Efficacy of the my health too online cognitive behavioral therapy program for healthcare workers during the COVID-19 pandemic: A randomized controlled trial.

Background: Healthcare workers' mental health has been impacted by the COVID-19 pandemic, emphasizing the need for mental health interventions in this population. Online cognitive behavioral therapy (CBT) is efficient to reduce stress and may reach numerous professionals. We developed "MyHealthToo", an online CBT program to help reduce stress among healthcare workers during the COVID-19 pandemic. Objective: The aim of our study is to investigate the efficacy of an online CBT program on stress and mental health conditions among healthcare workers during a health crisis. Methods: We performed a multicentric randomized controlled trial among 155 participants allocated either to the experimental or active control group (bibliotherapy). The primary outcome was the decrease of perceived stress scores (PSS-10) post-treatment. Secondary outcomes included depression, insomnia and PTSD symptoms along with self-reported resilience and ruminations. Assessments were scheduled pretreatment, mid-treatment (4 weeks), post-treatment (8 weeks), and at 1-month and 4-months follow-up. Results: For both interventions, mean changes on the PSS-10 were significant post-therapy (W8), as at 1-month (W12) and 4-months (W24) follow-ups. The between-group comparison showed no difference at any time point (ps > 0.88). Work-related ruminations significantly decreased in the experimental group with a significant between-group difference at W8 (Δ = -1.83 [-3.57; -0.09], p = 0.04). Posttraumatic stress symptoms significantly decreased in the experimental group with a significant between-group difference at W12 (Δ = -1.41 [-2.68; -0.14], p = 0.03). The decrease in work-related ruminations at W8 mediated the decrease in posttraumatic stress symptoms at W12 (p = 0.048). Conclusion: The "MyHealthToo" online CBT intervention may help reduce ruminations about work and posttraumatic stress symptoms among healthcare workers during a major health crisis. Work-related ruminations may represent a relevant target of online interventions to improve mental health among healthcare workers.

My Health Too: Investigating the Feasibility and the Acceptability of an Internet-Based Cognitive-Behavioral Therapy Program Developed for Healthcare Workers.

Background: The COVID-19 crisis has had a considerable mental health impact on healthcare workers. High levels of psychological distress are expected to have a significant impact on healthcare systems, warranting the need for evidence-based psychological interventions targeting stress and fostering resilience in this population. Online cognitive behavioral therapy (CBT) has proved to be effective in targeting stress and promoting resilience. However, online CBT programs targeting stress in healthcare workers are lacking. Objective: The aim of our study is to evaluate the feasibility and acceptability of an internet-based CBT intervention, the My Health Too program we developed during the first COVID-19 epidemic peak in France. Methods: We recruited 10 participants among Alsace region hospital staff during the first peak of the pandemic in France. They were given 1 week to test the website and were then asked to answer an internet survey and a semi-structured phone interview. Results: We conducted a thematic analysis of the content from the phone interviews. Major themes were identified, discussed and coded: the technical aspects, the content of the website and its impact on participants' emotions and everyday life. Overall, the participants reported finding the website easy to use and interactive. They described the resources as easy to understand, readily usable, and useful in inducing calm and in helping them practice self-compassion. Conclusion: Our results suggest that the My Health Too online CBT program is highly feasible and acceptable to healthcare workers during the highly stressful times of the pandemic peak. The feedback provided helped to improve the program whose efficacy is to be tested.

Profiling at mRNA, protein, and metabolite levels reveals alterations in renal amino acid handling and glutathione metabolism in kidney tissue of Pept2-/- mice.

PEPT2 is an integral membrane protein in the apical membrane of renal epithelial cells that operates as a rheogenic transporter for di- and tripeptides and structurally related drugs. Its prime role is thought to be the reabsorption of filtered di- and tripeptides contributing to amino acid homeostasis. To elucidate the role of PEPT2 in renal amino acid metabolism we submitted kidney tissues of wild-type and a Pept2(-/-) mouse line to a comprehensive transcriptome, proteome and metabolome profiling and analyzed urinary amino acids and dipeptides. cDNA microarray analysis identified 147 differentially expressed transcripts in transporter-deficient animals, and proteome analysis by 2D-PAGE and MALDI-TOF-MS identified 37 differentially expressed proteins. Metabolite profiling by GC-MS revealed predominantly altered concentrations of amino acids and derivatives. Urinary excretion of amino acids demonstrated increased glycine and cysteine/cystine concentrations and dipeptides in urine were assessed by amino acid analysis of urine samples before and after in vitro dipeptidase digestion. Dipeptides constituted a noticeable fraction of urinary amino acids in Pept2(-/-) animals, only, and dipeptide-bound glycine and cystine were selectively increased in Pept2(-/-) urine samples. These findings were confirmed by a drastically increased excretion of cysteinyl-glycine (cys-gly). Urinary loss of cys-gly together with lower concentrations of cysteine, glycine, and oxoproline in kidney tissue and altered expression of mRNA and proteins involved in glutathione (GSH) metabolism suggests that PEPT2 is predominantly a system for reabsorption of cys-gly originating from GSH break-down, thus contributing to resynthesis of GSH.

Targeted disruption of the peptide transporter Pept2 gene in mice defines its physiological role in the kidney.

The peptide transporter PEPT2 mediates the cellular uptake of di- and tripeptides and selected drugs by proton-substrate cotransport across the plasma membrane. PEPT2 was functionally identified initially in the apical membrane of renal tubular cells but was later shown to be expressed in other tissues also. To investigate the physiological importance of PEPT2 and for a detailed analysis of the protein expression sites, we generated a Pept2 knockout mouse line in which the Pept2 gene was disrupted by insertion of a beta-galactosidase gene under the control of the PEPT2 promoter. The Pept2(-/-) mice showed no obvious phenotypic abnormalities but also no adaptive upregulation in the expression level of related genes in the kidney. The importance of PEPT2 in the reabsorption of filtered dipeptides was demonstrated in knockout animals by significantly reduced renal accumulation of a fluorophore-labeled and a radiolabeled dipeptide after in vivo administration of the tracers. This indicates that PEPT2 is the main system responsible for tubular reabsorption of peptide-bound amino acids, although this does not lead to major changes in renal excretion of protein or free amino acids.

Functional expression of the peptide transporter PEPT2 in the mammalian enteric nervous system.

The peptide transporter PEPT2 mediates transmembrane uptake of small peptides. So far, its expression has not been evidenced in the gastrointestinal tract. We have investigated peptide transport activity in the neuromuscular layers of the gastrointestinal tract by using the fluorescent tracer-dipeptide beta-Ala-Lys-Nepsilon-7-amino-4-methyl-coumarin-3-acetic acid (Ala-Lys-AMCA). Whole-mount preparations from mouse, rat, and guinea pig stomach and small and large intestine were incubated with Ala-Lys-AMCA in the presence or absence of the uptake-inhibitors L-histidine, D-phenylalanyl-L-alanine (D-Phe-Ala), glycyl-L-sarcosine (Gly-Sar), glycyl-L-glutamine (Gly-Gln), benzylpenicillin, and cefadroxil. Fluorescence microscopy revealed that Ala-Lys-AMCA specifically accumulated in both ganglionic layers of the enteric nervous system (ENS) in all regions and species studied. This could be inhibited by Gly-Sar, D-Phe-Ala, Gly-Gln, and cefadroxil, but not by free histidine and benzylpenicillin, indicating uptake via PEPT2. Accordingly, dipeptide uptake was completely abolished in PEPT2-deficient mice. Reverse transcriptase-polymerase chain reaction analysis detected a PEPT2-specific transcript in extracts from the ganglionic ENS layers of mouse small and large intestine, further proving that enteric dipeptide transport activity is specifically mediated via PEPT2. The cellular site of dipeptide uptake was immunohistochemically localized to enteric glial cells and tissue-resident macrophages. In addition, dipeptide uptake occurred in a neurochemically defined subset of neurons in the guinea pig ENS. Our results constitute the first functional evidence for dipeptide transport activity in the ENS. PEPT2-mediated dipeptide transport in enteric glia could contribute to the clearance of neuropeptides in the ENS. In addition, the fluorophore-coupled dipeptide uptake via PEPT2 is a novel vital marker for glial cells in the ENS.

Helminth therapy for organic diseases?

Autoimmune and chronic inflammatory organic diseases represent a "postindustrial revolution epidemics," and their frequency has increased dramatically in the last century. Today, it is assumed that the increase in hygiene standards reduced the interactions with helminth parasites that coevolved with the immune system and are crucial for its proper functioning. Several helminths have been proposed and tested in the search of the ideal therapeutic. In this review, the authors summarize the translational and clinical studies and review the caveats and possible solutions for the optimization of helminth therapies.

Evaluation of a new hands-up ergonomics for chest radiography in geriatric patients.

RATIONALE AND OBJECTIVES: Pneumonia is the leading cause of death after the age of 85 years. Chest radiography (CXR) requires forced inspiration for accurate assessment, but kyphosis, denutrition, muscular weakness, and neurologic disorders limit active inspiration. The aim of this study was to evaluate a new passive expansion technique, by raising the patient's arms above the head, in the radiographic diagnosis of pneumonia. METHODS: During a 10-month period, CXR were performed in 1452 geriatric patients for pulmonary acute disorders in our geriatric university hospital. When fewer than five anterior rib segments were visible on the conventional front view, a second CXR was performed with the patient's arms being raised above the head by a radiologist. The diagnostic questions were: Are more than five anterior rib segments present? Is pneumonia visible? The chest radiographs were independently analyzed (3-step confidence scale) by two radiologists and compared by interobserver kappa-coefficients calculation. RESULTS: One hundred three patients (97 female, 6 male), representing 7% of the examined population, with an average age of 86.5 years (range, 70-104 years) were included. An additional anterior rib segment was visible on the front CXR when the arms were raised above the head (P < 0.001). Pneumonia was diagnosed in 59 patients with high agreement (kappa = 0.84) by the passive expansion technique, whereas the pneumonia infiltrate was visible in only 44 patients with considerably lower agreement (kappa = 0.36) when the arms were positioned along the trunk (P < 0.03). CONCLUSIONS: Raising the arms above the head optimizes the quality of CXR and increases the detection of pneumonia in the geriatric patient. New ergonomics and adequate contention are required.

Inhibition of intracellular dipeptide hydrolysis uncovers large outward transport currents of the peptide transporter PEPT1 in Xenopus oocytes.

The "reversed transport mode" of electrogenic carriers is usually difficult to assess, as substrates are metabolized after reaching the cell, and the cytosolic surface is only accessible in special experimental settings such as giant-patch techniques. In the present experiments with the two-electrode voltage clamp, we demonstrate a unique feature of the peptide transporter PEPT1 that produces huge outward transport currents when oocytes are preloaded with hydrolysis-resistant dipeptides or when intracellular hydrolysis is prevented by aminopeptidase inhibition. A rapid intracellular degradation of dipeptides in oocytes and a parallel decline of outward currents were observed by analysis of amino acids in the cells. Dipeptide hydrolysis could almost completely be blocked by preincubation of oocytes with the aminopeptidase-inhibitor bestatin, itself a substrate of PEPT1. Dipeptide-driven outward currents of bestatin-treated oocytes remained stable over at least 10 min. Unexpectedly, the outward currents at a membrane potential of +60 mV were about five times higher than the corresponding inward currents measured before preloading at -60 mV under symmetrical conditions. The huge outward current was carried by PEPT1 and did not result from opening of potassium or chloride conductances in the membrane. Dipeptide-preloading of oocytes also increased inward currents evoked by substrates provided on the outside and equal substrate concentrations on both membrane surfaces in the absence of a pH gradient resulted in a linear current-voltage relation crossing the current axis at the origin. Our data and preliminary model calculations suggest a faster turnover rate of rPEPT1 in the presence of high substrate concentrations on the cytosolic surface.

Slc7a9 knockout mouse is a good cystinuria model for antilithiasic pharmacological studies.

Cystinuria is a hereditary disorder caused by a defect in the apical membrane transport system for cystine and dibasic amino acids in renal proximal tubules and intestine, resulting in recurrent urolithiasis. Mutations in SLC3A1 and SLC7A9 genes, that codify for rBAT/b(0,+)AT transporter subunits, cause type A and B cystinuria, respectively. In humans, cystinuria treatment is based on the prevention of calculi formation and its dissolution or breakage. Persistent calculi are treated with thiols [i.e., d-penicillamine (DP) and mercaptopropionylglycine (MPG)] for cystine solubilization. We have developed a new protocol with DP to validate our Slc7a9 knockout mouse model for the study of the therapeutic effect of drugs in the treatment of cystine lithiasis. We performed a 5-wk treatment of individually caged lithiasic mutant mice with a previously tested DP dose. To appraise the evolution of lithiasis throughout the treatment a noninvasive indirect method of calculi quantification was developed: calculi mass was quantified by densitometry of X-ray images from cystinuric mice before and after treatment. Urine was collected in metabolic cage experiments to quantify amino acids in DP-treated and nontreated, nonlithiasic mutant mice. We found significant differences between DP-treated and nontreated knockout mice in calculi size and in urinary cystine excretion. Histopathological analysis showed that globally nontreated mutant mice had more severe and diffuse urinary system damage than DP-treated mice. Our results validate the use of this mouse model for testing the efficacy of potential new drugs against cystinuria.

Phenotype analysis of mice deficient in the peptide transporter PEPT2 in response to alterations in dietary protein intake.

The peptide transporter PEPT2 mediates cellular uptake of di- and tripeptides driven by an inwardly directed electrochemical proton gradient. In mammals PEPT2 is found in a variety of organs such as kidney, lung, brain, enteric nervous system, and mammary gland. Highest expression levels are observed in renal proximal tubules where PEPT2 contributes to reabsorption of filtered di- and tripeptides. To assess the physiological importance of the transporter in overall metabolism, we have generated a Pept2-/- mouse line that lacks a functional PEPT2 protein. Here we present data on body weight, organ weights, and blood pressure. Mice were then fed diets containing either 10, 20, or 30% (w/w) protein, and food and water intake rates as well as plasma and urine parameters were determined. In spite of PEPT2 expression in a variety of tissues, only subtle phenotypic changes were observed. Male PEPT2 null mice displayed lower bodyweight and lower relative heart weight, whereas, relative kidney weight was lower in female Pept2-/- mice. No differences were found in blood pressure. When fed diets with different protein contents, Pept2-/- mice adapted food intake to dietary protein content with higher consumption rates on low protein and reduced food intake rates on the high protein diet.