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1.
Cell Physiol Biochem ; 58(2): 156-171, 2024 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-38639213

RESUMEN

BACKGROUND/AIMS: The physiological phenotype of individuals can influence and shape real-life phenomena in that it can contribute to the development of specific characteristics that can affect the immune response to specific stimuli. In this study we aimed to understand whether the sphingosine/sphingosine-1-phoshate (S1P) axis can modulate the immunotype of circulating cells. METHODS: To pursue this goal, we performed bioinformatic analyses of public datasets. RESULTS: The transcriptomic profile of healthy subjects of GSE192829 dataset identified two clusters with different transcriptional repertoire. Cluster 1 expressed higher levels of enzymes for S1P formation than cluster 0 which was characterized by enzymes that lead to ceramide formation, which represent the opposite metabolic direction. Inference analysis showed that cluster 1 was higher populated by monocytes, CD4+ T and B cells than cluster 0. Of particular interest was the phenotype of the monocytes in cluster 1 which showed an immunosuppressive nature compared to those in cluster 0. The role of S1P signature in healthy PBMCs was confirmed with other dataset analyses, supporting that circulating monocytes positive to the ceramidase, unlike the negative ones, had an immunosuppressive phenotype characterized by hub immunosuppressive markers (i.e. TYROBP, FCER1G, SYK, SIRPA, CSF1R, AIF1, FCGR2A, CLEC7A, LYN, PLCG2, LILRs, HCK, GAB2). This hub genes well discriminated the immunotype of healthy subjects. CONCLUSION: In conclusion this study highlights that S1P-associated hub markers can be useful to discriminate subjects with pronounced immunosuppression.


Asunto(s)
Monocitos , Esfingosina , Esfingosina/análogos & derivados , Humanos , Esfingosina/metabolismo , Monocitos/metabolismo , Lisofosfolípidos/metabolismo , Inmunosupresores , Fenotipo
2.
Hum Brain Mapp ; 45(1): e26554, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38224543

RESUMEN

Every brain is unique, having its structural and functional organization shaped by both genetic and environmental factors over the course of its development. Brain image studies tend to produce results by averaging across a group of subjects, under the common assumption that it is possible to subdivide the cortex into homogeneous areas while maintaining a correspondence across subjects. We investigate this assumption: can the structural properties of a specific region of an atlas be assumed to be the same across subjects? This question is addressed by looking at the network representation of the brain, with nodes corresponding to brain regions and edges to their structural relationships. Using an unsupervised graph matching strategy, we align the structural connectomes of a set of healthy subjects, considering parcellations of different granularity, to understand the connectivity misalignment between regions. First, we compare the obtained permutations with four different algorithm initializations: Spatial Adjacency, Identity, Barycenter, and Random. Our results suggest that applying an alignment strategy improves the similarity across subjects when the number of parcels is above 100 and when using Spatial Adjacency and Identity initialization (the most plausible priors). Second, we characterize the obtained permutations, revealing that the majority of permutations happens between neighbors parcels. Lastly, we study the spatial distribution of the permutations. By visualizing the results on the cortex, we observe no clear spatial patterns on the permutations and all the regions across the context are mostly permuted with first and second order neighbors.


Asunto(s)
Encéfalo , Conectoma , Humanos , Encéfalo/diagnóstico por imagen , Algoritmos , Conectoma/métodos , Corteza Cerebral , Imagen por Resonancia Magnética/métodos
3.
Br J Clin Pharmacol ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830622

RESUMEN

AIMS: Early clinical studies have indicated that the pharmacokinetics of Atuliflapon (AZD5718) are time and dose dependent. The reason(s) for these findings is(are) not fully understood, but pre-clinical profiling suggests that time-dependent CYP3A4 inhibition cannot be excluded. In clinical practice, Atuliflapon will be co-administered with CYP3A4 substrates; thus, it is important to determine the impact of Atuliflapon on the pharmacokinetics (PK) of CYP3A4 substrates. The aim of this study was to evaluate the effect of Atuliflapon on the pharmacokinetics of a sensitive CYP3A4 substrate, midazolam, and to explore if the time-/dose-dependent effect seen after repeated dosing could be an effect of change in CYP3A4 activity. METHODS: Open-label, fixed-sequence study in healthy volunteers to assess the PK of midazolam alone and in combination with Atuliflapon. Fourteen healthy male subjects received single oral dose of midazolam 2 mg on days 1 and 7 and single oral doses of Atuliflapon (125 mg) from days 2 to 7. A physiologically based pharmacokinetic (PBPK) model was developed to assess this drug-drug interaction. RESULTS: Mean midazolam values of maximum plasma concentration (Cmax) and area under the curve (AUC) to infinity were increased by 39% and 56%, respectively, when co-administered with Atuliflapon vs. midazolam alone. The PBPK model predicted a 27% and 44% increase in AUC and a 23% and 35% increase in Cmax of midazolam following its co-administrations with two predicted therapeutically relevant doses of Atuliflapon. CONCLUSIONS: Atuliflapon is a weak inhibitor of CYP3A4; this was confirmed by the validated PBPK model. This weak inhibition is predicted to have a minor PK effect on CYP3A4 metabolized drugs.

4.
Neuroradiology ; 66(7): 1189-1197, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38609687

RESUMEN

PURPOSE: Detection and prediction of the rate of brain volume loss with age is a significant unmet need in patients with primary progressive multiple sclerosis (PPMS). In this study we construct detailed brain volume maps for PPMS patients. These maps compare age-related changes in both cortical and sub-cortical regions with those in healthy individuals. METHODS: We conducted retrospective analyses of brain volume using T1-weighted Magnetic Resonance Imaging (MRI) scans of a large cohort of PPMS patients and healthy subjects. The volume of brain parenchyma (BP), cortex, white matter (WM), deep gray matter, thalamus, and cerebellum were measured using the robust SynthSeg segmentation tool. Age- and gender-related regression curves were constructed based on data from healthy subjects, with the 95% prediction interval adopted as the normality threshold for each brain region. RESULTS: We analyzed 495 MRI scans from 169 PPMS patients, aged 20-79 years, alongside 563 exams from healthy subjects aged 20-86. Compared to healthy subjects, a higher proportion of PPMS patients showed lower than expected brain volumes in all regions except the cerebellum. The most affected areas were BP, WM, and thalamus. Lower brain volumes correlated with longer disease duration for BP and WM, and higher disability for BP, WM, cortex, and thalamus. CONCLUSIONS: Constructing age- and gender-related brain volume maps enabled identifying PPMS patients at a higher risk of brain volume loss. Monitoring these high-risk patients may lead to better treatment decisions and improve patient outcomes.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Esclerosis Múltiple Crónica Progresiva , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Imagen por Resonancia Magnética/métodos , Anciano , Esclerosis Múltiple Crónica Progresiva/diagnóstico por imagen , Esclerosis Múltiple Crónica Progresiva/patología , Estudios Retrospectivos , Tamaño de los Órganos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Anciano de 80 o más Años , Progresión de la Enfermedad , Mapeo Encefálico/métodos
5.
Stereotact Funct Neurosurg ; : 1-17, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38986460

RESUMEN

INTRODUCTION: This scoping review aimed to synthesize the fragmented evidence on ethical concerns related to the use of electrical and magnetic neuromodulation technologies, as well as brain-computer interfaces for enhancing brain function in healthy individuals, addressing the gaps in understanding spurred by rapid technological advancements and ongoing ethical debates. METHODS: The following databases and interfaces were queried: MEDLINE (via PubMed), Web of Science, PhilPapers, and Google Scholar. Additional references were identified via bibliographies of included citations. References included experimental studies, reviews, opinion papers, and letters to editors published in peer-reviewed journals that explored the ethical implications of electrical and magnetic neuromodulation technologies and brain-computer interfaces for enhancement of brain function in healthy adult or pediatric populations. RESULTS: A total of 23 articles were included in the review, of which the majority explored expert opinions in the form of qualitative studies or surveys as well as reviews. Two studies explored the view of laypersons on the topic. The majority of evidence pointed to ethical concerns relating to a lack of sufficient efficacy and safety data for these new technologies, with the risks of invasive procedures potentially outweighing the benefits. Additionally, concerns about potential socioeconomic consequences were raised that could further exacerbate existing socioeconomic inequalities, as well as the risk of changes to person and environment. CONCLUSION: This scoping review highlights a critical shortage of ethical research on electrical and magnetic neuromodulation technologies and brain-computer interfaces for enhancement of brain function in healthy individuals, with key concerns regarding the safety, efficacy, and socioeconomic impacts of neuromodulation technologies. It underscores the urgent need for integrating ethical considerations into neuroscientific research to address significant gaps and ensure equitable access and outcomes.

6.
J Exerc Sci Fit ; 22(3): 179-186, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38495300

RESUMEN

Background/objectives: Respiratory muscle training (RMT) was recognized as an effective means to improve respiratory muscle (RM) strength and enhance exercise performance. The purpose of this study was to examine the effect of low-intensity RMT on RM strength, pulmonary function, and performance. Methods: Fourteen healthy active adults were assigned randomly to either a training or placebo group. The training group completed six weeks of RMT, which consisted of a first week, 1 set of 15 min/d, 5 d/wk at 10-25% of maximal inspiratory pressure (PImax), and the remaining 5 weeks, 2 sets of 15 min/d, 5 d/wk, at 30% PImax. The placebo group followed the same protocol but with almost no additional ventilatory resistance. Measurement of RM strength and endurance, spirometry, and endurance exercise performance were obtained before and after the RMT program. Results: In the training group, PImax (+14%) and maximal expiratory pressure (PEmax, +27%), forced vital capacity (FVC, +3.6%), maximal oxygen uptake (VO2max, +11%), and time to exhaustion (Tlim90%, +25%) increased significantly from baseline values (P < 0.05). No significant changes were observed in the placebo group. Also, no significant interaction in maximum voluntary ventilation (MVV12), minute ventilation (VE), and respiratory rate (RR) were detected. Conclusions: These data suggest that low-intensity RMT is an effective tool to improve RM strength, pulmonary elastic properties and endurance exercise performance.

7.
Pol Merkur Lekarski ; 52(2): 208-215, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38642357

RESUMEN

OBJECTIVE: Aim: To determine the normal range of serum levels of total 25(OH)VD in Iraqi healthy adult subjects and to relate its level with demographic profile and socioeconomic status.. PATIENTS AND METHODS: Materials and Methods: This cross sectional study was carried out at Iraq and the samples were collected during the period from August 2019 to January 2020. It included 649 adult subjects apparently healthy, from three governorates (Baghdad, Al-Anbar and Al-Basrah), Investigations included serum measurement of total 25(OH)D in all included individuals by using ELISA technique. Age, gender, marital state, blood pressure, smoking, sunshine exposure (%), hours of exposure/day, percentage of body surface area exposed, body mass index (BMI) subgroups, waist circumference (WC) subgroups, diet type, sport type and time, geographic factor (governorate) were measured and / or calculated and the levels of 25(OH)D were studied according to each of these factors. RESULTS: Results: The mean ± SD level of 25(OH)D in total (n=649) studied Iraqi subjects was (16.29 ± 8.22 ng/ml), with women were significantly deficient than men (15.76 ± 6.89 ng/ml, 17.14 ± 6.85 ng/ml; p < 0.01 respectively). However, there was no significant differences in mean values of serum 25(OH)D levels among studied governorates, subgroups of BMI, WC, marital status, smokers and nonsmoker and subgroups of age. The mean value of serum 25(OH)D was found to be decreased in January, October and November as well as according to diet and sport types. There was significant positive correlation between total 25(OH)D and sun exposed surface area, sun exposure duration and with sun exposure area. CONCLUSION: Conclusions: The mean (±SD) value of serum total 25(OH)D in Iraqi healthy subjects was 16.29 ng/ml (±8.22) reflecting the actual body status of this vitamin with lower concentration in women than in men. Type and time of sport and diet type were the major vitamin D dependent factors.


Asunto(s)
Deficiencia de Vitamina D , Masculino , Adulto , Humanos , Femenino , Irak , Deficiencia de Vitamina D/epidemiología , Estudios Transversales , Valores de Referencia , Vitamina D , Vitaminas , Factores Socioeconómicos , Demografía
8.
BMC Bioinformatics ; 24(1): 474, 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-38097965

RESUMEN

With new advances in next generation sequencing (NGS) technology at reduced costs, research on bacterial genomes in the environment has become affordable. Compared to traditional methods, NGS provides high-throughput sequencing reads and the ability to identify many species in the microbiome that were previously unknown. Numerous bioinformatics tools and algorithms have been developed to conduct such analyses. However, in order to obtain biologically meaningful results, the researcher must select the proper tools and combine them to construct an efficient pipeline. This complex procedure may include tens of tools, each of which require correct parameter settings. Furthermore, an NGS data analysis involves multiple series of command-line tools and requires extensive computational resources, which imposes a high barrier for biologists and clinicians to conduct NGS analysis and even interpret their own data. Therefore, we established a public gut microbiome database, which we call Twnbiome, created using healthy subjects from Taiwan, with the goal of enabling microbiota research for the Taiwanese population. Twnbiome provides users with a baseline gut microbiome panel from a healthy Taiwanese cohort, which can be utilized as a reference for conducting case-control studies for a variety of diseases. It is an interactive, informative, and user-friendly database. Twnbiome additionally offers an analysis pipeline, where users can upload their data and download analyzed results. Twnbiome offers an online database which non-bioinformatics users such as clinicians and doctors can not only utilize to access a control set of data, but also analyze raw data with a few easy clicks. All results are customizable with ready-made plots and easily downloadable tables. Database URL: http://twnbiome.cgm.ntu.edu.tw/ .


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Humanos , Biología Computacional/métodos , Algoritmos , Bases de Datos Factuales , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Programas Informáticos
9.
J Magn Reson Imaging ; 57(2): 403-417, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35762913

RESUMEN

BACKGROUND: Although inspiratory muscle training (IMT) is an effective intervention for improving breath perception, brain mechanisms have not been studied yet. PURPOSE: To examine the effects of IMT on insula and default mode network (DMN) using resting-state functional MRI (RS-fMRI). STUDY TYPE: Prospective. POPULATION: A total of 26 healthy participants were randomly assigned to two groups as IMT group (n = 14) and sham IMT groups (n = 12). FIELD STRENGTH/SEQUENCE: A 3-T, three-dimensional T2* gradient-echo echo planar imaging sequence for RS-fMRI was obtained. ASSESSMENT: The intervention group received IMT at 60% and sham group received at 15% of maximal inspiratory pressure (MIP) for 8 weeks. Pulmonary and respiratory muscle function, and breathing patterns were measured. Groups underwent RS-fMRI before and after the treatment. STATISTICAL TESTS: Statistical tests were two-tailed P < 0.05 was considered statistically significant. Student's t test was used to compare the groups. One-sample t-test for each group was used to reveal pattern of functional connectivity. A statistical threshold of P < 0.001 uncorrected value was set at voxel level. We used False discovery rate (FDR)-corrected P < 0.05 cluster level. RESULTS: The IMT group showed more prominent alterations in insula and DMN connectivity than sham group. The MIP was significantly different after IMT. Respiratory rate (P = 0.344), inspiratory time (P = 0.222), expiratory time (P = 1.000), and inspiratory time/total breath time (P = 0.572) of respiratory patterns showed no significant change after IMT. All DMN components showed decreased, while insula showed increased activation significantly. DATA CONCLUSION: Differences in brain activity and connectivity may reflect improved ventilatory perception with IMT with a possible role in regulating breathing pattern by processing interoceptive signals. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 4.


Asunto(s)
Inhalación , Fuerza Muscular , Humanos , Voluntarios Sanos , Inhalación/fisiología , Estudios Prospectivos , Fuerza Muscular/fisiología , Ejercicios Respiratorios/métodos
10.
BMC Pulm Med ; 23(1): 66, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36793023

RESUMEN

BACKGROUND: Maximal inspiratory pressure (MIP) is currently the most commonly used measure for respiratory muscle strength (RMS) estimation, however, requires significant effort. Falsely low values are therefore common, especially in fatigue-prone subjects, such as neuromuscular disorder patients. In contrast, sniff nasal inspiratory pressure (SNIP) requires a short, sharp sniff; this is a natural manoeuvre, decreasing required effort. Consequently, it has been suggested that use of SNIP could confirm the accuracy of MIP measurements. However, no recent guidelines regarding the optimal method of SNIP measurement exist, and varied approaches have been described. OBJECTIVES: We compared SNIP values from three conditions, namely with 30, 60 or 90 s time intervals between repeats, the right (SNIPR) and left (SNIPL) nostril, and the contralateral nostril occluded (SNIPO) or non-occluded (SNIPNO). Additionally, we determined the optimal number of repeats for accurate SNIP measurement. METHOD: 52 healthy subjects (23 males) were recruited for this study, of which a subset of 10 subjects (5 males) completed tests comparing the time interval between repeats. SNIP was measured from functional residual capacity via a probe in one nostril, while MIP was measured from residual volume. RESULTS: There was no significant difference in SNIP depending on the interval between repeats (P = 0.98); subjects preferred the 30 s. SNIPO was significantly higher than SNIPNO (P < 0.00001) but SNIPL and SNIPR did not significantly differ (P = 0.60). There was an initial learning effect for the first SNIP test; SNIP did not decline during 80 repeats (P = 0.64). CONCLUSIONS: We conclude that SNIPO is a more reliable RMS indicator than SNIPNO, as there is reduced risk of RMS underestimation. Allowing subjects to choose which nostril to use is appropriate, as this did not significantly affect SNIP, but may increase ease of performance. We suggest that twenty repeats is sufficient to overcome any learning effect and that fatigue is unlikely after this number of repeats. We believe these results are important in aiding the accurate collection of SNIP reference value data in the healthy population.


Asunto(s)
Cavidad Nasal , Masculino , Humanos , Voluntarios Sanos , Presión , Pruebas de Función Respiratoria , Capacidad Residual Funcional
11.
Eur Spine J ; 32(2): 562-570, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36380010

RESUMEN

PURPOSE: To investigate the age-specific normative values of whole-body sagittal alignment (WBSA) including global balance parameters in healthy adults and to clarify the correlations among parameters based on the data from three international multicenter. METHODS: Three hundred and seventeen healthy subjects (range: 20-84 y.o., mean: 43.8 ± 14.7 y.o.) were included and underwent whole-body biplanar X-ray imaging system. Spinopelvic parameters and knee flexion (KF), the center of acoustic meatus (CAM)-hip axis (HA), and C2 dentiform apophyse (OD)-HA, the cranial center (Cr)-HA were evaluated radiologically. Sub-analysis for correlation analysis between age and parameters and among parameters was performed to investigate age-specific change and compensatory mechanisms. RESULTS: For age-related change, C2-7 angle (r = .326 for male/.355 for female), KF (r = .427/.429), and SVA (r = .234/.507) increased with age in both male and female group. For global parameters related to the center of the gravity, correlations with age were not significant (r = .120/.161 for OD-HA, r = .163/.275 for Cr-HA, r = .149/.262 for CAM-HA). Knee flexion (KF) has correlation with global parameters (i.e., SVA, OD-HA, Cr-HA, CAM-HA) and does not have correlations with local spinopelvic alignment. CONCLUSION: While several local alignment changes with age were found, changes in global parameters related to the center of gravity were kept relatively mild by the chain of compensation mechanisms including the lower limbs. We showed the normative values for a comprehensive WBSA in standing posture from large international healthy subjects' database.


Asunto(s)
Lordosis , Posición de Pie , Humanos , Adulto , Masculino , Femenino , Postura , Extremidad Inferior , Gravitación , Factores de Edad
12.
Biomed Chromatogr ; 37(6): e5613, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36849133

RESUMEN

Fluvoxamine is a selective serotonin reuptake inhibitor commonly used for various types of depression. The purpose of this study was to evaluate the pharmacokinetics and bioequivalence of fluvoxamine maleate tablets orally on an empty stomach and after a meal in healthy adult Chinese subjects and to preliminarily evaluate their safety. A single-center, randomized, open-label, two-drug, two-period, crossover, single-dose trial protocol was designed. Sixty healthy Chinese participants were enrolled and randomly classified into fasting (n = 30) and fed groups (n = 30). Each week, subjects took fluvoxamine maleate tablets 50 mg orally once as a test preparation or as a reference preparation on an empty stomach/after meals. To evaluate the bioequivalence of test and reference tables, the concentration of fluvoxamine maleate in the plasma of the subjects at different time points after administration was detected by liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters including the maximum plasma drug concentration (Cmax ), the time to reach maximum concentration (Tmax ), the area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t ) and the area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞ ) were calculated. Our data revealed that the 90% confidence intervals of the geometric mean ratio of the test or reference drugs for the Cmax , AUC0-t and AUC0-∞ fell within the acceptance range for bioequivalence (92.30-102.77%). The absorption, measured by AUC, did not show a significant difference between the two groups. There were no suspected serious adverse reactions or serious adverse events over the entire trial. Our results demonstrated that the test and reference tablets were bioequivalent under fasting and fed conditions.


Asunto(s)
Fluvoxamina , Adulto , Humanos , Área Bajo la Curva , China , Estudios Cruzados , Pueblos del Este de Asia , Ayuno , Fluvoxamina/farmacocinética , Voluntarios Sanos , Comprimidos , Espectrometría de Masas en Tándem , Equivalencia Terapéutica
13.
Psychol Health Med ; 28(2): 548-554, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36148490

RESUMEN

Whole-body magnetic resonance imaging (WB-MRI) is an all-in-one non-invasive technique that can be used also in early cancer diagnosis in asymptomatic individuals. The aim of this work was to identify the personal characteristics predicting the satisfaction for the WB-MRI in a sample of healthy subjects. Before undergoing a WB-MRI examination, 154 participants completed a questionnaire covering sociodemographics (age, gender, education), personality traits (agreeableness, conscientiousness, emotional stability, extroversion, openness), and expectations about the procedure (expected usefulness, risks, noise, lack of air, duration). After the examination, participants reported their satisfaction with the WB-MRI. Results showed that agreeableness had a significant and positive effect on satisfaction. Expectations about its utility and the possible noise had a positive effect on satisfaction. Expectations of lack of air showed a negative significant effect on satisfaction. Sociodemographics showed no significant effects. Our study confirmed the important impact of individuals' personality and expectations on satisfaction with the procedure. Moreover, it provides useful insights for developing consultations aimed at increasing the acceptability of the procedure.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias , Humanos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/psicología , Imagen de Cuerpo Entero/métodos , Imagen de Cuerpo Entero/psicología , Satisfacción Personal
14.
Int Ophthalmol ; 43(1): 51-61, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35821362

RESUMEN

OBJECTIVE: To assess the pupil response with a new handheld pupillometer in healthy subjects. METHODS: Sixty-four eyes of 32 healthy subjects (mean age 21.2 years) were tested. After dark adaptation for 10 min, pupil responses to 1 s red and blue light stimuli at 100 cd/m2 were measured in the order from right to left eyes with a 1 min interval. The initial pupil size (D1, mm), minimum pupil size (D2, mm), and constriction rate (CR, %) were obtained. Intra-examiner reproducibility was examined using the coefficient of variation (CV, %) and the Bland-Altman plot. Inter-examiner consistency was examined using the interclass correlation coefficient (ICC) and the agreements with a conventional device, by Pearson's correlation coefficient (r). RESULTS: The CV of all parameters have high reproducibility in the red (11.0-20.7%) and blue (5.5-12.1%) light stimuli. Bland-Altman plot analysis showed no bias with both light stimuli. "Almost perfect" and "substantial" correlations between the examiners were obtained in the red (ICC = 0.78-0.94) and blue (ICC = 0.71-0.89) light stimuli. "Excellent" and "good" correlations between the devices were obtained, except for the CR parameter in the red (D1: r = 0.90; p < 0.001, D2: 0.72; p < 0.001, and CR: 0.08; p = 0.631, respectively) and blue (D1: r = 0.87; p < 0.001, D2: 0.70; p < 0.001, and CR: 0.19; p = 0.274, respectively) light stimuli. CONCLUSION: The novel pupillometer is useful for assessing pupil response. However, because of their different constructions, the CR values cannot be compared directly between the devices.


Asunto(s)
Técnicas de Diagnóstico Oftalmológico , Pupila , Humanos , Adulto Joven , Adulto , Pupila/fisiología , Voluntarios Sanos , Reproducibilidad de los Resultados , Luz
15.
Eur J Neurosci ; 56(8): 5287-5298, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36017669

RESUMEN

Daily routines are getting increasingly stressful. Interestingly, associations between stress perception and amygdala volume, a brain region implicated in emotional behaviour, have been observed in both younger and older adults. Life stress, on the other hand, has become pervasive and is no longer restricted to a specific age group or life stage. As a result, it is vital to consider stress as a continuum across the lifespan. In this study, we investigated the relationship between perceived stress and amygdala size in 272 healthy participants with a broad age range. Participants were submitted to a structural magnetic resonance imaging (MRI) to extract amygdala volume, and the Perceived Stress Scale (PSS) scores were used as the independent variable in volumetric regressions. We found that perceived stress is positively associated with the right amygdala volume throughout life.


Asunto(s)
Amígdala del Cerebelo , Longevidad , Anciano , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/patología , Humanos , Imagen por Resonancia Magnética , Percepción , Estrés Psicológico/diagnóstico por imagen , Estrés Psicológico/psicología
16.
Invest New Drugs ; 40(4): 756-761, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35435627

RESUMEN

PURPOSE: Pyrotinib (PTN), an irreversible EGFR/HER2 dual tyrosine kinase inhibitor used for treating HER2-positive breast cancer, is primarily metabolized by cytochrome P450 (CYP)3A4 isozyme. Rifampicin (RIF) is a strong index CYP3A4 inducer. Therefore, the study aimed to elucidate the effect of RIF on PTN pharmacokinetics (PK) in Chinese healthy volunteers. METHODS: This phase I, open-label study investigated the effects of steady-state RIF administration on single-dose PK of PTN. 18 healthy participants were enrolled in this trial, who received a single oral dose of 400 mg of PTN on days 1 and 13, and were administrated with RIF 600 mg qd on days 6 through 16. RIF was administrated on an empty stomach, PTN were administrated orally in the morning 30 min after the start of the standard meal. Serial PK samples for PTN were collected on days 1 and days 13. Safety assessments were performed via clinical laboratory tests throughout the study. RESULTS: 18 subjects were enrolled and 16 completed the study. RIF significantly reduced PTN exposure: Geometric least-squares mean ratios (90% CI) for PTN + RIF versus PTN alone were 0.04 (0.034,0.049), 0.04 (0.037,0.054), and 0.11 (0.09,0.124) for area under the curve from time zero to time of last quantifiable concentration (AUC0 - t), area under the curve from time zero to infinity (AUC0-∞ ), and maximum observed plasma concentration(Cmax), respectively. PTN alone and co-administered with RIF was well tolerated. CONCLUSION: The exposure of PTN was significantly affected by the action of RIF. The findings suggest that concomitant strong CYP3A4 inducers should be avoided during PTN treatment. Concurrent administration of PTN and RIF was well tolerated.


Asunto(s)
Antineoplásicos , Rifampin , Acrilamidas , Aminoquinolinas , Antineoplásicos/efectos adversos , Área Bajo la Curva , Citocromo P-450 CYP3A/metabolismo , Inductores del Citocromo P-450 CYP3A/farmacocinética , Interacciones Farmacológicas , Voluntarios Sanos , Humanos , Maleatos , Inhibidores de Proteínas Quinasas/efectos adversos , Rifampin/efectos adversos
17.
Respir Res ; 23(1): 83, 2022 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-35382813

RESUMEN

INTRODUCTION: The 6-min walking distance (6MWD) test is a useful tool to obtain a measure of functional exercise capacity. However, reference equations have been mainly based on selected populations or small samples. The purpose of this study was to determine the reference equations to predict the 6MWD in a large Italian population sample of healthy adults of a wide age range. METHODS: In the frame of the multi case-control population-based study Gene Environment Interaction in Respiratory Diseases (GEIRD), we studied 530 healthy subjects: 287 females ranging 21-76 and 243 males ranging 21-78 years of age. We measured 6MWD, demographic and anthropometric data and collected the reported physical activity. A multiple linear regression model for the 6MWD included age, age2, height, weight and physical activity for both sex equations. The two-way interaction age-height and age-weight and the quadratic terms of weight and height were also tested for inclusion separately in each model. RESULTS: The mean ± SD for 6MWD was 581.4 ± 66.5 m (range 383-800 m) for females and 608.7 ± 80.1 m (range 410-875 m) for males. The reference equations were 6MWD = 8.10*age + 1.61*heightcm-0.99*weightkg + 22.58*active-0.10*age2 + 222.55 for females (R squared = 0.238) and 6MWD = 26.80*age + 8.46*heightcm-0.45*weightkg-2.54*active-0.06*age2-0.13*age*heightcm-890.18 for males (R squared = 0.159), where "active" is 1 when the subject is physically active, 0 otherwise. CONCLUSION: This study is the first to describe the 6MWD in a large population sample of young, middle aged and elderly healthy Caucasian subjects, and to determine reference equations. These findings will help to improve the evaluation of Italian and European patients with diseases influencing their functional capacity.


Asunto(s)
Estatura , Caminata , Adulto , Anciano , Niño , Preescolar , Prueba de Esfuerzo , Femenino , Voluntarios Sanos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estándares de Referencia , Valores de Referencia
18.
J Magn Reson Imaging ; 56(4): 1256-1264, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35146822

RESUMEN

BACKGROUND: Dual-venc 4D flow MRI, recently introduced for the assessment of intracranial hemodynamics, may provide a promising complementary approach to well-established tools such as transcranial Doppler ultrasound (TCD) and overcome some of their disadvantages. However, data comparing intracranial flow measures from dual-venc 4D flow MRI and TCD are lacking. PURPOSE: To compare cerebral blood flow velocity measures derived from dual-venc 4D flow MRI and TCD. STUDY TYPE: Prospective cohort. SUBJECTS: A total of 25 healthy participants (56 ± 4 years old, 44% female). FIELD STRENGTH/SEQUENCE: A 3 T/dual-venc 4D flow MRI using a time-resolved three-dimensional phase-contrast sequence with three-dimensional velocity encoding. ASSESSMENT: Peak velocity measurements in bilateral middle cerebral arteries (MCA) were quantified from dual-venc 4D flow MRI and TCD. The MRI data were quantified by two independent observers (S.M and Y.M.) and TCD was performed by a trained technician (A.L.M.). We assessed the agreement between 4D flow MRI and TCD measures, and the interobserver agreement of 4D flow MRI measurements. STATISTICAL TESTS: Peak velocity from MRI and TCD was compared using Bland-Altman analysis and coefficient of variance. Intraclass correlation coefficient (ICC) was used to assess MRI interobserver agreement. A P value < 0.05 was considered statistically significant. RESULTS: There was excellent interobserver agreement in dual-venc 4D flow MRI-based measurements of peak velocity in bilateral MCA (ICC = 0.97 and 0.96 for the left and right MCA, respectively). Dual-venc 4D flow MRI significantly underestimated peak velocity in the left and right MCA compared to TCD (bias = 0.13 [0.59, -0.33] m/sec and 0.15 [0.47, -0.17] m/sec, respectively). The coefficient of variance between dual-venc 4D flow MRI and TCD measurements was 26% for the left MCA and 22% for the right MCA. DATA CONCLUSION: There was excellent interobserver agreement for the assessment of MCA peak velocity using dual-venc 4D flow MRI, and ≤20% under-estimation compared with TCD. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.


Asunto(s)
Angiografía por Resonancia Magnética , Ultrasonografía Doppler Transcraneal , Velocidad del Flujo Sanguíneo/fisiología , Femenino , Hemodinámica , Humanos , Angiografía por Resonancia Magnética/métodos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
19.
Eur J Nutr ; 61(5): 2571-2583, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35220442

RESUMEN

PURPOSE: This study investigated whether UVB-exposed wheat germ oil (WGO) is capable to improving the vitamin D status in healthy volunteers. METHODS: A randomized controlled human-intervention trial in parallel design was conducted in Jena (Germany) between February and April. Ultimately, 46 healthy males and females with low mean 25-hydroxyvitamin D (25(OH)D) levels (34.9 ± 10.6 nmol/L) were randomized into three groups receiving either no WGO oil (control, n = 14), 10 g non-exposed WGO per day (- UVB WGO, n = 16) or 10 g WGO, which was exposed for 10 min to ultraviolet B-light (UVB, intensity 500-630 µW/cm2) and provided 23.7 µg vitamin D (22.9 µg vitamin D2 and 0.89 µg vitamin D3) (+ UVB WGO, n = 16) for 6 weeks. Blood was obtained at baseline, after 3 and 6 weeks and analyzed for serum vitamin D-metabolite concentrations via LC-MS/MS. RESULTS: Participants who received the UVB-exposed WGO were characterized by an increase of circulating 25(OH)D2 after 3 and 6 weeks of intervention. However, the 25(OH)D3 concentrations decreased in the + UVB WGO group, while they increased in the control groups. Finally, the total 25(OH)D concentration (25(OH)D2 + 25(OH)D3) in the + UVB WGO group was lower than that of the non-WGO receiving control group after 6 weeks of treatment. In contrast, circulating vitamin D (vitamin D2 + vitamin D3) was higher in the + UVB WGO group than in the control group receiving no WGO. CONCLUSION: UVB-exposed WGO containing 23.7 µg vitamin D can increase 25(OH)D2 levels but do no improve total serum levels of 25(OH)D of vitamin D-insufficient subjects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03499327 (registered, April 13, 2018).


Asunto(s)
Ergocalciferoles , Deficiencia de Vitamina D , 25-Hidroxivitamina D 2 , Calcifediol , Colecalciferol , Cromatografía Liquida , Femenino , Humanos , Masculino , Aceites de Plantas , Espectrometría de Masas en Tándem , Vitamina D/análogos & derivados , Vitaminas
20.
Acta Pharmacol Sin ; 43(12): 3130-3138, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35296780

RESUMEN

VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE). A total of 86 healthy subjects were enrolled in the studies. VV116 tablets or placebo were administered per protocol requirements. Blood samples were collected at the scheduled time points for pharmacokinetic analysis. 116-N1, the metabolite of VV116, was detected in plasma and calculated for the PK parameters. In SAD, AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25-800 mg. T1/2 was within 4.80-6.95 h. In MAD, the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116. In FE, the standard meal had no effect on Cmax and AUC of VV116. No serious adverse event occurred in the studies, and no subject withdrew from the studies due to adverse events. Thus, VV116 exhibited satisfactory safety and tolerability in healthy subjects, which supports the continued investigation of VV116 in patients with COVID-19.


Asunto(s)
COVID-19 , Nucleósidos , Humanos , SARS-CoV-2 , Voluntarios Sanos , Método Doble Ciego , Área Bajo la Curva , China , Administración Oral , Relación Dosis-Respuesta a Droga
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