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A radical approach to late-stage functionalization using photoredox and Diversinate™ chemistry on the Open Source Malaria (OSM) triazolopyrazine scaffold (Series 4) resulted in the synthesis of 12 new analogues, which were characterized by NMR, UV, and MS data analysis. The structures of four triazolopyrazines were confirmed by X-ray crystal structure analysis. Several minor and unexpected side products were generated during these studies, including two resulting from a possible disproportionation reaction. All compounds were tested for their ability to inhibit the growth of the malaria parasite Plasmodium falciparum (3D7 and Dd2 strains) and for cytotoxicity against a human embryonic kidney (HEK293) cell line. Moderate antimalarial activity was observed for some of the compounds, with IC50 values ranging from 0.3 to >20 µM; none of the compounds displayed any toxicity against HEK293 at 80 µM.

Background: Resting-state electroencephalography (rsEEG) is usually obtained to assess seizures in comatose patients with traumatic brain injury (TBI). We aim to investigate rsEEG measures and their prediction of early recovery of consciousness in patients with TBI., Methods: This is a retrospective study of comatose patients with TBI who were admitted to a trauma center (October 2013 to January 2022). Demographics, basic clinical data, imaging characteristics, and EEGs were collected. We calculated the following using 10-min rsEEGs: power spectral density, permutation entropy (complexity measure), weighted symbolic mutual information (wSMI, global information sharing measure), Kolmogorov complexity (Kolcom, complexity measure), and heart-evoked potentials (the averaged EEG signal relative to the corresponding QRS complex on electrocardiography). We evaluated the prediction of consciousness recovery before hospital discharge using clinical, imaging, and rsEEG data via a support vector machine., Results: We studied 113 of 134 (84%) patients with rsEEGs. A total of 73 (65%) patients recovered consciousness before discharge. Patients who recovered consciousness were younger (40 vs. 50 years, p = 0.01). Patients who recovered also had higher Kolcom (U = 1688, p = 0.01), increased beta power (U = 1,652 p = 0.003) with higher variability across channels (U = 1534, p = 0.034) and epochs (U = 1711, p = 0.004), lower delta power (U = 981, p = 0.04), and higher connectivity across time and channels as measured by wSMI in the theta band (U = 1636, p = 0.026; U = 1639, p = 0.024) than those who did not recover. The area under the receiver operating characteristic curve for rsEEG was higher than that for clinical data (using age, motor response, pupil reactivity) and higher than that for the Marshall computed tomography classification (0.69 vs. 0.66 vs. 0.56, respectively; p < 0.001)., Conclusions: We describe the rsEEG signature in recovery of consciousness prior to discharge in comatose patients with TBI. rsEEG measures performed modestly better than the clinical and imaging data in predicting recovery., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Recent seroepidemiological studies have suggested that tularemia could be an endemic bacterial zoonosis in Iran., Methods: From January 2016 to June 2018, disease cases characterized by fever, cervical lymphadenopathy and ocular involvement were reported in Youzband Village of Kaleybar County, in the East Azerbaijan Province, northwestern Iran. Diagnostic tests included Francisella tularensis serology (including tube agglutination test and ELISA), PCR, and culture., Results: Among 11 examined case-patients, the tularemia tube agglutination test was positive in ten and borderline in one. PCR detected the F. tularensis ISFtu2 elements and fopA gene in one rodent and a spring water sample from the same geographic area., Conclusions: Based on the clinical manifestations of the disease suggesting an oropharyngeal form of tularemia, serology results in case patients, and F. tularensis detection in the local fauna and aquatic environment, the water supply of the village was the likely source of the tularemia outbreak. Intervention such as dredging and chlorination of the main water storage tank of the village and training of villagers and health care workers in preventive measures and treatment of the illness helped control the infection.

Tularemia is a zoonotic disease that transmitted to humans and domestic animals by wildlife, especially rodents. There are some evidences of the circulation of F. tularensis in rodents, livestock, human populations, and surface waters in western parts of Iran. In this study, we investigated the exposure of livestock and ranchers to F. tularensis in the endemic regions of western Iran. Blood samples were collected from 289 sheep, 103 cattle, and 51 ranchers in 2018. Animal sera were tested by standard tube agglutination method. The specific IgGs against F. tularensis were evaluated by ELISA in human sera. Moreover, the extracted DNAs from 50 sheep spleen samples were evaluated using TaqMan real-time PCR for the presence of ISFtu2 and FopA genes. All animal sera and spleen samples were negative for tularemia. Of the 51 human samples, two samples were seropositive and one sample showed a borderline status for tularemia. Serologic evidence of F. tularensis in the ranchers but negative results in the livestock indicates different transmission routes in human populations and domestic animals in western Iran. Therefore, drinking contaminated water, contact to wildlife or rodents and arthropod bite should be considered as probable routes in the suspicious areas., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The etiologic agent of tularemia, Francisella tularensis, is transmitted to humans via ingestion of contaminated water or food, arthropods bite, respiratory aerosols, or direct contact with infected animals body fluids or tissues. In the current study, due to the importance of water in transmitting the disease and the report of the disease in different regions of Iran, surface water of Kurdistan province were evaluated for the presence of F.tularensis., Materials and Methods: Sampling was carried out in five-counties of Kurdistan province. Sixty-six specimens of surface water were collected. The detection was carried out by targeting ISFtu2 and fopA genes using TaqMan real-time PCR. Moreover, the samples were both cultured and inoculated into NMRI inbreed mice. Spleens of inoculated mice and bacterial isolates were tested by TaqMan real-time PCR., Results: Despite the lack of isolation of F. tularensis, the results of the molecular testing indicate the presence of bacteria in surface water. Molecular positivity of one sample (1.51%) was confirmed using a real-time PCR for both ISFtu2 and fopA genes. Moreover, 4.54% of the samples were positive for ISFtu2., Conclusion: Since the in vitro isolation of bacteria from environmental samples is associated with a very low success rate and depends on various environmental parameters, the use of molecular techniques for monitoring of the bacteria in the contaminated areas is fully recommended., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest in this work., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aims: Exposure to recurrent hypoglycemia (RH) is common in diabetic patients receiving glucose-lowering therapies and is implicated in causing cognitive impairments. Despite the significant effect of RH on hippocampal function, the underlying mechanisms are currently unknown. Our goal was to determine the effect of RH exposure on hippocampal metabolism in treated streptozotocin-diabetic rats., Methods: Hyperglycemia was corrected by insulin pellet implantation. Insulin-treated diabetic (ITD) rats were exposed to mild/moderate RH once a day for 5 consecutive days., Results: The effect of RH on hippocampal metabolism revealed 65 significantly altered metabolites in the RH group compared with controls. Several significant differences in metabolite levels belonging to major pathways (eg, Krebs cycle, gluconeogenesis, and amino acid metabolism) were discovered in RH-exposed ITD rats when compared to a control group. Key glycolytic enzymes including hexokinase, phosphofructokinase, and pyruvate kinase were affected by RH exposure., Conclusion: Our results demonstrate that the exposure to RH leads to metabolomics alterations in the hippocampus of insulin-treated streptozotocin-diabetic rats. Understanding how RH affects hippocampal metabolism may help attenuate the adverse effects of RH on hippocampal functions., (© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)