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Artificial Intelligence in Medicine Jan 2020Antibiotic resistance is one of the major challenges we face in modern times. Antibiotic use, especially their overuse, is the single most important driver of antibiotic...
Antibiotic resistance is one of the major challenges we face in modern times. Antibiotic use, especially their overuse, is the single most important driver of antibiotic resistance. Efforts have been made to reduce unnecessary drug prescriptions, but limited work is devoted to optimising dosage regimes when they are prescribed. The design of antibiotic treatments can be formulated as an optimisation problem where candidate solutions are encoded as vectors of dosages per day. The formulation naturally gives rise to competing objectives, as we want to maximise the treatment effectiveness while minimising the total drug use, the treatment duration and the concentration of antibiotic experienced by the patient. This article combines a recent mathematical model of bacterial growth including both susceptible and resistant bacteria, with a multi-objective evolutionary algorithm in order to automatically design successful antibiotic treatments. We consider alternative formulations combining relevant objectives and constraints. Our approach obtains shorter treatments, with improved success rates and smaller amounts of drug than the standard practice of administering daily fixed doses. These new treatments consistently involve a higher initial dose followed by lower tapered doses.
Topics: Algorithms; Anti-Bacterial Agents; Antimicrobial Stewardship; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Humans; Models, Theoretical; Stochastic Processes; Treatment Outcome
PubMed: 31980097
DOI: 10.1016/j.artmed.2019.101759 -
Animals : An Open Access Journal From... Nov 2021Antibiotics are major disruptors of the gastrointestinal microbiota, depleting bacterial species beneficial for the host health and favoring the emergence of potential... (Review)
Review
Antibiotics are major disruptors of the gastrointestinal microbiota, depleting bacterial species beneficial for the host health and favoring the emergence of potential pathogens. Furthermore, the intestine is a reactor of antibiotic resistance emergence, and the presence of antibiotics exacerbates the selection of resistant bacteria that can disseminate in the environment and propagate to further hosts. We reviewed studies analyzing the effect of antibiotics on the intestinal microbiota and antibiotic resistance conducted on animals, focusing on the main food-producing and companion animals. Irrespective of antibiotic classes and animal hosts, therapeutic dosage decreased species diversity and richness favoring the bloom of potential enteropathogens and the selection of antibiotic resistance. These negative effects of antibiotic therapies seem ineluctable but often were mitigated when an antibiotic was administered by parenteral route. Sub-therapeutic dosages caused the augmentation of taxa involved in sugar metabolism, suggesting a link with weight gain. This result should not be interpreted positively, considering that parallel information on antibiotic resistance selection was rarely reported and selection of antibiotic resistance is known to occur also at low antibiotic concentration. However, studies on the effect of antibiotics as growth promoters put the basis for understanding the gut microbiota composition and function in this situation. This knowledge could inspire alternative strategies to antibiotics, such as probiotics, for improving animal performance. This review encompasses the analysis of the main animal hosts and all antibiotic classes, and highlights the future challenges and gaps of knowledge that should be filled. Further studies are necessary for elucidating pharmacodynamics in animals in order to improve therapy duration, antibiotic dosages, and administration routes for mitigating negative effects of antibiotic therapies. Furthermore, this review highlights that studies on aminoglycosides are almost inexistent, and they should be increased, considering that aminoglycosides are the first most commonly used antibiotic family in companion animals. Harmonization of experimental procedures is necessary in this research field. In fact, current studies are based on different experimental set-up varying for antibiotic dosage, regimen, administration, and downstream microbiota analysis. In the future, shotgun metagenomics coupled with long-reads sequencing should become a standard experimental approach enabling to gather comprehensive knowledge on GIM in terms of composition and taxonomic functions, and of s. Decorticating GIM in animals will unveil revolutionary strategies for medication and improvement of animals' health status, with positive consequences on global health.
PubMed: 34828011
DOI: 10.3390/ani11113280 -
Psychiatry Research. Neuroimaging Dec 2019The rs6994992 polymorphism has been reported as a candidate variant associated with schizophrenia (SZ). Neuroimaging studies have revealed that SZ is associated with...
The rs6994992 polymorphism has been reported as a candidate variant associated with schizophrenia (SZ). Neuroimaging studies have revealed that SZ is associated with widespread structural and functional alterations in brain. However, whether the allele dosage of rs6994992 is associated with brain structural or functional features is unclear. We aimed to investigate the association between the risk allele dosage of rs6994992 and whole-brain structural and functional characteristics and to further explore the relationship between these characteristics and cognition. Magnetic resonance images and the rs6994992 genotype were obtained from 53 healthy participants. A general linear model was used to determine the effects of risk allele dosage of rs6994992 on brain characteristics. Spearman correlation analysis was employed to calculate the correlation between altered brain characteristics and cognitive scores. Our results demonstrated that regions with significant differences in structural characteristics between groups with different dosages of rs6994992 were mainly located in the frontal and temporal lobes, hippocampus and angular gyrus. Moreover, significant regions of functional connectivity (FC) partly overlapped with the structural results. Measurements in those significant regions and FCs were correlated with the cognition scales. This association can inform our understanding of the mechanisms through which rs6994992 variants increase the risk for SZ.
Topics: Adult; Alleles; Brain; Cognition; Female; Genotype; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Polymorphism, Genetic; Schizophrenia; Temporal Lobe; Young Adult
PubMed: 31202487
DOI: 10.1016/j.pscychresns.2019.05.005 -
Frontiers in Surgery 2022This study aimed to explore the clinical effects of different dosages of dexmedetomidine (Dex) combined with a target-controlled infusion of propofol in hysteroscopic...
OBJECTIVE
This study aimed to explore the clinical effects of different dosages of dexmedetomidine (Dex) combined with a target-controlled infusion of propofol in hysteroscopic submucosal myomectomy.
METHODS
Ninety patients who underwent hysteroscopic submucosal myomectomy between September 2021 and March 2022 were enrolled and randomly divided into three groups, with 30 patients in each group. Patients in Groups A, B, and C received injections of 0.25, 0.5, or 0.75 µg/kg of Dex, respectively, by intravenous pump over 10 min. After this time, a maintenance dosage of 0.5 µg/kg/h was administered by intravenous infusion until the end of the surgery. Anesthesia was induced using 1.5 mg/kg of propofol and 0.3 µg/kg of sufentanil that were introduced through a laryngeal mask. The plasma concentration of propofol was maintained at 3 µg/ml by target-controlled infusion until the end of the surgery. The mean arterial pressure (MAP), heart rate (HR), and electroencephalographic bispectral index (BIS) were observed when the patient entered the operating room (T0), after catheter indwelling for anesthesia (T1), at the time of cervical dilation (T2), at the time of hysteroscopic surgery (T3), and at the end of the surgery (T4) in all three groups. The total dosage of propofol for induction and maintenance, anesthesia awakening time, orientation recovery time, Visual Analog Scale (VAS) score of the post-awakening uterine contraction pain, and adverse reactions were recorded.
RESULTS
The intraoperative reductions of MAP and HR in patients were significant in Group C when compared with those in Groups A and B (< 0.05), and BIS was significantly lower in Group C at T2 and T3 when compared with the baseline measurement at T0 (< 0.05). The dosage of propofol was significantly higher for Group A than for Groups B and C (< 0.05). The anesthesia awakening time and orientation recovery time were significantly longer for patients in Group C when compared with patients in Groups A and B (< 0.05). Within 5-30 min after awakening, the VAS scores in Groups B and C were significantly lower than those for Group A (< 0.05). The incidence of adverse reactions in Group B was significantly less than that for Groups A and C (< 0.05).
CONCLUSION
The continuous pumping of 0.5 µg/kg of Dex combined with a target-controlled infusion of propofol in hysteroscopic submucosal myomectomy resulted in positive anesthetic and analgesia effects and fewer adverse reactions. It therefore has high clinical significance.
PubMed: 36684220
DOI: 10.3389/fsurg.2022.1025592 -
International Journal of Molecular... Oct 2021Sublethal dosages of imidacloprid cause long-term destructive effects on honey bees at the individual and colony levels. In this review, the molecular effects of... (Review)
Review
Sublethal dosages of imidacloprid cause long-term destructive effects on honey bees at the individual and colony levels. In this review, the molecular effects of sublethal imidacloprid were integrated and reported. Several general effects have been observed among different reports using different approaches. Quantitative PCR approaches revealed that imidacloprid treatments during the adult stage are expressed as changes in immuneresponse, detoxification, and oxidation-reduction response in both workers and queens. In addition, transcriptomic approaches suggested that phototransduction, behavior, and somatic muscle development also were affected. Although worker larvae show a higher tolerance to imidacloprid than adults, molecular evidence reveals its potential impacts. Sublethal imidacloprid treatment during the larval stage causes gene expression changes in larvae, pupae, and adults. Transcriptome profiles suggest that the population and functions of affected differentially expressed genes, DEGs, vary among different worker ages. Furthermore, an early transcriptomic switch from nurse bees to foragers was observed, suggesting that precocious foraging activity may occur. This report comprehensively describes the molecular effects of sublethal dosages of imidacloprid on the honey bee . The corresponding molecular pathways for physiological and neurological responses in imidacloprid-exposed honey bees were validated. Transcriptomic evidence suggests a global and sustained sublethal impact of imidacloprid on honey bee development.
Topics: Animals; Bees; Larva; Neonicotinoids; Nitro Compounds; Transcriptome
PubMed: 34769266
DOI: 10.3390/ijms222111835 -
Briefings in Bioinformatics Nov 2023Large-scale imputation reference panels are currently available and have contributed to efficient genome-wide association studies through genotype imputation. However,...
Large-scale imputation reference panels are currently available and have contributed to efficient genome-wide association studies through genotype imputation. However, whether large-size multi-ancestry or small-size population-specific reference panels are the optimal choices for under-represented populations continues to be debated. We imputed genotypes of East Asian (180k Japanese) subjects using the Trans-Omics for Precision Medicine reference panel and found that the standard imputation quality metric (Rsq) overestimated dosage r2 (squared correlation between imputed dosage and true genotype) particularly in marginal-quality bins. Variance component analysis of Rsq revealed that the increased imputed-genotype certainty (dosages closer to 0, 1 or 2) caused upward bias, indicating some systemic bias in the imputation. Through systematic simulations using different template switching rates (θ value) in the hidden Markov model, we revealed that the lower θ value increased the imputed-genotype certainty and Rsq; however, dosage r2 was insensitive to the θ value, thereby causing a deviation. In simulated reference panels with different sizes and ancestral diversities, the θ value estimates from Minimac decreased with the size of a single ancestry and increased with the ancestral diversity. Thus, Rsq could be deviated from dosage r2 for a subpopulation in the multi-ancestry panel, and the deviation represents different imputed-dosage distributions. Finally, despite the impact of the θ value, distant ancestries in the reference panel contributed only a few additional variants passing a predefined Rsq threshold. We conclude that the θ value substantially impacts the imputed dosage and the imputation quality metric value.
Topics: Humans; Genome-Wide Association Study; Gene Frequency; Polymorphism, Single Nucleotide; Genotype
PubMed: 38221906
DOI: 10.1093/bib/bbad509 -
The American Journal of Clinical... Jan 2022There remains a lack of evidence demonstrating a potential relationship between vitamin D and cardiometabolic risk among children. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
There remains a lack of evidence demonstrating a potential relationship between vitamin D and cardiometabolic risk among children.
OBJECTIVES
We examined the effect of 3 different dosages of vitamin D on cardiometabolic risk factors among children at risk of deficiency.
METHODS
Racially diverse schoolchildren aged 8-15 y were randomly assigned in a double-blind fashion to supplementation with 600, 1000, or 2000 IU vitamin D3/d for 6 mo. Changes in HDL cholesterol, triglycerides, LDL cholesterol, total cholesterol, and blood glucose over 6 mo and at 12 mo (6 mo post-supplementation) were assessed. Subgroup analyses were also performed by weight status and race.
RESULTS
Among 604 children, 40.9% were vitamin D-inadequate at baseline (<20 ng/mL; mean ± SD: 22.0 ± 6.8 ng/mL), 46.4% were overweight/obese, and 60.9% had ≥1 suboptimal blood lipids or glucose. Over 6 mo, serum 25-hydroxyvitamin D increased in all 3 dosage groups from baseline (mean ± SE change: 4.4 ± 0.6 ng/mL, 5.7 ± 0.7 ng/mL, and 10.7 ± 0.6 ng/mL for 600, 1000, and 2000 IU/d, respectively; P < 0.001). Whereas HDL cholesterol and triglycerides increased in the 600 IU group (P = 0.002 and P = 0.02, respectively), LDL cholesterol and total cholesterol decreased across dosage groups. At 6 mo post-supplementation, HDL cholesterol remained elevated in the 600 and 1000 IU groups ( P < 0.001 and P = 0.02, respectively) whereas triglycerides remained elevated in the 1000 and 2000 IU groups (P = 0.04 and P = 0.006, respectively). The suppression of LDL cholesterol and total cholesterol persisted in the 2000 IU group only (P = 0.04 and P < 0.001, respectively). There were no significant changes in blood glucose and similar responses were observed overall by weight status and racial groups across dosages.
CONCLUSIONS
Vitamin D supplementation demonstrated generally positive effects on HDL cholesterol, LDL cholesterol, and total cholesterol, especially at the lower dosage of 600 IU/d, with several significant changes persisting during the post-supplementation period. Increases in triglycerides across dosage groups may be due to natural changes during adolescence warranting further study.This trial was registered at clinicaltrials.gov as NCT01537809.
Topics: Adolescent; Blood Glucose; Cardiometabolic Risk Factors; Child; Child Nutritional Physiological Phenomena; Cholecalciferol; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Pediatric Obesity; Triglycerides; Vitamin D; Vitamin D Deficiency
PubMed: 34550329
DOI: 10.1093/ajcn/nqab319 -
Frontiers in Nutrition 2023There is growing concern regarding elevated levels of circulating unmetabolized folic acid (UMFA) due to excessive intake of folic acid (FA). However, no randomized...
Association of folic acid dosage with circulating unmetabolized folic acid in Chinese adults with H-type hypertension: a multicenter, double-blind, randomized controlled trial.
BACKGROUND
There is growing concern regarding elevated levels of circulating unmetabolized folic acid (UMFA) due to excessive intake of folic acid (FA). However, no randomized clinical trial has been conducted to examine the FA-UMFA dose-response relationship.
OBJECTIVE
This study aimed to investigate the FA-UMFA dose-response relationship in Chinese adults with hypertension and elevated homocysteine (H-type hypertension), a population with clear clinical indication for FA treatment.
METHODS
The data for this study were derived from a randomized, double-blind, multicenter clinical trial of 8 FA dosages on efficacy of homocysteine (Hcy) lowering. The parent trial had three 3 stages: screening period (2-10 days), run-in period (0-2 weeks, baseline visit), and double-blind treatment period (8 weeks) with follow-up visits at the end of the 2nd, 4th, 6th, and 8th weeks of treatment. Participants were randomly assigned to 8 treatment groups corresponding to FA dosages of 0, 0.4, 0.6, 0.8, 1.2, 1.6, 2.0 mg to 2.4 mg.
RESULTS
This study included 1,567 Chinese adults aged ≥45 years with H-type hypertension. There was a positive but non-linear association between FA supplementation and UMFA levels in the dosage range of 0 mg to 2.4 mg. In the regression analysis, the coefficients for the linear and quadratic terms of FA dosage were both statistically significant ( < 0.001). Notably, the slope for UMFA was greater for FA dosages >0.8 mg (ß = 11.21, 95% CI: 8.97, 13.45) compared to FA dosages ≤0.8 mg (ß = 2.94, 95% CI: 2.59, 3.29). Furthermore, FA dosages higher than 0.8 mg did not confer additional benefits in terms of increasing 5-methyl tetrahydrofolic acid (5-MTHF, active form of folate) or reducing homocysteine (Hcy).
CONCLUSION
In Chinese adults with H-type hypertension, this study showed a positive, non-linear, dosage-response relationship between FA supplementation ranging from 0 to 2.4 mg and circulating UMFA levels. It revealed that 0.8 mg FA is an optimal dosage in terms of balancing efficacy (increasing 5-MTHF and lowering Hcy) while minimizing undesirable elevation of UMFA.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT03472508?term=NCT03472508&draw=2&rank=1, identifier NCT03472508.
PubMed: 37781132
DOI: 10.3389/fnut.2023.1191610 -
Ecotoxicology and Environmental Safety Dec 2023Allelopathy has been demonstrated to be an environmentally friendly way to control harmful algal blooms. Allelochemicals of submerged plants have attracted extensive...
Allelopathy has been demonstrated to be an environmentally friendly way to control harmful algal blooms. Allelochemicals of submerged plants have attracted extensive research due to their bioavailability. The dose-response of submerged plant extracts on algae growth is worth further study to improve the efficiency of bioremediation. In this study, the ultrasonic-enzymatic assistance method was utilized to extract allelochemicals from Ceratophyllum, Myriophyllum spicatum, and Vallisneria. The effects of low-dosage and high-dosage extracts on the growth of Microcystis aeruginosa were compared based on cell biomass and morphology, photosynthetic parameters, reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels. The results showed that the three submerged plant extracts exhibited hormetic effects at low dosages and inhibitory effects at high dosages on algal growth. Within 48 h of cultivation, the enzymatic activities of Microcystis aeruginosa fluctuated, suggesting that the extracts of the three submerged plants induced different oxidative reactions. After 120 h of cultivation with high-dosage extracts, the physiological and biochemical reactions of Microcystis aeruginosa significantly decreased, indicating the effectiveness of the allelopathy of Ceratophyllum, Myriophyllum spicatum, and Vallisneria extracts in controlling algal blooms. The phenomenon of hormesis and inhibition effect confirmed a significant dose-response relationship between the allelochemicals of submerged plant extracts and Microcystis aeruginosa, which could be attributed to the composition and content of allelochemicals. These findings highlight the importance of the relative concentration of the biological algaecide and will benefit other researchers in determining the safe dosage of plant allelochemicals when used in water.
Topics: Microcystis; Hormesis; Plants; Plant Extracts; Harmful Algal Bloom; Pheromones
PubMed: 37979364
DOI: 10.1016/j.ecoenv.2023.115703 -
Cureus Oct 2022Vitamin A deficiency is an epidemiologically significant concern in all age groups, especially in preterm and term infants. Its deficiency causes various developmental... (Review)
Review
Vitamin A deficiency is an epidemiologically significant concern in all age groups, especially in preterm and term infants. Its deficiency causes various developmental malformations. Vitamin A supplementation has been a practiced alternative for many decades, but its effectiveness is debatable in the medical system. The bioavailability of beta-carotenes varies greatly and ranges from 2% to 30%, depending on how it is present in the plant's cellular composition. Vitamin A has a bioavailability of up to 75%. The bioavailability of beta-carotenes is positively impacted by several activities but mainly by mechanical ones that allow cellular interaction. These include enough chewing, mincing, and pureeing. The bioavailability of beta-carotene can be increased by moderate cooking and combining high-quality lipids. The WHO recommends waiting for a minimum of one month between vitamin A dosages. Six months is the maximum amount of time between dosages. For instance, giving the optimum dosage to a child who has not had vitamin A in two months is preferable to skipping the dose and making the child wait eight months (i.e., two months plus six months) before receiving the following amount. There were no discernible variations in the occurrence of momentarily increased aspartate aminotransferase (AST), alanine transaminase (ALT), or alkaline phosphatase between the leading group and the trace group. However, patients in the top group experienced high blood triacylglycerol levels more frequently than those in the trace group, suggesting that hypertriacylglycerolemia may be a side effect of vitamin A administration. It is imperative to memo that neonatal vitamin A supplementation negatively affects subsequent diphtheria-pertussis-tetanus (DPT) vaccination in females. Since many children are delayed in obtaining their initial DPT series, several nations prescribe DPT boosters, so older children may be affected if vitamin A supplementation negatively interacts with DPT in such children.
PubMed: 36381685
DOI: 10.7759/cureus.30242