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A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry.Hepatology Communications Jun 2024Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We...
BACKGROUND
Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis.
METHODS
Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037). It was validated in 2 additional independent cohorts from the UK Biobank with diagnosed ALC (N=467) and high-risk drinking controls (N=8981) and participants in the Indiana Biobank Liver cohort with alcohol-associated liver disease (N=121) and controls without liver disease (N=3239).
RESULTS
A 20-single-nucleotide polymorphisms PRS for ALC (PRSALC) was generated that stratified risk for ALC comparing the top and bottom deciles of PRS in the 2 validation cohorts (ORs: 2.83 [95% CI: 1.82 -4.39] in UK Biobank; 4.40 [1.56 -12.44] in Indiana Biobank Liver cohort). Furthermore, PRSALC improved the prediction of ALC risk when added to the models of clinically known predictors of ALC risk. It also stratified the risk for metabolic dysfunction -associated steatotic liver disease -cirrhosis (3.94 [2.23 -6.95]) in the Indiana Biobank Liver cohort -based exploratory analysis.
CONCLUSIONS
PRSALC incorporates 20 single-nucleotide polymorphisms, predicts increased risk for ALC, and improves risk stratification for ALC compared with the models that only include clinical risk factors. This new score has the potential for early detection of heavy drinking patients who are at high risk for ALC.
Topics: Humans; Polymorphism, Single Nucleotide; Liver Cirrhosis, Alcoholic; Male; Female; Middle Aged; Genome-Wide Association Study; White People; Multifactorial Inheritance; Aged; Risk Assessment; Alcohol Drinking; Adult; Risk Factors; Genetic Predisposition to Disease; United Kingdom; Genetic Risk Score
PubMed: 38727677
DOI: 10.1097/HC9.0000000000000431 -
Bulletin of Emergency and Trauma 2024This study investigated the demographic characteristics and factors influencing burn injuries, primarily in low socioeconomic societies where such incidents are...
OBJECTIVE
This study investigated the demographic characteristics and factors influencing burn injuries, primarily in low socioeconomic societies where such incidents are prevalent due to factors such as illiteracy and poverty.
METHODS
This cross-sectional study included all burn patients admitted to Shahid Motahari Hospital in Tehran, Iran. Demographic data such as age, sex, occupation, education level, and residence as well as detailed information about the burn incidents such as date, time, location, number of people present at the scene, and referral place was collected. Additionally, comprehensive burn details such as cause, extent, severity, previous history, and need for hospitalization directly at the emergency department were documented.
RESULTS
The study included 2213 patients (mean age 34.98±19.41 years; range 1-96), with a men predominance (60.6%). The majority of burns (64.4%) occurred at home, primarily due to accidents (99.6%), with boiling water being the most common cause (39.2%). The most frequent burns were second-degree burns (91.8%), with an average injured body area of 6.31±6.67%. There were significant correlations between burn severity and demographic factors such as age, sex, occupation, cause of burn, hospital admission, outcome, and length of stay. Remarkably, the extent of burns was negatively correlated with the distance to the hospital, while positively correlated with the length of hospital stay.
CONCLUSION
Burn injuries were significantly influenced by demographic factors. Enhancing treatment facilities and reducing the time and distance to medical care could be crucial in high-risk cases.
PubMed: 38689794
DOI: 10.30476/BEAT.2024.99775.1456 -
Bulletin of Emergency and Trauma 2024This study aimed to assess and compare the effects of intranasal administration of lidocaine and remifentanil on the condition of LMA insertion and cardiovascular...
OBJECTIVE
This study aimed to assess and compare the effects of intranasal administration of lidocaine and remifentanil on the condition of LMA insertion and cardiovascular response.
METHODS
From March 2019 to March 2020, this double-blind randomized clinical trial study was conducted on 60 patients, who underwent general anesthesia with LMA insertion at Faiz Hospital, Isfahan, Iran. After induction of anesthesia and before placing the laryngeal mask, the first group received remifentanil 1 μg/Kg, the second group received lidocaine 2% 1 mg/Kg, and the third group received normal saline with the same volume intranasally. The conditions of LMA insertion and hemodynamic changes that occurred during its insertion were investigated.
RESULTS
In terms of demographics characteristics (>0.05), success in placing the LMA on the first try (=0.73), number of attempts to insert LMA (=0.61), performance of LMA (=0.73), need for additional propofol (=0.53), frequency of gagging (=0.53), cough (=0.15) p), and laryngospasm (=0.99) did not differ significantly. In the remifentanil group, the cardiovascular response to LMA injection was less than that of the lidocaine group. Moreover, both groups were lower than the saline group, but no significant difference was observed.
CONCLUSION
In facilitating LMA insertion, the effect of intranasal remifentanil was comparable to intranasal lidocaine. Intranasal remifentanil was somewhat more effective than intranasal lidocaine in weakening the cardiovascular response to LMA insertion, but it did not outperform lidocaine.
PubMed: 38689789
DOI: 10.30476/BEAT.2024.100861.1480 -
Journal of Veterinary Internal Medicine 2024Sinus node dysfunction because of abnormal impulse generation or sinoatrial conduction block causes bradycardia that can be difficult to differentiate from high...
BACKGROUND
Sinus node dysfunction because of abnormal impulse generation or sinoatrial conduction block causes bradycardia that can be difficult to differentiate from high parasympathetic/low sympathetic modulation (HP/LSM).
HYPOTHESIS
Beat-to-beat relationships of sinus node dysfunction are quantifiably distinguishable by Poincaré plots, machine learning, and 3-dimensional density grid analysis. Moreover, computer modeling establishes sinoatrial conduction block as a mechanism.
ANIMALS
Three groups of dogs were studied with a diagnosis of: (1) balanced autonomic modulation (n = 26), (2) HP/LSM (n = 26), and (3) sinus node dysfunction (n = 21).
METHODS
Heart rate parameters and Poincaré plot data were determined [median (25%-75%)]. Recordings were randomly assigned to training or testing. Supervised machine learning of the training data was evaluated with the testing data. The computer model included impulse rate, exit block probability, and HP/LSM.
RESULTS
Confusion matrices illustrated the effectiveness in diagnosing by both machine learning and Poincaré density grid. Sinus pauses >2 s differentiated (P < .0001) HP/LSM (2340; 583-3947 s) from sinus node dysfunction (8503; 7078-10 050 s), but average heart rate did not. The shortest linear intervals were longer with sinus node dysfunction (315; 278-323 ms) vs HP/LSM (260; 251-292 ms; P = .008), but the longest linear intervals were shorter with sinus node dysfunction (620; 565-698 ms) vs HP/LSM (843; 799-888 ms; P < .0001).
CONCLUSIONS
Number and duration of pauses, not heart rate, differentiated sinus node dysfunction from HP/LSM. Machine learning and Poincaré density grid can accurately identify sinus node dysfunction. Computer modeling supports sinoatrial conduction block as a mechanism of sinus node dysfunction.
Topics: Animals; Dogs; Dog Diseases; Machine Learning; Heart Rate; Sinoatrial Block; Male; Female; Sinoatrial Node; Sick Sinus Syndrome; Electrocardiography
PubMed: 38682817
DOI: 10.1111/jvim.17071 -
Sports Medicine - Open Apr 2024Ultra-endurance events are gaining popularity in multiple exercise disciplines, including cycling. With increasing numbers of ultra-cycling events, aspects influencing... (Review)
Review
BACKGROUND
Ultra-endurance events are gaining popularity in multiple exercise disciplines, including cycling. With increasing numbers of ultra-cycling events, aspects influencing participation and performance are of interest to the cycling community.
MAIN BODY
The aim of this narrative review was, therefore, to assess the types of races offered, the characteristics of the cyclists, the fluid and energy balance during the race, the body mass changes after the race, and the parameters that may enhance performance based on existing literature. A literature search was conducted in PubMed, Scopus, and Google Scholar using the search terms 'ultracycling', 'ultra cycling', 'ultra-cycling', 'ultra-endurance biking', 'ultra-bikers' and 'prolonged cycling'. The search yielded 948 results, of which 111 were relevant for this review. The studies were classified according to their research focus and the results were summarized. The results demonstrated changes in physiological parameters, immunological and oxidative processes, as well as in fluid and energy balance. While the individual race with the most published studies was the Race Across America, most races were conducted in Europe, and a trend for an increase in European participants in international races was observed. Performance seems to be affected by characteristics such as age and sex but not by anthropometric parameters such as skin fold thickness. The optimum age for the top performance was around 40 years. Most participants in ultra-cycling events were male, but the number of female athletes has been increasing over the past years. Female athletes are understudied due to their later entry and less prominent participation in ultra-cycling races. A post-race energy deficit after ultra-cycling events was observed.
CONCLUSION
Future studies need to investigate the causes for the observed optimum race age around 40 years of age as well as the optimum nutritional supply to close the observed energy gap under consideration of the individual race lengths and conditions. Another research gap to be filled by future studies is the development of strategies to tackle inflammatory processes during the race that may persist in the post-race period.
PubMed: 38679655
DOI: 10.1186/s40798-024-00715-7 -
Nutrients Apr 2024Circadian and homeostatic declines in cognitive performance are observed during the day, most commonly at 14:00. Additionally, postprandial reductions in cognitive... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Circadian and homeostatic declines in cognitive performance are observed during the day, most commonly at 14:00. Additionally, postprandial reductions in cognitive ability have been widely demonstrated 1 h after lunch consumption, affecting domains of executive functioning (EF), episodic memory (EM), and attention. Existing evidence shows that anthocyanin-rich foods such as berries may improve or attenuate the decline in EF and EM in ageing adults. Further research is required to assess whether extracts such as wild blueberry extract (WBE) may be beneficial for cognitive function across an acute timeframe, including known periods of reduced functioning.
OBJECTIVES
(1) Study 1: ROAB: To investigate the efficacy of WBE in maintaining EF and EM throughout the day alongside measures of cardiovascular outcomes in healthy older adults. A range of WBE doses were utilised to identify the optimal dose at which cognitive and cardiovascular effects occur. (2) Study 2: BEAT: To replicate alleviation of cognitive decline during a predicted post-lunch dip whilst also improving cardiovascular outcomes following acute WBE 222 mg supplementation.
METHODS
Both studies employed a randomised, double-blind, cross-over, placebo-controlled design to explore the effects of WBE intervention versus placebo on several outcomes, including EM, EF, blood pressure, and heart rate in a healthy older adult population (aged 68-75). In ROAB, 28 participants received a single dose of WBE 111 mg, 222 mg, 444 mg, or 888 mg or placebo over a 5-week period, each separated by a 1-week washout. Outcomes were measured at 0 h, 2 h, 4 h, and 6 h post intervention, with intervention occurring immediately after baseline (0 h). In BEAT, 45 participants received WBE 222 mg and placebo (1-week washout). Outcomes were measured at 0 h and 6 h (14:00) when a post-lunch dip was anticipated. This was further enhanced by consumption of lunch 1 h prior to cognitive testing. The WBE 222 mg intervention aligned with known peaks in plasma blueberry polyphenol metabolites at 2 h post dosing, which would coincide with a predicted drop in post-lunch performance.
RESULTS
ROAB: A significant dip in executive function was apparent at the 4 h timepoint for placebo only, indicating attenuation for WBE doses. Strikingly, WBE 222 mg produced acute reductions in both systolic and diastolic blood pressure compared with placebo. BEAT: EF reaction time was found to be significantly faster for WBE 222 compared to placebo at the predicted post-lunch dip (14:00), with no other notable benefits on a range of cognitive and cardiovascular outcomes.
CONCLUSION
These two studies indicate that WBE may have cardiovascular benefits and attenuate the natural cognitive decline observed over the course of the day, particularly when a decline is associated with a circadian rhythm-driven postprandial dip. However, it is important to acknowledge that effects were subtle, and benefits were only observed on a small number of outcomes. Further research is required to explore the utility of WBE in populations already experiencing mild cognitive impairments.
Topics: Humans; Blueberry Plants; Aged; Female; Male; Cognition; Plant Extracts; Double-Blind Method; Heart Rate; Blood Pressure; Cross-Over Studies; Executive Function; Memory, Episodic; Anthocyanins; Postprandial Period; Dietary Supplements; Fruit
PubMed: 38674870
DOI: 10.3390/nu16081180 -
Frontiers in Physiology 2024A jump in the atrioventricular (AV) conduction curve is the current clinical criterion of dual-pathway electrophysiology. However, the assumption that a jump indicates...
A jump in the atrioventricular (AV) conduction curve is the current clinical criterion of dual-pathway electrophysiology. However, the assumption that a jump indicates a switch from fast pathway (FP) to slow pathway (SP) conduction remains unconfirmed. This study was carried out to investigate whether a jump indeed indicates a transition from FP to SP conduction, and if not, what the potential cause is. Eighty-one experimental records from rabbit AV nodal preparations containing the following data were analyzed: 1) had at least one AV conduction curve and 2) had recording of His electrogram alternans (a validated new index of dual-pathway conduction). Most cases also had intracellular action potential recordings from the AV nodal fibers. Of the 81 preparations, 11 (13%) showed a jump in the AV conduction curve. The jumps always occurred after the FP to SP transition. The FP-SP transition occurred at prematurity at 196 ± 39 ms the jump at 114 ± 13 ms ( < 0.001). The beat with a jump showed an SP-FP pattern in seven and an SP-SP pattern in four preparations. The jumps were always associated with and most likely caused by the formation of intranodal/nodal-atrial reentry and its subsequent conduction, rather than a switch from FP to SP conduction. Contrary to what has been assumed, a transition from FP to SP conduction does not produce a jump in the AV conduction curve. A jump in the AV conduction curve is most likely caused by the formation of intranodal/nodal-atrial reentry and its subsequent conduction.
PubMed: 38617058
DOI: 10.3389/fphys.2024.1367509 -
Phenomics (Cham, Switzerland) Feb 2024Primary ciliary dyskinesia (PCD) is a rare disorder characterized by extensive genetic heterogeneity. However, in the genetic pathogenesis of PCD, copy number...
UNLABELLED
Primary ciliary dyskinesia (PCD) is a rare disorder characterized by extensive genetic heterogeneity. However, in the genetic pathogenesis of PCD, copy number variation (CNV) has not received sufficient attention and has rarely been reported, especially in China. Next-generation sequencing (NGS) followed by targeted CNV analysis was used in patients highly suspected to have PCD with negative results in routine whole-exome sequencing (WES) analysis. Quantitative real-time polymerase chain reaction (qPCR) and Sanger sequencing were used to confirm these CNVs. To further characterize the ciliary phenotypes, high-speed video microscopy analysis (HSVA), transmission electron microscopy (TEM), and immunofluorescence (IF) analysis were used. Patient 1 (F1: II-1), a 0.6-year-old girl, came from a nonconsanguineous family-I. She presented with situs inversus totalis, neonatal respiratory distress, and sinusitis. The nasal nitric oxide level was markedly reduced. The respiratory cilia beat with reduced amplitude. TEM revealed shortened outer dynein arms (ODA) of cilia. chr5:13717907-13722661del spanning exons 71-72 was identified by NGS-based CNV analysis. Patient 2 (F2: IV-4), a 37-year-old man, and his eldest brother Patient 3 (F2: IV-2) came from a consanguineous family-II. Both had sinusitis, bronchiectasis and situs inversus totalis. The respiratory cilia of Patient 2 and Patient 3 were found to be uniformly immotile, with ODA defects. Two novel homozygous deletions chr5:13720087_13733030delinsGTTTTC and chr5:13649539_1 3707643del, spanning exons 69-71 and exons 77-79 were identified by NGS-based CNV analysis. Abnormalities in DNA copy number were confirmed by qPCR amplification. IF showed that the respiratory cilia of Patient 1 and Patient 2 were deficient in dynein axonemal heavy chain 5 (DNAH5) protein expression. This report identified three novel disease-associated variants by WES-based CNV analysis. Our study expands the genetic spectrum of PCD with in the Chinese population.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s43657-023-00130-0.
PubMed: 38605905
DOI: 10.1007/s43657-023-00130-0 -
Med (New York, N.Y.) May 2024Early diagnosis of atrial fibrillation (AF) is important for preventing stroke and other complications. Predicting AF risk in advance can improve early diagnostic...
BACKGROUND
Early diagnosis of atrial fibrillation (AF) is important for preventing stroke and other complications. Predicting AF risk in advance can improve early diagnostic efficiency. Deep learning has been used for disease risk prediction; however, it lacks adherence to evidence-based medicine standards. Identifying the underlying mechanisms behind disease risk prediction is important and required.
METHODS
We developed an explainable deep learning model called HBBI-AI to predict AF risk using only heart beat-to-beat intervals (HBBIs) during sinus rhythm. We proposed a possible AF mechanism based on the model's explainability and verified this conjecture using confirmed AF risk factors while also examining new AF risk factors. Finally, we investigated the changes in clinicians' ability to predict AF risk using only HBBIs before and after learning the model's explainability.
FINDINGS
HBBI-AI consistently performed well across large in-house and external public datasets. HBBIs with large changes or extreme stability were critical predictors for increased AF risk, and the underlying cause was autonomic imbalance. We verified various AF risk factors and discovered that autonomic imbalance was associated with all these factors. Finally, cardiologists effectively understood and learned from these findings to improve their abilities in AF risk prediction.
CONCLUSIONS
HBBI-AI effectively predicted AF risk using only HBBI information through evaluating autonomic imbalance. Autonomic imbalance may play an important role in many risk factors of AF rather than in a limited number of risk factors.
FUNDING
This study was supported in part by the National Key R&D Program and the National Natural Science Foundation of China.
Topics: Atrial Fibrillation; Humans; Risk Assessment; Deep Learning; Heart Rate; Male; Risk Factors; Female; Artificial Intelligence; Electrocardiography; Aged; Middle Aged; Early Diagnosis
PubMed: 38492571
DOI: 10.1016/j.medj.2024.02.006 -
Science Progress 2024This study examined the histological aberrations in the gill and liver tissues and behavioural changes of fingerlings exposed to lethal concentrations of used...
This study examined the histological aberrations in the gill and liver tissues and behavioural changes of fingerlings exposed to lethal concentrations of used Oilfield-based emulsifiers for 96 h. Various concentrations of the surfactants were tested, ranging from 0.0 to 15.0 ml/L. The behaviour of the fish was observed throughout the experiment, and the results showed that increasing concentrations of the surfactants led to progressively abnormal behaviour, including hyperventilation and altered opercular beat frequency. These behavioural changes indicated respiratory distress and neurotoxic effects. Histological analysis revealed structural aberrations in the gill and liver tissues, with higher concentrations causing more severe damage, such as lesions, necrosis, inflammation, and cellular degeneration. This implies that surfactants released even at low concentrations are capable of inducing changes in the tissues of aquatic organisms. These findings highlight the toxic effects of the surfactants on fish health and provide biomarkers of toxicity. Future research should focus on understanding the specific mechanisms and long-term consequences of surfactant toxicity on fish genetic composition, populations, and ecosystems to implement effective conservation measures.
Topics: Animals; Tilapia; Ecosystem; Oil and Gas Fields; Papua New Guinea; Liver; Surface-Active Agents; Water Pollutants, Chemical
PubMed: 38490166
DOI: 10.1177/00368504241231663