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Stroke is a significant disability and death cause worldwide and is conventionally defined as a neurological impairment relating to the intense focal harm of the central nervous system (CNS) by vascular causative components. Although the applicability of robotic rehabilitation is a topic with considerable practical significance because it has produced noticeably higher improvements in motor function than regular (physical and occupational) therapy and exempted the therapists, most of the existing bibliometric papers were not focused on stroke survivors. Additionally, a modular system is designed by joining several medical end-effector devices to a single limb segment, which addresses the issue of potentially dangerous pathological compensatory motions. Searching the Web of Science database, 31,930 papers were identified, and using the VOSviewer software and science mapping technology, data were extracted on the most prolific countries, the connections between them, the most valuable journals according to certain factors, their average year of publication, the most influential papers, and the most relevant topical issues (bubble map of term occurrence). The most prolific country in the analyzed field and over the entire period evaluated (1975–2022) is the United States, and the most prolific journal is Neurorehabilitation and Neural Repair, observing a marked increase in the three periods of scientific interest for this field. The present paper assesses numerous scientific publications to provide, through statistical interpretation of the data, a detailed description of the use of robotic rehabilitation in stroke survivors. The findings may aid scientists, academics, and clinicians in establishing precise goals in the optimization of the management of stroke survivors via robotic rehabilitation, but also through easier access to scientifically validated literature. [ABSTRACT FROM AUTHOR]

Alcohol consumption is common in many societies and has increased considerably, resulting in many socioeconomic and public health problems. In this sense, studies have been carried out in order to understand the mechanisms involved in alcohol consumption and related harmful effects. This study aimed to identify and map the knowledge and to perform bibliometric analysis of the neurotoxicology of alcohol based on the 100 most cited articles. A search was carried out in the Web of Science Core Collection database and information was extracted regarding the journal, authors, keywords, year of publication, number of citations, country and continent of the corresponding author. For each selected manuscript, the study design, alcohol exposure model, dose, period of exposure, and effect on the central nervous system and research hotspots were mapped. The journal with the highest number of publications was Alcoholism: Clinical and Experimental Research (n = 11 papers), the author who contributed the most was Crews FT (n = 8 papers), the studies had a total of 288 keywords and 75% of the publications were from the United States of America. The experimental studies evaluated the effects of prenatal and postnatal exposure and were conducted in rats and mice using doses ranging from 2.5 to 14 g/kg/day, with administration by subcutaneous, intraperitoneal, intragastric, or inhalation route or with free access through drinking bottles. Among the studies mapped, the oldest one (1989) aimed to understand the systemic damage and mechanisms of action involved, while the most recent focused on understanding the receptors and mechanisms involved in addiction, as well as genetic factors. Our results show the panorama of the most widespread scientific production in the scientific community on the neurotoxicology of ethanol, a high prevalence was observed in studies that addressed fetal alcohol syndrome and/or the effects of ethanol on neurodevelopment. [ABSTRACT FROM AUTHOR]

Background: The management of various central nervous system (CNS) disorders has been challenging, due to highly compact blood-brain barrier (BBB) impedes the access of most pharmacological agents to the brain. Among multiple strategies proposed to circumvent this challenge, intranasal delivery route has sparked great interest for brain targeting in the past decades. The aim of this study was to apply scientometric method to estimate the current status and future trends of the field from a holistic perspective. Methods: All relevant publications during 1998–2020 were retrieved from the Web of Science Core Collection (SCIE, 1998-present). Two different scientometric software including VOS viewer and CiteSpace, and one online platform were used to conduct co-authorship, co-citation, and co-occurrence analysis of journals, countries, institutes, authors, references and keywords. Results: A total of 2,928 documents, including 2,456 original articles and 472 reviews, were retrieved. Our analysis revealed a significant increasing trend in the total number of scientific publications over the past 2 decades (R 2 = 0.98). The United States dominated the field, reflecting in the largest amount of publications (971), the highest H-index (99), and extensive international collaboration. Jamia Hamdard contributed to most publications. Frey WH and Illum L were key researchers with the highest number of publications and citations, respectively. The International Journal of Pharmaceutics was the most influential academic journal, and Pharmacology/Pharmacy and Neurosciences/Neurology were the hottest research categories in this field. Based on keywords occurrence analysis, four main topics were identified, and the current research focus of this field has shifted from cluster 4 (pathways and mechanisms of intranasal delivery) to cluster 2 (the study of nasal drug delivery systems), especially the nanostructured and nano-sized carrier systems. Keywords burst detection revealed that the research focus on oxidative stress, drug delivery, neuroinflammation, nanostructured lipid carrier, and formulation deserves our continued attention. Conclusion: To the authors' knowledge, this is the first scientometric analysis regarding intranasal delivery research. This study has demonstrated a comprehensive knowledge map, development landscape and future directions of intranasal delivery research, which provides a practical and valuable reference for scholars and policymakers in this field. [ABSTRACT FROM AUTHOR]

Background This study examined the trends and patterns of opioid and non-opioid pharmacotherapy use among a large national sample of privately insured pediatric patients with cancer in the United States. Materials and Methods We identified pediatric (aged < 21) patients diagnosed with central nervous system (CNS), lymphoma, gonadal, leukemia, or bone cancer from MarketScan data 2005-2019. We examined the proportion of patients who filled a prescription for the following 5 types of pharmacotherapy: opioid, anticonvulsant, non-steroidal anti-inflammatory drug (NSAID), antidepressant, and muscle relaxant during active cancer treatment. We assessed the trends and patterns in pharmacotherapy using multivariable logistic regressions. Results Among 4174 patients included, 2979 (71%) had an opioid prescription; 746 (18%), 384 (9%), 202 (5%), and 169 (4%) had anticonvulsant, NSAID, antidepressant and muscle relaxant prescriptions, respectively. Multivariable logistic regression showed a nonlinear trend in the use of opioids among pediatric patients with cancer over time such that use slightly increased until 2012 (OR of 1.40 [95% CI, 1.12-1.73] for 2012 vs. 2006) but then decreased thereafter (OR of 0.51 [0.37-0.68] for 2018 vs. 2012). The use of anticonvulsants, NSAIDs, and muscle relaxants increased significantly linearly over time (all P  < .005). Conclusion There has been a downward trend in the use of opioids in recent years among pediatric patients with cancer and an upward trend in the use of non-opioid pharmacotherapy for pain management potentially as an alternative to opioids. [ABSTRACT FROM AUTHOR]

This paper summarizes the findings gleaned from detailed clinical examinations of three groups of residents who were exposed to trichloroethylene in well water. Also summarized are diagnostic findings for peripheral neuropathy. A detailed description of the neuropsychological test results is included, as well as a summary of domain-specific findings and diagnostic outcomes. A high rate of cognitive deficits of the type seen in patients with central nervous system dysfunction attributable to solvent exposure was seen. In addition, there was a clear developmental trend: subjects who were younger at the time of TCE exposure showed deficits in a larger variety of cognitive realms than did subjects who had already reached adulthood by the time of exposure. In particular, language deficits were seen in the younger, but not older, exposed subjects., (Copyright 1997 Academic Press.)

This paper presents the results of a study performed by the U.S. Food & Drug Administration (FDA) under the Conformance Assessment to Voluntary Standards program. The ASTM voluntary standard F647-85 (American Society for Testing and Materials: Standard Practice for Evaluating and Specifying Implantable Shunt Assemblies for Neurological Applications) was evaluated as to the adequacy of its test methods and the reasonableness of its application to currently marketed shunt devices. The objective of this study was to assess the impact of ASTM: F647-85 on the safety and effectiveness of shunt devices and thereby assist the FDA in setting priorities for its mandatory standards development activities. By searching the FDA's postmarketing surveillance database and by testing seventeen shunt devices and three catheters from six manufacturers, it was determined that these devices conform with most of the ASTM standard requirements. However, no single device conformed to all of the requirements of the standard. Suggestions for improving the voluntary standard's impact on the safety of shunt devices are presented.

Background: Pain in osteoarthritis (OA) has been attributed traditionally to local tissue injury causing 'nociceptive pain'. However, recent studies suggest that neuropathic and central sensitization mechanisms may contribute to the pain experience. However, the relationship between these pain mechanisms and physical function has not been thoroughly addressed. This study aimed to assess the association of central sensitization and neuropathic pain with physical function in knee OA. Results: Participants with a positive central sensitization inventory score (CSI) (≥ 40) had a decreased total Knee injury and Osteoarthritis Outcome Score (KOOS) and its subscales (p < 0.001), a longer timed up and go test time (p = 0.002) and a higher PainDETECT questionnaire (PD-Q) and visual analogue scale (p < 0.001, p = 0.026 respectively). The severity of Kellgren-Lawrence grading (KL) (p < 0.001), depressive and anxiety symptoms (p < 0.001) increased with neuropathic pain severity. In addition, participants with a high PD-Q score (≥ 19) had a longer timed up and go test time (p < 0.001) and a decreased total KOOS score (p < 0.001). Moreover, we found that CSI score, KOOS score, and KL grading were significantly predicted the PD-Q score (p = 0.046, p < 0.001, p = 0.007, respectively). Regarding the physical function predictors, multivariate linear regression analysis revealed that pressure pain threshold at right elbow and right knee (p = 0.005, p < 0.001) in addition to PD-Q (P < 0.001) were significantly associated with KOOS score, while CSI and Hospital Anxiety Depression Scale were not. Conclusion: Knee OA patients with significant central sensitization and neuropathic pain reported increased pain, more functional impairment, more anxiety and depressive symptoms than OA patients without central sensitization and neuropathic pain. Additionally, neuropathic pain and presence of central sensitization were significant predictors for functional ability. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of disability with limited effective interventions that improve recovery in the subacute phase. This protocol aims to evaluate the safety and efficacy of a non-invasive, extremely low-frequency, low-intensity, frequency-tuned electromagnetic field treatment [Electromagnetic Network Targeting Field (ENTF) therapy] in reducing disability and promoting recovery in people with subacute ischemic stroke (IS) with moderate-severe disability and upper extremity (UE) motor impairment. Following a sample-size adaptive design with a single interim analysis, at least 150 and up to 344 participants will be recruited to detect a 0.5-point (with a minimum of 0.33 points) difference on the modified Rankin Scale (mRS) between groups with 80% power at a 5% significance level. This ElectroMAGnetic field Ischemic stroke-Novel subacutE treatment (EMAGINE) trial is a multicenter, double-blind, randomized, sham-controlled, parallel two-arm study to be conducted at approximately 20 United States sites, and enroll participants with subacute IS and moderate-severe disability with UE motor impairment. Participants will be assigned to active (ENTF) or sham treatment, initiated 4-21 days after stroke onset. The intervention, applied to the central nervous system, is designed for suitability in multiple clinical settings and at home. Primary endpoint is change in mRS score from baseline to 90 days post-stroke. Secondary endpoints: change from baseline to 90 days post-stroke on the Fugl-Meyer Assessment - UE (lead secondary endpoint), Box and Block Test, 10-Meter Walk, and others, to be analyzed in a hierarchical manner. EMAGINE will evaluate whether ENTF therapy is safe and effective at reducing disability following subacute IS. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to determine the epidemiologic characteristics and survival of patients with primary brain and other central nervous system (CNS) tumors in Korea and to compare our findings with those from the United States. Materials and Methods We collected data on primary brain and CNS tumors diagnosed between 2007 and 2016 from the Korea Central Cancer Registry. The age-standardized incidence rates (ASRs) and 5-year relative survival rates (RSRs) were evaluated. We applied the classification and definitions of the Central Brain Tumor Registry of the United States to our analysis for direct comparison with United States data. Results A total of 115,050 primary brain and CNS tumors were identified, and the ASR of all tumors was 22.01 per 100,000 individuals, which was lower than the 23.41 in the United States. However, the ASR of malignant tumors was significantly lower herein (4.27) than in the United States (7.08). Meningeal tumors were the most common histologic group among all tumors (ASR, 8.32). The 5-year RSR of all primary brain and other CNS tumors was 86.4%, and that of all malignant tumors was 44.1%, which was higher than the 35.8% observed in the United States. Among malignant tumors, glioblastomas had the lowest 5-year RSR (12.1%). Conclusion In Korea, malignant brain and other CNS tumors have a lower incidence and better survival outcome. [ABSTRACT FROM AUTHOR]

Background: Gliomas are the most common type of primary malignant brain tumor in adults, representing one third of all primary and central nervous system (CNS) tumors and 80% of malignant tumors diagnosed in the Western world. Epidemiological data indicate that the overall incidence and mortality of cancer is higher in males, while females have a better prognosis. The goal of this study is to determine whether there are sex differences in the time to treat and clinical outcomes in patients with glioma Methods: Glioblastoma (GB) and Lower Grade Glioma (LGG) patients were defined per the Central Brain Tumor Registry of the United States (CBTRUS) from the National Cancer Database (NCDB) for diagnosis years 2004 to 2016. Associations between sex and time to treatment variables as well as associations between sex and multiple clinical outcomes were assessed using univariable and multivariable models. Results: A total of 176,100 patients were used for analysis (124,502 GBM and 51,598 LGG). Males had a statistically significant association with >7 days to surgery (OR = 1.09, CI 1.05–1.13, p < 0.001) but this association was not observed in the multivariable model (OR = 1.05, CI 0.96–1.16, p = 0.25). After adjustment for key variables including time to treat variables, males with GB and LGG had a higher risk of death (HR = 1.11, CI 1.09–1.13, p < 0.001, HR = 1.09, CI 1.03–1.15, p < 0.001; respectfully). Sex differences in 90-day mortality for GBM were not found after adjustment (OR for males = 0.99, CI 0.91–1.08, p = 0.93). For LGG, both the univariable and multivariable logistic regression models showed no sex differences in 90-day mortality (OR for males = 1.03, CI 0.94–1.12, p = 0.45; multivariable OR for males = 0.81, CI 0.62–1.06, p = 0.13). Conclusions: Based on NCDB data, there were no statistically significant differences in time to treatment between males and females, however males had a higher proportion of GB and LGG as well as a higher risk of death compared to females. [ABSTRACT FROM AUTHOR]

Background: The United States faces a national crisis involving opioid medications, where currently more than 130 people die every day. To combat this epidemic, a better understanding is needed of how opioids penetrate into the central nervous system (CNS) to facilitate pain relief and, potentially, result in addiction and/or misuse. Animal models, however, are a poor predictor of blood–brain barrier (BBB) transport and CNS drug penetration in humans, and many traditional 2D cell culture models of the BBB and neurovascular unit have inadequate barrier function and weak or inappropriate efflux transporter expression. Here, we sought to better understand opioid transport mechanisms using a simplified microfluidic neurovascular unit (NVU) model consisting of human brain microvascular endothelial cells (BMECs) co-cultured with astrocytes. Methods: Human primary and induced pluripotent stem cell (iPSC)-derived BMECs were incorporated into a microfluidic NVU model with several technical improvements over our previous design. Passive barrier function was assessed by permeability of fluorescent dextrans with varying sizes, and P-glycoprotein function was assessed by rhodamine permeability in the presence or absence of inhibitors; quantification was performed with a fluorescent plate reader. Loperamide, morphine, and oxycodone permeability was assessed in the presence or absence of P-glycoprotein inhibitors and cortisol; quantification was performed with mass spectrometry. Results: We first report technical and methodological optimizations to our previously described microfluidic model using primary human BMECs, which results in accelerated barrier formation, decreased variability, and reduced passive permeability relative to Transwell models. We then demonstrate proper transport and efflux of loperamide, morphine, and oxycodone in the microfluidic NVU containing BMECs derived from human iPSCs. We further demonstrate that cortisol can alter permeability of loperamide and morphine in a divergent manner. Conclusions: We reveal a novel role for the stress hormone cortisol in modulating the transport of opioids across the BBB, which could contribute to their abuse or overdose. Our updated BBB model represents a powerful tool available to researchers, clinicians, and drug manufacturers for understanding the mechanisms by which opioids access the CNS. [ABSTRACT FROM AUTHOR]

The negative side effects of opioid-based narcotics underscore the search for alternative non-opioid bioactive compounds that act on the peripheral nervous system to avoid central nervous system-mediated side effects. The transient receptor potential V1 ion channel (TRPV1) is a peripheral pain generator activated and sensitized by heat, capsaicin, and a variety of endogenous ligands. TRPV1 contributes to peripheral sensitization and hyperalgesia, in part, via triggering the release of proinflammatory peptides, such as calcitonin gene-related peptide (CGRP), both locally and at the dorsal horn of the spinal cord. Ultrapotent exogenous TRPV1 agonists, such as resiniferatoxin identified in the latex of the exotic Euphorbia resinifera , trigger hyperalgesia followed by long lasting, peripheral analgesia. The present study reports on the analgesic properties of Euphorbia bicolor , a relative of E. resinifera , native to the Southern United States. The study hypothesized that E. bicolor latex extract induces long-lasting, non-opioid peripheral analgesia in a rat model of inflammatory pain. Both inflamed and non-inflamed adult male and female rats were injected with the methanolic extract of E. bicolor latex into the hindpaw and changes in pain behaviors were reassessed at various time points up to 4 weeks. Primary sensory neuron cultures also were treated with the latex extract or vehicle for 15 min followed by stimulation with the TRPV1 agonist capsaicin. Results showed that E. bicolor latex extract evoked significant pain behaviors in both male and female rats at 20 min post-injection and lasting around 1–2 h. At 6 h post-injection, analgesia was observed in male rats that lasted up to 4 weeks, whereas in females the onset of analgesia was delayed to 72 h post-injection. In sensory neurons, latex extract significantly reduced capsaicin-evoked CGRP release. Blocking TRPV1, but not opioid receptors, attenuated the onset of analgesia and capsaicin-induced CGRP release. Latex was analyzed by mass spectrometry and eleven candidate compounds were identified and reported here. These findings indicate that phytochemicals in the E. bicolor latex induce hyperalgesia followed by peripheral, non-opioid analgesia in both male and female rats, which occurs in part via TRPV1 and may provide novel, non-opioid peripheral analgesics that warrant further examination. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis is a common infection in the western and southwestern United States as well as parts of Mexico and Central and South America and is due to the soil-dwelling fungi Coccidioides. Central nervous system (CNS) infection is an uncommon manifestation that is nearly always fatal if untreated. The presentation is subtle, commonly with headache and decreased mentation. The diagnosis should be considered in patients with these symptoms in association with a positive serum coccidioidal antibody test. The diagnosis can only be established by analysis of cerebrospinal fluid (CSF), which typically demonstrates a lymphocytic pleocytosis, hypoglycorrhachia, elevated protein, and positive CSF coccidioidal antibody. Cultures are infrequently positive but a proprietary coccidioidal antigen test has reasonable sensitivity. Current therapy usually begins with fluconazole at 800 mg daily but other triazole antifungals also have efficacy and are often used if fluconazole fails. Triazole therapy should be lifelong. Intrathecal amphotericin B, the original treatment, is now reserved for those in whom triazoles have failed. There are several distinct complications of CNS coccidioidal infection, the most common of which is hydrocephalus. This is nearly always communicating and requires mechanical shunting in addition to antifungal therapy. Other complications include cerebral vasculitis, brain abscess, and arachnoiditis. Management of these is difficult and not well established. [ABSTRACT FROM AUTHOR]

Objective: Medications for treatment of substance use disorders are underutilized in treatment programs in the United States. Little is known about how insurance enrollment within states affects treatment program decisions about whether to offer medications. The primary objective of the study was to examine the impact of health insurance enrollment on availability of substance use disorder medications among treatment programs.Methods: Data from the 2012 National Survey of Substance Abuse Treatment Services, National Survey on Drug Use and Health, American Community Survey, Area Health Resource File, and the Substance Abuse and Mental Health Services Administration were combined to examine the impact of state insurance enrollment on availability of substance use disorder medications in treatment programs (N=9,888). A two-level, random-intercept logistic regression model was estimated to account for potential unobserved heterogeneity among treatment programs nested in states.Results: The percentage of state residents with employer-based insurance and Medicaid was associated with greater odds of offering at least one medication among treatment programs. A 5% increase in the rate of private insurance enrollment was associated with a 7.7% increase in the probability of offering at least one medication, and a 5% increase in the rate of state Medicaid enrollment was associated with a 9.3% increase in the probability of offering at least one medication.Conclusions: Results point to the potential significance of health insurance enrollment in shaping the availability of substance use disorder medications. Significant expansions in health insurance enrollment spurred by the Affordable Care Act have the potential to increase access to medications for many Americans. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggested increased cancer incidence and mortality in workers exposed to solvents and other chemicals in computer manufacturing jobs. Most previous studies were of small cohorts and findings were inconsistent. A lawsuit involving a large U.S. company produced a data file for analysis. This study sought to elucidate patterns of mortality in workers who were engaged manufacturing computers and related electronic components in the largest database available to date. Methods: A proportional mortality and proportional cancer mortality analysis of deaths in eligible workers between 1969 and 2001 was carried out, with U.S. population mortality data as the standard for comparison. Mortality and work history data was from corporate mortality and work history files produced during litigation and standard U.S. and state mortality files. The study base comprised 31,941 decedents who died between 1969 and 2001, who had worked for at least five years and whose death information was collected in the corporate mortality file. Proportional mortality ratios (PMRs) and Proportional Cancer Mortality Ratios (PCMRs) and their 95%confidence intervals were computed for 66 causes of death in males and females. Results: PMRs for all cancers combined were elevated in males (PMR = 107; 95% CI = 105-109) and females (PMR = 115; 95% CI = 110-119); several specific cancers and other causes of death were also significantly elevated in both males and females. There were reduced deaths due to nonmalignant respiratory disease in males and females and heart disease in females; several specific cancers and other causes of death were significantly reduced in both males and females. Proportional cancer mortality ratios (PCMRs) for brain and central nervous system cancer were elevated (PCMR = 166; 95% CI = 129-213), kidney cancer (PCMR = 162; 95% CI = 124-212),melanoma of skin (PCMR = 179; 95% CI = 131-244) and pancreatic cancer (PCMR = 126; 95% CI= 01-157) were significantly elevated in male manufacturing workers. Kidney cancer (PCMR =212; 95% CI = 116-387) and cancer of all lymphatic and hematopoietic tissue (PCMR = 162; 95%CI = 121-218) were significantly elevated in female manufacturing workers. Conclusion: Mortality was elevated due to specific cancers and among workers more likely to be exposed to solvents and other chemical exposures in manufacturing operations. Due to lack of individual exposure information, no conclusions are made about ssociations with any particular agent. [ABSTRACT FROM AUTHOR]

Injury of the spinal cord has been known since antiquity. There is no cure for the injury and until modern times patients died rapidly from a combination of pressure sores and urinary tract infection. Treatment consists of preventing complications until the spine has stabilised and the patient can be rehabilitated to an independent life. This article explores how this treatment developed in the ancient world, the middle ages, in Europe, Great Britain, and latterly in the United States. It describes how these principles of treatment were recognised particularly in Germany, the United Stales, and Great Britain and evaluates the relative contributions made by the different pioneers. [ABSTRACT FROM AUTHOR]

The transplantation of living cells and tissues to restore function and/or provide therapeutic molecules has been an active and ongoing area of research interest for over 25 years. Several of these potential therapies have reached initial clinical trials, and it is likely that applications will continue to expand, and that novel and improved approaches will be explored over the next several years. In the past, many of these experimental approaches were tested in early clinical trials without the oversight of regulatory agencies such as the Food and Drug Administration. However, as novel cellular therapies move from preclinical laboratory findings to the clinical arena, researchers and regulators face new and continually evolving issues and uncertainties involving long-term safety and efficacy. Using adrenal medullary transplantation in the spinal cord for pain as an example, this review presents an overview of past and current regulatory guidelines for moving these promising, novel cellular transplantation therapies from the laboratory to the human. [ABSTRACT FROM AUTHOR]

The article focuses on the study conducted in the U.S. regarding the impact of pain on neuropeptides and monoamigernic neurotransmitters. The authors discuss the importance of discovering oligopeptides in the central nervous system and its significance to the identification of the amino acid sequence. Moreover, he talks about the back up systems of the central nervous system.