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1.
Intern Emerg Med ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38864971

ABSTRACT

Point-of-care ultrasound (POCUS) is an important tool for clinical diagnosis and decision-making in critical and non-critical scenarios. Dyspnea, chest pain, and shock are conditions susceptible to evaluation with ultrasound considering diagnostic accuracy and clinical impact already proven. There is scarce evidence in diagnosis agreement using ultrasound as an extension of physical examination. We aimed to evaluate ED patients in whom POCUS was performed, to analyze agreement between clinical initial diagnosis using ultrasound images and final diagnosis. Furthermore, we analyze failed diagnosis, inconclusive POCUS exams, and discuss details. A cross-sectional analytical study was conducted on adults who visited the emergency department with any of these three chief complaints: dyspnea, chest pain, and shock. All were evaluated with ultrasound at admission. Agreement between initial diagnosis using POCUS and final definite diagnosis was calculated. Failed diagnosis and inconclusive exams were analyzed. A total of 209 patients were analyzed. Populations: mostly males, mean age 64 years old, hypertensive. Agreement on patients with dyspnea and suspicion of acute decompensated heart failure was 0.98; agreement on chest pain suspicion of non-ST acute coronary syndrome was 0.96; agreement on type of shock was 0.90. Among the population, 12 patients had an inconclusive POCUS exam, and 16 patients had a failed diagnosis. The use of POCUS in the emergency department shows almost perfect agreement when compared with the final diagnosis in individuals experiencing acutely decompensated heart failure, acute coronary syndrome, and shock. Prospective studies are needed to evaluate the impact of this tool on mortality and prognosis when there are diagnostic errors.

2.
Int J Mol Sci ; 25(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38891917

ABSTRACT

The European "Green Deal" policies are shifting toward more sustainable and environmentally conscious agricultural practices, reducing the use of chemical fertilizer and pesticides. This implies exploring alternative strategies. One promising alternative to improve plant nutrition and reinforce plant defenses is the use of beneficial microorganisms in the rhizosphere, such as "Plant-growth-promoting rhizobacteria and fungi". Despite the great abundance of iron (Fe) in the Earth's crust, its poor solubility in calcareous soil makes Fe deficiency a major agricultural issue worldwide. Among plant promoting microorganisms, the yeast Debaryomyces hansenii has been very recently incorporated, for its ability to induce morphological and physiological key responses to Fe deficiency in plants, under hydroponic culture conditions. The present work takes it a step further and explores the potential of D. hansenii to improve plant nutrition and stimulate growth in cucumber plants grown in calcareous soil, where ferric chlorosis is common. Additionally, the study examines D. hansenii's ability to induce systemic resistance (ISR) through a comparative relative expression study by qRT-PCR of ethylene (ET) biosynthesis (ACO1), or ET signaling (EIN2 and EIN3), and salicylic acid (SA) biosynthesis (PAL)-related genes. The results mark a significant milestone since D. hansenii not only enhances nutrient uptake and stimulates plant growth and flower development but could also amplify induced systemic resistance (ISR). Although there is still much work ahead, these findings make D. hansenii a promising candidate to be used for sustainable and environmentally friendly integrated crop management.


Subject(s)
Crop Production , Fertilizers , Crop Production/methods , Iron/metabolism , Cucumis sativus/microbiology , Cucumis sativus/growth & development , Cucumis sativus/metabolism , Crops, Agricultural/microbiology , Crops, Agricultural/growth & development , Crops, Agricultural/metabolism , Iron Deficiencies , Gene Expression Regulation, Plant , Debaryomyces/metabolism , Rhizosphere , Ethylenes/metabolism , Soil Microbiology , Salicylic Acid/metabolism
3.
Healthcare (Basel) ; 12(12)2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38921281

ABSTRACT

The main objective of this study was to analyze the relationship between Geriatric Syndromes (GSs) and in-hospital mortality in adults aged 65 and older admitted to the Emergency Department (ED). The study included 202 Older Adults (OAs) who met the inclusion criteria. We conducted a Comprehensive Geriatric Assessment and collected clinical and demographic data. A univariate analysis was carried out for each of the GSs analyzed. Those variables with p < 0.05 were entered into a multiple logistic regression using the backward stepwise entry method to analyze the independent predictor variables. The average number of GSs per individual was 4.65 (±2.76). Frailty syndrome was the most prevalent (70.2% of patients). Our study found an association between mortality and some GSs, such as frailty (p = 0.042), risk of falls (p = 0.010), delirium, cognitive impairment, dependence, and risk of ulcers (p < 0.001). We found that cognitive impairment (adjusted OR, 6.88; 95% CI, 1.41-33.5; p = 0.017) and dependence (adjusted OR, 7.52; 95% CI, 1.95-29.98; p = 0.003) were independent predictors associated with mortality in our population. It is necessary to develop new care strategies in the ED that respond to the needs of aging societies, including the use of new technologies and personnel with experience in gerontology.

4.
Sports Biomech ; : 1-15, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38915207

ABSTRACT

The aim of this study was to explore the reliability and feasibility of the isometric mid-thigh pull (IMTP) and dynamic strength index (DSI) in semi-professional handball players (seventeen male and eighteen female). A cross-sectional design was used to determine the test-retest reliability of several kinetic metrics registered with a force plates. The peak force, peak relative force, rate of force development (RFD 0-250 ms), and impulse 0-250 ms were selected from the IMTP test, whereas the peak propulsive force was chosen from the countermovement jump test to obtain the DSI. The intraclass correlation coefficient (ICC), coefficient of variation (CV), standard error of the measurement (SEM) and smallest detectable difference (SDD) were calculated. A paired sample t-test was also performed. No significant differences were found between the testing sessions for all variables, except for peak propulsive force for all players (p = 0.036) and DSI for female players (p = 0.037). Reliability for all kinetic metrics was good to excellent (ICC = 0.78-0.97), with low variability (CV ≤ 8.64%), being the SEM scores lower than SDD. In conclusion, the IMTP test and DSI are highly reliable and feasible tools for assessing neuromuscular performance in semi-professional handball players.

5.
Eur J Pediatr ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38916739

ABSTRACT

An early prediction of outcomes of neonatal hypoxic-ischemic encephalopathy (NE) is of key importance in reducing neonatal mortality and morbidity. The objectives were (i) to analyze the characteristics of miRNA expression and metabolic patterns of neonates with NE and (ii) to assess their predictive performance for neurodevelopmental outcomes. Plasma samples from moderate/severe NE patients (N = 92) of the HYPOTOP study were collected before, during, and after therapeutic hypothermia (TH) and compared to a control group (healthy term infants). The expression of miRNAs and concentrations of metabolites (hypoxia-related and energy, steroid, and tryptophan metabolisms) were analyzed. Neurodevelopmental outcomes were evaluated at 24 months postnatal age using Bayley Scales of Infant Development, ed. III, BSID-III. Differences in miRNA and metabolic profiles were found between NE vs. control infants, abnormal (i.e., mildly and moderately abnormal and severe) vs. normal, and severe vs. non-severe (i.e., normal and mildly and moderately abnormal) BSID-III. 4-Androstene-3,17-dione, testosterone, betaine, xanthine, and lactate were suitable for BSID-III outcome prediction (receiver operating characteristic areas under the curve (AUCs) ≥ 0.6), as well as 68 miRNAs (AUCs of 0.5-0.9). Significant partial correlations of xanthine and betaine levels and the expression of several miRNAs with BSID-III sub-scales were found. Conclusion: We have identified metabolites/miRNAs that might be useful to support the prediction of middle-term neurodevelopmental outcomes of NE. What is known and what is new: • The early prediction of outcomes of neonatal hypoxic-ischemic encephalopathy (NE) is of key importance in reducing neonatal mortality and morbidity. • Alterations of the metabolome and miRNAs had been observed in NE. • We performed miRNA sequencing and quantified selected metabolites (i.e., lactate, pyruvate, ketone bodies, Krebs cycle intermediates, tryptophan pathway, hypoxia-related metabolites, and steroids) by GC- and LC-MS. • Specific miRNAs and metabolites that allow prediction of middle-term neurodevelopmental outcomes of newborns with NE undergoing hypothermia treatment were identified.

6.
Data Brief ; 54: 110444, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38708304

ABSTRACT

This paper aims to provide a comprehensive and innovative 12-lead electrocardiogram (ECG) dataset tailored to understand the unique needs of professional football players. Other ECG datasets are available but collected from common people, normally with diseases confirmed, while it is well known that ECG characteristics change in athletes and elite players as a result of their intense long-term physical training. This initiative is part of a broader research project employing machine learning (ML) to analyse ECG data in this athlete population and explore them according to the International criteria for ECG interpretation in athletes. The dataset is generated through the establishment of a prospective observational cohort consisting of 54 male football players from La Liga, representing a UEFA Pro-level team. Named the Pro-Football 12-lead Resting Electrocardiogram Database (PF12RED), it comprises 163 10-s ECG recordings, offering a detailed examination of the at-rest heart activity of professional football athletes. Data collection spans five phases over multiple seasons, including the 2018-2019 postseason, the 2019-20 preseason, the 2020-21 preseason, and the 2021-22 preseason. Athletes undergo medical evaluations that include a 10-s resting 12-lead ECG performed with General Electric's USB-CAM 14 module (https://co.services.gehealthcare.com/gehcstorefront/p/900995-002), with data saved using General Electric's CardioSoft V6.73 12SL V21 ECG Software. (https://www.gehealthcare.es/products/cardiosoft-v7) The data collection adheres to ethical principles, with clearance granted by the Autonomous Community of Andalusia Ethics Committee (Spain) under protocol number 1573-N-19 in December 2019. Participants provide informed consent, and data sharing is permitted following anonymization. The study aligns with the Declaration of Helsinki and adheres to the recommendations of the International Committee of Medical Journal Editors (ICMJE). The generated dataset serves as a valuable resource for research in sports cardiology and cardiac health. Its potential for reuse encompasses:1.International Comparison: Enabling cross-regional comparisons of cardiac characteristics among elite football players, enriching international studies.2.ML Model Development: Facilitating the development and refinement of machine learning models for arrhythmia detection, serving as a benchmark dataset.3.Validation of Diagnostic Methods: Allowing the validation of automatic diagnostic methods, contributing to enhanced accuracy in detecting cardiac conditions.4.Research in Sports Cardiology: Supporting future investigations into specific cardiac adaptations in elite athletes and their relation to cardiovascular health.5.Reference for Athlete Protection Policies: Influencing athlete protection policies by providing data on cardiac health and suggesting guidelines for medical assessments.6.Health Professionals Training: Serving as a training resource for health professionals interested in interpreting ECGs in sports contexts.7.Tool and Application Development: Facilitating the development of tools and applications related to the visualization, simulation and analysis of ECG signals in athletes.

9.
Rev Bras Parasitol Vet ; 33(2): e001524, 2024.
Article in English | MEDLINE | ID: mdl-38695451

ABSTRACT

Rhipicephalus (Boophilus) microplus is a leading cause of significant economic losses in the livestock industry, and tick populations have developed multiple forms of resistance to acaricides; therefore, the potential of novel natural bioactive compounds that are effective for targeting ticks must be addressed. The aim of this study was to evaluate the acaricidal and anticholinesterase activities of R. aculeata seeds and to identify naturally occurring compounds that potentially inhibit anticholinesterase through in silico docking. The acaricidal activity of the extract of R. aculeata seeds against larval and adult R. microplus ticks was assessed through immersion tests. Inhibition of anticholinesterase activity was measured spectrophotometrically. Extracts of R. aculeata seeds showed activity against larvae and engorged females of R. microplus, and a reduction in the reproductive index were also observed. Rutin, chlorogenic acid, quercetin, and epicatechin exhibited noteworthy interactions with the active site residues of RmAChE. These findings could significantly contribute to the exploration of novel natural products that can potentially inhibit RmAChE and could be used in the development of new acaricides for tick control.


Subject(s)
Acaricides , Cholinesterase Inhibitors , Plant Extracts , Rhipicephalus , Seeds , Animals , Rhipicephalus/drug effects , Acaricides/pharmacology , Plant Extracts/pharmacology , Plant Extracts/chemistry , Seeds/chemistry , Cholinesterase Inhibitors/pharmacology , Computer Simulation , Female , Molecular Docking Simulation
10.
Sci Rep ; 14(1): 9984, 2024 05 01.
Article in English | MEDLINE | ID: mdl-38693352

ABSTRACT

The aim of this work is to quantitatively assess the wavefront phase of keratoconic eyes measured by the ocular aberrometer t·eyede (based on WaveFront Phase Imaging Sensor), characterized by a lateral resolution of 8.6 µm without requiring any optical element to sample the wavefront information. We evaluated the parameters: root mean square error, Peak-to-Valley, and amplitude of the predominant frequency (Fourier Transform analysis) of a section of the High-Pass filter map in keratoconic and healthy cohorts. Furthermore, we have analyzed keratoconic eyes that presented dark-light bands in this map to assess their period and orientation with the Fourier Transform. There are significant statistical differences (p value < 0.001) between healthy and keratoconic eyes in the three parameters, demonstrating a tendency to increase with the severity of the disease. Otherwise, the quantification of the bands reveals that the width is independent of eye laterality and keratoconic stage as orientation, which tends to be oblique. In conclusion, the quantitative results obtained with t·eyede could help to diagnose and monitor the progression of keratoconus.


Subject(s)
Keratoconus , Keratoconus/diagnostic imaging , Keratoconus/diagnosis , Humans , Adult , Female , Male , Corneal Topography/methods , Young Adult , Aberrometry/methods , Cornea/diagnostic imaging , Cornea/pathology , Fourier Analysis
11.
FEBS J ; 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38588274

ABSTRACT

Coenzyme F430 is a nickel-containing tetrapyrrole, serving as the prosthetic group of methyl-coenzyme M reductase in methanogenic and methanotrophic archaea. During coenzyme F430 biosynthesis, the tetrapyrrole macrocycle is reduced by the nitrogenase-like CfbC/D system consisting of the reductase component CfbC and the catalytic component CfbD. Both components are homodimeric proteins, each carrying a [4Fe-4S] cluster. Here, the ligands of the [4Fe-4S] clusters of CfbC2 and CfbD2 were identified revealing an all cysteine ligation of both clusters. Moreover, the midpoint potentials of the [4Fe-4S] clusters were determined to be -256 mV for CfbC2 and -407 mV for CfbD2. These midpoint potentials indicate that the consecutive thermodynamically unfavorable 6 individual "up-hill" electron transfers to the organic moiety of the Ni2+-sirohydrochlorin a,c-diamide substrate require an intricate interplay of ATP-binding, hydrolysis, protein complex formation and release to drive product formation, which is a common theme in nitrogenase-like systems.

12.
Medicina (Kaunas) ; 60(4)2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38674288

ABSTRACT

Background and Objectives: Dementia grief in family caregivers of people with dementia refers to grieving prior to the death of the care recipient. It is related to psychosocial risk factors that may have a negative impact on the health of these family caregivers. This study aimed to describe the relationship between depressive symptoms, caregiver strain, and social support with dementia grief in family caregivers of people with dementia. Materials and Methods: A descriptive correlational cross-sectional study was conducted. A total of 250 family caregivers of people with dementia participated. Dementia grief was the main variable, and depressive symptoms, caregiver strain, and social support were assessed. Additionally, socio-demographic data were collected. Descriptive statistics were calculated, and a bivariate correlation analysis and a multiple linear regression analysis were performed for dementia grief. Results: Higher scores for dementia grief were found in women, in family caregivers of patients at advanced stages of dementia, and in family caregivers with a low level of education. High levels of depressive symptoms and caregiver strain and low levels of social support indicated greater intensity of dementia grief. Depressive symptomatology was the variable with the greatest influence on dementia grief. Caregiver strain and social support also related to dementia grief, but to a lesser extent. Conclusions: In family caregivers, depressive symptoms, caregiver strain, and social support are related to the intensity of dementia grief, with a greater influence of depressive symptoms. Moreover, being female, having a low level of education, and caring for a care recipient at an advanced stage of dementia are factors associated with increased dementia grief. Concerning study limitations, the sample was restricted, belonging to a specific region of Spain and to a Provincial Federation of associations. It is necessary to exercise caution in generalizing results due to the sociodemographic and geographical characteristics of the sample.


Subject(s)
Caregivers , Dementia , Depression , Grief , Social Support , Humans , Female , Male , Caregivers/psychology , Dementia/psychology , Cross-Sectional Studies , Aged , Depression/psychology , Middle Aged , Aged, 80 and over , Adult , Surveys and Questionnaires , Stress, Psychological/psychology , Stress, Psychological/etiology
13.
Heliyon ; 10(7): e28058, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38601606

ABSTRACT

Skin blemishes can be caused by multiple events or diseases and, in some cases, it is difficult to distinguish where they come from. Therefore, there may be cases with a dangerous origin that go unnoticed or the opposite case (which can lead to overcrowding of health services). To avoid this, the use of artificial intelligence-based classifiers using images taken with mobile devices is proposed; this would help in the initial screening process and provide some information to the patient prior to their final diagnosis. To this end, this work proposes an optimization mechanism based on two phases in which a global search for the best classifiers (from among more than 150 combinations) is carried out, and, in the second phase, the best candidates are subjected to a phase of evaluation of the robustness of the system by applying the cross-validation technique. The results obtained reach 99.95% accuracy for the best case and 99.75% AUC. Comparing the developed classifier with previous works, an improvement in terms of classification rate is appreciated, as well as in the reduction of the classifier complexity, which allows our classifier to be integrated in a specific purpose system with few computational resources.

14.
JMIR Res Protoc ; 13: e50157, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38608263

ABSTRACT

BACKGROUND: Fatigue is the most common symptom in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, impacting patients' quality of life; however, there is currently a lack of evidence-based context-aware tools for fatigue self-management in these populations. OBJECTIVE: This study aimed to (1) address fatigue in ME/CFS and long COVID through the development of digital mobile health solutions for self-management, (2) predict perceived fatigue severity using real-time data, and (3) assess the feasibility and potential benefits of personalized digital mobile health solutions. METHODS: The MyFatigue project adopts a patient-centered approach within the participatory health informatics domain. Patient representatives will be actively involved in decision-making processes. This study combines inductive and deductive research approaches, using qualitative studies to generate new knowledge and quantitative methods to test hypotheses regarding the relationship between factors like physical activity, sleep behaviors, and perceived fatigue in ME/CFS and long COVID. Co-design methods will be used to develop a personalized digital solution for fatigue self-management based on the generated knowledge. Finally, a pilot study will evaluate the feasibility, acceptance, and potential benefits of the digital health solution. RESULTS: The MyFatigue project opened to enrollment in November 2023. Initial results are expected to be published by the end of 2024. CONCLUSIONS: This study protocol holds the potential to expand understanding, create personalized self-management approaches, engage stakeholders, and ultimately improve the well-being of individuals with ME/CFS and long COVID. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50157.

15.
J Dermatolog Treat ; 35(1): 2345728, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38684228

ABSTRACT

OBJECTIVES: Generalized pustular psoriasis (GPP) is a rare, life-threatening skin inflammatory disorder. This study aimed to describe the disease course, treatment strategies, and healthcare utilization among patients with GPP in Portugal. METHODS: This multicentric, observational, retrospective study included consecutive adult patients with GPP undergoing a dermatology evaluation in different reporting institutions by experienced dermatologists between 2002 and 2023. RESULTS: A total of 59 patients were assessed. Most of the cohort had a previous history of plaque psoriasis (71%) and 83% presented at least one comorbidity. At the initial encounter, 64% of the cohort needed hospitalization. Systemic involvement was common, including fever (37%), and elevated white blood cell count and erythrocyte sedimentation rate/C-reactive protein (49%). Nearly, 73% of patients initiated systemic drugs, and 70% had to discontinue the first treatment. During the study, 98% of patients experienced at least one flare. At the last visit, 3.4% of patients had died, and 71.2% exhibited signs of active disease despite undergoing treatment. CONCLUSIONS: Our study demonstrates that GPP is a chronic, debilitating condition associated with systemic involvement, frequent flares, and hospitalizations, despite receiving multiple systemic treatments. Improved disease awareness and new treatments are needed to improve patient care and decrease the burden of the disease.


Subject(s)
Cost of Illness , Hospitalization , Psoriasis , Humans , Psoriasis/therapy , Psoriasis/pathology , Psoriasis/drug therapy , Psoriasis/diagnosis , Retrospective Studies , Portugal/epidemiology , Male , Female , Middle Aged , Adult , Hospitalization/statistics & numerical data , Aged , Comorbidity , Dermatologic Agents/therapeutic use , Patient Acceptance of Health Care/statistics & numerical data , Severity of Illness Index
16.
Food Chem Toxicol ; 188: 114650, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38599273

ABSTRACT

Pesticides and mycotoxins, prominent chemical hazards in the food chain, are commonly found in plant-based foods, contributing to their pervasive presence in the human body, as evidenced by biomonitoring programs. Despite this, there is limited knowledge about their co-occurrence patterns. While intervention studies have demonstrated that organic diets can significantly reduce pesticide levels, their impact on mycotoxin exposure has been overlooked. To address this gap, this study pursued two objectives: first, to characterize the simultaneous presence of mycotoxins and pesticides in human urine samples by means of the control of the biomarkers of exposure, and second, to investigate the influence of consuming organic foods on these co-exposure patterns. A pilot study involving 20 healthy volunteers was conducted, with participants consuming either exclusively organic or conventional foods during a 24-h diet intervention in autumn 2021 and spring 2022 to account for seasonal variability. Participants provided detailed 24-h dietary records, and their first-morning urine samples were collected, minimally treated and analysed using LC-Q-ToF-MS by means of a multitargeted method in order to detect the presence of these residues. Results indicated that among the 52 screened compounds, four mycotoxins and seven pesticides were detected in over 25% of the samples. Deoxynivalenol (DON) and the non-specific pesticide metabolite diethylphosphate (DEP) exhibited the highest frequency rates (100%) and concentration levels. Correlations were observed between urine levels of mycotoxins (DON, ochratoxin alpha [OTα], and enniatin B [ENNB]) and organophosphate pesticide metabolites DEP and 2-diethylamino-6-methyl-4-pyrimidinol (DEAMPY). The pilot intervention study suggested a reduction in ENNB and OTα levels and an increase in ß-zearalenol levels in urine after a short-term replacement with organic food. However, caution is advised due to the study's small sample size and short duration, emphasizing the need for further research to enhance understanding of the human chemical exposome and refine chemical risk assessment.


Subject(s)
Mycotoxins , Pesticides , Humans , Mycotoxins/urine , Pesticides/urine , Male , Adult , Spain , Female , Pilot Projects , Food, Organic , Food Contamination/analysis , Diet , Biological Monitoring/methods , Young Adult , Middle Aged
18.
Genes (Basel) ; 15(4)2024 04 16.
Article in English | MEDLINE | ID: mdl-38674430

ABSTRACT

Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B , Cytochrome P-450 CYP3A , Immunosuppressive Agents , Kidney Transplantation , Polymorphism, Single Nucleotide , Tacrolimus , Humans , Cytochrome P-450 CYP3A/genetics , Kidney Transplantation/adverse effects , Tacrolimus/blood , Tacrolimus/pharmacokinetics , Tacrolimus/administration & dosage , ATP Binding Cassette Transporter, Subfamily B/genetics , Female , Male , Polymorphism, Single Nucleotide/genetics , Adult , Mexico , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/blood , Immunosuppressive Agents/administration & dosage , Middle Aged , Genotype , Graft Rejection/genetics
19.
Entropy (Basel) ; 26(3)2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38539732

ABSTRACT

Machine learning (ML) methods are increasingly being applied to analyze biological signals. For example, ML methods have been successfully applied to the human electroencephalogram (EEG) to classify neural signals as pathological or non-pathological and to predict working memory performance in healthy and psychiatric patients. ML approaches can quickly process large volumes of data to reveal patterns that may be missed by humans. This study investigated the accuracy of ML methods at classifying the brain's electrical activity to cognitive events, i.e., event-related brain potentials (ERPs). ERPs are extracted from the ongoing EEG and represent electrical potentials in response to specific events. ERPs were evoked during a visual Go/NoGo task. The Go/NoGo task requires a button press on Go trials and response withholding on NoGo trials. NoGo trials elicit neural activity associated with inhibitory control processes. We compared the accuracy of six ML algorithms at classifying the ERPs associated with each trial type. The raw electrical signals were fed to all ML algorithms to build predictive models. The same raw data were then truncated in length and fitted to multiple dynamic state space models of order nx using a continuous-time subspace-based system identification algorithm. The 4nx numerator and denominator parameters of the transfer function of the state space model were then used as substitutes for the data. Dimensionality reduction simplifies classification, reduces noise, and may ultimately improve the predictive power of ML models. Our findings revealed that all ML methods correctly classified the electrical signal associated with each trial type with a high degree of accuracy, and accuracy remained high after parameterization was applied. We discuss the models and the usefulness of the parameterization.

20.
Eur J Gastroenterol Hepatol ; 36(5): 615-621, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38477862

ABSTRACT

BACKGROUND AND AIMS: Carvedilol has emerged as the preferred ß-blocker for treating portal hypertension. However, there is still a debate in dosing regimen, with a potential lower bioavailability in once-daily regimens. The aim of this study is to assess the acute effects of carvedilol posology in patients with clinically significant portal hypertension (CSPH), as a surrogate marker of bioavailability. METHODS: In this experimental study, 34 patients with CSPH receiving carvedilol twice daily were asked to suppress the night dose of carvedilol, creating a standardized 24-hour dose interval. Spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by transient elastography (TE) were performed, with the exact interval between the last carvedilol administration and TE measurements consistently maintained at 24 hours and compared with values prior and under treatment. RESULTS: Thirty-four patients were included, predominantly male (82.9%). SSM after suspending carvedilol for 24 hours [mean, 73.9kPa (SD, 17.0)] was significantly higher ( P < 0.001) than under treatment [mean, 56.3kPa (SD, 13.2)] and was not significantly different ( P = 0.908) from SSM prior to introduction of carvedilol [mean, 74.5kPa (SD, 12.4)]. Differences were also found in stratified analysis for carvedilol dosage, D'Amico classification stages, MELDNa scores, MELD3.0 scores, Child-Pugh class A and CSPH due to alcoholic cirrhosis. LSM after suspension was not significantly different from both under treatment and prior to treatment. CONCLUSION: The differences in SSM after skipping one dose of carvedilol show both the importance of strict adherence to the prescribed dosing regimen to achieve the expected therapeutic benefits and the impact of twice daily prescription in bioavailability throughout the day.


Subject(s)
Elasticity Imaging Techniques , Hypertension, Portal , Humans , Male , Female , Carvedilol , Hypertension, Portal/diagnostic imaging , Hypertension, Portal/drug therapy , Hypertension, Portal/etiology , Adrenergic beta-Antagonists/therapeutic use , Spleen/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/drug therapy , Liver Cirrhosis/pathology , Liver/pathology
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