Environmental toxins, infection, and allergens lead to a transient mucous cell hyperplasia (MCH) in airway epithelia; however, the mechanisms for reducing mucous cell numbers during recovery are largely unknown. This study investigated Bcl-2 expression in mucous cells induced by a neutrophilic or eosinophilic inflammatory response. Brown Norway rats intratracheally instilled with lipopolysaccharide (LPS) showed an inflammatory response characterized primarily by neutrophils. Secreted mucin was increased fourfold at 1 day, and the number of mucous cells was increased fivefold 2, 3, and 4 days post-LPS instillation compared with those in noninstilled rats. None of the mucous cells in non- or saline-instilled control animals expressed Bcl-2, whereas 20-30% of mucous cells were Bcl-2 positive 1 and 2 days post-LPS instillation. Brown Norway rats immunized and challenged with ovalbumin (OVA) for 2, 4, and 6 days showed an inflammatory response characterized primarily by eosinophils. Secreted mucin increased fivefold, and mucous cell number increased fivefold after 4 and 6 days of OVA exposure compared with water-immunized control rats challenged with OVA aerosols. Approximately 10-25% of mucous cells were Bcl-2 positive in OVA-immunized and -challenged rats. These data demonstrate Bcl-2 expression in hyperplastic mucous cells of Brown Norway rats regardless of the type of inflammatory response and indicate that apoptotic mechanisms may be involved in the resolution of MCHs.

Background SARS-CoV-2 has disproportionately affected nursing homes (NH). In Ireland, the first NH case COVID-19 occurred on 16/03/2020. A national point-prevalence testing program of all NH residents and staff took place (18/04/2020–05/05/2020). Aims To examine characteristics of NHs across three Irish Community Health Organisations (CHOs), proportions with COVID-19 outbreaks, staff and resident infection rates symptom-profile, and resident case-fatality. Methods Forty-five NHs surveyed requesting details on occupancy, size, COVID-19 outbreak, outbreak timing, total symptomatic/asymptomatic cases, and outcomes for residents from 29/02/2020–22/05/2020. Results Surveys were returned from 62.2% (28/45) of NHs (2043 residents, 2,303 beds). Three-quarters (21/28) had COVID-19 outbreaks (1741 residents, 1972 beds). Median time from first COVID-19 case in Ireland to first case in these NHs was 27.0 days. Resident incidence was 43.9% (764/1741): 40.8% (710/1741) laboratory-confirmed, with 27.2% (193/710) asymptomatic, and 3.1% (54/1741) clinically-suspected. Resident case-fatality was 27.6% (211/764) for combined laboratory-confirmed/clinically-suspected COVID-19. Similar proportions of residents in NHs with “early-stage” (<28 days) versus “later-stage” outbreaks developed COVID-19. Lower proportions of residents in “early” outbreak NHs had recovered compared to those with “late” outbreaks (37.4% vs 61.7%; χ2 = 56.9, P < 0.001). Of 395 NH staff across twelve sites with confirmed COVID-19, 24.7% (99/398) were asymptomatic. There was a significant correlation between the proportion of staff with symptomatic COVID-19 and resident numbers with confirmed/suspected COVID-19 (Spearman’s rho = 0.81, P < 0.001). Conclusion This study demonstrates the significant impact of COVID-19 on the NH sector. Systematic point-prevalence testing is necessary to reduce risk of transmission from asymptomatic carriers and manage outbreaks in this setting.

Background: SARS-CoV-2 has disproportionately affected nursing home (NH) residents. In Ireland, the first NH case of COVID-19 occurred on 16/03/2020. A national point-prevalence testing program of all NH residents and staff took place from 18/04/2020-05/05/2020. Aims: To examine characteristics of NHs across three Community Health Organisations (CHOs) in Ireland, proportions with COVID-19 outbreaks, staff and resident, symptom-profile and resident case-fatality. Methods: Forty-five NHs surveyed across three CHOs requesting details on occupancy, size, COVID-19 outbreak, timing of outbreak, total symptomatic/asymptomatic cases, and outcomes for residents from 29/02/2020-22/05/2020. Results: Surveys were returned from (62.2%, 28/45) of NHs (2043 residents, 2303 beds). Three-quarters (21/28) had COVID-19 outbreaks (1741 residents, 1972 beds). Median time from first case of COVID-19 in Ireland to first case in these NHs was 27.0 days. Resident COVID-19 incidence was (43.9%, 764/1741): laboratory-confirmed (40.1%, 710/1741) with (27.2%, 193/710 asymptomatic), and clinically-suspected (3.1%, 54/1741). Resident case-fatality was (27.6%, 211/764) for combined laboratory-confirmed/clinically-suspected COVID-19. Similar proportions of residents in NH with an early outbreak (<28days) versus a later outbreak developed confirmed/suspected COVID-19. A lower proportion of residents in NHs with early outbreaks had recovered compared to those with late outbreaks (37.4% vs 61.7%; X2=56.9, p<0.001). Among 675 NH staff across twenty-four sites who had confirmed/suspected COVID-19 (23.6%, 159/675) were asymptomatic. There was a significant correlation between the proportion of staff with symptomatic COVID-19 and resident numbers with confirmed/suspected COVID-19 (Spearmans rho=0.81, p<0.001). Conclusion: This study demonstrates COVID-19 impact on NH residents and staff. High infection rates lead to challenges in care provision.

The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRFdependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated by these receptors. To address these issues, the current studies used a viral vector-based approach to chemogenetically activate or inhibit PFC CRF neurons in working memory-tested male rats. Chemogenetic activation of caudal, but not rostral, dmPFC CRF neurons potently impaired working memory, whereas inhibition of these neurons improved working memory. Importantly, the cognition-impairing actions of PFC CRF neurons were dependent on local CRF receptors coupled to protein kinase A. Additional electrophysiological recordings demonstrated that chemogenetic activation of caudal dmPFC CRF neurons elicits a robust degradation of task-related coding properties of dmPFC pyramidal neurons and, to a lesser extent, medium spiny neurons in the dorsomedial striatum. Collectively, these results demonstrate that local CRF release within the caudal dmPFC impairs frontostriatal cognitive and circuit function and suggest that CRF may represent a potential target for treating frontostriatal cognitive dysfunction. Significance StatementThe dorsomedial PFC and its striatal targets play a critical role in higher cognitive function. PFC-dependent cognitive dysfunction is associated with many psychiatric disorders. Although it has long-been known that corticotropin-releasing factor (CRF) neurons are prominent within the PFC, their role in cognition has remained unclear. Using a novel chemogenetic viral vector system, the present studies demonstrate that PFC CRF neurons impair working memory via activation of local PKA-coupled CRF receptors, an action associated with robust degradation in task-related frontostriatal neuronal coding. Conversely, suppression of constitutive PFC CRF activity improved working memory. Collectively, these studies provide novel insight into the neurobiology of cognition and suggest that CRF may represent a novel target for the treatment of cognitive dysfunction.

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