Discovery of Benzopyrone-Based Candidates as Potential Antimicrobial and Photochemotherapeutic Agents through Inhibition of DNA Gyrase Enzyme B: Design, Synthesis, In Vitro and In Silico Evaluation.

Bacterial DNA gyrase is considered one of the validated targets for antibacterial drug discovery. Benzopyrones have been reported as promising derivatives that inhibit bacterial DNA gyrase B through competitive binding into the ATP binding site of the B subunit. In this study, we designed and synthesized twenty-two benzopyrone-based derivatives with different chemical features to assess their antimicrobial and photosensitizing activities.

A randomized trial of behavioral interventions yielding sustained reductions in distracted driving.

Distracted driving is responsible for nearly 1 million crashes each year in the United States alone, and a major source of driver distraction is handheld phone use. We conducted a randomized, controlled trial to compare the effectiveness of interventions designed to create sustained reductions in handheld use while driving (NCT04587609). Participants were 1,653 consenting Progressive® Snapshot® usage-based auto insurance customers ages 18 to 77 who averaged at least 2 min/h of handheld use while driving in the month prior to study invitation.

Feedback and Financial Incentives for Reducing Cell Phone Use While Driving: A Randomized Clinical Trial.

Importance: Handheld phone use while driving is a major factor in vehicle crashes. Scalable interventions are needed to encourage drivers not to use their phones.

Objective: To test whether interventions involving social comparison feedback and/or financial incentives can reduce drivers' handheld phone use.

The first use of a photogrammetry drone to estimate population abundance and predict age structure of threatened Sumatran elephants.

Wildlife monitoring in tropical rainforests poses additional challenges due to species often being elusive, cryptic, faintly colored, and preferring concealable, or difficult to access habitats. Unmanned aerial vehicles (UAVs) prove promising for wildlife surveys in different ecosystems in tropical forests and can be crucial in conserving inaccessible biodiverse areas and their associated species. Traditional surveys that involve infiltrating animal habitats could adversely affect the habits and behavior of elusive and cryptic species in response to human presence.

Utilizing mobile robotics for pelvic perturbations to improve balance and cognitive performance in older adults: a randomized controlled trial.

Late-life balance disorders remain a severe problem with fatal consequences. Perturbation-based balance training (PBT), a form of rehabilitation that intentionally introduces small, unpredictable disruptions to an individual's gait cycle, can improve balance. The Tethered Pelvic Assist Device (TPAD) is a cable-driven robotic trainer that applies perturbations to the user's pelvis during treadmill walking.

Regulation of renal nitric oxide and eNOS/iNOS expression by tadalafil participates in the mitigation of amphotericin B-induced renal injury: Down-regulation of NF-κB/iNOS/caspase-3 signaling.

Amphotericin B (AmB)-induced acute kidney injury (AKI) is a common health problem having an undesirable impact on its urgent therapeutic utility for fatal systemic fungal infections. Tadalafil (TAD), a phosphodiesterase-5 (PDE-5) inhibitor, has been observed to have a wide range of pharmacological actions, including nephroprotection. The study's objective was to examine the possible underlying protective mechanism of TAD against AmB-induced nephrotoxicity.

Drivers of habitat availability for terrestrial mammals: Unravelling the role of livestock, land conversion and intrinsic traits in the past 50 years.

The global decline of terrestrial species is largely due to the degradation, loss and fragmentation of their habitats. The conversion of natural ecosystems for cropland, rangeland, forest products and human infrastructure are the primary causes of habitat deterioration. Due to the paucity of data on the past distribution of species and the scarcity of fine-scale habitat conversion maps, however, accurate assessment of the recent effects of habitat degradation, loss and fragmentation on the range of mammals has been near impossible.

Role of canagliflozin in ameliorating isoprenaline induced cardiomyocyte oxidative stress via the heme oxygenase-1 mediated pathway.

Canagliflozin (CZ) is commonly prescribed for management of type-2 diabetes mellitus (T2DM); it also can reduce the risk of myocardial infarction. We used 80 albino Wistar rats to investigate the cardioprotective potential of CZ against oxidative stress caused by administration of isoprenaline (ISO). We found that ISO stimulates production of reactive oxygen species and that CZ administration caused up-regulation of antioxidants and down-regulation of oxidants due to nuclear factor erythroid-2 related factor-2, as well as by enhancement of the heme oxygenase-1 mediated cascade.

Novel VEGFR-2 inhibitors as antiangiogenic and apoptotic agents via paracrine and autocrine cascades: Design, synthesis, and biological evaluation.

Appertaining to its paracrine and autocrine signaling loops, VEGFR-2 succeeded in grabbing attention as one of the leading targets in cancer treatment. Based on the foregoing and our comprehensive studies regarding pharmacophoric features and activity of sorafenib, novel phenylpyridazinone based VEGFR-2 inhibitors 4, 6a-e, 7a,b, 9a,b, 12a-c, 13a,b, 14a,b, 15a,b, and 17a-d were optimized. An assortment of biological assays was conducted to assess the antiangiogenic and apoptotic activities of the synthesized derivatives.

Utilizing Mobile Robotics for Pelvic Perturbations to Improve Balance and Cognitive Performance in Older Adults: A Randomized Controlled Trial.

Late-life balance disorders remain a severe problem with fatal consequences. Perturbation-based balance training (PBT), a form of rehabilitation that intentionally introduces small, unpredictable disruptions to an individual's gait cycle, can improve balance. The Tethered Pelvic Assist Device (TPAD) is a cable-driven robotic trainer that applies perturbations to the user's pelvis during treadmill walking.

Impact of Universal Screening and Automated Clinical Decision Support for the Treatment of Opioid Use Disorder in Emergency Departments: A Difference-in-Differences Analysis.

Study Objective: Emergency department (ED)-initiated buprenorphine improves outcomes in patients with opioid use disorder; however, adoption varies widely. To reduce variability, we implemented a nurse-driven triage screening question in the electronic health record to identify patients with opioid use disorder, followed by targeted electronic health record prompts to measure withdrawal and guide next steps in management, including initiation of treatment. Our objective was to assess the impact of screening implementation in 3 urban, academic EDs.

Synchronous ipsilateral papillary renal cell carcinoma and urothelial carcinoma: A case report.

Concurrence of renal cell carcinoma (RCC) and urothelial carcinoma (UC) in the same kidney is a rare phenomenon. It is critical to define this unusual disease to avoid a delay in diagnosis and improve the prognosis. The present study describes a case of a 71-year-old patient with synchronous ipsilateral RCC and UC of the renal pelvis and ureter.

Patient with myelodysplastic syndrome presented with recurrent pericardial effusion diagnosed as epicardial hemangioma; Case report of a rare diagnosis with rare presentation.

Primary cardiac tumors are extremely rare and cardiac hemangiomas comprise less than 3% of them. Presentation of such disease with recurrent pericardial effusion is even rarer. Our patient is known case of myelodysplastic syndrome and up to our knowledge there are no reported case in which cardiac hemangioma was diagnosed in a patient with myelodysplastic syndrome.

Antibiotic-Lysobacter enzymogenes proteases combination as a novel virulence attenuating therapy.

Minimizing antibiotic resistance is a key motivation strategy in designing and developing new and combination therapy. In this study, a combination of the antibiotics (cefixime, levofloxacin and gentamicin) with Lysobacter enzymogenes (L. enzymogenes) bioactive proteases present in the cell- free supernatant (CFS) have been investigated against the Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and the Gram-negative Escherichia coli (E.

Renal cell carcinoma T staging: Diagnostic accuracy of preoperative contrast-enhanced computed tomography.

Renal cell carcinoma (RCC) accounts for 1-2% of all malignancies and is the most common renal tumor in adults. Imaging studies are used for diagnosis and staging. Tumor-Node-Metastasis staging strongly affects prognosis and management, while contrast-enhanced computed tomography (CECT) is regarded as a standard imaging technique for local and distant staging.

Balancing renal Ang-II/Ang-(1-7) by xanthenone; an ACE2 activator; contributes to the attenuation of Ang-II/p38 MAPK/NF-κB p65 and Bax/caspase-3 pathways in amphotericin B-induced nephrotoxicity in rats.

Despite the great importance of amphotericin B for the management of life-threatening systemic fungal infections, its nephrotoxic effect restricts its repeated administration. This study was designed to examine the prospective modulatory effects of xanthenone, an ACE2 activator, against amphotericin B nephrotoxicity. Male Wistar rats were allocated into four groups; control (1), Xanthenone (2), Amphotericin B (3), and Xanthenone + Amphotericin B (4).

Mouse embryonic stem cell-derived motor neurons are susceptible to ferroptosis.

Ferroptosis is a regulated form of cell death driven by the lethal accumulation of lipid peroxides in cell membranes. Several regulators of ferroptosis have been identified using cancer cell lines. However, the cellular pathways of ferroptosis in neurons remain poorly characterized.

Molecular diagnosis with the corresponding clinical symptoms of canine distemper virus infection in javan leopard ( ssp. ).

Diseases are one of the possible threats to the conservation of wild cat populations. One disease that has been reported to infect and cause death, including in various wildlife, is the canine distemper virus (CDV). Here, we report the first case of CDV in an adolescent melanistic Javan female leopard in Indonesia.

Drivers of Three Most Charismatic Mammalian Species Distribution across a Multiple-Use Tropical Forest Landscape of Sumatra, Indonesia.

Tropical Rainforest Heritage sites of Sumatra are some of the most irreplaceable landscapes in the world for biodiversity conservation. These landscapes harbor many endangered Asiatic mammals all suffering multifaceted threats due to anthropogenic activities. Three charismatic mammals in Sumatra: , , and are protected and listed as Critically Endangered (CR) within the IUCN Red List.

Scaffold Repurposing Reveals New Nanomolar Phosphodiesterase Type 5 (PDE5) Inhibitors Based on Pyridopyrazinone Scaffold: Investigation of In Vitro and In Silico Properties.

Inhibition of PDE5 results in elevation of cGMP leading to vascular relaxation and reduction in the systemic blood pressure. Therefore, PDE5 inhibitors are used as antihypertensive and antianginal agents in addition to their major use as male erectile dysfunction treatments. Previously, we developed a novel series of 34 pyridopyrazinone derivatives as anticancer agents (series -).

In Vitro and In Vivo Antidiabetic Activity, Phenolic Content and Microscopical Characterization of .

Terfezia claveryi (T. claveryi) is used by traditional healers in the Middle East region to treat several diseases, including diabetes. The present study evaluated the total phenolic and investigated the blood-glucose-lowering potential of different aqueous extracts of this selected truffle using in vitro and in vivo models.