Idiopathic pulmonary fibrosis: Addressing the current and future therapeutic advances along with the role of Sotatercept in the management of pulmonary hypertension.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and debilitating lung disease characterized by irreversible scarring of the lungs. The cause of IPF is unknown, but it is thought to involve a combination of genetic and environmental factors. There is no cure for IPF, and treatment is focused on slowing disease progression and relieving symptoms. AIMS: We aimed in this review to investigate and provide the latest insights into IPF management modalities, including the potential of Saracatinibas a substitute for current IPF drugs. We also investigated the therapeutic potential of Sotatercept in addressing pulmonary hypertension associated with IPF. MATERIALS AND METHODS: We conducted a comprehensive literature review of relevant studies on IPF management. We searched electronic databases, including PubMed, Scopus, Embase, and Web of science. RESULTS: The two Food and Drug Administration-approved drugs for IPF, Pirfenidone, and Nintedanib, have been pivotal in slowing disease progression, yet experimental evidence suggests that Saracatinib surpasses their efficacy. Preclinical trials investigating the potential of Saracatinib, a tyrosine kinase inhibitor, have shown to be more effective than current IPF drugs in slowing disease progression in preclinical studies. Also, Sotatercept,a fusion protein, has been shown to reduce pulmonary vascular resistance and improve exercise tolerance in patients with PH associated with IPF in clinical trials. CONCLUSIONS: The advancements discussed in this review hold the promise of improving the quality of life for IPF patients and enhancing our understanding of this condition. There remains a need for further research to confirm the efficacy and safety of new IPF treatments and to develop more effective strategies for managing exacerbations.

Effect of an Emergency Department Process Improvement Package on Suicide Prevention: The ED-SAFE 2 Cluster Randomized Clinical Trial.

Importance: Suicide is a leading cause of deaths in the US. Although the emergency department (ED) is an opportune setting, ED-initiated interventions remain underdeveloped and understudied. Objective: To determine if an ED process improvement package, with a subfocus on improving the implementation of collaborative safety planning, reduces subsequent suicide-related behaviors. Design, Setting, and Participants: The Emergency Department Safety Assessment and Follow-up Evaluation 2 (ED-SAFE 2) trial, a stepped-wedge cluster randomized clinical trial conducted in 8 EDs across the US, used an interrupted time series design with three 12-month sequential phases: baseline, implementation, and maintenance. A random sample of 25 patients per month per site 18 years and older who screened positive on the Patient Safety Screener, a validated suicide risk screener, were included. The primary analyses focused on those who were discharged from the ED, while secondary analyses focused on all patients who screened positive, regardless of disposition. Data were collected on patients who presented for care from January 2014 to April 2018, and data were analyzed from April to December 2022. Interventions: Each site received lean training and built a continuous quality improvement (CQI) team to evaluate the current suicide-related workflow in the ED, identify areas of improvement, and implement efforts to improve. Each site was expected to increase their universal suicide risk screening and implement collaborative safety planning for patients at risk of suicide who were discharged home from the ED. Site teams were centrally coached by engineers experienced in lean CQI and suicide prevention specialists. Main Outcomes and Measures: The primary outcome was a composite comprising death by suicide or suicide-related acute health care visits, measured over a 6-month follow-up window. Results: Across 3 phases, 2761 patient encounters were included in the analyses. Of these, 1391 (50.4%) were male, and the mean (SD) age was 37.4 (14.5) years. A total of 546 patients (19.8%) exhibited the suicide composite during the 6-month follow-up (9 [0.3%] died by suicide and 538 [19.5%] of a suicide-related acute health care visit). A significant difference was observed for the suicide composite outcome between the 3 phases (baseline, 216 of 1030 [21%]; implementation, 213 of 967 [22%]; maintenance, 117 of 764 [15.3%]; P = .001). The adjusted odds ratios of risk of the suicide composite during the maintenance phase was 0.57 (95% CI, 0.43-0.74) compared with baseline and 0.61 (0.46-0.79) compared with the implementation phase, which reflect a 43% and 39% reduction, respectively. Conclusions and Relevance: In this multisite randomized clinical trial, using CQI methods to implement a department-wide change in suicide-related practices, including the implementation of a safety plan intervention, yielded a significant decrease in suicide behaviors in the maintenance period of the study. Trial Registration: ClinicalTrials.gov Identifier: NCT02453243.

Determination of antimicrobial and antioxidant potential of agro-waste peels.

Natural products from plants are pulling in more interest in exploration due to their therapeutic properties like, mainly because of the drug-resistance in microbes against synthetic drugs. Thus, the present study was designed to assess the antimicrobial and antioxidant actions of some Agro-waste (garlic, ginger, onion, potato) peel extracts. Ginger peel extracts exhibited the highest FRAP (0.273±0.044 mm Fe2+ Eq/g dry weight) while garlic peel extracts exhibited the highest TAC (0.47±0.0452 mm AAE/g dry weight) values among all selections. The antimicrobial activity of the peels was evaluated against different pathogenic bacterial and fungal strains i.e.; Escherichia coli, Bacillus megaterium, Bacillus cereus, Staphylococcus aureus, Colletotrichum falcatum, Fusarium moniliforme, and Rhizoctonia solani. Among all extracts, ginger peel extracts exhibited maximum inhibition against all bacterial strains, while onion peel extracts exhibited zero inhibition against any bacterial strains. All extracts exhibited maximum inhibition against Staphylococcus aureus except onion peel extracts. Positive inhibition against all fungal strains was observed for all samples, with maximum inhibition against Colletotrichum falcatum. The outcomes of the study, therefore reveal that Agro-wastes have a powerful antimicrobial and antioxidant potency and thus can be used for many medicinal purposes, which will likewise be helpful in waste management and environmental safety.

Development and pilot study of simple suicide risk rulers for use in the emergency department.

BACKGROUND: Many patients treated in the emergency department (ED) for non-psychiatric complaints have elevated suicide risk. Universal screening can detect occult suicide risk, but gold standard risk measurement tools, such as the Beck Scale for Suicidal Ideation (BSS), are too long and cumbersome for ED use. OBJECTIVE: To test the performance of seven novel 0- to 10-point suicide risk "rulers" against the BSS. METHOD: 399 patients from three EDs completed seven novel risk rulers, traditional binary screening items, and the BSS. Using BSS criterion references, we tested the diagnostic performance of each risk ruler and examined correlations between the rulers and BSS scores. RESULTS: By varying thresholds on the risk rulers, high levels of sensitivity and specificity were obtained. A threshold of 3 on the "sadness" ruler gave 89% sensitivity for the BSS criterion reference, and a threshold of 1 on the "wish to be dead" ruler provided 94-97% specificity. CONCLUSION: Our novel risk rulers may be an efficient way to detect risk and triage potentially suicidal patients, showing good concurrent validity with the BSS. Clinicians can obtain high sensitivity and high specificity using just two rulers. Further research should examine the rulers' ability to predict independent clinician risk ratings and prospective suicidal behavior.

IGFBP-5 enhances epithelial cell adhesion and protects epithelial cells from TGFß1-induced mesenchymal invasion.

TGFß1 is a major fibrotic factor and its actions involve induction of epithelial cell death, together with the stimulation and transdifferentiation of fibroblasts into collagen- and fibronectin-secreting myofibroblasts. These actions of TGFß1 are also consistent with a pro-metastatic role, by aiding epithelial cell escape through mesenchymal tissues. Recently IGFBP-5 has been described as a pro-fibrotic (pro-metastatic?) agent and the aim of this study was to compare and contrast the actions of IGFBP-5 with TGFß1. We used NMuMG cells and cloned stable epithelial and mesenchymal lines from the parent cells. TGFß1 induced apoptosis and/or EMT in the epithelial cells, whereas it enhanced mesenchymal cell survival and migration. IGFBP-5, in contrast, enhanced both cell-cell and cell-ECM adhesion and also improved wound closure in epithelial cells whereas, in mesenchymal cells, IGFBP-5 decreased adhesion and migration. Furthermore, IGFBP-5 was able to antagonise the actions of TGFß1. In a co-culture model simulating epithelial-mesenchymal boundaries, IGFBP-5 was able to antagonise the disruptive transgressions induced by TGFß1. Overall, these findings suggest that IGFBP-5 is important in maintaining epithelial-mesenchymal boundaries and thus may limit metastasis and fibrosis by inducing an orderly repair mechanism, very distinct from the fibrotic disruption induced by TGFß1. A role for IGFBP-5 in the inhibition of metastasis is supported by immunohistochemical studies of breast cancer microarrays, where we show that elevated IGFBP-5 expression is associated with increased disease-free survival.

A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions.

Complex amino acids with an α-acyloxycarbonyl functionality in the side chain are easily available through epoxide opening by chelated enolates and subsequent oxidation/Passerini reaction. This protocol works with both, aldehyde and ketone intermediates, as long as the ketones are activated by electron-withdrawing groups. In principle Ugi reactions are also possible, allowing the generation of diamino acid derivatives.

Simplified gene synthesis: a one-step approach to PCR-based gene construction.

PCR-based gene synthesis conventionally requires two steps: first, all overlapping oligonucleotides are assembled by self-priming; then an additional pair of primers is used to amplify the full-length gene product. Here we propose a simplified method of gene synthesis which combines these two steps into one. We have found that the efficiency of this one-step method, which we term "Simplified Gene Synthesis", is affected by multiple parameters of the PCR reactions. In particular, the choice of polymerase is critical for successful one-step assembly. Other important factors include the concentration of assembly oligonucleotides and amplification primers. Moreover, we offer a general method to estimate, given a known mutation rate, how many clones should be sequenced in order to be confident of obtaining at least one correct gene product. Having determined the accuracy of gene products synthesized under optimal conditions with Simplified Gene Synthesis, we show that our estimation works well. Overall, the simplified gene synthesis provides an easier and more efficient approach to gene synthesis, providing a further step towards the future goal of generalized automation for this process.