Search

Background: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19., Methods: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350 mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728)., Findings: Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group., Interpretation: BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19., Funding: Biophytis., Competing Interests: Biophytis declares that potential commercial interests had no impact on the scientific conduct of the study nor on the analysis/interpretation of data. Cendrine Tourette, Luis Esmeraldino, Pierre Jean Dilda, René Lafont, Serge Camelo, Sandrine Rabut, Waly Dioh, Rob van Maanen and Stanislas veillet are Biophytis company employees, Anait Azbekyan Samuel Agus and Mounia Chabane are former Biophytis company employees. Jean Mariani is emeritus professor at Sorbonne University and consultant for Biophytis, Richard Kay is a consultant for Biophytis. Alpesh Amin, MD declares that as principal investigator or co-investigator of clinical trials sponsored by NIH/NIAID, NeuroRx Pharma, Pulmotect, Blade Therapeutics, Novartis, Takeda, Humanigen, Eli Lilly, PTC Therapeutics, OctaPharma, Fulcrum Therapeutics, Alexion, BioPhysitis its institution received payments and that he personnally received consultant fees from BMS, Pfizer, BI, Portola, Sunovion, Mylan, Salix, Alexion, AstraZeneca, Novartis, Nabriva, Paratek, Bayer, Tetraphase, Achogen LaJolla, Ferring, Seres, Spero, Eli Lilly, Gilead, Millenium, HeartRite, Aseptiscope, and Sprightly; but that these relationships were unrelated to the current work. Shaheen Islam, MD declares that he received grants or was in contract as a principal or sub investigator from the following companies:–Pliant therapeutics: INTEGRIS-ARDS, drug (PLN74809) Covid -trial 2021 (PI).—CytoDyn, Inc.: CD12-COVID 19 Drug: Leronlimab COVID trial 2020 (PI). -Pluristem Ltd.: PLX-COV-01. Drug PLX-PAD, COVID Trial 2020 (Sub-I).—Edesa Biotech Inc.: EB05-04-2020. Drug: EB05 COVID Trial 2020 (Sub-I). Fabiano Ramos, MD declares that its institution: Hospital São Lucas da Pontíficia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil received financial resources to conduct the study from Biophytis. Brian Snyder, MD declares that he receives research funding from Biophytis as part of the present clinical trial. Moreover, he declares that he received grants or has contracts with Behring, and Rheonix as part of COVID research studies. None of the other investigators declare any relationship related to the current work., (© 2023 The Author(s).)

Financial burden due to poor occupational safety practices remains high although occupational health and safety (OHS) have improved in recent years. Conducting risk assessment is one way to improve OHS. Workplaces may not have sufficient expertise in risk assessment. The aim of this study was to identify the needed OHS risk assessment skills, current support in the workplaces and the ways to improve risk assessment skills. This study was conducted with the Delphi survey for OHS experts ( n = 13) and with interviews ( n = 41) in the case companies. OHS experts agreed that the most significant skills were for employees to identify hazards and minimize risks in one's work; for supervisors to influence others with a good example; and for OHS experts to understand and manage the wholeness of safety practices and understand and manage the meaning, concepts, and criteria of risk assessment. The current main support methods were learning at work, training and written instructions. However, many of the interviewees felt that they had not received risk assessment training and that the support depended on their activity. Finally, the OHS experts determined that the most feasible ways to improve risk assessment skills were training, coaching and giving clear instructions. Likewise, the interviewees suggested various training methods. Based on these results, concrete development plans to improve risk assessment skills can be made.

Objective: This study aims to investigate the association between the immunohistochemical expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and plasma zinc in women with fibroadenoma., Methods: This cross-sectional study included 37 premenopausal women with fibroadenoma. Waist circumference and body mass index of the participants were measured. Plasma zinc concentrations were determined using atomic flame absorption spectrophotometry. Fragments of breast tissue were fixed and incubated with primary mouse monoclonal antibodies (monoclonal antibodies matrix metalloproteinase -2 -507 and monoclonal antibodies matrix metalloproteinase -9-439). Semi-quantitative analysis of matrix metalloproteinase-2 and matrix metalloproteinase-9 immunoreactivity was performed. Spearman's test and Friedman's test were used for statistical analyses. The p<0.05 were considered statistically significant., Results: The average age of the participants was 32.81±9.51 years. The body mass index and waist circumference values were within the normal range. The mean plasma zinc concentration was 42.73±13.84 µg/dL, with 94.6% inadequacy. A statistically significant difference was found between the positive expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 (p=0.0184). There was no significant correlation between the matrix metalloproteinase expression and the plasma zinc levels., Conclusions: Women with fibroadenoma had hypozincemia and positive expression of metalloproteinases.

The demand for information on the soil resource to support the establishment of public policies for land use and management has grown exponentially in the last years. However, there are still difficulties to the proper use of already existing information for soil mapping. Here we aimed to establish a protocol for soil mapping using legacy data, magnetic signature and soil attributes evaluation. A total of 493 soil samples were collected at 0-0.20 m in the geological domain of Western Plateau of São Paulo State. This work has three parts: First, we performed a classification analysis using soil mapping units (SMU) extracted from conventional soil map and Support Vector Machines algorithm (SVM). As covariates, we used categorical information, such as geology, dissection and landform maps. Second, we used soil attributes to perform a cluster analysis using k-means as partitioning method. To choose the optimal number of clusters, the same number of SMU showed in the conventional soil map (e.g. 34 clusters) were used. The last step was to compare soil and clusters maps predicted by SVM with the conventional soil map. Results showed good performance of SVM for both classifications (clusters and SMU), with overall accuracy of 0.60 and 0.90 respectively. In addition, the distribution of soil attributes within each cluster was more homogeneous and well distributed than within SMU, showing that is very possible to use numerical classification for soil mapping. Future soil surveys could use cluster analysis as a preliminary evaluation for better understanding of tropical soil variations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The overexpression of Metallothionein-1 (MT-1) may play an important role in breast cancer; however, few studies have compared MT-1 expression between breast cancer and fibroadenoma. A cross-sectional controlled study was performed in 66 premenopausal women, aged 20-49 years, who had been histologically diagnosed with breast fibroadenoma or breast cancer. The patients were divided into two groups: group A, control (fibroadenoma, n = 36) and group B, study (breast cancer, n = 30). Immunohistochemistry was performed on tissue samples of fibroadenoma and breast cancer patients to evaluate the expression of metallothionein using an anti-MT-1 polyclonal antibody (rabbit polyclonal anti-metallothionein-Catalog Number biorbyt-orb11042) at a dilution of 1:100. The data were analyzed using NOVA (p < 0.05). Microscopic analysis showed a higher concentration of anti-MT-1-stained nuclei in breast cancer tissues than in fibroadenoma tissues. The mean proportion of cells with anti-MT-1-stained nuclei was 26.93% and 9.10%, respectively, in the study and control groups (p < 0.001). Histological grade 3 tumors showed a significantly higher MT-1 expression than hitological grade 1 (p < 0.05), while breast tumors negative for estrogen-, progesterone- and HER2- receptors had a significantly higher MT-1 expression than positive breast tumors positive for these parameters (p < 0.05). MT-1 protein in women of reproductive age was significantly higher in breast cancer than in fibroadenoma in this study. Furthermore, there was higher MT-1 immunoreactivity in more aggressive tumors.

Background: Drug-induced liver injury (DILI) sometimes resembles autoimmune hepatitis (AIH) in its hepatic histology. However, there is lacking data of a comparison of the characteristics between such DILI and DILI without histological findings like AIH., Methods: We enrolled 62 patients with DILI who were diagnosed using the Roussel Uclaf Causality Assessment Method, and performed a liver biopsy. These patients were classified into two groups: DILI with histology like AIH (group A, n = 23) and DILI without such histology (group B, n = 39). Sixteen patients of group A could be further classified into two groups: patients with relapse of the liver injury (group C, n = 8) and without relapse (group D, n = 8), after the recovery of the DILI. We compared the clinical and histological findings between group A and B, and group C versus D., Results: Group A was characterized by an older age (p = 0.043), higher immunoglobulin G level (p = 0.017), positive antinuclear antibody status (p = 0.044), and a higher frequency of complementary alternative medicines and Chinese herbal medicines as the causative drug (p = 0.008). There were no significant differences between group C and D regarding the clinical data and liver histological findings., Conclusions: The clinical characteristics of DILI, which showed histological findings similar to AIH, were revealed. In such patients, a liver biopsy is recommended in order to determine the appropriate treatment strategy. In DILI with histology like AIH patients, long-term follow-up is needed to perceive the relapse.