Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson's disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study.

Background and objectives: Intermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson's disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity. Methods: A total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS. Discussion: The findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD.

Neuropsychological and Neuropsychiatric Features of Chronic Migraine Patients during the Interictal Phase.

This study aimed to examine the presence of neuropsychological deficits and their relationships with clinical, pharmacological, and neuropsychiatric characteristics in chronic migraine (CM) patients assessed during a headache-free period. We enrolled 39 CM patients (mean age: 45.4 years; male/female ratio: 3/36) and 20 age-, sex-, and education-matched healthy controls (HCs, mean age: 45.5 years; male/female ratio: 2/18) in a case-control study. All CM patients underwent a full and extensive clinical, neuropsychiatric, and neuropsychological evaluation to evaluate cognitive domains, including sustained attention (SA), information processing speed (IPS), visuospatial episodic memory, working memory (WM), and verbal fluency (VF), as well as depressive and anxiety symptoms. CM patients exhibited higher scores than HCs for all clinical and neuropsychiatric measures, but no differences were found in personality characteristics. Although more than half of the CM patients (54%) showed mild-to-severe neuropsychological impairment (NI), with the most frequent impairments occurring in short- and long-term verbal episodic memory and inhibitory control (in approximately 90% of these patients), almost half of the patients (46%) showed no NI. Moreover, the severity of NI was positively associated with the number of pharmacological treatments received. Remarkably, disease-related symptom severity and headache-related disability explained global neuropsychological performance in CM patients. The presence of cognitive and neuropsychiatric dysfunction during the interictal phase occurred in more than half of CM patients, increasing migraine-related disability and possibly exerting a negative impact on health-related quality of life and treatment adherence.

Neuropsychiatric Symptoms in Clinically Defined Parkinson's Disease: An Updated Review of Literature.

Background: Neuropsychiatric symptoms (NPS) are a common and potentially serious manifestation of Parkinson's disease (PD) but are frequently overlooked in favor of a focus on motor symptomatology. Here, we conducted a literature review of the prevalence and type of NPS experienced by PD patients with a clinically defined course of their illness. Methods: We identified reports of NPS in patients with PD and mean disease duration over 3 years. Three databases-PubMed, Scopus, and Dialnet-were searched for relevant literature published between 2010 and 2020. Predefined exclusion criteria were applied prior to a descriptive analysis of the literature base. Results: In all, 87 unique reports were identified and 30 met inclusion and exclusion criteria. These included 7142 patients with PD (male: 67.3%; mean age: 66.2 years; mean disease duration: 6.7 years). The most frequent NPS were mood disorders (apathy, depression, and anxiety), psychosis, and impulse control disorders (ICD). Treatment with dopamine agonists was identified as an important risk factor for ICD. Co-occurrence of NPS and cognitive dysfunction was also evidenced in a number of studies. Patients with more significant cognitive deficits and higher levels of NPS appeared to be of older age with a longer disease duration and to have more severe motor symptoms. Conclusions: NPS, most commonly mood disorders (apathy, depression, and anxiety), psychosis, and ICDs are frequent manifestations of PD. The results of this review reflect the need to develop unified validated assessment protocols for NPS in PD, as well as to improve their management in clinical practice.

Subthalamic Beta Activity in Parkinson's Disease May Be Linked to Dorsal Striatum Gray Matter Volume and Prefrontal Cortical Thickness: A Pilot Study.

Background: Excessive oscillations at beta frequencies (13-35 Hz) in the subthalamic nucleus (STN) represent a pathophysiological hallmark of Parkinson's disease (PD), which correlates well with parkinsonian symptoms and is reduced in response to standard disease treatments. However, the association of disease-specific regional gray matter (GM) atrophy or cortical thickness (CT) with the presence of STN beta oscillatory activity has been poorly investigated but is of relevance given the potential of these variables for extracting information about PD pathophysiology. This exploratory study investigated the involvement of regional GM volume and CT in the basal ganglia-cortical network and its potential association with the presence of STN beta oscillatory activity in PD. Methods: We acquired preoperative GM densities on T1-weighted magnetic resonance imaging scans and we carried out regional estimation of GM volume and CT. LFP activities from the STN were recorded post-operatively in 7 cognitively preserved PD patients off dopaminergic medication undergoing deep-brain stimulation surgery. Oscillatory beta power was determined by power spectral density of 4-min resting state STN LFP activity. Spearman partial correlations and regression analysis were used to screen the presence of STN beta power for their relationship with GM volume and CT measurements. Results: After controlling for the effects of age, educational level, and disease duration, and after correcting for multiple testing, enhanced STN beta power showed significant and negative correlations between, first, volume of the right putamen and left caudate nucleus, and second, smaller CT in frontal regions involving the left rostral middle frontal gyrus (MFG) and left medial orbitofrontal gyrus. A lower volume in the right putamen and a lower CT in the left MFG demonstrated the strongest associations with increased STN beta power. Conclusions: These tentative results seem to suggest that STN LFP beta frequencies may be mainly linked to different but ongoing parallel neurodegenerative processes, on the one hand, to GM volume reduction in dorsal striatum, and on the other hand, to CT reduction of prefrontal-"associative" regions. These findings could further delineate the brain structural interactions underpinning the exaggerated STN beta activity commonly observed in PD patients.

Cortical Thickness and Serum NfL Explain Cognitive Dysfunction in Newly Diagnosed Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: To determine the relative importance of global or regional MRI and blood markers of neurodegeneration and neuroaxonal injury in predicting cognitive performance for recently diagnosed patients with multiple sclerosis (MS). METHODS: Thirty-five newly diagnosed patients with relapsing-remitting MS (RRMS) and 23 healthy controls (HCs) simultaneously completed a full clinical and neuropsychological assessment, structural brain MRI, and serum neurofilament light chain (sNfL) level test. Linear regression analyses were performed to determine which global or regional measures of gray matter (GM) atrophy and cortical thickness (CT), in combination with sNfL levels and clinical scores, are most strongly related to neuropsychological impairment. RESULTS: Compared with HCs, patients with MS showed bilateral thalamic GM atrophy (left, p = 0.033; right, p = 0.047) and diminished CT, particularly in the right superior and transverse temporal gyri (p = 0.045; p = 0.037). Regional atrophy failed to add predictive variance, whereas anxiety symptoms, sNfL, and global CT were the best predictors (R2 = 0.404; p < 0.001) of cognitive outcomes, with temporal thickness accounting for greater variance in cognitive deficits than global CT. DISCUSSION: Thalamic GM atrophy and thinning in temporal regions represent a distinctive MRI trait in the early stages of MS. Although sNfL levels alone do not clearly differentiate HCs and patients with RRMS, in combination with global and regional CT, sNfL levels can better explain the presence of underlying cognitive deficits. Hence, cortical thinning and sNfL increases can be considered 2 parallel neurodegenerative markers in the pathogenesis of progression in newly diagnosed patients with MS.

Predicting Neuropsychological Impairment in Relapsing Remitting Multiple Sclerosis: The Role of Clinical Measures, Treatment, and Neuropsychiatry Symptoms.

OBJECTIVE: This retrospective observational study aimed to define neuropsychological impairment (NI) profiles and determine the influence of clinical, demographic, and neuropsychiatric measures in specific cognitive domains in a cohort of relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: Ninety-one RRMS patients underwent a neurological examination and a brief neuropsychological assessment. Patients were classified according to the disease-modifying therapies (DMTs) received (platform or high-efficacy). Differences between groups and multiple regression analyses were performed to determine the predictive value of the assessed measures in cognitive performance. RESULTS: More than two-thirds of the patients showed NI. Specifically, mild to moderate NI was presented in approximately half of the participants. Paced Auditory Serial Addition Test (PASAT-3) and Symbol Digit Modalities Test (SDMT) were the most frequently impaired cognitive tests (45.3% and 41.3%, respectively) followed by phonemic verbal fluency (PVF) (27.8%). Expanded Disability Status Scale (EDSS), age, depressive symptoms, and disease duration were the best predictors of SDMT (R2 = .34; p < .01), whereas disease duration, EDSS, and anxiety-state levels predicted PASAT-3 (R2 = .33, p < .01). Educational level, age, EDSS, and depressive symptoms demonstrated the strongest association with PVF (R2 = .31, p < .01). CONCLUSIONS: Our results indicated a significant prevalence of NI in RRMS patients that was not dependent on the DMT type. In addition to the meaningful working memory (PASAT-3) and information processing speed (SDMT) impairments found, PVF deficits may also be an important marker of cognitive impairment in RRMS patients. This study supports the relevance of standard clinical measures and reinforces the importance of quantifying clinical and neuropsychiatric symptoms to predict subsequent cognitive performance on a similar multiple sclerosis phenotype and disease stage.

Kinetic-Pharmacodynamic Model of Platelet Time Course in Patients With Moderate-to-Severe Atopic Dermatitis Treated With Oral Janus Kinase 1 Inhibitor Abrocitinib.

The oral Janus kinase 1 (JAK1) inhibitor abrocitinib reduced signs and symptoms of atopic dermatitis (AD) in a placebo-controlled, randomized, double-blind, phase IIb trial (dose range 10-200 mg). A kinetic-pharmacodynamic (K-PD) model consisting of proliferation, maturation, and blood circulation compartments was developed to characterize platelet count changes during the study. The K-PD model consisted of a drug elimination constant, four system parameters describing platelet dynamics, variance terms, correlation, and residual errors. Overall, these patients exhibited mean transit time from progenitor cells to platelets of 8.2 days (longer than the reported megakaryocyte life span), likely arising from JAK1-induced perturbations of platelet progenitor homeostasis. The final model described dose-related platelet count declines until nadir at treatment week 4 and return to baseline levels thereafter. The model was deemed suitable to support the design of subsequent abrocitinib AD trials and indicated limited clinically relevant platelet reductions in the range of doses studied.

Effect of Innovative Food Processing Technologies on the Physicochemical and Nutritional Properties and Quality of Non-Dairy Plant-Based Beverages.

Increase in allergenicity towards cow's milk, lactose intolerance, the prevalence of hypercholesterolemia, and flexitarian choice of food consumption have increased the market for cow's milk alternatives. Non-dairy plant-based beverages are useful alternatives because of the presence of bioactive components with health-promoting properties, which attract health-conscious consumers. However, the reduced nutritional value and sensory acceptability of the plant-based beverages (such as flavor, taste, and solubility) compared to cow's milk pose a big threat to its place in the market. Thermal treatments are commonly used to ensure the quality of plant-based beverages during storage. However, the application of high temperatures can promote the degradation of thermolabile compounds and some detrimental reactions, thus reducing protein digestibility and amino acid availability of non-dairy plant-based beverages substitutes. New and advanced food processing technologies, such as high-pressure processing, high-pressure homogenization, pulsed electric fields, and ultrasound, are being researched for addressing the issues related to shelf life increase, emulsion stability, preservation of nutritional content and sensorial acceptability of the final product. However, the literature available on the application of non-thermal processing technologies on the physicochemical and nutritional properties of plant-based beverages is scarce. Concerted research efforts are required in the coming years in the functional plant-based beverages sector to prepare newer, tailor-made products which are palatable as well as nutritionally adequate.

Integration of Pharmacometrics and Pharmacoeconomics to Quantify the Value of Improved Forgiveness to Nonadherence: A Case Study of Novel Xanthine Oxidase Inhibitors for Gout.

Linked pharmacometric and pharmacoeconomic models provide a structured approach for assessing the value of candidate drugs in development. The aim of this study was to assess the utility of such an approach for identifying the properties of xanthine oxidase inhibitors (XOi) providing improved forgiveness to nonadherence and estimate the maximum reimbursement price. The pharmacometric and pharmacoeconomic models were used to simulate the time course of serum uric acid concentrations and estimate quality-adjusted life years and costs for the XOi febuxostat and a range of hypothetical analogues. Compounds with reduced clearance or increased potency were more forgiving to missed doses, however, even following relatively large changes in these properties the predicted maximum reimbursement prices represented an increase of only 19% above febuxostat 80 mg. Linked pharmacometric and pharmacoeconomic modeling methods have the potential to inform early drug development by providing an indication of pricing options that may permit reimbursement.

Evaluating the impact of supercritical-CO2 pressure on the recovery and quality of oil from "horchata" by-products: Fatty acid profile, α-tocopherol, phenolic compounds, and lipid oxidation parameters.

The effect of supercritical carbon dioxide (SC-CO2) (10-40 MPa) and conventional extraction (CE) to recover oil from by-products obtained during "horchata" production was assessed. To evaluate both extraction techniques, the fatty acid composition, polyphenols, α-tocopherol, antioxidant capacity and lipid oxidation parameters of the extracts obtained were analysed. A linear relationship between extraction pressure and oil yield was observed. However, the highest oil yield was obtained under conventional extraction. The by-products from "horchata" presented a profile where monounsaturated fatty acids (MUFA) were the predominant, representing ≈ 70% of total fatty acids. The amount of saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA) was higher and MUFA lower at 10 MPa samples compared to the oils extracted using SC-CO2 at 20, 30 or 40 MPa, where no differences were detected. The content of α-tocopherol was significantly higher after SC-CO2 treatments compared to conventional extraction, independently of the applied treatment. On the other hand, the values of phenolic compounds and total antioxidant activity (TAC) increased as the pressure conditions of the SC-CO2 extraction increased, presenting a linear adjustment of the data. Regarding lipid oxidation, the lower oxidation indexes were obtained when the SC-CO2 pressure increased. Finally, our results confirmed that the application of SC-CO2 could be a potential alternative to conventional extraction in order to obtain oils from "horchata" by-products rich in high-added value compounds without the use of organic solvents which can be toxic.

Influence of Temperature, Solvent and pH on the Selective Extraction of Phenolic Compounds from Tiger Nuts by-Products: Triple-TOF-LC-MS-MS Characterization.

The aim of this study was to assess the effect of temperature, solvent (hydroethanolic mixtures) and pH on the recovery of individual phenolic compounds from "horchata" by-products. These parameters were optimized by response surface methodology and triple-TOF-LC-MS-MS was selected as the analytical tool to identify and quantify the individual compounds. The optimum extraction conditions were 50% ethanol, 35 °C and pH 2.5, which resulted in values of 222.6 mg gallic acid equivalents (GAE)/100 g dry matter and 1948.1 µM trolox equivalent (TE)/g of dry matter for total phenolic content (TPC) and trolox equivalent antioxidant capacity (TEAC), respectively. The extraction of phenolic compounds by the conventional solvent method with agitation was influenced by temperature (p = 0.0073), and more strongly, by the content of ethanol in the extraction solution (p = 0.0007) while the pH did not show a great impact (p = 0.7961). On the other hand, the extraction of phenolic acids was affected by temperature (p = 0.0003) and by ethanol amount (p < 0.0001) but not by the pH values (p = 0.53). In addition, the percentage of ethanol influenced notably the extraction of both 4-vinylphenol (p = 0.0002) and the hydroxycinnamic acids (p = 0.0039). Finally, the main individual phenolic extracted with hydroethanolic mixtures was 4-vinylphenol (303.3 µg/kg DW) followed by spinacetin3-O-glucosyl-(1→6)-glucoside (86.2 µg/kg DW) and sinensetin (77.8 µg/kg DW).

Phenolic profile of oils obtained from "horchata" by-products assisted by supercritical-CO2 and its relationship with antioxidant and lipid oxidation parameters: Triple TOF-LC-MS-MS characterization.

In this study, the effect of different supercritical CO2 (SC-CO2) pressures (10-40 MPa) on phenolic compounds extraction in oils obtained from "horchata" by-products was evaluated, and the results were compared to those obtained after conventional oil extraction (CE). Moreover, the relationship between the individual phenolic compounds and the total antioxidant capacity as well as oil oxidative quality parameters was compared. The phenolic profile and contents were largely influenced by extracting conditions. The main phenolic compound obtained by SC-CO2 was the isohydroxymatairesinol, particularly at 30 and 40 MPa, while 3-vinylphenol was the predominant compound in oils extracted by CE procedure. Increasing SC-CO2 extraction pressures enhanced the extraction of phenolic compounds, along with improving the antioxidant capacity and oxidative quality of extracted oil. The principal component analysis indicated that the main phenolic compounds associated with TEAC values were those extracted by SC-CO2, which were inversely correlated to oxidative indexes.

Impact of Non-Adherence and Flare Resolution on the Cost-Effectiveness of Treatments for Gout: Application of a Linked Pharmacometric/Pharmacoeconomic Model.

BACKGROUND: Dual urate-lowering therapy (ULT) with lesinurad in combination with either allopurinol or febuxostat is an option for patients with gout unsuccessfully treated on either monotherapy. Treatment failure is often a result of poor medication adherence. Imperfect adherence in clinical trials may lead to biased estimates of treatment effect and confound the results of cost-effectiveness analyses. OBJECTIVES: To estimate the impact of varying medication adherence on the cost effectiveness of lesinurad dual therapy and estimate the value-based price of lesinurad at which the incremental cost-effectiveness ratio is equal to £20,000 per quality-adjusted life-year (QALY). METHODS: Treatment effect was simulated using published pharmacokinetic-pharmacodynamic models and scenarios representing adherence in clinical trials, routine practice, and perfect use. The subsequent cost and health impacts, over the lifetime of a patient cohort, were estimated using a bespoke pharmacoeconomic model. RESULTS: The base-case incremental cost-effectiveness ratios comparing lesinurad dual ULT with monotherapy ranged from £39,184 to £78,350/QALY gained using allopurinol and £31,901 to £124,212/QALY gained using febuxostat, depending on the assumed medication adherence. Results assuming perfect medication adherence imply a per-quarter value-based price of lesinurad of £45.14 when used in dual ULT compared with allopurinol alone and £57.75 compared with febuxostat alone, falling to £25.41 and £3.49, respectively, in simulations of worsening medication adherence. CONCLUSIONS: The estimated value-based prices of lesinurad only exceeded that which has been proposed in the United Kingdom when assuming both perfect drug adherence and the eradication of gout flares in sustained treatment responders.

Enhancing Bioactive Antioxidants' Extraction from "Horchata de Chufa" By-Products.

During the production of a traditional drink produced from the tubers of Cyperus esculentus L. also known as "horchata de chufa," a high quantity of by-products are generated. These by-products are rich with valuable biological compounds, hence, there is a need to report their extraction conditions for further use in food production as raw materials. Therefore, the objective of this study was to evaluate and improve the conventional extraction process, applied for recovery of phenolic compounds, total flavonoids, and total antioxidant capacity from the by-products. Independent variables for extraction were: (i) Solvent type (mixtures of ethanol-water (v/v) at 0%, 25% and 50%); (ii) temperature (40, 50 and 60 °C), and (iii) extraction time (1, 2 and 3 h). The obtained results showed that solvent type, temperature, and time significantly influenced (p < 0.05) all investigated parameters. The highest content of total polyphenols (16.02 mg GAE/100 g of dry matter; d.m.), and total flavonoids (30.09 mg CE/100 g d.m.) was achieved by ethanol at 25% (v/v), after 3 h of extraction with temperatures of 60 °C and 50 °C, respectively. The highest value of antioxidant capacity (1759.81 µM Trolox equivalents/g d.m.) was observed with 50% aqueous ethanol (v/v), at 60 °C, and 3 h of extraction. From the obtained results, it can be concluded that the by-products of "Horchata de Chufa" are an important source of antioxidant bioactive compounds.

Thermal and non-thermal preservation techniques of tiger nuts' beverage "horchata de chufa". Implications for food safety, nutritional and quality properties.

"Horchata de chufa" is a traditional Spanish beverage produced from tiger nuts (Cyperus esculentus L.). Due to its richness in nutritional compounds, it is highly perishable and its conservation by pasteurization and/or adding preservatives is required. Although efficient, conventional thermal treatment for pasteurization induces changes in the nutritional and sensory properties. Replacing conventional pasteurization by non-thermal technologies such as pulsed electric fields, ultraviolet, and high pressure, combined with moderate temperatures (<40°C) allows a reduction of energy consumption, along with the preservation of the most thermo-sensitive molecules. Accordingly, this review deals with the description of the most relevant non-thermal technologies applied to preserve "horchata" beverage in order to extend the shelf life and inactivate pathogenic microorganisms as well as to preserve the nutritional and quality properties of this food beverage.

Impact of non-adherence on the safety and efficacy of uric acid-lowering therapies in the treatment of gout.

AIMS: Dual-urate-lowering therapy (ULT) with xanthine oxidase inhibitor and uricosuric medications is a treatment option for severe gout. Uricosuric agents can cause hyperuricosuria, a risk factor for nephrolithiasis and acute uric acid nephropathy. The aims of the present study were to simulate the relationship between suboptimal drug adherence and efficacy, and to quantify the risk of hyperuricosuria in gout patients receiving mono- and dual-ULTs. METHODS: The impact of poor medication adherence was studied using two-compartment pharmacokinetic (PK) models based on published evidence, and a semi-mechanistic four-compartment pharmacodynamic (PD) model. The PKPD model was used to simulate mono and dual-ULT in gout patients with either under-excretion (lowered clearance) or overproduction of uric acid, with suboptimal adherence modelled as either a single drug holiday of increasing duration or doses taken at random. RESULTS: Simulation results showed a surge in urinary uric acid occurring when dosing is restarted following missed doses. For under-excreters taking a 20-day drug holiday, the addition of 200 mg (or 400 mg) lesinurad to 80 mg febuxostat increased the percentage of patients experiencing hyperuricosuria from 0% to 1.4% (or 3.1%). In overproducers, restarting ULTs following drug holidays of more than 5 days leads to over 60% of patients experiencing hyperuricosuria. CONCLUSIONS: Suboptimal medication adherence may compromise the safety and efficacy of mono- and dual-ULTs, especially in patients with gout resulting from an overproduction of uric acid. Clinicians and pharmacists should consider counselling patients with respect to the risks associated with partial adherence, and offer interventions to improve adherence or tailor treatments, where appropriate.

Transcranial static magnetic field stimulation (tSMS) of the visual cortex decreases experimental photophobia.

Background Transcranial static magnetic field stimulation (tSMS) reduces cortical excitability in humans. Methods The objective of this study was to determine whether tSMS over the occipital cortex is effective in reducing experimental photophobia. In a sham-controlled double-blind crossover study, tSMS (or sham) was applied for 10 minutes with a cylindrical magnet on the occiput of 20 healthy subjects. We assessed subjective discomfort induced by low-intensity and high-intensity visual stimuli presented in a dark room before, during and after tSMS (or sham). Results Compared to sham, tSMS significantly reduced the discomfort induced by high-intensity light stimuli. Conclusions The visual cortex may contribute to visual discomfort in experimental photophobia, providing a rationale for investigating tSMS as a possible treatment for photophobia in migraine.

Current and New Insights in the Sustainable and Green Recovery of Nutritionally Valuable Compounds from Stevia rebaudiana Bertoni.

The South American plant Stevia rebaudiana Bertoni is a great source of noncaloric sweeteners (steviol glycosides), mainly concentrated in its leaves, but also has important antioxidant compounds (vitamin C, polyphenols, chlorophylls, and carotenoids) and other important macro- and micronutrients such as folic acid and all of the essential amino acids except tryptophan. Traditionally, conventional methods have been used to recover nutritionally valuable compounds from plant food matrices. However, nowadays, the need for obtaining greener, sustainable, and viable processes has led both food industries and food scientists to develop new processes in full correspondence with the green extraction concept. This review focuses on some of the most promising nonconventional and emerging technologies, which may constitute a potential alternative to conventional methods or even could be combined to obtain a synergistic effect, thus reducing extraction time as well as solvent consumption and avoiding the use of toxic solvents.