XPS Investigation on Improving Hydrogen Sorption Kinetics of the KSiH3 System by Using Zr-Based Catalysts

The superior hydrogen storage properties makes the KSiH₃ system a potential hydrogen storage material for practical applications. A theoretical capacity of 4.3 wt% bring this material to the front line of all the available hydrogen storage materials; however, the activation barrier of the reaction restricts the system to absorb and desorb hydrogen reversibly at elevated temperatures even if the thermodynamics suggest its room temperature operation. Several catalysts have already been tested to enhance its kinetic properties. In this work, the efforts were made to reduce the activation energy by using Zr-based catalysts to the KSi/KSiH₃ system. The value of activation energy was found to be lowest (i.e., 87 kJ mol⁻¹⁾ for the ZrH₂-added KSiH₃ system. The mechanism of this improvement was investigated by using X-ray photoelectron spectroscopy (XPS).     

SARS-CoV-2 Monitoring in Wastewater Reveals Novel Variants and Biomarkers of Infection

Wastewater-based epidemiology (WBE) is a popular tool for the early indication of community spread of infectious diseases. WBE emerged as an effective tool during the COVID-19 pandemic and has provided meaningful information to minimize the spread of infection. Here, we present a combination of analyses using the correlation of viral gene copies with clinical cases, sequencing of wastewater-derived RNA for the viral mutants, and correlative analyses of the viral gene copies with the bacterial biomarkers. Our study provides a unique platform for potentially using the WBE-derived results to predict the spread of COVID-19 and the emergence of new variants of concern. Further, we observed a strong correlation between the presence of SARS-CoV-2 and changes in the microbial community of wastewater, particularly the significant changes in bacterial genera belonging to the families of Lachnospiraceae and Actinomycetaceae. Our study shows that microbial biomarkers could be utilized as prediction tools for future infectious disease surveillance and outbreak responses. Overall, our comprehensive analyses of viral spread, variants, and novel bacterial biomarkers will add significantly to the growing body of literature on WBE and COVID-19.     

Mutations responsible for the carbapenemase activity of SME-1

SME-1 is a carbapenemase, produced by Serratia marcescens organism and causes nosocomial infections such as in bloodstream, wounds, urinary tract, or respiratory tract infections. Treatment of such infections becomes very complex due its resistance towards penicillins, cephalosporins, monobactams, and carbapenems. Resistance to such antibiotics is of great medical concern. The misuse and overuse of these antibiotics result in the clinical mutation and production of novel β-lactamase enzymes such as SME-1, which show resistance to carbapenems. Class A contains most of the clinically significant extended spectrum of β-lactamase enzymes and carbapenemases. In this study, class A β-lactamase SME-1 sequence, structure, and binding were compared with naturally mutated class A β-lactamase enzymes and a wild-type TEM-1. This study was performed for revealing mutations, which could be responsible for the carbapenemase activity of SME-1. The dynamic characteristics of SME-1 enzymes manifest a different degree of conservation and variability, which confers them to possess carbapenemase activities. Met69Cys, Glu104Tyr, Tyr105His, Ala237Ser, and Gly238Cys mutations occur in SME-1 as compared to wild-type TEM-1. These mutated residues are present close to active site residues such as Ser70, Lys73, Ser130, Asn132, Glu166, and Asn170, which participate in the hydrolytic reaction of β-lactam antibiotics. Furthermore, these mutated residues demonstrate altered interactions with the β-lactam antibiotics (results in altered binding) and within themselves (results in active site structure alterations), which results in expanding the spectrum of activity of these enzymes. This study provides important insights into the structure and activity relationship of SME-1 enzymes. This is evident from the Ω-loop structure modification, which forms the wall of the active site and repositioning of residues involved in hydrolytic reactions, when present in the complex with meropenem in a stable state of MD simulation at 50 ns. Hence, Met69Cys, Glu104Tyr, Tyr105His, Ala237Ser, and Gly238Cys mutations could result in an altered active site structure, binding, and activity of SME-1 with meropenem and thus become resistantant against meropenem, which is a carbapenem.

Sequencing, molecular docking and dynamics, analysis of naturally mutated class A β-lactamase SME-1 was done to compared with 13 naturally mutated class A β-lactamase including SHV-1 and wild class A β-lactamase TEM-1.     

A Current Review of Cypermethrin-Induced Neurotoxicity and Nigrostriatal Dopaminergic Neurodegeneration

Cypermethrin, a class II pyrethroid pesticide, is used to control insects in the household and agricultural fields. Despite beneficial roles, its uncontrolled and repetitive applications lead to unintended effects in non-target organisms. Cypermethrin crosses the blood-brain barrier and induces neurotoxicity and motor deficits. Cypermethrin prolongs the opening of sodium channel, a major site of its action, leading to hyper-excitation of the central nervous system. In addition to sodium channel, cypermethrin modulates chloride, voltage-gated calcium and potassium channels, alters the activity of glutamate and acetylcholine receptors and adenosine triphosphatases and induces DNA damage and oxidative stress in the neuronal cells. Cypermethrin also modulates the level of neurotransmitters, including gamma-aminobutyric acid and dopamine. It is one of the most commonly used pesticides in neurotoxicology research not only because of its variable responses depending upon the doses, time and routes of exposure and strain, age, gender and species of animals used across multiple studies but also owing to its ability to induce the nigrostriatal dopaminergic neurodegeneration. This article describes the effect of acute, chronic, developmental and adulthood exposures to cypermethrin in experimental animals. The article sheds light on cypermethrin-induced changes in the central nervous system, including its contribution in the onset of specific features, which are associated with the nigrostriatal dopaminergic neurodegeneration. Resemblances and dissimilarities of cypermethrin-induced nigrostriatal dopaminergic neurodegeneration with sporadic and chemicals-induced disease models along with its advantages and pitfalls are also discussed.     

Does Scalp Cooling Have the Same Efficacy in Black Patients Receiving Chemotherapy for Breast Cancer?

Lessons Learned

• Despite U.S. Food and Drug Administration approval to reduce alopecia, data on efficacy of scalp cooling in Black patients with cancer are limited by lack of minority representation in prior clinical trials.
• Scalp cooling devices may have less efficacy in Black patients; additional studies are required to explore the possible causes for this, including hair texture and cap design.

BackgroundThe Paxman scalp cooling (SC) device is U.S. Food and Drug Administration (FDA)‐approved for prevention of chemotherapy‐induced alopecia. Studies report 50%–80% success rates and high patient satisfaction, yet there have been no studies of SC in Black patients. We conducted a phase II feasibility study of Paxman SC with a planned enrollment of 30 Black patients receiving chemotherapy for stage I–III breast cancer.MethodsBlack patients who planned to receive at least four cycles of chemotherapy with non‐anthracycline (NAC) or anthracycline (AC) regimens were eligible. Alopecia was assessed by trained oncology providers using the modified Dean scale (MDS) prior to each chemotherapy session. Distress related to alopecia was measured by the Chemotherapy Alopecia Distress Scale (CADS).ResultsFifteen patients enrolled in the intervention before the study was closed early because of lack of efficacy. Median MDS and CADS increased after SC, suggesting increased hair loss (p < .001) and alopecia distress (p = .04). Only one participant was successful in preventing significant hair loss; the majority stopped SC before chemotherapy completion because of grade 3 alopecia (>50% hair loss).ConclusionSC may not be efficacious in preventing alopecia in Black women. Differences in hair thickness, hair volume, and limitations of cooling cap design are possible contributing factors.     

Multiple contrast type tests for the evaluation of animal carcinogenicity studies

The Cochran–Armitage (CA) test is frequently used for testing the dose–response relationship in tumor incidence. This test is based on a weighted linear regression of proportions. It is well known that the CA test lacks power for nonlinear tumor outcomes. For general shape of outcomes, Hothorn and Bretz (2000) proposed a multiple contrast (MC) test. This test suggests the use of the maximum over several single contrasts, where each of them is chosen appropriately to cover a specific dose–response shape. In this work, two new test procedures are proposed and they are compared to the CA and MC tests using power.