Understanding Symptom Self-Monitoring Needs Among Postpartum Black Patients: Qualitative Interview Study.

BACKGROUND: Pregnancy-related death is on the rise in the United States, and there are significant disparities in outcomes for Black patients. Most solutions that address pregnancy-related death are hospital based, which rely on patients recognizing symptoms and seeking care from a health system, an area where many Black patients have reported experiencing bias. There is a need for patient-centered solutions that support and encourage postpartum people to seek care for severe symptoms. OBJECTIVE: We aimed to determine the design needs for a mobile health (mHealth) patient-reported outcomes and decision-support system to assist Black patients in assessing when to seek medical care for severe postpartum symptoms. These findings may also support different perinatal populations and minoritized groups in other clinical settings. METHODS: We conducted semistructured interviews with 36 participants-15 (42%) obstetric health professionals, 10 (28%) mental health professionals, and 11 (31%) postpartum Black patients. The interview questions included the following: current practices for symptom monitoring, barriers to and facilitators of effective monitoring, and design requirements for an mHealth system that supports monitoring for severe symptoms. Interviews were audio recorded and transcribed. We analyzed transcripts using directed content analysis and the constant comparative process. We adopted a thematic analysis approach, eliciting themes deductively using conceptual frameworks from health behavior and human information processing, while also allowing new themes to inductively arise from the data. Our team involved multiple coders to promote reliability through a consensus process. RESULTS: Our findings revealed considerations related to relevant symptom inputs for postpartum support, the drivers that may affect symptom processing, and the design needs for symptom self-monitoring and patient decision-support interventions. First, participants viewed both somatic and psychological symptom inputs as important to capture. Second, self-perception; previous experience; sociocultural, financial, environmental, and health systems-level factors were all perceived to impact how patients processed, made decisions about, and acted upon their symptoms. Third, participants provided recommendations for system design that involved allowing for user control and freedom. They also stressed the importance of careful wording of decision-support messages, such that messages that recommend them to seek care convey urgency but do not provoke anxiety. Alternatively, messages that recommend they may not need care should make the patient feel heard and reassured. CONCLUSIONS: Future solutions for postpartum symptom monitoring should include both somatic and psychological symptoms, which may require combining existing measures to elicit symptoms in a nuanced manner. Solutions should allow for varied, safe interactions to suit individual needs. While mHealth or other apps may not be able to address all the social or financial needs of a person, they may at least provide information, so that patients can easily access other supportive resources.

The hierarchical radiation of phyllostomid bats as revealed by adaptive molar morphology.

Adaptive radiations are bursts in biodiversity that generate new evolutionary lineages and phenotypes. However, because they typically occur over millions of years, it is unclear how their macroevolutionary dynamics vary through time and among groups of organisms. Phyllostomid bats radiated extensively for diverse diets-from insects to vertebrates, fruit, nectar, and blood-and we use their molars as a model system to examine the dynamics of adaptive radiations. Three-dimensional shape analyses of lower molars of Noctilionoidea (Phyllostomidae and close relatives) indicate that different diet groups exhibit distinct morphotypes. Comparative analyses further reveal that phyllostomids are a striking example of a hierarchical radiation; phyllostomids' initial, higher-level diversification involved an "early burst" in molar morphological disparity as lineages invaded new diet-affiliated adaptive zones, followed by subsequent lower-level diversifications within adaptive zones involving less dramatic morphological changes. We posit that strong selective pressures related to initial shifts to derived diets may have freed molars from morpho-functional constraints associated with the ancestral molar morphotype. Then, lineages with derived diets (frugivores and nectarivores) diversified within broad adaptive zones, likely reflecting finer-scale niche partitioning. Importantly, the observed early burst pattern is only evident when examining molar traits that are strongly linked to diet, highlighting the value of ecomorphological traits in comparative studies. Our results support the hypothesis that adaptive radiations are commonly hierarchical and involve different tempos and modes at different phylogenetic levels, with early bursts being more common at higher levels.

Perceptions of patient-reported outcome data access and sharing among patients with heart failure: ethical implications for research.

AIMS: In the face of growing expectations for data transparency and patient engagement in care, we evaluated preferences for patient-reported outcome (PRO) data access and sharing among patients with heart failure (HF) using an ethical framework. METHODS AND RESULTS: We conducted qualitative interviews with a purposive sample of patients with HF who participated in a larger 8-week study that involved the collection and return of PROs using a web-based interface. Guided by an ethical framework, patients were asked questions about their preferences for having PRO data returned to them and shared with other groups. Interview transcripts were coded by three study team members using directed content analysis. A total of 22 participants participated in semi-structured interviews. Participants were mostly male (73%), White (68%) with a mean age of 72. Themes were grouped into priorities, benefits, and barriers to data access and sharing. Priorities included ensuring anonymity when data are shared, transparency with intentions of data use, and having access to all collected data. Benefits included: using data as a communication prompt to discuss health with clinicians and using data to support self-management. Barriers included: challenges with interpreting returned results, and potential loss of benefits and anonymity when sharing data. CONCLUSION: Our interviews with HF patients highlight opportunities for researchers to return and share data through an ethical lens, by ensuring privacy and transparency with intentions of data use, returning collected data in comprehensible formats, and meeting individual expectations for data sharing.

Using Patient Decision Aids for Cardiology Care in Diverse Populations.

PURPOSE OF REVIEW: Patient decision aids (PDAs) are tools that help guide treatment decisions and support shared decision-making when there is equipoise between treatment options. This review focuses on decision aids that are available to support cardiac treatment options for underrepresented groups. RECENT FINDINGS: PDAs have been developed to support multiple treatment decisions in cardiology related to coronary artery disease, valvular heart disease, cardiac arrhythmias, heart failure, and cholesterol management. By considering the unique needs and preferences of diverse populations, PDAs can enhance patient engagement and promote equitable healthcare delivery in cardiology. In this review, we examine the benefits, challenges, and current trends in implementing PDAs, with a focus on improving decision-making processes and outcomes for patients from underrepresented racial and ethnic groups. In addition, the article highlights key considerations when implementing PDAs and potential future directions in the field.

Returning study results to research participants: Data access, format, and sharing preferences.

INTRODUCTION: Research participants have a growing expectation for transparency with their collected information; however, there is little guidance on participant preferences for receiving health information and how researchers should return this information to participants. METHODS: We conducted a cross-sectional online survey with a representative sample of 502 participants in the United States. Participants were asked about their preferences for receiving, sharing, and the formatting of health information collected for research purposes. RESULTS: Most participants wanted their health information returned (84 %) to use it for their own knowledge and to manage their own health. Email was the most preferred format for receiving health data (67 %), followed by online website (44 %), and/or paper copy (32 %). Data format preferences varied by age, education, financial resources, subjective numeracy, and health literacy. Around one third of Generation Z (25 %), Millennials (30 %), and Generation X (29 %) participants preferred to receive their health information with a mobile app. In contrast, very few Baby Boomers (12 %) and none from the Silent Generation preferred the mobile app format. Having a paper copy of the data was preferred by 38 % of participants without a college degree compared to those with a college degree. Preferences were highest for sharing all health information with doctors and nurses (77 %), and some information with friends and family (66 %). CONCLUSION: Study findings support returning research information to participants in multiple formats, including email, online websites, and paper copy. Preferences for whom to share information with varied by stakeholders and by sociodemographic characteristics. Researchers should offer multiple formats to participants and tailor data sharing options to participants' preferences. Future research should further explore combinations of individual characteristics that may further influence data sharing and format preferences.

Health professional students at the University of Illinois Chicago (HOLISTIC) Cohort Study: A protocol.

OBJECTIVES: The objectives of the HOLISTIC Cohort Study are to establish a prospective cohort study covering a period of three years that characterizes the health of students within and across health professional education programs at the University of Illinois Chicago (UIC) during the coronavirus disease 2019 (COVID-19) pandemic, implement an interprofessional student research team, and generate a meaningful dataset that is used to inform initiatives that improve student health. This report describes the protocol of the HOLISTIC Cohort Study, including survey development, recruitment strategy, and data management and analysis. METHODS: An interprofessional student research team has been organized with the goal of providing continuous assessment of study design and implementation across the seven health science colleges (applied health sciences, dentistry, medicine, nursing, pharmacy, public health, and social work) at the University of Illinois Chicago in Chicago, IL. To be eligible to participate in the HOLISTIC Cohort Study, students are required to be 1) age 18 years or older; 2) enrolled full- or part-time in one or more of UIC's seven health science colleges; and 3) enrolled in a program that prepares its graduates to enter a healthcare profession. The study protocol includes a series of three recruitment waves (Spring 2021 [April 14, 2021, to May 5, 2021; completed], Spring 2022, Spring 2023). In the first recruitment wave, eligible students were sent an invitation via electronic mail (e-mail) to complete an online survey. The online survey was based on the U.S. Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System 2019 survey and the 2014 World Health Organization Report of the Strategic Advisory Group of Experts Working Group Vaccine Hesitancy Scale. Electronic informed consent and study data are collected and managed using Research Electronic Data Capture (REDCap) tools. This study utilizes convenience sampling from all seven health science colleges at UIC with a target recruitment total of 2,000 participants. DISCUSSION AND FUTURE DIRECTIONS: A total of 555 students across all seven health science colleges (10.8% of 5,118 students who were invited; 27.6% of target sample size) enrolled in the cohort during the first recruitment wave. The pilot data establishes the feasibility of the study during the COVID-19 pandemic. Adaptations to overcome barriers to study implementation, including the use of remote, rather than in-person, study meetings, staff training, and participant recruitment are discussed. For the second and third waves of recruitment, the student research team will seek institutional review board (IRB) approval to implement additional enrollment strategies that are tailored to each health science college, such as online newsletters, virtual townhalls, flyers on bulletin boards near classrooms tailored to each health science college.

Building trust in research through information and intent transparency with health information: representative cross-sectional survey of 502 US adults.

OBJECTIVE: Participation in healthcare research shapes health policy and practice; however, low trust is a barrier to participation. We evaluated whether returning health information (information transparency) and disclosing intent of data use (intent transparency) impacts trust in research. MATERIALS AND METHODS: We conducted an online survey with a representative sample of 502 US adults. We assessed baseline trust and change in trust using 6 use cases representing the Social-Ecological Model. We assessed descriptive statistics and associations between trust and sociodemographic variables using logistic and multinomial regression. RESULTS: Most participants (84%) want their health research information returned. Black/African American participants were more likely to increase trust in research with individual information transparency (odds ratio (OR) 2.06 [95% confidence interval (CI): 1.06-4.34]) and with intent transparency when sharing with chosen friends and family (3.66 [1.98-6.77]), doctors and nurses (1.96 [1.10-3.65]), or health tech companies (1.87 [1.02-3.40]). Asian, Native American or Alaska Native, Native Hawaiian or Pacific Islander, Multirace, and individuals with a race not listed, were more likely to increase trust when sharing with health policy makers (1.88 [1.09-3.30]). Women were less likely to increase trust when sharing with friends and family (0.55 [0.35-0.87]) or health tech companies (0.46 [0.31-0.70]). DISCUSSION: Participants wanted their health information returned and would increase their trust in research with transparency when sharing health information. CONCLUSION: Trust in research is influenced by interrelated factors. Future research should recruit diverse samples with lower baseline trust levels to explore changes in trust, with variation on the type of information shared.

Hyper-phosphorylation of Rb S249 together with CDK5R2/p39 overexpression are associated with impaired cell adhesion and epithelial-to-mesenchymal transition: Implications as a potential lung cancer grading and staging biomarker.

Prediction of lung cancer metastasis relies on post-resection assessment of tumor histology, which is a severe limitation since only a minority of lung cancer patients are diagnosed with resectable disease. Therefore, characterization of metastasis-predicting biomarkers in pre-resection small biopsy specimens is urgently needed. Here we report a biomarker consisting of the phosphorylation of the retinoblastoma protein (Rb) on serine 249 combined with elevated p39 expression. This biomarker correlates with epithelial-to-mesenchymal transition traits in non-small cell lung carcinoma (NSCLC) cells. Immunohistochemistry staining of NSCLC tumor microarrays showed that strong phospho-Rb S249 staining positively correlated with tumor grade specifically in the squamous cell carcinoma (SCC) subtype. Strong immunoreactivity for p39 positively correlated with tumor stage, lymph node invasion, and distant metastases, also in SCC. Linear regression analyses showed that the combined scoring for phospho-Rb S249, p39 and E-cadherin in SCC is even more accurate at predicting tumor staging, relative to each score individually. We propose that combined immunohistochemistry staining of NSCLC samples for Rb phosphorylation on S249, p39, and E-cadherin protein expression could aid in the assessment of tumor staging and metastatic potential when tested in small primary tumor biopsies. The intense staining for phospho-Rb S249 that we observed in high grade SCC could also aid in the precise sub-classification of poorly differentiated SCCs.

Cigarette Smoke Disrupted Lung Endothelial Barrier Integrity and Increased Susceptibility to Acute Lung Injury via Histone Deacetylase 6.

Epidemiologic evidence indicates that cigarette smoke (CS) is associated with the development of acute lung injury (ALI). We have previously shown that brief CS exposure exacerbates lipopolysaccharide (LPS)-induced ALI in vivo and endothelial barrier dysfunction in vitro. In this study, we found that CS also exacerbated Pseudomonas-induced ALI in mice. We demonstrated that lung microvascular endothelial cells (ECs) isolated from mice exposed to CS had a greater permeability or incomplete recovery after challenges by LPS and thrombin. Histone deacetylase (HDAC) 6 deacetylates proteins essential for maintenance of endothelial barrier function. We found that HDAC6 phosphorylation at serine-22 was increased in lung tissues of mice exposed to CS and in lung ECs exposed to cigarette smoke extract (CSE). Inhibition of HDAC6 attenuated CSE-induced increases in EC permeability and CS priming of ALI. Similar barrier protection was provided by the microtubule stabilizer taxol, which preserved α-tubulin acetylation. CSE decreased α-tubulin acetylation and caused microtubule depolymerization. In coordination with increased HDAC6 phosphorylation, CSE inhibited Akt and activated glycogen synthase kinase (GSK)-3ß; these effects were ameliorated by the antioxidant N-acetyl cysteine. Our results suggest that CS increases lung EC permeability, thereby enhancing susceptibility to ALI, likely through oxidative stress-induced Akt inactivation and subsequent GSK-3ß activation. Activated GSK-3ß may activate HDAC6 via phosphorylation of serine-22, leading to α-tubulin deacetylation and microtubule disassembly. Inhibition of HDAC6 may be a novel therapeutic option for ALI in cigarette smokers.

Patient-Centered Care Transition for Patients Admitted through the ED: Improving Patient and Employee Experience.

With increasing wait times in emergency departments (ED) across America, there is a need to streamline the inpatient admission process in order to decrease wait times and more important, to increase patient and employee satisfaction. One inpatient unit at New York-Presbyterian Weill Cornell Medical Center initiated a program to help expedite the inpatient admission process from the ED. The goal of the ED Bridge program is to ease the patient's transition from the ED to an inpatient unit by visiting the patient in the ED and introducing and setting expectations for the inpatient environment (i.e. telemetry alarms, roommates, hourly comfort rounds). Along with improving the patient experience, this program intends to improve the collaboration between ED nurses and inpatient nurses. With the continued support of our nurse management, hospital administrators and most important, our staff, this concept is aimed to increase patient satisfaction scores and subsequently employee satisfaction.

Mitochondrial reactive oxygen species regulate transforming growth factor-ß signaling.

TGF-ß signaling is required for normal tissue repair; however, excessive TGF-ß signaling can lead to robust profibrotic gene expression in fibroblasts, resulting in tissue fibrosis. TGF-ß binds to cell-surface receptors, resulting in the phosphorylation of the Smad family of transcription factors to initiate gene expression. TGF-ß also initiates Smad-independent pathways, which augment gene expression. Here, we report that mitochondrial reactive oxygen species (ROS) generated at complex III are required for TGF-ß-induced gene expression in primary normal human lung fibroblasts. TGF-ß-induced ROS could be detected in both the mitochondrial matrix and cytosol. Mitochondrially targeted antioxidants markedly attenuated TGF-ß-induced gene expression without affecting Smad phosphorylation or nuclear translocation. Genetically disrupting mitochondrial complex III-generated ROS production attenuated TGF-ß-induced profibrotic gene expression. Furthermore, inhibiting mitochondrial ROS generation attenuated NOX4 (NADPH oxidase 4) expression, which is required for TGF-ß induced myofibroblast differentiation. Lung fibroblasts from patients with pulmonary fibrosis generated more mitochondrial ROS than normal human lung fibroblasts, and mitochondrially targeted antioxidants attenuated profibrotic gene expression in both normal and fibrotic lung fibroblasts. Collectively, our results indicate that mitochondrial ROS are essential for normal TGF-ß-mediated gene expression and that targeting mitochondrial ROS might be beneficial in diseases associated with excessive fibrosis.

Cigarette smoke-induced oxidative stress in skeletal muscles of mice.

Cigarette smoke (CS)-induced oxidative stress may cause muscle alterations in chronic conditions such as chronic obstructive pulmonary disease (COPD). We sought to explore in AKR/J mice exposed to CS for 6 months and in control animals, levels of protein oxidation, oxidized proteins (immunoblotting, proteomics) and antioxidant mechanisms in both respiratory and limb muscles, body weight modifications, systemic inflammation, and lung structure. Compared to control mice, CS-exposed animals exhibited a reduction in body weight gain at 3 months and thereafter, showed lung emphysema, and exhibited increased oxidative stress levels in their diaphragms and gastrocnemius at 6 months. Proteins involved in glycolysis, ATP production and distribution, carbon dioxide hydration, and muscle contraction were carbonylated in respiratory and limb muscles. Blood tumor necrosis factor (TNF)-alpha levels were significantly greater in CS-exposed mice than in control animals. In AKR/J mice, chronic exposure to CS induces lung emphysema concomitantly with greater oxidative modifications on muscle proteins in both respiratory and limb muscles, and systemic inflammation.

Critical issues in delivery of RNAi therapeutics in vivo.

RNA interference (RNAi) is a fundamental mechanism of gene regulation and has been harnessed to produce a new class of drugs for treatment of various diseases. A key issue in these applications is how to effectively deliver RNAi therapeutics into target cells. This review is focused on advances in RNA delivery in vivo. To achieve it, novel strategies have been developed to enhance stability of RNA in cells and tissues, overcome barriers to transport of RNA or its carriers in the body, and reduce immunogenicity and cytotoxicity of treatment. Approaches to RNA delivery are divided into three categories in this review: biological, chemical, and physical. Advantages and disadvantages of each method are discussed. At present, effective delivery of RNAi therapeutics in vivo is still a challenge although significant advances have been made in this field.

Proteasomal inhibition after injury prevents fibrosis by modulating TGF-ß(1) signalling.

BACKGROUND: The development of organ fibrosis after injury requires activation of transforming growth factor ß(1) which regulates the transcription of profibrotic genes. The systemic administration of a proteasomal inhibitor has been reported to prevent the development of fibrosis in the liver, kidney and bone marrow. It is hypothesised that proteasomal inhibition would prevent lung and skin fibrosis after injury by inhibiting TGF-ß(1)-mediated transcription. METHODS: Bortezomib, a small molecule proteasome inhibitor in widespread clinical use, was administered to mice beginning 7 days after the intratracheal or intradermal administration of bleomycin and lung and skin fibrosis was measured after 21 or 40 days, respectively. To examine the mechanism of this protection, bortezomib was administered to primary normal lung fibroblasts and primary lung and skin fibroblasts obtained from patients with idiopathic pulmonary fibrosis and scleroderma, respectively. RESULTS: Bortezomib promoted normal repair and prevented lung and skin fibrosis when administered beginning 7 days after the initiation of bleomycin. In primary human lung fibroblasts from normal individuals and patients with idiopathic pulmonary fibrosis and in skin fibroblasts from a patient with scleroderma, bortezomib inhibited TGF-ß(1)-mediated target gene expression by inhibiting transcription induced by activated Smads. An increase in the abundance and activity of the nuclear hormone receptor PPARγ, a repressor of Smad-mediated transcription, contributed to this response. CONCLUSIONS: Proteasomal inhibition prevents lung and skin fibrosis after injury in part by increasing the abundance and activity of PPARγ. Proteasomal inhibition may offer a novel therapeutic alternative in patients with dysregulated tissue repair and fibrosis.

Leptin promotes fibroproliferative acute respiratory distress syndrome by inhibiting peroxisome proliferator-activated receptor-γ.

RATIONALE: Diabetic patients have a lower incidence of acute respiratory distress syndrome (ARDS), and those who develop ARDS are less likely to die. The mechanisms that underlie this protection are unknown. OBJECTIVES: To determine whether leptin resistance, a feature of diabetes, prevents fibroproliferation after lung injury. METHODS: We examined lung injury and fibroproliferation after the intratracheal instillation of bleomycin in wild-type and leptin-resistant (db/db) diabetic mice. We examined the effect of leptin on transforming growth factor (TGF)-ß(1)-mediated transcription in primary normal human lung fibroblasts. Bronchoalveolar lavage fluid (BAL) samples from patients with ARDS and ventilated control subjects were obtained for measurement of leptin and active TGF-ß(1) levels. MEASUREMENTS AND MAIN RESULTS: Diabetic mice (db/db) were resistant to lung fibrosis. The db/db mice had higher levels of peroxisome proliferator-activated receptor-γ (PPARγ), an inhibitor of the transcriptional response to TGF-ß(1), a cytokine critical in the pathogenesis of fibroproliferative ARDS. In normal human lung fibroblasts, leptin augmented the transcription of profibrotic genes in response to TGF-ß(1) through a mechanism that required PPARγ. In patients with ARDS, BAL leptin levels were elevated and correlated with TGF-ß(1) levels. Overall, there was no significant relationship between BAL leptin levels and clinical outcomes; however, in nonobese patients, higher BAL leptin levels were associated with fewer intensive care unit- and ventilator-free days and higher mortality. CONCLUSIONS: Leptin signaling is required for bleomycin-induced lung fibrosis. Leptin augments TGF-ß(1) signaling in lung fibroblasts by inhibiting PPARγ. These findings provide a mechanism for the observed protection against ARDS observed in diabetic patients.