Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects

Antibiotics have been used to cure bacterial infections for more than 70 years, and these low-molecular-weight bioactive agents have also been used for a variety of other medicinal applications. In the battle against microbes, antibiotics have certainly been a blessing to human civilization by saving millions of lives. Globally, infections caused by multidrug-resistant (MDR) bacteria are on the rise. Antibiotics are being used to combat diversified bacterial infections. Synthetic biology techniques, in combination with molecular, functional genomic, and metagenomic studies of bacteria, plants, and even marine invertebrates are aimed at unlocking the world’s natural products faster than previous methods of antibiotic discovery. There are currently only few viable remedies, potential preventive techniques, and a limited number of antibiotics, thereby necessitating the discovery of innovative medicinal approaches and antimicrobial therapies. MDR is also facilitated by biofilms, which makes infection control more complex. In this review, we have spotlighted comprehensively various aspects of antibiotics viz. overview of antibiotics era, mode of actions of antibiotics, development and mechanisms of antibiotic resistance in bacteria, and future strategies to fight the emerging antimicrobial resistant threat

Enhancing Heat Transfer in Blood Hybrid Nanofluid Flow with <inline-formula><math display="inline"><semantics><mrow><mi mathvariant="bold-italic">A</mi><mi mathvariant="bold-italic">g</mi></mrow></semantics></math></inline-formula>–<inline-formula><math display="inline"><semantics><mrow><mi mathvariant="bold-italic">T</mi><mi mathvariant="bold-italic">i</mi><msub><mi mathvariant="bold-italic">O</mi><mn mathvariant="bold">2</mn></msub></mrow></semantics></math></inline-formula> Nanoparticles and Electrical Field in a Tilted Cylindrical W-Shape Stenosis Artery: A Finite Difference Approach

The present research examines the unsteady sensitivity analysis and entropy generation of blood-based silver–titanium dioxide flow in a tilted cylindrical W-shape symmetric stenosis artery. The study considers various factors such as the electric field, joule heating, viscous dissipation, and heat source, while taking into account a two-dimensional pulsatile blood flow and periodic body acceleration. The finite difference method is employed to solve the governing equations due to the highly nonlinear nature of the flow equations, which requires a robust numerical technique. The utilization of the response surface methodology is commonly observed in optimization procedures. Drawing inspiration from drug delivery techniques used in cardiovascular therapies, it has been proposed to infuse blood with a uniform distribution of biocompatible nanoparticles. The figures depict the effects of significant parameters on the flow field, such as the electric field, Hartmann number, nanoparticle volume fraction, body acceleration amplitude, Reynolds number, Grashof number, and thermal radiation, on velocity, temperature (nondimensional), entropy generation, flow rate, resistance to flow, wall shear stress, and Nusselt number. The velocity and temperature profiles improve with higher values of the wall slip parameter. The flow rate profiles increase with an increment in wall velocity but decrease with the Womersley number. Increasing the intensity of radiation and decreasing magnetic fields both result in a decrease in the rate of heat transfer. The blood temperature is higher with the inclusion of hybrid nanoparticles than the unitary nanoparticles. The total entropy generation profiles increase for higher values of the Brickman number and temperature difference parameters. Unitary nanoparticles exhibit a slightly higher total entropy generation than hybrid nanoparticles, particularly when positioned slightly away from the center of the artery. The total entropy production decreases by 17.97% when the thermal radiation is increased from absence to 3. In contrast, increasing the amplitude of body acceleration from 0.5 to 2 results in a significant enhancement of 76.14% in the total entropy production

The ChoCO-W prospective observational global study: Does COVID-19 increase gangrenous cholecystitis?

BACKGROUND: The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not. METHODS: Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not. RESULTS: A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p < 0.0001), diabetes (p < 0.0001), and severe chronic obstructive airway disease (p = 0.005) were significantly more frequent in the COVID-19 group. Markers of sepsis severity including ARDS (p < 0.0001), PIPAS score (p < 0.0001), WSES sepsis score (p < 0.0001), qSOFA (p < 0.0001), and Tokyo classification of severity of acute cholecystitis (p < 0.0001) were significantly higher in the COVID-19 group. The COVID-19 group had significantly higher postoperative complications (32.2% compared with 11.7%, p < 0.0001), longer mean hospital stay (13.21 compared with 6.51 days, p < 0.0001), and mortality rate (13.4% compared with 1.7%, p < 0.0001). The incidence of gangrenous cholecystitis was doubled in the COVID-19 group (40.7% compared with 22.3%). The mean wall thickness of the gallbladder was significantly higher in the COVID-19 group [6.32 (SD: 2.44) mm compared with 5.4 (SD: 3.45) mm; p < 0.0001]. CONCLUSIONS: The incidence of gangrenous cholecystitis is higher in COVID patients compared with non-COVID patients admitted to the emergency department with acute cholecystitis. Gangrenous cholecystitis in COVID patients is associated with high-grade Clavien-Dindo postoperative complications, longer hospital stay and higher mortality rate. The open cholecystectomy rate is higher in COVID compared with non -COVID patients. It is recommended to delay the surgical treatment in COVID patients, when it is possible, to decrease morbidity and mortality rates. COVID-19 infection and gangrenous cholecystistis are not absolute contraindications to perform laparoscopic cholecystectomy, in a case by case evaluation, in expert hands

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu