Project description:In this review, we have collected the existing data on the bioactivity of antioxidants (N-acetylcysteine, polyphenols, vitamin C) which are traditionally used in experimental biology and, in some cases, in the clinic. Presented data show that, despite the capacity of these substances to scavenge peroxides and free radicals in cell-free systems, their ability to exhibit these properties in vivo, upon pharmacological supplementation, has not been confirmed so far. Their cytoprotective activity is explained mainly by the ability not to suppress, but to activate multiple redox pathways, which causes biphasic hormetic responses and highly pleiotropic effects in cells. N-acetylcysteine, polyphenols, and vitamin C affect redox homeostasis by generating low-molecular-weight redox-active compounds (H2O2 or H2S), known for their ability to stimulate cellular endogenous antioxidant defense and promote cytoprotection at low concentrations but exert deleterious effects at high concentrations. Moreover, the activity of antioxidants strongly depends on the biological context and mode of their application. We show here that considering the biphasic and context-dependent response of cells on the pleiotropic action of antioxidants can help explain many of the conflicting results obtained in basic and applied research and build a more logical strategy for their use.
Project description:Humans are constantly exposed to a rich tapestry of visual information in a potentially changing environment. To cope with the computational burden this engenders, our perceptual system must use prior context to simultaneously prioritise stimuli of importance and suppress irrelevant surroundings. This study investigated the influence of prediction and attention in visual perception by investigating event-related potentials (ERPs) often associated with these processes, N170 and N2pc for prediction and attention, respectively. A contextual trajectory paradigm was used which violated visual predictions and neglected to predetermine areas of spatial interest, to account for the potentially unpredictable nature of a real-life visual scene. Participants (N = 36) viewed a visual display of cued and non-cued shapes rotating in a five-step predictable trajectory, with the fifth and final position of either the cued or non-cued shape occurring in a predictable or unpredictable spatial location. To investigate the predictive coding theory of attention we used factors of attention and prediction, whereby attention was manipulated as either cued or non-cued conditions, and prediction manipulated in either predictable or unpredictable conditions. Results showed both enhanced N170 and N2pc amplitudes to unpredictable compared to predictable stimuli. Stimulus cueing status also increased N170 amplitude, but this did not interact with stimulus predictability. The N2pc amplitude was not affected by stimulus cueing status. In accordance with previous research these results suggest the N170 is in part a visual prediction error response with respect to higher-level visual processes, and furthermore the N2pc may index attention reorientation. The results demonstrate prior context influences the sensitivity of the N170 and N2pc electrophysiological responses. These findings add further support to the role of N170 as a prediction error signal and suggest that the N2pc may reflect attentional reorientation in response to unpredicted stimulus locations.
Project description:Coprolites, or mummified feces, are valuable sources of information on ancient cultures as they contain ancient DNA (aDNA). In this study, we analyzed ancient plant DNA isolated from coprolites belonging to two pre-Columbian cultures (Huecoid and Saladoid) from Vieques, Puerto Rico, using shotgun metagenomic sequencing to reconstruct diet and lifestyles. We also analyzed DNA sequences of putative phytopathogenic fungi, likely ingested during food consumption, to further support dietary habits. Our findings show that pre-Columbian Caribbean cultures had a diverse diet consisting of maize (Zea mays), sweet potato (Ipomoea batatas), chili peppers (Capsicum annuum), peanuts (Arachis spp.), papaya (Carica papaya), tomato (Solanum lycopersicum) and, very surprisingly cotton (Gossypium barbadense) and tobacco (Nicotiana sylvestris). Modelling of putative phytopathogenic fungi and plant interactions confirmed the potential consumption of these plants as well as edible fungi, particularly Ustilago spp., which suggest the consumption of maize and huitlacoche. These findings suggest that a variety of dietary, medicinal, and hallucinogenic plants likely played an important role in ancient human subsistence and societal customs. We compared our results with coprolites found in Mexico and the United States, as well as present-day faeces from Mexico, Peru, and the United States. The results suggest that the diet of pre-Columbian cultures resembled that of present-day hunter-gatherers, while agriculturalists exhibited a transitional state in dietary lifestyles between the pre-Columbian cultures and larger scale farmers and United States individuals. Our study highlights differences in dietary patterns related to human lifestyles and provides insight into the flora present in the pre-Columbian Caribbean area. Importantly, data from ancient fecal specimens demonstrate the importance of ancient DNA studies to better understand pre-Columbian populations.
Project description:BackgroundFrom November 2014 to November 2015, an experiment in French community pharmacies replaced traditional pre-packed boxes by per-unit dispensing of pills in the exact numbers prescribed, for 14 antibiotics.MethodsA cluster randomised control trial was carried out in 100 pharmacies. 75 pharmacies counted out the medication by units (experimental group), the other 25 providing the treatment in the existing pharmaceutical company boxes (control group). Data on patients under the two arms were compared to assess the environmental, economic and health effects of this change in drug dispensing. In particular, adherence was measured indirectly by comparing the number of pills left at the end of the prescribed treatment.ResultsOut of the 1185 patients included during 3 sessions of 4 consecutive weeks each, 907 patients experimented the personalized delivery and 278 were assigned to the control group, consistent with a 1/3 randomization-rate at the pharmacy level. 80% of eligible patients approved of the per-unit dispensing of their treatment. The initial packaging of the drugs did not match with the prescription in 60% of cases and per-unit dispensing reduced by 10% the number of pills supplied. 13.1% of patients declared that they threw away pills residuals instead of recycling-no differences between groups. Finally, per-unit dispensing appeared to improve adherence to antibiotic treatment (marginal effect 0.21, IC 95, 0.14-0.28).ConclusionsSupplying antibiotics per unit is not only beneficial in terms of a reduced number of pills to reimburse or for the environment (less pills wasted and non-recycled), but also has a positive and unexpected impact on adherence to treatment, and thus on both individual and public health.
Project description:Motor inhibition is a key control mechanism that allows humans to rapidly adapt their actions in response to environmental events. One of the hallmark signatures of rapidly exerted, reactive motor inhibition is the non-selective suppression of cortico-spinal excitability (CSE): unexpected sensory stimuli lead to a suppression of CSE across the entire motor system, even in muscles that are inactive. Theories suggest that this reflects a fast, automatic, and broad engagement of inhibitory control, which facilitates behavioral adaptations to unexpected changes in the sensory environment. However, it is an open question whether such non-selective CSE suppression is truly due to the unexpected nature of the sensory event, or whether it is sufficient for an event to be merely infrequent (but not unexpected). Here, we report data from two experiments in which human subjects experienced both unexpected and expected infrequent events during a two-alternative forced-choice reaction time task while CSE was measured from a task-unrelated muscle. We found that expected infrequent events can indeed produce non-selective CSE suppression-but only when they occur during movement initiation. In contrast, unexpected infrequent events produce non-selective CSE suppression relative to frequent, expected events even in the absence of movement initiation. Moreover, CSE suppression due to unexpected events occurs at shorter latencies compared to expected infrequent events. These findings demonstrate that unexpectedness and stimulus infrequency have qualitatively different suppressive effects on the motor system. They also have key implications for studies that seek to disentangle neural and psychological processes related to motor inhibition and stimulus detection.
Project description:Crystallization is in many cases a critical step for solving the three-dimensional structure of a protein molecule. Determining which set of chemicals to use in the initial screen is typically agnostic of the protein under investigation; however, crystallization efficiency could potentially be improved if this were not the case. Previous work has assumed that sequence similarity may provide useful information about appropriate crystallization cocktails; however, the authors are not aware of any quantitative verification of this assumption. This research investigates whether, given current information, one can detect any correlation between sequence similarity and crystallization cocktails. BLAST was used to quantitate the similarity between protein sequences in the Protein Data Bank, and this was compared with three estimations of the chemical similarities of the respective crystallization cocktails. No correlation was detected between proteins of similar (but not identical) sequence and their crystallization cocktails, suggesting that methods of determining screens based on this assumption are unlikely to result in screens that are better than those currently in use.
Project description:Here we performed a before-after ABA-design study in police cadets (N = 82) to compare the effects of unexpected (event-triggered) and expected (anticipatory) stressors on aggression. On the first day of the study, participants filled in the Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale (BIS) and were fitted with heart rate (HR) monitors, which remained attached till the end of the study. On day 2, they were instructed to perform a police intervention in a realistic training environment. The intervention was preceded either by a warning or by a reassuring audio recording that forecasted violent or routine interventions, respectively. Both groups encountered hostile suspects at the intervention site, the behavior of which, however, did not justify the use of force e.g., aggression. The warning resulted in a gradually developing anticipatory stress as shown by HRs. Cadets exposed to the reassuring audio recording showed minimal anticipatory stress but responded to the hostile suspects by an abrupt increase in HRs, which was missing in the warned group. The magnitude of HR responses was similar in the two groups, only their temporal evolution differed. Although aggression showed some associations with BPAQ and BIS scores, the main predictors of behavior were HR changes according to a Multiple Regression analysis. The gradually developing anticipatory stress was associated with low, whereas the abrupt increase in HRs was associated with high aggression. Our findings suggest that the anticipation of a stressful event improves behavioral control whereas an unexpected stress strongly promotes aggression.
Project description:Background: Coronavirus disease 2019 prompted the rapid adoption of telehealth to provide physical therapy. Patients' perceptions about telehealth physical therapy are mostly unknown. This study describes perceptions of telehealth physical therapy among patients with chronic low back pain (LBP). Methods: This study surveyed participants in an ongoing multisite clinical trial of nonpharmacological LBP treatments. Participants were asked about their willingness to use telehealth for physical therapy and with other providers and completed the PROMIS-29. Results: Surveys were received from 102 participants (mean age = 48.5 [standard deviation; SD = 11.6]). Thirty-six (35.3%) expressed willingness to receive telehealth physical therapy, 22 were neutral (21.6%), and 44 were unwilling (43.1%). The percentage expressing willingness for telehealth physical therapy was lower than it was for family medicine (p < 0.001) or mental health (p < 0.001). Older (p = 0.049) and Black participants (p = 0.01) more likely expressed willingness to use telehealth for physical therapy. Conclusion: Education and familiarity may help patients view telehealth physical therapy more favorably. Clinical Trial Registration (clinicaltrials.gov NCT03859713).