Generating universal anti-CD19 CAR T cells with a defined memory phenotype by CRISPR/Cas9 editing and safety evaluation of the transcriptome.

Introduction: Chimeric antigen receptor-expressing T cells (CAR T cells) have revolutionized cancer treatment, particularly in B cell malignancies. However, the use of autologous T cells for CAR T therapy presents several limitations, including high costs, variable efficacy, and adverse effects linked to cell phenotype. Methods: To overcome these challenges, we developed a strategy to generate universal and safe anti-CD19 CAR T cells with a defined memory phenotype. Our approach utilizes CRISPR/Cas9 technology to target and eliminate the B2M and TRAC genes, reducing graft-versus-host and host-versus-graft responses. Additionally, we selected less differentiated T cells to improve the stability and persistence of the universal CAR T cells. The safety of this method was assessed using our CRISPRroots transcriptome analysis pipeline, which ensures successful gene knockout and the absence of unintended off-target effects on gene expression or transcriptome sequence. Results: In vitro experiments demonstrated the successful generation of functional universal CAR T cells. These cells exhibited potent lytic activity against tumor cells and a reduced cytokine secretion profile. The CRISPRroots analysis confirmed effective gene knockout and no unintended off-target effects, validating it as a pioneering tool for on/off-target and transcriptome analysis in genome editing experiments. Discussion: Our findings establish a robust pipeline for manufacturing safe, universal CAR T cells with a favorable memory phenotype. This approach has the potential to address the current limitations of autologous CAR T cell therapy, offering a more stable and persistent treatment option with reduced adverse effects. The use of CRISPRroots enhances the reliability and safety of gene editing in the development of CAR T cell therapies. Conclusion: We have developed a potent and reliable method for producing universal CAR T cells with a defined memory phenotype, demonstrating both efficacy and safety in vitro. This innovative approach could significantly improve the therapeutic landscape for patients with B cell malignancies.

Capacity-building during public health emergencies: perceived usefulness and cost savings of an online training on SARS-CoV-2 real-time polymerase chain reaction (qPCR) diagnostics in low- and middle-income settings during the COVID-19 pandemic.

Introduction: Upon the onset of the COVID-19 pandemic, the Public Health Laboratory Support Unit (ZIG4) at the Robert Koch Institute (RKI), the German National Public Health Institute, developed and delivered an online training on SARS-CoV-2 qPCR diagnostics to 17 partner countries in low- and middle-income countries (LMIC). This article analyses the usefulness and cost savings of this training. Methods: The authors performed a concurrent mixed-methodology study based on key informant interviews, interviewer-administered questionnaires, and document reviews. Economic costs were estimated from the perspective of RKI. Results: Responding participants indicated that the course provided good and comprehensive information on up-to-date scientific knowledge and laboratory practice in PCR diagnostics. Respondents appreciated how the technical content of the training enhanced their ability to apply diagnostic methods in their daily work. Interviewees highlighted that the fast implementation and the low threshold of attending an online training had allowed them to quickly build skills that were crucial during, and beyond, the COVID-19 crisis. The total estimated cost of the online SARS-CoV-2 qPCR training was 61,644 euros. The total estimated cost of the equivalent face-to-face training was estimated at 267,592 euros. Programme weaknesses identified included the top-down approaches taken, lack of interactive components and opportunities to directly engage with other course participants and with teachers. Conclusions: An online training was developed and implemented to support RKI partner countries in SARS-CoV-2 qPCR diagnostics during the COVID-19 pandemic, thereby strengthening pandemic response and health system resilience. The training incurred in important cost savings compared to the equivalent face-to-face training. Post-pandemic studies could usefully build on these research findings and explore ways to enhance end user involvement and improve interactive features to build stronger communities of learners and facilitate exchange of information and mutual learning.

Structural and biochemical characterization of SmoPG1, an exo-polygalacturonase from Selaginella moellendorffii.

Polygalacturonases (PGs) can modulate chemistry and mechanical properties of the plant cell wall through the degradation of pectins, one of its major constituents. PGs are largely used in food, beverage, textile, and paper industries to increase processes' performances. To improve the use of PGs, knowledge of their biochemical, structural and functional features is of prime importance. Our study aims at characterizing SmoPG1, a polygalacturonase from Selaginella moellendorffii, that belongs to the lycophytes. Transcription data showed that SmoPG1 was mainly expressed in S. moellendorffii shoots while phylogenetic analyses suggested that SmoPG1 is an exo-PG, which was confirmed by the biochemical characterization following its expression in heterologous system. Indeed, LC-MS/MS oligoprofiling using various pectic substrates identified galacturonic acid (GalA) as the main hydrolysis product. We found that SmoPG1 was most active on polygalacturonic acid (PGA) at pH 5, and that its activity could be modulated by different cations (Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Na2+, Zn2+). In addition, SmoPG1 was inhibited by green tea catechins, including (-)-epigallocatechin-3-gallate (EGCG). Docking analyses and MD simulations showed in detail amino acids responsible for the SmoPG1-EGCG interaction. Considering its expression yield and activity, SmoPG1 appears as a prime candidate for the industrial production of GalA.

The burden and treatment of non-communicable diseases among healthcare workers in sub-Saharan Africa: a multi-country cross-sectional study.

Introduction: Non-communicable diseases (NCDs), the leading cause of death globally, are estimated to overtake communicable diseases in sub-Sahara Africa, where healthcare workers (HCWs) play a crucial role in prevention and treatment, but are in extreme shortage, thereby increasing the burden of NCDs among this specific population. To provide evidence for policy-making, we assessed the NCD burden, associated factors and treatment among HCWs in four sub-Saharan African countries. Materials and methods: We conducted a cross-sectional study across four sub-Saharan African countries [Côte d'Ivoire (CIV), Democratic Republic of the Congo (DRC), Madagascar (MDG), and Nigeria (NIG)] between February and December 2022. In a standardized questionnaire, sociodemographic, chronic disease and treatment data were self-reported. We estimated the prevalence of (1) at least one chronic disease, (2) hypertension, and used backward elimination logistic regression model to identify risk factors. Results: We recruited a total of 6,848 HCWs. The prevalence of at least one chronic disease ranged between 9.7% in NIG and 20.6% in MDG, the prevalence of hypertension between 5.4% in CIV and 11.3% in MDG. At most, reported treatment rates reached 36.5%. The odds of each of both outcomes increased with age (at least one chronic disease adjusted odds ratio: CIV: 1.04; DRC: 1.09; MDG: 1.06; NIG: 1.10; hypertension: CIV: 1.10; DRC: 1.31; MDG: 1.11; NIG: 1.11) and with BMI (at least one chronic disease: CIV: 1.10; DRC: 1.07; MDG: 1.06; NIG: 1.08; hypertension: CIV: 1.10; DRC: 1.66; MDG: 1.13; NIG: 1.07). Odds of both outcomes were lower among males, except in CIV. In NIG, the odds of both outcomes were higher among medical doctors and odds of hypertension were higher among those working in secondary care. In MDG, working in secondary care increased and working as auxiliary staff decreased the odds of at least one chronic disease. Conclusion: The prevalence of self-reported chronic disease varied across the four sub-Saharan countries with potentially very low treatment rates. We identified several individual (age, sex, and BMI) and occupational (profession, level of healthcare) factors that influence the odds of NCDs. These factors should be taken into account when developing interventions addressing the burden and management of NCDs among HCWs.

An Unusual Case of an Intradiploic Arachnoid Cyst of the Orbit.

This study reported a case of an arachnoid cyst of the sphenoid bone causing orbital signs and symptoms in a 58-year-old man with progressive proptosis and nonspecific discomfort in the OS. Orbital MRI showed a 3-cm homogeneous cyst within the left greater wing of the sphenoid bone. To the best of our knowledge, this is the first report of an intradiploic arachnoid cyst in the sphenoid bone with atypical radiological features, causing clinical symptoms, and managed through an eyelid approach, achieving a complete resolution with no complications.

Effects of Face Mask Mandates on COVID-19 Transmission in 51 Countries: Retrospective Event Study.

BACKGROUND: The question of the utility of face masks in preventing acute respiratory infections has received renewed attention during the COVID-19 pandemic. However, given the inconclusive evidence from existing randomized controlled trials, evidence based on real-world data with high external validity is missing. OBJECTIVE: To add real-world evidence, this study aims to examine whether mask mandates in 51 countries and mask recommendations in 10 countries increased self-reported face mask use and reduced SARS-CoV-2 reproduction numbers and COVID-19 case growth rates. METHODS: We applied an event study approach to data pooled from four sources: (1) country-level information on self-reported mask use was obtained from the COVID-19 Trends and Impact Survey, (2) data from the Oxford COVID-19 Government Response Tracker provided information on face mask mandates and recommendations and any other nonpharmacological interventions implemented, (3) mobility indicators from Google's Community Mobility Reports were also included, and (4) SARS-CoV-2 reproduction numbers and COVID-19 case growth rates were retrieved from the Our World in Data-COVID-19 data set. RESULTS: Mandates increased mask use by 8.81 percentage points (P=.006) on average, and SARS-CoV-2 reproduction numbers declined on average by -0.31 units (P=.008). Although no significant average effect of mask mandates was observed for growth rates of COVID-19 cases (-0.98 percentage points; P=.56), the results indicate incremental effects on days 26 (-1.76 percentage points; P=.04), 27 (-1.89 percentage points; P=.05), 29 (-1.78 percentage points; P=.04), and 30 (-2.14 percentage points; P=.02) after mandate implementation. For self-reported face mask use and reproduction numbers, incremental effects are seen 6 and 13 days after mandate implementation. Both incremental effects persist for >30 days. Furthermore, mask recommendations increased self-reported mask use on average (5.84 percentage points; P<.001). However, there were no effects of recommendations on SARS-CoV-2 reproduction numbers or COVID-19 case growth rates (-0.06 units; P=.70 and -2.45 percentage points; P=.59). Single incremental effects on self-reported mask use were observed on days 11 (3.96 percentage points; P=.04), 13 (3.77 percentage points; P=.04) and 25 to 27 (4.20 percentage points; P=.048 and 5.91 percentage points; P=.01) after recommendation. Recommendations also affected reproduction numbers on days 0 (-0.07 units; P=.03) and 1 (-0.07 units; P=.03) and between days 21 (-0.09 units; P=.04) and 28 (-0.11 units; P=.05) and case growth rates between days 1 and 4 (-1.60 percentage points; P=.03 and -2.19 percentage points; P=.03) and on day 23 (-2.83 percentage points; P=.05) after publication. CONCLUSIONS: Contrary to recommendations, mask mandates can be used as an effective measure to reduce SARS-CoV-2 reproduction numbers. However, mandates alone are not sufficient to reduce growth rates of COVID-19 cases. Our study adds external validity to the existing randomized controlled trials on the effectiveness of face masks to reduce the spread of SARS-CoV-2.

Screening of positive dysphotopsia before multifocal intraocular lens implantation.

PURPOSE: To assess the photic phenomena (PP) and positive dysphotopsia in candidates for presbyopia or cataract surgery and to evaluate their relationship with cataract grading systems. DESIGN: Retrospective observational. METHODS: Monocular data for 82 subjects measured during the preoperative screening were retrospectively retrieved from our database. The evaluated variables consisted of two methods for PP measurement: light distortion index (LDI) and parameters obtained from a simulator, both of which were combined with subjective bother related to PP. The cutoff for LDI that better predicted patients passing from slightly to moderately bothersome was estimated. The relationships between LDI and the following objective cataract grading methods were also assessed: objective scatter index (OSI), dysfunctional lens index (DLI), and Pentacam Nucleus Staging (PNS). RESULTS: LDI was the best method for measuring PP, which showed a significant correlation with the bothersome question (rho = 0.34, P = 0.002) and also with OSI (rho = 0.67, P < 0.0005), DLI (rho = -0.29, P = 0.007), and PNS (rho = 0.48, P < 0.0005). The number/percentage of patients who found it bothersome was as follows: "Not at all" (18/22%), "Slightly" (41/50%), "Moderately" (15/18.3%), and "Very" (8/9.7%). The cutoff value that predicted the transition from slightly to moderately bothersome was ≥15.20% according to LDI, which could be estimated with the following values for grading: ≥2.8 for OSI, ≤7.6 for DLI, and ≥2 for PNS. CONCLUSIONS: Patients reporting moderately or higher bothersome levels in the preoperative period and with LDI <15.20%, <2.8 for OSI, >7.6 for DLI, and <2 for PNS might deserve special attention in the multifocal intraocular lens selection.

Thulium Fiber Laser Versus Holmium:Yttrium Aluminum Garnet for Lithotripsy: A Systematic Review and Meta-analysis.

CONTEXT: Thulium fiber laser (TFL) emerged as a competitor of holmium:yttrium aluminum garnet (Ho:YAG) laser for the treatment of urinary stones. OBJECTIVE: To compare the efficacy between Ho:YAG and TFL for laser lithotripsy of renal and ureteral stones. EVIDENCE ACQUISITION: A literature search was conducted using PubMed/Medline, Embase, and Web of Science databases to identify reports published until May 2023. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed to identify eligible studies. The primary outcome was to compare the stone-free rate (SFR) between Ho:YAG and TFL for laser lithotripsy. EVIDENCE SYNTHESIS: Eleven studies met our inclusion criteria, and data from 1286 and 880 patients who underwent, respectively, Ho:YAG and TFL laser lithotripsy were reviewed. Most studies included ureteroscopy (URS) and retrograde intrarenal surgeries as procedures, two included percutaneous nephrolithotomy, and one included URS exclusively. Only two studies reported results in pediatric patients. TFL was associated with a higher SFR (odds ratio [OR] 1.84, 95% confidence interval [CI]: 1.06-3.20; p = 0.031) when no residual fragment is considered, but not when SFR refers to the presence of fragments <3 mm (OR 2.48, 95% CI: 0.98-6.29; p = 0.055) or when only Ho:YAG with MOSES is considered (p = 0.068). According to the stones' location, TFL was associated with higher SFRs than Ho:YAG for renal (OR 3.14, 95% CI: 1.69-5.86; p < 0.001) but not for ureteral (p = 0.8) stones. TFL was associated with a lower intraoperative complication rate (OR 0.34, 95% CI: 0.19-0.63; p < 0.001). No difference was found in major (p = 0.4) or overall (p = 0.4) complication rate, operative time (p = 0.051), and laser time (p = 0.9). CONCLUSIONS: TFL is a promising laser for the treatment of urinary stones with some advantages over Ho:YAG. Further high-quality studies are needed to confirm these findings and optimize the surgical settings. PATIENT SUMMARY: The use of thulium fiber laser rather than holmium:yttrium aluminum garnet permits to reach a higher stone-free rate in stones located in the kidney rather than in the ureter.

Applicability of the Barcelona scale to assess the quality of cleanliness of mucosa at esophagogastroduodenoscopy.

BACKGROUND AND OBJECTIVES: There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD. METHODS: We developed a cleanliness scale (Barcelona scale) with a score (0-2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times. RESULTS: In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45-0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45-0.93). The intra-observer variability was 0.89 (0.76-0.99). CONCLUSIONS: The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD.

Combination treatment with monoclonal antibodies: Dupilumab and ustekinumab for the treatment of severe atopic dermatitis and Crohn disease.

Evidence of effectiveness and safety in combined therapies is scarce and based on case reports and small case series. We report a case of dual biologic therapy with ustekinumab and dupilumab in a patient with severe Crohn disease and atopic dermatitis. There was no interference between these drugs after a 7-month follow-up.

Association of Parity With Insulin Resistance Early in Pregnant Women: ECLIPSES Study.

CONTEXT: Little is known about whether parity is associated with elevated early-pregnancy insulin resistance (IR), or whether overweight/obesity contributes to increasing the possible effect. OBJECTIVE: We determined the associations between parity and glucose metabolism parameters in the first trimester of pregnancy in a Mediterranean pregnant population, and whether these associations are affected by overweight/obesity. METHODS: A cross-sectional study was conducted of 264 healthy pregnant women from the ECLIPSES study who were recruited at 12 weeks of gestation. At baseline, details on socioeconomic status, obstetric history (including parity, ie, number of births), lifestyle factors, anthropometry, and blood samples were collected. Fasting serum glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed in the first trimester. Elevated IR was defined as the upper HOMA-IR tertile (≥1.58). Multivariable linear regression and Cox regression model with constant time were performed. RESULTS: Parity ranged from 0 to 4. After multivariable adjustment, the insulin levels (ß [% change]: 20.92; 95% CI, 4.08-37.71) and HOMA-IR index (ß [% change]: 19.72; 95% CI, 2.43-40.49) were positively associated with parity. Additionally, multiparous women, as compared to nulliparous, were more likely to have higher HOMA-IR levels (primiparous [1 birth], ß [% change[: 16.88; 95% CI, -1.00 to 37.99; multiparous [≥2 births), ß [% change]: 32.18; 95% CI, 3.56-68.71), and an increased relative risk (RR) of an elevated IR (primiparous [1 birth], RR: 1.55; 95% CI, 1.03-2.36; multiparous (≥2 births), RR: 1.72; 95% CI, 1.05-2.83). The combination of multiparity and overweight/obesity conferred a 3.04-fold increase in the RR of elevated IR, which increased proportionally to the number of parities. CONCLUSION: This study demonstrates that parity may have a negative effect on early-pregnancy IR and that maternal overweight/obesity appears to further aggravate this relationship.

Total recovery of visual acuity in a pediatric patient with compressive optic neuropathy secondary to sphenoid sinus mucocele / Recuperação total da acuidade visual na neuropatia óptica compressiva secundária à mucocele do seio esfenoidal em paciente pediátrico

ABSTRACT We present an unusual case of a 13-year-old male pediatric patient with a diagnosis of sphenoid sinus mucocele. The patient suffered a progressive loss of visual acuity over three months followed by a total recovery of his visual acuity after surgery. The patient presented at the emergency room complaining of progressive loss of visual acuity in his left eye which decreased to hand motion over the preceding months. Imaging studies revealed a cystic mass, suggestive of sphenoid sinus mucocele, which was causing compressive optic neuropathy and proptosis. The patient was scheduled for a sphenoidectomy and resection of the mass. Three days after surgery, the patient's visual acuity in the left eye was 20/20, indicating complete recovery from his symptoms. We suggest that the excellent outcome in this patient may be attributable to his age. His ongoing physical development might have been the decisive factor in the recovery of his visual acuity following compressive optic neuropathy secondary to sphenoid sinus mucocele. Further research is needed to verify this proposed explanation.

RESUMO Apresentamos um caso incomum de paciente pediátrico com diagnóstico de mucocele de seio esfenoidal, que apresentou perda progressiva da acuidade visual ao longo de três meses, resultando em recuperação total da acuidade visual após a cirurgia. Paciente do sexo masculino, 13 anos, procurou o pronto-socorro, queixando-se de perda progressiva da acuidade visual do olho esquerdo nos últimos três meses. Exames de imagem revelaram uma massa cística sugestiva de mucocele de seio esfenoidal, causando neuropatia óptica compressiva e proptose. O paciente foi agendado para esfenoidectomia e ressecção da massa. Três dias após a cirurgia, a acuidade visual do paciente no olho esquerdo era de 20/20, apresentando recuperação completa dos sintomas. Diante dos resultados de nosso paciente, sugerimos que a idade do paciente pode ser decisiva na recuperação da acuidade visual de uma neuropatia óptica compressiva secundária à mucocele de seio esfenoidal. Mais pesquisas são necessárias para verificação desses dados.

A visual questioning answering approach to enhance robot localization in indoor environments.

Navigating robots with precision in complex environments remains a significant challenge. In this article, we present an innovative approach to enhance robot localization in dynamic and intricate spaces like homes and offices. We leverage Visual Question Answering (VQA) techniques to integrate semantic insights into traditional mapping methods, formulating a novel position hypothesis generation to assist localization methods, while also addressing challenges related to mapping accuracy and localization reliability. Our methodology combines a probabilistic approach with the latest advances in Monte Carlo Localization methods and Visual Language models. The integration of our hypothesis generation mechanism results in more robust robot localization compared to existing approaches. Experimental validation demonstrates the effectiveness of our approach, surpassing state-of-the-art multi-hypothesis algorithms in both position estimation and particle quality. This highlights the potential for accurate self-localization, even in symmetric environments with large corridor spaces. Furthermore, our approach exhibits a high recovery rate from deliberate position alterations, showcasing its robustness. By merging visual sensing, semantic mapping, and advanced localization techniques, we open new horizons for robot navigation. Our work bridges the gap between visual perception, semantic understanding, and traditional mapping, enabling robots to interact with their environment through questions and enrich their map with valuable insights. The code for this project is available on GitHub https://github.com/juandpenan/topology_nav_ros2.

Effect of the Nature of the Electrolyte on the Behavior of Supercapacitors Based on Transparent ZnMn2O4 Thin Films.

Transparent ZnMn2O4 thin films on indium tin oxide (ITO) were prepared through spray pyrolysis and implemented as electrodes in symmetric supercapacitors (SSCs). A specific capacitance value of 752 F g-1 at 0.5 A g-1 and a 70% retention over 3000 galvanostatic charge-discharge (GCD) cycles were reached with a 1.0 M Na2SO4 electrolyte in a three-electrode electrochemical cell. Analysis of the cycled electrodes with 1.0 M Na2SO4 revealed a local loss of electrode material; this loss increases when electrodes are used in SCCs. To avoid this drawback, solid polyvinylpyrrolidone-LiClO4 (PVP-LiClO4) and quasi-solid polyvinylpyrrolidone-ionic liquid (PVP-ionic liquid) electrolytes were tested in SSCs as substitutes for aqueous Na2SO4. An improvement in capacitance retention without a loss of electrode material was observed for the PVP-ionic liquid and PVP-LiClO4 electrolytes. With these non-aqueous electrolytes, the tetragonal structure of the ZnMn2O4 spinel was maintained throughout the cyclic voltammetry (CV) cycles, although changes occurred in the stoichiometry from ZnMn2O4 to Mn-rich Zn1-xMn3-xO4. In the case of the electrolyte 1.0 M Na2SO4, the loss of Zn2+ led to the formation of MnO2 via Zn1-xM3-xO4. The location of the three SCCs in the Ragone plot shows supercapacitor behavior. The electrochemical results prove that the pseudocapacitance is the major contributor to the electrode capacitance, and the SCCs can therefore be considered as pseudocapacitors.

Dry Eye Para-Inflammation Treatment: Evaluation of a Novel Tear Substitute Containing Hyaluronic Acid and Low-Dose Hydrocortisone.

Purpose: The purpose of this study was to check the efficacy and safety of a novel tear substitute containing hyaluronic acid and low-dose hydrocortisone in the treatment of moderate dry eye disease. Methods: In this prospective randomized study, 38 patients with moderate dry eye disease were divided into two treatment groups: Group 1 received one drop of 0.2% sodium hyaluronate and 0.001% hydrocortisone four times daily for 3 months, while Group 2 received 0.15% sodium hyaluronate and 3% trehalose at the same dosage. OSDI and SANDE questionnaires, Non-Invasive Break-Up time (NIBUT), Tear Meniscus Height (TMH), meibography, Lipid Layer Thickness (LLT), Tear Break-Up Time (TBUT), Corneal Staining Score (CFS), and Intraocular Pressure (IOP) were evaluated at baseline and after 1, 2, and 3 months of treatment. Results: During the treatment period, Group 1 showed statistically significant improvement in OSDI score (p = 0.002), SANDE score (p = 0.01), NIBUT (p < 0.0001), LLT (p < 0.0001), TBUT (p = 0.01), and CFS (p = 0.02). In Group 2, significant improvement was observed only in the TBUT score (p < 0.05). Comparison of the two groups showed that NIBUT and LLT were significantly different at the end of treatment (p = 0.001 for both comparisons), with more favorable results for sodium hyaluronate and hydrocortisone than for sodium hyaluronate and trehalose. No significant variations in intraocular pressure were observed in either group during the treatment period (p > 0.05). Conclusions: The study confirms that a 3-months treatment with hyaluronic acid 0.2% in combination with low-dose hydrocortisone 0.001% improves the signs and symptoms of moderate DED and that a low-dosage 0.001% hydrocortisone can be helpful in preventing the progression to chronic stages of DED.

Study protocol: assessment of the usefulness and practicability of a psychoeducational intervention to prevent the negative psychological impact of the COVID-19 pandemic on primary care health workers.

BACKGROUND: The COVID-19 pandemic has constituted an extraordinarily stressful situation for healthcare professionals and has led to psychological distress and an increase in various mental disorders. In the post-pandemic context, it is necessary to provide professionals with strategies and skills to manage this stressful situation and prevent or minimize its negative impact. METHODS: Aims: To assess the feasibility and clinical effects of a group psychoeducational program focused on preventing the adverse psychological and emotional effects of the pandemic on primary care workers, and to explore the experience and perceptions of participants with regard to the program from a qualitative perspective. DESIGN: A single-arm, before-and-after study conducted in primary care. SETTING: The 332 primary care centers of the Catalan Institute of Health (Catalonia, Spain) Participants: The target population of the intervention is primary care workers, including clinical profiles (e.g., nurses and doctors), and non-clinical profiles (e.g., administrative staff). The implementation strategy will also involve community psychologists, who will lead the psychoeducational groups, and the health organization promoting the implementation. INTERVENTION: A group psychoeducational program targeting primary care workers to promote emotional well-being and the ability to cope with stressful situations. Community psychologists will deliver it in the primary care centers they are linked to. MEASURES: Mixed-methods evaluation, combining quantitative and qualitative research. A prospective assessment of the main outcomes (professional quality of life, psychological state, and resilience) will be performed using online questionnaires before and immediately after the intervention, and at 3 and 6 months. A qualitative study will be conducted, comprising focus groups and individual in-depth interviews with the participants in the intervention and the psychologists who provide it. ETHICS: The Research Ethics Committee of the Jordi Gol Primary Care Research Institute (IDIAP) has approved the protocol (22/086-PCV). DISCUSSION: This project proposes an intervention to promote mental health and psychological well-being in primary care workers by learning skills and integrating them into personal and professional life. The expected results will allow us to determine the usefulness and effectiveness of this psychoeducational intervention under the conditions of real clinical practice, provide data to model and perfect it, and promote its dissemination. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05720429; registered on 09/02/2023.