Climate change and epilepsy: insights from clinical and basic science studies

Climate change is with us. As professionals who place value on evidence-based practice, climate change is something we cannot ignore. The current pandemic of the novel coronavirus, SARS-CoV-2, has demonstrated how global crises can arise suddenly and have a significant impact on public health. Global warming, a chronic process punctuated by acute episodes of extreme weather events, is an insidious global health crisis needing at least as much attention. Many neurological diseases are complex chronic conditions influenced at many levels by changes in the environment. This review aimed to collate and evaluate reports from clinical and basic science about the relationship between climate change and epilepsy. The keywords climate change, seasonal variation, temperature, humidity, thermoregulation, biorhythm, gene, circadian rhythm, heat, and weather were used to search the published evidence. A number of climatic variables are associated with increased seizure frequency in people with epilepsy. Climate change-induced increase in seizure precipitants such as fevers, stress, and sleep deprivation (e.g. as a result of more frequent extreme weather events) or vector-borne infections may trigger or exacerbate seizures, lead to deterioration of seizure control, and affect neurological, cerebrovascular, or cardiovascular comorbidities and risk of sudden unexpected death in epilepsy. Risks are likely to be modified by many factors, ranging from individual genetic variation and temperature-dependent channel function, to housing quality and global supply chains. According to the results of the limited number of experimental studies with animal models of seizures or epilepsy, different seizure types appear to have distinct susceptibility to seasonal influences. Increased body temperature, whether in the context of fever or not, has a critical role in seizure threshold and seizure-related brain damage. Links between climate change and epilepsy are likely to be multifactorial, complex, and often indirect, which makes predictions difficult. We need more data on possible climate-driven altered risks for seizures, epilepsy, and epileptogenesis, to identify underlying mechanisms at systems, cellular, and molecular levels for better understanding of the impact of climate change on epilepsy. Further focussed data would help us to develop evidence for mitigation methods to do more to protect people with epilepsy from the effects of climate change. (C) 2021 Elsevier Inc. All rights reserved.Paroxysmal Cerebral Disorder

Breast cancer resistance protein in drug resistance of primitive CD34+38- cells in acute myeloid leukemia

Contains fulltext : 47713.pdf (publisher's version ) (Closed access)PURPOSE: Acute myeloid leukemia (AML) is considered a stem cell disease. Incomplete chemotherapeutic eradication of leukemic CD34+38- stem cells is likely to result in disease relapse. The purpose of this study was to investigate the role of the breast cancer resistance protein (BCRP/ATP-binding cassette, subfamily G, member 2) in drug resistance of leukemic stem cells and the effect of its modulation on stem cell eradication in AML. EXPERIMENTAL DESIGN: BCRP expression (measured flow-cytometrically using the BXP21 monoclonal antibody) and the effect of its modulation (using the novel fumitremorgin C analogue KO143) on intracellular mitoxantrone accumulation and in vitro chemosensitivity were assessed in leukemic CD34+38- cells. RESULTS: BCRP was preferentially expressed in leukemic CD34+38- cells and blockage of BCRP-mediated drug extrusion by the novel fumitremorgin C analogue KO143 resulted in increased intracellular mitoxantrone accumulation in these cells in the majority of patients. This increase, however, was much lower than in the mitoxantrone-resistant breast cancer cell line MCF7-MR and significant drug extrusion occurred in the presence of BCRP blockage due to the presence of additional drug transport mechanisms, among which ABCB1 and multiple drug resistance protein. In line with these findings, selective blockage of BCRP by KO143 did not enhance in vitro chemosensitivity of leukemic CD34+38- cells. CONCLUSIONS: These results show that drug extrusion from leukemic stem cells is mediated by the promiscuous action of BCRP and additional transporters. Broad-spectrum inhibition, rather than modulation of single mechanisms, is therefore likely to be required to circumvent drug resistance and eradicate leukemic stem cells in AML

The CAREFALL Triage instrument identifying risk factors for recurrent falls in elderly patients

OBJECTIVE: To validate the CAREFALL Triage Instrument (CTI), a self-administered questionnaire concerning modifiable risk factors for recurrent falls in elderly patients who experienced fall. METHODS: This study in patients 65 years or older who experienced fall was performed at the accident and emergency department of a tertiary university hospital in the Netherlands. The construct validity was determined in 200 patients and 100 matched controls. The test-retest reliability was determined in 27 patients who answered the CTI twice. The clinical validity was determined in 111 high-risk patients who visited the Fall Prevention Clinic (FPC). The risk factors were as follows: medication, balance and mobility, fear of falling, orthostatic hypotension, mood, high risk of osteoporosis, impaired vision, and urinary incontinence. RESULTS: Construct Validity Recurrent falls correlated with more risk factors. Age, female gender, and 6 risk factors correlated with recurrent falls. Clinical validity: the agreement between the CTI and FPC was fair for balance and mobility, orthostatic hypotension, and urinary incontinence, moderate for mood, fear of falling, and high risk of osteoporosis, and substantial for "medication and impaired vision. Test-retest reliability: the agreement between the 2 CTIs was substantial for medication, high risk of osteoporosis, moderate for balance and mobility, mood, fair for orthostatic hypotension, impaired vision, and urinary incontinence, and poor for fear of falling. CONCLUSION: The CTI is reliable and valid in assessing risk factors for recurrent falls in elderly patients who experienced fal

Spatial self-organized patterning in seagrasses along a depth gradient of an intertidal ecosystem

The spatial structure of seagrass landscapes is typically ascribed to the direct influence of physical factors such as hydrodynamics, light, and sediment transport. We studied regularly interspaced banded patterns, formed by elongated patches of seagrass, in a small-scale intertidal ecosystem. We investigated (1) whether the observed spatial patterns may arise from feedback interactions between seagrass and its abiotic environment and (2) whether changes in abiotic conditions may lead to predictable changes in these spatial patterns. Field measurements, experiments, and a spatially explicit computer model identified a “scale-dependent feedback” (a mechanism for spatial self-organization) as a possible cause for the banded patterns. Increased protection from uprooting by improved anchoring with increasing seagrass density caused a local positive feedback. Sediment erosion around seagrass shoots increased with distance through the seagrass bands, hence causing a long-range negative feedback. Measurements across the depth gradient of the intertidal, together with model simulations, demonstrated that seagrass cover and mean patch size were predictably influenced by additional external stress caused by light limitation and desiccation. Thus, our study provides direct empirical evidence for a consistent response of spatial self-organized patterns to changing abiotic conditions, suggesting a potential use for self-organized spatial patterns as stress indicators in ecosystems.

Assessing the prevalence of modifiable risk factors in older patients visiting an ED due to a fall using the CAREFALL Triage Instrument

OBJECTIVE: Falls in older people are a common presenting complaint. Knowledge of modifiable risk factors may lead to a more tailored approach to prevent recurrent falls and/or fractures. We investigated prevalence of 8 modifiable risk factors for recurrent falling and/or a serious consequence of the fall among older patients visiting the emergency department after a fall with the Combined Amsterdam and Rotterdam Evaluation of Falls Triage Instrument (CTI), a self-administrated questionnaire that consists of questions concerning demographics, possible cause(s) of the fall, and questions relating to (modifiable) risk factors for falling. METHODS: After treatment for their injuries, 1077 consecutive patients 65 years or older visiting the accident and emergency department due to a fall were evaluated by the CTI. The following were assessed: impaired vision, mobility disorder, fear of falling, mood disorder, high risk of osteoporosis, orthostatic hypotension, incontinence, and polypharmacy. RESULTS: The percentage of respondents who returned the questionnaire was 59.3%. The mean (SD) age was 78.5 (7.5) years, and 57.8% experienced a fall with serious consequences. There were 60.9% of patients with a recurrent fall versus 51% with a first fall who experienced with a serious consequence (P = .025). Age and risk factors mobility disorder (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3), high risk of osteoporosis (OR, 2.0; 95% CI, 1.2-3.2), incontinence (OR, 1.7; 95% CI, 1.0-2.7), fear of falling (OR, 2.2; 95% CI, 1.3-3.7), and orthostatic hypotension (OR, 2.4; 95% CI, 1.4-4.2) were independently associated with a recurrent fall. Age and high risk of osteoporosis were the only risk factors predicting a serious consequence of a fall (OR, 4.6; 95% CI, 2.9-7.2). CONCLUSIONS: Age and 5 modifiable risk factors assessed with the CTI were independently associated with a recurrent fall. Only high risk of osteoporosis was associated with a serious consequence. (aut. ref.

Impaired breast cancer resistance protein mediated drug transport in plasma cells in multiple myeloma

Contains fulltext : 47619.pdf (publisher's version ) (Closed access)The breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding-cassette transporter involved in the transport of drugs used in the treatment of multiple myeloma (MM). Its expression, function and clinical significance in MM, however, are unknown. We report that BCRP is preferentially expressed and functionally active in normal plasma cells but that its function is significantly impaired in plasma cells in newly diagnosed MM. The data presented argue against a role for BCRP in primary drug resistance in MM and the utilisation as a molecular target as such but warrant research into its (patho)physiological role in normal and malignant plasma cells

Reply to Schmidt et al.: A robust surge of cognitive distortions in historical language

Applied ProbabilityQuantum Computin