Phenotypic and Genotypic Characterization of Pan-Drug-Resistant Klebsiella pneumoniae Isolated in Qatar.

In secondary healthcare, carbapenem-resistant Enterobacterales (CREs), such as those observed in Klebsiella pneumoniae, are a global public health priority with significant clinical outcomes. In this study, we described the clinical, phenotypic, and genotypic characteristics of three pan-drug-resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for the acquisition of multidrug-resistant organisms, while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents, such as ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, suggested as one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria, including CREs, pointing toward its potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial-resistant genes (ARGs), including blaNMD-5 and blaOXA derivative types, as well as a mutated outer membrane porin protein (OmpK37).

Additively Manufactured Parts from AA2011-T6 Large-Diameter Feedstocks Using Friction Stir Deposition.

The current work investigates the possibility of fabricating additive manufacturing products in solid-state form, from AA2011-T6 of 40 mm diameter rods as a feedstock, using an additive friction stir deposition (A-FSD) technique. The use of large diameter feedstocks, especially high-strength aluminum alloys (2XXX series), is a challenge, as it necessitates high power and the critical selection of the optimal A-FSD parameters, such as feed rate and spindle rotation speed. The study included applying a wide range of spindle rotation speeds, ranging from 400 to 1200 rpm, at three levels of feeding rates of 1, 3, and 5 mm/min. The AA2011-T6 friction stir deposited parts (FSDPs) were visually evaluated. This was followed by an examination of macrostructures through the thickness of the fabricated specimens. The characterization of microstructures was also carried out using optical microscopy and a scanning electron microscope equipped with advanced EDS analysis. Furthermore, the mechanical properties in terms of hardness and compressive strength of the AA2011-T6 base material (BM) and deposited materials were evaluated. Sound, additively manufactured products were successfully fabricated from 40 mm diameter AA2011-T6 feedstocks using the suggested deposition variables of 600 and 800 rpm spindle speeds and feeding rates of 1, 3, and 5 mm/min. The results indicated that the spindle speed and feeding rate govern the quality of the FSDPs. Furthermore, the axial load during the A-FSD process increased with increasing these parameters. In comparison to the AA2011-T6 BM, the additively deposited materials showed a refined grain structure and uniform dispersion of the fragment precipitates in their continuous multi-layers. The reduction ratio in grain size attains 71.56%, 76%, and 81.31% for the FSDPs processed at 800 rpm spindle speed and feeding rates of 1, 3 and 5 mm/min, respectively, compared to the grain size of BM. The Al2Cu and Al7Cu2Fe intermetallics are detected in the AA2011-T6 BM, and their deposited parts are in different shapes of spherical, almost spherical, irregular, and rod-like shapes. The compressive strength and hardness of the deposited parts increased with increasing spindle speed and feeding speeds. At a spindle speed of 800 rpm and a 5 mm/min feeding rate, the higher hardness and compressive strength gained were 85% and 93%, respectively, from that of the AA2011-T6 feedstock.

The Additive Manufacturing of Aluminum Matrix Nano Al2O3 Composites Produced via Friction Stir Deposition Using Different Initial Material Conditions.

The current work investigates the viability of utilizing a friction stir deposition (FSD) technique to fabricate continuous multilayer high-performance, metal-based nanoceramic composites. For this purpose, AA2011/nano Al2O3 composites were successfully produced using AA2011 as a matrix in two temper conditions (i.e., AA2011-T6 and AA2011-O). The deposition of matrices without nano Al2O3 addition was also friction stir deposited for comparison purposes. The deposition process parameters were an 800 rpm rod rotation speed and a 5 mm/min feed rate. Relative density and mechanical properties (i.e., hardness, compressive strength, and wear resistance) were evaluated on the base materials, deposited matrices, and produced composites. The microstructural features of the base materials and the friction stir deposited materials were investigated using an optical microscope (OM) and a scanning electron microscope (SEM) equipped with an EDS analysis system. The worn surface was also examined using SEM. The suggested technique with the applied parameters succeeded in producing defect-free deposited continuous multilayer AA2011-T6/nano Al2O3 and AA2011-O/nano Al2O3 composites, revealing well-bonded layers, grain refined microstructures, and homogeneously distributed Al2O3 particles. The deposited composites showed higher hardness, compressive strengths, and wear resistance than the deposited AA2011 matrices at the two temper conditions. Using the AA2011-T6 temper condition as a matrix, the produced composite showed the highest wear resistance among all the deposited and base materials.

COVID-19 and its impact on the cardiovascular system.

OBJECTIVES: The clinical impact of SARS-CoV-2 has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare National Health Service Trust, UK. METHODS: We retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7 March to 7 April 2020. Patient data were collected for baseline demographics, comorbidities and in-hospital outcomes, especially relating to cardiovascular intervention. RESULTS: Mean age was 67.4±16.1 years and 62.2% (n=310) were male. 64.1% (n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4% (n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%, p<0.001). Only four COVID-19 patients had invasive coronary angiography, two underwent percutaneous coronary intervention and one required a permanent pacemaker implantation. 7.0% (n=35) of patients had an inpatient echocardiogram. Acute myocardial injury (OR 2.39, 95% CI 1.31 to 4.40, p=0.005) and history of hypertension (OR 1.88, 95% CI 1.01 to 3.55, p=0.049) approximately doubled the odds of in-hospital mortality in patients admitted with COVID-19 after other variables had been controlled for. CONCLUSION: Hypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.

Synthesis, in silico experiments and biological evaluation of 1,3,4-trisubstituted pyrazole derivatives as antimalarial agents.

New 1,3,4-trisubstituted pyrazole derivatives were synthesized and evaluated for their antiplasmodial activity. Compounds 4b, 4c, 7a and 7d were the most potent antiplasmodial agents against P. berghei with percent of suppression ranging from 90 to 100%. They were also screened for their in vitro antimalarial activity against the chloroquine resistant strain P. falciparum, (RKL9). Compound 4c displayed the highest in vitro antimalarial activity; 13-fold higher than standard chloroquine phosphate. Molecular docking of the most active compounds against the wildtype and quadruple mutant pf DHFR-TS structures rationalized the in vitro antimalarial activity. Furthermore, these compounds exhibited reasonable in silico drug-likeness and pharmacokinetic properties. Toxicity studies of the most active compounds revealed that all tested compounds were non-toxic and well-tolerated up to 150 mg/kg via oral route and 75 mg/kg via parentral route. According to RBC hemolysis assay, it was found that compound 7a was the most potent anti-inflammatory and least toxic derivative with IC50 value 71-fold higher than IC50 value related to the antimalarial activity. Moreover, cytotoxicity assessment revealed that compound 4c was the least toxic derivative with IC50 value 70000-fold higher than IC50 value related to the antimalarial activity.

New heterocyclic hybrids of pyrazole and its bioisosteres: design, synthesis and biological evaluation as dual acting antimalarial-antileishmanial agents.

A new series of pyrazole derivatives were synthesized by hybridization with five-membered heterocyclic moieties such as thiazoles, thiazolidinones, 1,3,4-thiadiazoles and pyrazolines. The compounds were evaluated for their in vivo antimalarial activity against Plasmodium berghei infected mice and the most active derivatives were further examined for their in vitro antimalarial activity against chloroquine resistant (RKL9) strain of Plasmodium falciparum. Compounds 2c, 2d, 4b, 4c, 4d, 5a, 6c, 8c and 9b had more than 90% parasite suppression activity of that found with the antimalarial reference standard drug, chloroquine phosphate and had lower IC50 values than chloroquine. Compounds 4b and 9b were the most active derivatives, and their activities were 5-fold higher than chloroquine. All the newly synthesized compounds were evaluated for their in vitro antileishmanial activity against Leishmania aethiopica promastigotes and amastigote. The results showed that compounds 2c, 2d, 3d, 4b, 4c, 4d and 5a had lower or similar IC50 values than the reference standard drugs, amphotericin B and miltefosine. Compound 3d had the highest antileishmanial activity. Collectively, compounds 2c, 2d, 4b, 4c, 4d and 5a exhibited dual activity against malaria and leishmaniasis and were safe and well tolerated by the experimental animals orally up to 300 mg/kg and parenterally up to 100 mg/kg.

Synthesis, biological evaluation and molecular docking studies of some pyrimidine derivatives.

Some novel pyrimidine-5-carbonitrile derivatives bearing various substituent have been synthesized. The structures of target compounds were confirmed by elemental analysis and spectral data. Some selected members of the newly synthesized compounds were investigated for their cytotoxic potency against certain human tumor cell lines. Five representative active anticancer compounds 6a, 6c, 6d, 17a and 18a were subjected to docking using MOE program on the 3D structure of two enzymes, namely; thymidylate synthase and dihydrofolate reductase. The antimicrobial activities of the synthesized compounds were tested against Staphylococcus aureus, Pseudomonas aeruginosa, Shigella flexneri and Candida albicans. Compounds 2c, 7a and 9c showed broad spectrum antimicrobial activity.