Objective: To understand awareness and fluctuations of awareness in Alzheimer’s disease (AD), it is fruitful to consider the objects of awareness, e.g., cognitive functioning or recognition of the disease, as well as the mechanisms and modes of expression underlying awareness. With a holistic and discourse-centered approach, we aimed to identify different awareness profiles and test whether these profiles were stable or whether transitions from one profile to another occurred over short time intervals.Methods: Twenty-eight residents of nursing homes with a diagnosis of AD participated in four semistructured interviews at biweekly intervals. These interviews were cluster analyzed to determine profiles of awareness. A Markov chain was applied to model their fluctuation.Results: Five awareness profiles were observed that differed in terms of objects and underlying processes. Awareness proved to be quite stable for four of the five profiles. Interindividual variability in awareness was also observed through numerous different trajectories that were identified.Discussion: Self-awareness and disease awareness are characterized by profiles that vary subtly between individuals. Fluctuations in awareness underscore the need to employ assessment intervals that closely reflect daily life in institutions.
Determination of Gluten Immunogenic Peptides (GIP) in feces is a direct tool for gluten exposure detection. The sensitivity of GIP detection methods for cases of unintentional low gluten intakes is unknown. We studied the interindividual variability in the kinetic of excretion under homogeneously controlled dietary conditions, and the sensitivity of fecal GIP tests after low amounts of punctual gluten ingestions.
Participants (n = 20) followed the same gluten-free menu for 12 days in which two separated doses of gluten (50 mg and 2 g) were ingested and all the depositions were collected. GIP from stool samples were analyzed by ELISA and lateral flow immunoassay (LFIA) tests.
Most participants had detectable GIP after 50 mg and 2 g gluten ingestions using ELISA test (72.2% and 95%, respectively), whereas the LFIA test showed less sensitivity (22.2% and 80%, respectively). GIP were detected at higher either frequency or concentration in the range of 12–36 h after 50 mg intake, and 12–84 h after 2 g consumption. Considering this period, diagnostic sensitivity of GIP detection after a single 50 mg ingestion may be significatively increased analyzing three stool samples per individual. High variability among participants was found in the time and amount of GIP excretion; however, some individuals showed common patterns for both gluten intakes.
Sporadic gluten exposure detection may require several fecal samples to achieve level of sensitivity above 90%. Interindividual variability in the dynamic of GIP excretion may suggest patterns of gluten metabolism.
Epileptic seizure prediction is one of the most used therapeutic adjuvant strategies for drug-resistant epilepsy. Conventional methods are usually trained and tested on the same patient due to the interindividual variability. However, the challenging problem of the domain shift between different subjects remains unsolved, resulting in low prevalence of clinical application. In this study, a generic model based on the domain adaptation (DA) technique is proposed to alleviate such problems. Ensemble learning is employed by developing a hierarchical vote collective of seven DA modules over multi-modality data, such that the predictive performance is improved by training multiple models. Moreover, to increase the feasibility of its implementation, this study mimics the data distribution of clinical sampling and tests the model under this simulated realistic condition. Based on the performance of seven subnetworks, the applicability of each DA algorithm for seizure prediction is evaluated, which is the first study that provides the assessment. Experimental results on both intracranial and scalp EEG databases demonstrate that this method can reduce the domain gap effectively compared with previous studies.
The efficacy of anti-obesity drugs usually does not consider the high degree of interindividual variability in responses to the drug which could affect the decision to withdraw the drug early due to ineffectiveness or to continue therapy according to specific expectations of success. The aim of this study was to analyze body weight loss in kilograms during the first month (1 mo-BWLkg) of treatment with 30 mg phentermine and development of tolerance to phentermine, on its 6-month efficacy. One hundred sixty-six subjects with obesity were individually or jointly analyzed in the study. Subjects with 1 mo-BWLkg of <1 kg, 1–3 kg, 3–5 kg, and ≥5 kg reached 6-month mean percentage body weight reductions (BWR%) of approximately 3%, 5%, 10%, and 15%, respectively. Development of late tolerance (4–6 months) to phentermine had a lower impact than early tolerance (2–3 months). Subjects with 1 mo-BWLkg <3 kg who developed early tolerance did not achieve relevant BWR% (≥5%) at month 6, while the rest of the subgroups achieved increasing and progressive BWR%, according to their 1 mo-BWLkg range and time of onset of tolerance. The 1 mo-BWLkg and development of tolerance to phentermine could be useful to predict the expected 6-month efficacy trends in obese patients treated with 30 mg phentermine.
AbstractThe global virtual reality (VR) market is significantly expanding and being challenged with an increased demand owing to COVID-19. Unfortunately, VR is not useful for everyone due to large interindividual variability existing in VR suitability. To understand the neurobiological basis of this variability, we obtained neural structural and functional data from the participants using 3T magnetic resonance imaging. The participants completed one of two tasks (sports training or cognitive task) using VR, which differed in the time scale (months/minutes) and domain (motor learning/attention task). Behavioral results showed that some participants improved their motor skills in the real world after 1-month training in the virtual space or obtained high scores in the 3D attention task (high suitability for VR), whereas others did not (low suitability for VR). Brain structure analysis revealed that the structural properties of the superior and inferior parietal lobes contain information that can predict an individual’s suitability for VR.
AbstractTo fully understand the mechanisms governing learning and memory, animal models with minor interindividual variability and higher cognitive function are required. THA rats established by crossing those with high learning capacity exhibit excellent learning and memory abilities, but the factors underlying their phenotype are completely unknown. In the current study, we compare the hippocampi of parental strain Wistar rats to those of THA rats via metabolomic analysis in order to identify molecules specific to the THA rat hippocampus. Higher branched-chain amino acid (BCAA) levels and enhanced activation of BCAA metabolism-associated enzymes were observed in THA rats, suggesting that acetyl-CoA and acetylcholine are synthesized through BCAA catabolism. THA rats maintained high blood BCAA levels via uptake of BCAAs in the small intestine and suppression of BCAA catabolism in the liver. Feeding THA rats with a BCAA-reduced diet decreased acetylcholine levels and learning ability, thus, maintaining high BCAA levels while their proper metabolism in the hippocampus is the mechanisms underlying the high learning ability in THA rats. Identifying appropriate BCAA nutritional supplements and activation methods may thus hold potential for the prevention and amelioration of higher brain dysfunction, including learning disabilities and dementia.
This study aimed to measure protein deposition (PD) in pigs fed with daily tailored diets where either dietary lysine (Lys) or threonine (Thr) were provided at independent levels (ignoring an ideal ratio). A total of 95 growing pigs (35 kg body weight (BW)) with electronic ear tags granting them access to automatic feeders were randomly assigned to treatments. The setup was an unbalanced 2 × 5 factorial arrangement with Lys and Thr provided at five levels (i.e., 60%, 80%, 100%, 120%, and 140% of the estimated individual requirements of Lys and Thr), resulting in 25 treatments for 21 days. The observed PD variation to Lys and Thr provisions was large, with Lys and Thr intake explaining only 11% of the variation. Cluster analysis discriminated pigs with low (167 g/d, n = 16), medium (191 g/d, n = 38), and high (213 g/d, n = 37) PD, but with a similar amino acid intake. Differences in PD were associated with differences in nutrient efficiency of utilization. Providing Lys and Thr in a factorial mode, ignoring an ideal ratio, did not decrease the variability in PD. Future research efforts should focus on identifying and investigating the sources of interindividual variability—a necessary step before final recommendations can be made for AA in precision-fed pigs.
Haemolysis of serum samples is the leading cause of preanalytical errors in clinical laboratories. Little is known about the potential alterations in the concentrations of mineral elements in haemolyzed serum and the phenomenon has not been specifically studied in bovine serum samples. We investigate how haemolysis affects the mineral content of bovine samples. We used ICP-MS to measure the concentrations of 12 mineral elements (Ca, Co, Cr, Cu, Fe, Mg, Mn, Mo, Ni, P, Se and Zn) in bovine whole blood, serum and gradually haemolyzed samples and observed significant differences between the different types of samples, particularly in the Fe and Zn concentrations. However, in practice, the high interindividual variability makes it difficult to establish whether a given value corresponds to normal or haemolyzed samples. In response to this problem, we propose to consider that a result is significantly biased when the haemolysis threshold (the degree of haemolysis above which the concentration of an element in serum is significantly altered) of a given element is surpassed. The haemolysis threshold values for the different elements considered were found as follows: 0.015 g Hb L−1 for Fe, 2 g for Zn, 4 g for Cr and 8 g for Ca, Se and Mo.