Triheptanoin Did Not Show Benefit versus Placebo for the Treatment of Paroxysmal Movement Disorders in Glut1 Deficiency Syndrome: Results of a Randomized Phase 3 Study.

BACKGROUND: Paroxysmal movement disorders are common in Glut1 deficiency syndrome (Glut1DS). Not all patients respond to or tolerate ketogenic diets. OBJECTIVES: The objective was to evaluate the effectiveness and safety of triheptanoin in reducing the frequency of disabling movement disorders in patients with Glut1DS not receiving a ketogenic diet. METHODS: UX007G-CL301 was a randomized, double-blind, placebo-controlled, phase 3 crossover study. After a 6-week run-in, eligible patients were randomized 1:1 to the first sequence (triheptanoin/placebo or placebo/triheptanoin) titration plus maintenance, followed by washout and the opposite sequence titration plus maintenance. The placebo (safflower oil) matched the appearance, taste, and smell of triheptanoin. Open-label triheptanoin was administered in the extension. The frequency of disabling paroxysmal movement disorder events per 4 weeks (recorded by diary during maintenance; primary endpoint) was assessed by Wilcoxon rank-sum test. RESULTS: Forty-three patients (children, n = 16; adults, n = 27) were randomized and treated. There was no difference between triheptanoin and placebo in the mean (interquartile range) number of disabling paroxysmal movement disorder events (14.3 [4.7-38.3] vs. 11.8; [3.2-28.7]; Hodges-Lehmann estimated median difference: 1.46; 95% confidence interval, -1.12 to 4.36; P = 0.2684). Treatment-emergent adverse events were mild/moderate in severity and included diarrhea, vomiting, upper abdominal pain, headache, and nausea. Two patients discontinued the study because of non-serious adverse events that were predominantly gastrointestinal. The study was closed early during the open-label extension because of lack of effectiveness. Seven patients continued to receive triheptanoin compassionately. CONCLUSION: There were no significant differences between the triheptanoin and placebo groups in the frequency of disabling movement disorder events during the double-blind maintenance period. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Definition, diagnosis and classification of infection-related movement disorders: Consensus proposal.

BACKGROUND: Infection-related movement disorders (IRMD) present a complex diagnostic challenge due to the broad phenotypic spectrum, the variety of possible infectious aetiologies, and the complicated underlying mechanisms. Yet, a comprehensive framework for classifying IRMD is lacking. METHODS: An international consensus panel under the directives of the Movement Disorders Society Infection-Related Movement Disorders Study Group developed a comprehensive definition and a consensus classification system. Case scenarios were used for validation. RESULTS: A definition for IRMD and a two-axis-based classification system consisting of six descriptors are proposed, intended as tools for researchers and clinicians. Collected information on clinical characteristics, investigational findings, the infectious organism and presumed pathogenesis facilitate the evaluation of diagnostic certainty. CONCLUSION: The proposed framework will serve for optimised diagnostic algorithms, systematic aggregation of informative datasets across studies, and ultimately improved care and outcome of patients with IRMDs.

Movement Disorders in Patients with Subacute Sclerosing Panencephalitis: A Systematic Review.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a complication of measles, occurring after a latency of 4-10 years. It continues to occur in developing countries although resurgence is being reported from developed countries. Characteristic features include progressive neuropsychiatric issues, myoclonus, seizures, movement disorders and visual impairment. Electroencephalography (EEG) typically shows periodic generalized discharges, and elevated CSF anti-measles antibodies are diagnostic. Movement disorders are being increasingly recognized as part of the clinical spectrum, and range from hyperkinetic (chorea, dystonia, tremor, tics) to hypokinetic (parkinsonism) disorders and ataxia. OBJECTIVES: This article aims to comprehensively review the spectrum of movement disorders associated with SSPE. METHODS: A literature search was conducted in PubMed and EMBASE databases in December 2023 and articles were identified for review. RESULTS: Movement disorders reported in SSPE included hyperkinetic (chorea, dystonia, tremor and tics), hypokinetic (parkinsonism), ataxia and extraocular movement disorders. Myoclonus, a core clinical feature, was the most frequent "abnormal movement." Movement disorders were observed in all clinical stages, and could also be a presenting feature, even sans myoclonus. Hyperkinetic movement disorders were more common than hypokinetic movement disorders. An evolution of movement disorders was observed, with ataxia, chorea and dystonia occurring earlier, and parkinsonism later in the disease. Neuroradiological correlates of movement disorders remained unclear. CONCLUSION: A wide spectrum of movement disorders was observed throughout the clinical stages of SSPE. Most data were derived from case reports and small case series. Multicentric longitudinal studies are required to better delineate the spectrum and evolution of movement disorders in SSPE.

Causes of macrophyte mass development and management recommendations.

Aquatic plants (macrophytes) are important for ecosystem structure and function. Macrophyte mass developments are, however, often perceived as a nuisance and are commonly managed by mechanical removal. This is costly and often ineffective due to macrophyte regrowth. There is insufficient understanding about what causes macrophyte mass development, what people who use water bodies consider to be a nuisance, or the potential negative effects of macrophyte removal on the structure and function of ecosystems. To address these gaps, we performed a standardized set of in situ experiments and questionnaires at six sites (lakes, reservoirs, and rivers) on three continents where macrophyte mass developments occur. We then derived monetary values of ecosystem services for different scenarios of macrophyte management ("do nothing", "current practice", "maximum removal"), and developed a decision support system for the management of water courses experiencing macrophyte mass developments. We found that (a) macrophyte mass developments often occur in ecosystems which (unintentionally) became perfect habitats for aquatic plants, that (b) reduced ecosystem disturbance can cause macrophyte mass developments even if nutrient concentrations are low, that (c) macrophyte mass developments are indeed perceived negatively, but visitors tend to regard them as less of a nuisance than residents do, that (d) macrophyte removal lowers the water level of streams and adjacent groundwater, but this may have positive or negative overall societal effects, and that (e) the effects of macrophyte removal on water quality, greenhouse gas emissions, and biodiversity vary, and likely depend on ecosystem characteristics and macrophyte life form. Overall, we found that aquatic plant management often does not greatly affect the overall societal value of the ecosystem, and we suggest that the "do nothing" option should not be easily discarded in the management of perceived nuisance mass developments of aquatic plants.

A shift in habitat use patterns of brown trout (Salmo trutta): A behavioural response to macrophyte removal.

Mass development of macrophytes is an increasing problem worldwide and they are frequently removed where they are in conflict with local waterway users. Yet, macrophytes can provide important refuge and nursery habitats for fish. Little is known about the consequences of macrophyte removal for fish behavioural space use and habitat selection. We hypothesised that macrophyte removal would affect brown trout (Salmo trutta) movement during the partial removal of the aquatic plant Juncus bulbosus (L.) in an oligotrophic impounded Norwegian river.We tagged 94 brown trout and tracked them using passive acoustic telemetry for 10 months and mapped the cover of J. bulbosus. Trout behavioural patterns were quantified as space use (utilisation areas 50% and 95%) which was linked to habitat use and selection for J. bulbosus. Removal of J. bulbosus influenced space use of brown trout by reducing the core utilisation area by 22%. Habitat use and selection were likewise influenced by removal with increased use and selection of areas with low J. bulbosus cover (<25%) with corresponding reduction in high J. bulbosus cover (>25-75%). Finally, diurnal differences in space use and habitat use were found, with 19% larger utilisation areas at night and higher use of areas with low J. bulbosus during daytime. Yet, all effect sizes were relatively small compared to the size of the study area. This research provides a detailed case study on the effects of macrophyte removal on fish behavioural patterns in a section of a large Norwegian river with macrophyte mass development. We found no large effects of removal on trout behaviour but noted an increased use of areas with low macrophyte cover. This research is relevant for water managers and policy makers of freshwater conservation and provides a template for using acoustic telemetry to study the effects of macrophyte removal on fish.

Trial of N-Acetyl-l-Leucine in Niemann-Pick Disease Type C.

BACKGROUND: Niemann-Pick disease type C is a rare lysosomal storage disorder. We evaluated the safety and efficacy of N-acetyl-l-leucine (NALL), an agent that potentially ameliorates lysosomal and metabolic dysfunction, for the treatment of Niemann-Pick disease type C. METHODS: In this double-blind, placebo-controlled, crossover trial, we randomly assigned patients 4 years of age or older with genetically confirmed Niemann-Pick disease type C in a 1:1 ratio to receive NALL for 12 weeks, followed by placebo for 12 weeks, or to receive placebo for 12 weeks, followed by NALL for 12 weeks. NALL or matching placebo was administered orally two to three times per day, with patients 4 to 12 years of age receiving weight-based doses (2 to 4 g per day) and those 13 years of age or older receiving a dose of 4 g per day. The primary end point was the total score on the Scale for the Assessment and Rating of Ataxia (SARA; range, 0 to 40, with lower scores indicating better neurologic status). Secondary end points included scores on the Clinical Global Impression of Improvement, the Spinocerebellar Ataxia Functional Index, and the Modified Disability Rating Scale. Crossover data from the two 12-week periods in each group were included in the comparisons of NALL with placebo. RESULTS: A total of 60 patients 5 to 67 years of age were enrolled. The mean baseline SARA total scores used in the primary analysis were 15.88 before receipt of the first dose of NALL (60 patients) and 15.68 before receipt of the first dose of placebo (59 patients; 1 patient never received placebo). The mean (±SD) change from baseline in the SARA total score was -1.97±2.43 points after 12 weeks of receiving NALL and -0.60±2.39 points after 12 weeks of receiving placebo (least-squares mean difference, -1.28 points; 95% confidence interval, -1.91 to -0.65; P<0.001). The results for the secondary end points were generally supportive of the findings in the primary analysis, but these were not adjusted for multiple comparisons. The incidence of adverse events was similar with NALL and placebo, and no treatment-related serious adverse events occurred. CONCLUSIONS: Among patients with Niemann-Pick disease type C, treatment with NALL for 12 weeks led to better neurologic status than placebo. A longer period is needed to determine the long-term effects of this agent in patients with Niemann-Pick disease type C. (Funded by IntraBio; ClinicalTrials.gov number, NCT05163288; EudraCT number, 2021-005356-10.).

Light and temperature controls of aquatic plant photosynthesis downstream of a hydropower plant and the effect of plant removal.

Many rivers worldwide are regulated, and the altered hydrology can lead to mass development of aquatic plants. Plant invasions are often seen as a nuisance for human activities leading to costly remedial actions with uncertain implications for aquatic biodiversity and ecosystem functioning. Mechanical harvesting is often used to remove aquatic plants and knowledge of plant growth rate could improve management decisions. Here, we used a simple light-temperature theoretical model to make a priori prediction of aquatic plant photosynthesis. These predictions were assessed through an open-channel diel change in O2 mass balance approach. A Michaelis-Menten type model was fitted to observed gross primary production (GPP) standardised at 10 °C using a temperature dependence from thermodynamic theory of enzyme kinetics. The model explained 87 % of the variability in GPP of a submerged aquatic plant (Juncus bulbosus L.) throughout an annual cycle in the River Otra, Norway. The annual net plant production was about 2.4 (1.0-3.8) times the standing biomass of J. bulbosus. This suggests a high continuous mass loss due to hydraulic stress and natural mechanical breakage of stems, as the biomass of J. bulbosus remained relatively constant throughout the year. J. bulbosus was predicted to be resilient to mechanical harvesting with photosynthetic capacity recovered within two years following 50-85 % plant removal. The predicted recovery was confirmed through a field experiment where 72 % of J. bulbosus biomass was mechanically removed. We emphasise the value of using a theoretical approach, like metabolic theory, over statistical models where a posteriori results are not always easy to interpret. Finally, the ability to predict ecosystem resilience of aquatic photosynthesis in response to varying management scenarios offers a valuable tool for estimating aquatic ecosystem services, such as carbon regulation. This tool can benefit the EU Biodiversity Strategy and UN Sustainable Development Goals.

Phenotype and natural history of mitochondrial membrane protein-associated neurodegeneration.

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is an ultraorphan neurogenetic disease from the group of neurodegeneration with brain iron accumulation (NBIA) disorders. Here we report cross-sectional and longitudinal data to define the phenotype, to assess disease progression and to estimate sample sizes for clinical trials. We enrolled patients with genetically confirmed MPAN from the Treat Iron-Related Childhood-Onset Neurodegeneration (TIRCON) registry and cohort study, and from additional sites. Linear mixed-effect modelling (LMEM) was used to calculate annual progression rates for the Unified Parkinson's Disease Rating Scale (UPDRS), Barry-Albright Dystonia (BAD) scale, Schwab and England Activities of Daily Living (SE-ADL) scale and the Pediatric Quality of Life Inventory (PedsQL). We investigated 85 MPAN patients cross-sectionally, with functional outcome data collected in 45. Median age at onset was 9 years and the median diagnostic delay was 5 years. The most common findings were gait disturbance (99%), pyramidal involvement (95%), dysarthria (90%), vision disturbances (82%), with all but dysarthria presenting early in the disease course. After 16 years with the disease, 50% of patients were wheelchair dependent. LMEM showed an annual progression rate of 4.5 points in total UPDRS. The total BAD scale score showed no significant progression over time. The SE-ADL scale and the patient- and parent-reported PedsQL showed a decline of 3.9%, 2.14 and 2.05 points, respectively. No patient subpopulations were identified based on longitudinal trajectories. Our cross-sectional results define the order of onset and frequency of symptoms in MPAN, which will inform the diagnostic process, help to shorten diagnostic delay and aid in counselling patients, parents and caregivers. Our longitudinal findings define the natural history of MPAN, reveal the most responsive outcomes and highlight the need for an MPAN-specific rating approach. Our sample size estimations inform the design of upcoming clinical trials.

Understanding temporal variability across trophic levels and spatial scales in freshwater ecosystems.

A tenet of ecology is that temporal variability in ecological structure and processes tends to decrease with increasing spatial scales (from locales to regions) and levels of biological organization (from populations to communities). However, patterns in temporal variability across trophic levels and the mechanisms that produce them remain poorly understood. Here we analyzed the abundance time series of spatially structured communities (i.e., metacommunities) spanning basal resources to top predators from 355 freshwater sites across three continents. Specifically, we used a hierarchical partitioning method to disentangle the propagation of temporal variability in abundance across spatial scales and trophic levels. We then used structural equation modeling to determine if the strength and direction of relationships between temporal variability, synchrony, biodiversity, and environmental and spatial settings depended on trophic level and spatial scale. We found that temporal variability in abundance decreased from producers to tertiary consumers but did so mainly at the local scale. Species population synchrony within sites increased with trophic level, whereas synchrony among communities decreased. At the local scale, temporal variability in precipitation and species diversity were associated with population variability (linear partial coefficient, ß = 0.23) and population synchrony (ß = -0.39) similarly across trophic levels, respectively. At the regional scale, community synchrony was not related to climatic or spatial predictors, but the strength of relationships between metacommunity variability and community synchrony decreased systematically from top predators (ß = 0.73) to secondary consumers (ß = 0.54), to primary consumers (ß = 0.30) to producers (ß = 0). Our results suggest that mobile predators may often stabilize metacommunities by buffering variability that originates at the base of food webs. This finding illustrates that the trophic structure of metacommunities, which integrates variation in organismal body size and its correlates, should be considered when investigating ecological stability in natural systems. More broadly, our work advances the notion that temporal stability is an emergent property of ecosystems that may be threatened in complex ways by biodiversity loss and habitat fragmentation.

Quantitative brain morphometry identifies cerebellar, cortical, and subcortical gray and white matter atrophy in late-onset Tay-Sachs disease.

Cerebellar atrophy is a characteristic sign of late-onset Tay-Sachs disease (LOTS). Other structural neuroimaging abnormalities are inconsistently reported. Our study aimed to perform a detailed whole-brain analysis and quantitatively characterize morphometric changes in LOTS patients. Fourteen patients (8 M/6F) with LOTS from three centers were included in this retrospective study. For morphometric brain analyses, we used deformation-based morphometry, voxel-based morphometry, surface-based morphometry, and spatially unbiased cerebellar atlas template. The quantitative whole-brain morphometric analysis confirmed the finding of profound pontocerebellar atrophy with most affected cerebellar lobules V and VI in LOTS patients. Additionally, the atrophy of structures mainly involved in motor control, including bilateral ventral and lateral thalamic nuclei, primary motor and sensory cortex, supplementary motor area, and white matter regions containing corticospinal tract, was present. The atrophy of the right amygdala, hippocampus, and regions of occipital, parietal and temporal white matter was also observed in LOTS patients in contrast with controls (p < 0.05, FWE corrected). Patients with dysarthria and those initially presenting with ataxia had more severe cerebellar atrophy. Our results show predominant impairment of cerebellar regions responsible for speech and hand motor function in LOTS patients. Widespread morphological changes of motor cortical and subcortical regions and tracts in white matter indicate abnormalities in central motor circuits likely coresponsible for impaired speech and motor function.

Rights and duties of genetic counsellors in Germany related to relatives at risk: comparative thoughts on the German Genetic Diagnostics Act.

Genetic testing has familial implications. Counsellors find themselves in (moral) conflict between medical confidentiality (towards the patient) and a potential right or even duty to warn at-risk relatives. Legal regulations vary between countries. English literature about German law is scarce. We reviewed the literature of relevant legal cases, focussing on German law, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This article aims to familiarise counsellors with their responsibilities, compare the situation between countries and point out legally unresolved areas.According to the German Genetic Diagnostics Act (Gendiagnostikgesetz) in case of an 'avoidable or treatable' genetic disorder, geneticists ought to confine themselves to the obligated advice to the patient. Whether a breach of the duty of confidentiality can be justified in exceptional cases by 'necessity as justification' for actively informing relatives at risk remains legally unclear. In case of a 'neither avoidable nor treatable' genetic disease, geneticists should also refrain from actively informing relatives as the justifiable state of emergency does not permit to break the duty of confidentiality.

Current advancements in therapy for Niemann-Pick disease: progress and pitfalls.

INTRODUCTION: Niemann-Pick disease type C (NPC) is a rare, autosomal recessive, lysosomal storage disorder. To combat the progressive neurodegeneration in NPC, disease-modifying treatment needs to be introduced early in the course of the disease. The only approved, disease-modifying treatment is a substrate-reduction treatment, miglustat. Given miglustat's limited efficacy, new compounds are under development, including gene therapy; however, many are still far from clinical use. Moreover, the phenotypic heterogeneity and variable course of the disease can impede the development and approval of new agents. AREAS COVERED: Here, we offer an expert review of these therapeutic candidates, with a broad scope not only on the main pharmacotherapies, but also on experimental approaches, gene therapies, and symptomatic strategies. The National Institute of Health (NIH) database PubMed has been searched for the combination of the words 'Niemann-Pick type C'+ 'treatment' or 'therapy' or 'trial.' The website clinicaltrials.gov has also been consulted. EXPERT OPINION: We conclude a combination of treatment strategies should be sought, with a holistic approach, to improve the quality of life of affected individuals and their families.

COVID19-associated new-onset movement disorders: a follow-up study.

BACKGROUND: Neurological symptoms are common manifestation in acute COVID-19. This includes hyper- and hypokinetic movement disorders. Data on their outcome, however, is limited. METHODS: Cases with new-onset COVID-19-associated movement disorders were identified by searching the literature. Authors were contacted for outcome data which were reviewed and analyzed. RESULTS: Movement disorders began 12.6 days on average after the initial onset of COVID-19. 92% of patients required hospital admission (mean duration 23 days). In a fraction of patients (6 of 27; 22%; 4 males/2 females, mean age 66.8 years) the movement disorder (ataxia, myoclonus, tremor, parkinsonism) was still present after a follow-up period of 7.5 ± 3 weeks. Severe COVID-19 in general and development of encephalopathy were risk factors, albeit not strong predictors, for the persistence. CONCLUSIONS: The prognosis of new-onset COVID-19-associated movement disorder appears to be generally good. The majority recovered without residual symptoms within several weeks or months. Permanent cases may be due to unmasking of a previous subclinical movement disorder or due to vascular/demyelinating damage. Given the relatively low response rate of one third only and the heterogeneity of mechanisms firm conclusions on the (long-term) outome cannot, however, be drawn.

Plastid DNA sequences and oospore characters of some European taxa of Tolypella section Tolypella (Characeae) identify five clusters, including one new cryptic Tolypella taxon from Sardinia, but they do not coincide with current morphological descriptions.

In Europe, the genus Tolypella (Characeae) comprises four to eight Tolypella taxa in sections Rothia and Tolypella that have been distinguished by vegetative morphology and gametangial characters such as antheridial size and oospore wall ornamentation. However, morphological differentiation is difficult in some cases due to overlapping and variable vegetative features, which in many cases are difficult to observe clearly. To clarify the taxonomic status of the five European taxa of Tolypella in section Tolypella, sequence data of the plastid genes atpB, rbcL and psbC for Tolypella glomerata (Desv.) Leonh., Tolypella hispanica Allen, Tolypella nidifica (O.F. Müll.) A. Braun, Tolypella normaniana (Nordst.) Nordst. and Tolypella salina Cor. were combined with data on oospore morphology, including oospore wall ornamentation. Gene sequence data identified five distinct clusters, but they were not consistent with the morphologically identified five taxa. T. glomerata consisted of some of the samples morphologically identified as T. glomerata and seven samples of T. normaniana, while the remaining T. glomerata samples clustered with specimens of unclear affiliation (Tolypella sp.). We identified two clusters of T. hispanica within the European material: cluster T. hispanica I consisted of samples from various locations, whereas the second cluster (T. hispanica II) consisted of samples of T. hispanica from Sardinia Island. The remaining cluster consisted of all the specimens that had been determined as T. salina or T. nidifica in addition to two specimens of T. normaniana. Oospore morphology was most clearly distinguishable for T. glomerata. Oospore characteristics for all other taxa were not as informative but showed some geographical and/or environmentally influenced differences, especially for T. nidifica and T. salina. Our results suggest the need to further check the different taxonomy of Tolypella sect. Tolypella in which specimens normally identified as T. glomerata might be two different taxa, T. glomerata and an unidentified taxon; T. nidifica and T. salina are not separate taxa; T. normaniana is a diminutive variant of two different Tolypella taxa; and T. hispanica comprises two different taxa, one from the Mediterranean island Sardinia.

Thyroid Disorders and Movement Disorders-A Systematic Review.

Background: There is overlap between movement disorders and neuroendocrine abnormalities. Objectives and methods: To provide a systematic review on the association of thyroid dysfunction and movement disorders. Thyroid physiological function and classical thyroid disorders highlighting typical and atypical manifestations including movement disorders, as well as diagnostic procedures, and treatments are discussed. Results: Hypothyroidism may be associated with hypokinetic and hyperkinetic disorders. There is debate whether their concomitance reflects a causal link, is coincidence, or the result of one unmasking the other. Hypothyroidism-associated parkinsonism may resemble idiopathic Parkinson's disease. Hypothyroidism-associated hyperkinetic disorders mainly occur in the context of steroid-responsive encephalopathy with autoimmune thyroiditis, that is, Hashimoto disease, mostly manifesting with tremor, myoclonus, and ataxia present in 28-80%, 42-65% and 33-65% in larger series. Congenital hypothyroidism manifesting with movement disorders, mostly chorea and dystonia, due to Mendelian genetic disease are rare.Hyperthyroidism on the other hand mostly manifests with hyperkinetic movement disorders, typically tremor (present in three quarters of patients). Chorea (present in about 2% of hyperthyroid patients), dystonia, myoclonus, ataxia and paroxysmal movement disorders, as well as parkinsonism have also been reported, with correlation between movement intensity and thyroid hormone levels.On a group level, studies on the role of thyroid dysfunction as a risk factor for the development of PD remain non-conclusive. Conclusions: In view of the treatability of movement disorders associated with thyroid disease, accurate diagnosis is important. The pathophysiology remains poorly understood. More detailed case documentation and systematic studies, along with experimental studies are needed.

Drivers of Perceived Nuisance Growth by Aquatic Plants.

Mass developments of macrophytes occur frequently worldwide and are often considered a nuisance when interfering with human activities. It is crucial to understand the drivers of this perception if we are to develop effective management strategies for ecosystems with macrophyte mass developments. Using a comprehensive survey spanning five sites with different macrophyte species in four countries (Norway, France, Germany and South Africa), we quantified the perception of macrophyte growth as a nuisance among residents and visitors, and for different recreational activities (swimming, boating, angling, appreciation of biodiversity, appreciation of landscape and birdwatching). We then used a Bayesian network approach to integrate the perception of nuisance with the consequences of plant removal. From the 1234 responses collected from the five sites, a range of 73-93% of the respondents across the sites considered macrophyte growth a nuisance at each site. Residents perceived macrophytes up to 23% more problematic than visitors. Environmental mindedness of respondents did not influence the perception of nuisance. Perceived nuisance of macrophytes was relatively similar for different recreational activities that were possible in each case study site, although we found some site-specific variation. Finally, we illustrate how Bayesian networks can be used to choose the best management option by balancing people's perception of macrophyte growth with the potential consequences of macrophyte removal.

Seizure in Neurodegeneration with Brain Iron Accumulation: A Systematic Review.

BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) is a rare genetic disorder. Its clinical manifestations comprise a wide spectrum mainly movement disorders. Seizure as a clinical manifestation is known to occur in some NBIAs, but the exact prevalence of epilepsy in each individual disorder is not well elucidated. The aim of this review was to investigate the frequency of seizures in NBIA disorders as well as to determine the associated features of patients with seizures. METHOD: The electronic bibliographic databases PubMed, Scopus, Embase, and Google Scholar were systematically searched for all cases in any type of article from inception to December 16, 2019. All the reported cases of NBIA (with or without genetic confirmation) were identified. Case reports with an explicit diagnosis of any types of NBIA, which have reported occurrence (or absence) of any type of seizure or epilepsy, in the English language, were included. Seizure incidence rate, type, and age of onset were reported as frequencies and percentages. RESULT: 1698 articles were identified and 51 were included in this review. Of 305 reported cases, 150 (49.2%) had seizures (phospholipase A2-associated neurodegeneration (PLAN) = 64 (50.8%), beta-propeller protein-associated neurodegeneration (BPAN) = 57 (72.1%), pantothenate kinase-associated neurodegeneration (PKAN) = 11 (23.4%), and others = 18 (very variable proportions)). The most frequent seizure type in NBIA patients was generalized tonic-clonic seizure with the mean age of seizure onset between 2 and 36 years. However, most of these papers had been published before the new classification of epilepsy became accessible. Affected patients were more likely to be females. CONCLUSION: Seizures are common in NBIA, particularly in PLAN and BPAN. In PKAN, the most common type of NBIA, around 10% of patients are affected by seizures. BPAN is the most possible NBIA accompanying seizure. Most of the findings regarding the seizure characteristics in the NBIAs are biased due to the huge missing data. Therefore, any conclusions should be made with caution and need further investigations.

Efficacy and Safety of N-Acetyl-l-Leucine in Children and Adults With GM2 Gangliosidoses.

BACKGROUND AND OBJECTIVES: GM2 gangliosidoses (Tay-Sachs and Sandhoff diseases) are rare, autosomal recessive, neurodegenerative diseases with no available symptomatic or disease-modifying treatments. This clinical trial investigated N-acetyl-l-leucine (NALL), an orally administered, modified amino acid in pediatric (≥6 years) and adult patients with GM2 gangliosidoses. METHODS: In this phase IIb, multinational, open-label, rater-blinded study (IB1001-202), male and female patients aged ≥6 years with a genetically confirmed diagnosis of GM2 gangliosidoses received orally administered NALL for a 6-week treatment period (4 g/d in patients ≥13 years, weight-tiered doses for patients 6-12 years), followed by a 6-week posttreatment washout period. For the primary Clinical Impression of Change in Severity analysis, patient performance on a predetermined primary anchor test (the 8-Meter Walk Test or the 9-Hole Peg Test) at baseline, after 6 weeks on NALL, and again after a 6-week washout period was videoed and evaluated centrally by blinded raters. Secondary outcomes included assessments of ataxia, clinical global impression, and quality of life. RESULTS: Thirty patients between the age of 6 and 55 years were enrolled. Twenty-nine had an on-treatment assessment and were included in the primary modified intention-to-treat analysis. The study met its CI-CS primary end point (mean difference 0.71, SD = 2.09, 90% CI 0.00, 1.50, p = 0.039), as well as secondary measures of ataxia and global impression. NALL was safe and well tolerated, with no serious adverse reactions. DISCUSSION: Treatment with NALL was associated with statistically significant and clinically relevant changes in functioning and quality of life in patients with GM2 gangliosidosis. NALL was safe and well tolerated, contributing to an overall favorable risk:benefit profile. NALL is a promising, easily administered (oral) therapeutic option for these rare, debilitating diseases with immense unmet medical needs. TRIAL REGISTRATION INFORMATION: The trial is registered with ClinicalTrials.gov (NCT03759665; registered on November 30, 2018), EudraCT (2018-004406-25), and DRKS (DRKS00017539). The first patient was enrolled on June 7, 2019. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that NALL improves outcomes for patients with GM2 gangliosidoses.

Short-term effects of macrophyte removal on aquatic biodiversity in rivers and lakes.

Mass development of macrophytes is an increasing problem in many aquatic systems worldwide. Dense mats of macrophytes can negatively affect activities like boating, fishing or hydropower production and one of the management measures often applied is mechanical removal. In this study, we analyzed the effect of mechanical macrophyte removal on phytoplankton, zooplankton, and macroinvertebrate (pelagic and benthic samples) assemblages. Our study covered five sites in four countries in Europe and Africa with highly variable characteristics. In all sites, dense mats of different macrophyte species (Juncus bulbosus in a river in Norway; a mix of native macrophytes in a German river, Elodea nuttallii in a lake in Germany, Ludwigia spp. In a French lake and Pontederia crassipes in a South African lake) are problematic and mechanical removal was applied. In every country, we repeated the same BACI (Before-After-Control-Impact) design, including "before", "one week after", and "six weeks after" sampling in a control and an impact section. Repeating the same experimental design at all sites allowed us to disentangle common effects across all sites from site-specific effects. For each taxonomic group, we analyzed three structural and three functional parameters, which we combined in a scoring system. Overall, the removal of macrophytes negatively affected biodiversity, in particular of zooplankton and macroinvertebrate assemblages. In contrast, plant removal had positive effects on the phytoplankton assemblages. Effects were more pronounced one week after removal than six weeks after. Consequently, we suggest a stronger consideration of the effect of plant removal on biodiversity to arrive at more sustainable management practices in the future.

Causes of Stress among Healthcare Professionals and Successful Hospital Management Approaches to Mitigate It during the COVID-19 Pandemic: A Cross-Sectional Study.

The outbreak of the COVID-19 pandemic posed an immediate challenge to the management of hospitals in Germany and elsewhere. The risk of stress for front-line healthcare professionals forced occupational health and safety units to adopt a variety of protective measures, not all of which have been thoroughly validated. The main objective of the present analysis is to assess what the most important sources of stress were and which of the protective measures applied to counteract stress among healthcare staff had the greatest impact. A better understanding of these factors will improve hospital management and worker safety in a future health crisis situation and may also prove to be beneficial in non-crisis situations. For this purpose, in 2020, an exploratory, cross-sectional and quantitative study using a questionnaire created for this purpose was carried out on a total of 198 professionals-133 nurses and 65 physicians-at the Klinikum Mittelbaden Balg hospital in Baden-Baden, Germany, during the first wave of the pandemic. Statistical analyses showed that nurses suffer more stress than physicians and that stress is higher among professionals in critical care and emergency units than in units that are less exposed to infected patients. It was also found that measures such as salary incentives, encouragement of work in well-integrated teams, and perceived support from hospital management mitigate stress. These findings highlight the importance of support measures from management and superiors. Knowing the actual effectiveness of the measures applied by management and the factors mentioned above could help to protect healthcare professionals in the event of another pandemic or similar situations and may still be of value in dealing with the continuing COVID-19 pandemic.