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Isolated rapid eye movement sleep behavior disorder (IRBD) is a well-established clinical risk factor for Lewy body diseases (LBDs), such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB).To elucidate whether serum microRNA (miRNA) deregulation in IRBD can antedate the diagnosis of LBD by performing a longitudinal study in different progression stages of IRBD before and after LBD diagnosis and assessing the predictive performance of differentially expressed miRNAs by machine learning-based modeling.Using genome-wide miRNA analysis and real-time quantitative polymerase chain reaction validation, we assessed serum miRNA profiles from patients with IRBD stratified by dopamine transporter (DaT) single-photon emission computed tomography into DaT-negative IRBD (n = 17) and DaT-positive IRBD (n = 21), IRBD phenoconverted into LBD (n = 13), and controls (n = 20). Longitudinally, we followed up the IRBD cohort by studying three time point serum samples over 26 months.We found sustained cross-sectional and longitudinal deregulation of 12 miRNAs across the RBD continuum, including DaT-negative IRBD, DaT-positive IRBD, and LBD phenoconverted IRBD (let-7c-5p, miR-19b-3p, miR-140, miR-22-3p, miR-221-3p, miR-24-3p, miR-25-3p, miR-29c-3p, miR-361-5p, miR-425-5p, miR-4505, and miR-451a) (false discovery rate P 0.05). Age- and sex-adjusted predictive modeling based on the 12 differentially expressed miRNA biosignatures discriminated IRBD and PD or DLB from controls with an area under the curve of 98% (95% confidence interval: 89-99%).Besides clinical diagnosis of IRBD or imaging markers such as DaT single-photon emission computed tomography, specific miRNA biosignatures alone hold promise as progression biomarkers for patients with IRBD for predicting PD and DLB clinical outcomes. Further miRNA studies in other PD at-risk populations, such as LRRK2 mutation asymptomatic carriers or hyposmic subjects, are warranted. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Management of chronic pain is crucial to improve the quality of life of cancer and palliative care patients. Opioid-based treatments used to control pain can be prolonged over time. Unfortunately, constipation is one of the most disturbing adverse effects of long-term use of opioids. Opioid-induced constipation (OIC) occurs when opioids bind to the specific receptors present in the gastrointestinal (GI) tract, and can affect any patients receiving chronic opioid therapy, including cancer patients. The limited efficacy of laxatives to treat OIC symptoms prompted the search for new therapeutic strategies. Peripherally acting μ-opioid receptor antagonists (PAMORAs) have recently emerged as new effective drugs for OIC management due to their specific binding to enteric μ-receptors. Little information is available on the use of PAMORAs in real-life practice for OIC treatment in cancer patients. In this paper, a panel of experts specializing in cancer and palliative care pools their clinical experience with PAMORAs in cancer patients presenting OIC and highlights the importance of timing and choice of therapy in achieving prompt OIC management and benefitting patients.

Resumen El uso extendido de los opioides, sobre todo los fentanilos de accion rapida para el tratamiento del dolor oncologico, ha producido la aparicion de conductas aberrantes asociadas a su administracion prolongada y un resurgimiento de antiguos mitos de la morfina como la adiccion; hoy dia se manejan nuevos terminos: seudoadiccion, seudotolerancia y afrontamiento quimico (chemical coping). En este articulo se analizan los distintos conceptos y comportamientos que deben hacer sospechar estos diagnosticos, los factores asociados al riesgo de mal uso de opioides, asi como las recomendaciones terapeuticas para realizar una prescripcion segura y eficiente. Para prevenir la aparicion de adiccion, seudoadiccion y afrontamiento quimico en un paciente con dolor asociado al cancer, es necesario un abordaje multidisciplinar de cada una de sus dimensiones (fisica, psicologica, social y espiritual), con especial interes en el manejo de la ansiedad y la depresion.

In this paper, we describe the discovery and characterization of shelled structures that occur inside galleries of Pyrenees mines. The structures are formed by the mineralization of iron and zinc oxides, dominantly franklinite (ZnFe2O4) and poorly ordered goethite (α-FeO(OH)). Subsurface oxidation and hydration of polymetallic sulfide orebodies produce solutions rich in dissolved metal cations including Fe2+/3+ and Zn2+. The microbially precipitated shell-like structure grows by lateral or vertical stacking of thin laminae of iron oxide particles which are accreted mostly by fungal filaments. The resulting structures are composed of randomly oriented aggregates of needle-like, uniform-sized crystals, suggesting some biological control in the structure formation. Such structures are formed by the integration of two separated shells, following a complex process driven likely by different strategies of fungal microorganisms that produced the complex macrostructure.

To determine the usefulness of dopamine transporter (DAT) imaging to identify idiopathic rapid eye movement sleep behavior disorder (IRBD) patients at risk for short-term development of clinically defined synucleinopathy.Eighty-seven patients with polysomnography-confirmed IRBD underwentBaseline DAT deficit was found in 51 (58.6%) patients. During follow-up, 25 (28.7%) subjects developed clinically defined synucleinopathy (Parkinson's disease in 11, dementia with Lewy bodies in 13, and multiple system atrophy in 1) with mean latency of 3.2 ± 1.9 years from imaging. Kaplan-Meier survival analysis showed increased risk of incident synucleinopathy in patients with abnormal DAT-SPECT than with normal DAT-SPECT (20% vs 6% at 3 years, 33% vs 18% at 5 years; log rank test, p = 0.006). Receiver operating characteristics curve revealed that reduction of FP-CIT uptake in putamen greater than 25% discriminated patients with DAT deficit who developed synucleinopathy from patients with DAT deficit that remained disease free after 3 years of follow-up. At 5-year follow-up, DAT-SPECT had 75% sensitivity, 51% specificity, 44% positive predictive value, 80% negative predictive value, and likelihood ratio 1.54 to predict synucleinopathy.DAT-SPECT identifies IRBD patients at short-term risk for synucleinopathy. Decreased FP-CIT putamen uptake greater than 25% predicts synucleinopathy after 3 years' follow-up. These observations may be useful to select candidates for disease modification trials in IRBD. Ann Neurol 2017;82:419-428.

Sleep-related movement and behaviour disorders may have an impact on sleep quality and lead to daytime symptoms. These groups of conditions include diseases such as restless legs syndrome, periodic leg movements, and REM and NREM parasomnias. The knowledge of their clinical features and management is of utmost importance for the neurologist and sleep specialist. Frequently, these patients are referred to such specialists and it is relevant to know that certain sleep disorders may be associated with other neurological conditions.

Objective: The aim of the present study was to determine the predictive value of olfactory dysfunction for the early development of a synuclein-mediated neurodegenerative disease in subjects with idiopathic REM sleep behavior disorder (iRBD) over an observational period of 5 years. Methods: Thirty-four patients with polysomnography-confirmed iRBD underwent olfactory testing using the entire Sniffin9 Sticks test assessing odor identification, odor discrimination, and olfactory threshold. Patients with iRBD were prospectively followed up over a period of 4.9 ± 0.3 years (mean ± SD). The diagnosis of neurodegenerative diseases was based on current clinical diagnostic criteria. Results: After 2.4 ± 1.7 years (mean ± SD), 9 patients (26.5%) with iRBD developed a Lewy body disease (6 Parkinson disease and 3 dementia with Lewy bodies). The entire Sniffin9 Sticks test and the identification subtest had the same overall diagnostic accuracy of 82.4% (95% confidence interval: 66.1%–92.0%) in predicting conversion. The relative risk for a Lewy body disease in the lowest tertile of olfactory function was 7.3 (95% confidence interval: 1.8–29.6) compared with the top 2 tertiles. Conclusions: Assessment of olfactory function, particularly odor identification, may help to predict the development of a Lewy body disease in patients with iRBD over a relatively short time period and thus to identify patients suitable for future disease modification trials.

Recently, we reported downregulated circulating levels of the microRNAs miR-19b, miR-29a, and miR-29c in Parkinson disease. Here we investigated the expression of these microRNAs in serum samples from 56 patients with idiopathic rapid eye movement sleep behavior disorder, before and after their conversion into a synucleinopathy. Compared to controls, we found that the expression level of miR-19b is downregulated in patients with idiopathic rapid eye movement sleep behavior disorder and antedates the diagnosis of Parkinson disease and dementia with Lewy bodies after 4.67 ± 2.61 years of follow-up. Our findings indicate that dysregulation of the microRNA miR-19b occurs in the prodromal stage of synucleinopathies.