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1.
Article in English | MEDLINE | ID: mdl-39358698

ABSTRACT

Additive manufacturing electrochemistry is an ever-expanding field; however, it is limited to aqueous environments due to the conductive filaments currently available. Herein, the production of a conductive poly(propylene) filament, which unlocks the door to organic electrochemistry and electrosynthesis, is reported. A filament with 40 wt % carbon black possessed enhanced thermal stability, excellent low-temperature flexibility, and high conductivity. The filament produced highly reproducible additive manufactured electrodes that were electrochemically characterized, showing a k0 of 2.00 ± 0.04 × 10-3 cm s-1. This material was then applied to three separate electrochemical applications. First, the electroanalytical sensing of colchicine within environmental waters, where a limit of detection of 10 nM was achieved before being applied to tap, bottled, and river water. Second, the electrodes were stable in organic solvents for 100 cyclic voltammograms and 15 days. Finally, these were applied toward an electrosynthetic reaction of chlorpromazine, where the electrodes were stable for 24-h experiments, outperforming a glassy carbon electrode, and were able to be reused while maintaining a good electrochemical performance. This material can revolutionize the field of additive manufacturing electrochemistry and expand research into a variety of new fields.

2.
Sci Rep ; 14(1): 23195, 2024 10 05.
Article in English | MEDLINE | ID: mdl-39369124

ABSTRACT

Colorectal cancer (CRC) is a severe gastrointestinal cancer and a leading cause of cancer-related deaths in Ghana. The potential role of gut Enterobacteriaceae in the increasing incidence of CRC in Ghana is yet to be thoroughly investigated. In this study, Enterobacteriaceae from CRC patients and healthy control participants were analyzed by whole genome sequencing to identify genomic features that are associated with CRC. Socio-demographic data showed a significant association between age and alcohol consumption and CRC. Escherichia coli was the most abundant Enterobacteriaceae isolated from the study participants and they were predominantly intestinal commensals. Escherichia coli isolates belonging to phylogroup D encoded the highest number of virulence genes. The agn43 and int genes were widespread in Escherichia coli isolates from the CRC patients. Multilocus sequence types of potentially pathogenic Escherichia coli from the CRC patients also encoded genes involved in aggregation, adherence and biofilm formation. The ampC2 and ampH antimicrobial resistance genes were also widespread in the genome of the Escherichia coli isolates. This study highlights the virulence tendencies of Escherichia coli from CRC patients and their ability to transfer virulence determinants to other Enterobacteriaceae residing in the gut.


Subject(s)
Colorectal Neoplasms , Enterobacteriaceae , Tertiary Care Centers , Humans , Ghana/epidemiology , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/genetics , Female , Male , Middle Aged , Case-Control Studies , Enterobacteriaceae/genetics , Enterobacteriaceae/pathogenicity , Enterobacteriaceae/isolation & purification , Aged , Escherichia coli/genetics , Escherichia coli/isolation & purification , Escherichia coli/pathogenicity , Whole Genome Sequencing , Genome, Bacterial , Adult , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/epidemiology , Virulence Factors/genetics , Genomics/methods
3.
BMC Public Health ; 24(1): 2686, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39370520

ABSTRACT

BACKGROUND: Despite the ubiquity of adolescent screen use, there are limited longitudinal studies that examine the prospective relationships between screen time and child behavioral problems in a large, diverse nationwide sample of adolescents in the United States, which was the objective of the current study. METHODS: We analyzed cohort data of 9,538 adolescents (9-10 years at baseline in 2016-2018) with two years of follow-up from the Adolescent Brain Cognitive Development (ABCD) Study. We used mixed-effects models to analyze associations between baseline self-reported screen time and parent-reported mental health symptoms using the Child Behavior Checklist, with random effects adjusted for age, sex, race/ethnicity, household income, parent education, and study site. We tested for effect modification by sex and race/ethnicity. RESULTS: The sample was 48.8% female and racially/ethnically diverse (47.6% racial/ethnic minority). Higher total screen time was associated with all mental health symptoms in adjusted models, and the association was strongest for depressive (B = 0.10, 95% CI 0.06, 0.13, p < 0.001), conduct (B = 0.07, 95% CI 0.03, 0.10, p < 0.001), somatic (B = 0.06, 95% CI 0.01, 0.11, p = 0.026), and attention-deficit/hyperactivity symptoms (B = 0.06, 95% CI 0.01, 0.10, p = 0.013). The specific screen types with the greatest associations with depressive symptoms included video chat, texting, videos, and video games. The association between screen time and depressive, attention-deficit/hyperactivity, and oppositional defiant symptoms was stronger among White compared to Black adolescents. The association between screen time and depressive symptoms was stronger among White compared to Asian adolescents. CONCLUSIONS: Screen time is prospectively associated with a range of mental health symptoms, especially depressive symptoms, though effect sizes are small. Video chat, texting, videos, and video games were the screen types with the greatest associations with depressive symptoms. Future research should examine potential mechanisms linking screen use with child behavior problems.


Subject(s)
Screen Time , Humans , Female , Male , Prospective Studies , Child , Adolescent , United States/epidemiology , Mental Health/statistics & numerical data , Longitudinal Studies , Adolescent Development , Adolescent Behavior/psychology
4.
Front Vet Sci ; 11: 1417278, 2024.
Article in English | MEDLINE | ID: mdl-39372901

ABSTRACT

Introduction: The morphological characteristics of eyes in fishes are highly diverse and have evolved to meet the specific visual requirements as per their habitats. These morphological features of eyes are important for researchers and ecologists. The dusky spinefoot (Siganus luridus) is a tropical teleost fish with a laterally flattened body which lives in the Mediterranean Sea. Currently, there are no histological data relating to the Siganus luridus eye. Methods: In this study, the morphology of the Siganus luridus eye was examined to enhance our understanding of its structure and its relationship to fish ecology. Detailed gross and microscopic features were recorded using light and scanning microscopy. Results: The key observations describe the main structural features of the eye of Siganus luridus, specifically, the diameter of the orbit, architecture of three tunics of eye and detailed lens description. The choroid was divided into four layers, and had a rete mirabile, consisting of numerous small blood vessels in the choroidal gland. The tapetum lucidum was observed, which is interesting since Siganus luridus is herbivore and herbivores typically lack a tapetum lucidum. Discussion: These observations shed new light on the intricate eye structure of Siganus luridus and provide valuable insights into its visual abilities and adaptations to the aquatic environment and feeding behavior.

5.
CNS Neurosci Ther ; 30(10): e70008, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39374157

ABSTRACT

BACKGROUND: Manganism, a central nervous system dysfunction correlated with neurological deficits such as Parkinsonism, is caused by the substantial collection of manganese chloride (MnCl2) in the brain. OBJECTIVES: To explore the neuroprotective effects of natural compounds, namely, micronized zeolite clinoptilolite (ZC) and punicalagin (PUN), either individually or in combination, against MnCl2-induced Parkinson's disease (PD). METHODS: Fifty male albino rats were divided into 5 groups (Gps). Gp I was used as the control group, and the remaining animals received MnCl2 (Gp II-Gp V). Rats in Gps III and IV were treated with ZC and PUN, respectively. Gp V received both ZC and PUN as previously reported for the solo-treated plants. RESULTS: ZC and/or PUN reversed the depletion of monoamines in the brain and decreased acetyl choline esterase activity, which primarily adjusted the animals' behavior and motor coordination. ZC and PUN restored the balance between glutamate/γ-amino butyric acid content and markedly improved the brain levels of brain-derived neurotrophic factor and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and decreased glycogen synthase kinase-3 beta activity. ZC and PUN also inhibited inflammatory and oxidative markers, including nuclear factor kappa-light-chain-enhancer of activated B cells, Toll-like receptor 4, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 and caspase-1. Bcl-2-associated X-protein and B-cell leukemia/lymphoma 2 protein (Bcl-2) can significantly modify caspase-3 expression. ZC and/or PUN ameliorated PD in rats by decreasing the levels of endoplasmic reticulum (ER) stress markers (p-protein kinase-like ER kinase (PERK), glucose-regulated protein 78, and C/EBP homologous protein (CHOP)) and enhancing the levels of an autophagy marker (Beclin-1). DISCUSSION AND CONCLUSION: ZC and/or PUN mitigated the progression of PD through their potential neurotrophic, neurogenic, anti-inflammatory, antioxidant, and anti-apoptotic activities and by controlling ER stress through modulation of the PERK/CHOP/Bcl-2 pathway.


Subject(s)
Chlorides , Hydrolyzable Tannins , Neuroprotective Agents , Zeolites , Animals , Male , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Rats , Zeolites/pharmacology , Hydrolyzable Tannins/pharmacology , Hydrolyzable Tannins/therapeutic use , Chlorides/toxicity , Manganese Compounds/pharmacology , Disease Models, Animal , Brain/drug effects , Brain/metabolism
7.
Ann R Coll Surg Engl ; 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39377689

ABSTRACT

INTRODUCTION: Metacarpal shaft fractures (MSF) are common injuries that predominantly affect young, economically active people. However, there is limited evidence to guide their management. The aims of this study were to: evaluate the management of extra-articular MSF of the fingers; assess equipoise for surgical and nonsurgical treatments; and explore factors influencing clinician decision making to inform the design of a randomised controlled trial (RCT) comparing surgical and nonsurgical treatments. METHODS: A cross-sectional, web-based survey was distributed to UK hand surgeons using membership directories of different professional networks. Practice setting, clinical experience, management strategies, willingness to participate in a RCT and factors affecting suitability for randomisation were recorded. RESULTS: There were 108 responses eligible for analysis. Distribution of clinical experience ranged from <5 to >20 years. A variety of treatments were used for transverse, long oblique/spiral and comminuted MSF. Rotational deformity (90%), step-off deformity (5%) and angulation (5%) were the most important indications for surgical fixation. Acceptable limits of fracture angulation and shortening varied among surgeons. Over 85% expressed interest in participating in a RCT and most showed equipoise and were willing to offer operative or nonoperative treatment as part of a research study. CONCLUSIONS: This survey demonstrates that UK hand surgeons have varying views on treatments, acceptable parameters of deformity and indications for surgical fixation of displaced MSF. There is equipoise for surgical and nonsurgical treatments, variability in factors influencing clinical decision making and support for RCTs to investigate best practice.

8.
Mol Biol (Mosk) ; 58(2): 204-219, 2024.
Article in Russian | MEDLINE | ID: mdl-39355879

ABSTRACT

The study of molecular and genetic mechanisms of sex determination in the poplar is of interest not only in the fundamental science, but also in the applied research. In landscaping of large settlements, it is advisable to use male individuals of the Populus genus due to their hypoallergenicity and increased resistance to environmental pollution, stress conditions, and pathogens. However, sex determination in poplars is complicated by the complex genetic structure of the sex-determining region of the genome (SDR). In this review, the emergence, evolution, structure, and function of the SDR in the genus Populus are discussed. Current insights into the structure and function of the key regulator of sex selection in poplars, orthologue of the ARR16/ARR17 gene and the possible roles of other genes that are differentially expressed between male and female plants, including microRNAs, in this process are discussed in detail. The great diversity of species and the high complexity of SDR organization justify the need for further study of the molecular mechanisms of sex determination in poplars.


Subject(s)
Populus , Sex Determination Processes , Populus/genetics , Sex Determination Processes/genetics , Gene Expression Regulation, Plant , MicroRNAs/genetics , MicroRNAs/metabolism , Plant Proteins/genetics , Genome, Plant
9.
Mol Biol (Mosk) ; 58(2): 234-245, 2024.
Article in Russian | MEDLINE | ID: mdl-39355881

ABSTRACT

Oral cancer is an aggressive and rapidly progressive disease. The oral cavity is home to over 700 species of microorganisms that regulate metabolism, immune function, and health. There are three types of mechanisms by which bacteria may participate in carcinogenesis. First, bacteria cause chronic inflammation, which stimulates the production of cytokines, including interleukins, interferons, and tumor necrosis factor. Second, bacteria can interact directly with host cells by secreting toxins or by binding to membrane receptors. Finally, the production of metabolites by bacteria may also contribute to carcinogenesis. The importance of the bacteria level and composition in the transition of oral precancerous lesions to cancer has been demonstrated. The relationships of changes in microbiome composition with smoking, inflammation in healthy individuals, as well as with the development of oral cancer in patients, have been studied.


Subject(s)
Microbiota , Mouth Neoplasms , Mouth , Humans , Mouth Neoplasms/microbiology , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Mouth/microbiology , Cytokines/metabolism , Smoking/adverse effects , Inflammation/microbiology , Carcinogenesis , Bacteria/metabolism , Bacteria/genetics , Bacteria/pathogenicity , Precancerous Conditions/microbiology , Precancerous Conditions/pathology , Precancerous Conditions/metabolism , Precancerous Conditions/genetics
10.
Mol Biol (Mosk) ; 58(2): 325-332, 2024.
Article in Russian | MEDLINE | ID: mdl-39355889

ABSTRACT

We have previously shown that 5-arylaminouracil derivatives can inhibit HIV-1, herpesviruses, mycobacteria, and other pathogens through various mechanisms. The purpose of this study was to evaluate the potential of 5-arylaminouracils and their derivatives against leukemia, neuroblastoma, and glial brain tumors. 5-Aminouracils with various substituents and their 5'-norcabocyclic and ribo derivatives were screened for cytotoxicity against two neuroblastoma cell lines (SH-SY5Y and IMR-32), K-562 lymphoblastic cells, HL-60 promyeoloblastic cells, and low-passage variants of well-differentiated glioblastoma multiforme (GBM5522 and GBM6138). Cytotoxicity assessment by the standard MTT test showed that most of the compounds lack significant toxicity towards the above cells. However, 5-(4-isopropylphenylamine)uracil and 5-(4-tert-butylphenylamine)uracil exhibited a dose-dependent toxic effect towards the GBM6138 cell line with half-maximal inhibitory concentrations (IC50) of 9 and 2.3 µÐœ, respectively. Antitumor activity was for the first time demonstrated for compounds of this type and can serve as a starting point for further research.


Subject(s)
Uracil , Humans , Uracil/analogs & derivatives , Uracil/pharmacology , Uracil/toxicity , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , HL-60 Cells , Glioblastoma/drug therapy , Glioblastoma/pathology , Neuroblastoma/drug therapy , Neuroblastoma/pathology
11.
Mol Biol (Mosk) ; 58(2): 295-304, 2024.
Article in Russian | MEDLINE | ID: mdl-39355886

ABSTRACT

Multiple exogenous or endogenous factors alter gene expression patterns by different mechanisms that are poorly understood. We used RNA-Seq analysis in order to study changes in gene expression in melanoma cells that are capable of vasculogenic mimicry that is inhibited upon the action of an inhibitor of vasculogenic mimicry. Here, we show that the drug induces a strong upregulation of 50 genes that control the cell cycle and microtubule cytoskeleton coupled with a strong downregulation of 50 genes that control different cellular metabolic processes. We found that both groups of genes are simultaneously regulated by multiple sets of transcription factors. We conclude that one way for coordinated regulation of large groups of genes is regulation simultaneously by multiple transcription factors.


Subject(s)
Gene Expression Regulation, Neoplastic , Melanoma , Humans , Gene Expression Regulation, Neoplastic/drug effects , Melanoma/genetics , Melanoma/metabolism , Melanoma/pathology , Melanoma/drug therapy , Cell Line, Tumor , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/pathology , Transcription Factors/genetics , Transcription Factors/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Neoplasm Proteins/biosynthesis , Cell Cycle/drug effects
12.
Rev Sci Instrum ; 95(10)2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39356194

ABSTRACT

Neutron measurement is the primary tool in the SPARC tokamak for fusion power (Pfus) monitoring, research on the physics of burning plasmas, validation of the neutronics simulation workflows, and providing feedback for machine protection. A demanding target uncertainty (10% for Pfus) and coverage of a wide dynamic range (>8 orders of magnitude going up to 5 × 1019 n/s), coupled with a fast-track timeline for design and deployment, make the development of the SPARC neutron diagnostics challenging. Four subsystems are under design that exploit the high flux of direct DT and DD plasma neutrons emanating from a shielded opening in a midplane diagnostic port. The systems comprise a set of ∼15 flux monitors, mainly ionization chambers and proportional counters for measurement of the neutron yield rate, two independent foil activation systems for measurement of the neutron fluence, a spectrometric radial neutron camera for poloidal profiling of the plasma emissivity, and a high-resolution magnetic proton recoil spectrometer for measurement of the core neutron spectrum. Together, the four systems ensure redundancy of sensors and methods and aim to provide high resolutions of time (10 ms), space (∼7 cm), and energy (<2% at 14 MeV). This paper presents the broader objectives behind the preliminary design of the SPARC neutron diagnostics and discusses the ongoing studies on neutronics, detector comparisons, prototyping, and integration with the unique infrastructure of SPARC. Engineering details of the four subsystems and the concepts for in situ neutron calibration are also highlighted.

13.
Article in English | MEDLINE | ID: mdl-39356319

ABSTRACT

The well-known antibiotic gentamicin (GEN) works well against a variety of pathogenic bacteria, nevertheless its therapeutic use might be limited by the possibility of nephrotoxicity. The naturally occurring flavonoid galangin (GAL) has several interesting anti-inflammatory and antioxidant properties. The present study evaluated the nephroprotective effect of GAL on GEN-induced renal injury. Rats received GAL for 14 days and GEN from day 8 to day 14. There was a significant increase in serum urea and creatinine along with several histopathological changes in the kidney following GEN administration. GEN-treated rats also showed increased levels of kidney MDA and NO, and decreased GSH content and activities of antioxidant enzymes. Rats received GEN also demonstrated increased NF-κB p65, iNOS, TNF-α, IL-1ß and IL-6 levels in the kidney. GAL remarkably prevented tissue injury, attenuated MDA and NO levels, improved antioxidants, and decreased levels of inflammatory mediators in the kidney of GEN-treated rats. Furthermore, GEN-administrated rats exhibited increased Bax and caspase-3 with concomitant decline in Bcl-2 levels in the kidney, an effect that GAL attenuated. In conclusion, GAL prevents GEN-induced nephrotoxicity by attenuating oxidative stress, inflammation, and apoptosis and augmenting antioxidant defense, suggesting its therapeutic potential against drug nephrotoxicity.

14.
Vet Res Commun ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39361097

ABSTRACT

Swimmer puppy syndrome (SPS) is a rare condition that affects neonatal animals. The affected puppies are unable to stand, remain in sternal recumbency with their legs splayed laterally and ambulate with typical swimmer-like movements. This study reports the clinical findings and discusses the treatments and outcomes in four puppies of various breeds with clinical signs of SPS. Previous medical records of the animals were reviewed for history, clinical features, radiographic findings and choice of treatment. Treatment follow-up was evaluated at 15, 30, 45 days and 6 months. In three puppies all limbs were affected. In one case only the forelimbs were affected, while the hind limbs remained normal. Clinical, orthopaedic and neurological examinations, routine laboratory findings and tidal breathing flow-volume loop measurements were normal. Concurrent problems occurred in two animals and included slightly deformed chest and ventrodorsal flattening of the thorax with a slight right displacement of the heart. For the management of SPS, chest and hobble bandages were used, as well as physiotherapy and environmental management. Three puppies recovered completely after 45 days of treatment. In one case the therapy was discontinued after 2 weeks. In this case, the puppy could stand, but mild abduction of the forelimbs and lameness were obvious after 6 months. Intensive physiotherapy contributed to positive outcomes even in older puppies. Also, to the authors' knowledge, this is the first report of tidal breathing flow-volume loop measurement for dogs with pectus excavatum.

15.
Ann R Coll Surg Engl ; : rcsann20240082, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39361132

ABSTRACT

INTRODUCTION: The aim of this study was to investigate comparative outcomes of laparoscopic and open repair for peptic ulcer perforation (PUP). METHODS: A PRISMA-compliant systematic review with a PROSPERO-registered protocol (registration number CRD42024529286) was conducted. All randomised controlled trials (RCTs) involving PUP patients managed by laparoscopic or open repair were identified and their risk of bias assessed. Outcome syntheses for perioperative mortality and morbidities, need for reoperation, procedure time and length of hospital stay were conducted using random-effects modelling to calculate risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). FINDINGS: Nine RCTs met the inclusion criteria, enrolling 670 patients of whom 317 were randomised to receive laparoscopic surgery and 353 were managed with open surgery. Laparoscopic repair of PUP significantly reduced mortality (RR 0.37, p = 0.03), total complications (RR 0.57, p = 0.0009), ileus (RR 0.43, p = 0.04), wound complications (RR 0.36, p < 0.0001) and length of hospital stay (MD -2.37, p = 0.0003) compared with the open approach. There were no significant differences in rate of postoperative leak (RR 2.00, 95% CI 0.74-5.41, p = 0.17), abdominal collection (RR 1.19, 95% CI 0.46-3.07, p = 0.72), sepsis (RR 1.17, 95% CI 0.39-3.52, p = 0.65), respiratory complications (RR 0.68, 95% CI 0.32-1.46, p = 0.32), reoperation (RR 1.74, 95% CI 0.57-5.30, p = 0.33) and operating time (MD 15.31, 95% CI -4.86 to 35.47, p = 0.14) between the two groups. CONCLUSIONS: Laparoscopic repair of PUP is associated with significantly lower mortality and morbidity and shorter length of stay compared with the open approach. The laparoscopic approach should be the management of choice subject to the existence of laparoscopic expertise.

16.
Front Digit Health ; 6: 1288776, 2024.
Article in English | MEDLINE | ID: mdl-39360195

ABSTRACT

Objectives: This study aims to design and test a platform of key performance indicators (KPIs) and indices emphasizing achievements and improvement and helping decision-making. Methods: An operations research study was designed to analyze data from the Hospital Management Information System (HMIS) from July 2017 to June 2018 at the Research Institute of Ophthalmology (RIO), Giza, Egypt. The HMIS data were submitted to reform covering parameters in service delivery and corresponding indicators and indices. Data were grouped into four themes: human resources and outpatient, inpatient, and surgical operations. A total of 14 performance indicators were deployed to four specific indices and total performance indices and applied to six teams of ophthalmologists at RIO. The decision matrices were deliberated to demonstrate achievements and provide recommendations for subsequent improvements. Results: Throughout 1 year, six teams of ophthalmologists (n = 222) at RIO provided the following services: outpatient (n = 116,043), inpatient (n = 8,081), and surgical operations (n = 9,174). Teams 2, 1, and 6 were the top teams in the total performance index. Team 4 had plunges in the outpatient index, and Team 5 faced limitations in the inpatient index. Conclusion: The study provided a model for upgrading the performance of the management information system (MIS) in health organizations. The KPIs and indices were used not only for documenting successful models of efficient service delivery but also as examples of limitations for further support and interventions.

17.
Vopr Virusol ; 69(4): 329-340, 2024 Sep 26.
Article in Russian | MEDLINE | ID: mdl-39361927

ABSTRACT

INTRODUCTION: For four years, SARS-CoV-2, the etiological agent of COVID-19, has been circulating among humans. By the end of the second year, an absence of immunologically naive individuals was observed, attributable to extensive immunization efforts and natural viral exposure. This study focuses on delineating the molecular and biological patterns that facilitate the persistence of SARS-CoV-2, thereby informing predictions on the epidemiological trajectory of COVID-19 toward refining pandemic countermeasures. The aim of this study was to describe the molecular biological patterns identified that contribute to the persistence of the virus in the human population. MATERIALS AND METHODS: For over three years since the beginning of the COVID-19 pandemic, molecular genetic monitoring of SARS-CoV-2 has been conducted, which included the collection of nasopharyngeal swabs from infected individuals, assessment of viral load, and subsequent whole-genome sequencing. RESULTS: We discerned dominant genetic lineages correlated with rising disease incidence. We scrutinized amino acid substitutions across SARS-CoV-2 proteins and quantified viral loads in swab samples from patients with emerging COVID-19 variants. Our findings suggest a model of viral persistence characterized by 1) periodic serotype shifts causing substantial diminutions in serum virus-neutralizing activity (> 10-fold), 2) serotype-specific accrual of point mutations in the receptor-binding domain (RBD) to modestly circumvent neutralizing antibodies and enhance receptor affinity, and 3) a gradually increasing amount of virus being shed in mucosal surfaces within a single serotype. CONCLUSION: This model aptly accounts for the dynamics of COVID-19 incidence in Moscow. For a comprehensive understanding of these dynamics, acquiring population-level data on immune tension and antibody neutralization relative to genetic lineage compositions is essential.


Subject(s)
COVID-19 , SARS-CoV-2 , Viral Load , Humans , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , COVID-19/epidemiology , COVID-19/virology , COVID-19/immunology , Genome, Viral/genetics , Amino Acid Substitution , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Pandemics , Phylogeny , Nasopharynx/virology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Female , Antibodies, Viral/blood , Antibodies, Viral/immunology , Male
19.
Eur J Cancer ; 212: 115056, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39368226

ABSTRACT

BACKGROUND: Adjuvant anti-PD-1 therapy improves relapse free survival in stage III melanoma, but also leads to immune-related adverse events (irAEs). Older patients are of particular interest due to comorbidities and frailty, which may impact their ability to tolerate irAEs and benefit from anti-PD-1 therapy. This study aimed to explore associations between clinical parameters and the occurrence of grade ≥ 3 irAEs and recurrence-free survival (RFS) in older patients with radically resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy. METHODS: Patients aged ≥ 65 with resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy between 2018 and 2022 were selected using real-world data from the nationwide Dutch Melanoma Treatment Registry (DMTR). A univariate and multivariable logistic regression was used to compare determinants of grade ≥ 3 irAEs, and univariate and multivariable Cox-proportional hazard models were fitted to identify factors influencing RFS. RESULTS: The study included 885 patients, with 280 aged 75 and older. The incidence of grade ≥ 3 irAEs was 15.5 % in the 65-74 age group and 13.9 % in the ≥ 75 age group. No significant correlation was found between age and grade ≥ 3 irAEs. However, an increasing number of comorbidities was associated with a higher risk of grade ≥ 3 irAEs (multivariable analyses: OR 1.83, 95 % C.I. 0.99-3.40). The 1-year RFS rate of 80.0 % of this study was comparable to those reported in previous registration trials and real-world data. Having ≥ 3 comorbidities was significantly associated with a decrease in RFS (HR: 1.68, 95 % C.I. 1.15-2.44). CONCLUSION: Older patients had similar benefit of adjuvant immunotherapy compared to older subgroups in previous trials. However, patients with multiple comorbidities were at increased risk of grade ≥ 3 irAEs and had a lower RFS. This should be considered when deciding upon adjuvant treatment.

20.
Theriogenology ; 230: 314-321, 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39368453

ABSTRACT

The aim of the present work was to gain insight into the metabolism of pigs derived from assisted reproductive technologies during their adulthood. Approximately 4h after feeding, a blood sample was taken from 3.5 year old sows born by artificial insemination (AI group, n = 7) and transfer of in vitro produced embryos (IVP group, n = 11) to determine the physiological concentrations of the main biomarkers of carbohydrates (glucose and lactate), proteins (albumin, creatinine and urea) and lipids (cholesterol and triglycerides). Four weeks later, an oral glucose tolerance test (OGTT; 1.75g glucose/kg body weight) was performed after an overnight fast and 1h of water withdrawal. Blood samples were obtained prior (T = 0 min; fasting conditions) and 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min after glucose intake. At each time point, glycemia was measured immediately using glucometer test strips, and serum was collected to determine the above metabolites along with insulin and glucagon. After OGTT, the area under the curve (AUC) between sampling times and homeostasis model assessment of insulin resistance (HOMA) indices were calculated. Under physiological conditions, the concentration of metabolites studied was similar between AI and IVP sows. In both groups, fasting decreased cholesterol and increased triglycerides and urea (P < 0.001). However, creatinine and lactate were similar in both groups under physiological and fasting conditions. The expected increase in albuminemia and decrease in glycaemia after fasting was only observed in IVP sows. OGTT revealed a different glucose curve pattern (monophasic in AI and biphasic in IVP group), a lower mean concentration of cholesterol, glucose, lactate, triglycerides in IVP compared to AI pigs (P < 0.01), and a higher mean concentration of albumin, creatinine and insulin in IVP compared to AI group (P < 0.05). On the contrary, no differences were found between groups for mean serum glucagon and urea levels, nor for glucose homeostasis indices HOMA-IR and HOMA-%B. The AUC differed between groups at several time points with larger AUC for creatinine, and smaller AUC for glucose, glucagon, and triglycerides, in IVP pigs than in AI pigs at 180-210 min (P < 0.05). In conclusion, under physiological conditions the metabolic profile of fully-grown AI and IVP sows is similar and within normal ranges. Glucose challenge revealed differences in metabolic and insulin responses between groups but with normal glucose tolerance in both cases.

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