Fine particulate matter (PM2.5) can cause brain damage and diseases. Of note, ultrafine particles (UFPs) with an aerodynamic diameter less than or equal to 100 nm are a growing concern. Evidence has suggested toxic effects of PM2.5 and UFPs on the brain and links to neurological diseases. However, the underlying mechanism has not yet been fully illustrated due to the variety of the study models, different endpoints, etc. The adverse outcome pathway (AOP) framework is a pathway-based approach that could systematize mechanistic knowledge to assist health risk assessment of pollutants. Here, we constructed AOPs by collecting molecular mechanisms in PM-induced neurotoxicity assessments. We chose particulate matter (PM) as a stressor in the Comparative Toxicogenomics Database (CTD) and identified the critical toxicity pathways based on Ingenuity Pathway Analysis (IPA). We found 65 studies investigating the potential mechanisms linking PM2.5 and UFPs to neurotoxicity, which contained 2, 675 genes in all. IPA analysis showed that neuroinflammation signaling and glucocorticoid receptor signaling were the common toxicity pathways. The upstream regulator analysis (URA) of PM2.5 and UFPs demonstrated that the neuroinflammation signaling was the most initially triggered upstream event. Therefore, neuroinflammation was recognized as the MIE. Strikingly, there is a clear sequence of activation of downstream signaling pathways with UFPs, but not with PM2.5. Moreover, we found that inflammation response and homeostasis imbalance were key cellular events in PM2.5 and emphasized lipid metabolism and mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in UFPs. Previous AOPs, which only focused on phenotypic changes in neurotoxicity upon PM exposure, we for the first time propose AOP framework in which PM2.5 and UFPs may activate pathway cascade reactions, resulting in adverse outcomes associated with neurotoxicity. Our toxicity pathway-based approach not only advances risk assessment for PM-induced neurotoxicity but shines a spotlight on constructing AOP frameworks for new chemicals.

OBJECTIVE: To explore the experiences of utilising distal-extremity cryotherapy in reducing chemotherapy-induced peripheral neuropathy during Paclitaxel treatment on physical functioning, clinical and patient-reported outcomes, compared to standard care in people affected by breast cancer.
METHODS: Four databases and one register were searched on 11 April 2023 to identify all relevant studies meeting the inclusion and exclusion criteria. These were CINAHL (via EBSCOhost), Cochrane Central Register of Controlled Trials, Medline (via EBSCOhost), Scopus, and Web of Science Core Collection, with no limiters placed on any of the searches. Additionally, relevant systematic reviews were scrutinised for potentially relevant studies for screening.
RESULTS: Distal-extremity cryotherapy is a safe intervention with minimal risk for serious adverse events. However, insufficient data supports the mainstay clinical use of cryotherapy in reducing chemotherapy-induced peripheral neuropathy from Paclitaxel use within the breast cancer population. Heterogeneity in study design, cryotherapy mode, and measurement tools underscore the need for additional research.
CONCLUSIONS: Despite limited data on the impact of distal-extremity cryotherapy in preventing chemotherapy-induced peripheral neuropathy, there are valuable implications for nursing practice arising from this review.
CONCLUSIONS: Nurses play a vital role in the clinical and experiential journey of people with breast cancer, it is important that they understand the available evidence and act as patient advocates. Assisting patients in understanding current research and encouraging participation in future studies, thereby enhancing our knowledge, and strengthening the available evidence base.

Natural bioactives possess a wide range of chemical structures that can exert a plethora of pharmacological and toxicological actions, resulting in neuroprotection or neurotoxicity. These pharmacodynamic properties can positively or negatively impact human and animal global healthcare. Remarkably, Ayurvedic botanical Cannabis has been used worldwide by different ethnicities and religions for spiritual, commercial, recreational, nutraceutical, cosmeceutical, and medicinal purposes for centuries. Cannabis-based congeners have been approved by the United States of America\'s (USA) Food & Drug Administration (FDA) and other global law agencies for various therapeutic purposes. Surprisingly, the strict laws associated with possessing cannabis products have been mitigated in multiple states in the USA and across the globe for recreational use. This has consequently led to a radical escalation of exposure to cannabis-related substances of abuse. However, there is a lacuna in the literature on the acute and chronic effects of Cannabis and its congeners on various neuropathologies. Moreover, in the post-COVID era, there has been a drastic increase in the incidence and prevalence of numerous neuropathologies, leading to increased morbidity and mortality. There is an impending necessity for a safe, economically viable, multipotent, natural bioactive to prevent and treat various neuropathologies. The ayurvedic herb, Cannabis is one of the oldest botanicals known to humans and has been widely used. However, the comprehensive effect of Cannabis on various neuropathologies is not well established. Hence, this review presents effects of Cannabis on various neuropathologies.

BACKGROUND: Contrast-induced neurotoxicity (CIN), is an increasingly recognised complication of endovascular procedures, presenting as a spectrum of neurological symptoms that mimic ischaemic stroke. The diagnosis of CIN remains a clinical challenge, and stereotypical imaging findings are not established. This study was conducted to characterise the neuroimaging findings in patients with CIN, to raise diagnostic awareness and improve decision making.
METHODS: We performed a systematic review of PubMed and Embase databases from inception (1946/1947) to June 2023 for reports of CIN following administration of iodinated contrast media. Studies with a final diagnosis of CIN, which provided details of neuroimaging were included. All included cases were pooled and descriptive analysis was conducted.
RESULTS: A total of 84 patients were included, with a median age of 64 years. A large proportion of patients had normal imaging (CT 40.8 %, MRI 53.1 %). CT abnormalities included cortical/subarachnoid hyperattenuation (42.1 %), cerebral oedema/sulcal effacement (26.3 %), and loss of grey-white differentiation (7.9 %). Frequently reported MRI abnormalities included brain parenchymal MRI signal change (40.8 %) and cerebral oedema (12.2 %), most commonly observed on FLAIR sequences (26.5 %). Characterisation of imaging findings according to anatomical location and clinical symptoms has been conducted.
CONCLUSIONS: Neuroimaging is an essential part of the diagnostic workup of CIN. Analysis of the anatomical location and laterality of imaging abnormalities may suggest relationship between radiological features and actual clinical symptoms, although this remains to be confirmed with dedicated study. Radiological abnormalities, particularly CT, appear to be transient and reversible in most patients.

The Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) is a rare but concerning neurological complication resulting from lithium intoxication. Despite being reported since the 1960s, SILENT remains poorly understood and previous reviews on this topic commonly have been narrative. We therefore conducted a scoping review to assess the nature and scope of the research literature on the long-term neurological sequelae of lithium toxicity and determine the current knowledge of SILENT. A comprehensive and systematic literature search, using the MEDLINE, Embase, and Web of Science databases (from inception to July 2023), was conducted for English and Dutch articles, assessing the long-term neurological sequelae of lithium intoxication. Key information concerning clinical manifestations, risk factors, therapeutic approaches, or preventive measurements was extracted. We reviewed 91 articles, extracting information from 117 cases of SILENT. The prevailing outcome observed was persistent cerebellar dysfunction (77% of cases), often in combination with other sequelae. Other common sequelae included cognitive problems, parkinsonism, choreoathetosis, tardive dyskinesia, and peripheral neuropathy. The most common (61.4%) acute neurological symptom in the development of SILENT is an altered level of consciousness ranging from confusion to comatose states. Cerebellar sequelae were mentioned in 77% of cases as most common persistent sequelae. Antipsychotic use was mentioned in 59% of cases and fever was reported in 37.6% of cases. Scientific knowledge about this phenomenon has not advanced much since its initial reports in the 1960s and 1970s. While the use of lithium has become much more stringent than it had been in years past, and the occurrence of SILENT is rather exceptional, raising awareness about SILENT nevertheless remains crucial to avoid deleterious neurological consequences. Comprehensive, high-quality research in a systematic and standardized manner is therefore urgently needed to better understand this phenomenon.

Several studies suggest that crack cocaine users exhibit higher prevalence of both psychiatric and psychosocial problems, with an aggressive pattern of drug use. Nevertheless, few experimental studies attempted to verify the neurotoxicity after crack cocaine exposure, especially when compared with other routes of cocaine administration. This systematic review aimed to verify whether in vitro and/or in vivo crack cocaine exposure is more neurotoxic than cocaine exposure (snorted or injected). A search was performed in the PubMed, EMBASE, Scopus, Web of Science, and LILACS databases for in vitro and in vivo toxicological studies conducted with either rats or mice, with no distinction with regard to sex or age. Other methods including BioRxiv, BDTD, Academic Google, citation searching, and specialist consultation were also adopted. Two independent investigators screened the titles and abstracts of retrieved studies and subsequently performed full-text reading and data extraction. The quality of the included studies was assessed by the Toxicological data Reliability assessment Tool (ToxRTool). The study protocol was registered with the Prospective Registry of Systematic Reviews (PROSPERO; CRD42022332250). Of the twelve studies included, three were in vitro and nine were in vivo studies. According to the ToxRTool, most studies were considered reliable either with or without restrictions, with no one being considered as not reliable. The studies found neuroteratogenic effects, decreased threshold for epileptic seizures, schizophrenic-like symptoms, and cognitive deficits to be associated with crack cocaine exposure. Moreover, both in vitro and in vivo studies reported a worsening in cocaine neurotoxic effect caused by the anhydroecgonine methyl ester (AEME), a cocaine main pyrolysis product, which is in line with the more aggressive pattern of crack cocaine use. This systematic review suggests that crack cocaine exposure is more neurotoxic than other routes of cocaine administration. However, before the scarcity of studies on this topic, further toxicological studies are necessary.

Ertapenem-induced neurotoxicity has not been well characterized and is potentially underreported. We conducted a systematic review of the literature and included 11 additional cases from the University of Washington Medicine health system. A total of 125 individual patient cases were included in the data analysis. The mean age was 72 years, and 62% and 42% of patients had renal dysfunction and preexisting central nervous system (CNS) conditions, respectively. Only 15% of patients received inappropriately high ertapenem dosing based on kidney function. Patients developed neurological signs and symptoms after a median of 4 days (interquartile range, 3-9 days). The most common clinical features were seizures (70%), altered level of consciousness or delirium (27%), and hallucinations (17%). An estimated incidence in our health system was 1 in 102 courses of ertapenem. Ertapenem neurotoxicity should be suspected when a patient with renal dysfunction or predisposing CNS conditions develops neurological signs and symptoms, especially within several days after initiating the antibiotic. This study underscores the need for a large prospective study to assess the true incidence and outcomes of ertapenem neurotoxicity.

Toxic leukoencephalopathy (TL) refers to damage to the brain white matter following exposure to toxic agents. Multiple agents are incriminated in this condition, including chemotherapy drugs. 5-Fluorouracil, widely used in oncology, is responsible for neurotoxicity in less than 5% of cases. We report the case of a 54-year-old male patient who presented with neurological symptoms following 5-FU-based chemotherapy for gastric adenocarcinoma, and whose MRI scan revealed signs suggestive of toxic leukoencephalopathy. We also report on the evolution of the abnormalities described on his MRI after 1 year.

N, N-diethyl-meta-toluamide (DEET) has been considered the \'gold standard\' for insect repellent use since the 1950s and constitutes most insect repellents on the market. However, conflicting data in the scientific literature and confusing information in the media are at the core of debates about the safety of DEET insect repellents for the protection of children against arthropod bites. The few fatal occurrences involving DEET insect repellents and complications of their use in the pediatric population are typically the result of accidental overdoses or misuse of insect repellents that disregard warnings on product labels. With appropriate application, the safety record of DEET insect repellents continues to be excellent with few side effects. The purpose of this review is to provide a summary of the literature on safety outcomes of DEET insect repellent use in children; outline the pediatric recommendations relating to DEET insect repellents; and provide an overview of EPA-approved and naturally derived alternatives to DEET that possess low toxicity while providing a similar level of protection to synthetic insect repellents.

The increasing use of immune checkpoint inhibitors (ICI) in cancer therapy has brought attention to their associated neurotoxicities, termed neurological immune-related adverse events (n-irAEs). Despite their relatively rare incidence, n-irAEs pose a significant risk, potentially leading to severe, long-lasting disabilities or even fatal outcomes. This narrative review aims to provide a comprehensive overview of n-irAEs, focusing on their recognition and management. The review addresses a spectrum of n-irAEs, encompassing myositis, myasthenia gravis, various neuropathies, and central nervous system complications, such as encephalitis, meningitis, and demyelinating diseases. The key features of n-irAEs are emphasized in this review, including their early onset after initiation of ICIs, potential association with non-neurological irAEs and/or concurrent oncological response, the significance of ruling out other etiologies, and the expected improvement upon discontinuation of ICIs and/or immunosuppression. Furthermore, this review delves into considerations for ICI re-challenge and the intricate nature of n-irAEs within the context of pre-existing autoimmune and paraneoplastic syndromes. It underscores the importance of a multidisciplinary approach to diagnosis and treatment, highlighting the pivotal role of severity grading in guiding treatment decisions.