BacA: a possible regulator that contributes to the biofilm formation of Pseudomonas aeruginosa.

Previously, we pointed out in P. aeruginosa PAO1 biofilm cells the accumulation of a hypothetical protein named PA3731 and showed that the deletion of the corresponding gene impacted its biofilm formation capacity. PA3731 belongs to a cluster of 4 genes (pa3732 to pa3729) that we named bac for "Biofilm Associated Cluster." The present study focuses on the PA14_16140 protein, i.e., the PA3732 (BacA) homolog in the PA14 strain. The role of BacA in rhamnolipid secretion, biofilm formation and virulence, was confirmed by phenotypic experiments with a bacA mutant. Additional investigations allow to advance that the bac system involves in fact 6 genes organized in operon, i.e., bacA to bacF. At a molecular level, quantitative proteomic studies revealed an accumulation of the BAC cognate partners by the bacA sessile mutant, suggesting a negative control of BacA toward the bac operon. Finally, a first crystallographic structure of BacA was obtained revealing a structure homologous to chaperones or/and regulatory proteins.

Additive and Specific Effects of Elicitor Treatments on the Metabolic Profile of Arabidopsis thaliana.

Several elicitors of plant defense have been identified and numerous efforts to use them in the field have been made. Exogenous elicitor treatments mimic the in planta activation of pattern-triggered immunity (PTI), which relies on the perception of pathogen-associated molecular patterns (PAMPs) such as bacterial flg22 or fungal chitins. Early transcriptional responses to distinct PAMPs are mostly overlapping, regardless of the elicitor being used. However, it remains poorly known if the same patterns are observed for metabolites and proteins produced later during PTI. In addition, little is known about the impact of a combination of elicitors on PTI and the level of induced resistance to pathogens. Here, we monitored Arabidopsis thaliana resistance to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pto DC3000) following application of flg22 and chitosan elicitors, used individually or in combination. A slight, but not statistically significant increase in induced resistance was observed when the elicitors were applied together when compared with individual treatments. We investigated the effect of these treatments on the metabolome by using an untargeted analysis. We found that the combination of flg22 and chitosan impacted a higher number of metabolites and deregulated specific metabolic pathways compared with the elicitors individually. These results contribute to a better understanding of plant responses to elicitors, which might help better rationalize their use in the field. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Night-to-night variability in sleep and amyloid beta burden in normal aging.

INTRODUCTION: Alzheimer's disease is associated with sleep disturbances and accumulation of cerebral amyloid beta. The objective was to examine whether actigraphy-detected sleep parameters might be biomarkers for early amyloid burden. METHODS: Participants underwent a week of actigraphy and an amyloid positron emission tomography (PET) scan. Sleep duration and continuity disruption (sleep fragmentation and nocturnal awakenings) were extracted and compared between amyloid-positive and amyloid-negative participants. Then multiple linear regressions were used between mean or night-to-night intra-individual variability (standard deviation) of sleep parameters and brain amyloid burden in a voxel-wise analysis. RESULTS: Eighty-six subjects were included (80.3 ± 5.4 years; 48.8% of women). Amyloid-positive participants had a higher variability of sleep fragmentation compared to amyloid-negative participants. This parameter was associated with a higher amyloid burden in the frontal and parietal regions, and in the precuneus, in the whole sample. DISCUSSION: This study highlights the relevance of using variability in sleep continuity as a potential biomarker of early amyloid pathogenesis.

Feasibility of advanced composite endpoint analysis: Post-hoc insights from the vitamin intervention for stroke prevention randomized control trial.

BACKGROUND AND AIMS: Stroke is a major cause of mortality and disability, highlighting the importance of prevention. Clinical trials play an important role in evaluating interventions that can maximize stroke prevention. Traditional composite endpoints (TCE) used in clinical trials have limitations, as they pool together events of varying clinical importance. Weighted composite endpoints (WCE) have emerged as a solution to address these limitations and provide more accurate assessments of outcomes. In this study, we investigate the use of WCE in a previously reported negative clinical trial for stroke prevention. METHODS AND RESULTS: We analyzed data from the Vitamin Intervention for Stroke Prevention (VISP) trial, which compared high dose and low dose multivitamin therapy. We utilized weighted methods to analyze time-to-event outcomes with censoring. The primary outcomes of interest were time to nonfatal stroke, nonfatal coronary events, and death. We calculated modified Kaplan-Meier (KM) curves for each intervention group. We also performed a modified log-rank test to assess significant differences based on the weighted KM curves. The analysis included 3668 VISP trial participants, and most remained event-free throughout the study period. The TCE KM curve showed no significant difference in outcomes between high dose and low dose groups. Similarly, the WCE KM curves, with different weights assigned to each outcome, did not reveal significant differences in outcomes between the studied groups. CONCLUSION: This post-hoc analysis confirms the negative trial results of VISP and demonstrates the feasibility of using WCE in assessing nutrition-based interventions for stroke prevention.

[Advanced Practice and Digital Health]. / Pratique avancée et santé numérique.

Digital health has become indispensable and inseparable from the current healthcare system. However, it is still often presented as a mysterious world that needs to be tamed in order to participate in innovations from their conception and to best accompany patients towards improving the quality and safety of care.

A Self-Help Virtual Therapeutic Experience Intervention for Overcoming Psychological Distress Related to the COVID-19 Pandemic: Results From the European Multicentric COVID Feel Good Trial.

OBJECTIVE: The general objective of the current study was to investigate the efficacy of a novel self-help virtual therapeutic experience (specifically, the COVID Feel Good intervention) in lowering the psychological burden experienced during the COVID-19 lockdowns in four European countries. METHODS: We focused on participants recruited from June 2020 to May 2021 in the context of a European multicenter project including four university/academic sites. The total number of participants in the longitudinal studies was 107 (study 1, N = 40; study 2, N = 29; study 3, N = 38). The randomized controlled trial (study 4) included 31 participants in total, 16 in the intervention group and 15 in the control group. Primary outcome measures were depression, anxiety, stress symptoms, perceived stress level, and perceived hopelessness. The secondary outcome was experienced social connectedness. RESULTS: Using separate linear mixed-effects models, the most consistent result across countries was a reduction in perceived stress after the participation in the COVID Feel Good intervention. By pooling the results of the models using a random-effects meta-analysis, we found that after the COVID Feel Good intervention, participants reported a decrease in perceived general distress (mean standardized effect size for general distress in the treatment groups compared with the control conditions was -0.52 [ p = .008, 95% confidence interval = -0.89 to -0.14]) and an increase in the perceived social connection (mean standardized effect size for social connection using COVID Feel Good compared with the control conditions was 0.50 [ p ≤ .001, 95% confidence interval = 0.25 to 0.76]). CONCLUSIONS: Findings of this study indicate that a virtual self-help intervention is effective in reducing psychological distress. These results contribute to the growing literature supporting the use of digital psychological therapies to relieve psychological distress among the general population during the COVID-19 pandemic.Trial Registration : ISRCTN63887521.

Problems or prospects? Being a parent in the early phase of the COVID-19 pandemic in Germany.

Background: In the early phase of the COVID-19 pandemic, many restrictions hit people in ways never seen before. Mental wellbeing was affected and burden was high, especially for high-risk groups such as parents. However, to our knowledge no research has yet examined whether being a parent was not only a risk for psychological burden but also a way to cope with the COVID-19 pandemic. Methods: An online survey was used to collect data from 1,121 participants from April to June 2020. In addition to demographic variables, risk factors (financial burden, problems complying with COVID-19 restrictions, and pre-treatment due to mental health problems) and protective factors (emotion regulation, humor, and crisis self-efficacy) were collected. The dataset was divided into three groups: parents whose children lived at home (n = 395), parents whose children did not (no longer) live at home (n = 165), and people who were not parents (n = 561). Results: A linear mixed effect model showed that parents had no higher burden than non-parents, and even less when children did not live at home. Expected risk factors were generally less important, and there were no differences between parents and non-parents. In contrast, parents had advantages in protective factors. Conclusion: In the early phase of the COVID-19 pandemic, it was shown that parents (with and without their children at home) were not necessarily at risk due to additional burden, but also had prospects of coping better with the situation than people without children.

COVID Feel Good: Evaluation of a Self-Help Protocol to Overcome the Psychological Burden of the COVID-19 Pandemic in a German Sample.

The COVID-19 pandemic has severe consequences for physical as well as mental well-being. In times of restricted social contact, online self-help programs offer a low-threshold first aid to cope with the psychological burden. This current study evaluates the online self-help protocol "COVID Feel Good" in a German sample. The multicentric study was designed as a single cohort with a waiting list control condition. The convenience sample consisted of 38 German individuals who experienced at least two months of restrictions during the COVID-19 pandemic. The 7-day self-help protocol included the VR video "Secret Garden" as well as a social or cognitive exercise each day. General distress, depression, anxiety, stress, and hopelessness were assessed as primary outcomes. Social connectedness and fear of coronavirus were measured as secondary outcomes. Results showed a significant decrease in all primary outcomes except for hopelessness. Furthermore, the results indicated a significant improvement in social connectedness. Treatment effects on general distress, depression, stress, and anxiety persisted for two weeks after participation. The present study indicates that VR-based self-help protocols can mitigate the psychological burden associated with the pandemic, supporting recent findings.

Successful Pre-Rewarming Resuscitation after Cardiac Arrest in Severe Hypothermia: A Retrospective Cohort Study from the International Hypothermia Registry.

The aim of our study is to investigate successful pre-rewarming resuscitation after hypothermic cardiac arrest (HCA). The hypothermic heart may be insensitive to defibrillation when core temperature is below 30 °C and after successful defibrillation, sinus rhythm often returns into ventricular fibrillation. Recurrent defibrillation attempts may induce myocardial injury. Discrepancy exists concerning pre-rewarming defibrillation between the guidelines of the European Resuscitation Council and American Heart Association. The International Hypothermia Registry (IHR) gathers hypothermia cases. The primary outcome was survival. Secondary outcomes were the characteristics of defibrillation, the effect of Adrenaline administration under 30 °C, and the duration of CPR. Of the 239 patients, eighty-eight were in cardiac arrest at arrival of the rescue team. Successful pre-rewarming resuscitation was obtained in 14 patients. The outcome showed: seven deaths, one vegetative state, two patients with reversible damage, and four patients with full recovery. A total of five patients had a shockable rhythm, and defibrillation was successful in four patients. The response rate to Adrenaline was reported as normal in six patients. There were no statistically significant differences in the presence of a shockable rhythm, the success of defibrillation, and the effect on Adrenaline administration between the survivors and non-survivors. Successful resuscitation in severe hypothermia is possible before active rewarming and arrival in the hospital, thus improving the chance of survival.

Measuring Walking Speed Failed to Predict Early Death and Toxicity in Elderly Patients with Metastatic Non-Small-Cell Lung Cancer (NSCLC) Selected for Undergoing First-Line Systemic Treatment: An Observational Exploratory Study.

Walking speed (WS) has emerged as a potential predictor of mortality in elderly cancer patients, yet data involving non-small-cell lung cancer (NSCLC) patients are scarce. Our prospective exploratory study sought to determine whether WS would predict early death or toxicity in patients with advanced NSCLC receiving first-line systemic intravenous treatment. Overall, 145 patients of ≥70 years were diagnosed with NSCLC over 19 months, 91 of whom displayed locally-advanced or metastatic cancer. As first-line treatment, 21 (23%) patients received best supportive care, 13 (14%) targeted therapy, and 57 (63%) chemotherapy or immunotherapy. Among the latter, 38 consented to participate in the study (median age: 75 years). Median cumulative illness rating scale for geriatrics (CIRS-G) was 10 (IQR: 8−12), and median WS 1.09 (IQR: 0.9−1.31) m/s. Older age (p = 0.03) and comorbidities (p = 0.02) were associated with Grade 3−4 treatment-related adverse events or death within 6 months of accrual. Overall survival was 14.3 (IQR: 6.1-NR) months for patients with WS < 1 m/s versus 17.3 (IQR: 9.2−26.5) for those with WS ≥ 1 m/s (p = 0.78). This exploratory study revealed WS to be numerically, yet not significantly, associated with early mortality in older metastatic NSCLC patients. Following these hypothesis-generating results, a larger prospective, multicenter study appears to be required to further investigate this outcome.

[The care pathway coordination nurse, an emerging profession]. / L'infirmier de coordination de parcours de soins, un métier émergent.

The care pathway coordination nurse acts in close collaboration with the various professionals in the health, social and medico-social fields to improve the patient's pathway. His or her coordination of the care pathway, over a given period of time, promotes personalized support within the framework of structured care that also considers the patient's health and life paths.

Emotions and emotion up-regulation during the COVID-19 pandemic in Germany.

In stressful situations such as the COVID-19-pandemic, unpleasant emotions are expected to increase while pleasant emotions will likely decrease. Little is known about the role cognitive appraisals, information management, and upregulating pleasant emotions can play to support emotion regulation in a pandemic. In an online survey (N = 1682), we investigated predictors of changes in pleasant and unpleasant emotions in a German sample (aged 18-88 years) shortly after the first restrictions were imposed. Crisis self-efficacy and felt restriction were predictors of changes in unpleasant emotions and joy alike. The application of emotion up-regulation strategies was weakly associated with changes in joy. Among the different upregulation strategies, only "savouring the moment" predicted changes in joy. Our study informs future research perspectives assessing the role of upregulating pleasant emotions under challenging circumstances.

Towards understanding the extensive diversity of protein N-glycan structures in eukaryotes.

N-glycosylation is an important post-translational modification of proteins that has been highly conserved during evolution and is found in Eukaryota, Bacteria and Archaea. In eukaryotes, N-glycan processing is sequential, involving multiple specific steps within the secretory pathway as proteins travel through the endoplasmic reticulum and the Golgi apparatus. In this review, we first summarize the different steps of the N-glycan processing and further describe recent findings regarding the diversity of N-glycan structures in eukaryotic clades. This comparison allows us to explore the different regulation mechanisms of N-glycan processing among eukaryotic clades. Recent findings regarding the regulation of protein N-glycosylation are highlighted, especially the regulation of the biosynthesis of complex-type N-glycans through manganese and calcium homeostasis and the specific role of transmembrane protein 165 (TMEM165) for which homologous sequences have been identified in several eukaryotic clades. Further research will be required to characterize the function of TMEM165 homologous sequences in different eukaryotic clades.

Effects of rhythmic eye movements during a virtual reality exposure paradigm for spider-phobic patients.

Rhythmic eye movements performed during eye movement desensitization and reprocessing (EMDR) therapy have been shown to evoke a physiological de-arousal pattern. OBJECTIVES: Here, we examined whether the efficacy of a virtual reality exposure therapy (VRET) paradigm for phobic patients could be improved by adding rhythmic eye movements. DESIGN: Spider-phobic patients (N = 53) were randomly assigned to either a group performing rhythmic eye movements or a control group undergoing exposure without such eye movements. METHODS: During the VRET session, heart rate, electrodermal activity, eye movements, and subjective fear ratings were recorded. Participants underwent behavioural avoidance tests before and after treatment as well as a follow-up 10-14 days later. Questionnaire data were assessed before exposure and at follow-up. RESULTS: There were clear treatment effects in both groups with almost no group differences (i.e., the subjective fear ratings and the skin conductance response). CONCLUSIONS: Contrary to our expectation, the implementation of rhythmic eye movements during virtual exposure did not enhance the effectiveness of the treatment. However, the eye movement group did show a significantly lower heart rate during exposure compared with the control group which might indicate a less stressful treatment. PRACTITIONER POINTS: One-session Virtual Reality Exposure Therapy reduced fear of spiders effectively. Performing rhythmic eye movements during exposure did not enhance therapy effects. Rhythmic eye movements during exposure resulted in lower heart rate than standard exposure.

Arterial Preparation by Longitudinal Micro-Incisions Before Balloon Angioplasty of the Superficial Femoral and Popliteal Artery: Acute and 12-Month Results.

PURPOSE: Percutaneous transluminal angioplasty (PTA) with conventional plain old balloon (POBA) and/or drug-coated balloon (DCB) is the primary intervention to treat peripheral artery stenoses. However, acute dissections during the procedure and potential for future target lesion revascularization remain procedural complications. The purpose of this study was to assess the acute and 12-month outcomes in patients who underwent novel vessel preparation with longitudinal, controlled-depth micro-incisions prior to PTA. MATERIALS AND METHODS: Patients with symptomatic lower extremity peripheral arterial disease with a Rutherford class of 2 to 6 and >70% de novo stenosis of the superficial femoral or popliteal arteries were included in this retrospective study. Patients with thrombotic or embolic lesions, restenosis, or in-stent restenosis were excluded. The FLEX Vessel Prep System (FLEX VP) was used to prepare the vessel prior to PTA by creating micro-incisions at the target lesion. The FLEX VP was followed by POBA or paclitaxel DCB. RESULTS: The study included 65 patients. Lesion characteristics were 90% median stenosis (range = 70%-100%), 75.4% mild-to-severe calcifications, and 33.8% occlusion rate, and median lesion length was 196 (range = 10-480) mm. Following vessel preparation, 82.1% of the patients had low severity dissection or no flow-limiting dissection. The provisional stent rate postprocedure was 16.9%, with a median stent length of 60 mm. The freedom from target lesion revascularization (FFTLR) in 63 evaluable patients at 6 and 12 months was 98.4% and 93.7%, respectively. Freedom from amputation was 100%. CONCLUSION: In this real-world/all-comers patient population with long, stenotic lesions across the calcification spectrum, vessel preparation with longitudinal micro-incisions prior to PTA was associated with low dissection rate, low dissection severity, low stent implantation, and high FFTLR with the absence of amputation at 12 months relative to published reports in long-lesion cohorts. These results support vessel preparation via micro-incisions.

Simplified therapeutic guidelines: the main tool of antimicrobial stewardship programs associated with optimal antibiotic therapy.

Hospitals regularly seek to upgrade their antimicrobial stewardship program (ASP). Our aim was to evaluate the impact of simplified therapeutic guidelines (STGs) compared to various established tools for ASP on the rate of optimal antibiotic therapy (OAT) and antibiotic consumption. Audits of antibiotic prescriptions were carried out over a 24-month period. Feedback information led to STGs (e.g., ≤ 15 drugs). The impact of STGs was based on the rate of OAT, defined as a diagnosis of the infectious disease in the patient's medical records associated with the corresponding therapy indicated in the STGs or in other guidelines. STGs were compared to five other means of ASP: internal or national guidelines, audit, information regarding antibiotic consumption and bacterial resistance, and restricted access to targeted antibiotics. Antibiotic consumption was measured in defined daily doses/1000 days of hospital stay, focusing on third-generation cephalosporins (TGC) and fluoroquinolones (FQ). Twenty-six hospitals were audited from April 2017 to June 2019. A total of 1,028 antibiotic prescriptions were analyzed, including 204 (20%) after STG implementation in seven hospitals. In multivariate analysis, OAT (n = 176, 17%) was associated with STGs, AOR 2.21 [1.51-3.22], and with three tools in place, 1.75 [1.24-2.48]. The relative variations of consumption of TGC and FQ for hospitals with or without STGs were - 13.1 vs. + 9.4% and - 18.5 vs. - 2.7%, respectively, from 2018 to 2019. STGs were more likely than other ASP tools to improve the rate of OAT and to reduce the consumption of antibiotics.

Two Carbohydrate-Based Natural Extracts Stimulate in vitro Pollen Germination and Pollen Tube Growth of Tomato Under Cold Temperatures.

To date, it is widely accepted by the scientific community that many agricultural regions will experience more extreme temperature fluctuations. These stresses will undoubtedly impact crop production, particularly fruit and seed yields. In fact, pollination is considered as one of the most temperature-sensitive phases of plant development and until now, except for the time-consuming and costly processes of genetic breeding, there is no immediate alternative to address this issue. In this work, we used a multidisciplinary approach using physiological, biochemical, and molecular techniques for studying the effects of two carbohydrate-based natural activators on in vitro tomato pollen germination and pollen tube growth cultured in vitro under cold conditions. Under mild and strong cold temperatures, these two carbohydrate-based compounds significantly enhanced pollen germination and pollen tube growth. The two biostimulants did not induce significant changes in the classical molecular markers implicated in pollen tube growth. Neither the number of callose plugs nor the CALLOSE SYNTHASE genes expression were significantly different between the control and the biostimulated pollen tubes when pollens were cultivated under cold conditions. PECTIN METHYLESTERASE (PME) activities were also similar but a basic PME isoform was not produced or inactive in pollen grown at 8°C. Nevertheless, NADPH oxidase (RBOH) gene expression was correlated with a higher number of viable pollen tubes in biostimulated pollen tubes compared to the control. Our results showed that the two carbohydrate-based products were able to reduce in vitro the effect of cold temperatures on tomato pollen tube growth and at least for one of them to modulate reactive oxygen species production.

Psychological Burden During the COVID-19 Pandemic in Germany.

After the first COVID-19 case was diagnosed in Germany, various measures limiting contact between people were introduced across the country. The implementation of these measures varied between jurisdictions and potentially had a negative impact on the psychological well-being of many people. However, the prevalence, severity, and type of symptoms of psychological burden has not been documented in detail. In the current study, we analysed various self-reported symptoms of psychological burden in a German sample. The dataset was collected between April 8th and June 1st, 2020, through an online survey measuring psychological burden using the ICD-10-symptom rating scale. More than 2,000 individuals responded to the survey, with a total of 1,459 complete datasets. Data was then sampled to compare (1) the new data to an existing demographically comparable reference dataset including a total of 2,512 participants who did not undergo any kind of contact restrictions or other pandemic measurements, and (2) psychological burden in two different German states. In line with recent observations from Germany, Italy, China, Austria and Turkey, we found a high prevalence of depressive symptoms in comparison to the reference sample. Furthermore, we found a high prevalence of eating disorder and compulsion symptoms. Especially younger adults and women reported a higher symptom severity compared to other groups during our measurement period. However, no difference between the two states in psychological burden was found.