Prevention Of Human Diseases Research Articles

An investigative study on Yersinia enterocolitica in animals, humans and dried milk in New Valley Governorate, Egypt

BackgroundYersiniosis is one of the most significant intestinal disorders caused by Yersinia enterocolitica and affects both humans and animals. This study aimed to investigate the prevalence of Y. enterocolitica in New Valley Governorate, Egypt in animals, humans, fresh milk and dried milk. Additionally, this study analyzed the presence of virulence genes, including ail and Yst in tested isolates and conducted a phylogenetic analysis to determine the genetic similarity between human, and animal Y. enterocolitica isolates. Finally, the antimicrobial resistance patterns of the isolates were examined.ResultsAmong the 982 samples examined, the prevalence of Y. enterocolitica based on ISO10273-2017 was 11.7% in animal samples including 12.8% of animal faeces, and 10.4% in milk samples. Moreover, the prevalence of Y. enterocolitica was 13.2% in human stool, and 9.5% in dried milk samples. The molecular characterization of the six randomly selected isolates showed that the 16S rRNA, ail and Yst genes were found in 50, 33.3 and 100% of the examined Y. enterocolitica isolates, respectively. Phylogenetic analysis of animal and human isolates based on the 16S rRNA gene revealed a high degree of similarity between the isolates. All the tested animal and human Y. enterocolitica isolates (100%) were resistant to ampicillin and cefotaxime, but highly sensitive to norfloxacin.ConclusionsThe high prevalence of Y. enterocolitica in animal and human samples with high degrees of genetic similarity poses a threat to public and animal health. Animal faeces, milk and milk powder represent the main sources of Y. enterocolitica infection in humans. Additionally, high levels of antibiotic resistance of Y. enterocolitica can cause public health hazards by leading to the failure of disease prevention and treatment programs in humans and animals.

How Pharmaceutical Residues Occur, Behave, and Affect the Soil Environment.

Many pharmaceuticals (PhMs), compounds for the treatment or prevention of diseases in humans and animals, have been identified as pollutants of emerging concern (PECs) due to their wide environmental distribution and potential adverse impact on nontarget organisms and populations. They are often found at significant levels in soils due to the continuous release of effluent and sludge from wastewater treatment plants (WWTPs), the release of which occurs much faster than the removal of PhMs. Although they are generally present at low environmental concentrations, conventional wastewater treatment cannot successfully remove PhMs from influent streams or biosolids. In addition, the soil application of animal manure can result in the pollution of soil, surface water, and groundwater with PhMs through surface runoff and leaching. In arid and semiarid regions, irrigation with reclaimed wastewater and the soil application of biosolids are usual agricultural practices, resulting in the distribution of a wide number of PhMs in agricultural soils. The ability to accurately study the fate of PhMs in soils is critical for careful risk evaluation associated with wastewater reuse or biosolid return to the environment. The behavior and fate of PhMs in soils are determined by a number of processes, including adsorption/desorption (accumulation) to soil colloids, biotic (biodegradation) and abiotic (chemical and photochemical degradation) degradation, and transfer (movement) through the soil profile. The sorption/desorption of PhMs in soils is the main determinant of the amount of organic chemicals taken up by plant roots. The magnitude of this process depends on several factors, such as crop type, the physicochemical properties of the compound, environmental properties, and soil-plant characteristics. PhMs are assumed to be readily bioavailable in soil solutions for uptake by plants, and such solutions act as carriers to transport PhMs into plants. Determining microbial responses under exposure conditions can assist in elucidating the impact of PhMs on soil microbial activity and community size. For all of the above reasons, soil remediation is critical when soil pollutants threaten the environment.

Plant-Derived as Alternatives to Animal-Derived Bioactive Peptides: A Review of the Preparation, Bioactivities, Structure–Activity Relationships, and Applications in Chronic Diseases

Background/Objectives: At present, a large number of bioactive peptides have been found from plant sources with potential applications for the prevention of chronic diseases. By promoting plant-derived bioactive peptides (PDBPs), we can reduce dependence on animals, reduce greenhouse gas emissions, and protect the ecological environment. Methods: In this review, we summarize recent advances in sustainably sourced PDBPs in terms of preparation methods, biological activity, structure–activity relationships, and their use in chronic diseases. Results: Firstly, the current preparation methods of PDBPs were summarized, and the advantages and disadvantages of enzymatic method and microbial fermentation method were introduced. Secondly, the biological activities of PDBPs that have been explored are summarized, including antioxidant, antibacterial, anticancer and antihypertensive activities. Finally, based on the biological activity, the structure–activity relationship of PDBPs and its application in chronic diseases were discussed. All these provide the foundation for the development of PDBPs. However, the study of PDBPs still has some limitations. Conclusions: Overall, PDBPs is a good candidate for the prevention and treatment of chronic diseases in humans. This work provides important information for exploring the source of PDBPs, optimizing its biological activity, and accurately designing functional foods or drugs.

Baru nut oil physicochemical properties, fatty acid and mineral nutritional quality: a high source of oligoelement selenium

Baru nut (Dipteryx alata Vogel) oil obtained by cold pressed machine yielded 24% (mg g–1), primarily composed of unsaturated fatty acids (⁓ 79%), with oleic and linoleic acids in the proportion of 2:1. The oxidative stability assessed by Rancimat method, Thermogravimetry analysis and Differential Scanning Calorimetry revealed thermal stability, which attributed to a higher amount of oleic than linoleic fatty acids, synergistic action of the natural antioxidants and low iodine index. The nutritional qualities were calculated to atherogenic (AI = 0.07), thrombogenic (TI = 0.22) and hypocholesterolemic/ hypercholesterolemic (HH = 13.77), and physicochemical indices: acidity (0.62), peroxide (9.99), saponification (179.93) were higher, whereas iodine (93.00) and relative density (0.9121) were found between the recommended Codex Alimentarius parameters. Mineral elements were quantified using ICP OES (inductively coupled plasma optical emission spectroscopy) in decreased order of Mg > Se > Zn > Mn > Al > Cu, whereas As, Co, Cd, Cr, Fe, Ni, and Pb < LOD. In addition, this oil showed optimal indices to non-cancer risk (CR < 10–6), and non-carcinogenic: hazard quotient (HQ), and total hazard indices (HI) < 1. Nevertheless, major attention is necessary for children and Se hypersensitive consumers, which baru oil daily consumption quantity was estimated based on selenium (Se) trace element at 0.7964 g kg–1. Thus, we recommend the consumption of baru nut oil for human health promotion and metabolic disease prevention.

Advances in the Synthesis and Bioactivity of Polysaccharide Selenium Nanoparticles: A Review.

Selenium, an essential trace element of the human body, is pivotal in human health and disease prevention. Nevertheless, the narrow therapeutic index of selenium, where the toxic and therapeutic doses are close, limits its clinical utility. Significantly, nanoscale selenium synthesized by different methods using polysaccharides as stabilizers has low toxicity properties and exhibits excellent bioactivity. Its biological activities, such as anti-tumor, anti-inflammatory, antioxidant, antibacterial, and immune function enhancement, are improved compared with traditional organic and inorganic selenium compounds, conferring greater potential for application in biomedicine. Therefore, this review evaluates the advancements in various synthesis methodologies for polysaccharide selenium nanoparticles (Se NPs) and their biological activities. It aims to provide a comprehensive theoretical basis and research directions for the future development of highly efficient, minimally toxic, and biocompatible polysaccharide-Se NPs and the application of polysaccharide-Se NPs in biomedicine.

Potential Human Health Benefits of Phaseolus vulgaris L. var Venanzio: Effects on Cancer Cell Growth and Inflammation.

It is widely recognized that foods, biodiversity, and human health are strongly interconnected, and many efforts have been made to understand the nutraceutical value of diet. In particular, diet can affect the progression of intestinal diseases, including inflammatory bowel disease (IBD) and intestinal cancer. In this context, we studied the anti-inflammatory and antioxidant activities of extracts obtained from a local endangered variety of Phaseolus vulgaris L. (Fagiola di Venanzio, FV). Using in vitro intestinal cell models, we evaluated the activity of three different extracts: soaking water, cooking water, and the bioaccessible fraction obtained after mimicking the traditional cooking procedure and gastrointestinal digestion. We demonstrated that FV extracts reduce inflammation and oxidative stress prompted by interleukin 1β through the inhibition of cyclooxygenase 2 expression and prostaglandin E2 production and through the reduction in reactive oxygen species production and NOX1 levels. The reported data outline the importance of diet in the prevention of human inflammatory diseases. Moreover, they strongly support the necessity to safeguard local biodiversity as a source of bioactive compounds.

Methylsulfinyl Hexyl Isothiocyanate (6-MSITC) from Wasabi Is a Promising Candidate for the Treatment of Cancer, Alzheimer's Disease, and Obesity.

Methylsulfinyl hexyl isothiocyanate (6-MSITC) isolated from Eutrema japonicum is a promising candidate for the treatment of breast cancer, colorectal and stomach cancer, metabolic syndrome, heart diseases, diabetes, and obesity due to its anti-inflammatory and antioxidant properties. Also, its neuroprotective properties, improving cognitive function and protecting dopaminergic neurons, make it an excellent candidate for treating neurodegenerative diseases like dementia, Alzheimer's, and Parkinson's disease. 6-MSITC acts on many signaling pathways, such as PPAR, AMPK, PI3K/AKT/mTOR, Nrf2/Keap1-ARE, ERK1/2-ELK1/CHOP/DR5, and MAPK. However, despite the very promising results of in vitro and in vivo animal studies and a few human studies, the molecule has not yet been thoroughly tested in the human population. Nonetheless, wasabi should be classified as a "superfood" for the primary and secondary prevention of human diseases. This article reviews the current state-of-the-art research on 6-MSITC and its potential clinical uses, discussing in detail the signaling pathways activated by the molecule and their interactions.

Advances in gut-brain organ chips.

The brain and gut are sensory organs responsible for sensing, transmitting, integrating, and responding to signals from the internal and external environment. In-depth analysis of brain-gut axis interactions is important for human health and disease prevention. Current research on the brain-gut axis primarily relies on animal models. However, animal models make it difficult to study disease mechanisms due to inherent species differences, and the reproducibility of experiments is poor because of individual animal variations, which leads to a significant limitation of real-time sensory responses. Organ-on-a-chip platforms provide an innovative approach for disease treatment and personalized research by replicating brain and gut ecosystems in vitro. This enables a precise understanding of their biological functions and physiological responses. In this article, we examine the history and most current developments in brain, gut, and gut-brain chips. The importance of these systems for understanding pathophysiology and developing new drugs is emphasized throughout the review. This article also addresses future directions and present issues with the advancement and application of gut-brain-on-a-chip technologies.

Photodynamic Inactivation as a Promising Method of Combating Resistant Strains of Staphylococci

Relevance. The development of antimicrobial drugs and alternative methods, technologies and means of prevention, diagnosis and treatment of human infectious diseases caused by antibiotic-resistant microorganisms is one of the priorities of ensuring the biological safety of the country. Aims. To evaluate the bactericidal activity of tetrapyrrole macroheterocycles (porphyrins) at different light irradiation durations in relation to staphylococci, in vitro. Materials and methods. Studied strains of microorganisms: museum strains of microorganisms – S. aureus ATCC 29213, S. epidermidis ATCC 14990 and antibiotic-resistant strains of bacteria of the genus Staphylococcus (n=18) isolated from clinical biomaterial and from environmental objects in a medical organization. The studied chemical compounds are three different compounds of water-soluble asymmetrically substituted porphyrins containing heterocyclic fragments on the periphery of the porphyrin cycle (residues of benzoxazole, N-methylbenzimidazole and benzothiazole). Results. The activity of all three porphyrin compounds in relation to museum strains of staphylococcus and 77.8% of clinical antibiotic-resistant strains (n=14; 95% CI 20.1-97.5) turned out to be maximal (complete lysis) after 10 minutes of irradiation. Conclusions. The tested tetrapyrrole macroheterocycles (porphyrins) exhibit bactericidal activity against museum and clinical strains of staphylococcus, with different levels of antibiotic resistance, which determines Keywords: antibiotic resistance, water-soluble porphyrin, photodynamic inactivation, photosensitizer, photochemistry, staphylococci No conflict of interest to declare.

The Role of Short Chain Fatty Acids in Inflammation and Body Health.

Short chain fatty acids (SCFAs), mainly including acetate, propionate and butyrate, are produced by intestinal bacteria during the fermentation of partially digested and indigestible polysaccharides. SCFAs play an important role in regulating intestinal energy metabolism and maintaining the homeostasis of the intestinal environment and also play an important regulatory role in organs and tissues outside the gut. In recent years, many studies have shown that SCFAs can regulate inflammation and affect host health, and two main signaling mechanisms have also been identified: the activation of G-protein coupled receptors (GPCRs) and inhibition of histone deacetylase (HDAC). In addition, a growing body of evidence highlights the importance of every SCFA in influencing health maintenance and disease development. In this review, we summarized the recent advances concerning the biological properties of SCFAs and their signaling pathways in inflammation and body health. Hopefully, it can provide a systematic theoretical basis for the nutritional prevention and treatment of human diseases.

Tapping into Nature's Arsenal: Harnessing the Potential of Natural Antioxidants for Human Health and Disease Prevention.

Numerous natural antioxidants commonly found in our daily diet have demonstrated significant benefits for human health and various diseases by counteracting the impact of reactive oxygen and nitrogen species. Their chemical properties enable a range of biological actions, including antihypertensive, antimicrobial, anti-inflammatory, anti-fibrotic, and anticancer effects. Despite promising outcomes from preclinical studies, ongoing debate persists regarding their reproducibility in human clinical models. This controversy largely stems from a lack of understanding of the pharmacokinetic properties of these compounds, coupled with the predominant focus on monotherapies in research, neglecting potential synergistic effects arising from combining different antioxidants. This study aims to provide an updated overview of natural antioxidants, operating under the hypothesis that a multitherapeutic approach surpasses monotherapy in efficacy. Additionally, this study underscores the importance of integrating these antioxidants into the daily diet, as they have the potential to prevent the onset and progression of various diseases. To reinforce this perspective, clinical findings pertaining to the treatment and prevention of non-alcoholic fatty liver disease and conditions associated with ischemia and reperfusion phenomena, including myocardial infarction, postoperative atrial fibrillation, and stroke, are presented as key references.

Toxicity Study of Sulfonamides Antibiotics

Antibiotics refer to organic substances produced by plants, animals, microorganisms and other organisms in the course of their life activities or obtained by other methods, which can selectively inhibit or affect other organisms at low concentrations. According to the chemical structure, sulfonamides (SAs), tetracycline, etc. can be divided into sulfonamides, and veterinary antibiotics, agricultural antibiotics, medical antibiotics, etc. can be divided into sulfonamides according to the source. Antibiotics can inhibit cell growth and reproduction, and have been continuously synthesized since the advent of penicillin in 1929. At present, antibiotics have become one of the most widely used and used drugs in the world, not only for the prevention and treatment of human and animal diseases, but also as animal feed.

Mechanisms of host adaptation by bacterial pathogens.

The emergence of new infectious diseases poses a major threat to humans, animals, and broader ecosystems. Defining factors that govern the ability of pathogens to adapt to new host species is therefore a crucial research imperative. Pathogenic bacteria are of particular concern, given dwindling treatment options amid the continued expansion of antimicrobial resistance. In this review, we summarize recent advancements in the understanding of bacterial host species adaptation, with an emphasis on pathogens of humans and related mammals. We focus particularly on molecular mechanisms underlying key steps of bacterial host adaptation including colonization, nutrient acquisition, and immune evasion, as well as suggest key areas for future investigation. By developing a greater understanding of the mechanisms of host adaptation in pathogenic bacteria, we may uncover new strategies to target these microbes for the treatment and prevention of infectious diseases in humans, animals, and the broader environment.

An Online Native Mass Spectrometry Approach for Fast, Sensitive, and Quantitative Assessment of Adeno-Associated Virus Capsid Content Ratios.

Adeno-associated viruses (AAVs) have emerged as a leading platform for in vivo therapeutic gene delivery and offer tremendous potential in the treatment and prevention of human disease. The fast-paced development of this growing class of therapeutics, coupled with their intrinsic structural complexity, places a high demand on analytical methods capable of efficiently monitoring product quality to ensure safety and efficacy, as well as to support manufacturing and process optimization. Importantly, the presence and relative abundance of both empty and partially filled AAV capsid subpopulations are of principal concern, as these represent the most common product-related impurities in AAV manufacturing and have a direct impact on therapeutic potential. For this reason, the capsid content, or ratio of empty and partial capsids to those packaged with the full-length therapeutic genome, has been identified by regulatory agencies as a critical quality attribute (CQA) that must be carefully controlled to meet clinical specifications. Established analytical methods for the quantitation of capsid content ratios often suffer from long turnaround times, low throughput, and high sample demands that are not well-suited to the narrow timelines and limited sample availability typical of process development. In this study, we present an integrated online native mass spectrometry platform that aims to minimize sample handling and maximize throughput and robustness for rapid and sensitive quantitation of AAV capsid content ratios. The primary advantages of this platform for AAV analysis include the ability to perform online buffer exchange under low flow conditions to maintain sample stability with minimal sample dilution, as well as the ability to achieve online charge reduction via dopant-modified desolvation gas. By exploiting the latter, enhanced spectral resolution of signals arising from empty, partial, and full AAV capsids was accomplished in the m/z domain to facilitate improved spectral interpretation and quantitation that correlated well with the industry standard analytical ultracentrifugation (AUC) method for capsid content ratio determination. The utility of this approach was further demonstrated in several applications, including the rapid and universal screening of different AAV serotypes, evaluation of capsid content for in-process samples, and the monitoring of capsid stability when subjected to thermal stress conditions.

Integration of artificial intelligence in clinical laboratory medicine: Advancements and challenges

AbstractArtificial intelligence (AI)‐driven analysis of comprehensive clinical parameters is bringing about a significant transformation in traditional routine clinical laboratory testing. This transformation impacts the prediction, prevention, diagnosis, and prognosis of human diseases. AI possesses the capability to efficiently analyze and process vast and intricate datasets, thereby facilitating the development of diverse and efficient diagnostic or predictive models. This advancement is fueling significant improvements in laboratory quality, automation, and the accuracy of diagnoses. In this context, we conducted a thorough review and discussion on the progression of AI applications in clinical laboratory medicine, encompassing advancements, implementation, and challenges. Our conclusion underscores that integrating AI into clinical laboratory testing will notably propel personalized precision medicine forward and enhance diagnostic accuracy, especially benefiting patients for whom accurate diagnoses are elusive through traditional laboratory testing systems.

Spatiotemporal pattern and suitable areas analysis of equine influenza in global scale (2005-2022).

Equine influenza (EI) is a severe infectious disease that causes huge economic losses to the horse industry. Spatial epidemiology technology can explore the spatiotemporal distribution characteristics and occurrence risks of infectious diseases, it has played an important role in the prevention and control of major infectious diseases in humans and animals. For the first time, this study conducted a systematic analysis of the spatiotemporal distribution of EI using SaTScan software and investigated the important environmental variables and suitable areas for EI occurrence using the Maxent model. A total of 517 occurrences of EI from 2005 to 2022 were evaluated, and 14 significant spatiotemporal clusters were identified. Furthermore, a Maxent model was successfully established with high prediction accuracy (AUC = 0.920 ± 0.008). The results indicated that annual average ultraviolet radiation, horse density, and precipitation of the coldest quarter were the three most important environmental variables affecting EI occurrence. The suitable areas for EI occurrence are widely distributed across all continents, especially in Asia (India, Mongolia, and China) and the Americas (Brazil, Uruguay, USA, and Mexico). In the future, these suitable areas will expand and move eastward. The largest expansion is predicted under SSP126 scenarios, while the opposite trend will be observed under SSP585 scenarios. This study presents the spatial epidemiological characteristics of EI for the first time. The results could provide valuable scientific insights that can effectively inform prevention and control strategies in regions at risk of EI worldwide.

Effects of Food Bioactive Compounds on Human Health and Disease Prevention in Botswana

Purpose: The aim of the study was to evaluate effects of food bioactive compounds on human health and disease prevention in Botswana. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: The study found that bioactive compounds found in a variety of foods, including fruits, vegetables, grains, and herbs, have been extensively studied for their potential health benefits, including antioxidant, anti-inflammatory, and anti-cancer properties. In Botswana, where NCDs such as diabetes, hypertension, and cardiovascular diseases are major public health concerns, integrating bioactive-rich foods into the diet plays a crucial role in reducing the prevalence and impact of these conditions. Unique Contribution to Theory, Practice and Policy: Nutritional Epidemiology Theory, Pharmacological Theory of Food Bioactive Compounds & Health Behavior Theory may be used to anchor future studies on effects of food bioactive compounds on human health and disease prevention in Botswana. Promote public awareness and education campaigns to highlight the importance of incorporating bioactive compounds into daily diets for health maintenance and disease prevention. This can include disseminating accessible information about bioactive-rich foods and their health benefits. Advocate for the inclusion of dietary guidelines that emphasize the consumption of bioactive-rich foods in national nutrition policies. This can involve collaborating with policymakers to integrate evidence-based recommendations into dietary guidelines and public health initiatives.

Ephedra: An anti-asthamatic medicinal plant

ailments such as cold, cough, asthma, fever and flu. It is distributed in many regions such as Asia, Europe, North Africa, Western North America and South America. It has more than 100 active compounds with effects. It contains flavonoids, alkanes, tannins, sugars and organic phenolic acids. It is used in the treatment of asthma, liver disease, skin disease and other diseases, the most important among the effectiveness of the treatment of the disease is COVID-19. It is considered an ancient group and is appreciated for its abundant fossil record. Ephedra, known as "Ephedra" in China, is a gymnosperm plant. It is a dry straw stalk associated with the lung and bladder meridians. Ephedra is one of the largest genera of the Ephedra family and is found in arid and semi-arid regions of the world. In traditional medicine in many countries, some of these species are frequently used to treat asthma, colds, flu, colds, fever, headaches, nasal congestion and cough. The chemical composition of the ephedra plant has been a focus of interest for decades due to its content of ephedrine alkaloids and its medicinal properties. Other chemical compounds such as phenolics and amino acid derivatives are also of interest and provide evidence-based support for the ethnomedical use of Ephedra. Medicinal plants contain many phytochemical compounds related to various treatments (Naiá et al., 2005; Ghoíbani, 2005). Therefore, this medicinal herb is used in various ephedrine formulations and has many adverse effects on diseases such as liver diseases, angle-closure glaucoma, kidney stones, neurodegenerative diseases and heart toxicity. Indian Ayurveda is a traditional herbal medicine with a long history and strong foundations. Medicinal plants play an important role in the prevention and treatment of human diseases. This plant usually grows on dry rocks and soil because it needs high, dry mountain forests to grow. Many parts of plants such as branches and roots are used in various applications for medicinal purposes. For example, the dry part of the plant is used in vartonic medicine systems such as Ayurveda, Siddha and traditional Chinese medicine to treat many diseases such as asthma, hay fever, pain or inflammation, lung disease, heart disease. Aches, coughs, and colds are considered flu-like symptoms.

Double base mismatches mediated catalytic hairpin assembly for enzyme-free single-base mutation detection: integrating signal recognition and amplification in one.

Single nucleotide polymorphism (SNP) biosensors are emerging rapidly for their promising applications in human disease prevention diagnosis, treatment, and prognosis. However, it remains a bottleneck in equipping simple and stable biosensors with the traits of high sensitivity, non-enzyme, and low cost. Double base mismatches mediated chain displacement reactions have attracted fascinating advantages of tailorable thermodynamics stability, non-enzyme, and excellent assembly compliance to involvement in SNP identification. As the base mismatch position and amount in DNA sequence can be artificially adjusted, it provides plenty of selectivity and specificity for exploring perfect biosensors. Herein, abiosensor with double base mismatches mediated catalytic hairpin assembly (CHA) is designed via one base mismatch in the toehold domain and the other base mismatch in the stem sequence of hairpin 1 (H1) by triggering CHA reaction to achieve selective amplification of the mutation target (MT) and fluorescence resonance energy transfer (FRET) effect that is composed of Cy3 and Cy5 terminally attached H1 and hairpin 2 (H2). Depending on the rationally designed base mismatch position and toehold length, the fabricated biosensors show superior SNP detection performance, exhibiting a good linearity with high sensitivity of 6.6 fM detection limitand a broad detection abundance of 1%. The proposed biosensor can be used to detect the KRAS mutation gene in real samples and obtain good recoveries between 106 and 116.99%. Remarkably, these extendible designs of base mismatches can be used for more types of SNP detection, providing flexible adjustment based on base mismatch position and toehold length variations, especially for their thermodynamic model for DNA-strand displacement reactions.

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients.

Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients. This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post-LET initiation; secondary outcomes included hematologic changes. A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R-), with LET initiated a median of 9.6 months post-transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p=.370). The median (interquartile range) white blood cell (WBC) count was3.1 (2.1-5.6)at LET initiation which increased to5.1 (3.9-7.2)at the end of follow-up (p <.001). For VGCV controls, WBC was4.8 (3.4-7.2)at baseline and5.4 (3.6-7.2)at the end of follow-up; this difference was not statistically significant (p=.395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001). LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.