A New Class of Antibiotic That Prevents Drug Tolerance, Persistence, and Resistance By Controlling Emergence of Phenotypes.

The fight against bacterial infections and innovations in antibiotic therapy has never halted throughout human history. However, bacteria have evolved smartly and resistance against practically all conventional antibiotics has been developed. Furthermore, bacteria can form biofilms, which are surface-attached multicellular colonies. Biofilms shield bacteria against antibiotics and makes it harder to entirely eradicate infections . Under antibiotics stress, bacteria evolve into different phenotypes like hyper motile, hyper adherent and hyper virulent which are tolerant and persistent to antibiotic treatment. The use of antibiotic therapy to combat such resilient bacterial phenotypes is extremely tough. As a result, the scientific community is always looking for novel ways to defeat these resilient phenotypes. It important to notice that all antibiotic induce tolerant and persistent phenotypes and there is no direct remedy for eradication of these phenotypes. On other hands, resistance to one antibiotic can be tackled by alternative antibiotic usage.Here, we demonstrate a class of small molecules that inhibits a wide range of phenotypes of Pseudomonas aeruginosa and enables the antibiotics to kill tolerant bacteria and to prevent formation of new persistent bacteria. We identified two proteins, type IV pili and lectin LecA as receptors for our molecules by different methods, including a new label-free assay based on bacterial motility sensing the environment, chemical inhibition of bacteriophage adsorption on pili appendages of bacteria, and fluorescence polarization. Structure-activity relationship studies reveal a molecule that inhibits only pili appendage, and a class of chimeric ligands that inhibit both LecA and pili, with important structural elements of the ligand identified for each protein. This selective control of two proteins makes the correlation between the protein receptor to their controlled phenotypes. Inhibiting LecA results in reducing biofilm formation, eliminating small colony variants, and correlates with killing tolerant bacteria and preventing the development of new persistent bacteria. Inhibiting pili appendages impedes the swarming and twitching motilities, and pyocyanin and elastase production. Because these phenotypes are controlled by a broad range of signaling pathways, this approach simultaneously control the multiple signaling mechanisms, by which bacteria elude antibiotic treatments. Glycolipid, ganglio-N-tetraosylceramide (asialo-GM1), on the mammalian cells are known to be recognized by type IV pili of Pseudomonas aeruginosa. In this work, we show that asialo-GM1 can also be recognized by Lectin A (LecA), another adhesin protein of the P. aeruginosa, by a fluorescent polarization assay, a label-free bacterial motility enabled binding assay, and bacterial mutant studies. On hydrated semi-solid gel surfaces, asialo-GM1 enables swarming and twitching motilities, while on solid surfaces facilitates the bacterial adherence of P. aeruginosa. These results indicate that asialo-GM1 can modulate bioactivities, adherence, and motilities, that are controlled by opposite signaling pathways. We demonstrate that when a solution of pilin monomers or LecA proteins are spread on hydrated gel surfaces, the asialo-GM1 mediated swarming motility is inhibited. Treatment of artificial liposomes containing asialo-GM1 as a component of lipid bilayer with pilin monomers or LecA proteins caused transient leakage of encapsulated dye from liposomes. These results suggest that pili and LecA proteins not only bind to asialo-GM1 but can also cause asialo-GM1 mediated leakage. We also show that both pili and LecA mutants of P. aeruginosa adhere to asialo-GM1 coated solid surfaces, and that a class of synthetic ligands for pili and LecA inhibits both pili and LecA-mediated adherence of P. aeruginosa on asialo-GM1-coated surfaces. The inspired by adjuvant molecule\u27s control over different P. aeruginosa phenotypes, we here designed new class of antibiotics which showed broad spectrum activity against different bacteria. This class of antibiotics inhibits pili and lecA and hence control multiple phenotypes in P. aeruginosa. This antibiotic also did not show emergence any tolerant population. We also did not develop any resistance against this class of antibiotics after repeated exposure. Silver therapy is most commonly used against burn wounds to treat P. aeruginosa and S. aureus infections. These bacteria develop cooperative resistance against silver with the help of pyocyanin, a virulence factor of P. aeruginosa. Here, we showed Farnesol as adjuvant molecule with silver therapy against P. aeruginosa and S. aureus. Farnesol eradicates resistance against silver by inhibition of pyocyanin. Farnesol also potentiated silver against dual biofilms of P. aeruginosa and S. aureus

Examining the Social Determinants of Health in Urban Communities: A Comparative Analysis

This comparative analysis investigates the social determinants of health (SDOH) in urban communities, aiming to discern disparities and inform targeted interventions and policies. With a focus on three key determinants socioeconomic status, housing and neighborhoods, and access to healthcare the study examines selected urban communities to illuminate the intricacies of health disparities within these contexts. The paper commences with an exploration of the background and significance of SDOH, emphasizing the crucial role they play in shaping health outcomes. The literature review provides a comprehensive overview of SDOH, offering insights into historical perspectives and unique challenges faced by urban communities.The methodology section outlines the criteria for selecting urban communities, the sources of data, and the ethical considerations guiding the research. A comparative framework is established, incorporating metrics such as income disparities, educational attainment, housing quality, neighborhood environments, and access to healthcare facilities. The analysis of these determinants reveals patterns, trends, and significant disparities among the selected urban communities, shedding light on the multifaceted nature of health inequalities.The findings section summarizes the key results, emphasizing the implications for public health. Policy recommendations and targeted interventions are discussed, emphasizing the importance of addressing SDOH to enhance overall community well-being. This comparative analysis underscores the imperative of considering SDOH in urban contexts and provides a foundation for future research and action. By delving into the intricacies of health disparities, this study contributes valuable insights to the ongoing discourse on public health, urging a comprehensive and nuanced approach to address the root causes of health inequities in urban communities

Growth of hydrogenated nano-crystalline silicon (nc-Si:H) films by plasma enhanced chemical vapor deposition (PE-CVD)

Hydrogenated nanocrystalline silicon (nc-Si:H) thin films were prepared by home-made PE-CVD systemfromgas mixture of pure SiH4 and H2 at various deposition pressures. Obtained results exhibited that deposition rate increases with increase in deposition pressure. Raman spectroscopy analysis revealed that deposition pressure in PE-CVD is a critical process parameter to induce nanocrystallization in Si:H films. The FTIR spectroscopy analysis results indicate that with increase in deposition pressure hydrogen bonding in films shifts from Si-H to Si-H2 and (Si-H2)n bonded species bonded species. The bonded hydrogen content didn’t show particular trend with optical band gap with change in deposition pressure. The obtained results indicates that 400 mTorr is an optimized deposition pressure of our PE-CVD unit to synthesize nc-Si:H films. At this optimized deposition pressure nc-Si:H films with crystallite size ∼ 5.43 nm having good degree of crystallinity (∼77%) and high band gap (ETauc∼ 1.85 eV) were obtained with a low hydrogen content (4.28 at. %) at moderately high deposition rate (0.75 nm/s). The ease of the present work is to optimize deposition pressure to obtain device quality intrinsicnc-Si:H layer in view of its used in p-i-n solar cells

Solution of Abel's Integral Equation by using Soham Transform

Integral transform play very important role in solving ordinary, partial as well as fractional differential equations. It is also useful for solving integral equations, integro-differential equations and system of equations. In this paper we use Soham transform for solving Abel’s integral equations

Ruptured sinus of valsalva aneurysm: Clinical case presentation and management

A 27-year-old female presented with generalized body swelling and progressive shortness of breath for the past 4 months. On examination, she had a loud continuous murmur, elevated jugular venous pressure, and gross ascites. The examination findings, electrocardiogram, chest radiography, and echocardiogram are discussed in a step-wise manner to arrive at a diagnosis and plan of management of a patient with ruptured sinus of Valsalva aneurysm is discussed along with review of relevant literature

Microwave ECR Plasma Assisted MOCVD of Y(2)O(3) Thin Films Using Y(tod)(3) Precursor and Their Characterization

Yttrium oxide (Y(2)O(3)) thin films were deposited by microwave electron cyclotron resonance (ECR) plasma assisted metal organic chemical vapour deposition (MOCVD) process using indigenously developed metal organic precursors Yttrium 2,7,7-trimethyl-3,5-octanedionates, commonly known as Y(tod)(3) which were synthesized by an ultrasound method. A series of thin films were deposited by varying the oxygen flow rate from 1-9 sccm, keeping all other parameters constant. The deposited coatings were characterized by X-ray photoelectron spectroscopy, glancing angle X-ray diffraction and infrared spectroscopy. Thickness and roughness for the films were measured by stylus profilometry. Optical properties of the coatings were studied by the spectroscopic ellipsometry. Hardness and elastic modulus of the films were measured by nanoindentation technique. Being that microwave ECR CVD process is operating-pressure-sensitive, optimum oxygen activity is very essential for a fixed flow rate of precursor, in order to get a single phase cubic yttrium oxide in the films. To the best of our knowledge, this is the first effort that describes the use of Y(tod)(3) precursor for deposition of Y(2)O(3) films using plasma assisted CVD process