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2.
Ear Hear ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39049080

RESUMO

OBJECTIVES: To explore postural disability in Usher Syndrome (USH) patients using temporal posturographic analysis to better elucidate sensory compensation strategies of deafblind patients for posture control and correlate the Activities-specific Balance Confidence (ABC) scale with posturographic variables. DESIGN: Thirty-four genetically confirmed USH patients (11 USH1, 21 USH2, 2 USH 4) from the Otolaryngology Outpatient Clinic and 35 controls were prospectively studied using both classical and wavelet temporal analysis of center of pressure (CoP) under different visual conditions on static and dynamic platforms. The functional impact of balance was assessed with the ABC scale. Classical data in the spatial domain, Sensorial Organization Test, and frequency analysis of the CoP were analyzed. RESULTS: On unstable surfaces, USH1 had greater CoP surface area with eyes open (38.51 ± 68.67) and closed (28.14 ± 31.64) versus controls (3.31 ± 4.60), p < 0.001 and (7.37 ± 7.91), p < 0.001, respectively. On an unstable platform, USH consistently showed increased postural sway, with elevated angular velocity versus controls with eyes open (USH1 [44.94 ± 62.54]; USH2 [55.64 ± 38.61]; controls [13.4 ± 8.57]) (p = 0.003; p < 0.001) and closed (USH1 [60.36 ± 49.85], USH2 [57.62 ± 42.36]; controls [27.31 ± 19.79]) (p = 0.002; p = 0.042). USH visual impairment appears to be the primary factor influencing postural deficits, with a statistically significant difference observed in the visual Sensorial Organization Test ratio for USH1 (80.73 ± 40.07, p = 0.04) and a highly significant difference for USH2 (75.48 ± 31.67, p < 0.001) versus controls (100). In contrast, vestibular (p = 0.08) and somatosensory (p = 0.537) factors did not reach statistical significance. USH exhibited lower visual dependence than controls (30.31 ± 30.08) (USH1 [6 ± 11.46], p = 0.004; USH2 [8 ± 14.15], p = 0.005). The postural instability index, that corresponds to the ratio of spectral power index and canceling time, differentiated USH from controls on unstable surface with eyes open USH1 (3.33 ± 1.85) p < 0.001; USH2 (3.87 ± 1.05) p < 0.002; controls (1.91 ± 0.85) and closed USH1 (3.91 ± 1.65) p = 0.005; USH2 (3.92 ± 1.05) p = 0.045; controls (2.74 ± 1.27), but not USH1 from USH2. The canceling time in the anteroposterior direction in lower zone distinguished USH subtypes on stable surface with optokinetic USH1 (0.88 ± 1.03), USH2 (0.29 ± 0.23), p = 0.026 and on unstable surface with eyes open USH1 (0.56 ± 1.26), USH2 (0.072 ± 0.09), p = 0.036. ABC scale could distinguish between USH patients and controls, but not between USH subtypes and it correlated with CoP surface area on unstable surface with eyes open only in USH1(ρ = 0.714, p = 0.047). CONCLUSIONS: USH patients, particularly USH1, exhibited poorer balance control than controls on unstable platform with eyes open and appeared to rely more on proprioceptive information while suppressing visual input. USH2 seems to use different multisensory balance strategies that do not align as well with the ABC scale. The advanced analysis provided insights into sensory compensation strategies in USH subtypes.

3.
Front Psychol ; 15: 1390536, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39040970

RESUMO

Introduction: This study aimed to describe the fixation location and the time of the longer fixation of expert and novice futsal coaches before the ball was in play in futsal set pieces. Methods: A total of 10 experts (ages 48 ± 5) and 10 novice coaches (ages 40 ± 7) participated in the study. They observed that 38 video clips were created to mimic the attack and defensive set-piece moments of the game. Data were collected in a standardized video analysis task using the pupil invisible eye tracker and processed through the pupil cloud platform. The Mann-Whitney test was conducted to evaluate differences in gaze duration between game moments (attack and defense set pieces) and groups (expert vs. novice). Gaze duration was also compared for gaze location between groups. For further comparisons, the game moments (attack and defense set pieces) and the gaze location were summarized in two-dimensional graphics using correspondence analysis. Results and discussion: The results revealed higher values of gaze duration for attack and defense set pieces for the group of experts than for novices. When considering gaze duration, expert coaches had higher values than novices for the attacker 3, defender 3, barrier 1st, and barrier 2nd gaze locations. The correspondence analysis showed different strategies of visual search and, consequently, gaze locations for attack and defense set pieces. In particular, there was different correspondence for free kicks between the level of expertise and gaze location, while corner and sideline kicks revealed some correspondence between the groups and the gaze location. In free kicks, coaches should be particularly concerned about the relationship between attacker and defender three and the barrier 1st and 2nd line positions. In corner and sideline kicks, coaches should be particularly aware of the relationship between attackers' and defenders' positions.

4.
Int J Sports Physiol Perform ; : 1-7, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043362

RESUMO

PURPOSE: There are multiple postexercise recovery technologies available in the market based on the assumption of blood-flow enhancement. Lower-limb intermittent pneumatic compression (IPC) has been widely used, but the available scientific evidence supporting its effectiveness remains scarce, requiring a deeper investigation into its underlying mechanisms. The aim of this study was to assess the hemodynamic effects caused by the use of IPC at rest. METHODS: Twenty-two soccer and track and field athletes underwent two 15-minute IPC protocols (moderate- [80 mm Hg] and high-pressure [200 mm Hg]) in a randomized order. Systolic peak velocity, end-diastolic peak velocity, arterial diameter, and heart rate were measured before, during (at the eighth minute), and 2 minutes after each IPC protocol. RESULTS: Significant effects were observed between before and during (eighth minute) the IPC protocol for measures of systolic (P < .001) and end-diastolic peak velocities (P < .001), with the greater effects observed during the high-pressure protocol. Moreover, 2 minutes after each IPC protocol, hemodynamic variables returned to values close to baseline. Arterial diameter presented significant differences between pressures during the IPC protocols (P < .05), while heart rate remained unaltered. CONCLUSION: IPC effectively enhances transitory blood flow of athletes, particularly when applying high-pressure protocols.

6.
Yale J Biol Med ; 97(2): 225-238, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38947102

RESUMO

Joint hypermobility syndromes, particularly chronic pain associated with this condition, including Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD), present diagnostic challenges due to their multifactorial origins and remain poorly understood from biomechanical and genomic-molecular perspectives. Recent diagnostic guidelines have differentiated hEDS, HSD, and benign joint hypermobility, providing a more objective diagnostic framework. However, incorrect diagnoses and underdiagnoses persist, leading to prolonged journeys for affected individuals. Musculoskeletal manifestations, chronic pain, dysautonomia, and gastrointestinal symptoms illustrate the multifactorial impact of these conditions, affecting both the physical and emotional well-being of affected individuals. Infrared thermography (IRT) emerges as a promising tool for joint assessment, especially in detecting inflammatory processes. Thermal distribution patterns offer valuable insights into joint dysfunctions, although the direct correlation between pain and inflammation remains challenging. The prevalence of neuropathies among hypermobile individuals accentuates the discordance between pain perception and thermographic findings, further complicating diagnosis and management. Despite its potential, the clinical integration of IRT faces challenges, with conflicting evidence hindering its adoption. However, studies demonstrate objective temperature disparities between healthy and diseased joints, especially under dynamic thermography, suggesting its potential utility in clinical practice. Future research focused on refining diagnostic criteria and elucidating the underlying mechanisms of hypermobility syndromes will be essential to improve diagnostic accuracy and enhance patient care in this complex and multidimensional context.


Assuntos
Dor Crônica , Instabilidade Articular , Termografia , Humanos , Termografia/métodos , Instabilidade Articular/diagnóstico , Instabilidade Articular/fisiopatologia , Dor Crônica/diagnóstico , Dor Crônica/fisiopatologia , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/fisiopatologia , Inflamação/diagnóstico , Raios Infravermelhos
7.
Med Teach ; : 1-7, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012024

RESUMO

INTRODUCTION: ChatGPT has attracted a lot of interest worldwide for its versatility in a range of natural language tasks, including in the education and evaluation industry. It can automate time- and labor-intensive tasks with clear economic and efficiency gains. METHODS: This study evaluated the potential of ChatGPT to automate psychometric analysis of test questions from the 2020 Portuguese National Residency Selection Exam (PNA). ChatGPT was queried 100 times with the 150 MCQ from the exam. Using ChatGPT's responses, difficulty indices were calculated for each question based on the proportion of correct answers. The predicted difficulty levels were compared to the actual difficulty levels of the 2020 exam MCQ's using methods from classical test theory. RESULTS: ChatGPT's predicted item difficulty indices positively correlated with the actual item difficulties (r (148) = -0.372, p < .001), suggesting a general consistency between the real and the predicted values. There was also a moderate significant negative correlation between the difficulty index predicted by ChatGPT and the number of challenges (r (148) = -0.302, p < .001), highlighting ChatGPT's potential for identifying less problematic questions. CONCLUSION: These findings unveiled ChatGPT's potential as a tool for assessment development, proving its capability to predict the psychometric characteristics of high-stakes test items in automated item calibration without pre-testing in real-life scenarios.

8.
Micromachines (Basel) ; 15(7)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39064385

RESUMO

The evolution in the biomedical engineering field boosts innovative technologies, with microfluidic systems standing out as transformative tools in disease diagnosis, treatment, and monitoring. Numerical simulation has emerged as a tool of increasing importance for better understanding and predicting fluid-flow behavior in microscale devices. This review explores fabrication techniques and common materials of microfluidic devices, focusing on soft lithography and additive manufacturing. Microfluidic systems applications, including nucleic acid amplification and protein synthesis, as well as point-of-care diagnostics, DNA analysis, cell cultures, and organ-on-a-chip models (e.g., lung-, brain-, liver-, and tumor-on-a-chip), are discussed. Recent studies have applied computational tools such as ANSYS Fluent 2024 software to numerically simulate the flow behavior. Outside of the study cases, this work reports fundamental aspects of microfluidic simulations, including fluid flow, mass transport, mixing, and diffusion, and highlights the emergent field of organ-on-a-chip simulations. Additionally, it takes into account the application of geometries to improve the mixing of samples, as well as surface wettability modification. In conclusion, the present review summarizes the most relevant contributions of microfluidic systems and their numerical modeling to biomedical engineering.

9.
Biol Sport ; 41(3): 223-230, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38952912

RESUMO

This study compared the most common absolute sprint threshold (> 25.2 km/h) with relative and individualized thresholds (> 70%, > 75%, > 80%, > 85% and > 90% of peak match speed). Twenty elite soccer players, competing in the first division of the Portuguese League, were monitored using GNSS equipment during thirty-four official matches. Peak match speed was retrieved as the individual maximal speed reached during the full season. Distances were registered when speed overcame the absolute and the relative thresholds. Mean ± SD of peak speeds and distances covered were calculated, and Pearson correlation (r) and mean paired differences were performed to analyze relationships and differences between thresholds. The peak match speed was 32.9 ± 1.4 km/h. Correlations between distances covered using the absolute and relative thresholds varied from very strong (> 70%: r = 0.84, p < .001; > 75%: r = 0.89, p < .001; and > 80%: r = 0.88, p < .001), strong (> 85%: r = 0.79, p < .001), to moderate (> 90%: r = 0.59, p < .001). Overall, the > 75% (ES: 0.23 [95% CI: 0.16, 0.31]) and the > 90% (ES: -1.65 [95%CI: -1.85, -1.48]) relative thresholds presented the smallest and largest differences, respectively, with the absolute threshold. Differences were also found when considering the playing positions. While the distances covered by central midfielders were similar between the absolute and > 80% thresholds (-0.03 [-0.16, 0.10]), fullbacks covered largely more distance -1.88 [-2.42 -1.50]) in the absolute threshold than in the > 80% threshold. The distances covered by players varied based on the selected threshold, affecting the distances covered by different playing positions. Being the highest speed threshold within displacements thresholds, the absolute sprint threshold showed greater similarity to lower rather than higher relative thresholds.

10.
Acta Med Port ; 37(6): 455-466, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38848702

RESUMO

INTRODUCTION: Psychiatric comorbidities have a significant impact on patients' quality of life and often go undetected in neurologic practice. The aim of this study was to describe and characterize psychiatric comorbidities among patients hospitalized due to a neurologic disorder in mainland Portugal. METHODS: A retrospective observational study was performed by analyzing hospitalization with a primary diagnosis of neurologic disorder defined as categories 76, 77, 79 - 85, 95, 109 of the Clinical Classification Software for International Classification of Diseases, Ninth Revision, Clinical Modification, occurring between 2008 and 2015 in adult patients (≥ 18 years of age). Psychiatric comorbidities were determined as the presence of a secondary diagnosis belonging to the Clinical Classification Software categories 650 to 670. RESULTS: A total of 294 806 hospitalization episodes with a primary diagnosis of a neurologic disorder were recorded in adult patients between 2008 - 2015 in Portuguese public hospitals. Approximately 26.9% (n = 79 442) of the episodes had a recorded psychiatric comorbidity (22.1%; 32.2%, female versus male hospitalizations). Patients with registered psychiatric comorbidities were younger (66.2 ± 16.2 vs 68.6 ± 17.2 with no psychiatric comorbidities, p < 0.001), presented lower all-cause in-hospital mortality rates, and significantly longer mean hospital stays. 'Delirium, dementia, amnestic and other cognitive disorders' were recorded in 7.4% (n = 21 965) of the hospitalizations, followed by alcohol-related disorders in 6.5% (n = 19 302) and mood disorders in 6.1% (n = 18 079). Epilepsy/seizures were the neurologic disorders with the highest proportion of recorded psychiatric comorbidities (39.9%). CONCLUSION: Psychiatric comorbidities were recorded in more than a quarter of the hospitalizations with a primary diagnosis of a Neurologic disorder. Psychiatric comorbidities varied among neurological disorders and were associated with different demographic and clinical features.


Assuntos
Hospitalização , Transtornos Mentais , Doenças do Sistema Nervoso , Humanos , Estudos Retrospectivos , Portugal/epidemiologia , Masculino , Feminino , Idoso , Hospitalização/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Doenças do Sistema Nervoso/epidemiologia , Pessoa de Meia-Idade , Comorbidade , Idoso de 80 Anos ou mais , Adulto
11.
Cureus ; 16(5): e59603, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38826884

RESUMO

Transient global amnesia (TGA) is an uncommon neurologic disorder that consists of a sudden and temporary loss of memory, both present and past. Its causes and risk factors are not well known. We describe a case of a 58-year-old woman who was brought to the emergency department (ED) with sudden onset loss of memory and disorientation after a dive in the ocean. She presented memory deficits with incapacity to retain new memories and amnesia for the previous 24 hours. All exams ordered were normal, including computed tomography of the brain and laboratory analysis. After six hours of close monitoring in the ED, she gradually started to retain short-term memories and was discharged after 48 hours with no memory or other deficits. The diagnosis of TGA was made based on the clinical presentation and the patient's rapid improvement. Follow-up neurology consultation and further testing did not demonstrate any evidence to exclude this diagnosis. Further research is needed on this topic to allow the identification of risk factors and causes to prevent it.

12.
Front Sports Act Living ; 6: 1376024, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863569

RESUMO

Introduction: The aim of this study was to analyze the effects of space and number of players manipulation on the external and internal load demands of youth futsal athletes. Methods: Forty-two male U17 players (age = 15.62 ± 0.58 years) from three futsal teams participated in the study. In this cross-sectional study that lasted 8-week, the player's sample practiced six futsal tasks (T1-T6) and a futsal game played under the official rules (T7). From T1-T6, two task constraints were manipulated: (i) the number of players and, (ii) the space of play. The WIMU PRO™ Ultra-Wideband (UWB) tracking system was used to measure the external and internal load during the futsal tasks. External load was quantified using kinematic and mechanical variables extracted from positional data and, the internal load was quantified using Heart rate (HR) and rating of perceived exertion (RPE). Repeated measures ANOVA was used for comparison purposes. Results: In general, the results showed high external (total distance, distance 18.1-21, above 21 Km/h, and high intensity acceleration and deceleration, p < 0.001) and internal load (heart rate average and rating of perceived exertion, p < 0.001) in the tasks with low number of players and high area. In relation to the match, the tasks with small relative area per player (GK + 2 vs. 2 + GK and GK + 3 vs. 3 + GK in 20 × 20 m) promoted low external load. Conclusion: It was concluded that increasing the relative area by reducing the number of players involved in the tasks in the form of small-sided games (GK + 2 vs. 2 + GK and GK + 3 vs. 3 + GK), in relation to the futsal game (GK + 4 vs. 4 + GK), can be considered a pedagogical strategy to increase the external and internal load demands of young futsal players.

13.
Micromachines (Basel) ; 15(6)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38930640

RESUMO

Polydimethylsiloxane (PDMS) has attracted great attention in various fields due to its excellent properties, but its inherent hydrophobicity presents challenges in many applications that require controlled wettability. The purpose of this review is to provide a comprehensive overview of some key strategies for modifying the wettability of PDMS surfaces by providing the main traditional methods for this modification and the results of altering the contact angle and other characteristics associated with this property. Four main technologies are discussed, namely, oxygen plasma treatment, surfactant addition, UV-ozone treatment, and the incorporation of nanomaterials, as these traditional methods are commonly selected due to the greater availability of information, their lower complexity compared to the new techniques, and the lower cost associated with them. Oxygen plasma treatment is a widely used method for improving the hydrophilicity of PDMS surfaces by introducing polar functional groups through oxidation reactions. The addition of surfactants provides a versatile method for altering the wettability of PDMS, where the selection and concentration of the surfactant play an important role in achieving the desired surface properties. UV-ozone treatment is an effective method for increasing the surface energy of PDMS, inducing oxidation, and generating hydrophilic functional groups. Furthermore, the incorporation of nanomaterials into PDMS matrices represents a promising route for modifying wettability, providing adjustable surface properties through controlled dispersion and interfacial interactions. The synergistic effect of nanomaterials, such as nanoparticles and nanotubes, helps to improve wetting behaviour and surface energy. The present review discusses recent advances of each technique and highlights their underlying mechanisms, advantages, and limitations. Additionally, promising trends and future prospects for surface modification of PDMS are discussed, and the importance of tailoring wettability for applications ranging from microfluidics to biomedical devices is highlighted. Traditional methods are often chosen to modify the wettability of the PDMS surface because they have more information available in the literature, are less complex than new techniques, and are also less expensive.

14.
Vet Sci ; 11(6)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38921980

RESUMO

Bovine mastitis is an important and costly disease to dairy cattle. Diagnostic methods usually performed in Brazil are somatic cell counts (SCC) and milk microbiology. Low bacteria shedding in milk implies no colony growth in microbiological tests and false negative results. Streptococcus agalactiae and Staphylococcus aureus are principal pathogens of mixed mastitis. However, S. agalactiae has a higher bacterial release from the mammary gland than S. aureus, affecting microbiological sensitivity to diagnose S. aureus. This study aimed to estimate the SCC and total bacterial count (TBC) from cows according to pathogen isolated in milk and to evaluate variation in S. aureus diagnosis by a microbiological test during S. agalactiae treatment, which is called blitz therapy. Both S. agalactiae and S. aureus presented high SCC means, although S. agalactiae showed shedding of bacteria 2.3 times greater than S. aureus. Microbiological sensitivity to S. aureus increased for 5 months during S. agalactiae treatment. The prevalence of S. agalactiae fell after 5 months of therapeutic procedures. The prevalence of S. aureus increased to 39.0. The results showed that due to high sensitivity, the polymerase chain reaction (PCR) could be used at the beginning of blitz therapy with the goal of S. agalactiae eradication from the dairy herd.

15.
Res Q Exerc Sport ; : 1-8, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905702

RESUMO

Purpose: This longitudinal study analyzed the relationship between players' physical (sprint distances, number of high-intensity accelerations and decelerations assessed with individual and relative thresholds) and technical (retrieved from SofaScore platform) performances during competition. Methods: Twenty elite players were monitored across a full season. Physical performances were monitored with GNSS devices, retrieving time (s), velocity (km.h-1) and distance (m). Sprint distances were calculated as > 80% of the match peak speed registered across the season. High-intensity accelerations and decelerations were calculated as >75% of the peak values registered across the season. Pearson (r) correlations (with 95% confidence intervals) were calculated to assess the relationship among different physical performance variables and between the physical and technical performance variables. Results: Sprint distances correlated with the number of ball touches (r = -0.36 [-0.49, -0.23], p < .001), accurate passes (r = -0.45 [-0.56, -0.32], p < .001), and dribble attempts (r = 0.30 [0.16, 0.43], p < .001). If players touched the ball more frequently and pass the ball more accurately, they covered shorter sprint distances. However, if players attempted more dribbles, they covered longer sprint distances. Conclusion: Practitioners can develop tactical strategies considering the relationship between sprint distances and technical variables such as ball touches, accurate passes, and dribble attempts.

16.
PLoS One ; 19(6): e0305705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38941305

RESUMO

Ad hoc teamwork is a research topic in multi-agent systems whereby an agent (the "ad hoc agent") must successfully collaborate with a set of unknown agents (the "teammates") without any prior coordination or communication protocol. However, research in ad hoc teamwork is predominantly focused on agent-only teams, but not on agent-human teams, which we believe is an exciting research avenue and has enormous application potential in human-robot teams. This paper will tap into this potential by proposing HOTSPOT, the first framework for ad hoc teamwork in human-robot teams. Our framework comprises two main modules, addressing the two key challenges in the interaction between a robot acting as the ad hoc agent and human teammates. First, a decision-theoretic module that is responsible for all task-related decision-making (task identification, teammate identification, and planning). Second, a communication module that uses natural language processing to parse all communication between the robot and the human. To evaluate our framework, we use a task where a mobile robot and a human cooperatively collect objects in an open space, illustrating the main features of our framework in a real-world task.


Assuntos
Comportamento Cooperativo , Robótica , Humanos , Tomada de Decisões , Comunicação
17.
RSC Med Chem ; 15(5): 1652-1663, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38784460

RESUMO

MANIO is an efficient p53-activating anticancer agent with remarkable selectivity to the p53 pathway and promising antitumor activity against colorectal cancer (CRC). Herein, a library of novel MANIO derivatives, including hydroxymethyl- and bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles, was synthesized by rational structural modulation. The antiproliferative activity of twenty derivatives was evaluated in a panel of human CRC cells with different p53 status. From this library, five compounds with R- and S-configuration and with aromatic or heteroaromatic groups at position 3, including the enantiomer of MANIO, were identified as selective towards p53-expressing cancer cells. On the other hand, two compounds with S-configuration, 6-hydroxymethyl- and 7-hydroxymethyl-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazoles, showed high cytotoxicity against WTp53-expressing HCT116 colon cells but, unlike MANIO, exhibited p53-independent inhibitory activity in CRC. The results described provide relevant structural and pharmacophoric data for the design of new p53-activating agents for precision therapy of CRC or other p53-related cancers harboring both wild-type or mutated p53 forms.

18.
J Med Genet ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697782

RESUMO

BACKGROUND: Triokinase and FMN cyclase (TKFC) is a bifunctional enzyme involved in fructose metabolism. Triokinase catalyses the phosphorylation of fructose-derived glyceraldehyde (GA) and exogenous dihydroxyacetone (DHA), while FMN cyclase generates cyclic FMN. TKFC regulates the antiviral immune response by interacting with IFIH1 (MDA5). Previously reported pathogenic variants in TKFC are associated with either a multisystemic disease or isolated hypotrichosis with loose anagen hairs. METHODS: Whole-exome sequencing identified a homozygous novel variant in TKFC (c.1624G>A; p.Gly542Arg) in an individual with a complex primary immunodeficiency disorder. The variant was characterised using enzymatic assays and yeast studies of mutant recombinant proteins. RESULTS: The individual presented with chronic active Epstein-Barr virus disease and multiple bacterial and viral infections. Clinical investigations revealed hypogammaglobulinaemia, near absent natural killer cells and decreased memory B cells. Enzymatic assays showed that this variant displayed defective DHA and GA kinase activity while maintaining FMN cyclase activity. An allogenic bone marrow transplantation corrected the patient's immunodeficiency. CONCLUSION: Our report suggests that TKFC may have a role in the immunological system. The pathological features associated with this variant are possibly linked with DHA/GA kinase inactivation through a yet an unknown mechanism. This report thus adds a possible new pathway of immunometabolism to explore further.

19.
BMC Bioinformatics ; 25(1): 195, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760692

RESUMO

BACKGROUND: Pathogenic infections pose a significant threat to global health, affecting millions of people every year and presenting substantial challenges to healthcare systems worldwide. Efficient and timely testing plays a critical role in disease control and transmission prevention. Group testing is a well-established method for reducing the number of tests needed to screen large populations when the disease prevalence is low. However, it does not fully utilize the quantitative information provided by qPCR methods, nor is it able to accommodate a wide range of pathogen loads. RESULTS: To address these issues, we introduce a novel adaptive semi-quantitative group testing (SQGT) scheme to efficiently screen populations via two-stage qPCR testing. The SQGT method quantizes cycle threshold (Ct) values into multiple bins, leveraging the information from the first stage of screening to improve the detection sensitivity. Dynamic Ct threshold adjustments mitigate dilution effects and enhance test accuracy. Comparisons with traditional binary outcome GT methods show that SQGT reduces the number of tests by 24% on the only complete real-world qPCR group testing dataset from Israel, while maintaining a negligible false negative rate. CONCLUSION: In conclusion, our adaptive SQGT approach, utilizing qPCR data and dynamic threshold adjustments, offers a promising solution for efficient population screening. With a reduction in the number of tests and minimal false negatives, SQGT holds potential to enhance disease control and testing strategies on a global scale.


Assuntos
Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase em Tempo Real/métodos , Humanos
20.
Sci Rep ; 14(1): 8107, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582778

RESUMO

In 2023 Amazonia experienced both historical drought and warm conditions. On October 26th 2023 the water levels at the port of Manaus reached its lowest record since 1902 (12.70 m). In this region, October monthly maximum and minimum temperature anomalies also surpassed previous record values registered in 2015 (+ 3 °C above the normal considering the 1981-2020 average). Here we show that this historical dry and warm situation in Amazonia is associated with two main atmospheric mechanisms: (i) the November 2022-February 2023 southern anomaly of vertical integrated moisture flux (VIMF), related to VIMF divergence and extreme rainfall deficit over southwestern Amazonia, and (ii) the June-August 2023 downward motion over northern Amazonia related to extreme rainfall deficit and warm conditions over this region. Anomalies of both atmospheric mechanisms reached record values during this event. The first mechanism is significantly correlated to negative sea surface temperature (SST) anomalies in the equatorial Pacific (November-February La Niña events). The second mechanism is significantly correlated to positive SST anomalies in the equatorial Pacific, related to the impacts of June-September El Niño on the Walker Circulation. While previous extreme droughts were linked to El Niño (warmer North Tropical Atlantic SST) during the austral summer (winter and spring), the transition from La Niña 2022-23 to El Niño 2023 appears to be a key climatic driver in this record-breaking dry and warm situation, combined to a widespread anomalous warming over the worldwide ocean.

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