NeuroSci

Background: Systemic lupus erythematosus (SLE) is reported to be the most common rheumatological disorder associated with catatonia. To date, reports on catatonia manifestations in SLE patients are uncommon in published literature, which has often favored a fragmented vision. We performed a narrative review with the aim of identifying all published reports of catatonia in SLE patients to ascertain—in a comprehensive view—its clinical characteristics and to provide useful insights for daily clinical practice. Methods: Comprehensive literature searches were carried out on 10 March 2025 (subsequently repeated ahead of draft on 6 June) in all main bibliographic databases: MEDLINE and EMBASE (OVID interface); PsycINFO (ProQuest); and PubMed, to capture within-text references. All searches combined controlled (MESH, Entree, and APA Headings) and free-text elements for both areas under observation: systemic lupus erythematosus (SLE) AND catatonia, with primary focus on case reports and series. Sets of findings were reviewed separately by the authors, and the full text of selected items was sourced. Further useful references were retrieved through citation lists. Results: 39 cases of patients with SLE and catatonia were identified (35 females and 4 males), with a mean age of 22.64 years (range 11–46). Only three patients were over the age of 40; a total of 10 had catatonia at the same time of SLE onset and 5 within a month of SLE diagnosis. Antiphospholipid and anti-ribosomal P protein antibodies were rarely identified. Almost all the patients improved following treatment with lorazepam and/or electroconvulsive therapy. Only one case of malignant catatonia was reported. Finally, a large number of patients were Asian or Afro-American, at least in the reports where ethnicity was specified. Conclusions: Catatonia can occur in patients with SLE, and it may be its first clinical manifestation, especially in young patients. Its prognosis is mostly favorable. Full article

Advanced glycation end products (AGEs) are reactive compounds formed through non-enzymatic glycation in a process known as the Maillard reaction. While humans produce AGEs endogenously, these compounds can also enter the body through dietary sources, food preparation methods, and exposure to agricultural and food-related chemicals. AGEs can accumulate within cells and impair cellular function. In addition, when AGEs bind to receptors for advanced glycation end products (RAGE), they activate intracellular signaling pathways that promote the generation of reactive oxygen species (ROS), mitochondrial dysfunction, and inflammation. Sustained AGE-RAGE signaling drives chronic inflammation contributing to the development of various ailments, including neurodegenerative diseases. This review examines AGE formation, metabolism, and accumulation, with an emphasis on dietary sources as modifiable contributors to AGE-RAGE mediated pathology. We highlight the need for further research on dietary AGE restriction as a potential strategy to prevent or slow the progression of neurodegenerative and neuroinflammatory disorders. Full article

This study examines changes in frailty among patients hospitalized for acute ischemic stroke (AIS) in a nationwide hospital cohort in Germany. Data from AIS patients were compared between the period before the corona virus disease 2019 (COVID-19)-pandemic (1 January 2016 to 31 December 2019) vs the pandemic phase (1 January 2020 to 31 December 2022). Frailty was categorized using the Hospital Frailty Risk Score (HFRS). Inferential statistics were conducted using generalized linear mixed models. Among the 101,124 included AIS patients, the median HFRS decreased from 9.3 (interquartile range [IQR]: 5.2–15.5) in pre-pandemic years to 8.4 (IQR: 4.4–14.2) during the pandemic (p < 0.01). Among high frailty AIS patients, length of stay rose from 15.7 (±14.9) to 16.0 (±15.0) days, differing significantly from the decrease observed among low frailty patients from 5.9 (±3.7) to 5.0 (±3.5; p < 0.01) days. Compared to pre-pandemic levels, among low frailty patients, there was a significant increase in rates of thrombolysis (odds ratio [OR] 1.14 [95% CI 1.02–1.28; p = 0.020]) and thrombectomy (OR 1.35 [1.32–1.48; p = 0.047]). In this nationwide study in Germany, there was a longitudinal decrease in frailty among patients hospitalized for AIS which was accompanied by increased rates of thrombolysis and thrombectomy. Full article

Accessible, dependable cognitive assessment is integral to patient care of people with multiple sclerosis (PwMS). Traditional neuropsychological tests are well validated in the multiple sclerosis (MS) population, but not without limitations, such as the time and financial cost associated with traditional in person administration. Recent endeavors have sought to refine assessment, with particular attention to psychometric properties, accessibility, efficiency, and other practical considerations. One approach has been to streamline neuropsychological batteries to brief measures of essential domains, such as the Brief International Cognitive Assessment for MS (BICAMS). Another approach is the use of computerized neuropsychological assessment devices (CNADs). A systematic review of CNADs in PwMS was published in 2019. However, research has continued to expand in the years since. Here, we present an updated review of the BICAMS and further development of CNADs in MS. Tests with strong psychometric foundations are highlighted. Full article

Early detection of cognitive decline in older adults is essential for implementing timely interventions. This study aimed to compare the diagnostic accuracy of the Mini-Mental State Examination (MMSE^®) and the Montreal Cognitive Assessment (MoCA©) in identifying cognitive impairment among community-dwelling older adults, while considering the effect of educational level. A cross-sectional, analytical study was conducted with 90 individuals aged 60 years or older, classified into cognitively preserved and cognitively impaired groups using the Clinical Dementia Rating (CDR) scale. Cognitive performance was assessed using the MMSE and MoCA, with results analyzed using both standard and education-adjusted cut-off scores. Diagnostic accuracy was evaluated using Receiver Operating Characteristic (ROC) curves. The MoCA demonstrated superior discriminative ability compared to the MMSE, with a significantly larger area under the ROC curve (AUC = 0.943 vs. 0.826; p < 0.001), higher sensitivity (90.2% vs. 78.4%), and higher specificity (87.2% vs. 76.9%). When education-adjusted cut-off scores were applied, the MoCA achieved markedly improved diagnostic accuracy (87.8%) compared to the MMSE (71.1%), with stronger agreement with CDR classifications (κ = 0.746 vs. κ = −0.132). These findings demonstrate that the MoCA is more sensitive in detecting cognitive impairment and should be considered the preferred screening tool in clinical and research settings, particularly when appropriate educational adjustments are applied. Full article

The static orientation of the eyes during visual fixation is determined by the simultaneous operation of multiple equilibria. This phenomenon is collectively referred to as poly-equilibrium, which involves multiple systems that work together to cancel each other out and establish gaze direction. While other systems, such as audio- and cervico-ocular systems, may also contribute to gaze direction, this review focuses primarily on the commands issued by the vestibulo- and visuo-oculomotor systems that determine gaze direction, as they play a key role in the poly-equilibrium process. From the visual and vestibular activities accompanying the appearance of an object in the central visual field to the recruitment of premotor neurons responsible for the generation of slow and saccadic eye movements, a delicate balance is maintained. As long as the recruited channels convey commands that counterbalance each other, no movement is initiated. This alternative viewpoint leads to reconsidering the nature of saccadic and pursuit eye movements. Rather than viewing them as the dynamic reduction in brain signals encoding kinematic parameters such as position or velocity, they can be seen as the physical expression of intracerebral processes restoring balanced activities between sensorimotor channels whose recruitment leads to mutually opposed movements. Full article

Autism Spectrum Disorder presents one of the most complex challenges in contemporary neuroscience. This review adopts an unconventional narrative structure, drawing inspiration from song titles by The Beatles to explore the multifaceted biological, developmental, and social dimensions of autism. Spanning historical perspectives to embryonic origins and adult cognition, we examine critical topics including cortical folding, sensory processing, and the contributions of various brain regions such as the cerebellum and brainstem. The role of mirror neurons and other neural systems in shaping social behavior is discussed, alongside insights from animal models that have advanced our understanding of autism’s underlying mechanisms. Ultimately, this manuscript argues that autism is not merely a biomedical challenge, but a broader societal issue intersecting with education, human rights, and identity. Following the long and winding road of scientific discovery, we advocate for a more empathetic, interdisciplinary, and human-centered approach to autism research. Though the path ahead remains uncertain, every step informed by evidence and driven by collaboration brings us closer to deeper understanding, greater inclusion, and more effective support. Full article

Interest in ketamine as a novel treatment for substance use disorders (SUDs) has been increasing due to its N-methyl-D-aspartate (NMDA) glutamate receptor antagonism and mounting evidence that glutamate neurotransmission is involved in the pathogenesis of both depression and addictions. This narrative review provides an outline of clinical evidence reported in the literature from the 1970s to 2025 that examines the efficacy of ketamine for the treatment of SUDs, focusing primarily on randomized blinded controlled trials (RBCTs). Key cohort studies, retrospective studies, secondary analyses, case reports, and relevant basic neuroscience studies are reviewed to complement the more rigorous human controlled trial data. Thus far, ketamine has been tested in nine RBCTs targeting cocaine (three studies), alcohol (three studies), opioid use disorder (two studies), and nicotine (one study), suggesting efficacy for addiction in combination with psychotherapies, and often when doses produce subjectively reported mystical or psychedelic experiences. This review highlights promising preliminary evidence, and the need for more rigorous studies to elucidate the scope of drug addictions ketamine may target, its optimal dosing or route of administration, the importance of concurrent psychotherapies, professional supervision and safety monitoring, and which psychiatric comorbidities or contexts may contraindicate its use for SUDs. Full article

Objective: We aimed to quantify multiple sclerosis (MS)-related work productivity and to illustrate the longitudinal trends for relapses, disease progression, and utilization of health care resources in a nationally representative cohort of working North Americans living with MS. Background: The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) is a multicentered physician-reported registry which prospectively collects clinical information including imaging data over a long period of time from people with MS from sites across the U.S. and Canada. The Health Economics Outcomes Research (HEOR) Advisory Group has also incorporated Health-Related Productivity and Health Resource Utilization questionnaires, which collect information about health care economics of people with MS and its effects on daily life. Design/Methods: This is a prospective observational study utilizing data from NARCRMS. Socio-demographic, clinical, and health economic outcome data were collected through previously validated and structured questionnaires. Logistic regression was used to calculate the relative odds of symptom impact, with a generalized logit link for number of relapses. Cox proportional hazards regression was used to calculate hazard ratios for time to first relapse. Results: Six hundred and eighty-two (682) people with MS were enrolled in NARCRMS and had completed the HEOR questionnaires at the time of the analysis. Among the participants, 61% were employed full-time and 11% were employed part time. Fatigue was the leading symptom reported to impact both work and household chores. Among the employed participants, 13% reported having missed work with a median of 6.8 (IQR: 3.0–9.0) missed hours due to MS symptoms (absenteeism), while 35% reported MS having impacted their work output (presenteeism). The odds of higher disease severity (EDSS 2.0–6.5 vs. 0.0–1.5) were 2.29 (95% CI = 1.08, 4.88; p = 0.011) times higher for participants who identified reduction of work output. Fatigue was the most identified symptom attributed to work output reduction. Among all participants, 33% reported having missed planned household work with a median of 3.0 (IQR: 2.0–5.0) hours. The odds of higher disease severity were 2.49 (95% CI = 1.37, 4.53; p = 0.006) times higher for participants who identified reduction in household work output, and 1.70 (CI = 1.27, 2.49; p = 0.006) times higher for those whose fatigue affected housework output as compared to other symptoms. Conclusions: A preliminary review of the first 682 patients showed that people with MS had reduced work and housework productivity even at an early disease state. Multiple sclerosis (MS) can significantly impair individuals’ ability to function fully at work and at home, with fatigue overwhelmingly identified as the primary contributing factor. The economic value of finding an effective treatment for MS-related fatigue is substantial, underscoring the importance of these findings for policy development, priority setting, and the strategic allocation of healthcare resources for this chronic and disabling condition. Full article

Background: The literature shows that anterior communicating artery (AcoA) aneurysms are the most common intracranial aneurysms. To date, there has only been one postmortem study focused on the correlations between autopsy findings and imaging results in cases of intracranial aneurysms associated with anatomical variants of the circle of Willis (CW). Methods: We investigated the anatomical variants of the CW associated with the occurrence and rupture of AcoA aneurysms by performing comparative analyses, in the same patients, of postmortem autopsy data with antemortem computed tomography–angiography (CTA) results obtained in the first 48 h after the onset of subarachnoid hemorrhage. Our retrospective observational study identified the anatomical variants of the CW at autopsy in 16 deceased adult Romanian patients with AcoA aneurysms over a 12-year period (2010–2022). Results: The autopsy findings revealed that the AcoA ruptured aneurysms had a mean external diameter of 9.50 mm, and 71.4% of them presented three or four anatomical variants inside the same CW. The initial antemortem CTA examination correctly located the AcoA aneurysms in all cases (100%), and an anatomical variant of the CW was only noted in 18.75% of patients. The final postmortem re-analyzed the same CTA images identified in all cases (100%), focusing on both the AcoA aneurysm and all anatomical variants of the CW found during the autopsies. Conclusions: Although it was previously thought that the occurrence of AcoA aneurysms is related only to the hemodynamic changes induced by the nearby arterial anatomical variants, we identified the simultaneous involvement of at least one hypoplastic artery and one or two PCA fetal-type anatomical variants that were located in both the anterior and posterior parts of the CW. Furthermore, if sufficient time is devoted to the CT–angiography analysis and interpretation of the images, anatomical variants of the circle of Willis associated with AcoA aneurysms can be identified as accurately as they are in invasive postmortem autopsy examinations. Full article

This perspective paper proposes a theoretical framework for investigating potential associations between Long COVID and rising autism spectrum disorder (ASD) prevalence through established epidemiological methodologies. I propose examining temporal correlations, biological mechanisms, and rigorous methodological approaches, including Mendelian randomization, animal models, and evidence-based analyses, that could distinguish association from causation. The proposed framework recognizes autism as neurodiversity while suggesting investigation of environmental factors that may influence expression of genetic predispositions. Hypothesized key mechanisms include neuroinflammation, cytokine alterations, and immune dysfunction. I emphasize the critical distinction between demonstrating statistical associations and establishing causal influence, proposing specific experimental designs that could test causality. This paper presents conceptual frameworks requiring future empirical validation and does not include original data analysis. Full article

Seizure clusters can be observed in patients with epilepsy as well as in individuals without a previous history of epilepsy. However, there are no data on whether seizure clusters differ between these two populations. The purpose of this study was to investigate the clinical presentation, diagnostic findings, presence of seizure triggers, outcomes and complications of seizure clusters in patients with epilepsy and individuals without epilepsy in their medical history. The results indicate that epilepsy history was not independently associated with the number of seizures during cluster; however, increasing age was significantly associated with a lower seizure burden, and pneumonia demonstrated a marginal positive association. Structural brain lesions were prevalent in both groups; particularly chronic post-stroke lesions and frontal lobe lesions were significantly more common among epilepsy patients. Over half of patients without prior epilepsy received a new epilepsy diagnosis following the cluster event. No severe complications, including status epilepticus or postictal psychosis, were observed. Our findings suggest that age, acute comorbidities, and structural brain pathology likely exert greater influence on frequency of seizures during cluster. Chronic post-stroke lesions, which have not yet been reported as a risk factor for seizure clusters, were the most frequent brain pathology in both groups and may thus be considered as an additional risk factor for this clinical entity. Prospective and larger-scale studies are needed to further clarify these associations. Full article

The menstrual cycle affects the autonomic nervous system (ANS), cognition, and emotional valence in all biological women. There exists a complex relationship between hormonal fluctuations, ANS, cognition, and emotional valence during the different phases of the menstrual cycle, which includes menstruation, the follicular phase, ovulation, and the luteal phase. Hence, this narrative review is an attempt to comprehensively understand the effects of the menstrual cycle on the structural and functional integrity of the ANS. In order to provide a comprehensive understanding of the complex relationship between the menstrual cycle, hormonal fluctuations, and ANS function in biological women, this review examines key parameters, including heart rate variability (HRV), baroreflex sensitivity (BRS), muscle sympathetic nerve activity (MSNA), and pupillary light reflex (PLR), to investigate how these physiological systems are dynamically influenced by the cyclical changes in hormone levels and how these fluctuations impact various physiological and psychological outcomes, such as mood, cognition, and emotional regulation. There have been several studies previously performed to assess these parameters during different phases of the menstrual cycle. However, the results have been contradictory; therefore, this review explores possible reasons behind these inconsistent results, with likely reasons including irregularity in the menstrual cycles and differences in hormonal fluctuations between different women during similar phases of the menstrual cycle. Overall, there appears to be evidence to suggest that the menstrual cycle has both direct and indirect effects on ANS, cognition, and emotional valence, whilst measures of ANS may provide a means for assessing the effect of the menstrual cycle. Full article

Background: Spontaneous intracerebral hemorrhage (ICH) has the highest case fatality of all stroke types, yet recent epidemiological and outcome data from Central and Eastern Europe remain limited. Methods: We retrospectively analyzed prospectively collected data for 601 consecutive adults with primary ICH admitted to Sibiu County Clinical Emergency Hospital, Romania (2017–2023). Demographics, Glasgow Coma Scale (GCS), CT-derived hematoma volume (ABC/2), anatomical site, intraventricular extension (IVH), treatment, comorbidities, and in-hospital death were reported with exact counts and percentages; no imputation was performed. Results: Mean age was 68.4 ± 12.9 years, and 59.7% were male. Mean hematoma volume was 30.4 mL, and 23.0% exceeded 30 mL. IVH occurred in 40.1% and doubled mortality (50.6% vs. 16.7%). Overall case fatality was 29.6% and climbed to 74.5% for brain-stem bleeds. Men, although younger than women (66.0 vs. 71.9 years), died more often (35.4% vs. 21.1%; risk ratio 1.67, 95% CI 1.26–2.21). Systemic hazards amplified death risk: Oral anticoagulation, 44.2%; chronic alcohol misuse, 51.4%; thrombocytopenia, 41.0%; chronic kidney disease, 42.3%. Conservative management (74.9%) yielded 27.8% mortality overall and ≤15 for small-to-mid lobar or capsulo-lenticular bleeds; lobar surgery matched this (13.4%) only in large clots. Thalamic evacuation was futile (82.3% mortality), and cerebellar decompression performed late still carried 54.5% mortality versus 16.6% medically. Multivariable analysis confirmed that low GCS, IVH, large hematoma volume, thrombocytopenia, and chronic alcohol use independently predicted in-hospital mortality. Limitations: This retrospective study lacked post-discharge functional outcome data (e.g., mRS at 90 days). Conclusions: This study presents the largest Romanian single-center ICH cohort, establishing national benchmarks and underscoring modifiable risk factors. Early ICH lethality aligns with Western data but is amplified by exposures such as alcohol misuse, anticoagulation, thrombocytopenia, and CKD. Priorities include preventive strategies, timely surgical access, wider adoption of minimally invasive techniques, and development of a prospective regional registry. Full article

(1) Background: Choroid plexus papillomas (CPPs) are rare brain tumors that tend to occur in very young children. Mechanisms of CPP development remain unelucidated. Separately, the process of angiogenesis has been implicated in other primary brain tumors. We hypothesize that angiogenesis is a hallmark of CPP biology. This study aims to identify and validate angiogenic factors in CPPs. (2) Methods: Cerebrospinal fluid (CSF) and CPP tumor samples are collected. A multiplex immunoassay panel is used to identify differentially expressed cytokines in the CSF samples. Concurrently, patient-derived primary cell cultures and their supernatants are derived from CPP samples. Targeted proteome blot arrays and human umbilical vein endothelial cell (HUVEC) angiogenesis assays are used for validation studies. (3) Results: CSF profiling showed higher expressions of VEGF-A, MCP-1, MMP-1, TNF-α, and CD40L in CPP patient samples versus non-tumor controls. Next, assessment via online protein–protein network platforms reports that these cytokines are associated with endothelial cell regulation. Using an angiogenesis-focused approach, CPP-derived cell lines and supernatants showed similarly higher expressions of VEGF, MCP-1, and MMP-1. Next, sprouting of nodes and tubule formation were observed in HUVEC angiogenesis assay cultures when conditioned CPP cell culture media was added. (4) Conclusions: This proof-of-concept study demonstrates potential to explore angiogenesis in CPP. Full article

S100β is a significant signaling molecule and biomarker that is primarily expressed in the brain. At low physiological concentrations, S100β induces astrocyte maturation, microglial migration, and neural proliferation. However, high concentrations activate inflammatory and pro-apoptotic pathways. Due to this dual role, increased research is being invested into the role of S100β in neuronal homeostasis and inflammation. In fact, increased S100β expression is seen in many neuropathologies including Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, and traumatic brain injury. High S100β is generally associated with worsened disease outcome. Here, we provide an overview of the structure and role of S100β in various pathways, particularly in the context of neurological disorders. Modulation of S100β levels also holds promise as a therapeutic strategy. Micro-RNAs (miRNA) post-transcriptionally regulate gene expression and provide a novel approach reduce excess S100β protein. However, much of this research is still in its infancy. We outline current studies identifying miRNA in human and animal models of various neurological disorders. S100β itself has several predicted miRNA interactions although most have not yet been directly validated. Together, we compile the literature identifying S100β and miRNAs to guide future research in this field. We also comment on the feasibility and future uses of miRNA for pharmaceutical regulation of S100β, particularly for neurological treatments. Full article

Background: Neuropathic pain (NP), resulting from damage to the somatosensory nervous system, affects 7–10% of the global population and remains poorly managed despite available therapies. Smoking has been associated with increased pain severity and disease burden, yet its role in neuropathy/NP has not been systematically reviewed. This systematic review synthesizes the existing literature on smoking status and its relationship with neuropathy/NP incidence, prevalence, and severity. Methods: The review was conducted in accordance with PRISMA guidelines and included studies that assessed smoking consumption, dependency, quantity, and cessation in individuals with neuropathy/NP. Summary estimates were stratified by exposure type, and pooled odds ratios and relative risks were calculated. Results: Across 62 studies comprising cohort, case–control, and cross-sectional designs, smoking was consistently associated with greater NP prevalence and pain severity. Smoking dependency was linked to increased incidence, while cessation was associated with reduced risk of NP. Despite considerable heterogeneity and risk of bias, particularly from subjective exposure measurement and inconsistent classification, this relationship remained statistically significant. Conclusions: Findings support the role of smoking as a modifiable risk factor in various etiologies of neuropathy/NP. Cessation may represent a low-cost, low-risk, low-tech adjunctive therapy; however, further robust cessation interventional trials are needed, particularly for less common infectious causes of chronic NP such as leprosy. Full article

Background: Traumatic brain injury (TBI) remains a significant contributor to global mortality and long-term neurological disability. Accurate prognostic biomarkers are crucial for enhancing prognostic accuracy and guiding personalized clinical management. Objective: This review assesses the prognostic value of arterial spin labeling (ASL), a non-invasive MRI technique, in adult and pediatric TBI, with a focus on quantitative cerebral blood flow (CBF) and arterial transit time (ATT) measures. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and IEEE databases, including observational studies and clinical trials that applied ASL techniques (pCASL, PASL, VSASL, multi-PLD) in TBI patients with functional or cognitive outcomes, with outcome assessments conducted at least 3 months post-injury. Results: ASL-derived CBF and ATT parameters demonstrate potential as prognostic indicators across both acute and chronic stages of TBI. Hypoperfusion patterns correlate with worse neurocognitive outcomes, while region-specific perfusion alterations are associated with affective symptoms. Multi-delay and velocity-selective ASL sequences enhance diagnostic sensitivity in TBI with heterogeneous perfusion dynamics. Compared to conventional perfusion imaging, ASL provides absolute quantification without contrast agents, making it suitable for repeated monitoring in vulnerable populations. ASL emerges as a promising prognostic biomarker for clinical use in TBI. Conclusion: Integrating ASL into multiparametric models may improve risk stratification and guide individualized therapeutic strategies. Full article

Introduction: Despite clinical evidence for efficacy, there has been minimal uptake of transcranial direct current stimulation (tDCS) for musculoskeletal conditions. Thus, our objective was to explore the perceptions and experiences of people living with lower-limb musculoskeletal injury as well as healthy physically active populations and relate this to the usage of tDCS and key aspects of tDCS design that would improve the capacity for implementation. Methods: We conducted a qualitative descriptive study of 16 participants (44% women) using semi-structured focus groups to identify the descriptions and experiences of people living with lower-limb musculoskeletal injury and healthy physically active populations. A thematic template was used to create a coding structure. Codes were then grouped, and key themes were derived from the data. Results: Four primary themes were identified from focus groups. These were (i) the impact of musculoskeletal injuries on health and quality of life, (ii) performance and injury recovery as facilitators to using tDCS, (iii) barriers and facilitators to tCDS application and (iv) design and aesthetic factors for a tDCS device. Discussion: Our qualitative descriptive study identified four themes relevant to the successful implementation of tDCS into rehabilitative and performance practice. To increase the likelihood of successful tDCS implementation, these barriers should be addressed and facilitators promoted. This should include innovative approaches to device application and structure that allow for a stylish, user-friendly design. Full article