Antiurease Activity of Antibiotics: In Vitro, In Silico, Structure Activity Relationship, and MD Simulations of Cephalosporins and Fluoroquinolones.

Helicobacter pylori infection is widespread in 50% of the world's population and is associated with gastric ulcers and related disorders that ultimately culminate in gastric cancer. Levofloxacin-based, or clarithromycin-based, triple therapy is frequently used to inhibit the bacterial urease enzyme for the eradication of H. pylori. A comprehensive investigation based on the urease inhibitory profiles of antibiotics and their computational implications is lacking in the scientific literature. The present study was aimed specifically to determine the antiurease activities within the realms of cephalosporins and fluoroquinolones by in vitro methods supported with in silico investigations. The results demonstrate the jack bean urease inhibitory activity of cephalosporins, wherein cefadroxil, cefpodoxime, cefotaxime, and cefaclor displayed inhibitions (IC50 21.35 ± 0.64 to 62.86 ± 0.78 µM) compared with the standard thiourea (IC50 21.25 ± 0.15 µM). Among fluoroquinolones, levofloxacin, ofloxacin, and gemifloxacin (IC50 7.24 ± 0.29 to 16.53 ± 0.85 µM) unveiled remarkable inhibitory profiles. Levofloxacin and ofloxacin exhibited competitive inhibition against the said enzyme. Ciprofloxacin and moxifloxacin displayed weak urease inhibitions. During molecular docking studies, Asp362, Gly279, Arg338, Asn168, Asp223, Gln364, and Met366 were involved in hydrogen bonding in fluoroquinolones, and hydrogen bonding was established with Arg338, His248, Asn168 residues, and metal Ni601 and Ni602 of the enzyme. MD simulations and MMPBSA results demonstrated the existence of significant protein-ligand binding. Overall, these results warrant further investigations into the significance of these active molecules in relation to their inhibitory potential against the targeted urease enzyme.

Greenhouse gas emissions, carbon stocks and wheat productivity following biochar, compost and vermicompost amendments: comparison of non-saline and salt-affected soils.

Understanding the impact of greenhouse gas (GHG) emissions and carbon stock is crucial for effective climate change assessment and agroecosystem management. However, little is known about the effects of organic amendments on GHG emissions and dynamic changes in carbon stocks in salt-affected soils. We conducted a pot experiment with four treatments including control (only fertilizers addition), biochar, vermicompost, and compost on non-saline and salt-affected soils, with the application on a carbon equivalent basis under wheat crop production. Our results revealed that the addition of vermicompost significantly increased soil organic carbon content by 18% in non-saline soil and 52% in salt-affected soil compared to the control leading to improvements in crop productivity i.e., plant dry biomass production by 57% in non-saline soil with vermicompost, while 56% with the same treatment in salt-affected soil. The grain yield was also noted 44 and 50% more with vermicompost treatment in non-saline and salt-affected soil, respectively. Chlorophyll contents were observed maximum with vermicompost in non-saline (24%), and salt-affected soils (22%) with same treatments. Photosynthetic rate (47% and 53%), stomatal conductance (60% and 12%), and relative water contents (38% and 27%) were also noted maximum with the same treatment in non-saline and salt-affected soils, respectively. However, the highest carbon dioxide emissions were observed in vermicompost- and compost-treated soils, leading to an increase in emissions of 46% in non-saline soil and 74% in salt-affected soil compared to the control. The compost treatment resulted in the highest nitrous oxide emissions, with an increase of 57% in non-saline soil and 62% in salt-affected soil compared to the control. In saline and non-saline soils treated with vermicompost, the global warming potential was recorded as 267% and 81% more than the control, respectively. All treatments, except biochar in non-saline soil, showed increased net GHG emissions due to organic amendment application. However, biochar reduced net emissions by 12% in non-saline soil. The application of organic amendments increased soil organic carbon content and crop yield in both non-saline and salt-affected soils. In conclusion, biochar is most effective among all tested organic amendments at increasing soil organic carbon content in both non-saline and salt-affected soils, which could have potential benefits for soil health and crop production.

Investigating the internal structure of multiple mini interviews-A perspective from Pakistan.

BACKGROUND: Healthcare professionals require many personal attributes in addition to cognitive abilities and psychomotor skills for competent practice. Multiple Mini- Interviews are being employed globally to assess personality attributes of candidates for selection in health professions education at all level of entry; these attributes are namely, communication skills, critical thinking, honesty, responsibility, health advocacy, empathy and sanctity of life. Considering the high stakes involved for students, faculty, institutions and the society, rigorous quality assurance mechanisms similar to those used for student assessment must be employed for student selection, throughout the continuum of medical education. It is a difficult undertaking as these psychological constructs are difficult to define and measure. Though considered to yield reliable and valid scores, studies providing multiple evidences of internal structure especially dimensionality of Multiple Mini-Interviews are sparse giving rise to questions if they are measuring a single or multiple constructs and even if they are measuring what they are purported to be measuring. OBJECTIVE: The main objective is to provide statistical support of the multi-dimensional nature of our Multiple Mini Interviews, hypothesized a-priori, through CFA. Another objective is to provide multiple evidences for the internal structure. Our study highlights the link between content and internal structure evidences of the constructs, thus establishing that our Multiple Mini Interviews measure what they were intended to measure. METHOD: After securing permission from the Institutional review board, an a-priori seven factor-model was hypothesized based on the attributes considered most essential for the graduating student of the institution. After operationally defining the attributes through extensive literature search, scenarios were constructed to assess them. A 5-point rating scale was used to rate each item on the station. A total 259 students participated in the multiple mini interviews over a period of three days. A training workshop had been arranged for the participating faculty. RESULTS: The reliability coefficient using Cronbach's alpha were calculated (range from 0.73 to 0.94), Standard Error of Measurement (ranged from 0.80 to1.64), and item to station-total correlation ranged from 0.43-0.50 to 0.75-0.83. Inter-station correlation was also determined. Confirmatory factor analysis endorsed the results of Exploratory factor analysis in the study revealing a seven model fit with multiple indices of Goodness-of-fit statistics such as Root mean square error of approximation (RMSEA) value 0.05, Standardized root mean square residual (SRMR) value with less than 0.08. All these indices showed that model fit is good. The Confirmatory factor analysis confirmed the multi-dimensional nature of our MMIs and also confirmed that our stations measured the attributes that they were supposed to measure. CONCLUSION: This study adds to the validity evidence of Multiple Mini-Interviews, in selection of candidates, with required personality traits for healthcare profession. It provides the evidence for the multi-dimensional structure of Multiple Mini interviews administered with multiple evidences for its internal structure and demonstrates the independence of different constructs being measured.

Plastic footprint deteriorates dryland carbon footprint across soil-plant-atmosphere continuum.

Plastic fragments are widely found in the soil profile of terrestrial ecosystems, forming plastic footprint and posing increasing threat to soil functionality and carbon (C) footprint. It is unclear how plastic footprint affects C cycling, and in particularly permanent C sequestration. Integrated field observations (including 13C labelling) were made using polyethylene and polylactic acid plastic fragments (low-, medium- and high-concentrations as intensifying footprint) landfilling in soil, to track C flow along soil-plant-atmosphere continuum (SPAC). The result indicated that increased plastic fragments substantially reduced photosynthetic C assimilation (p < 0.05), regardless of fragment degradability. Besides reducing C sink strength, relative intensity of C emission increased significantly, displaying elevated C source. Moreover, root C fixation declined significantly from 21.95 to 19.2 mg m-2, and simultaneously root length density, root weight density, specific root length and root diameter and surface area were clearly reduced. Similar trends were observed in the two types of plastic fragments (p > 0.05). Particularly, soil aggregate stability was significantly lowered as affected by plastic fragments, which accelerated the decomposition rate of newly sequestered C (p < 0.05). More importantly, net C rhizodeposition declined averagely from 39.77 to 29.41 mg m-2, which directly led to significant decline of permanent C sequestration in soil. Therefore, increasing plastic footprint considerably worsened C footprint regardless of polythene and biodegradable fragments. The findings unveiled the serious effects of plastic residues on permanent C sequestration across SPAC, implying that current C assessment methods clearly overlook plastic footprint and their global impact effects.

Air pollution and climate change as grand challenges to sustainability.

There is a cross-disciplinary link between air pollution, climate crisis, and sustainable lifestyle as they are the most complex struggles of the present century. This review takes an in-depth look at this relationship, considering carbon dioxide emissions primarily from the burning of fossil fuels as the main contributor to global warming and focusing on primary SLCPs such as methane and ground-level ozone. Such pollutants severely alter the climate through the generation of greenhouse gases. The discussion is extensive and includes best practices from conventional pollution control technologies to hi-tech alternatives, including electric vehicles, the use of renewables, and green decentralized solutions. It also addresses policy matters, such as imposing stricter emissions standards, setting stronger environmental regulations, and rethinking some economic measures. Besides that, new developments such as congestion charges, air ionization, solar-assisted cleaning systems, and photocatalytic materials are among the products discussed. These strategies differ in relation to the local conditions and therefore exhibit a varying effectiveness level, but they remain evident as a tool of pollution deterrence. This stresses the importance of holistic and inclusive approach in terms of engineering, policies, stakeholders, and ecological spheres to tackle.

Hemophagocytic Lymphohistiocytosis Associated With Human Herpesvirus-6 (HHV-6) Infection in an Immunocompetent Adult: A Case Report.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder characterized by extreme immune activation and excessive inflammation. It has been reported in patients with familial cases, immunodeficiencies, malignancies, stem cell transplants, and viral etiologies. This report describes acquired HLH associated with Human herpesvirus-6 (HHV-6) infection in a 76-year-old previously healthy male. The patient was admitted to the hospital due to fever, chills, and abdominal pain. The diagnostic workup revealed gallbladder wall thickening on imaging, concerning for cholecystitis. The patient was started on treatment for sepsis. Further clinical deterioration led to an extensive infectious workup. The patient was found to have elevated soluble IL-2Ra levels, and a bone marrow biopsy was performed, which revealed HLH. A positive HHV-6 polymerase chain reaction in the cerebrospinal fluid and serum confirmed the viral infection. Treatment involved the initiation of high-dose steroids, etoposide, and ganciclovir. Despite these interventions, the patient's clinical status worsened, leading to the implementation of comfort measures, and the patient eventually died. This case underscores the importance of considering HHV-6 as a potential cause of HLH in immunocompetent adults. From this case, we infer that a heightened level of vigilance is necessary to recognize and intervene in this challenging condition promptly.

Resources needed by critical access hospitals to address identified infection prevention and control program gaps.

Objective: The study examined resources needed by Infection Preventionists (IP) to address infection prevention and control (IPC) program gaps. Design: A 49-question survey. Setting: Licensed Critical Access Hospitals (CAHs) in Federal Emergency Management Area (FEMA) Region VII. Participants: IP at licensed CAHs. Methods: The survey conducted between December 2020 and January 2021 consisted of questions focusing on four categories including IPC program infrastructure, competency-based training, audit and feedback, and identification of high-risk pathogens/serious communicable diseases (HRP/SCD). An IPC score was calculated for each facility by totaling "Yes" responses (which indicate best practices) to 49 main survey questions. Follow-up questions explored the resources needed by the CAHs to implement or further strengthen best practices and mitigate IPC practice gaps. Welch t-test was used to study differences in IPC practice scores between states. Results: 50 of 259 (19.3%) CAHs participated in the survey with 37 (14.3%) answering all 49 questions. CAHs responding to all questions had a median IPC score of 35. There was no significant difference between IPC practice scores of CAHs in NE and IA. The top three IPC gaps were absence of drug diversion program (77%), lack of audits and feedback for insertion and maintenance of central venous catheters (76%), and missing laboratory risk assessments to identify tests that can be offered safely for patients under investigation for HRP/SCD (76%). Standardized audit tools, educational resources, and staff training materials were cited as much-needed resources. Conclusion: IPC practice gaps exist in CAHs. Various resources are needed for gap mitigation.

Unveiling the Role of Electrografted Carbon-Based Electrodes for Vanadium Redox Flow Batteries.

Carbon-based electrodes are used in flow batteries to provide active centers for vanadium redox reactions. However, strong controversy exists about the exact origin of these centers. This study systematically explores the influence of structural and functional groups on the vanadium reactions at carbon surfaces. Pyridine, phenol and butyl containing groups are attached to graphite felt electrodes. To establish a unique comparison between the model and real-world behavior, both non-activated and commercially used thermally activated felts serve as a substrate. Results reveal enhanced half-cell performance in non-activated felt with introduced hydrophilic functionalities. However, this cannot be transferred to the thermally activated felt. Beyond a decrease in electrochemical activity, a reduced long-term stability can be observed. This work indicates that thermal treatment generates active sites that surpass the effect of functional groups and are even impeded by their introduction.

Effects of process intensification on homogeneity of an IgG1:κ monoclonal antibody during perfusion culture.

The pharmaceutical industry employs various strategies to improve cell productivity. These strategies include process intensification, culture media improvement, clonal selection, media supplementation and genetic engineering of cells. However, improved cell productivity has inherent risk of impacting product quality attributes (PQA). PQAs may affect the products' efficacy via stability, bioavailability, or in vivo bioactivity. Variations in manufacturing process may introduce heterogeneity in the products by altering the type and extent of N-glycosylation, which is a PQA of therapeutic proteins. We investigated the effect of different cell densities representing increasing process intensification in a perfusion cell culture on the production of an IgG1-κ monoclonal antibody from a CHO-K1 cell line. This antibody is glycosylated both on light chain and heavy chain. Our results showed that the contents of glycosylation of IgG1-κ mAb increased in G0F and fucosylated type glycans as a group, whereas sialylated type glycans decreased, for the mAb whole protein. Overall, significant differences were observed in amounts of G0F, G1F, G0, G2FS1, and G2FS2 type glycans across all process intensification levels. G2FS2 and G2 type N-glycans were predominantly quantifiable from light chain rather than heavy chain. It may be concluded that there is a potential impact to product quality attributes of therapeutic proteins during process intensification via perfusion cell culture that needs to be assessed. Since during perfusion cell culture the product is collected throughout the duration of the process, lot allocation needs careful attention to process parameters, as PQAs are affected by the critical process parameters (CPPs). KEY POINTS: • Molecular integrity may suffer with increasing process intensity. • Galactosylated and sialylated N-glycans may decrease. • Perfusion culture appears to maintain protein charge structure.

Food selection and effect of home preparation procedure for antibiotic food mixtures on homogeneity, stability, and dissolution.

Amoxicillin, doxycycline, and clindamycin are among the commonly used antibiotics to treat bacterial infections. However, dosage forms of antibiotics for pediatric patients may not be as readily available as the formulations for adult patients. As such, it is anticipated that during a public health emergency, special instruction may need to be provided on home preparation and administration procedures to dose pediatric patients using available stockpiles of oral tablet and capsule dosage forms. Mixing crushed tablets or capsule contents with soft- or liquid- foods is one of the most common home preparation procedures. To gain knowledge for safe and effective use of prepared drug product instead of the intended intact dosage form, the impact of manipulation of the dosage form was studied. Capsule opening, capsule content assay and uniformity, dissolution, homogeneity, and stability studies of drug mixed with various liquid and soft foods were carried out using intact capsules of amoxicillin, doxycycline, and clindamycin. Higher recovery of capsule contents was achieved when using hands or knives to open capsules compared to using scissors. The capsules of all three antibiotic products contained the labeled amount of active pharmaceutical ingredients (API). The peanut butter-drug mixtures failed both United States Pharmacopeia (USP) assay and dissolution criteria because the peanut butter significantly affected the solubility of the drugs, and hence it was omitted from further study. All drug-food mixtures of the three antibiotic products and 15 selected foods exhibited fast dissolution (e.g., >80 % in 60 min) in the tested medium, except for the amoxicillin-chocolate pudding mixture. Three household containers (cups, plates, and bowls) and four mixing times (0.5 min, 1 min, 2 min, and 5 min) were found to be suitable for preparation of homogeneous mixtures of the antibiotics and foods. For practical purposes, 1 to 2 min mixing time is sufficient to produce homogeneous mixtures. The results of this study provided product quality data on the interactions between the antibiotics and the foods and can potentially support future development of home preparation instructions of antibiotics for pediatric patients or patients with swallowing difficulties.

Extending the lifetime of vanadium redox flow batteries by reactivation of carbon electrode materials.

The degradation and aging of carbon felt electrodes is a main reason for the performance loss of Vanadium Redox Flow Batteries over extended operation time. In this study, the chemical mechanisms for carbon electrode degradation are investigated and distinct differences in the degradation mechanisms on positive and negative electrodes have been revealed. A combination of surface analysis techniques such as X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and Electrochemical Impedance Spectroscopy (EIS) was applied for this purpose. In addition to understanding the chemical and physical alterations of the aged electrodes, a thermal method for reactivating aged electrodes was developed. The reactivation process was successfully applied on artificially aged electrodes as well as on electrodes from a real-world industrial vanadium redox flow battery system. The aforementioned analysis methods provided insight and understanding into the chemical mechanisms of the reactivation procedure. By applying the reactivation method, the lifetime of vanadium redox flow batteries can be significantly extended.

Evaluating radiofrequency electromagnetic field exposure in confined spaces: a systematic review of recent studies and future directions.

This study reviews recent research on Radiofrequency Electromagnetic Field (RF-EMF) exposure in confined environments, focusing on methodologies and parameters. Studies typically evaluate RF-EMF exposure using an electric field and specific absorption rate but fail to consider temperature rise in the tissues in confined environments. The study highlights the investigation of RF-EMF exposure in subterranean environments such as subways, tunnels and mines. Future research should evaluate the exposure of communication devices in such environments, considering the surrounding environment. Such studies will aid in understanding the risks and developing effective mitigation strategies to protect workers and the general public.

Erratum: Pharmacist interventions for appropriate COVID-19 antiviral therapy in long-term care facilities: A public health initiative - ERRATUM.

[This corrects the article DOI: 10.1017/ash.2023.246.].

pH-sensitive docetaxel-loaded chitosan/thiolated hyaluronic acid polymeric nanoparticles for colorectal cancer.

Aim: This study aimed to develop and evaluate pH-sensitive docetaxel-loaded thiolated hyaluronic acid (HA-SH) nanoparticles (NPs) for targeted treatment of colon cancer. Materials & methods: HA-SH, synthesized via oxidation and subsequent covalent linkage to cysteamine, served as the precursor for developing HA-SH NPs through polyelectrolyte complexation involving chitosan and thiol-bearing HA. Results & conclusion: HA-SH NPs displayed favorable characteristics, with small particle sizes (184-270 nm), positive zeta potential (15.4-18.6 mV) and high entrapment efficiency (91.66-95.02%). In vitro, NPs demonstrated potent mucoadhesion and enhanced cytotoxicity compared with free docetaxel. In vivo assessments confirmed safety and biocompatibility, suggesting HA-SH NPs as promising pH-sensitive drug carriers with enhanced antitumor activity for colorectal cancer treatments.

Effect of hesperidin on growth, photosynthesis, antioxidant systems and uptake of cadmium, copper, chromium and zinc by Celosia argentea plants.

Rapid industrialization and extensive agricultural practices are the major causes of soil heavy metal contamination, which needs urgent attention to safeguard the soils from contamination. However, the phytotoxic effects of excessive metals in plants are the primary obstacle to efficient phytoextraction. The present study evaluated the effects of hesperidin (HSP) on metals (Cu, Cd, Cr, Zn) phytoextraction by hyperaccumulator (Celosia argentea L.) plants. For this purpose, HSP, a flavonoid compound with strong antioxidant potential to assist metal phytoextraction was used under metal stress in plants. Celosia argentea plants suffered significant (P ≤ 0.001) oxidative damage due to the colossal accumulation of metals (Cu, Cd, Cr, Zn). However, HSP supplementation notably (P ≤ 0.001) abated ROS generation (O2•‒, •OH, H2O2), lipoxygenase activity, methylglyoxal production, and relative membrane permeability that clearly indicated HSP-mediated decline in oxidative injury in plants. Exogenous HSP improved (P ≤ 0.001) the production of non-protein thiol, phytochelatins, osmolytes, and antioxidant compounds. Further, HSP enhanced (P ≤ 0.001) H2S and NO endogenous production, which might have improved the GSH: GSSG ratio. Consequently, HSP-treated C. argentea plants had higher biomass alongside elevated metal accumulation mirrored as profound modifications in translocation factor (TF), bioaccumulation coefficient (BAC), and bioconcentration factor (BCF). In this context, HSP significantly enhanced TF of Cr (P ≤ 0.001), Cd (P ≤ 0.001), and Zn (P ≤ 0.01), while BAC of Cr (P ≤ 0.001), Cd (P ≤ 0.001), and Zn (P ≤ 0.001). Further, BCF was significant (P ≤ 0.05) only in plants grown under Cr-spiked soil. Overall, HSP has the potential for phytoremediation of metals by C. argentea, which might be a suitable strategy for metal-polluted soils.

Treating Pulmonary Arterial Hypertension With Sotatercept: A Meta-Analysis.

Pulmonary arterial hypertension (PAH) results from proliferative remodeling and narrowing of the pulmonary vasculature. Sotatercept is a first-in-class fusion protein that has recently garnered attention for showing improvements in patients with PAH. This meta-analysis of randomized controlled trials (RCTs) assesses the overall efficacy of Sotatercept in treating PAH. PubMed, Google Scholar, and Clinicaltrials.gov were searched using relevant keywords and MeSH terms. Studies were included if RCTs compared Sotatercept with placebo in patients with PAH. Our comprehensive literature search yielded 3,127 results, of which two RCTs with 429 patients were included in this meta-analysis. The patients were on background therapy for PAH. Results of the meta-analysis show that when compared with placebo, Sotatercept improved the six-minute walk distance (mean difference [MD] 34.99; 95% confidence interval [CI] 19.02-50.95; P < 0.0001), the World Health Organization (WHO) functional class (odds ratio [OR] 2.50; 95% CI 1.50-4.15; P = 0.0004), and pulmonary vascular resistance (PVR, MD -253.90; 95% CI -356.05 to -151.75; P < 0.00001). However, reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP, MD -1563.14; 95% CI -3271.93 to 145.65; P = 0.07) was not statistically significant in the Sotatercept group versus placebo. In conclusion, Sotatercept improves the six-minute walk distance, WHO functional class, and PVR in patients with PAH receiving background therapy. However, the effect on NT-proBNP levels was not statistically significant. More research is needed to assess the clinical relevance of these findings.

Polyphenols and their nanoformulations as potential antibiofilm agents against multidrug-resistant pathogens.

The emergence of multidrug-resistant (MDR) pathogens is a major problem in the therapeutic management of infectious diseases. Among the bacterial resistance mechanisms is the development of an enveloped protein and polysaccharide-hydrated matrix called a biofilm. Polyphenolics have demonstrated beneficial antibacterial effects. Phenolic compounds mediate their antibiofilm effects via disruption of the bacterial membrane, deprivation of substrate, protein binding, binding to adhesion complex, viral fusion blockage and interactions with eukaryotic DNA. However, these compounds have limitations of chemical instability, low bioavailability, poor water solubility and short half-lives. Nanoformulations offer a promising solution to overcome these challenges by enhancing their antibacterial potential. This review summarizes the antibiofilm role of polyphenolics, their underlying mechanisms and their potential role as resistance-modifying agents.

Bacteria can become more difficult to kill by forming a protective layer called a biofilm. This is a problem because infections caused by these bacteria can be difficult to treat. Polyphenols are a natural compound found in plants. They have shown promise in fighting resistant bacteria by stopping bacteria from forming a biofilm. However, polyphenols have some limitations. These limitations can be overcome by using nanomaterials, which are types of tiny particles. When polyphenols are combined with nanomaterials, they become much better at fighting bacteria. This is a promising solution to treating resistant infections caused by biofilm-forming bacteria.