Mediator role of presence of meaning and self-esteem in the relationship of social support and death anxiety.

Introduction: Death anxiety has increased following the COVID-19 pandemic. Although terror management theory has suggested social support, presence of meaning and self-esteem functioned as death anxiety buffers, few existing works have explored the mechanism of how social support, presence of meaning, and self-esteem buffer death anxiety. To identify these mechanisms is the aim of this study. Methods: Our cross-sectional study was conducted with 1167 people in China from 19 May 2020 to 1 June 2020 during the COVID-19 outbreak. The average age of participants was 26 years. Data were by questionnaire, including demographic information, the Templer's Death anxiety scale, the multidimensional scale of perceived social support, the presence of meaning scale, and the Rosenberg self-esteem scale. Results: Results using structural equation modeling showed presence of meaning and self-esteem fully mediated the relationship between social support and death anxiety, respectively and sequentially. The proposed model showed good fit of indices: χ2 = 243.384, df = 58, p < 0.001; CFI = 0.968, TLI = 0.954, RMSEA = 0.052, SRMR = 0.044. Discussion: This study demonstrates significant mediator roles of presence of meaning and self-esteem in the relationship of social support and death anxiety. Multi-component interventions are needed to manage death anxiety by targeting increasing social support, presence of meaning and self-esteem and increasing presence of meaning and self-esteem when social support is diminished in the pandemic.

Internalised stigma, social support, coping and care-giving burden among Chinese family caregivers of adults diagnosed with schizophrenia: A parallel mediation analysis.

Care-giving burden and internalised stigma are prevalent among family caregivers of people diagnosed with schizophrenia. Internalised stigma has been regarded as a source of care-giving burden. But it remains unclear if high levels of internalised stigma directly contribute to an increased risk of care-giving burden or if the effects could be buffered by psychological factors. This cross-sectional study was to investigate the relationship between internalised stigma and care-giving burden, and to determine the mediating effects of coping styles and social support. Data were collected from 344 Chinese family caregivers of adults diagnosed with schizophrenia in a psychiatric outpatient department of a tertiary hospital in Changsha, Hunan between April and August 2018. A self-reported questionnaire was used to collect data anonymously. Instruments included the Simplified Coping Style Questionnaire, the Multidimensional Scale of Perceived Social Support, the Internalized Stigma of Mental Illness Scale and the Caregiver Burden Inventory. Data analysis was conducted using descriptive statistics, the Spearman correlation and regression analysis to estimate direct and indirect effects using bootstrap analysis. Results showed that internalised stigma, social support and passive coping were significant correlates of care-giving burden; social support partially mediated the relationship between internalised stigma and care-giving burden; active coping did not show impacts on internalised stigma and care-giving burden. This study provided social workers and healthcare providers with a better understanding of the development of care-giving burden. Comprehensive interventions should be designed to provide supportive resources and reduce the possibilities of internalisation of stigma and passive coping, to alleviate care-giving burden.

Quality of care in Hunan Province nursing homes: relationship to staffing and organizational climate.

Our objective was to examine the quality of care perceived by nursing staff and its relationship with the staffing and organizational climate in nursing homes. The participants in this cross-sectional study included 358 nursing staff from 26 nursing homes in Hunan Province, China. This study found that the interaction effect between nursing staff to resident ratio and physician to resident ratio exerted a significant effect on quality of care (p < 0.05). Higher scores on the relationships and communication scale (OR = 4.771, p = 0.002) and lower scores on the work stress scale (OR = 0.980, p = 0.050) were also associated with better quality of care. More work experience was related to lower quality of care (OR = 0.944, p = 0.048), and work experience was associated with relationships and communication (Beta = 0.172, p = 0.002) and work stress (Beta= = 0.259, p = 0.000). Staffing level, work experience, work stress, relationships and communication are key factors in providing higher quality of care in nursing homes.

Feasibility of brief distress screening for family caregivers of adults diagnosed with schizophrenia in Changsha, Hunan, China.

What is known on the subject? Distress screening amongst FGs is emphasized in worldwide studies, but existing general tools were found time-consuming and sometimes inconvenient when using them amongst FGs of patients diagnosed with schizophrenia. The DT, a single-item scale, was widely used to detect distress amongst FGs of cancer patients, showing good reliability, validity and discrimination power. The 21-item Depression Anxiety and Stress Scale (DASS21) can identify distress in the general population and serve as a criterion to determine an optimal cut-off score of the DT. WHAT DOES THE PAPER ADD TO EXISTING KNOWLEDGE?: The DT presented good reliability, validity and discriminatory power amongst FGs of adults diagnosed with schizophrenia. A cut-off score of six maximized sensitivity (77%) and specificity (76%). Over half of the FGs of adults diagnosed with schizophrenia reached this cut-off score and experienced significant distress. Distress was higher in FGs of male patients, when FGs were parents, and for FGs whose educational background was primary school or below. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The DT is an effective alternative to existing instruments in identifying distressed FGs of adults diagnosed with schizophrenia. It is important to provide FGs with distress screening programmes and interventions (e.g. skill-building psychoeducation) to identify and relieve distress. In addition, future research could explore brief measures to simultaneously recognize potential negative and positive impacts of caregiving in FGs.

Severity of illness and distress in caregivers of patients with schizophrenia: Do internalized stigma and caregiving burden mediate the relationship?

AIMS: To test a multiple mediation model of internalized stigma and caregiving burden in the relationship between severity of illness and distress among family caregivers of persons living with schizophrenia. DESIGN: This is a cross-sectional study. METHODS: Data were collected from a consecutive sample of 344 Chinese family caregivers of persons living with schizophrenia between April-August 2018. Instruments used in this research included the Clinical Global Impression-Severity of Illness, the Internalized Stigma of Mental Illness Scale, the Caregiver Burden Inventory, and the Distress Thermometer. Data analysis was conducted using descriptive statistics, the Spearman correlation, and regression analysis to estimate direct and indirect effects using bootstrap analysis. RESULTS: This research found that internalized stigma and caregiving burden can separately and sequentially mediate the relationship between severity of illness and distress. Moreover the mediation of internalized stigma plays the largest role among the multiple mediations. CONCLUSION: The severity of illness, internalized stigma, and caregiving burden are significant factors of distress among family caregivers of persons living with schizophrenia. The future intervention studies which be designed aiming at the three factors may be beneficial for family caregivers of persons living with schizophrenia. IMPACT: This research examined the psychosocial development of distress and indicated that interventions improving patients' symptoms and decreasing internalized stigma and caregiving burden can help to prevent or reduce distress among family caregivers.

Meaningful Use And Medical Home Functionality In Primary Care Practice.

To improve health care quality and decrease costs, both the public and private sectors continue to make substantial investments in the transformation of primary care. Central to these efforts is the patient-centered medical home model (PCMH) and the adoption and meaningful use of health information technology (IT). We used 2018 national family medicine data to provide a perspective on the implementation of PCMH and health IT elements in a variety of US physician practices. We found that 95 percent of family medicine-affiliated practices used electronic health records (EHRs) in 2018, but there was wide variation in whether those EHRs met meaningful-use criteria. Federally qualified health centers and military clinics were significantly more likely than other settings to have adopted PCMH elements. Adoption of PCMH elements was lowest among independently owned practices, which make up one-third of the primary care delivery system. Our findings suggest that achieving PCMH transformation across all types of practices will require a coordinated approach that aligns strong financial incentives with tailored technical assistance, an approach similar both to that used in federally qualified health centers over the past decade and to that used to drive EHR adoption a decade ago.

Internalized stigma and its correlates among family caregivers of patients diagnosed with schizophrenia in Changsha, Hunan, China.

WHAT IS KNOWN ON THE SUBJECT?: Schizophrenia is a severe and highly stigmatized mental illness. High internalized stigma affects FGs' quality of life and caregiving capacity. Worldwide studies aimed at internalized stigma among patients diagnosed with mental illness or their FGs have reported significant stigma and some correlates, but studies involving FGs that focus on a specific mental illness (e.g. schizophrenia) and report the impact of potential psychosocial variables (e.g. coping and hope) on internalized stigma are limited. WHAT DOES THE PAPER ADD TO EXISTING KNOWLEDGE?: Internalized stigma was common among Chinese FGs of patients diagnosed with schizophrenia and half of them presented at a mild level. Internalized stigma was negatively associated with hope and positively associated with passive coping. FGs, who live with patients, have difficulty supervising medication, or care for a male relative has higher internalized stigma. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Regarding informative support, interventions (e.g. enhancing mental health literacy programs and cognitive therapies) to provide knowledge about schizophrenia, the skills to manage patients' adherence to medications, the benefits of treatment and the possibilities of rehabilitation are necessary for FGs. Regarding psychosocial processes, effective interventions (e.g. group psychoeducation and group social skills training) aimed to enhance hope, social support and coping styles towards internalized stigma should be implemented among FGs. Both informative support and psychosocial interventions used to decrease FGs' internalized stigma can be delivered by healthcare providers or by peer caregivers. ABSTRACT: Introduction Internalized stigma is prevalent among patients diagnosed with schizophrenia. Their family caregivers (FGs) also suffer from internalized stigma, but limited studies have addressed the issue. Aim The aim of this study was to determine the severity of internalized stigma and its correlates among FGs of patients diagnosed with schizophrenia in Changsha, Hunan, China. Methods A consecutive sample of 299 FGs was recruited at the psychiatric outpatient department of a tertiary hospital in Changsha. This study explored the relationships between internalized stigma and potential factors. Results Nearly 50% of the FGs perceived mild internalized stigma, 24% of the FGs reported moderate level, and 6% had a severe level. Internalized stigma was associated with patients' characteristics (severity of illness) and FGs' characteristics (hope, social support, passive coping, age, education background, residence with the patient, caring for a male or a young patient and difficulty in supervising medication). Discussion and implications for practice Informative and psychosocial interventions based on education and contact for FGs such as enhancing mental health literacy programs, cognitive therapies and group psychoeducation can provide FGs with a better understanding of schizophrenia and to promote hope, active coping and social support.

A New Extension of the Binomial Error Model for Responses to Items of Varying Difficulty in Educational Testing and Attitude Surveys.

We put forward a new item response model which is an extension of the binomial error model first introduced by Keats and Lord. Like the binomial error model, the basic latent variable can be interpreted as a probability of responding in a certain way to an arbitrarily specified item. For a set of dichotomous items, this model gives predictions that are similar to other single parameter IRT models (such as the Rasch model) but has certain advantages in more complex cases. The first is that in specifying a flexible two-parameter Beta distribution for the latent variable, it is easy to formulate models for randomized experiments in which there is no reason to believe that either the latent variable or its distribution vary over randomly composed experimental groups. Second, the elementary response function is such that extensions to more complex cases (e.g., polychotomous responses, unfolding scales) are straightforward. Third, the probability metric of the latent trait allows tractable extensions to cover a wide variety of stochastic response processes.

Lesion of the olfactory epithelium accelerates prion neuroinvasion and disease onset when prion replication is restricted to neurons.

Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain.

Managing chronic illness: physician practices increased the use of care management and medical home processes.

The effective management of patients with chronic illnesses is critical to bending the curve of health care spending in the United States and is a crucial test for health care reform. In this article we used data from three national surveys of physician practices between 2006 and 2013 to determine the extent to which practices of all sizes have increased their use of evidence-based care management processes associated with patient-centered medical homes for patients with asthma, congestive heart failure, depression, and diabetes. We found relatively large increases over time in the overall use of these processes for small and medium-size practices as well as for large practices. However, the large practices used fewer than half of the recommended processes, on average. We also identified the individual processes whose use increased the most and show that greater use of care management processes is positively associated with public reporting of patient experience and clinical quality and with pay-for-performance.

Neutrophils select hypervirulent CovRS mutants of M1T1 group A Streptococcus during subcutaneous infection of mice.

Pathogen mutants arise during infections. Mechanisms of selection for pathogen variants are poorly understood. We tested whether neutrophils select mutations in the two-component regulatory system CovRS of group A Streptococcus (GAS) during infection using the lack of production of the protease SpeB (SpeB activity negative [SpeB(A-)]) as a marker. Depletion of neutrophils by antibodies RB6-8C5 and 1A8 reduced the percentage of SpeB(A-) variants (SpeB(A-)%) recovered from mice infected with GAS strain MGAS2221 by >76%. Neutrophil recruitment and SpeB(A-)% among recovered GAS were reduced by 95% and 92%, respectively, in subcutaneous MGAS2221 infection of CXCR2(-/-) mice compared with control mice. In air sac infection with MGAS2221, levels of neutrophils and macrophages in lavage fluid were reduced by 49% and increased by 287%, respectively, in CXCR2(-/-) mice compared with control mice, implying that macrophages play an insignificant role in the reduction of selection for SpeB(A-) variants in CXCR2(-/-) mice. One randomly chosen SpeB(A-) mutant outcompeted MGAS2221 in normal mice but was outcompeted by MGAS2221 in neutropenic mice and had enhancements in expression of virulence factors, innate immune evasion, skin invasion, and virulence. This and nine other SpeB(A-) variants from a mouse all had nonsynonymous covRS mutations that resulted in the SpeB(A-) phenotype and enhanced expression of the CovRS-controlled secreted streptococcal esterase (SsE). Our findings are consistent with a model that neutrophils select spontaneous covRS mutations that maximize the potential of GAS to evade neutrophil responses, resulting in variants with enhanced survival and virulence. To our knowledge, this is the first report of the critical contribution of neutrophils to the selection of pathogen variants.

CD11c⁺ cells primed with unrelated antigens facilitate an accelerated immune response to influenza virus in mice.

Recent evidence suggests that an individual's unique history and sequence of exposures to pathogens and antigens may dictate downstream immune responses to disparate antigens. We show that the i.n. delivery of nonreplicative virus-like particles (VLPs), which bear structural but no antigenic similarities to respiratory pathogens, acts to prime the lungs of both C56BL/6 and BALB/c mice, facilitating heightened and accelerated primary immune responses to high-dose influenza challenge, thus providing a nonpathogenic model of innate imprinting. These responses correspond closely to those observed following natural infection with the opportunistic fungus, Pneumocystis murina, and are characterized by accelerated antigen processing by DCs and alveolar macrophages, an enhanced influx of cells to the local tracheobronchial lymph node, and early upregulation of T-cell co-stimulatory/adhesion molecules. CD11c⁺ cells, which have been directly exposed to VLPs or Pneumocystis are necessary in facilitating enhanced clearance of influenza virus, and the repopulation of the lung by Ly-6C⁺ precursors relies on CCR2 expression. Thus, immune imprinting 72 h after VLP-priming, or 2 weeks after Pneumocystis-priming is CCR2-mediated and results from the enhanced antigen processing, maturation, and trafficking abilities of DCs and alveolar macrophages, which cause accelerated influenza-specific primary immune responses and result in superior viral clearance.

Inducible bronchus-associated lymphoid tissue (iBALT) synergizes with local lymph nodes during antiviral CD4+ T cell responses.

BACKGROUND: Exposure of the lungs to an antigen or pathogen elicits the formation of lymphoid satellite islands termed inducible bronchus-associated lymphoid tissue (iBALT). However, little is known about how the presence of iBALT, induced by a stimulus unrelated to the subsequent challenge agent, influences systemic immunity in distal locations, whether it be independently, antagonistically, or synergistically. Here, we determined the kinetics of the influenza-specific responses in the iBALT, tracheobronchial lymph node (TBLN), and spleen of mice with and without pre-formed iBALT. METHODS AND RESULTS: Mice with VLP-induced iBALT or no pre-formed iBALT were challenged with influenza. We found that, as we have previously described, those mice whose lungs contained pre-formed iBALT were protected from morbidity, and furthermore, that these mice had increased dendritic cell, and alveolar macrophage accumulation in both the iBALT and TBLNs. This translated to similarly accelerated kinetics and intensified influenza-specific CD4(+), but not CD8(+) T cell responses in the iBALT, TBLN, and spleen. This expansion was then followed by a more rapid T cell contraction in all lymphoid tissues in the mice with pre-formed iBALT. CONCLUSIONS: Thus, iBALT itself may not be responsible for the accelerated primary immune response we observe in mice with pre-formed iBALT, but may contribute to an overall accelerated local and systemic primary CD4(+), but not CD8(+) T cell response. Furthermore, less damaging immune responses observed in mice with pre-formed iBALT may be due to a quicker contraction of CD4(+) T cell responses in both local and systemic secondary lymphoid tissue.

Nuclear double-fluorescent reporter for in vivo and ex vivo analyses of biological transitions in mouse nuclei.

Cre-responsive dual-fluorescent alleles allow in situ marking of cell lineages or genetically modified cells. Here we report a dual-fluorescent allele, ROSA nT-nG , which directs nuclear accumulation of tdTomato in Cre-naïve lineages. Cre converts the allele to ROSA nG , which drives nuclear EGFP accumulation. Conditions were established for analyzing marked nuclei by flow cytometry on the basis of red-green fluorescence and ploidy, with a particular focus on liver nuclei. Hydrodynamic delivery of a Cre-expression plasmid was used to time-stamp arbitrary hepatocytes for lineage tracing. The distinct green fluorescence of nuclei from Cre-exposed lineages facilitated analyses of ploidy transitions within clones. To assess developmental transitions in liver nuclei, ROSA nT-nG was combined with the hepatocyte-specific AlbCre transgene, facilitating discrimination between hepatocyte and nonhepatocyte nuclei. Nuclei extracted from postnatal day 2 (P2) livers were 41 % green and 59 % red and reached a stable level of 84 % green by P22. Until P20, green nuclei were >98 % diploid (2N); at P40 they were ~56 % 2N, 43 % 4N, and <1 % 8N; and by P70 they reached a stable distribution of ~46 % 2N, 45 % 4N, and 9 % 8N. In conclusion, ROSA nT-nG will facilitate in vivo and ex vivo studies on liver and will likely be valuable for studies on tissues like muscle, kidney, or brain in which cells are refractory to whole-cell flow cytometry, or like trophectoderm derivatives or cancers in which cells undergo ploidy transitions.

Transforming primary care in the New Orleans safety-net: the patient experience.

BACKGROUND: The patient-centered medical home (PCMH) is a key service delivery innovation in health reform. However, there are growing questions about whether the changes in clinics promoted by the PCMH model lead to improvements in the patient experience. OBJECTIVE: To test the hypothesis that PCMH improvements in safety-net primary care clinics are associated with a more positive patient experience. RESEARCH DESIGN: Multilevel cross-sectional analysis of patients nested within the primary care clinics that serve them. SUBJECTS: Primary care clinic leaders and patients throughout the City of New Orleans health care safety-net. MEASURES: Dependent variables included patient ratings of accessibility, coordination, and confidence in the quality/safety of care. The key independent variable was a score measuring PCMH structural and process improvements at the clinic level. RESULTS: Approximately two thirds of patients in New Orleans gave positive ratings to their clinics on access and quality/safety, but only one third did for care coordination. In all but the largest clinics, patient experiences of care coordination were positively associated with the clinic's use of PCMH structural and process changes. Results for patient ratings of access and quality/safety were mixed. CONCLUSIONS: Among primary care clinics in the New Orleans safety-net, use of more PCMH improvements at the clinic level led to more positive patient rating of care coordination, but not of accessibility or confidence in quality/safety. Ongoing efforts to pilot, demonstrate, implement, and evaluate the PCMH should consider how the impact of medical practice transformation could vary across different aspects of the patient experience.

Virus-like particle-induced protection against MRSA pneumonia is dependent on IL-13 and enhancement of phagocyte function.

The importance of the priming of the lung environment by past infections is being increasingly recognized. Exposure to any given antigen can either improve or worsen the outcome of subsequent lung infections, depending on the immunological history of the host. Thus, an ability to impart transient alterations in the lung environment in anticipation of future insult could provide an important novel therapy for emerging infectious diseases. In this study, we show that nasal administration of virus-like particles (VLPs) before, or immediately after, lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA) of mice i) ensures complete recovery from lung infection and near absolute clearance of bacteria within 12 hours of challenge, ii) reduces host response-induced lung tissue damage, iii) promotes recruitment and efficient bacterial clearance by neutrophils and CD11c(+) cells, and iv) protects macrophages from MRSA-induced necrosis. VLP-mediated protection against MRSA relied on innate immunity. Complete recovery occurred in VLP-dosed mice with severe combined immunodeficiency, but not in wild-type mice depleted of either Ly6G(+) or CD11c(+) cells. Early IL-13 production associated with VLP-induced CD11c(+) cells was essential for VLP-induced protection. These results indicate that VLP-induced alteration of the lung environment protects the host from lethal MRSA pneumonia by enhancing phagocyte recruitment and killing and by reducing inflammation-induced tissue damage via IL-13-dependent mechanisms.

Protection orders protect against assault and injury: a longitudinal study of police-involved women victims of intimate partner violence.

The objective of this study was to measure the efficacy of protection orders (POs) in reducing assault and injury-related outcomes using a matched comparison group and tracking outcomes over time. This study was a retrospective review of police, emergency department, family court, and prosecutor administrative records for a cohort of police-involved female IPV victims; all events over a 4-year study period were abstracted. Victims who obtained POs were compared with a propensity-score-based match group without POs over three time periods: Before, During, and After the issuance of a PO. Having a PO in place was associated with significantly more calls to police for nonassaultive incidents and more police charging requests that were of multiple-count and felony-level. Comparing outcomes, PO victims had police incident rates that were more than double the matched group prior to the PO but dropped to the level of the matched group during and after the order. ED visits dropped over time for both groups. This study confirmed the protective effect of POs, which are associated with reduced police incidents and emergency department visits both during and after the order and reduced police incidents compared with a matched comparison group.

A virus-like particle vaccine platform elicits heightened and hastened local lung mucosal antibody production after a single dose.

We show that a model antigen, ovalbumin (OVA), can be chemically conjugated to the exterior of a small heat shock protein (sHsp) cage that has structural similarities to virus-like particles (VLPs). OVA-sHsp conjugation efficiency was dependent upon the stoichiometry and the length of the small molecule linker utilized, and the attachment position on the sHsp cage. When conjugated OVA-sHsp was delivered intranasally to naïve mice, the resulting immune response to OVA was accelerated and intensified, and OVA-specific IgG1 responses were apparent within 5 days after a single immunizing dose, illustrating its utility for vaccine development. If animals were pretreated with a disparate VLP, P22 (a non-replicative bacteriophage capsid), before OVA-sHsp conjugate immunization, OVA-specific IgG1 responses were apparent already by 4 days after a single immunizing dose of conjugate in OVA-naïve mice. Additionally, the mice pretreated with P22 produced high titer mucosal IgA, and isotype-switched OVA-specific serum IgG. Similarly, sHsp pretreatment enhanced the accumulation of lung germinal center B cells, T follicular helper cells, and increased polymeric Ig receptor expression, priming the lungs for subsequent IgG and IgA responses to influenza virus challenge. Thus, sHsp nanoparticles elicited quick and intense antibody responses and these accelerated responses could similarly be induced to antigen chemically conjugated to the sHsp. Pretreatment of mice with P22 further accelerated the onset of the antibody response to OVA-sHsp, demonstrating the utility of conjugating antigens to VLPs for pre-, or possibly post-exposure prophylaxis of lung, all without the need for adjuvant.

Accelerated shedding of prions following damage to the olfactory epithelium.

In this study, we investigated the role of damage to the nasal mucosa in the shedding of prions into nasal samples as a pathway for prion transmission. Here, we demonstrate that prions can replicate to high levels in the olfactory sensory epithelium (OSE) in hamsters and that induction of apoptosis in olfactory receptor neurons (ORNs) in the OSE resulted in sloughing off of the OSE from nasal turbinates into the lumen of the nasal airway. In the absence of nasotoxic treatment, olfactory marker protein (OMP), which is specific for ORNs, was not detected in nasal lavage samples. However, after nasotoxic treatment that leads to apoptosis of ORNs, both OMP and prion proteins were present in nasal lavage samples. The cellular debris that was released from the OSE into the lumen of the nasal airway was positive for both OMP and the disease-specific isoform of the prion protein, PrP(Sc). By using the real-time quaking-induced conversion assay to quantify prions, a 100- to 1,000-fold increase in prion seeding activity was observed in nasal lavage samples following nasotoxic treatment. Since neurons replicate prions to higher levels than other cell types and ORNs are the most environmentally exposed neurons, we propose that an increase in ORN apoptosis or damage to the nasal mucosa in a host with a preexisting prion infection of the OSE could lead to a substantial increase in the release of prion infectivity into nasal samples. This mechanism of prion shedding from the olfactory mucosa could contribute to prion transmission.