Development of Iron Speciation Reference Materials for Palaeoredox Analysis

The development and application of geochemical techniques to identify redox conditions in modern and ancient aquatic environments has intensified over recent years. Iron (Fe) speciation has emerged as one of the most widely used procedures to distinguish different redox regimes in both the water column and sediments, and is the main technique used to identify oxic, ferruginous (anoxic, Fe(II) containing) and euxinic (anoxic, sulfidic) water column conditions. However, an international sediment reference material has never been developed. This has led to concern over the consistency of results published by the many laboratories that now utilise the technique. Here, we report an interlaboratory comparison of four Fe speciation reference materials for palaeoredox analysis, which span a range of compositions and reflect deposition under different redox conditions. We provide an update of extraction techniques used in Fe speciation, and assess the effects of both test portion mass, and the use of different analytical procedures, on the quantification of different Fe fractions in sedimentary rocks. While atomic adsorption spectroscopy and inductively coupled plasma‐optical emission spectrometry produced comparable Fe measurements for all extraction stages, the use of ferrozine consistently underestimated Fe in the extraction step targeting mixed ferrous‐ferric minerals such as magnetite. We therefore suggest that the use of ferrozine is discontinued for this Fe pool. Finally, we report the combined data of four independent Fe speciation laboratories to characterise the Fe speciation composition of the reference materials. These reference materials are available to the community to provide an essential validation of in‐house Fe speciation measurements

Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease. Although an increasing number of genetic factors have been connected to this debilitating condition, the proportion of cases that can be attributed to distinct genetic defects is unknown. To provide a comprehensive analysis of the frequency and spectrum of pathogenic missense mutations and coding risk variants in nine genes previously implicated in DLB, we performed exome sequencing in 111 pathologically confirmed DLB patients. All patients were Caucasian individuals from North America. Allele frequencies of identified missense mutations were compared to 222 control exomes. Remarkably, ~ 25% of cases were found to carry a pathogenic mutation or risk variant in APP, GBA or PSEN1, highlighting that genetic defects play a central role in the pathogenesis of this common neurodegenerative disorder. In total, 13% of our cohort carried a pathogenic mutation in GBA, 10% of cases carried a risk variant or mutation in PSEN1, and 2% were found to carry an APP mutation. The APOE ε4 risk allele was significantly overrepresented in DLB patients (p-value < 0.001). Our results conclusively show that mutations in GBA, PSEN1, and APP are common in DLB and consideration should be given to offer genetic testing to patients diagnosed with Lewy body dementia

Expressing one’s feelings and listening to others increases emotional intelligence: a pilot study of Asian medical students

&lt;p&gt;Background: There has been considerable interest in Emotional Intelligence (EI) in undergraduate medical education, with respect to student selection and admissions, health and well-being and academic performance. EI is a significant component of the physician-patient relationship. The emotional well-being of the physician is, therefore, a significant component in patient care. The aim is to examine the measurement of TEIQue-SF in Asian medical students and to explore how the practice of listening to the feelings of others and expressing one’s own feelings influences an individual’s EI, set in the context of the emotional well-being of a medical practitioner.&lt;/p&gt; &lt;p&gt;Methods: A group of 183 international undergraduate medical students attended a half-day workshop (WS) about mental-health and well-being. They completed a self-reported measure of EI on three occasions, pre- and post-workshop, and a 1-year follow-up.&lt;/p&gt; &lt;p&gt;Result: The reliability of TEIQue-SF was high and the reliabilities of its four factors were acceptable. There were strong correlations between the TEIQue-SF and personality traits. A paired t-test indicated significant positive changes after the WS for all students (n=181, p= .014), male students (n=78, p= .015) and non-Japanese students (n=112, p= .007), but a repeated measures analysis showed that one year post-workshop there were significant positive changes for all students (n=55, p= .034), female students (n=31, p= .007), especially Japanese female students (n=13, p= .023). Moreover, 80% of the students reported that they were more attentive listeners, and 60% agreed that they were more confident in dealing with emotional issues, both within themselves and in others, as a result of the workshop.&lt;/p&gt; &lt;p&gt;Conclusion: This study found the measurement of TEIQue-SF is appropriate and reliable to use for Asian medical students. The mental health workshop was helpful to develop medical students’ EI but showed different results for gender and nationality. The immediate impact on the emotional awareness of individuals was particularly significant for male students and the non-Japanese group. The impact over the long term was notable for the significant increase in EI for females and Japanese. Japanese female students were more conscious about emotionality. Emotion-driven communication exercises might strongly influence the development of students’ EI over a year.&lt;/p&gt

Identification and prediction of Parkinson's disease subtypes and progression using machine learning in two cohorts.

The clinical manifestations of Parkinson's disease (PD) are characterized by heterogeneity in age at onset, disease duration, rate of progression, and the constellation of motor versus non-motor features. There is an unmet need for the characterization of distinct disease subtypes as well as improved, individualized predictions of the disease course. We used unsupervised and supervised machine learning methods on comprehensive, longitudinal clinical data from the Parkinson's Disease Progression Marker Initiative (n = 294 cases) to identify patient subtypes and to predict disease progression. The resulting models were validated in an independent, clinically well-characterized cohort from the Parkinson's Disease Biomarker Program (n = 263 cases). Our analysis distinguished three distinct disease subtypes with highly predictable progression rates, corresponding to slow, moderate, and fast disease progression. We achieved highly accurate projections of disease progression 5 years after initial diagnosis with an average area under the curve (AUC) of 0.92 (95% CI: 0.95 ± 0.01) for the slower progressing group (PDvec1), 0.87 ± 0.03 for moderate progressors, and 0.95 ± 0.02 for the fast-progressing group (PDvec3). We identified serum neurofilament light as a significant indicator of fast disease progression among other key biomarkers of interest. We replicated these findings in an independent cohort, released the analytical code, and developed models in an open science manner. Our data-driven study provides insights to deconstruct PD heterogeneity. This approach could have immediate implications for clinical trials by improving the detection of significant clinical outcomes. We anticipate that machine learning models will improve patient counseling, clinical trial design, and ultimately individualized patient care

Pregnancy in multiple system atrophy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Multiple system atrophy is a late, adult-onset α-synucleinopathy with no data on the effect of pregnancy on the disease course. Early stage multiple system atrophy can be difficult to distinguish from Parkinson's disease.</p> <p>Case presentation</p> <p>We describe the case of an Irish woman with parkinsonism starting at age 31, initially diagnosed as having dopa-responsive, idiopathic Parkinson's disease, who successfully delivered a full-term child at age 35. Her pregnancy was complicated by severe orthostatic hypotension and motor fluctuations. Two years post-partum, she underwent bilateral subthalamic nuclei deep brain stimulation for intractable motor fluctuations and disabling dyskinesia. After this treatment course she experienced deterioration of motor symptoms and death eight years after disease onset. Post-mortem neuropathological examination revealed striatonigral degeneration and α-synuclein-positive glial cytoplasmic inclusions in brain stem nuclei, basal ganglia and white matter tracts, consistent with a neuropathological diagnosis of multiple system atrophy.</p> <p>Conclusions</p> <p>Multiple system atrophy can affect women of child-bearing age and pregnancy may be associated with marked disease progression.</p

Dynamic anoxic ferruginous conditions during the end-Permian mass extinction and recovery

The end-Permian mass extinction, ~252 million years ago, is notable for a complex recovery period of ~5 Myr. Widespread euxinic (anoxic and sulfidic) oceanic conditions have been proposed as both extinction mechanism and explanation for the protracted recovery period, yet the vertical distribution of anoxia in the water column and its temporal dynamics through this time period are poorly constrained. Here we utilize Fe–S–C systematics integrated with palaeontological observations to reconstruct a complete ocean redox history for the Late Permian to Early Triassic, using multiple sections across a shelf-to-basin transect on the Arabian Margin (Neo-Tethyan Ocean). In contrast to elsewhere, we show that anoxic non-sulfidic (ferruginous), rather than euxinic, conditions were prevalent in the Neo-Tethys. The Arabian Margin record demonstrates the repeated expansion of ferruginous conditions with the distal slope being the focus of anoxia at these times, as well as short-lived episodes of oxia that supported diverse biota

Development of Iron Speciation Reference Materials for Palaeoredox Analysis

The development and application of geochemical techniques to identify redox conditions in modern and ancient aquatic environments has intensified over recent years. Iron (Fe) speciation has emerged as one of the most widely used procedures to distinguish different redox regimes in both the water column and sediments, and is the main technique used to identify oxic, ferruginous (anoxic, Fe(II) containing) and euxinic (anoxic, sulfidic) water column conditions. However, an international sediment reference material has never been developed. This has led to concern over the consistency of results published by the many laboratories that now utilise the technique. Here, we report an interlaboratory comparison of four Fe speciation reference materials for palaeoredox analysis, which span a range of compositions and reflect deposition under different redox conditions. We provide an update of extraction techniques used in Fe speciation and assess the effects of both test portion mass, and the use of different analytical procedures, on the quantification of different Fe fractions in sedimentary rocks. While atomic absorption spectroscopy and inductively coupled plasma‐optical emission spectrometry produced comparable Fe measurements for all extraction stages, the use of ferrozine consistently underestimated Fe in the extraction step targeting mixed ferrous–ferric minerals such as magnetite. We therefore suggest that the use of ferrozine is discontinued for this Fe pool. Finally, we report the combined data of four independent Fe speciation laboratories to characterise the Fe speciation composition of the reference materials. These reference materials are available to the community to provide an essential validation of in‐house Fe speciation measurements

Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients

Background: The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10) in brain tissue of multiple system atrophy (MSA) patients differ from those in elderly controls and in patients with other neurodegenerative diseases. Methods: Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA) type, 6 striatonigral degeneration (SND) type, and 5 mixed type] was used for this study. Elderly controls (n = 37) as well as idiopathic Parkinson's disease (n = 7), dementia with Lewy bodies (n = 20), corticobasal degeneration (n = 15) and cerebellar ataxia (n = 18) patients were used as comparison groups. CoQ10 was measured in cerebellar and frontal cortex tissue by high performance liquid chromatography. Results: We detected a statistically significant decrease (by 3–5%) in the level of CoQ10 in the cerebellum of MSA cases (P = 0.001), specifically in OPCA (P = 0.001) and mixed cases (P = 0.005), when compared to controls as well as to other neurodegenerative diseases [dementia with Lewy bodies (P<0.001), idiopathic Parkinson's disease (P<0.001), corticobasal degeneration (P<0.001), and cerebellar ataxia (P = 0.001)]. Conclusion: Our results suggest that a perturbation in the CoQ10 biosynthetic pathway is associated with the pathogenesis of MSA but the mechanism behind this finding remains to be elucidated