Heat stress in plants: sensing, signalling and ferroptosis.

In the current context of global warming, high temperature events are becoming more frequent and intense in many places around the world. In this context, understanding how plants sense and respond to heat is essential to develop new tools to prevent plant damage and address global food security, as high temperature events are threatening agricultural sustainability. This review summarizes and integrates our current understanding underlying the cellular, physiological, biochemical and molecular regulatory pathways triggered in plants under moderately high and extremely high temperature conditions. Given that extremely high temperatures can also trigger ferroptosis, the study of this cell death mechanism constitutes a strategic approach to understand how plants might overcome otherwise lethal temperature events.

[Videoconference Fatigue Coping Strategies]. / Bewältigungsstrategien von Videoconference Fatigue.

The COVID-19 pandemic has changed people's professional and private lives globally and has led to an increasing use of digital technologies, especially video conferencing systems (e.g. Zoom, Webex, Teams, Skype). Despite the possible advantages of these systems (e.g. savings in emissions by avoiding travelling), a negative phenomenon has been reported in science and practice: Videoconference Fatigue (VCF) (often synonymously referred to as Zoom Fatigue). This term describes the exhaustion and fatigue that results from the use of videoconferencing systems. In this article we report on an analysis of the academic literature, the aim of which is to document the current state of research on coping strategies. The analysis of coping strategies helps to better understand the phenomenon of VCF and to prevent or reduce fatigue and exhaustion. Furthermore, the results reported here are a basis for future work. Specifically, as of May 2022, we have identified 48 scientific articles on VCF, 37 of which also deal with coping strategies. We divide these strategies into organizational (e.g. taking breaks during and between meetings), personal (e.g. avoiding multitasking) and technological (e.g. use of the "together mode" in Teams). An important finding of our analysis is that with the exception of one paper, the effectiveness of the coping strategies has not yet been empirically examined and thus proven. This opens up enormous future research potential.

Ferroptosis in plants: regulation of lipid peroxidation and redox status.

Regulated cell death (RCD) is an essential process that plays key roles along the plant life cycle. Unlike accidental cell death, which is an uncontrolled biological process, RCD involves integrated signaling cascades and precise molecular-mediated mechanisms that are triggered in response to specific exogenous or endogenous stimuli. Ferroptosis is a cell death pathway characterized by the iron-dependent accumulation of lipid reactive oxygen species. Although first described in animals, ferroptosis in plants shares all the main core mechanisms observed for ferroptosis in other systems. In plants as in animals, oxidant and antioxidant systems outline the process of lipid peroxidation during ferroptosis. In plants, cellular compartments such as mitochondria, chloroplasts and cytosol act cooperatively and coordinately to respond to changing redox environments. This particular context makes plants a unique model to study redox status regulation and cell death. In this review, we focus on our most recent understanding of the regulation of redox state and lipid peroxidation in plants and their role during ferroptosis.

National Physician Survey for Nonvalvular Atrial Fibrillation (NVAF) Anticoagulation Comparing Knowledge, Attitudes and Practice of Cardiologist to PCPs.

INTRODUCTION: NVAF is estimated to affect between 6.4 and 7.4 million Americans in 2018, and increases the risk of stroke 5-fold. To mitigate this risk, guidelines recommend anticoagulating AF patients unless their stroke risk is very low. Despite these recommendations, 30.0-60.0% of NVAF patients do not receive indicated anticoagulation. To better understand why this may be, we surveyed PCPs and cardiologists nationwide on their attitudes, knowledge and practices toward managing NVAF with warfarin and direct-acting oral anticoagulants (DOACs). METHODS: We surveyed 1,000 PCPs and 500 cardiologists selected randomly from a master list of the American Medical Association, using a paper based, anonymous, self-administered, mailed scannable survey. The survey contained questions on key demographics and data concerning attitudes, knowledge and practices related to prescribing DOACs. The surveys went out in the fall/winter of 2017-8 with a $10 incentive gift card. Survey responses were scanned into an Excel database and analyzed using SAS 9.3 (Cary, NC) for descriptive and inferential statistics. RESULTS: Two hundred and forty-nine providers (167 PCPs, 82 cardiologists) participated in the study with a response rate of 18.8% (249/1320). Respondent mean years ±SD of experience since completing residency was 23.2 ± 13.8. Relative to cardiologists, less PCPs use CHADsVASC (36.8% vs. 74.4%) (p < 0.0001); more have never used HAS-BLED, HEMORR2HAGES, or ATRIA (38.5% vs. 9.8%) (p < .0001); more felt that their lack of knowledge/experience with DOACs was a barrier to prescribing the agents (p = 0.005); and more reported that they could use additional education on DOACs (87.0% vs. 47.0%) (p < 0.0001). Overall, cardiologists were more concerned about ischemic stroke outcomes, while PCPs were more concerned with GI bleeding. Cardiologists also felt that clinical trial data were most helpful in choosing the most appropriate DOAC for their patients, while PCPs felt that Real World Data was most useful. CONCLUSIONS: Cardiologists were more concerned with ischemic stroke while anticoagulating patients and utilized screening instruments like CHADsVASC in a majority of their patients. PCPs were concerned with GI bleeds when anticoagulating but nearly 40.0% utilized no screening tools to assess bleeding risk. Our findings show that future education about DOACs would be warranted especially with PCPs.

Development and validation of an asthma exacerbation prediction model using electronic health record (EHR) data.

Objective: Asthma exacerbations are associated with significant morbidity, mortality, and cost. Accurately identifying asthma patients at risk for exacerbation is essential. We sought to develop a risk prediction tool based on routinely collected data from electronic health records (EHRs).Methods: From a repository of EHRs data, we extracted structured data for gender, race, ethnicity, smoking status, use of asthma medications, environmental allergy testing BMI status, and Asthma Control Test scores (ACT). A subgroup of this population of patients with asthma that had available prescription fill data was identified, which formed the primary population for analysis. Asthma exacerbation was defined as asthma-related hospitalization, urgent/emergent visit or oral steroid use over a 12-month period. Univariable and multivariable statistical analysis was completed to identify factors associated with exacerbation. We developed and tested a risk prediction model based on the multivariable analysis.Results: We identified 37,675 patients with asthma. Of those, 1,787 patients with asthma and fill data were identified, and 979 (54.8%) of them experienced an exacerbation. In the multivariable analysis, smoking (OR = 1.69, CI: 1.08-2.64), allergy testing (OR = 2.40, CI: 1.54-3.73), obesity (OR = 1.66, CI: 1.29-2.12), and ACT score reflecting uncontrolled asthma (OR = 1.66, CI: 1.10-2.29) were associated with increased risk of exacerbation. The area-under-the-curve (AUC) of our model in a combined derivation and validation cohort was 0.67.Conclusion: Despite use of rigorous methodology, we were unable to produce a predictive model with an acceptable degree of accuracy and AUC to be clinically useful.

Identifying, Analyzing, and Visualizing Diagnostic Paths for Patients with Nonspecific Abdominal Pain.

BACKGROUND: Diagnosis is complex, uncertain, and error-prone. Symptoms such as nonspecific abdominal pain are especially challenging. A diagnostic path consists of diagnostic steps taken from initial presentation until a diagnosis is obtained or the evaluation ends for other reasons. Analysis of diagnostic paths can reveal patterns associated with more timely and accurate diagnosis. Visual analytics can be used to enhance both analysis and comprehension of diagnostic paths. OBJECTIVE: This article applies process-mining methods to extract and visualize diagnostic paths from electronic health records (EHRs). METHODS: Patient features, actions taken (i.e., tests, referrals, etc.), and diagnoses obtained for 501 adult patients (half female, half ≥50 years of age) presenting with abdominal pain were extracted from an EHR database to construct diagnostic paths from a hospital system in suburban Chicago, Illinois, United States. A stable diagnosis was defined as the same diagnosis recorded twice in a 12-month period; a working diagnosis was recorded only once. Three different types of path visualizations were obtained. RESULTS: A stable diagnosis was obtained in 63 (13%) patients after 12 months. In 271 (54%) patients, a working diagnosis was obtained. Mean path duration was 145.3 days (standard deviation, 195.1 days). These 63 patients received 75 stable diagnoses. CONCLUSION: Structured EHR data can be used to construct diagnostic paths to gain insight into diagnostic practices for complaints such as abdominal pain.

Identifying Diagnostic Paths for Undifferentiated Abdominal Pain from Electronic Health Record Data.

The diagnostic process is a complex, uncertain, and highly variable process which is under-studied and lacks evidence from randomized clinical trials. This study used a novel visual analytics method to identify and visualize diagnostic paths for undifferentiated abdominal pain, by leveraging electronic health record (EHR) data of 501 patients in the ambulatory setting of a single institution. A total of 63 patients reached diagnoses in the study sample. We illustrate steps in identifying diagnostic paths of the study patients, both individually and collectively, and visually present the diversity in their diagnostic processes. Patients in whom diagnoses were obtained generally had more clinical encounters and health services utilization, although their diagnostic paths were more variable than those of the undiagnosed group. The capability of identifying diagnostic paths demonstrated from this study allows us to study larger data sets to determine diagnostic paths associated with more timely, accurate, and cost-efficient diagnosis processes.

Text Messaging to Improve Disease Management in Patients With Painful Diabetic Peripheral Neuropathy.

Purpose The purpose of the study was to determine the impact of educational text messages on diabetes self-management activities and outcomes in patients with painful diabetic peripheral neuropathy (pDPN). Methods Patients with pDPN identified from a large integrated health system who agreed to participate were randomized to 6 months of usual care (UC) or UC plus twice-daily diabetes self-management text messages (UC+TxtM). Outcomes included the Pain Numerical Rating Scale, Summary of Diabetes Self-Care Activities (SDSCA), questions on diabetes health beliefs, and glycated hemoglobin (A1C). Changes from baseline were evaluated at 6 months and compared between groups. Results Demographic characteristics were balanced between groups (N = 62; 53% female, mean age = 63 years, 94% type 2 diabetes), as were baseline measures. After 6 months, pain decreased with UC+TxtM from 6.3 to 5.5 and with UC from 6.5 to 6.0, with no difference between groups. UC+TxtM but not UC was associated with significant improvements from baseline on all SDSCA subscales. On diabetes health beliefs, UC+TxtM patients reported significantly increased benefits and reduced barriers and susceptibility relative to UC at 6 months. A1C declined in both groups, but neither change was significant relative to baseline. Conclusions Patients with pDPN who receive twice-daily text messages regarding diabetes management reported reduced pain relative to baseline, although this change was not significant compared with usual care. In addition, text messaging was associated with increased self-management activities and improved diabetes health beliefs and total self-care. These results warrant further investigation.

Pediatric Hypertension: Provider Perspectives.

Pediatric hypertension is a risk for adult cardiovascular disease, making early detection important. The prevalence of pediatric essential hypertension is rising due to the increased prevalence of obesity. Though guidelines for screening, diagnosis, evaluation, and management are available, there are barriers to accurate diagnosis of pediatric hypertension, including lack of knowledge and complexity of blood pressure standards. We aimed to gain insights into reasons for low rates of diagnosis and treatment from primary care providers. As part of a multisite randomized controlled trial, we interviewed 8 providers in a community health center network. We used a grounded theoretical approach to analyze transcripts. Providers reflected on numerous barriers to diagnosis, management, and follow-up; recommendations for educational content; and how community health center systems can be improved. Findings informed development of a multifaceted intervention. Despite lack of training on essential hypertension, providers were comfortable recommending lifestyle changes to promote healthier weight and reduced blood pressure.

Identifying and analyzing diagnostic paths: a new approach for studying diagnostic practices.

Diagnostic error is a serious public health problem to which knowledge gaps and associated cognitive error contribute significantly. Identifying diagnostic approaches to common problems in ambulatory care associated with more timely and accurate diagnosis and lower cost and harm associated with diagnostic evaluation is an important priority for health care systems, clinicians, and of course patients. Unfortunately, guidance on how best to approach diagnosis in patients with common presenting complaints such as abdominal pain, dizziness, and fatigue is lacking. Exploring diagnostic practice variation and patterns of diagnostic evaluation is a potentially valuable approach to identifying best current diagnostic practices. A "diagnostic path" is the sequence of actions taken to evaluate a new complaint from first presentation until a diagnosis is established, or the evaluation ends for other reasons. A "big data" approach to identifying diagnostic paths from electronic health records can be used to identify practice variation and best practices from a large number of patients. Limitations of this approach include incompleteness and inaccuracy of electronic medical record data, the fact that diagnostic paths may not represent clinician thinking, and the fact that diagnostic paths may be used to identify best current practices, rather than optimal practices.

The Role Of NOACs in Atrial Fibrillation Management: A Qualitative Study.

Patients with atrial fibrillation (AF) benefit from anticoagulation to reduce stroke risk. However, 30-60% of patients with AF are not anticoagulated. This study explored physicians' reasons for under-treatment of AF, focusing on the role of the novel oral anticoagulants (NOACs). We interviewed primary care physicians and cardiologists involved in AF management in a variety of practice settings. We conducted interviews using a semi-structured format and analyzed the data using the Framework Method. Four themes emerged. First, the likelihood of physicians to prescribe NOACs depends upon their willingness to try new medications and their successful experience with them. Second, physicians typically balance the benefits and risks of anticoagulation in AF patients, although not always accurately. Third, patient convenience and preferences, as well as physician convenience, are important when considering anticoagulation. Finally, concerns regarding the out-of-pocket cost of NOACs deter many physicians from prescribing them. The persistence of under-treatment in AF despite the availability of effective therapies suggests that new strategies are needed to improve physician knowledge and practice. These strategies should enhance physician awareness of AF under-treatment, emphasize accurate assessment of bleeding risk among AF patients, compare the safety, efficacy, and convenience of NOACs relative to warfarin, and address physician concerns regarding the out-of-pocket cost of NOACs. Guidelines and decision supports which promote physician knowledge in these areas have the potential to increase oral anticoagulant use and reduce preventable morbidity and mortality.

Ingested (oral) tocilizumab inhibits EAE.

BACKGROUND: Blocking the activity of IL-6 can inhibit autoimmune diseases such as rheumatoid arthritis and Crohn's disease. OBJECTIVE: We examined whether an antibody against IL-6, tocilizumab (TCZ) (Actemra®), used clinically in rheumatoid arthritis (RA) would have similar anti-inflammatory effects in EAE after oral administration. DESIGN/METHOD: B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or TCZ during ongoing disease. Splenocytes, CD4(+) T cells or macrophages/monocyte lineage cells (CD11b(+)) from control fed or TCZ fed mice were adoptively transferred into active MOG peptide 35-55 immunized recipient mice during ongoing disease. Actively fed and recipient mice were examined for disease inhibition, inflammation, and cytokine responses. RESULTS: Ingested (oral) TCZ inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from TCZ fed donors protected against actively induced disease and decreased inflammation. There was a decrease in IL-6 in actively treated spleen, decrease in TNF-α, Th1-like cytokine IL-12 and increase in Th2-like cytokine IL-10 in active fed and adoptively treated recipients. CONCLUSIONS: Ingested (orally administered) TCZ can inhibit disease, CNS inflammation, decrease pro-inflammatory Th1-like cytokines and increase Th2-like anti-inflammatory cytokines.

Ingested (oral) thyrotropin releasing factor (TRH) inhibits EAE.

BACKGROUND: Ingested immunoactive proteins type I IFN, SIRS peptide 1-21, α-MSH, ACTH, SST inhibit clinical attacks and inflammation in acute EAE by decreasing Th1-like cytokines, increasing Th2-like cytokines or increasing T(reg) cell frequencies. OBJECTIVE: We examined whether another protein, thyrotropin releasing factor (TRH), would have similar anti-inflammatory effects in EAE after oral administration. DESIGN/METHODS: B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or TRH during ongoing disease. Splenocytes from mock fed or TRH fed mice were adoptively transferred into active MOG peptide 35-55 immunized recipient mice during ongoing disease. RESULTS: Ingested (oral) TRH inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from TRH fed donors protected against actively induced disease and decreased inflammation. In actively fed mice, oral TRH decreased IL-17 and TNF-α cytokines in both the spleen and the CNS. In recipients of donor cells from TRH fed mice there was a reduction of Th1 and Th17 and induction of Th2-like IL-13 cytokines in both the spleen and CNS. Oral TRH decreased clinical score and decreased inflammatory foci in both actively fed and recipients of actively fed mice. There was no significant increase in T(reg) cell frequencies in actively fed or recipients of TRH fed donor cells. CONCLUSIONS: Ingested (orally administered) TRH can inhibit clinical disease, inhibit CNS inflammation by decreasing Th1-like, Th17 and TNF-α cytokines and increasing Th2-like cytokines (IL-13) in the CNS.

Ingested (oral) neuropeptide Y inhibits EAE.

BACKGROUND: Ingested immunoactive proteins, type I IFN, SIRS peptide 1-21, α-MSH, ACTH, and SST inhibit clinical attacks and inflammation in acute EAE by decreasing Th1-like cytokines, increasing Th2-like cytokines or increasing T(reg) cell frequencies. OBJECTIVE: We examined whether another protein, neuropeptide Y, would have similar anti-inflammatory effects in EAE after oral administration. DESIGN/METHODS: B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or NPY during ongoing disease. Splenocytes from mock fed or NPY fed mice were adoptively transferred into active MOG peptide 35-55 immunized recipient mice during ongoing disease. RESULTS: Ingested (oral) NPY inhibited ongoing disease, and decreased inflammation. Adoptively transferred cells from NPY fed donors protected against actively induced disease and decreased inflammation. In actively fed mice, oral NPY decreased Th1-like cytokines and increased Th2-like IL-13 cytokines in both the spleen and the CNS. In recipients of donor cells from NPY fed mice there was a reduction of Th1 and Th17 and induction of Th2-like IL-13 cytokines in both the spleen and CNS. Oral NPY decreased clinical score and decreased inflammatory foci in both actively fed and recipients of actively fed mice. There was no significant increase in T(reg) cell frequencies in actively fed or recipients of NPY fed donor cells. CONCLUSIONS: Ingested (orally administered) NPY can inhibit clinical disease, inhibit CNS inflammation by decreasing Th17 and Th1-like cytokines and increasing Th2-like cytokines in the CNS.

Oral ACTH (H.P. Acthar(®)Gel) inhibits IL-1 and IL-17 secretion in humans.

OBJECTIVE: We have shown that oral corticotropin hormone (ACTH) decreased clinical score, inflammatory foci and T(eff) IL-17 in fed and adoptive transferred recipient mice with experimental autoimmune encephalomyelitis (EAE). Therefore, we determined whether oral administration of ACTH had immunological and endocrinological effects and was safe in humans. METHODS: Three groups of three healthy adult volunteers were assayed for total serum ACTH, cortisol and a set of pro-inflammatory and counter-regulatory cytokines after ingested dose(s) of ACTH 4 IU (n=3), 41 IU (n=3), or 123 IU (n=3) over 5 days. RESULTS: There were no safety issues during the trial. There was no increase in total ACTH levels after day 1 or day 5. There was no significant increase in total cortisol among the groups comparing day 1 to day 5. There were significant decreases in the inflammatory cytokine IL-1 and IL-17 secretion at day 6 compared to baseline with the 123 IU dose but not after the 4 IU and 41 IU doses. CONCLUSIONS: These data provide evidence for the safety and an immunological effect of oral ACTH in humans. It is unknown if the change in IL-1 and IL-17 reflects a local GI-mediated effect or effects following systemic absorption of ACTH.

A comparative analysis of effects of early versus late prenatal WIC participation on birth weight: NYS, 1995.

OBJECTIVES: This study examined the effects of prenatal participation in the NYS WIC Program on birth weight through enhanced control of selection bias and gestational age bias. Program effects were assessed separately for White, Black, and Hispanic women and subpopulations defined by values of Kotelchuck index of adequacy of prenatal care utilization. METHODS: 1995 New York State Vital Statistics records were linked to WIC certifications, administrative and check redemption files, and to the 1990 federal census of NY county level data. The final data set contained 77,601 records. Birth weight among WIC participants who enrolled early and participated longer were compared to those who enrolled late and participated a shorter time. Selection bias was addressed using classification tree methods as part of a propensity score analysis. Gestational age bias was addressed by analyzing preterm and full-term pregnancies separately. RESULTS: Adjusted estimates showed a significant positive effect of longer prenatal WIC participation on birth outcomes for all groups studied. Infants born to WIC participants who enrolled early were heavier than those who enrolled late by, on average, 70 g for full-term and 129 grams for preterm. Black and Hispanic full-term infants experienced larger WIC effects than Whites (79, 75, 43 g, respectively). Looking at full-term pregnancies using Kotelchuck's index indicated that effects of longer prenatal WIC participation were greatest for the inadequate prenatal care group (83 g). CONCLUSION: Longer prenatal WIC participation was associated with an increase in birth weight overall and for all groups studied. The effect on birth weight of longer participation in WIC was greatest in Black and Hispanic, inadequate and no prenatal care groups.