Exploring the therapeutic potential of an antinociceptive and anti-inflammatory peptide from wasp venom.

Animal venoms are rich sources of neuroactive compounds, including anti-inflammatory, antiepileptic, and antinociceptive molecules. Our study identified a protonectin peptide from the wasp Parachartergus fraternus' venom using mass spectrometry and cDNA library construction. Using this peptide as a template, we designed a new peptide, protonectin-F, which exhibited higher antinociceptive activity and less motor impairment compared to protonectin. In drug interaction experiments with naloxone and AM251, Protonectin-F's activity was decreased by opioid and cannabinoid antagonism, two critical antinociception pathways. Further experiments revealed that this effect is most likely not induced by direct action on receptors but by activation of the descending pain control pathway. We noted that protonectin-F induced less tolerance in mice after repeated administration than morphine. Protonectin-F was also able to decrease TNF-α production in vitro and modulate the inflammatory response, which can further contribute to its antinociceptive activity. These findings suggest that protonectin-F may be a potential molecule for developing drugs to treat pain disorders with fewer adverse effects. Our results reinforce the biotechnological importance of animal venom for developing new molecules of clinical interest.

Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. Both peptides controlled the experimental IPF, maintaining the tissue characteristics and standard function properties and regulating fibrotic-associated cytokine production. Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF.

High prevalence of mental disorder symptoms among medical and other health specialties residents during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic put healthcare professionals, including residents (postgraduate trainees of health professions), under intense physical and psychological stress, hence at risk for mental disorders. We evaluated the prevalence of mental disorders among healthcare residents during the pandemic. METHODS: From July to September 2020, residents in medicine and other healthcare specialties in Brazil were recruited. The participants completed electronic forms with validated questionnaires (DASS-21, PHQ-9, BRCS) to screen for depression, anxiety, and stress, and to evaluate resilience. Data on potential predisposing factors for mental disorders were also collected. Descriptive statistics, chi-squared, students t, correlation and logistic regression models were applied. The study received ethical approval, and all participants provided informed consent. RESULTS: We included 1313 participants (51.3% medical; 48.7% nonmedical) from 135 Brazilian hospitals; mean (SD) age: 27.8 (4.4) years; 78.2% females; 59.3% white race. Of all participants, 51.3%, 53.4% and 52.6% presented symptoms consistent with depression, anxiety, and stress, respectively; 61.9% showed low resilience. Nonmedical residents exhibited higher anxiety compared to medical residents (DASS-21 anxiety score, mean difference: 2.26; 95% CI: 1.15-3.37; p < 0.001). In multivariate analyses, having any pre-existent, nonpsychiatric chronic disease was associated with higher prevalence of symptoms indicative of depression (odds ratio, OR: 2.05; 95% CI: 1.47-2.85, on DASS-21 | OR: 2.26; 95% CI: 1.59-3.20, on PHQ-9), anxiety (OR: 2.07; 95% CI: 1.51-2.83, on DASS-21), and stress (OR: 1.53; 95% CI: 1.12-2.09, on DASS-21); other predisposing factors were identified; by contrast, high resilience (BRCS score) was protective against symptoms of depression (OR 0.82; 95% CI: 0.79-0.85, on DASS-21 | OR 0.85; 95% CI: 0.82-0.88, on PHQ-9), anxiety (OR 0.90; 95% CI: 0.87-0.93, on DASS-21), and stress (OR 0.88; 95% CI: 0.85-0.91, on DASS-21); p < 0.05 for all outcomes. CONCLUSIONS: We found a high prevalence of mental disorder symptoms among healthcare residents during COVID-19 pandemic in Brazil. Nonmedical residents exhibited higher levels of anxiety than medical ones. Some predisposing factors for depression, anxiety and stress among residents were identified.

High prevalence of burnout syndrome among medical and nonmedical residents during the COVID-19 pandemic.

BACKGROUND: Since the beginning of the COVID-19 pandemic, health professionals have been working under extreme conditions, increasing the risk of physical and mental illness. We evaluated the prevalence of burnout and its associated factors among postgraduate student residents in health professions during the global health crisis. METHODS: Healthcare residents were recruited from all across Brazil between July and September 2020 through digital forms containing instruments for assessing burnout (Oldenburg Burnout Inventory (OLBI)), resilience (brief resilient coping scale (BRCS)) and anxiety, stress and depression (depression, anxiety and stress scale (DASS-21) and Patient Health Questionnaire (PHQ-9)). Additionally, the relationships between burnout and chronic diseases, autonomy and educational adequacy in the residency programme, personal protective equipment (PPE), workload and care for patients with COVID-19 were evaluated. The chi-square test, Student's t test, Pearson's correlation test and logistic regression were performed. RESULTS: A total of 1,313 participants were included: mean (standard deviation) age, 27.8 (4.4) years; female gender, 78.1%; white race, 59.3%; and physicians, 51.3%. The overall prevalence of burnout was 33.4%. The odds (odds ratio [95% confidence interval]) of burnout were higher in the presence of pre-existing diseases (1.76 [1.26-2.47]) and weekly work > 60 h (1.36 [1.03-1.79]) and were lower in the presence of high resilience (0.84 [0.81-0.88]), autonomy (0.87 [0.81-0.93]), and educational structure (0.77 [0.73-0.82]), adequate availability of PPE (0.72 [0.63-0.83]) and non-white race (0.63 [0.47-0.83]). Burnout was correlated with anxiety (r = 0.47; p < 0.05), stress (r: 0.58; p < 0.05) and depression (r: 0.65; p < 0.05). CONCLUSIONS: We observed a high prevalence of burnout among residents during the COVID-19 pandemic. Individual characteristics and conditions related to the work environment were associated with a higher or lower occurrence of the syndrome.

Combined exercise training improved exercise capacity and lung inflammation in rats with hepatopulmonary syndrome.

AIM: Physical exercise training attenuates pulmonary inflammation, but its effects on impaired respiratory function caused by hepatopulmonary syndrome (HPS) have not been evaluated. We determined if the combination of moderate intensity aerobic and resistance training during HPS development modifies exercise capacity, respiratory system mechanics, and lung inflammation responses. MAIN METHODS: Wistar rats were randomly divided into sham, HPS, and HPS + combined exercise training groups. Fifteen days after HPS induction, a moderate intensity aerobic plus resistance exercise training protocol was performed five times a week for 5 weeks on alternate days. Exercise capacity, respiratory system mechanics, lung inflammation, pulmonary morphology, and immunohistochemistry were evaluated. KEY FINDINGS: Overall, our findings indicated that combined exercise training efficiently increased the maximal running and resistance capacity of HPS animals. The training regimen reduced the expression of P2X7 in parenchymal leukocytes (P < 0.01), partially restored the expression of interleukin-10 in airway epithelium (P < 0.01), and increased the expression of TFPI in the airway epithelium (P < 0.01) as well as reduced its expression in parenchymal leukocytes (P < 0.01). However, exercise training did not attenuate HPS-induced respiratory mechanical derangements or lung tissue remodeling. SIGNIFICANCE: Combined exercise training can elicit adaptation with regard to both maximal running capacity and maximum strength and modify the expression of P2X7 and TFPI in parenchymal leukocytes and that of IL-10 in airway epithelium.

Mental Health and Burnout Syndrome Among Postgraduate Students in Medical and Multidisciplinary Residencies During the COVID-19 Pandemic in Brazil: Protocol for a Prospective Cohort Study.

BACKGROUND: The COVID-19 pandemic has led to high levels of physical, psychological, and social stress among health care professionals, including postgraduate students in medical and multidisciplinary residencies. This stress is associated with the intense fear of occupational exposure to SARS-CoV-2, the virus known to cause COVID-19. These professionals are at risk of developing physical and mental illnesses not only due to the infection but also due to prolonged exposure to multidimensional stress and continued work overload. OBJECTIVE: This study aims to evaluate the prevalence of symptoms suggestive of mental disorders and burnout syndrome and determine the risk factors for burnout among postgraduate students in medical and multidisciplinary residencies in Brazil during the COVID-19 pandemic. METHODS: For this prospective cohort study with parallel groups, participants were recruited between July and September 2020 to achieve a sample size of at least 1144 participants. Research instruments such as Depression, Anxiety, and Stress Scale; Patient Health Questionnaire; Brief Resilient Coping Scale; and Oldenburg Burnout Inventory will be used to collect data. Data will be collected in 2 waves: the first wave will include data related to sample characterization and psychosocial evaluation, and the second wave will be launched 12 weeks later and will include an evaluation of the incidence of burnout as well as correlations with the potential predictive factors collected in the first wave. Additionally, we will collect data regarding participants' withdrawal from work. RESULTS: The recruitment took place from July 29 to September 5, 2020. Data analyses for this phase is already in progress. The second phase of the study is also in progress. The final data collection began on December 1, 2020, and it will be completed by December 31, 2020. CONCLUSIONS: We believe the findings of this study will help evaluate the impact of the COVID-19 pandemic on the mental health conditions of health professionals in Brazil as well as contribute to the planning and implementation of appropriate measures that can alleviate these mental health challenges. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24298.

Right ventricular dysfunction in patients with non-severe idiopathic pulmonary fibrosis: a cross-sectional prospective single-center study.

BACKGROUND: Little is known about right ventricular dysfunction in non-advanced idiopathic pulmonary fibrosis (IPF) patients without hypoxemia at rest. We evaluated it at rest and during exercise. RESEARCH DESIGN AND METHODS: 123 IPF patients were evaluated, and 27 met all the following criteria: Gender-Age-Physiology Index score ≤5, modified Medical Research Council dyspnea score ≤3, peripheral oxygen saturation ≥92% at rest, and no history of oxygen therapy. They were submitted to two-dimensional speckle-tracking echocardiography at rest and during cardiopulmonary exercise to analyze right ventricular global longitudinal strain. RESULTS: Abnormal speckle-tracking echocardiography findings were identified in 10/27 patients (37%), indicating right ventricular (RV) dysfunction. No patients had abnormalities observed in conventional echocardiographic parameters. Significant differences in mPAP were observed between patients with RV dysfunction and those without dysfunction (at rest: 26.0 ± 4.8 vs. 19.1 ± 4.2 mmHg, p = 0.001; during exercise: 51.3 ± 6.4 vs. 36.9 ± 14.7 mmHg, p = 0.002). CONCLUSIONS: RV dysfunction was detected in 37% of non-advanced IPF patients and early recognition was only possible using speckle-tracking echocardiography. Special attention should be given to these patients as RV dysfunction is suggestive of worse prognosis. These patients could benefit from new specific drugs or even oxygen therapy for transitory hypoxia.

Accuracy of chest auscultation in detecting abnormal respiratory mechanics in the immediate postoperative period after cardiac surgery.

OBJECTIVE: To investigate the accuracy of chest auscultation in detecting abnormal respiratory mechanics. METHODS: We evaluated 200 mechanically ventilated patients in the immediate postoperative period after cardiac surgery. We assessed respiratory system mechanics - static compliance of the respiratory system (Cst,rs) and respiratory system resistance (R,rs) - after which two independent examiners, blinded to the respiratory system mechanics data, performed chest auscultation. RESULTS: Neither decreased/abolished breath sounds nor crackles were associated with decreased Cst,rs (≤ 60 mL/cmH2O), regardless of the examiner. The overall accuracy of chest auscultation was 34.0% and 42.0% for examiners A and B, respectively. The sensitivity and specificity of chest auscultation for detecting decreased/abolished breath sounds or crackles were 25.1% and 68.3%, respectively, for examiner A, versus 36.4% and 63.4%, respectively, for examiner B. Based on the judgments made by examiner A, there was a weak association between increased R,rs (≥ 15 cmH2O/L/s) and rhonchi or wheezing (ϕ = 0.31, p < 0.01). The overall accuracy for detecting rhonchi or wheezing was 89.5% and 85.0% for examiners A and B, respectively. The sensitivity and specificity for detecting rhonchi or wheezing were 30.0% and 96.1%, respectively, for examiner A, versus 10.0% and 93.3%, respectively, for examiner B. CONCLUSIONS: Chest auscultation does not appear to be an accurate diagnostic method for detecting abnormal respiratory mechanics in mechanically ventilated patients in the immediate postoperative period after cardiac surgery.

Case report - Gluteal hematoma in two spinal cord patients on enoxaparin for venous thromboembolism prophylaxis: evidence needed for a wiser choice.

Introduction: Acute spinal cord injury is associated with an increased risk of thromboembolic events. Low-molecular-weight heparins are first-line medications for both the treatment and prevention of venous thromboembolism. Pharmacological prophylaxis may be indicated for high-risk patients and low-risk patients may be managed with non-pharmacological measures. Case presentation: We report two cases of gluteal hematomas that occurred in patients with chronic spinal cord injury who were under prophylactic doses of enoxaparin at a tertiary rehabilitation hospital. There was no local trauma. The patients needed multiple surgical interventions and rehabilitation treatment was delayed. Discussion: There is a lack of evidence to correctly estimate the thromboembolic risk in chronic spinal cord injury and the duration of prophylaxis. Over-prescription of pharmacological prophylaxis may expose patients to unnecessary risks. These patients frequently present with polypharmacy and reducing the amount of prescribed medication may begin with reducing prophylactic treatments for venous thromboembolism, which may be an overtreatment based on risk overestimation.

Comparison of two pharmacological prophylaxis strategies for venous thromboembolism in spinal cord injury patients: a retrospective study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare the cost and incidence of venous thromboembolism (VTE) and bleeding between two different VTE pharmacological prophylaxis strategies in individuals with spinal cord injury: one based on motor impairment (Protocol 1) and the other based on time from the lesion and presence of associated risk factors for VTE (Protocol 2). SETTING: A tertiary rehabilitation hospital in Brazil. METHODS: We retrospectively reviewed a total of 1475 charts of individual admissions: 814 individuals received pharmacological prophylaxis according to Protocol 1 and 661 according to protocol 2. These cohorts were compared with respect to age, time and level of injury, length of stay, AIS classification, type of injury, and occurrence of VTE and major bleeding. The number of prescribed doses of enoxaparin and expenditures associated with enoxaparin during each period were evaluated. RESULTS: The median lesion time was 3 years. The risk-based strategy drastically reduced the average monthly use of enoxaparin by 75% and the 12-month enoxaparin expenditure by $119,930.33, without increasing the risk of VTE. The incidence density of thromboembolic events was 0.55/10,000 patient-days, and all events occurred in individuals receiving prophylaxis according to Protocol 1. CONCLUSIONS: Time from injury and risk of VTE-based protocol for indication of pharmacological prophylaxis drastically reduced costs. No difference in occurrence of VTE was observed.

Accuracy of chest auscultation in detecting abnormal respiratory mechanics in the immediate postoperative period after cardiac surgery / Acurácia da ausculta torácica na detecção de mecânica respiratória anormal no pós-operatório imediato de cirurgia cardíaca

ABSTRACT Objective: To investigate the accuracy of chest auscultation in detecting abnormal respiratory mechanics. Methods: We evaluated 200 mechanically ventilated patients in the immediate postoperative period after cardiac surgery. We assessed respiratory system mechanics - static compliance of the respiratory system (Cst,rs) and respiratory system resistance (R,rs) - after which two independent examiners, blinded to the respiratory system mechanics data, performed chest auscultation. Results: Neither decreased/abolished breath sounds nor crackles were associated with decreased Cst,rs (≤ 60 mL/cmH2O), regardless of the examiner. The overall accuracy of chest auscultation was 34.0% and 42.0% for examiners A and B, respectively. The sensitivity and specificity of chest auscultation for detecting decreased/abolished breath sounds or crackles were 25.1% and 68.3%, respectively, for examiner A, versus 36.4% and 63.4%, respectively, for examiner B. Based on the judgments made by examiner A, there was a weak association between increased R,rs (≥ 15 cmH2O/L/s) and rhonchi or wheezing (ϕ = 0.31, p < 0.01). The overall accuracy for detecting rhonchi or wheezing was 89.5% and 85.0% for examiners A and B, respectively. The sensitivity and specificity for detecting rhonchi or wheezing were 30.0% and 96.1%, respectively, for examiner A, versus 10.0% and 93.3%, respectively, for examiner B. Conclusions: Chest auscultation does not appear to be an accurate diagnostic method for detecting abnormal respiratory mechanics in mechanically ventilated patients in the immediate postoperative period after cardiac surgery.

RESUMO Objetivo: Investigar a acurácia da ausculta torácica na detecção de mecânica respiratória anormal. Métodos: Foram avaliados 200 pacientes sob ventilação mecânica no pós-operatório imediato de cirurgia cardíaca. Foi avaliada a mecânica do sistema respiratório - complacência estática do sistema respiratório (Cest,sr) e resistência do sistema respiratório (R,sr) - e, em seguida, dois examinadores independentes, que desconheciam os dados referentes à mecânica do sistema respiratório, realizaram a ausculta torácica. Resultados: Nem murmúrio vesicular diminuído/abolido nem crepitações foram associados à Cest,sr reduzida (≤ 60 ml/cmH2O), independentemente do examinador. A acurácia global da ausculta torácica foi de 34,0% e 42,0% para os examinadores A e B, respectivamente. A sensibilidade e a especificidade da ausculta torácica para a detecção de murmúrio vesicular diminuído/abolido e/ou crepitações foi de 25,1% e 68,3%, respectivamente, para o examinador A, versus 36,4% e 63,4%, respectivamente, para o examinador B. Com base nos julgamentos feitos pelo examinador A, houve uma fraca associação entre R,sr aumentada (≥ 15 cmH2O/l/s) e roncos e/ou sibilos (ϕ = 0,31, p < 0,01). A acurácia global para a detecção de roncos e/ou sibilos foi de 89,5% e 85,0% para os examinadores A e B, respectivamente. A sensibilidade e a especificidade para a detecção de roncos e/ou sibilos foi de 30,0% e 96,1%, respectivamente, para o examinador A, versus 10,0% e 93,3%, respectivamente, para o examinador B. Conclusões: A ausculta torácica não parece ser um método diagnóstico acurado para a detecção de mecânica respiratória anormal em pacientes sob ventilação mecânica no pós-operatório imediato de cirurgia cardíaca.

Hipertensão portopulmonar / Portopulmonary hypertension

A hipertensão portopulmonar (POPH) é definida como hipertensão pulmonar na presença de hipertensão portal. Acomete cerca de 5% dos pacientes com hipertensão portal, cirróticos ou não, em avaliação para transplante hepático. A fisiopatologia dessa doença não está completamente elucidada. O hiperfluxo pulmonar e a formação conexões porto-sistêmicas, que permitem o acesso de bactérias e de substâncias inflamatórias aos pulmões, são mecanismos prováveis. Variações genéticas possivelmente estão implicadas na variabilidade do comprometimento vascular pulmonar dos pacientes com hipertensão portal. O ecocardiograma tem papel importante como rastreamento, sendo o diagnóstico definitivo realizado através do cateterismo cardíaco direito. A POPH pode ser considerada contraindicação ao transplante hepático, nos casos moderados e graves, no entanto, o tratamento com vasodilatadores pulmonares, indicado para esses pacientes, pode ser capaz de melhorar o perfil hemodinâmico e permitir que mais pacientes atinjam os critérios de segurança para o transplante. Com as novas abordagens terapêuticas, observou-se melhora no prognóstico desses pacientes nos últimos anos...

Portopulmonary hypertension (POPH) is defined as pulmonary hypertension in the presence of portal hypertension. It affects about 5% of patients with portal hypertension, cirrhotic or not, under evaluation for liver transplantation. The pathophysiology of this disease is not completely understood, but hyperdynamic state in pulmonary circulation and formation of porto-systemic connections, which allow access of intestinal bacteria and inflammatory substances to the lungs, are probably involved. Genetic variations possibly play a role in the variability of the pulmonary vascular impairment of patients with portal hypertension. Echocardiography is important for screening, but the definitive diagnosis is made by right heart catheterization. The POPH can be considered a contraindication for liver transplantation in moderate to severe cases, however, treatment with pulmonary vasodilators, indicated for these patients, may be able to improve hemodynamic profile and allow more patients meet the criteria for transplantation. With new therapeutic approaches, there was an improvement in the prognosis of these patients in recent years...

Accuracy of pulmonary auscultation to detect abnormal respiratory mechanics: a cross-sectional diagnostic study.

Pulmonary auscultation is a method used in clinical practice for the evaluation and detection of abnormalities relating to the respiratory system. This method has limitations, as it depends on the experience and hearing acuity of the examiner to determine adventitious sounds. In this context, it's important to analyze whether there is a correlation between auscultation of lung sounds and the behavior of the respiratory mechanical properties of the respiratory system in patients with immediate postoperative cardiac surgery.

Recomendações brasileiras de ventilação mecânica 2013. Parte 2 / Brazilian recommendations of mechanical ventilation 2013. Part 2

O suporte ventilatório artificial invasivo e não invasivo ao paciente grave tem evoluído e inúmeras evidências têm surgido, podendo ter impacto na melhora da sobrevida e da qualidade do atendimento oferecido nas unidades de terapia intensiva no Brasil. Isto posto, a Associação de Medicina Intensiva Brasileira (AMIB) e a Sociedade Brasileira de Pneumologia e Tisiologia (SBPT) - representadas por seu Comitê de Ventilação Mecânica e sua Comissão de Terapia Intensiva, respectivamente, decidiram revisar a literatura e preparar recomendações sobre ventilação mecânica, objetivando oferecer aos associados um documento orientador das melhores práticas da ventilação mecânica na beira do leito, com base nas evidências existentes, sobre os 29 subtemas selecionados como mais relevantes no assunto. O projeto envolveu etapas que visaram distribuir os subtemas relevantes ao assunto entre experts indicados por ambas as sociedades, que tivessem publicações recentes no assunto e/ou atividades relevantes em ensino e pesquisa no Brasil, na área de ventilação mecânica. Esses profissionais, divididos por subtemas em duplas, responsabilizaram-se por fazer uma extensa revisão da literatura mundial. Reuniram-se todos no Fórum de Ventilação Mecânica, na sede da AMIB, na cidade de São Paulo (SP), em 3 e 4 de agosto de 2013, para finalização conjunta do texto de cada subtema e apresentação, apreciação, discussão e aprovação em plenária pelos 58 participantes, permitindo a elaboração de um documento final.

Perspectives on invasive and noninvasive ventilatory support for critically ill patients are evolving, as much evidence indicates that ventilation may have positive effects on patient survival and the quality of the care provided in intensive care units in Brazil. For those reasons, the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB) and the Brazilian Thoracic Society (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT), represented by the Mechanical Ventilation Committee and the Commission of Intensive Therapy, respectively, decided to review the literature and draft recommendations for mechanical ventilation with the goal of creating a document for bedside guidance as to the best practices on mechanical ventilation available to their members. The document was based on the available evidence regarding 29 subtopics selected as the most relevant for the subject of interest. The project was developed in several stages, during which the selected topics were distributed among experts recommended by both societies with recent publications on the subject of interest and/or significant teaching and research activity in the field of mechanical ventilation in Brazil. The experts were divided into pairs that were charged with performing a thorough review of the international literature on each topic. All the experts met at the Forum on Mechanical Ventilation, which was held at the headquarters of AMIB in São Paulo on August 3 and 4, 2013, to collaboratively draft the final text corresponding to each sub-topic, which was presented to, appraised, discussed and approved in a plenary session that included all 58 participants and aimed to create the final document.