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Simple Summary: The fetal growth pattern in twin pregnancies is usually affected by the sex of the co-twin pairs, among other factors, with females being lighter than males at birth. We aimed to determine the effect of the sex of co-twins on lambs' birth weight in ovine pregnancies developed under natural undernourishment, a condition of sheep farming frequently encountered worldwide. Additionally, we sought to investigate whether the nutritional and/or antioxidant supplementation provided to ewes during pregnancy could modulate the potential effects associated with the sex of co-twins. We found that maternal nutrient restriction abolishes the sex differences in body weight at birth between co-twins. However, improving maternal nutrition and supplementation with antioxidants during gestation not only improves maternal weight and body condition but also tends to restore birth weight and its differences between female and male offspring, an effect that is enhanced with the combined supplementation of concentrated food and antioxidants. These results suggest that undernutrition not only may alter the intrauterine growth through the maternal–fetal relationship, but also through the feto–fetal relationship, which can be normalized via strategically targeting interventions such as maternal nutrient supplementation or antioxidant supplementation during gestation. Thus, a better understanding of the driving factors of this effect is of major relevance to improving fetal growth and lamb survival in harsh environments. In twin pregnancies of discordant sex, the male fetus grows larger than the female co-twin. Our study aimed to determine the effect of the sex of co-twins on lambs' birth weight in ovine pregnancies developed under natural undernourishment. Additionally, we investigated whether the nutritional and/or antioxidant supplementation provided to ewes during pregnancy could modulate the potential effects associated with the sex of co-twins. Ninety-six birth records of twin pregnancies of sheep grazing the natural Patagonian prairies were analyzed. The animals were divided into four groups: control (no supplementation), N (concentrate supplementation, 100% NRC), A (antioxidant supplementation), and NA (concentrate + antioxidant supplementation). Supplementation occurred from day 35 of gestation onwards until lambing. There were no differences in female or male birth weight in the control undernourished group. However, in group N, females or males with sex-discordant co-twins had a higher birth weight than did those with co-twins of the same sex. Group A males with female co-twins had a higher birth weight compared to males whose co-twins were also males. In NA lambs, males had a higher birth weight compared to females, regardless of their co-twin's sex. Therefore, chronic undernutrition abolished the differences in birth weight due to fetal sex. Restoring maternal nutrition or antioxidant supplementation tends to normalize birth weight and restore the differences between females and males. This effect is enhanced with the combined supplementation of concentrated food and antioxidants. [ABSTRACT FROM AUTHOR]

Simple Summary: Improvement of fetal growth in twin pregnancies is one of the major goals of extensive sheep production systems, as lambs' birth weight is correlated with their survival. This is especially relevant in harsh environments where natural maternal nutrient restriction is common. Maternal arginine (Arg) supplementation improves fetal growth, but Arg is degraded in the rumen, has a short biological half-life, and the high cost of protected forms limits its use in extensive sheep systems. N-carbamylglutamate (NCG) is not degraded in the rumen, increases arginine synthesis, and improves urea recycling, suggesting it may be an option as an alternative to Arg. The aim of this study was to evaluate the effect of oral NCG supplementation from 100 days of gestation (dga) to term in naturally nutrient-restricted grazing twin-bearing ewes, on maternal, placental, and fetal variables. The serum concentrations of NCG were increased 15-fold, and the plasma urea, albumin and phosphorus concentrations were reduced in supplemented ewes compared to controls, but there was no major effect on the dam or fetal body or organ weights nor the antioxidant markers and other blood biochemical parameters. These results indicate that NCG supplementation in mid-to-late gestation in grazing ewes was unable to rescue the negative production effects of severe natural nutritional restriction on both the dam and fetuses. The challenge of meeting the nutrient requirements of pregnant ewes in harsh environmental conditions reinforces the need for future research to identify novel strategies to improve lamb survival in such environments around the world. N-carbamylglutamate (NCG) is postulated to improve fetal growth in nutrient-restricted gestations when supplemented from day 35 to 110 of gestation, but the effects of supplementation from 100 days of gestation to birth have not been evaluated. The aim of this study was to evaluate the effect of oral NCG supplementation from 100 days of gestation (dga) to term in naturally nutrient-restricted grazing twin-bearing ewes, on the maternal body weight (BW), body condition score (BCS), placental morphology, fetal body and organ weights and blood biochemistry and antioxidant status in the ewe and fetuses. Eighteen twin-bearing ewes maintained under grazing management were randomly allocated to either a treatment group (NCG; n = 10), orally dosed once daily with 60 mg/kg of NCG from day 100 until 140 dga, or an unsupplemented control group (CON; n = 8). At 140 dga, blood gases, redox status, maternal and fetal plasma and fetal biometrics were obtained after caesarian section. The serum concentration of NCG was increased 15-fold in the NCG ewes compared to the CON. No major effects on dam or fetal body weight nor on blood biochemistry or antioxidant parameters were observed. These results indicate that NCG supplementation in mid-to-late gestation to grazing ewes was unable to rescue the negative production effects of severe natural nutritional restriction on both the dam and fetuses. [ABSTRACT FROM AUTHOR]

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Many state‐of‐the‐art methods for seizure prediction, using the electroencephalogram, are based on machine learning models that are black boxes, weakening the trust of clinicians in them for high‐risk decisions. Seizure prediction concerns a multidimensional time‐series problem that performs continuous sliding window analysis and classification. In this work, we make a critical review of which explanations increase trust in models' decisions for predicting seizures. We developed three machine learning methodologies to explore their explainability potential. These contain different levels of model transparency: a logistic regression, an ensemble of 15 support vector machines, and an ensemble of three convolutional neural networks. For each methodology, we evaluated quasi‐prospectively the performance in 40 patients (testing data comprised 2055 hours and 104 seizures). We selected patients with good and poor performance to explain the models' decisions. Then, with grounded theory, we evaluated how these explanations helped specialists (data scientists and clinicians working in epilepsy) to understand the obtained model dynamics. We obtained four lessons for better communication between data scientists and clinicians. We found that the goal of explainability is not to explain the system's decisions but to improve the system itself. Model transparency is not the most significant factor in explaining a model decision for seizure prediction. Even when using intuitive and state‐of‐the‐art features, it is hard to understand brain dynamics and their relationship with the developed models. We achieve an increase in understanding by developing, in parallel, several systems that explicitly deal with signal dynamics changes that help develop a complete problem formulation. [ABSTRACT FROM AUTHOR]

Perampanel is a promising antiepileptic drug (AED) for refractory epilepsy treatment due to its innovative mechanism of action. This study aimed to develop a population pharmacokinetic (PopPK) model to be further used in initial dose optimization of perampanel in patients diagnosed with refractory epilepsy. A total of seventy-two plasma concentrations of perampanel obtained from forty-four patients were analyzed through a population pharmacokinetic approach by means of nonlinear mixed effects modeling (NONMEM). A one-compartment model with first-order elimination best described the pharmacokinetic profiles of perampanel. Interpatient variability (IPV) was entered on clearance (CL), while the residual error (RE) was modeled as proportional. The presence of enzyme-inducing AEDs (EIAEDs) and body mass index (BMI) were found as significant covariates for CL and volume of distribution (V), respectively. The mean (relative standard error) estimates for CL and V of the final model were 0.419 L/h (5.56%) and 29.50 (6.41%), respectively. IPV was 30.84% and the proportional RE was 6.44%. Internal validation demonstrated an acceptable predictive performance of the final model. A reliable population pharmacokinetic model was successfully developed, and it is the first enrolling real-life adults diagnosed with refractory epilepsy. [ABSTRACT FROM AUTHOR]

This qualitative study investigated the gaps that hinder fruit and vegetable waste reduction in small distributors serving the last miles of the food chain. Fifteen Brazilian distributors operating far from the producers were analyzed. The findings contribute to the literature by showing several research gaps. The surplus in farmer planting increases waste generation at the level of distributors. We should know how to collect and process the relevant data to forecast the demand of each small farmer or distributor (e.g., tendencies in market demands or other farmers' planting plans). Sectoral entities should use these data to help actors define how much to plant or buy. The acceptance of waste by farmers and distributors has a financial reason. Changing such acceptance requires the demonstration of financial gain that a more sustainable approach may have. We need to know how to calculate the economic gains and losses related to waste reduction throughout the chain (before developing useful mitigators). We should also know how to induce entrepreneurs to invest in better resources or practices in transportation, handling, packaging, and storage. Selling items before their decline avoids waste. We need to know how to improve small actors' gains to increase sales of such products. [ABSTRACT FROM AUTHOR]

Low‐grade neuroepithelial tumors (LNETs) represent an important group of central nervous system neoplasms, some of which may be associated to epilepsy. The concept of long‐term epilepsy‐associated tumors (LEATs) includes a heterogenous group of low‐grade, cortically based tumors, associated to drug‐resistant epilepsy, often requiring surgical treatment. LEATs entities can sometimes be poorly discriminated by histological features, precluding a confident classification in the absence of additional diagnostic tools. This study aimed to provide an updated review on the genomic findings and DNA methylation profiling advances in LNETs, including histological entities of LEATs. A comprehensive search strategy was conducted on PubMed, Embase, and Web of Science Core Collection. High‐quality peer‐reviewed original manuscripts and review articles with full‐text in English, published between 2003 and 2022, were included. Results were screened based on titles and abstracts to determine suitability for inclusion, and when addressed the topic of the review was screened by full‐text reading. Data extraction was performed through a qualitative content analysis approach. Most LNETs appear to be driven mainly by a single genomic abnormality and respective affected signaling pathway, including BRAF p.V600E mutations in ganglioglioma, FGFR1 abnormalities in dysembryoplastic neuroepithelial tumor, MYB alterations in angiocentric glioma, BRAF fusions in pilocytic astrocytoma, PRKCA fusions in papillary glioneuronal tumor, between others. However, these molecular alterations are not exclusive, with some overlap amongst different tumor histologies. Also, clustering analysis of DNA methylation profiles allowed the identification of biologically similar molecular groups that sometimes transcend conventional histopathological classification. The exciting developments on the molecular basis of these tumors reinforce the importance of an integrative histopathological and (epi)genetic classification, which can be translated into precision medicine approaches. [ABSTRACT FROM AUTHOR]

Maternal nutrient restriction in twin- bearing ewes reduces the colostrum protein content, resulting in reduced postnatal growth and greater lamb mortality in twin- compared with single-bearing ewes. N-carbamylglutamate (NCG), an analogue of N-acetylglutamate increases endogenous arginine syn- thesis and is postulated to influence fetal growth and development and potentially lamb survival. The effect of maternal supplementation with NCG in mid-late gestation on colostrum quality and nutrient status of nutrient-restricted ewes has not been reported. The aim of this study was to evaluate the effect of oral maternal supplementation with NCG during mid–late gestation in nutrient restricted twin-bearing ewes on maternal body weight (BW) gain, body condition score (BCS), nutritional status and colostrum composition. Twin- bearing ewes (n = 20), managed in individual pens, were orally dosed once-daily with 60 mg/kg BW NCG in a water carrier from 100 d of gestation (dg) to lambing and were compared with unsupplemented controls (CON; n = 21). The ewes received a ration based on alfalfa (12.12% CP and 2.10 Mcal/kg ME) and pas- ture (6.85% CP and 2.13 Mcal/kg ME) hay, covering 50% of National Research Council nutritional require- ments for twin-bearing ewes to reflect commercial con- ditions. Maternal BW and BCS were recorded every 10 d, from 100 dg until lambing. Maternal blood samples were collected at 130 dg and 30 min after lambing and plasma beta-hydroxybutyrate (BHB), total protein, albumin and urea were evaluated. Colostrum was collected 30 min after the second lamb was delivered and fat, non-fat solids, density and protein contents were determined. The effect of treatment on ewe BW, BCS were analyzed using REML analysis in R (lme4 R package) with time (dg) and treatment (and their inter- action) as fixed effects. Plasma and colostrum metab- olites were analyzed using REML with treatment as the fixed effect. Ewe BW increased (P < 0.0001) and BCS decreased (P < 0.0001) with advancing gestation, but there was no effect of treatment (P > 0.05). At 130 dg plasma urea was a 12% greater (P = 0.02) and al- bumin tended to be 4% greater (P = 0.08) in NCG com- pared with CON ewes, but no treatment effect on BHB or total protein content was observed (P > 0.05). No treatment effect on maternal plasma metabolites were observed post lambing (P > 0.05). Colostrum protein content was 21% greater in NCG compared with CON (P = 0.04) ewes, but fat, non-fat solids or density (P > 0.05) did not differ between groups. Collectively, these results suggest that supplementation of nutritionally restricted ewes with 60 mg/kg BW from 100 dg to lambing may alter maternal nitrogen metabolism and colostrum protein content. The potential impact of these changes on lamb growth and/or survival, warrants further investigation. *Funded by FONDECYT Project N°1221042; AgResearch Strategic Science Investment Fund SSIF-A25765 and INIA Kampenaike. [ABSTRACT FROM AUTHOR]

Adherence to antiseizure drug treatment determines its effectiveness and safety, and consequently affects patients' quality of life. Herein, we assessed adherence to levetiracetam in Portuguese patients with refractory epilepsy (n = 115), with resort to a pharmacokinetic drug monitoring approach. The pharmacokinetic parameters of levetiracetam in each patient were determined in steady-state while admitted to the hospital. Then, adherence was assessed by comparing the plasma concentration of the drug observed on the first day of hospitalization with the predicted plasma concentration, considering previously determined pharmacokinetic parameters. The rate of adherence was assessed according to gender, age, diagnosis, and antiseizure drug regimen. Among 115 enrolled patients, 49 (42.6%) were identified as non-adherent, 30 (26.1%) classified as under-consumers, and 19 (16.5%) as over-consumers. A relationship between adherence, daily dose and plasma concentrations was herein reported for the first time. Adherent patients received higher daily doses of levetiracetam [2500 (2000–3000) mg] than non-adherent over-consumers [1500 (1000–2000) mg] and non-adherent under-consumers [2000 (1500–3000) mg]. Higher average steady-state plasma concentrations of levetiracetam were found in non-adherent under-consumers [27.28 (15.33–36.36) mg/L], followed by adherent patients [22.05 (16.62–29.81) mg/L] and non-adherent over-consumers [17.50 (10.69–24.37) mg/L]. This study demonstrates that adherence (or lack thereof) influences the plasma concentrations of levetiracetam in steady-state and its pharmacological effects. Moreover, it emphasizes the importance of educating patients to encourage adherence to therapy. Otherwise, the risk of developing toxic and subtherapeutic concentrations is undeniable, compromising the therapeutic effect and safety of treatment. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate the antiepileptic effects of cathodal transcranial direct current stimulation (c-tDCS) and mechanisms of action based on its effects on the neurotransmitters responsible for the abnormal synchrony patterns seen in pharmacoresistant epilepsy. This is the first study to test the impact of neurostimulation on epileptiform interictal discharges (IEDs) and to measure brain metabolites in the epileptogenic zone (EZ) and control regions simultaneously in patients with pharmacoresistant epilepsy. Methods: This is a hypothesis-driven pilot prospective single-blinded repeated measure design study in patients diagnosed with pharmacoresistant epilepsy of temporal lobe onset. We included seven patients who underwent two sessions of c-tDCS (sham followed by real). The real tDCS session was 20 min in duration and had a current intensity of 1.5 mA delivered via two surface electrodes that had dimensions of 3 x 4 cm. The cathode electrode was placed at FT7 in the center whereas the anode at Oz in the center. After each session, we performed electroencephalographic recording to count epileptiform IEDs over 30 min. We also performed magnetic resonance spectroscopy (MRS) to measure brain metabolite concentrations in the two areas of interest (EZ and occipital region), namely, gamma-aminobutyric acid (GABA), glutamate (Glx), and glutathione. We focused on a homogenous sample where the EZ and antiepileptic medications are shared among patients. Results: Real tDCS decreased the number of epileptiform IEDs per min (from 9.46 ± 2.68 after sham tDCS to 5.37 ± 3.38 after real tDCS), p = 0.018, as compared to sham tDCS. GABA was decreased in the EZ after real c-tDCS stimulation as compared to sham tDCS (from 0.129 ± 0.019 to 0.096 ± 0.018, p = 0.02). The reduction in EZ GABA correlated with the reduction in the frequency of epileptiform IED per min (rho: 0.9, p = 0.003). Conclusion: These results provide a window into the antiepileptic mechanisms of action of tDCS, based on local and remote changes in GABA and neural oscillatory patterning responsible for the generation of interictal epileptiform discharges. [ABSTRACT FROM AUTHOR]

Hypoxemia and oxidative stress, resulting in intrauterine growth restriction (IUGR) in undernourished twin sheep pregnancies, has been described in near-term studies. Our aim was to evaluate if the counteractive effects of maternal nutritional or antioxidant supplementation on the fetal redox status were evident before the accelerated fetal growth phase. Forty twin-bearing ewes grazing on natural Patagonian prairie were randomly assigned to four groups (n = 10 each; P: control ewes consuming mainly natural pasture; P+A: pasture plus antioxidants; P+C: pasture plus concentrate; P+A+C: pasture plus antioxidants and concentrate). Daily herbal antioxidants were supplemented in a feedstuff concentrate as a premix from day 35 until day 100 of gestation, when fetal venous cord blood samples and biometric measurements were obtained via cesarean section. The fetuses from group P were clearly hypoxemic. An analysis of variance showed that maternal antioxidant supplementation showed a trend of increased PO2, SatHb, and Ht, effects not observed in P+C fetuses. Antioxidants decreased the fetal MDA concentration (p < 0.05). Fetal TAC was increased by the antioxidants and concentrate (p < 0.05). Antioxidant supplementation showed a trend to increase fetal body weight but not biometry. The results suggest that negative effects of oxidative stress occur earlier than the overt growth arrest, and the maternal administration of antioxidants may constitute a good nutritional strategy for the early prevention of IUGR. [ABSTRACT FROM AUTHOR]

Seizure prediction may be the solution for epileptic patients whose drugs and surgery do not control seizures. Despite 46 years of research, few devices/systems underwent clinical trials and/or are commercialized, where the most recent state‐of‐the‐art approaches, as neural networks models, are not used to their full potential. The latter demonstrates the existence of social barriers to new methodologies due to data bias, patient safety, and legislation compliance. In the form of literature review, we performed a qualitative study to analyze the seizure prediction ecosystem to find these social barriers. With the Grounded Theory, we draw hypotheses from data, while with the Actor‐Network Theory we considered that technology shapes social configurations and interests, being fundamental in healthcare. We obtained a social network that describes the ecosystem and propose research guidelines aiming at clinical acceptance. Our most relevant conclusion is the need for model explainability, but not necessarily intrinsically interpretable models, for the case of seizure prediction. Accordingly, we argue that it is possible to develop robust prediction models, including black‐box systems to some extent, while avoiding data bias, ensuring patient safety, and still complying with legislation, if they can deliver human‐ comprehensible explanations. Due to skepticism and patient safety reasons, many authors advocate the use of transparent models which may limit their performance and potential. Our study highlights a possible path, by using model explainability, on how to overcome these barriers while allowing the use of more computationally robust models. [ABSTRACT FROM AUTHOR]

This paper proposes a method to obtain the reference currents of a shunt active power compensator based on the non-active power magnitudes defined in IEEE Standard 1459-2000. These reference currents are used to control a shunt active power compensator that features new selective compensating capabilities. Fundamental positive-sequence reactive power, unbalance power, and nonfundamental effective apparent power present in electric systems can be cancelled individually or combined with each other. Experimental results are obtained using a three-branch four-wire shunt active compensator. These results demonstrate that the proposed selective compensator works well in three-phase electrical systems with load currents, including phase shifts, unbalances and distortion, and with voltages, including asymmetries and harmonic components. The electric quality is improved with the use of the proposed selective control. Index Terms--Electrical quality, harmonic compensation, IEEE Standard 1459, reactive compensation, shunt active power compensators, unbalanced three-phase four-wire systems.

IEEE Standard 1459-2000 establishes that in an efficient electrical system, only the fundamental positive-sequence active power must be present. This paper proposes a new set of reference currents based on the IEEE Standard 1459-2000 for the control of a three-branch four-wire shunt active power compensator. Reactive, unbalance, and harmonic distortion phenomena can be cancelled out upstream from the point of connection, achieving maximum efficiency of the three-phase four-wire electrical system. In addition, a new current control and a three-dimensional space vector pulsewidth-modulation technique are proposed to develop a shunt active power compensator. Simulation and experimental results demonstrate that the proposed shunt active power compensator improves the upstream electrical quality of the power network, achieving maximum efficiency according to IEEE Standard 1459-2000 specifications. Index Terms--Active filters, active power compensators (APCs), current control, harmonic distortion, IEEE standards, power quality (PQ), pulsewidth modulation, reactive power.

A lack of engagement with the natural environment can reduce awareness of issues surrounding environmental and biodiversity conservation. Therefore, to increase students' awareness, science teachers should develop activities related to biodiversity, bringing students into closer connection with the natural environment. This study evaluated the ability of 115 Brazilian university students' to identify native and alien wild mammals. Patterns in university students' ability to identify species were predicted by a combination of variables (university-level, age, gender, experience linked to countryside, family farming, fishing, and hunting). Students correctly identified alien mammals more frequently than native mammals. We found distinct groups of species in function of students' experience (university-level, age group, fishing, and hunting). In addition, we found that the correct identification of native species was mainly associated with older male students who go regularly to the countryside, and participate in activities linked to farming, fishing, and hunting. Our findings support those from previous studies that show fieldwork classes are essential to increase the contact of an increasingly urbanized society with the local natural environment. We suggest that inclusion of fieldwork is necessary for the development of university students' awareness regarding the richness of native mammal species and consequently, the importance of their conservation. [ABSTRACT FROM AUTHOR]

A palette of copy number changes in long-term epilepsy-associated tumors (LEATs) have been reported, but the data are heterogeneous. To better understand the molecular basis underlying the development of LEATs, we performed array-comparative genomic hybridization analysis to investigate chromosomal imbalances across the entire genome in 8 cases of LEATs. A high number of aberrations were found in 4 patients, among which deletions predominated. Both whole-chromosome and regional abnormalities were observed, including monosomy 19, deletion of 1p, deletions of 4p, 12p, and 22q, and gain of 20p. The common altered regions are located mainly on chromosomes 19 and 4p, identifying genes potentially involved in biological processes and cellular mechanisms related to tumorigenesis. Our study highlights new genomic alterations and reinforces others previously reported, offering new molecular insights that may help in diagnosis and therapeutic decision-making. [ABSTRACT FROM AUTHOR]