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Purpose Lacosamide (LCM) is a third-generation anti-seizure medication (ASM) approved for focal onset epilepsy in patients aged ≥ 4.378 Previous studies have reported an efficacy of LCM as add-on treatment in brain tumor-related epilepsy (BTRE). To date, there are no studies in the literature focusing on lacosamide used in monotherapy to treat BTRE. In our retrospective study we investigated efficacy and tolerability of LCM in monotherapy in a multicenter national cohort of primary brain tumor patients. Methods We collected from 12 Italian Centers 132 patients with primary brain tumors who were treated with LCM in monotherapy. For each patient we evaluated seizure freedom at 3 and 6 months (primary endpoints), side effects and drop-out rate (secondary endpoints). Results Overall, LCM led to seizure freedom in 64.4% of patients at 3 months and 55% at 6 months. Patients who used two or more ASMs before LCM had a worse seizure control than patients in monotherapy with LCM as first choice. In 14 patients, we observed seizure control despite tumor progression on magnetic resonance (MRI). Multivariate analysis showed that gross-total resection at diagnosis was significantly associated with higher seizure freedom rate at 6 months. Side effects were mainly mild (grade 1–2 according to CTCAE classification) and drop-out rate was low (1.5%). Main side effects were dizziness and somnolence. Conclusions This is the first study showing a good efficacy and tolerability of LCM when used in monotherapy in BTRE. Further prospective studies are needed to confirm these preliminary data, investigating also quality of life and neurocognitive functions.

Background Myosin heavy chain 7 ( MYH7 )-related myopathies are emerging as an important group of muscle diseases of childhood and adulthood, with variable clinical and histopathological expression depending on the type and location of the mutation. Mutations in the head and neck domains are a well-established cause of hypertrophic cardiomyopathy whereas mutation in the distal regions have been associated with a range of skeletal myopathies with or without cardiac involvement, including Laing distal myopathy and Myosin storage myopathy. Recently the spectrum of clinical phenotypes associated with mutations in MYH7 has increased, blurring this scheme and adding further phenotypes to the list. A broader disease spectrum could lead to misdiagnosis of different congenital myopathies, neurogenic atrophy and other neuromuscular conditions. Results As a result of a multicenter Italian study we collected clinical, histopathological and imaging data from a population of 21 cases from 15 families, carrying reported or novel mutations in MYH7 . Patients displayed a variable phenotype including atypical pictures, as dropped head and bent spine, which cannot be classified in previously described groups. Half of the patients showed congenital or early infantile weakness with predominant distal weakness. Conversely, patients with later onset present prevalent proximal weakness. Seven patients were also affected by cardiomyopathy mostly in the form of non-compacted left ventricle. Muscle biopsy was consistent with minicores myopathy in numerous cases. Muscle MRI was meaningful in delineating a shared pattern of selective involvement of tibialis anterior muscles, with relative sparing of quadriceps. Conclusion This work adds to the genotype-phenotype correlation of MYH7 -relatedmyopathies confirming the complexity of the disorder.

Background Theacrine (1,3,7,9-tetramethyluric-acid) is a pure alkaloid with a similar structure to caffeine and acts comparably as an adenosine receptor antagonist. Early studies have shown non-habituating effects, including increases in energy and focus in response to Teacrine®, the compound containing pure theacrine. The purpose of this study was to determine and compare the effects of Teacrine® and caffeine on cognitive performance and time-to-exhaustion during a simulated soccer game in high-level male and female athletes. Methods Male and female soccer players ( N  = 24; M Age  = 20.96 ± 2.05y, M MaleVO2max  = 55.31 ± 3.39 mL/O 2 /kg, M FemaleVO2max  = 50.97 ± 3.90 mL/O 2 /kg) completed a 90-min simulated treadmill soccer match over four randomized sessions (TeaCrine®, caffeine, TeaCrine® + caffeine, placebo). Cognitive testing at halftime and end-of-game including simple reaction time (SRT), choice RT (CRT), and cognitive-load RT with distraction questions (COGRT/COGRT Wrong ) was performed, with a run time-to-exhaustion (TTE) at 85% VO 2max following end-of-game cognitive testing. Session times and pre-exercise nutrition were controlled. RM-MANOVAs with univariate follow-ups were conducted and significance was set at P  < 0.05. Results TTE trended towards significance in TeaCrine® and TeaCrine® + caffeine conditions compared to placebo ( P  < 0.052). A condition main effect ( P  < 0.05) occurred with faster CRT in caffeine and TeaCrine® + caffeine compared to placebo. COGRT Wrong showed a significant time main effect, with better accuracy at end-of-game compared to halftime ( P  < 0.05). A time x condition interaction in SRT ( P  < 0.05) showed placebo improved from halftime to end-of-game. Conclusions The 27–38% improvements in TTE reflect increased performance capacity that may have important implications for overtime scenarios. These findings suggest TeaCrine® favorably impacts endurance and the combination with caffeine provides greater benefits on cognitive function than either supplement independently.

Avelumab, a human anti–programmed death ligand 1 immunoglobulin G1 antibody, has shown efficacy and manageable safety in multiple tumors. A two‐compartment population pharmacokinetic model for avelumab incorporating intrinsic and extrinsic covariates and time‐varying clearance (CL) was identified based on data from 1,827 patients across three clinical studies. Of 14 tumor types, a decrease in CL over time was more notable in metastatic Merkel cell carcinoma and squamous cell carcinoma of the head and neck, which had maximum decreases of 32.1% and 24.7%, respectively. The magnitude of reduction in CL was higher in responders than in nonresponders. Significant covariate effects of baseline weight, baseline albumin, and sex were identified on both CL and central distribution volume. Significant covariate effects of black/African American race, C‐reactive protein, and immunogenicity were found on CL. None of the covariate or time‐dependent effects were clinically important or warranted dose adjustment.

Irisin is processed from fibronectin type III domain-containing protein 5 (FNDC5). However, a controversy exists concerning irisin origin, regulation and function. To elucidate the relationship between serum irisin and FNDC5 mRNA expression levels, we evaluated plasma irisin levels and FNDC5 gene expression in the hypothalamus, gastrocnemius muscle and different depots of adipose tissue in models of altered metabolism. In normal rats, blood irisin levels diminished after 48-h fast and with leptin, insulin and alloxan treatments and serum irisin concentrations increased in diabetic rats after insulin treatment and acute treatments of irisin increased blood insulin levels. No changes were observed during long-term experiments with different diets. We suggested that levels of circulating irisin are the result of the sum of the irisin produced by different depots of adipose tissue and skeletal muscle. This study shows for the first time that there are differences in FNDC5 expression depending on white adipose tissue depots. Moreover, a considerable decrease in visceral and epididymal adipose tissue depots correlated with increased FNDC5 mRNA expression levels, probably in an attempt to compensate the decrease that occurs in their mass. Hypothalamic FNDC5 expression did not change for any of the tested diets but increased with leptin, insulin and metformin treatments suggesting that the regulation of central and peripheral FNDC5 /irisin expression and functions are different.

Peel from unripe plantain is obtained when the pulp is used for the next production process as starch isolation or dry flour. Plantain peel flour (PPF) was obtained and its chemical composition, composition of the dietary fiber (DF), polyphenol content, antioxidant capacity, and functional properties were studied. PPF had more relevant amounts of protein, ash, total starch, and total dietary fiber (TDF). The main component of DF was the insoluble fraction, with a higher level of cellulose than hemicellulose and lignin. In the insoluble fraction uronic acid was the most predominant acidic monosaccharide, while mannose was in the soluble fraction. Extractable polyphenols were found in the lowest amount, but showed the highest antioxidant capacity. Water- and oil-holding capacity values increased when the temperature of the test increased. The PPF with high DF content, high antioxidant capacity, and functional characteristics could be used as a functional ingredient for the elaboration of food products.

Background and Purpose The aim was to investigate whether neurofilament light chain (NfL) and profilin‐1 (PFN‐1) might qualify as surrogate disease and treatment‐response biomarkers by correlating their concentrations dynamic with clinical status in a cohort of 30 adult spinal muscular atrophy type 3 patients during nusinersen therapy up to 34 months. Methods Neurofilament light chain was measured in cerebrospinal fluid at each drug administration with a commercial enzyme‐linked immunosorbent assay (ELISA); PFN‐1 concentrations were tested in serum sampled at the same time points with commercial ELISA assays. Functional motor scores were evaluated at baseline, at the end of the loading phase and at each maintenance dose and correlated to biomarker levels. The concurrent effect of age and clinical phenotype was studied. Results Neurofilament light chain levels were included in the reference ranges at baseline; a significant increase was measured during loading phase until 1 month. PFN‐1 was higher at baseline than in controls and then decreased during therapy until reaching control levels. Age had an effect on NfL but not on PFN‐1. NfL was partially correlated to functional scores at baseline and at last time point, whilst no correlation was found for PFN‐1. Conclusion Cerebrospinal fluid NfL levels did not qualify as an optimal surrogate treatment biomarker in adult spinal muscular atrophy patients with a long disease duration, whilst PFN‐1 might to a greater extent represent lower motor neuron pathological processes. The observed biomarker level variation during the first 2 months of nusinersen treatment might suggest a limited effect on axonal remodeling or rearrangement.

(1) Background: Molar-incisor hypomineralization (MIH) is a common clinical condition with critical negative consequences for dental health. The etiology of MIH is still not completely understood, although several theories have been suggested. (2) Aim: To investigate the etiology of MIH defects in a sample of Saudi school children. (3) Method: A total of 893 school children in the age range of 8–10 years participated in the study. The sample was taken from Riyadh City, Saudi Arabia. The participating children were examined for MIH using the European Academy of Pediatric Dentistry Criteria. The children’s parents were asked about the child’s pre, peri-, and postnatal condition utilizing a structured and validated questionnaire. (4) Results: A total of 362 children (168 males and 194 females) were affected with MIH, for a prevalence of 40.5%. Among all analyzed etiological factors, only jaundice was found to be significantly associated with MIH in children (OR = 1.35, p = 0.047). Multivariate logistic regression analysis confirmed that the only significant etiological factor for MIH was newborn jaundice (p = 0.04). (5) Conclusion: Newborn jaundice was the only etiological factor that showed a significant association with MIH in the studied Saudi school children.

This study sought to identify new sources of resistance to cowpea aphids (CPA) using molecular and phenotypic approaches and the inheritance pattern. Sixty cowpea genotypes were phenotyped for resistance to CPA using insect proof cages and further confirmed using markers linked to aphid resistance. Result revealed that among the cowpea genotypes, TVu 2897 and TVNu 1158 supported lowest number of aphids and plant damage scores. The seedlings of these genotypes also had high level of survival rates and were completely healthy with normal growth. This indicates that these genotypes are resistant to aphid attacks. However, the resistance in TVNu 1158 did not seem strong compared to the genotype TV U 2897 that was confirmed to be resistant to multiple aphid biotypes. The mechanism of resistance in TVu 2897 and TVNu 1158 were expressed as a hypersensitive response at the site of infestation on the leaves. The other genotypes especially Aloka local and keffi local supported the highest number of aphids, damage score and low level of survival rate, suggesting that they are susceptible to aphid attack. The cowpea genotype IT84S-224-6 previously reported to be resistant to aphids supported high number of aphids and was marked by stunted growth and high mortality rate. Molecular and phenotypic screening revealed that TVu-2876 has a strong resistance to cowpea aphid and should be a good source of resistance gene that can be used in breeding to develop new aphid resistant cowpea cultivars. Although, the results of phenotypic tests and molecular marker detection agreed in most cases, molecular markers detection was found more reliable in identifying genotypes for resistance to CPA. The segregation in F 2 and BC1 populations derived from the cross between TVNu 2876 and Keffi local indicated that resistance to cowpea aphids in TVu-2876 is controlled by a single dominant gene. Allelism test revealed that resistance gene in TVNu 2876 is non-allelic with the gene that confers resistance in SARC 1-57-2 and TVNu 1158.

BackgroundTactical athletes require fast reaction times (RT) along with high levels of vigilance and marksmanship performance. Caffeine has been shown to improve these measures but also results in increased blood pressure and jitteriness. Research on other purine alkaloids, such as methylliberine and theacrine, has suggested they do not increase blood pressure or jitteriness to the same extent, but their impact on tactical performance is unknown.MethodsA between-subjects, randomized, placebo-controlled design was used to test the effects of placebo (PLA), 300 mg caffeine (CAF), and a combination of 150 mg caffeine, 100 mg methylliberine, and 50 mg theacrine (CMT) on RT and marksmanship along with hemodynamic and arousal measures following a sustained vigilance task in tactical personnel (n = 48). Following consumption of the supplement, participants underwent a 150-min protocol consisting of two rounds. Each round began with leisurely reading followed by a 30-min vigilance task before beginning two trials of movement and marksmanship tasks. Hemodynamics and felt arousal were assessed throughout the protocol. Composite Z-scores were calculated for overall performance measures at each timepoint, and mixed-effects models were used to assess differences in RT, accuracy, and composite Z-scores along with hemodynamics and felt arousal. An α-level of 0.05 was used to determine statistical significance, and Cohen’s d was used to quantify effect sizes.ResultsA Group-by-Time interaction for vigilance RT (P = 0.038) indicated improvements for both CAF and CMT from round 1 to round 2 (P < 0.01) while PLA did not change (P = 0.27). No Group main effects or Group-by-Time interactions were found for movement or marksmanship performance (P > 0.20). Group main effects for systolic (SBP; P = 0.001) and diastolic blood pressure (DBP; P = 0.028) indicated higher SBP in CAF (P = 0.003, d= 0.84) and CMT (P = 0.007, d= 0.79) compared to PLA but only higher DBP in CAF (P = 0.025, d= 0.74). No Group-by-Time interaction or Group main effect was found for felt arousal (P > 0.16).ConclusionsThese findings suggest similar benefits on RT during a vigilance task between CAF, containing 300 mg caffeine, and CMT above PLA, though CAF resulted in slightly less favorable hemodynamic changes. This study is the first to provide data showing similar efficacy of combined caffeine, methylliberine, and theacrine compared to double the caffeine dose consumed alone on vigilance RT but without a significant rise in DBP above PLA in tactical personnel.