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Hypersensitivity pneumonitis (HP) is an extrinsic allergic alveolitis characterized by inflammation of the interstitium, bronchioles, and alveoli of the lung that leads to granuloma formation. We previously found that activation of protein kinase D1 (PKD1) in the lungs following exposures to contributes to the acute pulmonary inflammation, IL-17A expression in the lungs, and development of HP. In the present study, we investigated whether PKD1 in myeloid-lineage cells affects the pathogenic course of the -induced HP. Mice were exposed intranasally to once or 3 times/week for 3 weeks. The protein and mRNA expression levels of cytokines/chemokines were detected by enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. Flow cytometry was used to detect the different types of immune cells and the levels of surface proteins. Lung tissue sections were stained with hematoxylin and eosin, digital images were captured, and immune cells influx into the interstitial lung tissue were detected. Compared to control PKD1-sufficient mice, mice with PKD1 deficiency in myeloid-lineage cells (PKD1mKO) showed significantly suppressed expression of TNFα, IFNγ, IL-6, CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL10 and neutrophilic alveolitis after single intranasal exposure to . Substantially reduced levels of alveolitis and granuloma formation were observed in the PKD1mKO mice repeatedly exposed to for 3 weeks. In addition, expression levels of the Th1/Th17 polarizing cytokines and chemokines such as IFNγ, IL-17A, CXCL9, CXCL10, CXCL11, and CCL20 in lungs were significantly reduced in the PKD1mKO mice repeatedly exposed to . Moreover, accumulation of CXCR3+CCR6+ nonconventional Th1 in the lungs were significantly reduced in PKD1mKO mice repeatedly exposed to . Our results demonstrate that PKD1 in myeloid-lineage cells plays an essential role in the development and progress of HP caused by repeated exposure to by contributing Th1/Th17 polarizing proinflammatory responses, alveolitis, and accumulation of pathogenic nonconventional Th1 cells in the lungs.

[This corrects the article DOI: 10.3389/fimmu.2024.1403155.].

It is well established that antibody to the acetylcholine receptor (AChR) is responsible for the pathogenesis of disease in myasthenia gravis (MG). However, there are patients with characteristic myasthenic symptoms that have no detectable anti-AChR antibodies. MG patients also produce autoantibodies to other skeletal muscle components; identification of these antigens may reveal that the non-receptor autoantibodies play a role in the disease process. Western blot analysis of a human skeletal muscle flocculate extract (FE) revealed multiple non-receptor skeletal muscle antigens reactive with myasthenic sera. The fact that these antigens represent distinct muscle proteins rather than degradative fragments of a few muscle components, was demonstrated by the use of enzyme inhibitors. Identification of the antigens in FE was accomplished by comparing the electrophoretic mobilities of known muscle proteins with these antigens in SDS polyacrylamide gel electrophoresis. Known muscle proteins were also examined in western blot for their reactivity with myasthenic sera. Our myasthenic patient population did not possess antibodies to skeletal muscle tropomyosin, troponin, calmodulin, actin, or the Ca $\\sp{2+}$ -ATPase pump. Myasthenic patients had antibodies to skeletal muscle myosin,$\\alpha$ -actinin, calsequestrin, and smooth muscle filamin, as well as several other components in skeletal muscle microsome and sarcoplasmic reticulum (SR) preparations. One of the antigenic bands in FE was postulated to be$\\alpha$ -actinin. This was confirmed by the demonstration that the reaction of myasthenic sera with this band in western blot could be inhibited by the addition of purified skeletal muscle$\\alpha$ -actinin. A second antigenic band in the FE preparation co-migrated in SDS polyacrylamide gel electrophoresis with a major band in the SR preparation. This band was identified as calsequestrin based on its staining characteristics with \"stains-all\". Western blot analysis of skeletal muscle FE with individual myasthenic serum samples revealed various patterns of anti-muscle antibody specificities among patients. Patients with ocular MG produced few anti-muscle antibody specificities, whereas patients with systemic MG produced multiple antibody specificities. There were distinct differences in the antibody specificity patterns among systemic MG patients with thymoma, thymic hyperplasia, and normal thymic pathology. A complete analysis of the spectrum of anti-muscle antibodies produced by myasthenic patients may reveal correlations with clinical disease and provide insight into disease pathogenesis.

With little evidence that failing to complete a prescribed antibiotic course contributes to antibiotic resistance, it’s time for policy makers, educators, and doctors to drop this message, argue Martin Llewelyn and colleagues

Background:Global Health is an emerging field that refers to the health and well-being of the world's population. It is crucial that the next generation of nurses is prepared as global health advocates. There is no prior research of self-assessed global health competencies among nursing faculty in U.S. prelicensure programs. The aim of this study was to determine the level of global health competencies (knowledge and skills) of nursing faculty in U.S. prelicensure programs. Method:Attendees at the National League for Nursing Education Summit completed the Global Health Competencies survey. Results:Survey participants (N = 161) reported a 66.76% confidence in their knowledge of global health and 61.4% confidence in global health skills with patients from different backgrounds. Three areas of educational needs were identified: (a) the relationship between health and access to clean water, sanitation, and nutrition; (b) cultural competency; and (c) understanding the relationship between health and human rights. Conclusion:Nursing faculty participants identified several areas for improvement in their knowledge of global health issues. [J Nurs Educ. 2021;60(1):20–24.]

Cervical cancer can often be prevented through regular screening, but many people in the United States are behind on recommended tests. People who identify as lesbian, gay, bisexual, queer, or another sexual minority are less likely to get screened. Common reasons include discomfort or pain during clinic exams, past trauma, difficulty accessing care, and negative experiences with healthcare providers. This study looked at whether an at-home screening option could help reduce these barriers. Participants used the Teal Wand, a device that allows people to collect their own vaginal sample at home and mail it to a laboratory for HPV testing. The results were compared with samples collected by a healthcare provider during a clinic visit. The study included 609 participants, including 74 people who identified as a sexual minority. The at-home test was just as accurate as samples collected by a clinician. People who identified as a sexual minority were more likely to report pain and discomfort during past clinic exams and were more likely to have delayed or avoided screening in the past. When using the at-home option, sexual minority participants reported feeling more comfortable, more in control, and more empowered than during clinic-based screening. Most found the device easy to use and preferred at-home testing over a traditional exam. Many also said they would be more likely to stay up to date with screening if an at-home option were available. These findings show that at-home cervical cancer screening is a safe, effective, and more comfortable option, especially for people who face barriers to clinic-based care. Expanding access to at-home screening, along with telehealth support, may help reduce long-standing gaps in cervical cancer prevention and improve health outcomes for underserved sexual minority communities.

Introduction Cervical cancer (CxCa) screening rates are lower among women with high BMI in the US, leading to increased prevalence and worse outcomes from cervical dysplasia and cancer in this group. The main barriers to participation in screening relate to the in-clinic speculum exam, which could be overcome with an at-home self-collect (SC) screening device optimized for differing body types. Methods This prospective method comparison study recruited 609 screening-eligible participants aged 25 to 65 years, enrolled from November 20, 2023, to April 5, 2024. SC was performed by the participant in a simulated home environment, using a novel device optimized for differing body sizes. Eligible participants collected a vaginal sample with the SC device, followed immediately by a clinician-collection (CC) sample using a speculum and broom. The sample pairs were shipped to the lab, where the SC sample was eluted into PreservCyt and tested on an FDA-approved high-risk human papillomavirus (hrHPV) test approved for primary screening. Participants completed usability and preference surveys. Endpoints included the detection of hrHPV between SC and CC samples, as well as other study measures, such as clinical sensitivity for high-grade cervical dysplasia, usability, and preferences by BMI category. Five hundred ninety (590/599) participants had data available for this sub-analysis, based on body mass index (height and weight were recorded via self-report). Results and preferences of participants with a higher BMI (≥ 35) are highlighted herein. Results BMI ranged from 16 to 66 for the entire study group, with 114/590 (19.3%) representing a BMI of 35 or greater, comprising the analysis group. The agreement for detection of hrHPV was equivalent across BMI categories. Over a third (36.8%) of participants in Class II (BMI: 35–40) and Class III (BMI > 40) categories had delayed or avoided their cervical cancer screening, and 91% reported that they would be more likely to stay up to date with routine screening if an at-home self-collect option were available. Preferences for self-collect among women in Class II + categories were higher for a self-collect option for screening, reporting that SC made them feel more in control of their experience. Discussion In women with a BMI ≥ 35, cervical cancer screening by SC with this uniquely designed device demonstrated equivalent or superior HPV detection performance and was strongly preferred by participants. Offering this option could improve screening rates in women with BMI ≥ 35, a group that represents a significant portion of the US population who delay screening and help reduce disparities in cervical cancer incidence and outcomes.

ObjectiveDescribe the effects of the COVID-19 pandemic on subject enrollment in a multicenter randomized controlled trial.Study designWe assessed the number of eligible infants approached and consented for enrollment over five separate epochs including baseline, peak pandemic, and gradual but incomplete recovery.ResultThe pandemic had a major effect on ability to approach parents for consent. Parents approached dropped from 95.4% baseline to 13.1% in the peak pandemic epoch and has not recovered to baseline even in the just-completed post-pandemic epoch (84.9%). Despite the decrease in subjects approached, there was no significant change in the overall consent rate for the studyConclusionThe pandemic has significantly limited ability to approach parents of eligible infants for consent, with only partial recovery. Opportunities for interactions of investigators and study coordinators with parents continue to present challenges limiting full recovery.

To identify the main issues of importance when living with long-term conditions to refine a conceptual framework for informing the item development of a patient-reported outcome measure for long-term conditions. Semi-structured qualitative interviews (n=48) were conducted with people living with at least one long-term condition. Participants were recruited through primary care. The interviews were transcribed verbatim and analyzed by thematic analysis. The analysis served to refine the conceptual framework, based on reviews of the literature and stakeholder consultations, for developing candidate items for a new measure for long-term conditions. Three main organizing concepts were identified: impact of long-term conditions, experience of services and support, and self-care. The findings helped to refine a conceptual framework, leading to the development of 23 items that represent issues of importance in long-term conditions. The 23 candidate items formed the first draft of the measure, currently named the Long-Term Conditions Questionnaire. The aim of this study was to refine the conceptual framework and develop items for a patient-reported outcome measure for long-term conditions, including single and multiple morbidities and physical and mental health conditions. Qualitative interviews identified the key themes for assessing outcomes in long-term conditions, and these underpinned the development of the initial draft of the measure. These initial items will undergo cognitive testing to refine the items prior to further validation in a survey.