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Teleradiology allows contemporaneous interpretation of imaging exams performed at some distance from the interpreting radiologist. The transmitted images are usually static. However, there is benefit to real-time review of full-motion ultrasound (US) exams as they are performed. Telesonography is transmission of full-motion sonographic data to a remote site. We hypothesize that US exams, read after having been compressed utilizing Motion Picture Experts Group version 4 (MPEG-4) compression scheme, transmitted over the Internet as streaming multimedia, decompressed, and displayed, are equivalent in diagnostic accuracy to reading the examinations locally. MPEG-4 uses variable compression on each image frame to achieve a constant output bit rate. With less compression, the bit rate rises, and the only way the encoder can contain bit rate within the set bandwidth is by lowering frame rate or reducing image quality. We review the relevant technologies and industry standard components that will enable low-cost telesonography. [ABSTRACT FROM AUTHOR]

Introduction: A significant risk for overdose among patients prescribed opioid medications is co-use of alcohol. Community pharmacies are underutilized as a resource to prevent and address co-use. The barriers and facilitators that promote or impede the adoption of universal alcohol screening and intervention at point of opioid medication dispensing are unknown. We assessed community pharmacy leaders, pharmacists, and technician's perceptions towards the implementation of a pharmacy-based screening/intervention for the co-use of opioids and alcohol among patients., Methods: We conducted a multi-method study that included one-time key informant interviews combined with a close-ended survey to inform our understanding of pharmacy system/practice-level barriers and facilitators for universal screening and intervention. Participants were recruited from Utah and Tennessee and were required to have active employment as pharmacy leaders, pharmacists, or technicians, be English-speaking, and believe they could provide feedback regarding co-use screening and intervention within community pharmacies. Interviews used the Consolidated Framework for Implementation Research and the Organizational Readiness for Implementing Change assessment. Qualitative analysis included both inductive and deductive coding. Themes followed a cycle of open, initial coding whereby codes were derived inductively from the data., Results: Themes from interviews (N = 68) included a) emphasizing a need to overcome the stigma associated with patients who engage in co-use and a mindset shift to treat the challenges and risks associated, b) need for corporate-level support, management buy-in, and c) appropriate technology to support the workflow including system-wide changes to support the integration of medication therapy management services within community pharmacies. However, barriers were offset by pharmacists eager to understand their role in screening patients and reiterated a focus on patient-centered care to achieve this goal. From the ORIC assessment, 75 % (n = 51) of respondents reported that community pharmacy staff wanted to implement the screening and intervention, and 69.1 % (n = 47) reported motivation to implement the screening and intervention. Finally, 67.6 % (n = 46) felt that community pharmacies are committed to implementing the screening and intervention, but only 10.3 % (n = 7) expressed strong support to do "whatever it takes" to implement the screening and intervention., Conclusion: These results provide critical insights into implementation strategies for the adoption of brief intervention by community pharmacists. These data are foundational to developing strategies for a powered trial and possible future system/practice-level implementation of universal alcohol screening and intervention for co-use., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Aortic stenosis and prosthesis-patient mismatch complicate surgery for patients with small left ventricular outflow tracts. We present outcomes of a modified-Bentall single-patch Konno enlargement (BeSPoKE) technique for complex left ventricular outflow tract obstruction in adults., Methods: The BeSPoKE technique facilitates a true outflow tract enlargement through an anterior septoventriculoplasty, using a single pericardial patch, followed by composite aortic valve-graft root replacement. Postoperative outflow tract geometry and valvular physiology were compared against preoperative measurements using echocardiography and computed tomographic angiography. Clinical outcomes at 2 years were assessed., Results: From October 2017 to March 2022, 25 adults (median age, 60 years; 84% women) underwent a BeSPoKE repair. Mean preoperative aortic valve gradient was 44 ± 19 mm Hg. Twenty-one patients (84%) had previous aortic valve replacements with prosthesis-patient mismatch; median implant size preoperatively was 19 mm. Postoperatively, all patients received a prosthesis of at least 21 mm, with a median upsizing of 2 (15th-85th percentile, 2-3 sizes). Mean postoperative aortic valve gradient was 8.5 ± 4.1 mm Hg (P < .001). The mean 2-year gradient was 8.3 ± 1.3 mm Hg. All patients with bioprosthetic replacements qualified for future transcatheter valve replacements. Postoperative complications included atrial fibrillation in 9 (36%) and complete heart block requiring pacemaker placement in 8 (32%). There were no operative deaths, and no reoperations were reported. There were 2 late noncardiac-related deaths; 2-year survival was 92%., Conclusions: The BeSPoKE technique facilitates larger prosthesis placement, improves hemodynamics, and enables future transcatheter reinterventions. This approach is a safe treatment for complex left ventricular outflow tract obstruction and prosthesis-patient mismatch in adults., Competing Interests: Disclosures Eric Roselli reports a relationship with Cook, Artivion, Edwards Lifesciences, W. L. Gore & Associates, Medtronic, and Terumo Aortic that includes: consulting or advisory and speaking and lecture fees. The other authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Melanoma is increasing worldwide, with incidence rates of invasive melanoma and melanoma in situ (MIS) varying by country., Objective: To provide updated invasive melanoma and MIS incidence and mortality trends in Iceland and explore differences among sex and rurality., Methods: In this whole-population study using the Icelandic Cancer Registry, patients diagnosed with invasive melanoma or MIS between 1957 and 2021 were included. Sex-specific world standardized incidence (WSR) and mortality rates were assessed by rurality. Joinpoint analysis was used to calculate trends using annual per cent change (APC)., Results: Invasive melanoma incidence rates increased from 0.66 to 7.0 (men) and 1.6 to 11.0 (women) per 100,000 person-years, and from 0.2 to 4.0 and 0.9 to 9.5 per 100,000 person-years for MIS in men and women, respectively, with a statistically significant linear trend (p = 0.001). WSR peaked in both men and women (10.7, 17.9 per 100,000 person-years) between 2002 and 2006 and has since been trending down. Between 1991 and 2005, the rise in invasive melanoma occurred more frequently in urban regions. Between 2003 and 2005, joinpoint analysis demonstrated a downtrend in invasive melanoma in men and women (-0.29, -0.73; p < 0.05). For MIS, the WSR peaked at 12.4 per 100,000 person-years in women between 1997 and 2001 before down-trending to 4.2. In recent years (2017-2021), the WSR has been steadily increasing in women with an APC of 1.43. Melanoma-specific mortality has decreased since 2012 (-0.07; p < 0.05)., Conclusions: Declining invasive melanoma incidence and mortality rates in conjunction with the recent rise in MIS may reflect the impact of Iceland's sun safety and anti-sunbed educational campaigns, federal regulation of sunbeds and earlier melanoma detection in urban areas., (© 2024 European Academy of Dermatology and Venereology.)

The spotted seatrout, Cynoscion nebulosus, is a popular game fish in the southeastern USA. It is estimated that nearly 90% of the adult population in South Carolina estuaries are infected in their skeletal muscle by the myxosporean, Kudoa inornata. However, little is known about this parasite's biology, including the distribution and densities of myxospores within tissues of infected fish, which we expect affect the physiology of their hosts. In order to correlate densities with physiological parameters in future studies, we quantified the myxospores density in muscle and characterized the variation among individual fish. Naïve juvenile seatrout was experimentally infected via presumed K. inornata actinospores exposure to raw seawater. A plug of muscle was extracted from two bilaterally symmetrical regions in the epaxial fillet from fresh and frozen carcasses. Variation in density data was calculated both within and among individuals. Within individuals, density counts were compared between left- and right-side biopsies. There was no significant difference between fresh and frozen plugs, and variation among individuals accounted for the greatest proportion of variation at 68.8%, while variation within individuals was substantial at 25.6%. Simulation and correlation tests confirmed that bilaterally symmetrical replicates varied significantly within individuals. When sampled from areas surrounding the initial biopsies, myxospore density estimates were more similar than between sides. Our findings have important implications for sampling design, particularly for studies investigating physiological parameters at the cellular or molecular level in association with parasite infection., (© 2024. The Author(s).)

Background: Patients in late-stage Parkinson's disease (PD LS ) are caregiver-dependent, have low quality of life, and higher healthcare costs., Objective: To estimate the prevalence of PD LS patients in the current US healthcare system., Methods: We downloaded the 2010-2022 data from the TriNetX Diamond claims network that consists of 92 US healthcare sites. PD was identified using standard diagnosis codes, and PD LS was identified by the usage of wheelchair dependence, personal care assistance, and/or presence of diagnoses of dementia. Age of PD LS identification and survival information were obtained and stratified by demographic and the disability subgroups., Results: We identified 1,031,377 PD patients in the TriNetX database. Of these, 18.8% fitted our definition of PD LS (n = 194,297), and 10.2% met two or more late-stage criteria. Among all PD LS , the mean age of PD LS identification was 78.1 (±7.7) years, and 49% were already reported as deceased. PD LS patients were predominantly male (58.5%) with similar distribution across PD LS subgroups. The majority did not have race (71%) or ethnicity (69%) information, but for the available information >90% (n = 53,162) were White, 8.2% (n = 5121) Hispanic/Latino, 7.8% (n = 4557) Black, and <0.01% (n = 408) Asian. Of the PD LS cohort, 71.6% identified with dementia, 12.9% had personal care assistance, and 4.8% were wheelchair-bound., Conclusions: Late-stage patients are a significant part of the PD landscape in the current US healthcare system, and largely missed by traditional motor-based disability staging. It is imperative to include this population as a clinical, social, and research priority. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Impact of Merkel cell polyomavirus (MCPyV) associated Merkel cell carcinoma (MCC) has not been assessed in the Icelandic population, nor in a whole population elsewhere., Objectives: The primary objective was to assess trends in the incidence of MCC in Iceland and the association with MCPyV. Secondary objectives aimed to analyze MCC outcomes., Methods: In this retrospective cohort study, patients diagnosed with MCC between 1981 and 2021 were identified from the Icelandic Cancer Registry. Patients were separated into 2 groups based on MCPyV immunochemistry staining. Age-standardized incidence was calculated and Joinpoint analysis was used to assess incidence trends. A Cox proportional hazards model was used to assess survival differences between the 2 groups., Results: Overall incidence of MCC increased from 0.015 to 0.26 per 100,000 persons, though the incidence of MCPyV positive cases recently decreased while negative cases increased. MCPyV negative tumors were associated with sun exposure ( P  < .01), a history of keratinocyte carcinoma, smaller tumor size, and lower overall survival., Limitations: Even with population-level data, comprehensively investigating associations with MCC is difficult due to its rarity., Conclusion: MCPyV negative MCC tumors were associated with lower survival despite smaller tumor size. Thus, MCPyV status could be an important prognostic biomarker., Competing Interests: None disclosed., (© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Purpose: The mainstay of treatment for nonmelanoma skin cancer (NMSC) on thin skin remains surgical, but procedures on older hands may be complicated by skin fragility and dermal atrophy. Used without cooling, 595 nm (nm) pulsed dye laser (PDL) has the capability of destroying NMSC through nonspecific thermal necrosis. The purpose of this study was to understand recurrence of NMSC on dorsal hands of older patients after one or two treatments using 595 nm PDL., Methods: A retrospective chart review identified 147 cases of NMSC located on the dorsal hands treated with 595 nm PDL. Cases of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) were included. All patients received one to two treatments with PDL. The primary outcome was the recurrence of carcinoma., Results: Among NMSC cases treated with PDL, recurrence occurred in 12 patients (8.2%). No cases of BCC recurred during the study period. Recurrence of SCC was 4.7% for SCC in situ and 10.4% recurrence for invasive SCC (p = 0.34). Among 71 patients treated once, recurrence occurred in 10 patients (14.1%), and among 76 cases treated twice, recurrence occurred in 2 patients (2.6%, p = 0.01)., Conclusion: Two treatments of PDL for NMSC on the dorsal hands of older patients was well tolerated, had low recurrence, and seemed more effective than one treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Determining if an employment opportunity will be a good match can feel daunting, especially for veterinary graduates entering the workforce. To ease this transition, veterinary educators traditionally have attempted to provide career support through interspersed didactic lectures on career options and the preparation of employment documents. While well intended, this approach fails to address the multiple dimensions of effective career planning or the reality that career planning is a lifelong endeavor. For a career-planning teaching modality to be effective, it must address all stages of career planning and provide a framework that can be adapted throughout a career. Here we describe how a four-stage career-planning model, utilized throughout higher education, was employed to create a career planning assignment for guiding students in assessing organizational fit. We describe how student feedback was used to inform revisions, resulting in an improved educational experience as measured by students' perceptions of the utility of the assignment. Additional recommendations based on instructor reflection are provided to guide creation and implementation of future assignments. Given the growing support for professional skills training in veterinary medical education, we view incorporation of such learning activities as essential to preparing students to enter the modern veterinary workplace.

Introduction: Neuroinflammation and metabolic dysfunction are early alterations in Alzheimer's disease (AD) brain that are thought to contribute to disease onset and progression. Glial activation due to protein deposition results in cytokine secretion and shifts in brain metabolism, which have been observed in AD patients. However, the mechanism by which this immunometabolic feedback loop can injure neurons and cause neurodegeneration remains unclear., Methods: We used Luminex XMAP technology to quantify hippocampal cytokine concentrations in the 5xFAD mouse model of AD at milestone timepoints in disease development. We used partial least squares regression to build cytokine signatures predictive of disease progression, as compared to healthy aging in wild-type littermates. We applied the disease-defining cytokine signature to wild-type primary neuron cultures and measured downstream changes in gene expression using the NanoString nCounter system and mitochondrial function using the Seahorse Extracellular Flux live-cell analyzer., Results: We identified a pattern of up-regulated IFNγ, IP-10/CXCL10, and IL-9 as predictive of advanced disease. When healthy neurons were exposed to these cytokines in proportions found in diseased brain, gene expression of mitochondrial electron transport chain complexes, including ATP synthase, was suppressed. In live cells, basal and maximal mitochondrial respiration were impaired following cytokine stimulation., Conclusions: We identify a pattern of cytokine secretion predictive of progressing amyloid-β pathology in the 5xFAD mouse model of AD that reduces expression of mitochondrial electron transport complexes and impairs mitochondrial respiration in healthy neurons. We establish a mechanistic link between disease-specific immune cues and impaired neuronal metabolism, potentially causing neuronal vulnerability and susceptibility to degeneration in AD., Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-023-00782-y., Competing Interests: Conflict of interestMadison K. Kuhn declares that she has no conflict of interest. Rebecca M. Fleeman declares that she has no conflict of interest. Lynne M. Beidler declares that she has no conflict of interest. Amanda M. Snyder declares that she has no conflict of interest. Dennis C. Chan declares that he has no conflict of interest. Elizabeth A. Proctor declares that she has no conflict of interest., (© The Author(s) 2023.)

Since the 1970s, intramuscular triamcinolone (IMT) has been available as an option for systemic corticosteroid use in dermatology. Although shown to be safe and effective in early studies, this method of systemic corticosteroid delivery fell out of favor in the 1980s in many United States residency programs. To identify factors associated with US dermatologists' preferences for and use of IMT we surveyed a random sample of US board-certified dermatologists to assess knowledge, attitudes, and practices regarding IMT in dermatologists' daily clinical practice. A total of 844 out of 2000 dermatologists completed the survey (42.2%). Only 55.0% reported feeling comfortable using IMT for steroid-responsive dermatoses, while 90.4% felt comfortable using oral corticosteroids for steroid-responsive dermatoses. Most participants (59.2%) did not prefer IMT over oral corticosteroids when both were indicated. One third (33.3%) of the participants reported that none of the faculty during their residency advocated using IMT. Receiving education on IMT indications (OR = 1.96 [95% CI: 1.46-2.63]) and encouragement to use IMT (OR = 4.29 [95% CI: 3.01-6.11]) during residency were positively associated with use of IMT at least once a month in current practice. Current knowledge, attitudes, and practices surrounding IMT vary amongst practicing dermatologists. Modifiable factors such as training could improve comfort with use of this short-term systemic steroid treatment modality., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Patient-reported outcome measures (PROMs) capture disease severity metrics from the patient's perspective, including health-related quality of life (HRQL). Disease-specific validation of PROMs improves their clinical utility. We evaluated construct validity (HRQL) for Skindex-16 in routinely seen psoriasis patients and characterized instances of discordance between Skindex-16 scores and clinician-reported outcome measure of disease severity. We retrospectively studied psoriasis patients seen by University of Utah Dermatology from 2016 to 2020. Cross-sectional construct validity was assessed using quantile regression and Spearman correlation between overall physician global assessment (OPGA) score and Skindex-16 scores. Longitudinal within-subject correlation was performed using linear mixed models. Discordance (10th percentile or lower OPGA and 90th percentile or higher Skindex-16 score [clear skin, poor HRQL; cspHRQL] or the reverse [severe skin, good HRQL; ssgHRQL]) was characterized descriptively. 681 first-visit patients with psoriasis were included. Median overall Skindex-16 score varied by ≥ 10 points across all levels of OPGA scores. OPGA and Skindex-16 domain scores were moderately correlated (emotions ρ = 0.54, functioning ρ = 0.47, and symptoms ρ = 53). Longitudinal correlations were similar (emotion ρ xy  = 0.54, functioning ρ xy  = 0.65, symptoms ρ xy  = 0.47). Visits with cspHRQL discordance occurred for each Skindex-16 domain (emotions = 7, functioning = 13, symptoms = 12). The ssgHRQL group was observed within the emotions (n = 1) and functioning (n = 23) domains. Median Skindex-16 scores are different between different levels of OPGA and show moderate cross-sectional and longitudinal correlation. This supports construct validity in patients with psoriasis. Severe discordance was rare and most often for those with clear skin but poor HRQL. These discordances can prompt further patient-clinician conversation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We sought to understand the consequences itchiness has on daily life that may not be immediately obvious in clinical assessments for patients with atopic dermatitis (AD)., Methods: Focus groups and interviews involving 21 patients with AD and 12 family members examined aspects of the effects of itchiness on health-related quality of life (HRQL). Investigators conducted a thematic analysis where two researchers independently coded the narratives and arrived at a consensus on major themes., Results: Five themes emerged from our discussions. 1) Miserable experience: Itchiness was difficult to control and cease. 2) Physical damage: Damage to skin and hair occurred from scratching to alleviate the itchiness. 3) Effects on daily activities: Itchiness could affect everything participants did, including how they dressed, used make-up, and slept. 4) Effects on social activities and relationships: The discomfort and embarrassment from scratching in public and others' reactions hindered participants' social lives. 5) Emotional consequences: Various emotional responses to itchiness were reported, including embarrassment, depression, and irritation., Limitations: Though qualitative research provides a level of detail not often found in quantitative analyses, this study design is limited by small sample size and generalizability., Conclusion: Understanding these challenges can help clinicians open deeper conversations with their patients to learn more about what patients need from their dermatologic care. While itchiness from AD is well-known, this study shows that its effects on HRQL are not minimal and that patients may need further care for the consequences of this symptom., Competing Interests: DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article., (Copyright © 2023. Matrix Medical Communications. All rights reserved.)

With more disease- and symptom-specific measures available and research pointing to increased usefulness, patient-reported outcome measures (PROMs) can be routinely used in clinical care. PROMs increase efficiency in healthcare, improve the clinician-patient relationship, and increase patient satisfaction with their care. PROMs can be administered before, during, and after clinic visits using paper-and-pencil, mobile phones, tablets, and computers. Herein, we combine available literature with expert views to discuss overcoming barriers and helping dermatologists incorporate PROMs into routine patient-centered care. We believe dermatology patients will benefit from broader PROM implementation and routine clinical use. However, a few major barriers exist: (1) cost to implement the technology, (2) selecting the right PROMs for each disease, and (3) helping both patients and clinicians understand how PROMs add to and complement their current clinical experience. We provide recommendations to assist dermatologists when considering whether to implement PROMs in their practices., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Solid organ and stem cell transplants are increasingly common, and dermatologists will more frequently encounter and need to manage common skin diseases, such as psoriasis, in transplant patients. This review explores psoriasis remission and occurrence in recipients of solid organ and stem cell transplants. Hematopoietic and mesenchymal stem cell transplants may show potential for treating psoriasis in patients with leukemia or who have other medical conditions requiring stem cell transplant. The effects of solid organ transplant are less clear, partly due to limitations in the breadth of the literature. De novo psoriasis has been reported in recipients of solid organ transplants, but the reasons for this development have yet to be fully understood. Overall, the literature on this subject is limited to primarily case reports. Feasibility of studies on the subject may be a considerable barrier to further research assessing the use of transplant for treating psoriasis, but there is potential benefit from transplant for psoriasis patients. This subject should receive further exploration to fully understand these benefits., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chronic inflammatory skin diseases like atopic dermatitis (AD) and psoriasis can severely impact patients' quality of life (QOL). However, the effect of these diseases can diminish the QOL of patients' family members as well. The objective of this study was to understand the impact on QOL for family members of patients diagnosed with AD or psoriasis., Methods: We conducted focus groups and interviews with 23 individuals; 12 had a family member with AD, and 11 had a family member with psoriasis. After investigators independently coded the transcripts, thematic analysis was conducted., Results: Three major themes emerged: (1) lifestyle consequences-many daily activities for family members, including but not limited to leisure activities, sleep, and cleaning, were affected by AD or psoriasis; (2) emotional consequences-family members felt frustrated, worried, or embarrassed, among other concerns, because of their loved ones' AD or psoriasis; (3) relationships-relationships between family members and their loved ones with AD or psoriasis could become strained, and though family members might try to be sympathetic, doing so could be difficult because of their lack of understanding of how these diseases feel and personally affect their loved ones., Conclusions: This study highlights the impacts of AD and psoriasis on the whole family. Clinicians should be mindful of the effects on QOL not only for patients but also for family members who live with and care about these patients. Especially when family members assist with treatments, it is important to understand family members' experiences when making treatment decisions., (© 2022. International Society of Behavioral Medicine.)

Introduction: Neuroinflammation and metabolic dysfunction are early alterations in Alzheimer's disease brain that are thought to contribute to disease onset and progression. Glial activation due to protein deposition results in cytokine secretion and shifts in brain metabolism, which have been observed in Alzheimer's disease patients. However, the mechanism by which this immunometabolic feedback loop can injure neurons and cause neurodegeneration remains unclear., Methods: We used Luminex XMAP technology to quantify hippocampal cytokine concentrations in the 5xFAD mouse model of Alzheimer's disease at milestone timepoints in disease development. We used partial least squares regression to build cytokine signatures predictive of disease progression, as compared to healthy aging in wild-type littermates. We applied the disease-defining cytokine signature to wild-type primary neuron cultures and measured downstream changes in gene expression using the NanoString nCounter system and mitochondrial function using the Seahorse Extracellular Flux live-cell analyzer., Results: We identified a pattern of up-regulated IFNγ, IP-10, and IL-9 as predictive of advanced disease. When healthy neurons were exposed to these cytokines in proportions found in diseased brain, gene expression of mitochondrial electron transport chain complexes, including ATP synthase, was suppressed. In live cells, basal and maximal mitochondrial respiration were impaired following cytokine stimulation., Conclusions: An Alzheimer's disease-specific pattern of cytokine secretion reduces expression of mitochondrial electron transport complexes and impairs mitochondrial respiration in healthy neurons. We establish a mechanistic link between disease-specific immune cues and impaired neuronal metabolism, potentially causing neuronal vulnerability and susceptibility to degeneration in Alzheimer's disease., Competing Interests: Disclosure of Potential Conflicts of Interest Madison K. Kuhn declares that she has no conflict of interest. Rebecca M. Fleeman declares that she has no conflict of interest. Lynne M. Beidler declares that she has no conflict of interest. Amanda M. Snyder declares that she has no conflict of interest. Dennis C. Chan declares that he has no conflict of interest. Elizabeth A. Proctor declares that she has no conflict of interest.

The ε4 variant of apolipoprotein E (APOE) is the strongest and most common genetic risk factor for Alzheimer's disease (AD). While the mechanism of conveyed risk is incompletely understood, promotion of inflammation, dysregulated metabolism, and protein misfolding and aggregation are contributors to accelerating disease. Here we determined the concurrent effects of systemic metabolic changes and brain inflammation in young (3-month-old) and aged (18-month-old) male and female mice carrying the APOE4 gene. Using functional metabolic assays alongside multivariate modeling of hippocampal cytokine levels, we found that brain cytokine signatures are predictive of systemic metabolic outcomes, independent of AD proteinopathies. Male and female mice each produce different cytokine signatures as they age and as their systemic metabolic phenotype declines, and these signatures are APOE genotype dependent. Ours is the first study to identify a quantitative and predictive link between systemic metabolism and specific pathological cytokine signatures in the brain. Our results highlight the effects of APOE4 beyond the brain and suggest the potential for bi-directional influence of risk factors in the brain and periphery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Cutaneous hypersensitivity eruptions in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are a clinically and histologically heterogeneous group that can either precede, occur with, or follow the development of a hematologic malignancy. Therefore, establishing the diagnosis requires careful clinical and pathologic correlation and an understanding of the broad spectrum of presentations. Data is lacking on the correlation of skin disease with molecular/cytogenetic risk profiling of the tumor., Objectives: The aims of this study were to characterize the clinical, histological, and genetic aberrations in recurrent cutaneous hypersensitivity reactions in patients with CLL/SLL., Methods: A single site academic retrospective chart review of medical records, histopathology, molecular and cytogenetic data in CLL/SLL patients who developed biopsy-proven cutaneous hypersensitivity reactions., Results: Five hundred one new diagnoses of CLL/SLL with 73 patients requiring cutaneous biopsies for skin lesions or rashes were identified. With exclusion criteria, 20 biopsies were identified from 17 patients (mean age, 69.6 years, females = 9) with unexplained cutaneous eruptions. These were commonly pruritic, erythematous papules above the waist. Most biopsies had a prominent superficial, deep dermal eosinophilic infiltrate (85%), with a robust T-cell predominant dermal infiltrate in 40%. Five out of 17 patients (29%) had a predominately folliculocentric CD4+ T-cell infiltrate; all occurring on the head and neck. Overall, the prevalence of cutaneous hypersensitivity eruptions requiring biopsy was 3.4% ( n  = 17), and the prevalence of folliculocentric CD4+ T-cell infiltrate was 1% ( n  = 5)., Conclusion: Cutaneous hypersensitivity reactions in CLL/SLL are heterogeneous; however, folliculotropic CD4+ T-cell infiltrates may be seen in a small but distinct clinical subset of patients. Commonly tested cytogenetic aberrations in CLL/SLL do not appear to be correlated with the presence of cutaneous hypersensitivity reactions., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Antimicrobial resistance is a threat to animal and human health. As a commensal and zoonotic bacterium, Escherichia coli has the potential to be a pathogenic source of antimicrobial resistance. The purpose of this study aimed to investigate the antimicrobial resistance profile of E. coli isolated from litter collected from pens in a broiler chicken experiment. E. coli was isolated from litter samples (n = 68 isolates) of 16 pens housing broilers to d 53 of age. Resistance to 10 antimicrobials was observed by disc diffusion. The presence of 23 antimicrobial and heavy metal resistance genes, O serogroups, and avian pathogenic E. coli (APEC-like) minimal predictor genes were identified through PCR. E. coli isolates presented the greatest resistance to cephalothin (54.4%), tetracycline (27.9%), streptomycin (29.4%), ampicillin (20.6%), colistin (13.2%), sulphonamides (8.8%), and imipenem (1.5%). Multidrug resistance to at least 3 antimicrobials was observed in 22.1% of isolates. The identified O-types of the E. coli isolates were O15, O75, O78, and O91. There was a greater likelihood that the genes groEL, aph(3)IA, silP, sull, aadA, qacEdelta1, iroN, ompTp, and hlyF were present in isolates that exhibited ampicillin resistance (P ≤ 0.05). There was a greater likelihood that the groEL gene was present in isolates resistant to ampicillin, colistin, tetracycline, sulphonamides, or cephalothin (P ≤ 0.05). Further characterizing E. coli antimicrobial resistance is essential and aids in developing effective solutions, thereby furthering the One Health objective., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Despite the negative impacts of Salmonella intestinal colonization on human health, Salmonella is a natural colonizer of the gastrointestinal tract and is not overtly pathogenic to the avian host. It is of interest to understand the impacts and colonization rates of Salmonella across selected genetic lines such as slow-growing (SG) and conventional (CONV) broilers. The objective of this study was to characterize the relationship between Salmonella enterica serovar Typhimurium challenge and selected broiler genetic lines on the ileal and cecal microbiome. Male chicks of two broiler breeds ( n = 156/breed) were cohoused in an open floor pen until day 7. On day 13, the chicks were then separated into 12 isolators per breed (4 rooms, 6 isolators/room, 11 chicks/isolator). On day 14, chicks in the 12 treatment isolators (6 isolators/breed, 108 total) were challenged with Salmonella Typhimurium (ST) (1 × 10 8 CFU/ml) via oral gavage while the remaining chicks ( n = 108) were given an oral gavage of sterile tryptic soy broth control (C). Ileal and cecal contents were collected on day 7 from 24 chicks of each breed, and on days 13, 17, 21, and 24 from two chicks per isolator. Samples underwent DNA extraction and PCR amplification to obtain 16S rRNA amplicons that were sequenced with Illumina MiSeq. Salmonella Typhimurium colonization in the cecum was not different in the two broiler breeds. The main effect of breed had the greatest impact on the ileum microbiota of broilers 7 days of age where SG broilers had significantly lower diversity and richness compared to CONV broilers ( p < 0.05). Salmonella Typhimurium challenge consistently caused a change in beta diversity. Regardless of day or intestinal location, challenged broilers had many amplicon sequence variants (ASVs) with decreased abundance of likely beneficial bacteria such as Mollicutes RF39, Shuttleworthia , Flavonifractor , and Oscillibacter compared to broilers that were unchallenged with Salmonella Typhimurium ( p < 0.05). Additionally, there was a difference in the timing of when the microbiota alpha and beta diversity of each breed responded to Salmonella Typhimurium challenge. Thus, both broiler breed and Salmonella Typhimurium can impact the intestinal microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sheets, Wickware, Snyder, Weimer and Johnson.)

Background: Skin conditions can have profound negative symptomatic and psychological effects. Failure to address these effects can lead to poor treatment adherence and/or patient dissatisfaction. Despite patient-reported outcome (PRO) use being highly recommended, real-world adoption has been slow., Objectives: To assess clinicians' perceived facilitators and barriers to using PROs in daily practice., Methods: We conducted in-person semi-structured interviews with 19 clinicians and thematic analysis of transcripts., Results: Three main themes emerged: (1) clinicians' attitudes about the value of Skindex-16 in daily practice, (2) patient attitudes influencing clinicians' use of Skindex-16, and (3) clinicians' perceptions of their ability to use PROs successfully for clinical care. Clinicians recognized benefits to using Skindex-16, such as revealing patients' hidden concerns and highlighting discrepancies with the clinician's severity assessments. Conversely, clinicians also identified limitations, such as time constraints and lack of relevance for some skin conditions. Patient complaints about PRO relevance have influenced clinicians' use of Skindex-16 negatively. Finally, some clinicians recognized the need for more training in score interpretation and implementation strategies for optimal clinical flow., Conclusions: While most clinicians believed PROs like Skindex-16 can be useful for patient care, barriers need to be addressed to make PROs more practical for routine clinical care., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Fast growth rate in broiler chickens comes with welfare concerns and the contribution of growth rate to pathogen resistance and sickness behavior is relatively unknown. The objective of this study was to evaluate physiological and behavioral responses of conventional (CONV) and slow-growing (SG) male broilers challenged with Salmonella Typhimurium. CONV ( n = 156) and SG ( n = 156) chicks were raised in a pen with wood litter shavings until day 7 of age, when birds were transferred to 24 isolators ( n = 11 chicks/isolator). On day 14 of age, half of the birds ( n = 12 isolators) were challenged with S. Typhimurium (ST) and the other half ( n = 12 isolators) received a control (C). On days 7, 13, 17, 21, and 24, body weight was recorded, and blood, jejunum and ileum sections were collected from 2 birds/isolator ( n = 48 birds/sampling) to measure plasma IgA and IgG and intestinal histomorphology, respectively. On days 12, 16, 21, and 23, video was recorded to evaluate bird postures (sitting, standing, or locomoting) and behaviors (eating, drinking, preening, stretching, sham foraging, allopreening, and aggression). CONV birds were 70 g heavier ( p = 0.03) on day 21 and 140 g heavier ( p = 0.007) on day 24 than SG. On day 7, CONV jejunum villus height and crypt depth were 22 and 7 μm greater ( p ≤ 0.001), respectively, than SG. On day 24, ST ileum villus height was 95 μm shorter ( p = 0.009) than C. IgA increased after day 17 for all birds and at day 21, CONV IgA was greater ( p = 0.01) than SG. Although SG IgG was 344 μg/ml greater ( p = 0.05) than CONV on day 7, CONV IgG increased with age ( p < 0.0001) to greater ( p ≤ 0.03) concentrations than SG on day 21 and day 24 by 689 μg/ml and 1,474 μg/ml, respectively, while SG IgG remained at similar concentrations after day 13. Generally, a greater proportion of birds sham foraged as they aged ( p < 0.0001). A greater proportion of CONV tended to sit ( p = 0.09) and fewer locomoted ( p < 0.0001) than SG as they aged. The results illustrate conventional and slow-growing broilers differ in their behavior, immunity, and response to Salmonella ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Snyder, Riley, Robison, Karcher, Wickware, Johnson and Weimer.)

Clinical clerkships have long been a pillar of veterinary medical education. These experiences provide students a unique opportunity to apply skills learned in pre-clinical training through hands-on practice. However, the emergence of the novel coronavirus, SARS-CoV-2, and the subsequent global pandemic of 2020 forced many clinical instructors to adapt to teaching online. This teaching tip describes the use of backward design to create a three-part online clinical learning environment for the delivery of small animal primary care consisting of synchronous rounds, simulated online appointments, and independent learning activities. Results of a survey of students' perspectives on the experience demonstrate that the majority of students found that the online clinical experience met or exceeded expectations and provided a meaningful learning experience. Recommendations based on student feedback and instructor reflection are provided to guide creation and implementation of future online clinical courses. As the field of telemedicine grows, we view incorporation of such learning environments into veterinary medical education curriculum as essential to preparing students to enter the modern veterinary workplace.

Background: Psoriasis is a chronic skin condition with significant effects on quality of life, including impacts on emotional health. However, these experiences are not always addressed in clinic visits, despite their potential for significant effects on daily life. This study is part of a larger project on the effects of psoriasis on quality of life. The current information was analyzed separately because the amount of information on emotional impacts mentioned by participants was so significant that it warranted a separate analysis to thoroughly assess these experiences. Objective: To describe emotional consequences of psoriasis for patients and their family members. Methods: This project was conducted at an academic medical center in Utah. Experiences were discussed in interviews and focus groups with 25 patients and 11 family members. Thematic analysis was used to determine themes and subthemes. Results: This study sheds light on the damaging effects of psoriasis on emotional well-being, illustrating the challenges patients face from internal conflict, consequences for family members trying to cope with psoriasis in a loved one, and judgment from others who do not understand psoriasis and its challenges. Conclusion: Living with psoriasis leads to emotional consequences that may be left unaddressed in clinic visits, yet these experiences contribute significantly to quality of life. The stories told through this study can help clinicians understand how to identify and address emotional concerns to improve care for psoriasis patients and, as a result, improve quality of life for both patients and their families., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s) 2022.)

Background: Patients with psoriasis commonly report experiencing severe sensory symptoms, and the burden of these symptoms can extend beyond unpleasant experiences to impair patients' health-related quality of life (HRQL). However, the symptom of pain and its consequences are still poorly understood in psoriasis patients. Objective: To understand the quality and intensity of pain associated with psoriasis as well as its interference with daily function in patients with psoriasis. Methods: Three focus groups and four interviews with psoriasis patients were conducted (n = 25). A trained facilitator used a semi-structured interview guide based on a literature review and a theory-driven approach. Two researchers independently coded the narratives and reached a consensus on the major themes using NVivo 12 software. Results: Our analysis produced five main themes regarding pain. (1) Perception of pain was illustrated through intense descriptors. (2) Patients identified pain triggers, including self-inflicted triggers. (3) Patients found coping strategies to deal with pain, including suppression of sensory experience. (4) Emotional suffering was linked primarily to the compulsion to continue scratching despite repeated efforts to stop and the failure of physicians to acknowledge the burden of the pain, which led to inadequate pain management. (5) Pain led to an overt impact on HRQL in these patients through interference with daily activity, intimate relationships, and sleep. Conclusions: Pain can be a significant hardship for patients with psoriasis. We encourage clinicians to inquire about pain separate from pruritus and to consider HRQL impacts of their patients' pain when determining treatments., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

A growing body of evidence suggests nigral iron accumulation plays an important role in the pathophysiology of Parkinson's disease (PD), contributing to dopaminergic neuron loss in the substantia nigra pars compacta (SNc). Converging evidence suggests this accumulation might be related to, or increased by, serotonergic dysfunction, a common, often early feature of the disease. We investigated whether lower plasma serotonin in PD is associated with higher nigral iron. We obtained plasma samples from 97 PD patients and 89 controls and MRI scans from a sub-cohort (62 PD, 70 controls). We measured serotonin concentrations using ultra-high performance liquid chromatography and regional iron content using MRI-based quantitative susceptibility mapping. PD patients had lower plasma serotonin (p < 0.0001) and higher nigral iron content (SNc: p < 0.001) overall. Exclusively in PD, lower plasma serotonin was correlated with higher nigral iron (SNc: r(58) =  - 0.501, p < 0.001). This correlation was significant even in patients newly diagnosed (< 1 year) and stronger in the SNc than any other region examined. This study reveals an early, linear association between low serotonin and higher nigral iron in PD patients, which is absent in controls. This is consistent with a serotonin-iron relationship in the disease process, warranting further studies to determine its cause and directionality., (© 2021. The Author(s).)

Background: Pain is an underappreciated symptom of atopic dermatitis that can affect the health-related quality of life (HRQL) of patients., Objective: The aim of this study is to understand the effect of pain on patients with atopic dermatitis and their family members and to recognize how this symptom affects HRQL., Methods: We conducted focus groups and interviews with patients with atopic dermatitis and their family members. Researchers independently coded the transcripts and reached a consensus on the major themes., Results: A total of 33 adult participants, consisting of 21 patients with atopic dermatitis (median age 47 years, range 22-77) and 12 family members (median age 50, range 22-72), attended either focus groups (23/33, 70%) or interviews (10/33, 30%), where we assessed their experiences of pain. Four themes emerged in our study. Itchiness and pain can be intertwined: pain was often caused by or otherwise associated with itchiness and could result from open sores and excoriated skin. Characteristics of pain: pain was most often described as burning. Other descriptors included mild, persistent discomfort; stinging; and stabbing. Effects of pain: pain negatively affected various aspects of daily life, including choice of clothing, sleep, social activities, and relationships. The location of painful areas could also limit physical activity, including sex. Pain management: pain from atopic dermatitis could be managed to varying degrees with different over-the-counter and prescription treatments. Systemic agents that cleared the skin also resolved the pain associated with atopic dermatitis., Conclusions: Pain can be a significant factor in the HRQL of patients with atopic dermatitis and should be considered by clinicians when caring for patients with atopic dermatitis., (©Ashley M Snyder, Vanina L Taliercio, Adelheid U Brandenberger, Bianca E Rich, Lisa B Webber, Abram P Beshay, Joshua E Biber, Rachel Hess, Jamie L W Rhoads, Aaron M Secrest. Originally published in JMIR Dermatology (http://derma.jmir.org), 04.10.2021.)

Background: Pruritus is the most common symptom of psoriasis, with a significant impact on patient quality of life. In spite of this, the severity, persistence, and overall impact of itchiness has only been rarely formally assessed during standard psoriasis clinic visits. Objectives: We sought to understand the far-reaching impacts of itchiness on the lives of those with psoriasis and their families., Methods: We conducted a qualitative study with five focus groups and 10 semi-structured interviews from August 2018 to January 2019. We enrolled 25 individuals with a diagnosis of at least moderate plaque psoriasis and 11 family members (primarily significant others). Views and experiences were analyzed thematically via content analysis., Results: Itchiness considerably impacts those with plaque psoriasis and their families. Our narrative analysis produced three main themes relating to itchiness: the triggers of itchiness, including climate, emotions, and behaviors; the physical consequences of itchiness, including disruption of emotional well-being, sleep disturbance, and daily activities; and the prevention and treatment strategies used to alleviate itchiness., Conclusion: Itchiness impacts the quality of life in those with psoriasis and their family members. We strongly urge clinicians to inquire about and monitor the severity and impact of itchiness in psoriasis patients., Competing Interests: DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article., (Copyright © 2021. Matrix Medical Communications. All rights reserved.)

Delivery of therapeutic agents to the central nervous system is challenged by the barriers in place to regulate brain homeostasis. This is especially true for protein therapeutics. Targeting the barrier formed by the choroid plexuses at the interfaces of the systemic circulation and ventricular system may be a surrogate brain delivery strategy to circumvent the blood-brain barrier. Heterogenous cell populations located at the choroid plexuses provide diverse functions in regulating the exchange of material within the ventricular space. Receptor-mediated transcytosis may be a promising mechanism to deliver protein therapeutics across the tight junctions formed by choroid plexus epithelial cells. However, cerebrospinal fluid flow and other barriers formed by ependymal cells and perivascular spaces should also be considered for evaluation of protein therapeutic disposition. Various preclinical methods have been applied to delineate protein transport across the choroid plexuses, including imaging strategies, ventriculocisternal perfusions, and primary choroid plexus epithelial cell models. When used in combination with simultaneous measures of cerebrospinal fluid dynamics, they can yield important insight into pharmacokinetic properties within the brain. This review aims to provide an overview of the choroid plexuses and ventricular system to address their function as a barrier to pharmaceutical interventions and relevance for central nervous system drug delivery of protein therapeutics. Protein therapeutics targeting the ventricular system may provide new approaches in treating central nervous system diseases.

There is considerable interest in gene and environment interactions in neurodegenerative diseases. The HFE (homeostatic iron regulator) gene variant (H63D) is highly prevalent in the population and has been investigated as a disease modifier in multiple neurodegenerative diseases. We have developed a mouse model to interrogate the impact of this gene variant in a model of paraquat toxicity. Using primary astrocytes, we found that the H67D-Hfe(equivalent of the human H63D variant) astrocytes are less vulnerable than the WT-Hfe astrocytes to paraquat-induced cell death, mitochondrial damage, and cellular senescence. We hypothesized that the Hfe variant-associated protection is a result of the activation of the Nrf2 antioxidant defense system and found a significant increase in Nrf2 levels after paraquat exposure in the H67D-Hfe astrocytes than the WT-Hfe astrocytes. Moreover, decreasing Nrf2 by molecular or pharmaceutical manipulation resulted in increased vulnerability to paraquat in the H67D-Hfe astrocytes. To further elucidate the role of Hfe variant genotype in neuroprotection mediated by astrocytes, we added media from the paraquat-treated astrocytes to differentiated SH-SY5Y neuroblastoma cells and found a significantly larger reduction in the viability when treated with WT-Hfe astrocyte media than the H67D-Hfe astrocyte media possibly due to higher secretion of IL-6 observed in the WT-Hfe astrocytes. To further explore the mechanism of Nrf2 protection, we measured NQO1, the Nrf2-mediated antioxidant, in primary astrocytes and found a significantly higher NQO1 level in the H67D-Hfe astrocytes. To consider the translational potential of our findings, we utilized the PPMI (Parkinson's Progression Markers Initiative) clinical database and found that, consistent with the mouse study, H63D-HFE carriers had a significantly higher NQO1 level in the CSF than the WT-HFE carriers. Consistent with our previous reports on H63D-HFE in disease, these data further suggest that HFE genotype in the human population impacts the antioxidant defense system and can therefore alter pathogenesis., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A recurrent and devastating feature of addiction to a drug of abuse is its persistence, which is mediated by maladaptive long-term memories of the highly pleasurable experience initially associated with the consumption of the drug. We have recently found that members of the CPEB family of proteins (Cytoplasmic Polyadenylation Element-Binding Proteins) are involved in the maintenance of spatial memory. However, their possible role in the maintenance of memories that sustain addictive behavior has yet to be explored. Little is known about any of the mechanisms for maintaining memories for addictive behavior. To address the mechanisms whereby addictive behavior is maintained over time, we utilized a conditional transgenic mouse model expressing a dominant-negative version of CPEB1 that abolishes the activity in the forebrain of two of the four CPEB isoforms (CPEB1 and CPEB3). We found that, following cocaine administration, these dominant-negative (DN) CPEB mice showed a significant decrease, when compared to wild type (WT) mice, in both locomotor sensitizations and conditioned place preference (CPP), two indices of addictive behavior. Supporting these behavioral results, we also found a difference between WT and DN-CPEB1-3 mice in the cocaine-induced synaptic depression in the core of the Nucleus Accumbens (NAc). Finally, we found that (1) CPEB is reduced in transgenic mice following cocaine injections and that (2) FosB, known for its contribution to establishing the addictive phenotype, when its expression in the striatum is increased by drug administration, is a novel target of CPEBs molecules. Thus, our study highlights how CPEB1 and CPEB3 act on target mRNAs to build the neuroadaptative implicit memory responses that lead to the development of the cocaine addictive phenotypes in mammals., (Copyright © 2020 Drisaldi, Colnaghi, Levine, Huang, Snyder, Metzger, Theis, Kandel, Kandel and Fioriti.)

Objective: Assess the accuracy of 3 early warning scores for predicting severe adverse events in postoperative inpatients., Summary of Background Data: Postoperative clinical deterioration on inpatient hospital services is associated with increased morbidity, mortality, and cost. Early warning scores have been developed to detect inpatient clinical deterioration and trigger rapid response activation, but knowledge regarding the application of early warning scores to postoperative inpatients is limited., Methods: This was a retrospective cohort study of adult patients hospitalized on the wards after surgical procedures at an urban academic medical center from November, 2008 to January, 2016. The accuracies of the Modified Early Warning Score (MEWS), National Early Warning Score (NEWS), and the electronic cardiac arrest risk triage (eCART) score were compared in predicting severe adverse events (ICU transfer, ward cardiac arrest, or ward death) in the postoperative period using the area under the receiver operating characteristic curve (AUC)., Results: Of the 32,537 patient admissions included in the study, 3.8% (n = 1243) experienced a severe adverse outcome after the procedure. The accuracy for predicting the composite outcome was highest for eCART [AUC 0.79 (95% CI: 0.78-0.81)], followed by NEWS [AUC 0.76 (95% CI: 0.75-0.78)], and MEWS [AUC 0.75 (95% CI: 0.73-0.76)]. Of the individual vital signs and labs, maximum respiratory rate was the most predictive (AUC 0.67) and maximum temperature was an inverse predictor (AUC 0.46)., Conclusion: Early warning scores are predictive of severe adverse events in postoperative patients. eCART is significantly more accurate in this patient population than both NEWS and MEWS.

Objective: To determine students' stress while performing surgery and evaluate the ability of a mindfulness intervention to reduce this stress., Study Design: Quasi-experimental design., Sample Population: Eighteen fourth-year DVM program students (n = 9 student/group)., Methods: Utilizing a quasi-experimental design, students were randomly assigned to a control or treatment group. The treatment group performed a 5-minute breathing (mindfulness) exercise immediately prior to performing surgery. Each student provided 3 samples of saliva, at time 0, at 10 minutes before surgery, and at 10 minutes after surgery. Students' salivary cortisol and α-amylase levels were compared between groups. Students' self-reported mood measures were also correlated to levels of salivary biomarkers., Results: Cortisol and α-amylase levels of students in both groups greatly exceeded normative reference groups (>90th percentile) prior to surgery and diminished to average levels (50th-60th percentile) after surgery but did not differ between groups at any time point. Immediately prior to surgery when stress values were likely to peak, salivary α-amylase levels decreased approximately 30 U/L units for students in the treatment group compared with an increase of approximately 10 U/L units for students in the control group. Students in the treatment group reported being more calm (mean [M] 2.67, SD 1.03, d = 0.75) and relaxed (M 2.33, SD 1.51, d = 0.90) than students in the control group (M 3.44, SD 1.01 and M 3.44, SD 0.88, respectively)., Conclusion: This study provides some evidence that the mindfulness intervention temporarily decreased stress levels and improved students' sense of calmness and relaxation immediately before operating on a live animal., Clinical Impact: Students who are experiencing less stress may be less likely to commit a medical error and negatively impact animal health. This study, the first of its kind in veterinary surgery, may serve as a model for related future studies., (© 2019 The American College of Veterinary Surgeons.)

Background: Parkinsonisms are neurodegenerative disorders characterized pathologically by α-synuclein-positive (e.g., PD, diffuse Lewy body disease, and MSA) and/or tau-positive (e.g., PSP, cortical basal degeneration) pathology. Using R2* and quantitative susceptibility mapping, susceptibility changes have been reported in the midbrain of living parkinsonian patients, although the exact underlying pathology of these alterations is unknown., Objective: The current study investigated the pathological correlates of these susceptibility MRI measures., Methods: In vivo MRIs (T1- and T2-weighted, and T2*) and pathology were obtained from 14 subjects enrolled in an NINDS PD Biomarker Program (PDBP). We assessed R2* and quantitative susceptibility mapping values in the SN, semiquantitative α-synuclein, tau, and iron values, as well as neuronal and glial counts. Data were analyzed using age-adjusted Spearman correlations., Results: R2* was associated significantly with nigral α-synuclein (r = 0.746; P = 0.003). Quantitative susceptibility mapping correlated significantly with Perls' (r = 0.758; P = 0.003), but not with other pathological measurements. Neither measurement correlated with tau or glial cell counts (r ≤ 0.11; P ≥ 0.129)., Conclusions: Susceptibility MRI measurements capture nigral pathologies associated with parkinsonian syndromes. Whereas quantitative susceptibility mapping is more sensitive to iron, R2* may reflect pathological aspects of the disorders beyond iron such as α-synuclein. They may be invaluable tools in diagnosing differential parkinsonian syndromes, and tracking in living patients the dynamic changes associated with the pathological progression of these disorders. © 2018 International Parkinson and Movement Disorder Society., (© 2018 International Parkinson and Movement Disorder Society.)

Parkinson's disease is marked clinically by motor dysfunction and pathologically by dopaminergic cell loss in the substantia nigra and iron accumulation in the substantia nigra. The driver underlying iron accumulation remains unknown and could be genetic or environmental. The HFE protein is critical for the regulation of cellular iron uptake. Mutations within this protein are associated with increased iron accumulation including in the brain. We have focused on the commonly occurring H63D variant of the HFE gene as a disease modifier in a number of neurodegenerative diseases. To investigate the role of H63D HFE genotype, we generated a mouse model in which the wild-type (WT) HFE gene is replaced by the H67D gene variant (mouse homolog of the human H63D gene variant). Using paraquat toxicity as the model for Parkinson's disease, we found that WT mice responded as expected with significantly greater motor function, loss of tyrosine hydroxylase staining and increase microglial staining in the substantia nigra, and an increase in R 2 relaxation rate within the substantia nigra of the paraquat-treated mice compared to their saline-treated counterparts. In contrast, the H67D mice showed a remarkable resistance to paraquat treatment; specifically differing from the WT mice with no changes in motor function or changes in R 2 relaxation rates following paraquat exposure. At baseline, there were differences between the H67D HFE mice and WT mice in gut microbiome profile and increased L-ferritin staining in the substantia nigra that could account for the resistance to paraquat. Of particular note, the H67D HFE mice regardless of whether or not they were treated with paraquat had significantly less tyrosine hydroxylase immunostaining than WT. Our results clearly demonstrate that the HFE genotype impacts the expression of tyrosine hydroxylase in the substantia nigra, the gut microbiome and the response to paraquat providing additional support that the HFE genotype is a disease modifier for Parkinson's disease. Moreover, the finding that the HFE mutant mice are resistant to paraquat may provide a model in which to study resistant mechanisms to neurotoxicants., (© 2018 International Society for Neurochemistry.)

Amyotrophic lateral sclerosis (ALS) is the third most prevalent neurodegenerative disease affecting upper and lower motor neurons. An important pathway that may lead to motor neuron degeneration is neuroinflammation. Cerebrospinal Fluids of ALS patients have increased levels of the inflammatory cytokine IL-18. Because IL-18 is produced by dendritic cells stimulated by the platelet-activating factor (PAF), a major neuroinflammatory mediator, it is expected that PAF is involved in ALS. Here we show pilot experimental data on amplification of PAF receptor (PAFR) mRNA by RT-PCR. PAFR is overexpressed, as compared to age matched controls, in the spinal cords of transgenic ALS SOD1-G93A mice, suggesting PAF mediation. Although anti-inflammatory drugs have been tested for ALS before, no clinical trial has been conducted using PAFR specific inhibitors. Therefore, we hypothesize that administration of PAFR inhibitors, such as Ginkgolide B, PCA 4248 and WEB 2086, have potential to function as a novel therapy for ALS, particularly in SOD1 familial ALS forms. Because currently there are only two approved drugs with modest effectiveness for ALS therapy, a search for novel drugs and targets is essential.