Incontinence-associated dermatitis in older adults in residential care settings: a point prevalence study.

Incontinence-associated dermatitis (IAD) is a skin inflammation caused by contact with urine or faeces or both. It has a negative effect on the patient's quality of life and is indicative of the care provided. However, globally there is a lack of empirical data on the prevalence of IAD. AIM: To identify, for the first time, the proportion of older adults in extended care settings in Ireland affected by IAD. DESIGN: Cross-sectional, multisite, point prevalence survey, across three community extended care settings for older people in Ireland. METHODS: Two clinical nurse specialists, using the Scottish Excoriation and Moisture Related Skin Damage Tool, identified the presence of IAD through clinical observation and visual skin inspection. IAD prevalence was calculated for the total population and incontinent population sets using percentages and confidence intervals (CI). RESULTS: The prevalence of incontinence was 86.4% (n=165), a significantly higher proportion were female (P=0.003). The point prevalence of IAD across the total population and incontinent population was 11.5% (22/191; 95% CI, 7.4-19.9%) and 13.3% (22/164; 95% CI, 8.5-19.5%), respectively. Being incontinent was associated with being female, more dependent (Barthel), having possible cognitive impairment, poorer mobility (Braden and Waterlow) and a high risk of pressure ulcers (Waterlow). A logistic regression analysis found no predictor variables for IAD among the variables that met the cut-off point for this analysis. CONCLUSIONS: The study provides the first point prevalence empirical data on the occurrence of IAD in Ireland. It can inform decision-making on future planning and budgeting of new quality improvement projects and act as a benchmark for ongoing auditing of IAD.

Preparing health professional students for interprofessional practice related to neurodevelopmental disabilities: a pilot program.

Many health professional students have insufficient general knowledge about individuals with neurodevelopmental disabilities. Students lack the expertise required to work with this population and their families. Interprofessional practice education (IPE) programs, designed for working with individuals with specialized needs and their families, are needed to improve overall care provided. An IPE program related to neurodevelopmental disabilities for health professional students was implemented focusing on applied learning and community engagement to develop competencies for students related to neurodevelopmental disabilities at a state university in the U.S. The purpose of this research was to describe the development and implementation of an IPE program and to examine the effectiveness of the IPE program aimed at developing identified competencies and increase awareness related to care of individuals with ND for health professional students. The findings suggest the IPE program enhanced health professional students' perceived competencies to identify and provide culturally sensitive and family-centered care for individuals with neurodevelopmental disabilities and their families. This experience also provided an opportunity for personal/professional growth and increased awareness of the unique needs of these individuals with neurodevelopmental disabilities and their families.

Interprofessional bedside rounding improves quality of feedback to resident physicians.

PURPOSE: Obtaining high quality feedback in residency education is challenging, in part due to limited opportunities for faculty observation of authentic clinical work. This study reviewed the impact of interprofessional bedside rounds ('iPACE™') on the length and quality of faculty narrative evaluations of residents as compared to usual inpatient teaching rounds. METHODS: Narrative comments from faculty evaluations of Internal Medicine (IM) residents both on usual teaching service as well as the iPACE™ service (spanning 2017-2020) were reviewed and coded using a deductive content analysis approach. RESULTS: Six hundred ninety-two narrative evaluations by 63 attendings of 103 residents were included. Evaluations of iPACE™ residents were significantly longer than those of residents on usual teams (109 vs. 69 words, p < 0.001). iPACE™ evaluations contained a higher average occurrence of direct observations of patient/family interactions (0.72 vs. 0.32, p < 0.001), references to interprofessionalism (0.17 vs. 0.05, p < 0.001), as well as specific (3.21 vs. 2.26, p < 0.001), actionable (1.01 vs. 0.69, p < 0.001), and corrective feedback (1.2 vs. 0.88, p = 0.001) per evaluation. CONCLUSIONS: This study suggests that the iPACE™ model, which prioritizes interprofessional bedside rounds, had a positive impact on the quantity and quality of feedback, as measured via narrative comments on weekly evaluations.

Problem Solving Training for Veterans with Complex Comorbidities: Treatment Delivery Adaptations during COVID-19.

OBJECTIVES: To summarize adaptations due to COVID-19 for VA Problem Solving Training (PST) for clinicians serving medically complex patients and to compare patient mental health outcomes in the year before (2019) and during COVID-19 (2020). METHODS: Clinicians attended a multi-day workshop and up to 6 months of small-group consultation for two training cases. In 2019 and 2020, 122 Veteran patients completed baseline and posttreatment measures of depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7 item), and negative problem-solving beliefs (Negative Problem Orientation Questionnaire). Qualitative data were collected on clinician's pandemic-related treatment implementation challenges. RESULTS: Program adaptations during COVID-19 addressed challenges due to delivering treatment by telephone, video, or in person; Veteran patient recruitment barriers; and privacy issues for telephone and video. Veterans in both pre-pandemic and COVID-19 cohorts had significant improvements in depression, anxiety, and negative problem-solving beliefs, with no significant differences in the amount of improvement between the two cohorts. CONCLUSIONS: Flexibilities afforded to clinicians delivering the PST training program during the pandemic addressed key obstacles and barriers to recruitment, and implementation did not diminish the effectiveness of the intervention. CLINICAL IMPLICATIONS: Findings support continued implementation of the PST training program with added flexibility to treatment delivery beyond the pandemic.

The Red Legs RATED tool to improve diagnosis of lower limb cellulitis in the emergency department.

BACKGROUND: Lower limb cellulitis poses a significant burden for the Irish healthcare system. Accurate diagnosis is difficult, with a lack of validated evidence-based tools and treatment guidelines, and difficulties distinguishing cellulitis from its imitators. It has been suggested that around 30% of suspected lower limb cellulitis is misdiagnosed. An audit of 132 patients between May 2017 and May 2018 identified a pattern of misdiagnosis in approximately 34% of this cohort. OBJECTIVE: The aim of this pilot project was to develop a streamlined service for those presenting to the emergency department with red legs/suspected cellulitis, through introduction of the 'Red Leg RATED' tool for clinicians. METHOD: The tool was developed and introduced to emergency department clinicians. Individuals (n=24) presenting with suspected cellulitis over 4 weeks in 2018 were invited to participate in data gathering. Finally, clinician questionnaire feedback regarding the tool was evaluated. RESULTS: Fourteen participants consented, 6 female and 8 male with mean age of 65 years. The tool identified 50% (n=7) as having cellulitis, of those 57% (n=4) required admission, 43% (n=3) were discharged. The remainder who did not have cellulitis (n=7) were discharged. Before introduction of the tool, all would typically have been admitted to hospital for further assessment and management of suspected lower limb cellulitis. Overall, 72% (n=10) of patients who initially presented with suspected cellulitis were discharged, suggesting positive impact of the tool. Clinician feedback suggested all were satisfied with the tool and contents. CONCLUSION: The Red Leg RATED tool is user friendly and impacts positively on diagnosis treatment and discharge. Further evaluation is warranted.

Multidrug-Resistant Salmonella enterica Subspecies I Serovar 4,[5],12:i:- Isolates Recovered from Food Safety and Inspection Service-Regulated Products and Food Animal Ceca, 2007-2016.

Salmonella enterica subspecies I serovar 4,[5],12:i:- (Salmonella I 4,[5],12:i:-) is among the five most common serovars associated with human salmonellosis in the United States. In 2010, human infections with Salmonella I 4,[5],12:i:- which exhibited resistance to ampicillin, streptomycin, sulfonamides, and tetracycline (ASSuT) emerged as a public health concern. Outbreak investigations identified live animal settings, meat and poultry, and pets as confirmed and suspect sources of infection. To shed further light on possible sources of ASSuT-resistant Salmonella I 4,[5],12:i:- infections, we described isolates recovered from meat and poultry products regulated by the Food Safety and Inspection Service (FSIS) and from food animal ceca collected at FSIS-regulated slaughter establishments during 2007-2016. During the time period of interest, ASSuT-resistant Salmonella I 4,[5],12:i:- was found at low levels in multiple FSIS product classes including swine, turkey, cattle and chicken, which suggests this pathogen has a relatively wide host range. Monitoring trends in the various FSIS production classes over time and developing commodity profiles may help focus preventative strategies.

Implementing a Theoretical Debriefing Model in a Prelicensure BSN Program.

The National League for Nursing and International Nursing Association for Clinical Simulation and Learning stress that debriefing fosters critical reflection and is essential to all educational settings. The call to action for nurse educators is to incorporate theory-based debriefing throughout the curriculum. This article reports on how one school of nursing implemented the theory-based model, Debriefing for Meaningful Learning©, into the prelicensure baccalaureate curriculum.

ERBB2 signaling drives supporting cell proliferation in vitro and apparent supernumerary hair cell formation in vivo in the neonatal mouse cochlea.

In mammals, cochlear hair cells are not regenerated once they are lost, leading to permanent hearing deficits. In other vertebrates, the adjacent supporting cells act as a stem cell compartment, in that they both proliferate and differentiate into de novo auditory hair cells. Although there is evidence that mammalian cochlear supporting cells can differentiate into new hair cells, the signals that regulate this process are poorly characterized. We hypothesize that signaling from the epidermal growth factor receptor (EGFR) family may play a role in cochlear regeneration. We focus on one such member, ERBB2, and report the effects of expressing a constitutively active ERBB2 receptor in neonatal mouse cochlear supporting cells, using viruses and transgenic expression. Lineage tracing with fluorescent reporter proteins was used to determine the relationships between cells with active ERBB2 signaling and cells that divided or differentiated into hair cells. In vitro, individual supporting cells harbouring a constitutively active ERBB2 receptor appeared to signal to their neighbouring supporting cells, inducing them to down-regulate a supporting cell marker and to proliferate. In vivo, we found supernumerary hair cell-like cells near supporting cells that expressed ERBB2 receptors. Both supporting cell proliferation and hair cell differentiation were largely reproduced in vitro using small molecules that we show also activate ERBB2. Our data suggest that signaling from the receptor tyrosine kinase ERBB2 can drive the activation of secondary signaling pathways to regulate regeneration, suggesting a new model where an interplay of cell signaling regulates regeneration by endogenous stem-like cells.

Novel linezolid resistance plasmids in Enterococcus from food animals in the USA.

Objectives: To sequence the genomes and determine the genetic mechanisms for linezolid resistance identified in three strains of Enterococcus isolated from cattle and swine caecal contents as part of the US National Antimicrobial Resistance Monitoring System (NARMS) surveillance programme. Methods: Broth microdilution was used for in vitro antimicrobial susceptibility testing to assess linezolid resistance. Resistance mechanisms and plasmid types were identified from data generated by WGS on Illumina® and PacBio® platforms. Conjugation experiments were performed to determine whether identified mechanisms were transmissible. Results: Linezolid resistance plasmids containing optrA were identified in two Enterococcus faecalis isolates and one Enterococcus faecium. The E. faecium isolate also carried the linezolid resistance gene cfr on the same plasmid as optrA. The linezolid resistance plasmids had various combinations of additional resistance genes conferring resistance to phenicols (fexA), aminoglycosides [spc and aph(3')-III] and macrolides [erm(A) and erm(B)]. One of the plasmids was confirmed to be transmissible by conjugation, resulting in linezolid resistance in the transconjugant. Conclusions: To the best of our knowledge, this is the first identification of linezolid resistance in the USA in bacteria isolated from food animals. The oxazolidinone class of antibiotics is not used in food animals in the USA, but the genes responsible for resistance were identified on plasmids with other resistance markers, indicating that there may be co-selection for these plasmids due to the use of different antimicrobials. The transmissibility of one of the plasmids demonstrated the potential for linezolid resistance to spread horizontally. Additional surveillance is necessary to determine whether similar plasmids are present in human strains of Enterococcus.

First field evidence of the evolution from a non-virulent HPR0 to a virulent HPR-deleted infectious salmon anaemia virus.

The putatively non-virulent subtype of infectious salmon anaemia virus (ISAV), ISAV-HPR0, is proposed to act as a progenitor and reservoir for all virulent ISAVs and thus represent a potential risk factor for the emergence of infectious salmon anaemia (ISA) disease. Here, we provide the first evidence of genetic and functional evolution from an ISAV-HPR0 variant (FO/07/12) to a low-virulent ISAV virus (FO/121/14) in a Faroese Atlantic salmon marine farm. The FO/121/14 virus infection was not associated with specific clinical signs of ISA and was confined to a single net-pen, while various ISAV-HPR0 subtypes were found circulating in most epidemiologically linked marine and freshwater farms. Sequence analysis of all eight segments revealed that the FO/121/14 virus was identical, apart from a substitution in the fusion (F) gene (Q266L) and a deletion in the haemagglutinin-esterase (HE) gene, to the FO/07/12 variant from a freshwater farm, which supplied smolts exclusively to the FO/121/14-positive net-pen. An immersion challenge with the FO/121/14 virus induced a systemic infection in Atlantic salmon associated with a low mortality and mild clinical signs confirming its low pathogenicity. Our results demonstrate that mutations in the F protein and deletions in the highly polymorphic region (HPR) of the HE protein represent a minimum requirement for ISAV to gain virulence and to switch cell tropism from a localized epithelial infection to a systemic endotheliotropic infection. This documents that ISAV-HPR0 represents a reservoir and risk factor for the emergence of ISA disease.

Does imiquimod pretreatment optimize 308-nm excimer laser (UVB) therapy in psoriasis patients?

BACKGROUND/PURPOSE: Psoriasis continues to be a debilitating skin disease affecting 1-3% of the United States population. Although the effectiveness of several current biologic therapies have described this pathology as a IL-23, TNF-a and Th17-mediated disease, less invasive approaches are still in use and in need of refinement. One of these is the usage of narrow band-UVB (NB-UVB) therapy to deplete specifically intra-epidermal CD3+, CD4+ and CD8+ cells to clear psoriatic plaques. AIMS/OBJECTIVES: In order to improve NB-UVB therapy, we sought to determine whether skin pre-treatment with the TLR7 agonist imiquimod (IMQ) would help increase the efficiency of the former at resolving psoriatic plaques. MATERIALS AND METHODS: Eucerin® Original Moisturizing Lotion (topical vehicle) or Aldara® (imiquimod 5% topical cream) were applied for 5 days once daily to a maximum contiguous area of 25 cm2 (5 cm × 5 cm area). Patients were provided with sachets containing 12.5 mg of imiquimod each and were instructed to apply imiquimod (I) to two psoriasis plaques (5 sachets of imiquimod allotted to each plaque). A PHAROS excimer Laser EX-308 (Ra Medical Systems, Inc. Carlsbad, CA, USA) with an output of monochromatic 308-nm light and pulse width of 20-50 ns was used for all patients. Punch biopsies of psoriatic lesions (6 mm) were taken at 4 and 48 h after final application of topical treatment with or without excimer laser treatment. Real-time quantitative RT-PCR was performed according to manufacturer's instructions and Inmunohistochemistry was used as described before. RESULTS: Our results suggests that although IMQ seemed to activate the type I interferon pathway as previously described, its concomitant usage with NB-UVB for clearing psoriatic skin was ineffective. Although upregulation of genes MxA, GRAMD1A and DMXL2 suggested that IMQ treatment did induce skin changes in psoriasis patients, more optimal dosing of IMQ and NB-UVB might be necessary to achieve desired treatment responses. CONCLUSION: The observation that psoriasis involvement was not aggravated by usage of topical IMQ was encouraging. Additional observational studies might be necessary to further tailor the combination of IMQ with NB-UVB therapy to reliably improve the psoriatic pathology.

Effectiveness of a Technology-Based Intervention to Teach Evidence-Based Practice: The EBR Tool.

BACKGROUND: As the world becomes increasingly digital, advances in technology have changed how students access evidence-based information. Research suggests that students overestimate their ability to locate quality online research and lack the skills needed to evaluate the scientific literature. Clinical nurses report relying on personal experience to answer clinical questions rather than searching evidence-based sources. To address the problem, a web-based, evidence-based research (EBR) tool that is usable from a computer, smartphone, or iPad was developed and tested. The purpose of the EBR tool is to guide students through the basic steps needed to locate and critically appraise the online scientific literature while linking users to quality electronic resources to support evidence-based practice (EBP). METHODS: Testing of the tool took place in a mixed-method, quasi-experimental, and two-population randomized controlled trial (RCT) design in a U.S. and Middle East university. RESULTS: A statistically significant improvement in overall research skills was supported in the quasi-experimental nursing student group and RCT nutrition student group using the EBR tool. A statistically significant proportional difference was supported in the RCT nutrition and PharmD intervention groups in participants' ability to distinguish the credibility of online source materials compared with controls. The majority of participants could correctly apply PICOTS to a case study when using the tool. CONCLUSIONS: The data from this preliminary study suggests that the EBR tool enhanced student overall research skills and selected EBP skills while generating data for assessment of learning outcomes. LINKING EVIDENCE TO ACTION: The EBR tool places evidence-based resources at the fingertips of users by addressing some of the most commonly cited barriers to research utilization while exposing users to information and online literacy standards of practice, meeting a growing need within nursing curricula.

Mutation of Foxo3 causes adult onset auditory neuropathy and alters cochlear synapse architecture in mice.

Auditory neuropathy is a form of hearing loss in which cochlear inner hair cells fail to correctly encode or transmit acoustic information to the brain. Few genes have been implicated in the adult-onset form of this disease. Here we show that mice lacking the transcription factor Foxo3 have adult onset hearing loss with the hallmark characteristics of auditory neuropathy, namely, elevated auditory thresholds combined with normal outer hair cell function. Using histological techniques, we demonstrate that Foxo3-dependent hearing loss is not due to a loss of cochlear hair cells or spiral ganglion neurons, both of which normally express Foxo3. Moreover, Foxo3-knock-out (KO) inner hair cells do not display reductions in numbers of synapses. Instead, we find that there are subtle structural changes in and surrounding inner hair cells. Confocal microscopy in conjunction with 3D modeling and quantitative analysis show that synaptic localization is altered in Foxo3-KO mice and Myo7a immunoreactivity is reduced. TEM demonstrates apparent afferent degeneration. Strikingly, acoustic stimulation promotes Foxo3 nuclear localization in vivo, implying a connection between cochlear activity and synaptic function maintenance. Together, these findings support a new role for the canonical damage response factor Foxo3 in contributing to the maintenance of auditory synaptic transmission.

Silicon phthalocyanine 4 phototoxicity in Trichophyton rubrum.

Trichophyton rubrum is the leading pathogen that causes long-lasting skin and nail dermatophyte infections. Currently, topical treatment consists of terbinafine for the skin and ciclopirox for the nails, whereas systemic agents, such as oral terbinafine and itraconazole, are also prescribed. These systemic drugs have severe side effects, including liver toxicity. Topical therapies, however, are sometimes ineffective. This led us to investigate alternative treatment options, such as photodynamic therapy (PDT). Although PDT is traditionally recognized as a therapeutic option for treating a wide range of medical conditions, including age-related macular degeneration and malignant cancers, its antimicrobial properties have also received considerable attention. However, the mechanism(s) underlying the susceptibility of dermatophytic fungi to PDT is relatively unknown. As a noninvasive treatment, PDT uses a photosensitizing drug and light, which, in the presence of oxygen, results in cellular destruction. In this study, we investigated the mechanism of cytotoxicity of PDT in vitro using the silicon phthalocyanine (Pc) 4 [SiPc(OSi(CH3)2(CH2)3N(CH3)2)(OH)] in T. rubrum. Confocal microscopy revealed that Pc 4 binds to cytoplasmic organelles, and upon irradiation, reactive oxygen species (ROS) are generated. The impairment of fungal metabolic activities as measured by an XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay indicated that 1.0 µM Pc 4 followed by 670 to 675 nm light at 2.0 J/cm(2) reduced the overall cell survival rate, which was substantiated by a dry weight assay. In addition, we found that this therapeutic approach is effective against terbinafine-sensitive (24602) and terbinafine-resistant (MRL666) strains. These data suggest that Pc 4-PDT may have utility as a treatment for dermatophytosis.

Evaluating adherence to American Diabetes Association standards of care in diabetes and impacts of social determinants of health on patients at two nurse practitioner-owned clinics.

BACKGROUND: The COVID-19 pandemic created barriers in the management of type 2 diabetes mellitus (T2DM) and worsened social determinants of health (SDOH). A New Hampshire primary care office worked to adhere to T2DM standards of care and began screening for SDOH. This project assessed adherence to quality metrics, hemoglobin A1C, and SDOH screening as telehealth utilization decreased. LOCAL PROBLEM: A1C values have increased at the practice, especially since COVID-19. The practice also began screening for SDOH at every visit, but there was need to assess how needs were being documented and if/how they were addressed. METHODS: A retrospective chart review of patients with T2DM was performed. Demographic data and T2DM metrics were collected and compared with previous years and compared new versus established patients. Charts were reviewed to evaluate documentation of SDOH and appropriate referral. INTERVENTIONS: The practice transitioned from an increased utliization of telehealth back to prioritizing in-office visits. The practice also began routinely screening for SDOH in 2020; however, this process had not been standardized or evaluated. RESULTS: Adherence to nearly all quality metrics improved. Glycemic control improved after a year of nurse practitioner (NP) care, especially in new patients. All patients were screened for SDOH, but documentation varied, and affected patients had higher A1Cs, despite receiving comparable care. CONCLUSION: Nurse practitioners at this practice are adhering to American Diabetes Association guidelines, and A1C values improve under their care. Social determinants of health continue to act as unique barriers that keep patients from improving glycemic control, highlighting the need for individualized treatment of SDOH in T2DM care.

Corrigendum: Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation.

[This corrects the article DOI: 10.3389/fncel.2022.1096872.].

EGFR signaling is required for regenerative proliferation in the cochlea: conservation in birds and mammals.

Proliferation and transdifferentiaton of supporting cells in the damaged auditory organ of birds lead to robust regeneration of sensory hair cells. In contrast, regeneration of lost auditory hair cells does not occur in deafened mammals, resulting in permanent hearing loss. In spite of this failure of regeneration in mammals, we have previously shown that the perinatal mouse supporting cells harbor a latent potential for cell division. Here we show that in a subset of supporting cells marked by p75, EGFR signaling is required for proliferation, and this requirement is conserved between birds and mammals. Purified p75+ mouse supporting cells express receptors and ligands for the EGF signaling pathway, and their proliferation in culture can be blocked with the EGFR inhibitor AG1478. Similarly, in cultured chicken basilar papillae, supporting cell proliferation in response to hair cell ablation requires EGFR signaling. In addition, we show that EGFR signaling in p75+ mouse supporting cells is required for the down-regulation of the cell cycle inhibitor p27(Kip1) (CDKN1b) to enable cell cycle re-entry. Taken together, our data suggest that a conserved mechanism involving EGFR signaling governs proliferation of auditory supporting cells in birds and mammals and may represent a target for future hair cell regeneration strategies.

Increased recognition of non-O157 Shiga toxin-producing Escherichia coli infections in the United States during 2000-2010: epidemiologic features and comparison with E. coli O157 infections.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) are an important cause of diarrhea and the major cause of postdiarrheal hemolytic uremic syndrome. Non-O157 STEC infections are being recognized with greater frequency because of changing laboratory practices. METHODS: Foodborne Diseases Active Surveillance Network (FoodNet) site staff conducted active, population-based surveillance for laboratory-confirmed STEC infections. We assessed frequency and incidence of STEC infections by serogroup and examined and compared demographic factors, clinical characteristics, and frequency of international travel among patients. RESULTS: During 2000-2010, FoodNet sites reported 2006 cases of non-O157 STEC infection and 5688 cases of O157 STEC infections. The number of reported non-O157 STEC infections increased from an incidence of 0.12 per 100,000 population in 2000 to 0.95 per 100,000 in 2010; while the rate of O157 STEC infections decreased from 2.17 to 0.95 per 100,000. Among non-O157 STEC, six serogroups were most commonly reported: O26 (26%), O103 (22%), O111 (19%), O121 (6%), O45 (5%), and O145 (4%). Non-O157 STEC infections were more common among Hispanics, and infections were less severe than those caused by O157 STEC, but this varied by serogroup. Fewer non-O157 STEC infections were associated with outbreaks (7% versus 20% for O157), while more were associated with international travel (14% versus 3% for O157). CONCLUSIONS: Improved understanding of the epidemiologic features of non-O157 STEC infections can inform food safety and other prevention efforts. To detect both O157 and non-O157 STEC infections, clinical laboratories should routinely and simultaneously test all stool specimens submitted for diagnosis of acute community-acquired diarrhea for O157 STEC and for Shiga toxin and ensure that isolates are sent to a public health laboratory for serotyping and subtyping.

Neuroinflammation in a Mouse Model of Alzheimer's Disease versus Auditory Dysfunction: Machine Learning Interpretation and Analysis.

Background: Auditory dysfunction, including central auditory hyperactivity, hearing loss and hearing in noise deficits, has been reported in 5xFAD Alzheimer's disease (AD) mice, suggesting a causal relationship between amyloidosis and auditory dysfunction. Central auditory hyperactivity correlated in time with small amounts of plaque deposition in the inferior colliculus and medial geniculate body, which are the auditory midbrain and thalamus, respectively. Neuroinflammation has been associated with excitation to inhibition imbalance in the central nervous system, and therefore has been proposed as a link between central auditory hyperactivity and AD in our previous report. However, neuroinflammation in the auditory pathway has not been investigated in mouse amyloidosis models. Methods: Machine learning was used to classify the previously obtained auditory brainstem responses (ABRs) from 5xFAD mice and their wild type (WT) littermates. Neuroinflammation was assessed in six auditory-related regions of the cortex, thalamus, and brainstem. Cochlear pathology was assessed in cryosection and whole mount. Behavioral changes were assessed with fear conditioning, open field testing and novel objection recognition. Results: Reliable machine learning classification of 5xFAD and WT littermate ABRs were achieved for 6M and 12M, but not 3M. The top features for accurate classification at 6 months of age were characteristics of Waves IV and V. Microglial and astrocytic activation were pronounced in 5xFAD inferior colliculus and medial geniculate body at 6 months, two neural centers that are thought to contribute to these waves. Lower regions of the brainstem were unaffected, and cortical auditory centers also displayed inflammation beginning at 6 months. No losses were seen in numbers of spiral ganglion neurons (SGNs), auditory synapses, or efferent synapses in the cochlea. 5xFAD mice had reduced responses to tones in fear conditioning compared to WT littermates beginning at 6 months. Conclusions: Serial use of ABR in early AD patients represents a promising approach for early and inexpensive detection of neuroinflammation in higher auditory brainstem processing centers. As changes in auditory processing are strongly linked to AD progression, central auditory hyperactivity may serve as a biomarker for AD progression and/or stratify AD patients into distinct populations.