Pakistan's Emergency Medical Services (EMS) system & out-of-hospital-cardiac-arrest (OHCA): A narrative review of an EMS system of a low middle income country in context of OHCA.

Pakistan's Emergency Medical Services (EMS) are a critical component of its healthcare system, providing pre-hospital emergency care across a nation with over 220 million people. This article explores the evolutionary journey of Pakistan's EMS, highlighting both the challenges it faces and the strides it has made, with a specific emphasis on patients experiencing out-of-hospital cardiac arrest (OHCA). To extract relevant information, we searched MEDLINE & Embase data bases using MeSH terms "Emergency Medical Services" OR "EMS" AND "Out-of-Hospital-Cardiac-Arrest" OR "OHCA" AND "Pakistan". In addition, we also retrieved information from the EMS leadership in Pakistan through e-mails. We delve into the significance of key performance indicators for OHCA, advocate for the establishment of OHCA registries to improve patient outcomes, address regional disparities in pre-hospital care, and acknowledge the gradual progress of the EMS system.

Discovery of Quinoline-Derived Trifluoromethyl Alcohols as Antiepileptic and Analgesic Agents That Block Sodium Channels.

The discovery of novel analgesic agents with high potency, low toxicity and low addictive properties remain a priority. This study aims to identify the analgesic potential of quinoline derived α-trifluoromethylated alcohols (QTA) and their mechanism of action. We synthesized and characterized several compounds of QTAs and screened them for antiepileptic and analgesic activity using zebrafish larvae in high thorough-put behavior analyses system. Toxicity and behavioral screening of 9 compounds (C1-C9) identified four candidates (C2, C3, C7 and C9) with antiepileptic properties that induces specific and reversible reduction in photomotor activity. Importantly, compounds C2 and C3 relieved the thermal pain response in zebrafish larvae indicating analgesic property. Further, using novel in vivo CoroNa green assay, we show that compounds C2 and C3 block sodium channels and reduce inflammatory sodium signals released by peripheral nerve and tissue damage. Thus, we have identified novel QTA compounds with antiepileptic and analgesic properties which could alleviate neuropathic pain.

Discovery of Quinoline-Derived Trifluoromethyl Alcohols, Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model.

In this study the rational design, synthesis, and anticancer activity of quinoline-derived trifluoromethyl alcohols were evaluated. Members of this novel class of trifluoromethyl alcohols were identified as potent growth inhibitors in a zebrafish embryo model. Synthesis of these compounds was carried out with an sp(3) -C-H functionalization strategy of methyl quinolines with trifluoromethyl ketones. A zebrafish embryo model was also used to explore the toxicity of ethyl 4,4,4-trifluoro-3-hydroxy-3-(quinolin-2-ylmethyl)butanoate (1), 2-benzyl-1,1,1-trifluoro-3-(quinolin-2-yl)propan-2-ol (2), and trifluoro-3-(isoquinolin-1-yl)-2-(thiophen-2-yl)propan-2-ol (3). Compounds 2 and 3 were found to be more toxic than compound 1; apoptotic staining assays indicated that compound 3 causes increased cell death. In vitro cell proliferation assays showed that compound 2, with an LC50 value of 14.14 µm, has more potent anticancer activity than cisplatin. This novel class of inhibitors provides a new direction in the discovery of effective anticancer agents.

Total synthesis of Herbarin A and B, determination of their antioxidant properties and toxicity in zebrafish embryo model.

Herbarin A and B were isolated from the fungal strains of Cladosporium herbarum found in marine sponges Aplysina aerophoba and Callyspongia aerizusa. Total synthesis of Herbarin A and B was achieved by carrying out a multi-step synthesis approach, and the antioxidant properties were evaluated using FRAP assay. Toxicity of these compounds was determined using a zebrafish embryo model.