Magnetic iron oxide-based nanozymes: from synthesis to application.

Iron oxide nanozymes (IONzymes) are a class of magnetic nanoparticles that mimic the enzymatic activity of natural enzymes. These particles have received significant attention in recent years due to their unique properties, such as high stability, tunable magnetic responsiveness, and ability to act as biocatalysts for various chemical reactions. In this review, we aim to provide an overview of the production methods of magnetic nanozymes, including chemical, physical, and biological synthesis. The structure and design of magnetic nanozymes are also discussed in detail, as well as their applications in various fields such as biomedicine and environmental science. The results of various studies and the latest advances in the field of magnetic nanozymes are also discussed. This review provides valuable insights into the current state of magnetic nanozymes and highlights their potential for further development and application in various fields.

The Brain Health Imperative in the 21st Century-A Call to Action: The AAN Brain Health Platform and Position Statement.

Brain health is crucial to optimizing both the function and well-being of every person at each stage of life and is key to both individual and social progress. As a concept, brain health is complex and requires a multidisciplinary collaborative approach between many professional and public organizations to bring into effect meaningful change. Neurologists are uniquely positioned to serve as specialists in brain health and to advance the newly evolving field of preventive neurology, which aims to identify individuals at high risk of brain disorders and other neurologic conditions and offer strategies to mitigate disease emergence or progression. For decades, the American Academy of Neurology (AAN) has demonstrated a commitment to brain health through its public outreach and advocacy. The AAN's Brain Health Initiative launched in 2022 with a strategic plan prioritizing brain health as a key aspect of public engagement and positioning the AAN and neurologists as champions of brain health in collaboration with a broad range of other brain health providers. In this study, we present (1) the new definition of brain health developed by the AAN for neurologists, patients, partners in health care, and the public; (2) the strategic objectives of the AAN Brain Health Initiative; and (3) the AAN Brain Health Platform and Action Plan framework, including key positions on brain health, its 3 ambitious goals, and a national brain health vision. The top-line priorities of the AAN Brain Health Action Plan highlight the need for research, education, public policy, and direct-to-public messaging across the individual's life span and will serve as a catalyst for future cross-disciplinary collaborations within each epoch and longitudinally. The AAN Brain Health Platform is designed to communicate the AAN's vision for brain health and provide a blueprint toward achieving the future of optimal brain health across the life span for all. Through this position statement, we call upon neurologists and other stakeholders in brain health to join our collective efforts to accomplish the ultimate goal of transforming the current trajectory of public health of an increasing burden of neurologic disorders-from both illness and injury-to achieving optimal brain health for all.

Electroencephalographic (EEG) Biomarkers in Genetic Neurodevelopmental Disorders.

Collectively, neurodevelopmental disorders are highly prevalent, but more than a third of neurodevelopmental disorders have an identifiable genetic etiology, each of which is individually rare. The genes associated with neurodevelopmental disorders are often involved in early brain development, neuronal signaling, or synaptic plasticity. Novel treatments for many genetic neurodevelopmental disorders are being developed, but disease-relevant clinical outcome assessments and biomarkers are limited. Electroencephalography (EEG) is a promising noninvasive potential biomarker of brain function. It has been used extensively in epileptic disorders, but its application in neurodevelopmental disorders needs further investigation. In this review, we explore the use of EEG in 3 of the most prevalent genetic neurodevelopmental disorders-Angelman syndrome, Rett syndrome, and fragile X syndrome. Quantitative analyses of EEGs, such as power spectral analysis or measures of connectivity, can quantify EEG signatures seen on qualitative review and potentially correlate with phenotypes. In both Angelman syndrome and Rett syndrome, increased delta power on spectral analysis has correlated with clinical markers of disease severity including developmental disability and seizure burden, whereas spectral power analysis on EEG in fragile X syndrome tends to demonstrate abnormalities in gamma power. Further studies are needed to establish reliable relationships between quantitative EEG biomarkers and clinical phenotypes in rare genetic neurodevelopmental disorders.

Upregulation of Anti-Desmocollin 3 Antibodies in Pemphigus Diseases: A Case-control Study.

BACKGROUND: Pemphigus diseases are a subgroup of autoimmune bullous diseases characterized by autoantibodies against desmogleins and occasionally desmocollins. Desmocollin 3 is the main desmocollin isoform that contributes to cell adhesion in the epidermis. OBJECTIVE: To evaluate the presence and level of anti-desmocollin 3 antibodies in pemphigus diseases, and to investigate whether their presence is associated with a specific type, presentation, or clinical pattern. METHODS: Forty patients with pemphigus diseases and forty healthy controls were enrolled. Medical history, clinical examination, and pemphigus disease area index (PDAI) scoring were recorded for all patients. Serum samples were collected from both groups for assessment of anti-desmocollin 3 antibody reactivity by ELISA. RESULTS: The presence of anti-desmocollin 3 antibodies was significant among patients with pemphigus compared with controls (P=0.003). The level of anti-desmocollin 3 antibodies was also significantly higher in patients with pemphigus compared with controls (P=0.01). There was no significant relationship between the presence of anti-desmocollin 3 antibodies and any of the clinical presentations of pemphigus (type, severity, duration, activity, presence of annular pattern, or site of affection - mucosal, cutaneous, on the scalp, palmoplantar, or flexural). CONCLUSION: Anti-desmocollin 3 antibodies are upregulated in pemphigus diseases and can contribute to the pathogenesis of pemphigus. No specific clinical type, presentation, or pattern was found to be associated with the presence of anti-desmocollin 3 antibodies.

Accelerated Implementation of a Virtual Neurology Clerkship Amid a Global Crisis.

The standard neurology clinical experience in medical school focuses primarily on bedside patient encounters; however, the limitations of the clinical environment due to the current COVID-19 pandemic have accelerated the need for virtual curriculum development. To provide guidance to Neurology clerkship directors during this unprecedented time, the American Academy of Neurology (AAN) Undergraduate Education Subcommittee (UES) formed a workgroup to develop an outline for a virtual curriculum, provide recommendations, and describe models of integrating virtual curricula into the neurology clerkship. In this overview, we discuss different methods of virtual instruction, hybrid models of clerkship training and the challenges to its implementation, professionalism issues, and modification of feedback and assessment techniques specific to the virtual learning environment. We also offer suggestions for implementation of a hybrid virtual curriculum into the neurology clerkship. The virtual curriculum is intended to supplement the core neurology in-person clinical experience and should not be used for shortening or replacing the required neurology clinical clerkship.

Comparative Phytochemical Profile and Biological Activity of Four Major Medicinal Halophytes from Qassim Flora.

Four halophytic plants, Lycium shawii, Anabasis articulata, Rumex vesicarius, and Zilla spinosa, growing in the central Qassim area, Saudi Arabia, were phytochemically and biologically investigated. Their hydroalcoholic extracts' UPLC-ESIQ-TOF analyses demonstrated the presence of 44 compounds of phenolic acids, flavonoids, saponins, carbohydrates, and fatty acids chemical classes. Among all the plants' extracts, L. shawii showed the highest quantities of total phenolics, and flavonoids contents (52.72 and 13.01 mg/gm of the gallic acid and quercetin equivalents, respectively), along with the antioxidant activity in the TAA (total antioxidant activity), FRAP (ferric reducing antioxidant power), and DPPH-SA (2,2-diphenyl-1-picryl-hydrazyl-scavenging activity) assays with 25.6, 56.68, and 19.76 mg/gm, respectively, as Trolox equivalents. The hydroalcoholic extract of the L. shawii also demonstrated the best chelating activity at 21.84 mg/gm EDTA equivalents. Among all the four halophytes, the hydroalcoholic extract of L. shawii exhibited the highest antiproliferative activity against MCF7 and K562 cell lines with IC50 values at 194.5 µg/mL and 464.9 µg/mL, respectively. The hydroalcoholic extract of A. articulata demonstrated better cytotoxic activity amongst all the tested plants' extracts against the human pancreatic cancer cell lines (PANC1) with an IC50 value of 998.5 µg/mL. The L. shawii induced apoptosis in the MCF7 cell lines, and the percentage of the necrotic cells changed to 28.1% and 36.5% for the IC50 and double-IC50 values at 22.9% compared with the untreated groups. The hydroalcoholic extract of L. shawii showed substantial antibacterial activity against Bacillus cereus ATCC 10876 with a MIC value of 12.5 mg/mL. By contrast, the A. articulata and Z. spinosa exhibited antifungal activities against Aspergillus niger ATCC 6275 with MIC values at 12.5 and 50 mg/mL, respectively. These findings suggested that the L. shawii is a potential halophyte with remarkable biological properties, attributed to its contents of phenolics and flavonoid classes of compounds in its extract.

Contemporary Neuroscience Core Curriculum for Medical Schools.

Medical students need to understand core neuroscience principles as a foundation for their required clinical experiences in neurology. In fact, they need a solid neuroscience foundation for their clinical experiences in all other medical disciplines also, because the nervous system plays such a critical role in the function of every organ system. Due to the rapid pace of neuroscience discoveries, it is unrealistic to expect students to master the entire field. It is also unnecessary, as students can expect to have ready access to electronic reference sources no matter where they practice. In the pre-clerkship phase of medical school, the focus should be on providing students with the foundational knowledge to use those resources effectively and interpret them correctly. This article describes an organizational framework for teaching the essential neuroscience background needed by all physicians. This is particularly germane at a time when many medical schools are re-assessing traditional practices and instituting curricular changes such as competency-based approaches, earlier clinical immersion, and increased emphasis on active learning. This article reviews factors that should be considered when developing the pre-clerkship neuroscience curriculum, including goals and objectives for the curriculum, the general topics to include, teaching and assessment methodology, who should direct the course, and the areas of expertise of faculty who might be enlisted as teachers or content experts. These guidelines were developed by a work group of experienced educators appointed by the Undergraduate Education Subcommittee (UES) of the American Academy of Neurology (AAN). They were then successively reviewed, edited, and approved by the entire UES, the AAN Education Committee, and the AAN Board of Directors.

Predictors of Neurodevelopmental Impairment After Neonatal Bacterial Meningitis.

BACKGROUND: Neonatal bacterial meningitis has high rates of morbidity and mortality. Early clinical signs and neuroimaging suggest adverse outcomes, but little is known about their combined predictive properties. We evaluated the combination of findings most associated with death and neurodevelopmental impairment. METHODS: Single-center retrospective cohort study of term and late preterm neonates with bacterial meningitis. Predictors of death and neurodevelopmental impairment were identified on univariate analysis and incorporated into Lasso models to identify variables best predicting adverse outcomes. RESULTS: Of 103 neonates, 6 died acutely; 30% of survivors had neurodevelopmental impairment. Clinical variables (seizures, pressor support) predicted death and neurodevelopmental impairment better than the neuroimaging or combined findings (area under the curve 0.88 vs 0.79 and 0.83, respectively). Among survivors, neuroimaging findings (cerebrovascular lesions, ventriculomegaly) predicted neurodevelopmental impairment better than clinical or combined findings (area under the curve 0.82 vs 0.80 and 0.77, respectively). CONCLUSIONS: Seizures are important predictors of adverse outcomes in neonatal bacterial meningitis. Among survivors, neuroimaging findings help predict neurodevelopmental impairment.

Regional sequence expansion or collapse in heterozygous genome assemblies.

High levels of heterozygosity present a unique genome assembly challenge and can adversely impact downstream analyses, yet is common in sequencing datasets obtained from non-model organisms. Here we show that by re-assembling a heterozygous dataset with variant parameters and different assembly algorithms, we are able to generate assemblies whose protein annotations are statistically enriched for specific gene ontology categories. While total assembly length was not significantly affected by assembly methodologies tested, the assemblies generated varied widely in fragmentation level and we show local assembly collapse or expansion underlying the enrichment or depletion of specific protein functional groups. We show that these statistically significant deviations in gene ontology groups can occur in seemingly high-quality assemblies, and result from difficult-to-detect local sequence expansion or contractions. Given the unpredictable interplay between assembly algorithm, parameter, and biological sequence data heterozygosity, we highlight the need for better measures of assembly quality than N50 value, including methods for assessing local expansion and collapse.

High performance liquid chromatography - Mass spectrometric bioanalytical method for the determination of dapoxetine in human plasma: Application for bioequivalence study.

Dapoxetine is an oral medication used for treatment of premature ejaculation (PE) in men aged (18-64 years). In this study, we present a validated, precise and sensitive method for determination of dapoxetine in human plasma by liquid chromatography/ electrospray ionization-tandem mass spectrometry. Dapoxetine and the internal standard (Dapoxetine- d6) were extracted from plasma via liquid-liquid extraction (LLE). The LC separation was performed utilizing ACE C8 (4.6 X50) mm, 5 µm column. The mobile phase was composed of acetonitrile and buffer (0.01 M Ammonium acetate +0.02% Formic acid solution) (85:15, v/v). The method was linear within the concentration range of 5.0-600 ng/mL for Dapoxetine in human plasma. Short analytical run was achieved with 1.6 min run time. Intra-day and inter-day accuracy was between 97 and 106% with precision (CV, %) of ≤ 5% achieved across all the quality control samples. Dapoxetine was stable in several conditions with recovery rates > 90%. This method was utilized successfully in clinical pharmacokinetic study following oral administration of 60 mg Dapoxetine tablets in 36 healthy male subjects. The result for all 90% confidence intervals were within the preset ranges. The method proved to be highly reproducible and sensitive and thus can be employed in bioequivalence studies and large scale sample analysis of Dapoxetine.

Epigenetic Regulation of Neuregulin-1 Tunes White Adipose Stem Cell Differentiation.

Expansion of subcutaneous adipose tissue by differentiation of new adipocytes has been linked to improvements in metabolic health. However, an expandability limit has been observed wherein new adipocytes cannot be produced, the existing adipocytes become enlarged (hypertrophic) and lipids spill over into ectopic sites. Inappropriate ectopic storage of these surplus lipids in liver, muscle, and visceral depots has been linked with metabolic dysfunction. Here we show that Neuregulin-1 (NRG1) serves as a regulator of adipogenic differentiation in subcutaneous primary human stem cells. We further demonstrate that DNA methylation modulates NRG1 expression in these cells, and a 3-day exposure of stem cells to a recombinant NRG1 peptide fragment is sufficient to reprogram adipogenic cellular differentiation to higher levels. These results define a novel molecular adipogenic rheostat with potential implications for the expansion of adipose tissue in vivo.

Attracting neurology's next generation: A qualitative study of specialty choice and perceptions.

OBJECTIVES: To better understand the reasons medical students select or avoid a career in neurology by using a qualitative methodology to explore these factors, with the long-term objective of attracting more graduates to the field. METHODS: In 2017, 27 medical students and 15 residents participated in 5 focus groups, and 33 fourth-year medical students participated in semistructured individual interviews. Participants were asked predefined open-ended questions about specialty choice, experiences in their basic neuroscience course and neurology clerkship, and perceptions about the field. Interviews were audio recorded and transcribed. We used a flexible coding methodology to generate themes across groups and interviews. RESULTS: Four main analytical themes emerged: (1) early and broad clinical exposure allows students to "try on" neurology and experience the variety of career options; (2) preclerkship experiences and a strong neuroscience curriculum lay the foundation for interest in the field; (3) personal interactions with neurology providers may attract or deter students from considering the specialty; and (4) persistent stereotypes about neurologists, neurology patients, and treatment options harm student perceptions of neurology. CONCLUSION: Efforts to draw more students to neurology may benefit from focusing on clinical correlations during preclerkship neuroscience courses and offering earlier and more diverse clinical experiences, including hands-on responsibilities whenever possible. Finally, optimizing student interactions with faculty and residents and reinforcing the many positive aspects of neurology are likely to favorably affect student perceptions.

New-Onset Refractory Status Epilepticus in Children: Etiologies, Treatments, and Outcomes.

OBJECTIVES: To elucidate etiologies, treatment, functional and neurocognitive outcomes of children with new-onset refractory status epilepticus. DESIGN: A single-center retrospective study. SETTING: A tertiary care children's hospital. PATIENTS: All patients between 1 month and 21 years old admitted with new-onset refractory status epilepticus between January 2004 and July 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical presentation, laboratory data, imaging studies, and treatments were collected during hospitalization. Outcomes were assessed at hospital discharge and follow-up in the outpatient neurology clinic based on functional and neurocognitive outcomes as well as development of epilepsy. A total of 674 unique patients presented with status epilepticus of which 40 had new-onset refractory status epilepticus. Patients were classified into either refractory status epilepticus or super-refractory status epilepticus. The etiology of most children with new-onset refractory status epilepticus remained cryptogenic. The most common identified etiology was viral (20%). None of the patients had a contributory positive neuronal antibody test. Several treatments were tried including immunotherapy which was used in half of the patients. Five patients died (12.5%) during the acute phase of their disease, with four lost to follow-up. Twenty out of the remaining 31 patients (65%) developed epilepsy and 18 (58%) had persistent neurocognitive impairment. There was no statistical significant difference in various outcome measures and various etiologies, patients' characteristics, and treatments. CONCLUSIONS: In this single-center cohort, more than half of the children with new-onset refractory status epilepticus did not have an identifiable etiology. Unlike adult patients, the presence of positive neuronal antibody syndrome was rare. There was no difference in outcome between those with or without an identifiable etiology. As expected, patients with super-refractory status epilepticus had worse functional and neurocognitive outcomes. More standardized diagnostic and treatment algorithms are needed along with prospective multicenter studies.

Outcomes of High-Dose Steroid Therapy for Infantile Spasms in Children With Trisomy 21.

OBJECTIVE: We performed a retrospective chart review of patients with trisomy 21 and infantile spasms in our university-based pediatric epilepsy center between 2002 and 2016 in order to describe the clinical characteristics of children with these diagnoses as well as to evaluate their response to first-line treatments. METHODS: Patients with infantile spasms were identified via the neurophysiology database. Charts were reviewed with attention to infantile spasms diagnosis, presence of trisomy 21, age of reported clinical onset, treatment lag, treatments used, response to treatment, imaging findings, electroencephalography (EEG) data, and developmental outcomes. RESULTS: Of the 310 patients with infantile spasms, 24 also had trisomy 21. Three patients did not meet inclusion criteria. Ten of the 21 patients received nonstandard therapies first line; 2 of the 10 (20%) achieved spasm control, and 4 of the 8 who failed therapy (50%) progressed to Lennox-Gastaut syndrome. Eleven of the 21 patients received standard therapies as first-line treatments (10 with prednisolone according to the protocol in the United Kingdom Infantile Spasms Study [UKISS] and 1 with adrenocorticotrophic hormone [ACTH]). Nine of the 10 patients (90%) who received prednisolone achieved spasm resolution, 6 (60%) of these without relapse. The final patient (10%) failed prednisolone as well as ACTH. One patient received ACTH first line with success. CONCLUSION: This is the only series to follow children with trisomy 21 and infantile spasms in which a significant proportion received UKISS-protocol prednisolone. It adds to current knowledge about safety, tolerability, and effectiveness of prednisolone in this group.

Characteristics of graduating US allopathic medical students pursuing a career in neurology.

OBJECTIVES: To identify factors associated with medical students becoming neurologists because, despite the increasing burden of neurologic disorders, there is a growing neurologist shortage. METHODS: Deidentified data from the Association of American Medical Colleges Matriculating Student Questionnaire (MSQ) and Graduation Questionnaire (GQ) were obtained for the graduation years 2013 to 2014 through 2016 to 2017. Logistic regression was used to assess demographic characteristics and responses to training and career-related questions in association with specialty choice (intent to enter neurology). RESULTS: Of the 51,816 students with complete data, 1,456 (2.8%) indicated an intent to enter a neurology residency. Factors associated with an increased likelihood of entering neurology were a student's rating of excellent for their basic neuroscience course and neurology clerkship, participation in an MD/PhD program, majoring in neuroscience or psychology as an undergraduate, a selection response of "content of the specialty was a strong influence on career choice," and indicating interest in neurology on the MSQ. Factors associated with a decreased likelihood of entering neurology were a higher-priority response on the GQ for salary, work/life balance, and personal fit of the specialty. CONCLUSION: Data from surveys at the entry into and graduation from medical school suggest several approaches to increase the number of medical students entering neurology, including a focus on the student-reported quality of the basic neuroscience course and neurology clerkships, targeted engagement with MD/PhD students, and mentoring programs for students interested in neurology. Efforts to improve salaries for neurologists, to reduce medical school debt, and to improve work/life balance may also help to attract more students.

Therapeutic applications of adipose-derived stem cells in cardiovascular disease.

Cardiovascular disease (CVD) is the number one cause of death globally, and new therapeutic techniques outside of traditional pharmaceutical and surgical interventions are currently being developed. At the forefront is stem cell-centered therapy, with adipose derived stem cells (ADSCs), an adult stem population, providing significant clinical promise. When introduced into damaged heart tissue, ADSCs promote cardiac regeneration by a variety of mechanisms including differentiation into new cardiomyocytes and secretion of paracrine factors acting on endogenous cardiac cells. We discuss the application of ADSCs, their biochemical capabilities, availability, ease of extraction, clinical trial results, and areas of concern. The multipotent capacity of ADSCs along with their ability to secrete factors promoting cell survival and regeneration, along with their immunosuppressive capacity, make them an extremely promising approach in the field of CVD therapy.

Sorbent, device, matrix and application in microextraction by packed sorbent (MEPS): A review.

Microextraction by packed sorbent (MEPS) is a new miniaturized form of solid-phase extraction and it is a green sample pretreatment technology. MEPS has been widely accepted and used by several research groups online or offline as a sample preparation technique before instrument analysis. MEPS reduces the sample handling time and organic solvent consumption. MEPS is suitable for small sample volumes and can easily be connected with different chromatographic techniques without modification. The sorbent bed in MEPS is integrated into a liquid handling syringe that allows for low void volume sample manipulations either manually or in combination with laboratory robotics. MEPS is a simple, fast and robust sample preparation technique with several advantages, miniaturization, automation, fast operation course, on-line coupling with analytical instruments and low-cost operation with less solvent and low sample consumption. Sorbent type, device, and matrix are important factors in MEPS research and applications. The performance of MEPS has recently been illustrated by online with liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry assays for pharmaceutical, environmental, and food analyses. This paper deals with MEPS device-optimized sorbent, sample matrix, and application. The progress and potential development of the technique are also discussed.

Microextraction by packed sorbent.

Microextraction by packed sorbent (MEPS) is a miniaturized form of SPE. MEPS can handle small sample volumes and be connected on-line with LC or GC without any modifications. In addition, the MEPS sorbent bed is integrated into an injection syringe and can be used for more than 100 extractions. The key aspect of MEPS is that the solvent volume used for the elution of the analytes is of a suitable order of magnitude to be injected directly into GC or LC systems. MEPS has been used in many research fields such as environmental, biological and food analysis. This article gives an overview of the MEPS technique, including fields of application and common formats.