Learning to predict pain: differences in people with persistent neck pain and pain-free controls
Background Learning to predict threatening events enables an organism to engage in protective behavior and prevent harm. Failure to differentiate between cues that truly predict danger and those that do not, however, may lead to indiscriminate fear and avoidance behaviors, which in turn may contribute to disability in people with persistent pain. We aimed to test whether people with persistent neck pain exhibit contingency learning deficits in predicting pain relative to pain-free, gender-and age-matched controls. Method We developed a differential predictive learning task with a neck pain-relevant scenario. During the acquisition phase, images displaying two distinct neck positions were presented and participants were asked to predict whether these neck positions would lead to pain in a fictive patient with persistent neck pain (see fictive patient scenario details in Appendix A). After participants gave their pain-expectancy judgment in the hypothetical scenario, the verbal outcome (PAIN or NO PAIN) was shown on the screen. One image (CS+) was followed by the outcome “PAIN”, while another image (CS−) was followed by the outcome “NO PAIN”. During the generalization phase, novel but related images depicting neck positions along a continuum between the CS+ and CS− images (generalization stimuli; GSs) were introduced to assess the generalization of acquired predictive learning to the novel images; the GSs were always followed by the verbal outcome “NOTES UNREADABLE” to prevent extinction learning. Finally, an extinction phase was included in which all images were followed by “NO PAIN” assessing the persistence of pain-expectancy judgments following disconfirming information. Results Differential pain-expectancy learning was reduced in people with neck pain relative to controls, resulting from patients giving significantly lower pain-expectancy judgments for the CS+, and significantly higher pain-expectancy judgments for the CS−. People with neck pain also demonstrated flatter generalization gradients relative to controls. No differences in extinction were noted. Discussion The results support the hypothesis that people with persistent neck pain exhibit reduced differential pain-expectancy learning and flatter generalization gradients, reflecting deficits in predictive learning. Contrary to our hypothesis, no differences in extinction were found. These findings may be relevant to understanding behavioral aspects of chronic pain.
Harvie et al. (2020) Learning to predict pain: differences in people with persistent neck pain and pain-free controls. PeerJ 8:e9345 https://doi.org/10.7717/peerj.9345
SPANXN2 functions a cell migration inhibitor in testicular germ cell tumor cells
Background SPANX family members are thought to play an important role in cancer progression. The SPANXN2 is a gene expressed mainly in normal testis, but its role in testicular germ cell tumors (TGCTs) has yet to be investigated. TGCT is one of the most common solid tumors in young men and is associated with poor prognosis; however, effective prognostic indicators remain elusive. Therefore, we investigated the role of SPANXN2 in TGCT development. Methods SPANXN2 expression levels were validated by quantitative real-time polymerase chain reaction (qRT-PCR) analyses of 14 TGCT samples and five adjacent normal tissue samples. SPANXN2 was transiently overexpressed in TGCT cells to study the consequences for cell function. The effects of SPANXN2 on cell migration were evaluated in transwell and wound healing assays. The effects on cloning ability were evaluated in colony formation assays. MTT assays and cell cycle analysis were used to detect the effects of SPANXN2 on cell proliferation. The expression levels of EMT- and AKT-related proteins in cells overexpressing SPANXN2 were analyzed by Western blotting. Results Compared with adjacent normal tissues, the Gene Expression Profiling Interactive Analysis database showed SPANXN2 expression was downregulated in TGCTs which was consistent with the qRT-PCR analysis. SPANXN2 overexpression reduced cell migration and colony formation capability and downregulated expression of EMT- and AKT-related proteins, Vimentin, Snail, AKT, and p-AKT. Conclusion Our results suggest that SPANXN2 regulates TGCT cell migration via EMT- and AKT-related proteins although its role in the occurrence and development of TGCT remains to be fully elucidated.
Zhu et al. (2020) SPANXN2 functions a cell migration inhibitor in testicular germ cell tumor cells. PeerJ 8:e9358 https://doi.org/10.7717/peerj.9358
Life in a harsh environment: the effects of age, sex, reproductive condition, and season on hair cortisol concentration in a wild non-human primate
Hair cortisol concentration (HCC) provides a long-term retrospective measure of hypothalamic–pituitary–adrenal axis activity, and is increasingly used to assess the life history, health and ecology of wild mammals. Given that sex, age, season and pregnancy influence HCC, and that it may indicate ongoing stress, we examined HCC in common marmosets (Callithrix jacchus) naturally inhabiting a hot and dry semi-desert like habitat, Caatinga, in northeastern Brazil. We trapped, measured, weighed, marked and collected shaved hair from the back of the neck of 61 wild marmosets during the wet and dry seasons. Using enzyme immunoassay, we found that HCC was higher in the dry season compared with the wet season among all age/sex classes. Females had significantly higher HCC than males, juveniles had higher HCC than adults, and reproductively active adult females and non-pregnant/non lactating adult females did not differ in HCC. There were no interaction effects of sex, age, group, or season on HCC. The magnitude of the effect of this extremely hot and dry environment (average yearly rainfall was only 271 mm) on HCC in common marmosets is difficult to ascertain as these animals are also experiencing a variety of other stressors. However, the elevated HCC seen in common marmosets during the 5–8 month dry season, suggests these primates face an extended period of heat, water and possibly nutritional stress, which appears to result in a high rate of juvenile mortality.
Garber et al. (2020) Life in a harsh environment: the effects of age, sex, reproductive condition, and season on hair cortisol concentration in a wild non-human primate. PeerJ 8:e9365 https://doi.org/10.7717/peerj.9365
Measurement of lower-limb asymmetry in professional rugby league: a technical note describing the use of inertial measurement units
Background Quantifying lower-limb load and asymmetry during team sport match-play may be important for injury prevention and understanding performance. However, current analysis methods of lower-limb symmetry during match-play employ wearable microtechnology that may not be best suited to the task. A popular microtechnology is global positioning systems (GPS), which are torso worn. The torso location, and the summary workload measures calculated by GPS are not suited to the calculation of lower-limb load. Instead, research grade accelerometers placed directly on the lower-limb may provide better load information than GPS. This study proposes a new technique to quantify external mechanical load, and lower-limb asymmetry during on-field team sport play using inertial measurement units. Methods Four professional rugby league players (Age: 23.4 ± 3.1 years; Height: 1.89 ± 0.05 m; Mass: 107.0 ± 12.9 kg) wore two accelerometers, one attached to each foot by the boot laces, during match simulations. Custom Matlab (R2017b, The Mathworks Inc, Natick, MA) code was used to calculate total time, area under the curve (AUC), and percentage of time (%Time) spent in seven acceleration categories (negative to very high, <0 g to >16 g), as well as minimum and maximum acceleration during match simulations. Lower-limb AUC and %Time asymmetry was calculated using the Symmetry Angle Equation, which does not require normalization to a reference leg. Results The range of accelerations experienced across all participants on the left and right sides were 15.68–17.53 g, and 16.18–17.69 g, respectively. Clinically significant asymmetry in AUC and %Time was observed for all but one participant, and only in negative (<0 g) and very high accelerations (>16 g). Clinically significant AUC differences in very high accelerations ranged from 19.10%–26.71%. Clinically significant %Time differences in negative accelerations ranged from 12.65%–25.14%, and in very high accelerations from 18.59%–25.30%. All participants experienced the most AUC at very low accelerations (2–4 g), and the least AUC at very high accelerations (165.00–194.00 AU vs. 0.32–3.59 AU). The %Time results indicated that all participants spent the majority of match-play (73.82–92.06%) in extremely low (0–2 g) to low (4–6 g) acceleration intensities, and the least %Time in very high accelerations (0.01%–0.05%). Discussion A wearable located on the footwear to measure lower-limb load and asymmetry is feasible to use during rugby league match-play. The location of the sensor on the boot is suited to minimize injury risk occurring from impact to the sensor. This technique is able to quantify external mechanical load and detect inter limb asymmetries during match-play at the source of impact and loading, and is therefore likely to be better than current torso based methods. The results of this study may assist in preparing athletes for match-play, and in preventing injury.
Glassbrook et al. (2020) Measurement of lower-limb asymmetry in professional rugby league: a technical note describing the use of inertial measurement units. PeerJ 8:e9366 https://doi.org/10.7717/peerj.9366
Assessing bias in demographic estimates from joint live and dead encounter models
Joint encounter (JE) models estimate demographic rates using live recapture and dead recovery data. The extent to which limited recapture or recovery data can hinder estimation in JE models is not completely understood. Yet limited data are common in ecological research. We designed a series of simulations using Bayesian multistate JE models that spanned a large range of potential recapture probabilities (0.01–0.90) and two reported mortality probabilities (0.10, 0.19). We calculated bias by comparing estimates against known probabilities of survival, fidelity and reported mortality. We explored whether sparse data (i.e., recapture probabilities <0.02) compromised inference about survival by comparing estimates from dead recovery (DR) and JE models using an 18-year data set from a migratory bird, the lesser snow goose (Anser caerulescens caerulescens). Our simulations showed that bias in probabilities of survival, fidelity and reported mortality was relatively low across a large range of recapture probabilities, except when recapture and reported mortality probabilities were both lowest. While bias in fidelity probability was similar across all recapture probabilities, the root mean square error declined substantially with increased recapture probabilities for reported mortality probabilities of 0.10 or 0.19, as expected. In our case study, annual survival probabilities for adult female snow geese were similar whether estimated with JE or DR models, but more precise from JE models than those from DR models. Thus, our simulated and empirical data suggest acceptably minimal bias in survival, fidelity or reported mortality probabilities estimated from JE models. Even a small amount of recapture information provided adequate structure for JE models, except when reported mortality probabilities were <0.10. Thus, practitioners with limited recapture data should not be discouraged from use of JE models. We recommend that ecologists incorporate other data types as frequently as analytically possible, since precision of focal parameters is improved, and additional parameters of interest can be estimated.
Weegman et al. (2020) Assessing bias in demographic estimates from joint live and dead encounter models. PeerJ 8:e9382 https://doi.org/10.7717/peerj.9382
Lateralized alpha oscillations are irrelevant for the behavioral retro-cueing benefit in visual working memory
The limited capacity of visual working memory (vWM) necessitates the efficient allocation of available resources by prioritizing relevant over irrelevant items. Retro-cues, which inform about the future relevance of items after encoding has already finished, can improve the quality of memory representations of the relevant items. A candidate mechanism of this retro-cueing benefit is lateralization of neural oscillations in the alpha-band, but its precise role is still debated. The relative decrease of alpha power contralateral to the relevant items has been interpreted as supporting inhibition of irrelevant distractors or as supporting maintenance of relevant items. Here, we aimed at resolving this debate by testing how the magnitude of alpha-band lateralization affects behavioral performance: does stronger lateralization improve the precision of the relevant memory or does it reduce the biasing influence of the irrelevant distractor? We found that it does neither: while the data showed a clear retro-cue benefit and a biasing influence of non-target items as well as clear cue-induced alpha-band lateralization, the magnitude of this lateralization was not correlated with any performance parameter. This finding may indicate that alpha-band lateralization, which is typically observed in response to mnemonic cues, indicates an automatic shift of attention that only coincides with, but is not directly involved in mnemonic prioritization.
Mössing et al. (2020) Lateralized alpha oscillations are irrelevant for the behavioral retro-cueing benefit in visual working memory. PeerJ 8:e9398 https://doi.org/10.7717/peerj.9398
Modelling fatality curves of COVID-19 and the effectiveness of intervention strategies
The main objective of the present article is twofold: first, to model the fatality curves of the COVID-19 disease, as represented by the cumulative number of deaths as a function of time; and second, to use the corresponding mathematical model to study the effectiveness of possible intervention strategies. We applied the Richards growth model (RGM) to the COVID-19 fatality curves from several countries, where we used the data from the Johns Hopkins University database up to May 8, 2020. Countries selected for analysis with the RGM were China, France, Germany, Iran, Italy, South Korea, and Spain. The RGM was shown to describe very well the fatality curves of China, which is in a late stage of the COVID-19 outbreak, as well as of the other above countries, which supposedly are in the middle or towards the end of the outbreak at the time of this writing. We also analysed the case of Brazil, which is in an initial sub-exponential growth regime, and so we used the generalised growth model which is more appropriate for such cases. An analytic formula for the efficiency of intervention strategies within the context of the RGM is derived. Our findings show that there is only a narrow window of opportunity, after the onset of the epidemic, during which effective countermeasures can be taken. We applied our intervention model to the COVID-19 fatality curve of Italy of the outbreak to illustrate the effect of several possible interventions.
Vasconcelos et al. (2020) Modelling fatality curves of COVID-19 and the effectiveness of intervention strategies. PeerJ 8:e9421 https://doi.org/10.7717/peerj.9421
Biochemical and toxicological effects of methanolic extract of Asparagus africanus Lam in Sprague-Dawley rats
Asparagus africanus Lam. is a plant used traditionally to treat different ailments. Currently, scanty information is available on its safety. The aim of this study is to determine the acute toxicity of the methanolic extract on vital organs and its associated biochemical parameters. Fifteen female Sprague-Dawley rats were divided into five groups. Group I served as normal control, groups II, III, IV, and V were orally administered single dose of crude extract dissolved in distilled water at 5 mg/kg BW, 50 mg/kg BW, 300 mg/kg BW and 2,000 mg/kg BW. Rats were observed for 14 days and body weights were recorded. On day 15, the rats were sacrificed and blood samples were collected for biochemical and haematological analyses, while the liver and kidneys were sampled for histopathological examination. Body weight and haematology parameters results showed significance difference (p < 0.05) among means of HGB, RDW, RBC, and MCHC; likewise, (p < 0.001) for WBC and platelet among treated groups. Histopathology result showed that kidneys appeared normal while livers were congested with mildly swollen hepatocytes and occasional binucleation. Focal lobular hepatitis was observed in all treated animals. However, hepatic enzymes were not significantly affected and no histopathological harmful effects were observed in kidney. In conclusion, methanolic extracts of A. africanus are safe up to 2,000 mg/kg BW. The obtained results could be used as a justification for the traditional application of the plant for treatment of various ailments.
El-Ishaq et al. (2020) Biochemical and toxicological effects of methanolic extract of Asparagus africanus Lam in Sprague-Dawley rats. PeerJ 8:e9138 https://doi.org/10.7717/peerj.9138
Organic eutrophication increases resistance of the pulsating soft coral Xenia umbellata to warming
Recent research indicates that hard corals in a process that is termed phase shift are often replaced by soft corals in reefs. The simultaneous occurrence of local (i.e. organic eutrophication as highly under-investigated parameter) and global (i.e. ocean warming) factors may facilitate these phase shifts as hard corals are negatively affected by both ocean warming and organic eutrophication. Knowledge about soft coral responses to environmental change remains incomplete, although these organisms are becoming important players in reefs. The present study thus investigated the individual and combined effects of organic eutrophication (as glucose addition) and warming on the ecological data of the pulsating soft coral Xenia umbellata. We assessed health status, growth and pulsation rates of soft corals in a 45 day aquarium experiment, with first manipulation of organic eutrophication (no, low, medium and high glucose addition) over 21 days followed by step-wise increases in water temperature from 26 to 32 °C over 24 days. Findings revealed that glucose addition did not affect health status, growth and pulsation rates of the investigated soft corals. Under simulated ocean warming, soft corals that had experienced organic eutrophication before, maintained significantly higher pulsation rates (averaging 22 beats per minute—bpm) and no mortality compared to the controls that showed a decrease of 56% (averaging 15 bpm) in pulsation rates and mortality of 30% at water temperatures of 32 °C compared to 26 °C. This apparently positive effect of organic eutrophication on the ecological data of soft corals under an ocean warming scenario decreased with increasing water temperature. This study thus indicates that (a) organic eutrophication as additional energy source up to a certain threshold may increase the resistance of soft corals to ocean warming and (b) pulsation rates of soft corals may be used as inexpensive, easily detectable, and non-invasive early warning indicator for ocean warming effects on benthic reef communities. When comparing findings of this study for soft corals with previous results for hard corals, it can be assumed that soft corals under the predicted increases of organic eutrophication and warming gain more and more competitive advantages. This may further facilitate phase shifts from hard to soft corals in warming reefs.
Vollstedt et al. (2020) Organic eutrophication increases resistance of the pulsating soft coral Xenia umbellata to warming. PeerJ 8:e9182 https://doi.org/10.7717/peerj.9182
A game-theoretic model of Monkeypox to assess vaccination strategies
Monkeypox (MPX) is a zoonotic disease similar to smallpox. Its fatality rate is about 11% and it is endemic to the Central and West African countries. In this paper, we analyze a compartmental model of MPX dynamics. Our goal is to see whether MPX can be controlled and eradicated by voluntary vaccinations. We show that there are three equilibria—disease free, fully endemic and previously neglected semi-endemic (with disease existing only among humans). The existence of semi-endemic equilibrium has severe implications should the MPX virus mutate to increased viral fitness in humans. We find that MPX is controllable and can be eradicated in a semi-endemic equilibrium by vaccination. However, in a fully endemic equilibrium, MPX cannot be eradicated by vaccination alone.
Bankuru et al. (2020) A game-theoretic model of Monkeypox to assess vaccination strategies. PeerJ 8:e9272 https://doi.org/10.7717/peerj.9272