Emx2 in HCs lacks LPR. Tmie cKO, in which mechanotransduction was abolished selectively in HCs within the Emx2 expression domain also lacks bidirectional sensitivity. Analyses of both mutants indicate that LPR is specifically required for mice to swim comfortably and to traverse a balance beam efficiently, but LPR is not required for mice to stay on a rotating rod.

Visitor arrivals forecasts amid COVID-19: A perspective from the Asia and Pacific team.

It is important to provide scientific assessments concerning the future of tourism under the uncertainty surrounding COVID-19. To this purpose, this paper presents a two-stage three-scenario forecast framework for inbound-tourism demand across 20 countries. The main findings are as follows: in the first-stage ex-post forecasts, the stacking models are more accurate and robust, especially when combining five single models. The second-stage ex-ante forecasts are based on three recovery scenarios: a mild case assuming a V-shaped recovery, a medium one with a V/U-shaped, and a severe one with an L-shaped. The forecast results show a wide range of recovery (10%-70%) in 2021 compared to 2019. This two-stage three-scenario framework contributes to the improvement in the accuracy and robustness of tourism demand forecasting.

Emx2 regulates hair cell rearrangement but not positional identity within neuromasts.

Each hair cell (HC) precursor of zebrafish neuromasts divides to form two daughter HCs of opposite hair bundle orientations. Previously, we showed that transcription factor Emx2, expressed in only one of the daughter HCs, generates this bidirectional HC pattern (Jiang et al., 2017). Here, we asked whether Emx2 mediates this effect by changing location of hair bundle establishment or positions of HCs since daughter HCs are known to switch positions with each other. We showed this HC rearrangement, redefined as two processes named Rock and Roll, is required for positional acquisition of HCs. Apical protrusion formation of nascent HCs and planar polarity signaling are both important for the Rock and Roll. Emx2 facilitates Rock and Roll by delaying apical protrusion of its nascent HCs but it does not determine HCs' ultimate positions, indicating that Emx2 mediates bidirectional HC pattern by changing the location where hair bundle is established in HCs.

Urinary Cortisol Increases During a Respiratory Outbreak in Wild Chimpanzees.

In mammals, the excretion of cortisol can provide energy toward restoring homeostasis and is a major component of the stress response. However, chronically elevated cortisol levels also have suppressive effects on immune function. As mounting an immune response is energetically costly, sick individuals may conserve energy by exhibiting certain sickness behaviors, such as declining activity levels. Due to the complex interplay between immune function and sickness behaviors, endocrinological correlates have received growing attention in the medical community, but so far, this subject was investigated rarely. Furthermore, given the complexities of studying illnesses and immunity in natural settings, correlates of sickness behaviors have yet to be studied in non-human primates in the wild. Methods: We measured urinary cortisol levels using liquid chromatography-mass spectrometry in a group of wild habituated chimpanzees in Taï National Park, Côte d'Ivoire, before, during, and after a respiratory disease outbreak (main causative pathogen: human respiratory syncytial virus A, with coinfections of Streptococcus pneumoniae). Changes in cortisol levels were then related to urinary neopterin levels, a biomarker of immune system activation. Results: Urinary cortisol levels were found to be more than 10-fold higher during the outbreak in comparison with levels before and after the outbreak period. Increasing cortisol levels were also associated with increasing neopterin levels. Interestingly, rather atypical patterns in a diurnal decline of cortisol levels were found during infection periods, such that levels remained raised throughout the day. Conclusion: In conclusion, cortisol increase was related to cellular immune response. Our results suggest that cortisol is a mediator of infectious disease pathogenicity through its impact on the immune system and that wild chimpanzees may be facing energetic stress when sick. By monitoring immune challenges in wild-living animals, our study demonstrates that immune defenses have costs and that these costs are context-specific.

Live imaging of hair bundle polarity acquisition demonstrates a critical timeline for transcription factor Emx2.

Directional sensitivity of hair cells (HCs) is conferred by the aymmetric apical hair bundle, comprised of a kinocilium and stereocilia staircase. The mother centriole (MC) forms the base of the kinocilium and the stereocilia develop adjacent to it. Previously, we showed that transcription factor Emx2 reverses hair bundle orientation and its expression in the mouse vestibular utricle is restricted, resulting in two regions of opposite bundle orientation (Jiang et al., 2017). Here, we investigated establishment of opposite bundle orientation in embryonic utricles by live-imaging GFP-labeled centrioles in HCs. The daughter centriole invariably migrated ahead of the MC from the center to their respective peripheral locations in HCs. Comparing HCs between utricular regions, centriole trajectories were similar but they migrated toward opposite directions, suggesting that Emx2 pre-patterned HCs prior to centriole migration. Ectopic Emx2, however, reversed centriole trajectory within hours during a critical time-window when centriole trajectory was responsive to Emx2.

Retinoic acid synthesis and autoregulation mediate zonal patterning of vestibular organs and inner ear morphogenesis.

Retinoic acid (RA), a vitamin A (retinol) derivative, has pleiotropic functions during embryonic development. The synthesis of RA requires two enzymatic reactions: oxidation of retinol into retinaldehyde by alcohol dehydrogenases (ADHs) or retinol dehydrogenases (RDHs); and oxidation of retinaldehyde into RA by aldehyde dehydrogenases family 1, subfamily A (ALDH1as), such as ALDH1a1, ALDH1a2 and ALDH1a3. Levels of RA in tissues are regulated by spatiotemporal expression patterns of genes encoding RA-synthesizing and -degrading enzymes, such as cytochrome P450 26 (Cyp26 genes). Here, we show that RDH10 is important for both sensory and non-sensory formation of the vestibule of the inner ear. Mice deficient in Rdh10 exhibit failure of utricle-saccule separation, otoconial formation and zonal patterning of vestibular sensory organs. These phenotypes are similar to those of Aldh1a3 knockouts, and the sensory phenotype is complementary to that of Cyp26b1 knockouts. Together, these results demonstrate that RDH10 and ALDH1a3 are the key RA-synthesis enzymes involved in vestibular development. Furthermore, we discovered that RA induces Cyp26b1 expression in the developing vestibular sensory organs, which generates the differential RA signaling required for zonal patterning.

Retinoic acid degradation shapes zonal development of vestibular organs and sensitivity to transient linear accelerations.

Each vestibular sensory epithelium in the inner ear is divided morphologically and physiologically into two zones, called the striola and extrastriola in otolith organ maculae, and the central and peripheral zones in semicircular canal cristae. We found that formation of striolar/central zones during embryogenesis requires Cytochrome P450 26b1 (Cyp26b1)-mediated degradation of retinoic acid (RA). In Cyp26b1 conditional knockout mice, formation of striolar/central zones is compromised, such that they resemble extrastriolar/peripheral zones in multiple features. Mutants have deficient vestibular evoked potential (VsEP) responses to jerk stimuli, head tremor and deficits in balance beam tests that are consistent with abnormal vestibular input, but normal vestibulo-ocular reflexes and apparently normal motor performance during swimming. Thus, degradation of RA during embryogenesis is required for formation of highly specialized regions of the vestibular sensory epithelia with specific functions in detecting head motions.

Ocular findings and selected ophthalmic diagnostic tests in a group of young commercially available Guinea and Skinny pigs (Cavia porcellus).

OBJECTIVE: The purpose of this study is to evaluate a group of young commercially available Skinny pigs, to gain information regarding ocular findings in this breed of guinea pig. Comparisons of ocular findings are to be made between Skinny pigs and haired guinea pigs. ANIMAL STUDIED: Ten haired guinea pigs and ten Skinny pigs were examined. PROCEDURE: A complete ophthalmic examination including Schirmer tear test-II (STT-II), phenol red thread test (PRTT), rebound tonometry with TonoVet PLUS, Fluorescein and Rose Bengal stain was performed. Microbiology swabs for aerobic bacterial growth were collected from conjunctiva of both eyes prior to the ophthalmic examination. RESULTS: The ophthalmic examination revealed seven abnormal ocular findings: trichiasis, mucopurulent discharge, hyperemia/chemosis of the conjunctiva, corneal fibrosis, corneal vascularization, and foreign body on the cornea or conjunctiva. Skinny pigs had a significantly higher amount of mucopurulent discharge (P = .0133) and a significantly higher STT-II (P < .001) than haired guinea pigs. Although not significant, trichiasis, keratitis with corneal vascularization, and foreign body presence were more common in Skinny pigs. Significantly more Skinny pigs had Pasteurellaceae isolated from their conjunctiva than haired guinea pigs (P = .0112). Antimicrobial susceptibility for the five Pasteurellaceae organisms isolated revealed susceptibility toward oxytetracycline, tobramycin, ciprofloxacin, and ofloxacin, whereas resistance was found toward erythromycin, trimethoprim-sulfamethoxazole, and moxifloxacin. CONCLUSION: Young Skinny pigs have a higher risk of Pasteurellaceae-associated conjunctivitis. Oxytetracycline, tobramycin, ciprofloxacin, and ofloxacin were identified as topical antibiotics that may be useful for Pasteurellaceae-associated conjunctivitis in Skinny pigs.

Genetic interactions support an inhibitory relationship between bone morphogenetic protein 2 and netrin 1 during semicircular canal formation.

The semicircular canals of the mammalian inner ear are derived from epithelial pouches in which epithelial cells in the central region of each pouch undergo resorption, leaving behind the region at the rim to form a tube-shaped canal. Lack of proliferation at the rim and/or over-clearing of epithelial cells in the center of the pouch can obliterate canal formation. Otic-specific knockout of bone morphogenetic protein 2 (Bmp2) results in absence of all three semicircular canals; however, the common crus and ampullae housing the sensory tissue (crista) are intact. The lack of Bmp2 causes Ntn1 (which encodes netrin 1), which is required for canal resorption, to be ectopically expressed at the canal rim. Ectopic Ntn1 results in reduction of Dlx5 and Lmo4, which are required for rim formation. These phenotypes can be partially rescued by removing one allele of Ntn1 in the Bmp2 mutants, indicating that Bmp2 normally negatively regulates Ntn1 for canal formation. Additionally, non-resorption of the canal pouch in Ntn1-/- mutants is partially rescued by removing one allele of Bmp2 Thus, reciprocal inhibition between Bmp2 and netrin 1 is involved in canal formation of the vestibule.

Urinary neopterin levels increase and predict survival during a respiratory outbreak in wild chimpanzees (Taï National Park, Côte d'Ivoire).

Monitoring immune system activation of wild animals has garnered increasing interest within the field of ecological immunology, leading to an urgent need for non-invasive biomarkers measuring these changes. Urinary neopterin, a marker of the cell-mediated immune response, is validated as an immune-related biomarker in captive and laboratory animals. However, wild animals naturally host higher and chronic pathogen loads. Therefore, detection and quantification of additional infections via neopterin might not be possible against the background of a chronically challenged immune system. To assess the suitability of urinary neopterin in wild animals, we measured neopterin corrected for specific gravity with an enzyme immunoassay in 185 samples collected before, during and after a respiratory disease outbreak in 28 individuals from a group of wild chimpanzees (Taï National Park, Côte d'Ivoire). Urinary neopterin levels were significantly higher during periods when individuals showed respiratory symptoms versus before and after the outbreak. Furthermore, urinary neopterin levels were significantly higher in individuals that died, with higher levels already apparent before the outbreak, suggesting individuals may have an already activated immune system. Measuring urinary neopterin levels, with other biomarkers of energetic condition, stress challenges, and reproduction will contribute towards a deeper understanding of life-history trade-offs in wild animals.

Reciprocal Negative Regulation Between Lmx1a and Lmo4 Is Required for Inner Ear Formation.

LIM-domain containing transcription factors (LIM-TFs) are conserved factors important for embryogenesis. The specificity of these factors in transcriptional regulation is conferred by the complexes that they form with other proteins such as LIM-domain-binding (Ldb) proteins and LIM-domain only (LMO) proteins. Unlike LIM-TFs, these proteins do not bind DNA directly. LMO proteins are negative regulators of LIM-TFs and function by competing with LIM-TFs for binding to Ldb's. Although the LIM-TF Lmx1a is expressed in the developing mouse hindbrain, which provides many of the extrinsic signals for inner ear formation, conditional knock-out embryos of both sexes show that the inner ear source of Lmx1a is the major contributor of ear patterning. In addition, we have found that the reciprocal interaction between Lmx1a and Lmo4 (a LMO protein within the inner ear) mediates the formation of both vestibular and auditory structures. Lmo4 negatively regulates Lmx1a to form the three sensory cristae, the anterior semicircular canal, and the shape of the utricle in the vestibule. Furthermore, this negative regulation blocks ectopic sensory formation in the cochlea. In contrast, Lmx1a negatively regulates Lmo4 in mediating epithelial resorption of the canal pouch, which gives rise to the anterior and posterior semicircular canals. We also found that Lmx1a is independently required for the formation of the endolymphatic duct and hair cells in the basal cochlear region.SIGNIFICANCE STATEMENT The mammalian inner ear is a structurally complex organ responsible for detecting sound and maintaining balance. Failure to form the intricate 3D structure of this organ properly during development most likely will result in sensory deficits on some level. Here, we provide genetic evidence that a transcription factor, Lmx1a, interacts with its negative regulator, Lmo4, to pattern various vestibular and auditory components of the mammalian inner ear. Identifying these key molecules that mediate formation of this important sensory organ will be helpful for designing strategies and therapeutics to alleviate hearing loss and balance disorders.

Directional selectivity of afferent neurons in zebrafish neuromasts is regulated by Emx2 in presynaptic hair cells.

The orientation of hair bundles on top of sensory hair cells (HCs) in neuromasts of the lateral line system allows fish to detect direction of water flow. Each neuromast shows hair bundles arranged in two opposing directions and each afferent neuron innervates only HCs of the same orientation. Previously, we showed that this opposition is established by expression of Emx2 in half of the HCs, where it mediates hair bundle reversal (Jiang et al., 2017). Here, we show that Emx2 also regulates neuronal selection: afferent neurons innervate either Emx2-positive or negative HCs. In emx2 knockout and gain-of-function neuromasts, all HCs are unidirectional and the innervation patterns and physiological responses of the afferent neurons are dependent on the presence or absence of Emx2. Our results indicate that Emx2 mediates the directional selectivity of neuromasts by two distinct processes: regulating hair bundle orientation in HCs and selecting afferent neuronal targets.

Treatment of spontaneous chronic corneal epithelial defects (SCCEDs) with diamond burr debridement vs combination diamond burr debridement and superficial grid keratotomy.

OBJECTIVE: To evaluate the efficacy of diamond burr debridement (DBD) vs a combination of diamond burr debridement with superficial grid keratotomy (DBD+SGK) for the treatment of spontaneous chronic corneal epithelial defects (SCCEDs) in dogs. PROCEDURE: Medical records of dogs diagnosed with SCCEDs from three different institutions that received a DBD or DBD+SGK between 2003 and 2015 were reviewed. Age, breed, sex, history of a previous SCCED, procedures performed, time to healing, and complications were statistically analyzed. RESULTS: One hundred and ninety-four dogs met the inclusion criteria. Eighty-two of 106 eyes (77.4%) received a DBD and healed following the first treatment (13.3 ± 4.9 days to recheck, range 2-27). Sixty-eight of 88 eyes (77.3%) received a DBD+SGK and healed following the first treatment (15.4 ± 5.0 days to recheck, range 5-45). No significant difference in healing outcome was found between the two treatments (P = 1). For SCCEDs that healed after a single treatment (n = 150), complications occurred in 13.3% (n = 20) of eyes with no difference in complications between the DBD and DBD+SGK groups (P = .86). Thirty-five of 44 eyes (80.0%) healed after the second treatment (16 ± 8.2 days from second treatment to third visit, range 5-47); nine of 44 eyes (20.0%) were not healed (12 ± 6.2 days from second treatment to third visit, range 5-25). The second treatment method did not influence healing rates (P = .64). CONCLUSIONS: DBD and DBD+SGK are equally effective treatment methods for canine SCCEDs. No differences in complication rates after one treatment were observed between DBD and DBD+SGK.

Seasonal and inter-annual variation of malaria parasite detection in wild chimpanzees.

BACKGROUND: Cross-sectional surveys of chimpanzee (Pan troglodytes) communities across sub-Saharan Africa show large geographical variation in malaria parasite (Plasmodium spp.) prevalence. The drivers leading to this apparent spatial heterogeneity may also be temporally dynamic but data on prevalence variation over time are missing for wild great apes. This study aims to fill this fundamental gap. METHODS: Some 681 faecal samples were collected from 48 individuals of a group of habituated chimpanzees (Taï National Park, Côte d'Ivoire) across four non-consecutive sampling periods between 2005 and 2015. RESULTS: Overall, 89 samples (13%) were PCR-positive for malaria parasite DNA. The proportion of positive samples ranged from 0 to 43% per month and 4 to 27% per sampling period. Generalized Linear Mixed Models detected significant seasonal and inter-annual variation, with seasonal increases during the wet seasons and apparently stochastic inter-annual variation. Younger individuals were also significantly more likely to test positive. CONCLUSIONS: These results highlight strong temporal fluctuations of malaria parasite detection rates in wild chimpanzees. They suggest that the identification of other drivers of malaria parasite prevalence will require longitudinal approaches and caution against purely cross-sectional studies, which may oversimplify the dynamics of this host-parasite system.

Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest.

Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation.

Transcription factor Emx2 controls stereociliary bundle orientation of sensory hair cells.

The asymmetric location of stereociliary bundle (hair bundle) on the apical surface of mechanosensory hair cells (HCs) dictates the direction in which a given HC can respond to cues such as sound, head movements, and water pressure. Notably, vestibular sensory organs of the inner ear, the maculae, exhibit a line of polarity reversal (LPR) across which, hair bundles are polarized in a mirror-image pattern. Similarly, HCs in neuromasts of the zebrafish lateral line system are generated as pairs, and two sibling HCs develop opposite hair bundle orientations. Within these sensory organs, expression of the transcription factor Emx2 is restricted to only one side of the LPR in the maculae or one of the two sibling HCs in neuromasts. Emx2 mediates hair bundle polarity reversal in these restricted subsets of HCs and generates the mirror-image pattern of the sensory organs. Downstream effectors of Emx2 control bundle polarity cell-autonomously via heterotrimeric G proteins.

Wild African great apes as natural hosts of malaria parasites: current knowledge and research perspectives.

Humans and African great apes (AGAs) are naturally infected with several species of closely related malaria parasites. The need to understand the origins of human malaria as well as the risk of zoonotic transmissions and emergence of new malaria strains in human populations has markedly encouraged research on great ape Plasmodium parasites. Progress in the use of non-invasive methods has rendered investigations into wild ape populations possible. Present knowledge is mainly focused on parasite diversity and phylogeny, with still large gaps to fill on malaria parasite ecology. Understanding what malaria infection means in terms of great ape health is also an important, but challenging avenue of research and has been subject to relatively few research efforts so far. This paper reviews current knowledge on African great ape malaria and identifies gaps and future research perspectives.

Temporal coupling between specifications of neuronal and macular fates of the inner ear.

The inner ear is a complex organ comprised of various specialized sensory organs for detecting sound and head movements. The timing of specification for these sensory organs, however, is not clear. Previous fate mapping results of the inner ear indicate that vestibular and auditory ganglia and two of the vestibular sensory organs, the utricular macula (UM) and saccular macula (SM), are lineage related. Based on the medial-lateral relationship where respective auditory and vestibular neuroblasts exit from the otic epithelium and the subsequent formation of the medial SM and lateral UM in these regions, we hypothesized that specification of the two lateral structures, the vestibular ganglion and the UM are coupled and likewise for the two medial structures, the auditory ganglion and the SM. We tested this hypothesis by surgically inverting the primary axes of the otic cup in ovo and investigating the fate of the vestibular neurogenic region, which had been spotted with a lipophilic dye. Our results showed that the laterally-positioned, dye-associated, vestibular ganglion and UM were largely normal in transplanted ears, whereas both auditory ganglion and SM showed abnormalities suggesting the lateral but not the medial-derived structures were mostly specified at the time of transplantation. Both of these results are consistent with a temporal coupling between neuronal and macular fate specifications.