Synthesis of 3-[4-(2-furoyl)-1-piperazinyl]-N- (substituted)propanamides as promising antibacterial agents with mild cytotoxicity

Purpose: To evaluate the antibacterial activity and cytotoxicity of a series of molecules with amalgamation of furoyl, piperazine and amide moieties.Methods: New derivatives, namely 3-[4-(2-furoyl)-1-piperazinyl]-N-(substituted) propanamides, were synthesized and evaluated for their antibacterial activity and toxicity to mammalian cells. The synthesis was initiated by treating different aryl/aralkyl amines (1a-u) with 3-bromopropionyl chloride (2) to obtain the solid electrophiles 3a-u, which were collected by filtration. Thereafter, the different N-aryl/aralkyl-3- bromopropionamides (3a-u) and 2-furoyl-1-piperazine (4) at equimolar ratios were allowed to react in acetonitrile and in the presence of a base, K2CO3, to form the target compounds, 5a-u. Structural elucidation was carried out using EI-MS (electron impact mass spectrometry), IR (infrared) and 1H-NMR (proton nuclear magnetic resonance). The antibacterial activity of the synthesized compounds was evaluated against various bacterial strains. Furthermore, hemolysis was determined to assess cytotoxicity using bovine red blood cells.Results: Molecules 5g, 5a, 5p, 5g and 5i were found to be potent agents against S. aureus, S. typhi, P. aeruginosa, E. coli and B. subtilis with respective minimum inhibitory concentration (MIC) values of 8.34 ± 0.55, 8.37 ± 0.12, 8.65 ± 0.57, 8.97 ± 0.12 and 9.24 ± 0.50 μM, compared to 7.80 ± 0.19, 7.45 ± 0.58, 7.14 ± 0.58, 7.16 ± 0.58 and 7.29 ± 0.90 μM for the reference standard, ciprofloxacin. The most active compounds, 5a, 5g, 5i and 5p, showed a hemolysis of 15.48, 8.03, 5.52 and 4.35 %, respectively.Conclusion: The synthesized compounds exhibit good antibacterial activity. The hemolysis data indicate that these compounds have a low toxicity level. However, in vivo studies are required to ascertain their potentials as new drug candidates.Keywords: 4-(2-Furoyl)-1-piperazine, 1H-NMR, EI-MS, Antimicrobial activity, Hemolytic activit

Breast cancer risk factor knowledge among nurses in teaching hospitals of Karachi, Pakistan: a cross-sectional study

BACKGROUND: Breast cancer is the most common cancer among women in both the developed and the developing world. The incidence of breast cancer in Karachi, Pakistan is 69.1 per 100,000 with breast cancer presentation in stages III and IV being common (≥ 50%). The most pragmatic solution to early detection lies in breast cancer education of women. Nurses constitute a special group having characteristics most suited for disseminating breast cancer information to the women. We assessed the level of knowledge of breast cancer risk factors among registered female nurses in teaching hospitals of Karachi. We also identified whether selected factors among nurses were associated with their knowledge of breast cancer risk factors, so that relevant measures to improve knowledge of nurses could be implemented. METHODS: A cross-sectional survey was conducted in seven teaching hospitals of Karachi using stratified random sampling with proportional allocation. A total of 609 registered female nurses were interviewed using a structured questionnaire adapted from the Stager's Comprehensive Breast Cancer Knowledge Test. Knowledge of breast cancer risk factors was categorized into good, fair and poor categories. Ordinal regression was used to identify factors associated with risk knowledge among nurses. RESULTS: Thirty five percent of nurses had good knowledge of risk factors. Graduates from private nursing schools (aOR = 4.23, 95% CI: 2.93, 6.10), nurses who had cared for breast cancer patients (aOR = 1.41, 95% CI: 1.00, 1.99), those having received a breast examination themselves (aOR = 1.56, 95% CI: 1.08, 2.26) or those who ever examined a patient's breast (aOR = 1.87, 95% CI: 1.34, 2.61) were more likely to have good knowledge. CONCLUSION: A relatively small proportion of the nursing population had good level of knowledge of the breast cancer risk factors. This knowledge is associated with nursing school status, professional breast cancer exposure and self history of clinical breast examination. Since only about one-third of the nurses had good knowledge about risk factors, there is a need to introduce breast cancer education in nursing schools particularly in the public sector. Continuing nursing education at the workplace can be of additional benefit

Identifying Immunological and Clinical Predictors of COVID-19 Severity and Sequelae by Mathematical Modeling

Since its emergence as a pandemic in March 2020, coronavirus disease (COVID-19) outcome has been explored via several predictive models, using specific clinical or biochemical parameters. In the current study, we developed an integrative non-linear predictive model of COVID-19 outcome, using clinical, biochemical, immunological, and radiological data of patients with different disease severities. Initially, the immunological signature of the disease was investigated through transcriptomics analysis of nasopharyngeal swab samples of patients with different COVID-19 severity versus control subjects (exploratory cohort, n=61), identifying significant differential expression of several cytokines. Accordingly, 24 cytokines were validated using a multiplex assay in the serum of COVID-19 patients and control subjects (validation cohort, n=77). Predictors of severity were Interleukin (IL)-10, Programmed Death-Ligand-1 (PDL-1), Tumor necrosis factors-α, absolute neutrophil count, C-reactive protein, lactate dehydrogenase, blood urea nitrogen, and ferritin; with high predictive efficacy (AUC=0.93 and 0.98 using ROC analysis of the predictive capacity of cytokines and biochemical markers, respectively). Increased IL-6 and granzyme B were found to predict liver injury in COVID-19 patients, whereas interferon-gamma (IFN-γ), IL-1 receptor-a (IL-1Ra) and PD-L1 were predictors of remarkable radiological findings. The model revealed consistent elevation of IL-15 and IL-10 in severe cases. Combining basic biochemical and radiological investigations with a limited number of curated cytokines will likely attain accurate predictive value in COVID-19. The model-derived cytokines highlight critical pathways in the pathophysiology of the COVID-19 with insight towards potential therapeutic targets. Our modeling methodology can be implemented using new datasets to identify key players and predict outcomes in new variants of COVID-19

Efficacy and Safety of Single and Double Doses of Ivermectin versus 7-Day High Dose Albendazole for Chronic Strongyloidiasis

Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. We conducted a prospective, clinical study to compare the efficacy and safety of a 7-day course of oral albendazole with a single dose of oral ivermectin, or double doses, given 2 weeks apart, of ivermectin in Thai patients who developed this infection. Patients were regularly followed-up after initiation of treatment, until one year after treatment. Ninety patients were studied (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). The average duration of follow-up were 19 (range 2–76) weeks in albendazole group, 39 ( range 2–74) weeks in single dose ivermectin group, and 26 ( range 2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin, and double doses of oral ivermectin respectively. No serious adverse event associated with treatment was found in any of the groups. Therefore this study confirms that both a single, and a double dose of oral ivermectin taken two weeks apart, is more effective than a 7-day course of high dose albendazole for patients with chronic infection due to S. stercoralis

Contested Compliance Regimes in Global Production Networks: Insights from the Bangladesh Garment Industry

This article reports the findings of a field study on the emergence of collective agreements led by global brands enacting compliance measures to improve safety and working conditions in the Bangladesh garment industry. We explore how key actors in the Bangladesh garment sector who constitute the local production system of the global supply chain experienced the implementation of global agreements on factory safety. We argue that global safety compliance measures through multi-stakeholder initiatives provide legitimacy to multinational corporations and their global brands but do little to address the structural problems arising from exploitative pricing and procurement practices, which are the key reasons for deplorable working conditions in garment factories. Our findings indicate that neoliberal development policies of the state, where local economies are incorporated into global production networks, resulted in differential treatment and regulation of specific populations that comprise garment factory workers. The reconfiguration of state power to meet the demands of global supply chains also involved use of state violence to suppress dissent while undermining labour rights and working conditions. Our article contributes to the politicization of multinational corporations in global production chains by showing how contestations between workers, factory owners, the state, trade unions and multinational corporations create new private forms of governance and new regimes of compliance in the industr