•Enhanced variation in plasticity after correction of the lowermost percentile.•Large plasticity for anthesis-silking interval, grain yield and kernel number.•Reduced plasticity for developmental ...traits and kernel weight.•Mean inbreds phenotypic plasticity had a larger variation than that of hybrids.•Lack of relationship between traits heritability and their phenotypic plasticity.
Correct characterization of heritability and phenotypic plasticity (PP) is critical for breeding purposes. The latter refers to the variation range of a trait in response to changes in the environment and has been assessed as the difference between percentiles 10th (P10) and 90th (P90) of each trait, which does not reflect below the median (P50) variations to the same extent as the above the median ones. This inconsistency may affect the classification of stable (low PP) or plastic (high PP) given to traits, as well as their relative ranking and PP relationship with heritability. The objectives of current research were to evaluate corrected PP (PPC) variation in grain yield (GY) and related secondary traits among contrasting maize genotypic groups (inbreds and hybrids) grown under contrasting water regimes (WR) and nitrogen (N) availabilities. The relationship between PPC and broad-sense heritability (H2) was also assessed. Field experiments were conducted during three (N) or seven (WR) growing seasons at two mid-latitude environments of Argentina. Measured traits were days and thermal time to 50% anthesis (A50 and TTA) and to 50% silking (S50 and TTS), the anthesis-silking interval in days (ASID) and in TT (ASITT), plant height (Ph), prolificacy (Pr), GY, kernel numbers (KN), and kernel weight (KW). Values for percentiles 10th (P10), 50th (P50) and 90th (P90) of each trait were identified for each treatment combination. P50 was set to 1, and values obtained for P10 and P90 were expressed as ratios with P50. P10 was corrected (P10C= P50 – P50/P10) to reflect the below P50 variations to the same extent as those above P50. Corrected PP was estimated as PPC= P90 - P10C. P90 values of all traits corresponded to non-stressed plots whereas P10C values corresponded to stressed plots, except for ASIs (opposite trend). A large plasticity (PPC>mean PPC) was usually verified for ASIs, GY and KN. Mean inbreds PPC had a larger variation than mean hybrids PPC (+19% for WR and +29% for N), except for GY under contrasting WR (hybrids > inbreds). A common trend across all evaluated traits was the markedly larger effect on PPC of P10C than of P90, in agreement with the predominant representation of stressful conditions by the former and in contrast to previous studies where no correction was performed on P10. Our results demonstrated the lack of relationship between H2 and PP and improved current knowledge about the importance of environment modulation on PP of most expansion-related and production traits, highlighting the relevance of the evaluated resource (water or N) as well as of the genotypic group (hybrids or inbreds) on final phenotype expression.
The maturation status of seeds is fundamental at the harvest time to get high rates of germination and vigor. The aim of this study was to determine the effect of harvest time on the quality of ...pepper seeds. The trial was conducted in two bell type cultivars: Fyuco INTA and Lungo INTA. Fruits were harvested at 4, 5, 6, 7, 8 and 9 weeks after anthesis. Starting from the eighth week the average seed weight stabilized, coincidently with the change in the fruit colour to red. Germination percentage increased linearly as it increased the age of the seed. The electrical conductivity of the leachate was also stabilized in seeds got from fruit harvested from 8 weeks after anthesis, showing that they had reached physiological maturity. The results demonstrate to harvest the fruits of pepper cv Fyuco INTA and Lungo INTA with over 8 weeks of age after anthesis to reach high quality seeds.
We present a study of the chemoprotective effects of two caffeic acid phenethyl ester (CAPE)-related structures: LQM717 and LQM706. The modified resistant hepatocyte model in rats was used to study ...the chemoprevention of these CAPE analogues, which are inexpensive and easily obtained. In the liver cancer model used, we detected extensive necrosis and lipid peroxidation after 24 h, many altered hepatic foci, putatively preneoplastic lesions with γ-glutamyl transpeptidase staining after 30 days, and liver tumors at 12 months. We tested the effect of the CAPE analogues on necrosis, lipid peroxidation, proliferation, p65 activation, altered hepatic foci, and tumors. Both compounds exerted protective effects on lipid peroxidation, necrosis, cell proliferation, p65 activation, and preneoplastic lesions. Rats under a carcinogenic protocol showed a 52, 71.74, and 51.6% decrease in the number of preneoplastic nodules when pretreated with CAPE, LQM706, and LQM717, respectively. At 12 months after carcinogenic treatment, eight of eight rats developed liver cancer, whereas in the group of rats that received pretreatment with CAPE, LQM706, or LQM717, 62.5, 83.3, or 42.85%, respectively, had tumors. In conclusion, LQM717 has the potential to enhance chemoprotection activity much better than CAPE by markedly reducing the formation of liver cancers in this model, and this is a compound that is easy to obtain.
The replication of herpes simplex virus (HSV) type 1 and 2 in Vero cells is inhibited in the presence of enterocin CRL35 (ECRL), a bacteriocin produced by
Enterococcus faecium CRL35. Attempts to ...resolve the mode of action of ECRL indicate that virus adsorption and penetration are not affected. Instead, a late step of virus multiplication is hindered since the addition of 100
μg/ml of ECRL at 8
h post infection still causes a 90% inhibition of virus release. The effect of ECRL on HSV antigen expression was studied by immunofluorescence using a polyclonal serum and a monoclonal antibody against glycoprotein D (γ protein). These studies indicated that ECRL impeded the second round of infection, apparently as a consequence of the inhibition of glycoprotein D expression. The replication of syncytial mutants of HSV-1 was significantly inhibited at a ECRL concentration of 25
μg/ml. Both the percentage of fused cells and the polykaryocyte size were affected. Studies on the effect of ECRL on viral protein synthesis showed that in the presence of ECRL, HSV late γ proteins were not synthesized. From these findings, it is concluded that inhibition of HSV spreading by ECRL is due to the prevention of mainly late glycoprotein synthesis.
Seizure risk stratification is needed to boost inpatient seizure detection and to improve continuous electroencephalogram (cEEG) cost-effectiveness. 2HELPS2B can address this need but requires ...validation.
To use an independent cohort to validate the 2HELPS2B score and develop a practical guide for its use.
This multicenter retrospective medical record review analyzed clinical and EEG data from patients 18 years or older with a clinical indication for cEEG and an EEG duration of 12 hours or longer who were receiving consecutive cEEG at 6 centers from January 2012 to January 2019. 2HELPS2B was evaluated with the validation cohort using the mean calibration error (CAL), a measure of the difference between prediction and actual results. A Kaplan-Meier survival analysis was used to determine the duration of EEG monitoring to achieve a seizure risk of less than 5% based on the 2HELPS2B score calculated on first- hour (screening) EEG. Participants undergoing elective epilepsy monitoring and those who had experienced cardiac arrest were excluded. No participants who met the inclusion criteria were excluded.
The main outcome was a CAL error of less than 5% in the validation cohort.
The study included 2111 participants (median age, 51 years; 1113 men 52.7%; median EEG duration, 48 hours) and the primary outcome was met with a validation cohort CAL error of 4.0% compared with a CAL of 2.7% in the foundational cohort (P = .13). For the 2HELPS2B score calculated on only the first hour of EEG in those without seizures during that hour, the CAL error remained at less than 5.0% at 4.2% and allowed for stratifying patients into low- (2HELPS2B = 0; <5% risk of seizures), medium- (2HELPS2B = 1; 12% risk of seizures), and high-risk (2HELPS2B, ≥2; risk of seizures, >25%) groups. Each of the categories had an associated minimum recommended duration of EEG monitoring to achieve at least a less than 5% risk of seizures, a 2HELPS2B score of 0 at 1-hour screening EEG, a 2HELPS2B score of 1 at 12 hours, and a 2HELPS2B score of 2 or greater at 24 hours.
In this study, 2HELPS2B was validated as a clinical tool to aid in seizure detection, clinical communication, and cEEG use in hospitalized patients. In patients without prior clinical seizures, a screening 1-hour EEG that showed no epileptiform findings was an adequate screen. In patients with any highly epileptiform EEG patterns during the first hour of EEG (ie, a 2HELPS2B score of ≥2), at least 24 hours of recording is recommended.
Studies examining seizures (Szs) and epileptiform abnormalities (EAs) using continuous EEG in acute ischemic stroke (AIS) are limited. Therefore, we aimed to describe the prevalence of Sz and EA in ...AIS, its impact on anti-Sz drug management, and association with discharge outcomes.
The study included 132 patients with AIS who underwent continuous EEG monitoring >6 hours. Continuous EEG was reviewed for background, Sz and EA (lateralized periodic discharges LPD, generalized periodic discharges, lateralized rhythmic delta activity, and sporadic epileptiform discharges). Relevant clinical, demographic, and imaging factors were abstracted to identify risk factors for Sz and EA. Outcomes included all-cause mortality, functional outcome at discharge (good outcome as modified Rankin scale of 0-2 and poor outcome as modified Rankin scale of 3-6) and changes to anti-Sz drugs (escalation or de-escalation).
The frequency of Sz was 7.6%, and EA was 37.9%. Patients with Sz or EA were more likely to have cortical involvement (84.6% vs. 67.5% P = 0.028). Among the EAs, the presence of LPD was associated with an increased risk of Sz (25.9% in LPD vs. 2.9% without LPD, P = 0.001). Overall, 21.2% patients had anti-Sz drug changes because of continuous EEG findings, 16.7% escalation and 4.5% de-escalation. The presence of EA or Sz was not associated with in-hospital mortality or discharge functional outcomes.
Despite the high incidence of EA, the rate of Sz in AIS is relatively lower and is associated with the presence of LPDs. These continuous EEG findings resulted in anti-Sz drug changes in one-fifth of the cohort. Epileptiform abnormality and Sz did not affect mortality or discharge functional outcomes.
Recent studies indicate accelerated ageing processes, shorter telomere length and poorer cognitive functioning in patients with bipolar disorder. The neurobiology underlying cognitive function in ...bipolar disorder is yet to be established. We anticipated that accelerated ageing as indicated by shortened telomere length, would be associated with reduced cognitive performance in bipolar disorder, particularly for ageing sensitive functions such as memory and learning.
The study consisted of 647 participants (bipolar disorder n = 246 and healthy controls n = 401). All participants underwent a standardized neuropsychological test battery, including working memory, executive functioning, processing speed, verbal learning, and verbal memory. Leucocyte telomere length was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio). The T/S ratio was used as an estimate of the mean telomere length of each participant. All analyses were adjusted for medication, Daily Defined Dose (DDD), chronological age, sex, and ethnicity.
Patients had shorter telomere lengths than healthy controls (Cohen's d = 0.11, p = 0.01). Within patients', a positive association was observed for verbal learning and telomere length (β = 0.14, p = 0.025), along with a trend for verbal memory and telomere length (β = 0.11, p = 0.07). No other associations were observed for telomere length and cognitive functioning in the patient or the control group (p > 0.1).
Our study may suggest poorer brain health in bipolar disorder as indexed by shorter telomere length and reduced learning correlates. However, the role of telomere length on cognitive functioning in bipolar disorder seems limited.
•Bipolar patients had shorter telomere lengths than healthy controls.•Within patients', shorter telomere length was associated with poor verbal learning.•No other significant findings were observed between telomere length and cognition.
Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are ...scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance. There exists a critical unmet need for an automated method to classify SZs and other SZ-like events with expert-level reliability. This study was conducted to develop and validate a computer algorithm that matches the reliability and accuracy of experts in identifying SZs and SZ-like events, known as "ictal-interictal-injury continuum" (IIIC) patterns on EEG, including SZs, lateralized and generalized periodic discharges (LPD, GPD), and lateralized and generalized rhythmic delta activity (LRDA, GRDA), and in differentiating these patterns from non-IIIC patterns.
We used 6,095 scalp EEGs from 2,711 patients with and without IIIC events to train a deep neural network,
, to perform IIIC event classification. Independent training and test data sets were generated from 50,697 EEG segments, independently annotated by 20 fellowship-trained neurophysiologists. We assessed whether
performs at or above the sensitivity, specificity, precision, and calibration of fellowship-trained neurophysiologists for identifying IIIC events. Statistical performance was assessed by the calibration index and by the percentage of experts whose operating points were below the model's receiver operating characteristic curves (ROCs) and precision recall curves (PRCs) for the 6 pattern classes.
matches or exceeds most experts in classifying IIIC events based on both calibration and discrimination metrics. For SZ, LPD, GPD, LRDA, GRDA, and "other" classes,
exceeds the following percentages of 20 experts-ROC: 45%, 20%, 50%, 75%, 55%, and 40%; PRC: 50%, 35%, 50%, 90%, 70%, and 45%; and calibration: 95%, 100%, 95%, 100%, 100%, and 80%, respectively.
is the first algorithm to match expert performance in detecting SZs and other SZ-like events in a representative sample of EEGs. With further development,
may thus be a valuable tool for an expedited review of EEGs.
This study provides Class II evidence that among patients with epilepsy or critical illness undergoing EEG monitoring,
can differentiate (IIIC) patterns from non-IIIC events and expert neurophysiologists.
Background/Objectives
Epileptiform abnormalities (EA) on continuous electroencephalography (cEEG) are associated with increased risk of acute seizures; however, data on their association with ...development of long-term epilepsy are limited. We aimed to investigate the association of EA in patients with acute brain injury (ABI): ischemic or hemorrhagic stroke, traumatic brain injury, encephalitis, or posterior reversible encephalopathy syndrome, and subsequent development of epilepsy.
Methods
This was a retrospective, single-center study of patients with ABI who had at least 6 hours of cEEG during the index admission between 1/1/2017 and 12/31/2018 and at least 12 months of follow-up. We compared patients with EAs; defined as lateralized periodic discharges (LPDs), lateralized rhythmic delta activity (LRDA), generalized periodic discharges (GPDs), and sporadic interictal epileptiform discharges (sIEDs) to patients without EAs on cEEG. The primary outcome was the new development of epilepsy, defined as the occurrence of spontaneous clinical seizures following hospital discharge. Secondary outcomes included time to development of epilepsy and use of anti-seizure medications (ASMs) at the time of last follow-up visit.
Results
One hundred and one patients with ABI met study inclusion criteria. Thirty-one patients (30.7%) had EAs on cEEG. The median (IQR) time to cEEG was 2 (1–5) days. During a median (IQR) follow-up period of 19.1 (16.2–24.3) months, 25.7% of patients developed epilepsy; the percentage of patients who developed epilepsy was higher in those with EAs compared to those without EAs (41.9% vs. 18.6%,
p
= 0.025). Patients with EAs were more likely to be continued on ASMs during follow-up compared to patients without EAs (67.7% vs. 38.6%,
p
= 0.009). Using multivariable Cox regression analysis, after adjusting for age, mental status, electrographic seizures on cEEG, sex, ABI etiology, and ASM treatment on discharge, patients with EAs had a significantly increased risk of developing epilepsy compared to patients without EA (hazard ratio 3.39; 95% CI 1.39–8.26;
p
= 0.007).
Conclusions
EAs on cEEG in patients with ABI are associated with a greater than three-fold increased risk of new-onset epilepsy. cEEG findings in ABI may therefore be a useful risk stratification tool for assessing long-term risk of seizures and serve as a biomarker for new-onset epilepsy.
The validity of brain monitoring using electroencephalography (EEG), particularly to guide care in patients with acute or critical illness, requires that experts can reliably identify seizures and ...other potentially harmful rhythmic and periodic brain activity, collectively referred to as "ictal-interictal-injury continuum" (IIIC). Previous interrater reliability (IRR) studies are limited by small samples and selection bias. This study was conducted to assess the reliability of experts in identifying IIIC.
This prospective analysis included 30 experts with subspecialty clinical neurophysiology training from 18 institutions. Experts independently scored varying numbers of ten-second EEG segments as "seizure (SZ)," "lateralized periodic discharges (LPDs)," "generalized periodic discharges (GPDs)," "lateralized rhythmic delta activity (LRDA)," "generalized rhythmic delta activity (GRDA)," or "other." EEGs were performed for clinical indications at Massachusetts General Hospital between 2006 and 2020. Primary outcome measures were pairwise IRR (average percent agreement PA between pairs of experts) and majority IRR (average PA with group consensus) for each class and beyond chance agreement (κ). Secondary outcomes were calibration of expert scoring to group consensus, and latent trait analysis to investigate contributions of bias and noise to scoring variability.
Among 2,711 EEGs, 49% were from women, and the median (IQR) age was 55 (41) years. In total, experts scored 50,697 EEG segments; the median range number scored by each expert was 6,287.5 1,002, 45,267. Overall pairwise IRR was moderate (PA 52%, κ 42%), and majority IRR was substantial (PA 65%, κ 61%). Noise-bias analysis demonstrated that a single underlying receiver operating curve can account for most variation in experts' false-positive vs true-positive characteristics (median range of variance explained (Formula: see text): 95 93, 98%) and for most variation in experts' precision vs sensitivity characteristics (Formula: see text: 75 59, 89%). Thus, variation between experts is mostly attributable not to differences in expertise but rather to variation in decision thresholds.
Our results provide precise estimates of expert reliability from a large and diverse sample and a parsimonious theory to explain the origin of disagreements between experts. The results also establish a standard for how well an automated IIIC classifier must perform to match experts.
This study provides Class II evidence that an independent expert review reliably identifies ictal-interictal injury continuum patterns on EEG compared with expert consensus.
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