Systemic Signs Research Articles

Safety and Efficacy of Atogepant for the Preventive Treatment of Migraines in Adults: A Systematic Review and Meta-Analysis

Background: Migraine is a common neurological condition marked by unilateral recurrent pulsating headaches, often associated with systemic signs and symptoms. Recently, calcitonin gene-related peptide (CGRP) antagonists, including atogepant, an oral CGRP receptor antagonist, have emerged as effective and safe treatments. The current study sought to assess the efficacy and safety of atogepant for preventing episodic migraines in adults. Methods: A comprehensive search, following PRISMA guidelines, was conducted using PubMed, Web of Science, and Cochrane Library to identify randomized, double-blind, placebo-controlled trials published up to June 2024. Results: The studies included adult participants with episodic migraine treated with atogepant. The primary outcomes assessed were changes in mean monthly migraine days (MMDs) and monthly headache days (MHDs) over 12 weeks. Secondary outcomes included reduction in acute medication use, 50% responder rates, and adverse events. A meta-analysis using a random-effects model was performed to evaluate efficacy and safety. Six trials with 4569 participants were included. Atogepant significantly reduced mean monthly migraine days (MMDs) and monthly headache days (MHDs) compared to placebo at all doses (10 mg, 30 mg, 60 mg), with the 60 mg dose showing the greatest reduction (mean difference: −1.48 days, p < 0.001). Significant reductions in acute medication use and improved 50% responder rates were also observed for all doses. The safety profile of atogepant was favorable, with common adverse events being mild to moderate, such as constipation and nausea. There were no significant differences in serious adverse events between the atogepant and placebo groups. Conclusions: Atogepant is an effective and well-tolerated option for preventing episodic migraines, showing significant reductions in migraine frequency and acute medication use. However, further studies are necessary to assess its long-term safety and efficacy, especially at higher doses, and to investigate its potential role in personalized treatment strategies for migraine prevention.

Older patients affected by COVID-19: investigating the existence of biological phenotypes

IntroductionCOVID-19 provides an opportunity to examine biological phenotypes (observable morphological, functional and biological characteristics) in individuals who experience the same acute condition, potentially revealing differences in response to acute external stressors. The aim our study was to investigate biological phenotypes in older patients hospitalized for COVID-19, exploiting a panel of aging biomarkers.MethodsData were gathered from the FRACOVID Project, an observational multicenter study, aimed to evaluate the impact of frailty on health-related outcomes in patients 60 + with COVID-19 in Northern Italy. A hierarchical cluster analysis was run using log-transformed and scaled values of TNF-a, IL-1 beta, IL-6, PAI-1, GDF-15, NT-proBNP, and Cystatin C evaluated at admission.ResultsEighty-one participants (mean age 75.3 years; 60.5% male) were evaluated. Frailty was identified in 42% of the sample and 27.2% were unable to ambulate outdoors. The mean hospital stay was 24.7 days, with an in-hospital mortality rate of 18.5%. Three biological phenotypes were found: (1) ‘inflammatory’, with high inflammatory biomarkers; (2) ‘organ dysfunction’, characterized by elevated cystatin C and NT-proBNP, and lower inflammatory markers; and (3) ‘unspecific’, with lower NT-proBNP and GDF-15 levels, and intermediate concentrations of other biomarkers. The ’organ dysfunction’ phenotype showed the highest mean age and prevalence of frailty, disability, and chronic diseases. The ‘inflammatory‘ phenotype showed the highest burden of respiratory and systemic signs and symptoms of infection.ConclusionBiological phenotypes might be used to identify different clinical and functional phenotypes in individuals affected by COVID-19.

Optimizing location planning of tourism signage systems based on space syntax theory- a case of Lukang Old Street in Taiwan

Optimizing location planning of tourism signage systems based on space syntax theory- a case of Lukang Old Street in Taiwan

The “deliberate calculation of dress”: Strategic Uses of Fashion in George Egerton’s Keynotes and Discords

Abstract This article argues that George Egerton uses fashion as a sign system in the short stories included in Keynotes (1893) and Discords (1894). By utilizing minimalist physical descriptions of her protagonists’ dress, she privileges interiority and emphasizes how women achieve mobility of mind and body when they are freed from the physical suppression and psychological scrutiny associated with expectations for fashionable dress. In addition, she strategically manipulates the signifiers of bourgeois femininity by separating fashionable objects from the female body—often at the stress point of a story’s closure. Using a material culture approach that situates the stories within the context of late Victorian fashion plates, the article shows how Egerton delineates her primary theme—that women are defined by their interiority and not by the hyperfeminine, fashionable objects that are fetishized as integral to Victorian womanhood.

Long-term Outcome of a Chihuahua With Idiopathic Syndrome of Inappropriate Antidiuretic Hormone Secretion.

An approximately 3 yr old female Chihuahua was presented for evaluation of polyuria and polydipsia noted by the owner after adoption. Serum biochemistry and urinalysis revealed hyponatremia, hypochloremia, hypo-osmolality, and normal fractional excretion of sodium. Serum antidiuretic hormone concentration was 5.54 pg/mL and serum copeptin concentration was 135.40 pg/mL. The antidiuretic hormone value was above the reported range for healthy dogs and was considered inappropriate in light of serum osmolality. Idiopathic syndrome of inappropriate antidiuretic hormone secretion was considered the most likely diagnosis after excluding other potential causes, such as diuretic use, renal disease, adrenal disease, and thyroid dysfunction. The dog remains clinically well 2 yr after diagnosis without specific treatment other than minimal dietary salt supplementation. This case is unique because of the absence of systemic or neurologic signs, good long-term outcome without treatment, and use of novel diagnostic testing.

관광 기호 체계와 의미 생성 : 소쉬르의 구조언어학에 기반한 개념적 접근

This study explores the objective structures and mechanisms that generate meaning in tourism through a semiotic approach. It conceptualizes tourism as a non-linguistic sign system and reconfigures the tourism framework accordingly. Drawing on Saussure’s structural linguistics, the research examines the structures that underpin meaning creation in the tourism sign system. First, Ferdinand de Saussure’s views on language and epistemology are reviewed, along key concepts such as langue and parole, signifier and signified, syntagmatic and paradigmatic relations, and synchrony and diachrony. The study differentiates between signifier and signified in tourism signs, emphasizing that the ‘langue of tourism’ is not an independent 'substance' with inherent “content” but rather a “form” and “social fact” collectively constructed in the minds of potential tourists’ mind. Meaning in tourism emerges through syntagmatic and paradigmatic relations, demonstrating how meaning is produced in the tourism sign system. Through this process, the objective structures and mechanisms of meaning creation in the tourism sign system are revealed. This study complements prior semiotic research by providing a framework for understanding the objective foundations that enable subjective tourist experiences. Finally, the implications and limitations of this study are discussed.

Rezafungin versus caspofungin for patients with candidaemia or invasive candidiasis in the intensive care unit: pooled analyses of the ReSTORE and STRIVE randomised trials

BackgroundRezafungin is an echinocandin approved in the US and EU to treat candidaemia and/or invasive candidiasis. This post-hoc, pooled analysis of the Phase 2 STRIVE and Phase 3 ReSTORE trials assessed rezafungin versus caspofungin in patients with candidaemia and/or invasive candidiasis (IC) in the intensive care unit (ICU) at randomisation.MethodsSTRIVE and ReSTORE were randomised double-blind trials in adults with systemic signs and mycological confirmation of candidaemia and/or IC in blood or a normally sterile site ≤ 96 h before randomisation. Data were pooled for patients in the ICU at randomisation who received intravenous rezafungin (400 mg loading dose then 200 mg once weekly) or caspofungin (70 mg loading dose then 50 mg once daily) for ≤ 4 weeks. Outcomes were Day 30 all-cause mortality (primary outcome), Day 5 and 14 mycological eradication, time to negative blood culture, mortality attributable to candidaemia/invasive candidiasis, safety, and pharmacokinetics.ResultsOf 294 patients in STRIVE/ReSTORE, 113 were in the ICU at randomisation (rezafungin n = 46; caspofungin n = 67). At baseline, ~ 30% of patients in each group had impaired renal function and/or an Acute Physiologic Assessment and Chronic Health Evaluation II score ≥ 20. One patient (in the caspofungin group) was neutropenic at baseline. Day 30 all-cause mortality was 34.8% for rezafungin versus 25.4% for caspofungin. Day 5 and 14 mycological eradication was 78.3% and 71.7% for rezafungin versus 59.7% and 65.7% for caspofungin, respectively. Median time to negative blood culture was 18 (interquartile range, 12.6–43.0) versus 38 (interquartile range, 15.9–211.3) h for rezafungin versus caspofungin (stratified log-rank P = 0.001; nominal, not adjusted for multiplicity). Candidaemia/IC-attributable deaths occurred in two rezafungin patients versus one caspofungin patient. Safety profiles were similar between groups. Overall, 17.4% (rezafungin) versus 29.9% (caspofungin) of patients discontinued due to treatment-emergent adverse events. Rezafungin exposure following the initial 400-mg dose was comparable between patients in the ICU at randomisation (n = 50) and non-ICU patients (n = 117).ConclusionsRezafungin was well tolerated and efficacious in critically ill, mainly non-neutropenic patients with candidaemia and/or IC. This analysis provides additional insights into the efficacy and safety of rezafungin in the ICU population.

The role of root systems of Pinus sylvestris L. during the formation of secondary pine forests in deforestation in the Kola North

The role of the roots and root systems of Pinus sylvestris L. in the formation of secondary pine forests in the cuttings of the Kola North was studied. It has been established that in pine seedlings in disturbed areas, root and shoot systems are formed quite quickly. Already in the I-th grade of age, characteristic morphological signs of root systems appear, the feeding areas of trees begin to overlap each other. The bulk of the roots (80–85%) is concentrated in the upper 20-centimeter soil layer. A linear relationship between the taxation indicators of trees and the mass of root systems has been revealed. The conducted studies have shown that the formation of forest communities of Scots pine in the cuttings of the Kola North, their stability and productivity are directly dependent on the degree of development of individual roots and root systems as a whole.

New-onset complement-mediated thrombotic microangiopathy during the COVID-19 pandemic.

The coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus is alleged to enable a proinflammatory state, that leads to the activation of the coagulation and the complement cascade. In this study, we aimed to establish the impact of the COVID-19 pandemic on patients with new onset of cTMA/aHUS in the Vienna TMA cohort and whether COVID-19 or SARS-CoV-2 vaccinations would pose a greater risk of initial manifestation of cTMA/aHUS. We used the Vienna TMA cohort database to examine the prevalence of COVID-19 related and of SARS-CoV-2 vaccination-related aHUS/cTMA during the first 3 years of the COVID-19 pandemic in a large single-center cohort. Between March 2020 and May 2023, a total of 7 patients experienced their first aHUS/cTMA episode. No patient experienced a TMA relapse or more than one episode during the follow-up period. Three TMA episodes were attributable to either COVID-19 (n=1; 33%) or SARS-CoV-2 vaccination (n=2; 66%), respectively. All three patients had systemic signs of TMA and TMA was confirmed by kidney biopsy in all cases. Among the seven patients we recorded five infections that triggered one TMA episode (20%) and 19 vaccinations triggered two TMA episodes (10%; p=0.52, odds ratio 0.47; 95% CI 0.04-8.39). We speculate, that both SARS-CoV-2 vaccinations and COVID-19 episodes can represent a triggering factor for aHUS/cTMA episodes in (genetically) vulnerable individuals. However, COVID-19 might have a stronger association and might be a stronger trigger than the SARS-CoV-2 vaccines. The incidence of new aHUS cases did not differ from the pre-pandemic era in a large tertiary care centre cohort.

Myopia and systemic manifestation of tissue hyperlaxity: A population-based cross-sectional study.

Whether non-syndromic connective tissue hyperlaxity is associated with myopia is unknown. The aim of this study was to examine the association between systemic signs of tissue hyperlaxity and myopia among adolescents. Included were adolescents assessed before mandatory military service at the age of 16-18 years between 2011 and 2022. Diagnoses of hernias, pes planus, genu varus, genu valgum, and scoliosis, as well as joint injuries were used as surrogate markers for tissue hyperlaxity. The prevalence of these events among adolescents with myopia was evaluated and compared to the non-myopic population. Included were 920 806 adolescents. The mean age was 17.4 ± 1.4 years and 58.6% were men. Myopia was diagnosed in 290 759 adolescents (31.6%) and high myopia in 24 069 adolescents (2.6%). The prevalence of hernias was higher among adolescents with myopia, (2.76%, 95% confidence interval (95% CI): 2.69%-2.82% vs. 2.60%, 95% CI: 2.57%-2.65%), as were pes planus (14.92%, 95% CI: 14.79-15.05 vs. 13.51%, 95% CI: 13.42-13.59) and scoliosis (9.14%, 95% CI: 9.03-9.24 vs. 7.69%, 95%CI: 7.62-7.76). The prevalence of joint injuries was clinically similar between groups (less than 0.1% difference for ankle, shoulder, and knee injuries), as were genu varum and genu valgum (0.66%, 95%CI: 0.64%-0.69% vs. 0.68%, 95% CI: 0.66-0.70, respectively). Adjusted for possible confounders results remained consistent. Among a large sample of Israeli adolescents, those with myopia had a higher prevalence of hernias, pes planus, and scoliosis. These results could suggest a propensity for systemic conditions related to tissue laxity among myopic adolescents.

The effects of the traffic signs information volume on the visual characteristics and workload of novice and experienced drivers.

The effects of traffic sign information volume (TSIV) on the visual characteristics and workload of novice and experienced drivers were investigated in this study. TSIV plays a crucial role in road traffic safety, and understanding its impact on drivers is essential for designing effective traffic sign systems. This research aimed to compare the visual characteristics and workload of novice and experienced drivers under varying TSIV doses through simulated driving tests. The objective was to provide insights for optimizing the design of road TSIV. Six TSIV levels were considered: S0, S1, S2, S3, S4, and S5, representing different workload levels. Participants, including both novice and experienced drivers, were involved in simulated driving scenarios with varying TSIV levels. Eye movement data was collected using an eye tracker device. The study was conducted in China, and appropriate driving simulators and equipment were utilized. The findings revealed several valuable results. Experienced drivers exhibited a higher proportion of saccade behavior in the 30-90 ms time period and did not show rapid saccade behavior during the 0-30 ms period, indicating superior visual search strategies. Both novice and experienced drivers demonstrated improved visual cognitive abilities at the S3 level of TSIV, which corresponds to normal and safe driving conditions. Furthermore, a majority of both groups had saccade amplitudes in the range of 0°-4°, with experienced drivers showing a slightly higher proportion. About 82% of experienced drivers had saccade behavior within the range of 0°-2°, compared to 75% of novice drivers. The study concludes that the S3 level of TSIV, corresponding to 30 bits/km, is optimal for both novice and experienced drivers. This level promotes better visual performance and reduces visual workload, indicating that drivers' information acquisition capacity and visual search strategies are maximized while keeping the workload associated with driving at a minimum. These findings have significant implications for enhancing driving safety.

Yeni ‘Film’ veya ‘Sinema’ Tarihi: Sinema Tarihi Yazımında Yeni Gelişen İlkeler, Kuramlar ve Metodolojiler Üzerine Düşünceler

Film as an artefact has long been the subject of study by “film historians,” whether in terms of stylistic authenticity, genre specificity, or “high theory” analysis. Conversely, film history has been written as if films had no audiences (Biltereyst et al, 2012, p. 693). This kind of filmic-textual research tendency lies at the heart of the legacy of film studies discipline. In 1973, Jean Mitry proposed an ideal of film history as simultaneously, a history of its industry, its technologies, its systems of expression (or, more precisely, its systems of signification), and aesthetic structures, all bound together by the forces of the economic, psychosocial and cultural order (Maltby, 2006, p. 80). Humanities-based film studies were first re-conceptualized by the initiatives of International Federation of Film Archives (FIAF), during its 1974 and 1978 conferences. Drawing on the methodological stance of the French Annales school’s histoire totale, participants at the 1974 FIAF conference agreed on new historiographical methodologies for all rather than linear national cinema histories. In 1990, American historian Robert Sklar brought forward three types of “cinema historians” in which only second sub-type might be labeled as ‘film historian’ which has been emerged from one of the following disciplines: art history, philosophy, literary studies.

Frege’s Begriffsschrift: On the Visual Basis of Logical Articulation and Understanding

One of Gottlob Frege’s most original contributions to logic and philosophy was his logical notation, his ‘Begriffsschrift’. While long criticized, dismissed, or simply ignored, the recent secondary literature contains some helpful re-evaluations and partial defenses of it. These rely largely on technical, pragmatic, or cognitive-psychological considerations. In this paper, we reconsider Frege’s own reasons for valuing his notation highly. We argue that there is a further semiotic dimension, one that matters epistemologically. This dimension becomes evident once one takes seriously, partly also literally, some striking visual metaphors Frege uses. The result is an interpretation highlighting a side of Frege’s position that is not widely known. It involves his views about the indispensable role that language, or sign systems more generally, play for human thought, and especially, for logic and mathematics. More particularly and as we read Frege, a good logical notation allows for expressing conceptual/inferential relations in a ‘visually inscribed’, thus ‘perspicuous’ way, and this leads to a special kind of ‘insight’ in mathematics. Or as we elaborate this point further, it involves a kind of articulation and understanding hardly possible without it. Frege designed his Begriffsschrift with that specific goal in mind.

Kurdish Sign Language Recognition Using Convolutional Neural Network (CNN)

The present study examines the obstacles encountered by the deaf population, with a specific emphasis on the increasing significance of sign language in facilitating effective communication. The main mode of communication for deaf persons is Sign Language (SL), which is a visual and expressive method of communicating meaning via facial expressions, hand motions, and body gestures. The objective of this project is to automate the identification of sign language in order to improve accessibility and decrease reliance on interpreters. Specifically, the work focused on constructing an alphabet recognition system for Kurdish Sign Language (KSL). Due to its many intricacies and resemblances to the Arabic script, KSL requires a strong recognition model. The proposed method utilizes Convolutional Neural Networks (CNN) with an actual dataset to accurately recognize both numerical values and alphabetic characters in the Korean Sign Language (KSL). Real-time operation allows for rapid recognition of hand gestures and subsequent provision of textual output. The collection comprises 132,000 hand pictures, including 33 alphabetica and (0-9) numeral signs. Significantly, the use of MediaPipe, a method for processing 3D images, greatly improves the efficiency of detection. Multiple methodologies were investigated, and the integration of Convolutional Neural Networks (CNN), TensorFlow, and MediaPipe resulted in a remarkable accuracy of 99.87% with negligible dropout rates. This study establishes a foundation for enhanced communication and independence for the deaf population, representing a notable advancement in the automation of sign language recognition.

Appropriateness of antibiotic prescribing among patients treated for dental diseases in Mekelle city, Northern Ethiopia: a cross sectional study

BackgroundLocal operative treatments are generally preferred for most dental diseases, with antibiotics only recommended as an adjunct in specific cases. Misuse and overuse of antibiotics has been shown to significantly contribute to the development of resistant bacteria. However, the antibiotic prescribing practices of dentists in Ethiopia have not been thoroughly studied. This study aimed to assess the appropriateness of antibiotic prescribing for patients with dental diseases at dental clinics in Mekelle City, Northern Ethiopia.MethodsA cross sectional study was conducted in April and May 2020 among patients visiting dental clinics in Mekelle City. Data were collected through patient medical record reviews and dentist interviews. The appropriateness of antibiotic prescription was evaluated based on guidelines from the American Dental Association and the European Society of Endodontology. Data were analyzed using SPSS Statistics, version 29. Binary logistic regression analysis was performed, and the results were presented as odds ratios with 95% confidence intervals. A p value less than 0.05 was considered statistically significant.ResultsTwo hundred and thirty-one patients with dental diseases participated in the study. The mean age was 30.6 years with a standard deviation of 16.1. Most participants had dental pulp related disease. 89% of patients were prescribed antibiotics, with amoxicillin being the most common. Inappropriate antibiotic prescribing was identified in 175 (75.8%) of the study participants. The most common inappropriate prescribing was unnecessary antibiotic prescribing for dental conditions without systemic signs, assessed in 141 (80.1%) participants. Patients diagnosed with pulp related disease without systemic signs and those who had tooth extractions were significantly associated with inappropriate antibiotic prescription (p value < 0.001).ConclusionsThe study findings show that antibiotics are over-prescribed for dental conditions in this resource constrained setting, especially in patients who have had tooth extractions. Dentists need training on appropriate antibiotic use and antimicrobial stewardship interventions should be implemented in dental setting to reduce unnecessary antibiotic prescriptions and prevent antibiotic resistance development.

Analysis of Guidance Signage Systems from a Complex Network Theory Perspective: A Case Study in Subway Stations

Analysis of Guidance Signage Systems from a Complex Network Theory Perspective: A Case Study in Subway Stations

A multi-lingual sign language recognition system using machine learning

AbstractRecently, automatic sign language recognition field gets a great attention. Machine learning algorithms are mainly used to recognize hand gestures. Most of recent studies train their machine learning model using a specific sign language of a specific country such as the American Sign Language. In this paper, we propose a multi-lingual sign language system based machine learning that is called Multi-lingual Sign Languages Interpreter (MSLI) system. MSLI trains a machine learning model based on hand signs of multiple languages. It can detect the language of the input signs and their labels. In a case of input testing signs with the same language, the proposed system can provide two-steps recognition, where it only detects the language of the first sign, and then the rest signs are tested according to the recognized language. Also, MSLI can provide separate classification of signs per each language. Experiments were performed using 11 datasets with different languages. Separate and combined classification was performed on the input data. Experimental results show the accuracy of the proposed system. Training accuracy of the proposed system over most of the used separate different sign language datasets is approximately ranged from 90 to 100%. Also, most classification accuracy results of the test data of the separate datasets exceeded 90%. The combined classification of proposed MSLI archived training accuracy of 95.87% and testing accuracy of 92.33%.

A Concise Review on Herbal Immunity Booster

The main herbal components and their possible immune-boosting effects are covered in detail in this comprehensive assessment. The review emphasises the definition of immunity, many forms of immunity, The properties and roles of immune-related cells T and B lymphocytes. The immune system is shielded from infection by the anti-inflammatory, antioxidant, and immunomodulatory qualities of these herbs, which also have an impact on immune system signs and symptoms. Additionally, it investigates the effectiveness and safety of herbal immune boosters while taking into account both modern scientific research and traditional wisdom. The increasing popularity of herbal immune boosters—natural treatments made from plants—is covered in this abstract. Cardamom, Ashwagandha, Tulsi, Gingseng, Garlic, Ginger, Amla, and Black Pepper are well-liked natural immunity enhancers.

Communication in the Mirror of Social Semiotics

Introduction. The subject of this article is communicative resources, which are selected by partners from a huge variety of linguistic means, functional styles, rhetorical techniques, and subject activities, and through which a common semantic space between individuals is generated.Methodology and sources. As a methodological platform we propose the principles of praxis-oriented social semiotics. Being one of the relatively late trends of semiotic research, social semiotics focuses attention not so much on signs or sign systems as on social signifying practices as regular, repetitive, recognisable types of actions: the actions of communication participants are endowed with the properties of sign systems through which relations between individuals are discovered, made visible and meaningful. The mechanisms of meaning production, from the point of view of the participants of the event, are analysed using the concept of ‘discursive practices’, understood as speech actions in order to solve a variety of practical interpersonal tasks.Results and discussion. As an individual learns a variety of interpersonal discursive practices, different relational systems become available to him/her. Specific discursive practices allow individuals to present different versions of their self, justify their actions, maintain dominance and/or subordination relations, thus demonstrating mastery of the communicative situation. Following the principles of praxis-oriented social semiotics, it can be argued that interpersonal relationships involve what can be called a discourse of trust, personal involvement in relationships, intimacy/closeness.Conclusion. The described symbolic regulators allow not only to semiotically comprehend the social positions of interacting parties, but also to offer self-control procedures and an arsenal of communicative actions to the participants of interpersonal communication as means of behaviour management in situations of interpersonal communication.

S-Adenosylmethionine (SAMe) for Central Nervous System Health: A Systematic Review.

Background/Objectives: S-adenosylmethionine (SAMe) is a natural compound used to improve mood-related symptoms. Our aim was to determine the efficacy, safety, and optimal dose of SAMe in Central Nervous System (CNS) signs (e.g., mood, behavior). Methods: We conducted a PRISMA-based systematic review by searching PubMed, CINAHL, and Web of Science using MeSH search terms. Articles were independently reviewed by two researchers (with a third resolving conflicts) during title/abstract screening and full-text review. Data were extracted in the same approach, with a quality assessment of included articles. Results: Out of 1881 non-duplicated studies, 36 were included in the review focusing on CNS signs (mood, behavior, sleep). Most studies (n = 32) achieved a 4 or 5 out of 5 points, indicating high study quality. Overall, SAMe was effective in 24 of 36 studies, with adverse events mostly consisting of mild, transient gastrointestinal disturbances. Conclusions: Many patients in these studies did experience improvements in CNS signs from using SAMe alone or in combination with existing therapy. However, future studies are needed to further understand the long-term effects of SAMe in the CNS.