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Background Aims Materials and methods Results Conclusions Pregnant women have historically been excluded from participation in medication trials, in part due to the perceived risks of drug exposure to mothers and fetuses. However, little is known about pregnant women's attitudes toward risk and participation in such trials.To address this knowledge gap and to identify factors that influence trial participation.Australian women over the age of 18, currently pregnant or within six months of delivery, were recruited to participate in an online survey (n = 623) and follow‐up interviews (n = 11). The survey investigated willingness to participate in five hypothetical drug trial scenarios of varying risk. Demographic and obstetric information, including COVID‐19 vaccination status, was also collected. The impact of these factors on trial participation was analysed using ordinal regression. Interviews were subjected to thematic framework analysis using a priori and emergent themes.Nearly half of the respondents (48%) indicated a willingness to participate in at least one of the hypothetical trials. As trial risk increased participation likelihood decreased, especially if the risk was to the fetus, regardless of benefits to the mother. COVID‐19 vaccination status and medication hesitancy were predictors of an unwillingness to participate. Three broad themes emerged from the qualitative data: risk–benefit analysis, quality of evidence, and trust.Overall, participants expressed a positive attitude toward research and medication trials during pregnancy, but were concerned about fetal risk. The findings of this study may help enhance trial design and the participation of pregnant women in medication trials. [ABSTRACT FROM AUTHOR]

Objectives: Care for community‐dwelling people with dementia is frequently delegated to relatives, who find themselves in the role of informal caregivers with no practical management knowledge. This situation exposes caregivers to increased risk for emotional wellbeing. The current study aims to test whether the integration of the efficacy of an immersive virtual reality (VR) experience into an online psychoeducational program impacts caregiver empathy and therefore emotional wellbeing. Methods: One‐hundred informal caregivers of mild‐to‐moderate Alzheimer's disease (AD) patients will be enrolled and randomly assigned to (i) an online psychoeducational program (control arm); or (ii) an online psychoeducational program integrated with VR (experimental arm). VR will consist of 360‐degree videos involving the caregivers to an immersive experience of dementia symptoms from the patient's perspective. Before, after the intervention and after 2 months, all participants will complete validated clinical scales for caregiver burden and anxiety (primary outcomes) and sense of competence and dispositional empathy (secondary outcomes). A subsample of 50 participants will also undergo MRI exam, including structural and functional (resting‐state and task‐functional MRI [fMRI]) sequences. The fMRI task paradigm will use emotional stimuli to evaluate the neural correlate of empathy, by stressing its cognitive and affective components. The main outcome will be the change in the clinical assessment; the secondary outcome will be the change in brain connectivity of networks subserving the empathic and emotional functioning. Results: We expect that the psychoeducational program will decrease anxiety and stress, enabling caregivers to perceive themselves capable of managing AD patients at home, educating them on symptom handling and boosting their cognitive empathy. In the experimental intervention, the VR‐based experience will act as an add‐on to psychoeducation, leading to greater improvement in the assessed clinical dimensions. VR should, in fact, enable a deeper understanding of disease symptoms and improve caregivers' cognitive empathy. We expect that the experimental intervention will result in deeper comprehension of disease symptoms and further strengthen caregivers' cognitive empathy. At the neural level, we expect to observe increased activation in circuits subserving cognitive empathy and decreased activation in circuits underlying affective empathy. Conclusions: To the best of our knowledge, this will be the first randomized controlled trial assessing the effect of combining psychoeducational interventions with VR‐based experience in caregivers, and assessing both clinical and imaging outcomes. Trial Registration: Registered in ClinicalTrials.gov (NCT05780476) [ABSTRACT FROM AUTHOR]

Background and purpose: The use of multiple tests, including spirometry, arterial blood gas (ABG) analysis and overnight oximetry (OvOx), is highly recommended to monitor the respiratory function of patients with motor neuron disease (MND). In this study, we propose a composite score to simplify the respiratory management of MND patients and better stratify their prognosis. Materials and Methods: We screened the clinical charts of 471 non‐ventilated MND patients referred to the Neuro‐rehabilitation Unit of the San Raffaele Scientific Institute of Milan (January 2001–December 2019), collecting spirometric, ABG and OvOx parameters. To evaluate the prognostic role of each measurement, univariate Cox regression for death/tracheostomy was performed, and the variables associated with survival were selected to design a scoring system. Univariate and multivariate Cox regression analyses were then carried out to evaluate the prognostic role of the score. Finally, results were replicated in an independent cohort from the Turin ALS Center. Results: The study population included 450 patients. Six measurements were found to be significantly associated with survival and were selected to design a scoring system (maximum score = 8 points). Kaplan–Meier analysis showed significant stratification of survival and time to non‐invasive mechanical ventilation adaptation according to score values, and multivariate analysis confirmed the independent effect of the respiratory score on survival of each cohort. Conclusion: Forced vital capacity, ABG and OvOx parameters provide complementary information for the respiratory management and prognosis of MND patients and the combination of these parameters into a single score might help neurologists predict prognosis and guide decisions on the timing of the implementation of different diagnostic or therapeutic approaches. [ABSTRACT FROM AUTHOR]

Once considered the most speciose mostly azooxanthellate scleractinian group, the family Caryophylliidae is found to be highly polyphyletic based on molecular data and is undergoing a process of systematic revision. High‐throughput sequencing methods coupled with morphological analyses have facilitated revision of several scleractinian lineages, including the aforementioned family. In previous studies that relied on few mitochondrial and nuclear markers, the caryophylliid genera Stephanocyathus and Vaughanella were phylogenetically recovered in separate clades from the lineage that includes the type genus of the family, Caryophyllia, which is considered the 'true' Caryophylliidae. To help untangle the relationship among taxa of this family, here a new deep‐sea scleractinian family (Stephanocyathidae Vaga, Cairns & Kitahara fam. nov.) is proposed based on phylogenomic reconstructions coupled with molecular features, specifically gene order, of the complete mitochondrial genome. Evolutionary reconstructions were based on both mitochondrial and nuclear ultraconserved elements (UCEs) and exon loci data sets and confirmed the divergent position of the genera Stephanocyathus and Vaughanella. The new family shows a specific gene transposition in the mitochondrial genome, not present in the 'true' caryophylliid lineage, but instead already observed for the species Paraconotrochus antarcticus, recovered as sister taxon of the here proposed new family. Although its phylogenetic position is unknown, the genus Ericiocyathus is also added to the new family, based on macromorphological similarities. This study represents a step forward in our understanding of deep‐sea corals relationships and provide further information (e.g., mitochondrial gene order) that will aid in future efforts of assessing the systematic of caryophylliid lineages. [ABSTRACT FROM AUTHOR]

Numerous genomic methods developed over the past two decades have enabled the discovery and extraction of orthologous loci to help resolve phylogenetic relationships across various taxa and scales. Genome skimming (or low‐coverage genome sequencing) is a promising method to not only extract high‐copy loci but also 100s to 1000s of phylogenetically informative nuclear loci (e.g., ultraconserved elements [UCEs] and exons) from contemporary and museum samples. The subphylum Anthozoa, including important ecosystem engineers (e.g., stony corals, black corals, anemones, and octocorals) in the marine environment, is in critical need of phylogenetic resolution and thus might benefit from a genome‐skimming approach. We conducted genome skimming on 242 anthozoan corals collected from 1886 to 2022. Using existing target‐capture baitsets, we bioinformatically obtained UCEs and exons from the genome‐skimming data and incorporated them with data from previously published target‐capture studies. The mean number of UCE and exon loci extracted from the genome skimming data was 1837 ± 662 SD for octocorals and 1379 ± 476 SD loci for hexacorals. Phylogenetic relationships were well resolved within each class. A mean of 1422 ± 720 loci was obtained from the historical specimens, with 1253 loci recovered from the oldest specimen collected in 1886. We also obtained partial to whole mitogenomes and nuclear rRNA genes from >95% of samples. Bioinformatically pulling UCEs, exons, mitochondrial genomes, and nuclear rRNA genes from genome skimming data is a viable and low‐cost option for phylogenetic studies. This approach can be used to review and support taxonomic revisions and reconstruct evolutionary histories, including historical museum and type specimens. [ABSTRACT FROM AUTHOR]

The alteration in the neural circuits of both central and peripheral nervous systems is closely related to the onset of neurodegenerative disorders (NDDs). Despite significant research efforts, the knowledge regarding NDD pathological processes, and the development of efficacious drugs are still limited due to the inability to access and reproduce the components of the nervous system and its intricate microenvironment. 2D culture systems are too simplistic to accurately represent the more complex and dynamic situation of cells in vivo and have therefore been surpassed by 3D systems. However, both models suffer from various limitations that can be overcome by employing two innovative technologies: organ‐on‐chip and 3D printing. In this review, an overview of the advantages and shortcomings of both microfluidic platforms and extracellular matrix‐like biomaterials will be given. Then, the combination of microfluidics and hydrogels as a new synergistic approach to study neural disorders by analyzing the latest advances in 3D brain‐on‐chip for neurodegenerative research will be explored. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We investigated in vivo the microstructural integrity of the pathway connecting the locus coeruleus to the transentorhinal cortex (LC‐TEC) in patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD). METHODS: Diffusion‐weighted MRI scans were collected for 21 AD, 20 behavioral variants of FTD (bvFTD), and 20 controls. Fractional anisotropy (FA), mean, axial, and radial diffusivities (MD, AxD, RD) were computed in the LC‐TEC pathway using a normative atlas. Atrophy was assessed using cortical thickness and correlated with microstructural measures. RESULTS: We found (i) higher RD in AD than controls; (ii) higher MD, RD, and AxD, and lower FA in bvFTD than controls and AD; and (iii) a negative association between LC‐TEC MD, RD, and AxD, and entorhinal cortex (EC) thickness in bvFTD (all p < 0.050). DISCUSSION: LC‐TEC microstructural alterations are more pronounced in bvFTD than AD, possibly reflecting neurodegeneration secondary to EC atrophy. Highlights: Microstructural integrity of LC‐TEC pathway is understudied in AD and bvFTD.LC‐TEC microstructural alterations are present in both AD and bvFTD.Greater LC‐TEC microstructural alterations in bvFTD than AD.LC‐TEC microstructural alterations in bvFTD are associated to EC neurodegeneration. [ABSTRACT FROM AUTHOR]

Despite the introduction of targeted (BRAFi/MEKi) and immune checkpoint inhibitors (ICIs) has significantly reduced the recurrence rate and improved the overall survival (OS) of patients with Stage III and IV melanoma, only a percentage will benefit of durable disease control. The aim of this study was to examine whether the levels of circulating tumour DNA (ctDNA) in plasma of advanced melanoma patients undergoing BRAFi/MEKi or ICIs vary according to the patients' survival outcomes (i.e. progression‐free survival (PFS) and OS) and disease progression. Plasma samples of Stage III‐IV melanoma patients were collected at baseline (treatment initiation) and thereafter every 3 months. Circulating BRAFV600E/K and NRASQ61R/K mutations were analysed through droplet digital PCR (ddPCR, Bio‐Rad) in a total of 177 plasma samples from 48 melanoma patients (19 Stage III, 29 Stage IV). Baseline ctDNA concentration was significantly associated with OS (HR = 1.003, 95% CI = 1.000–1.006, p = 0.043) and PFS (HR = 1.004, 95% CI = 1.000–1.007, p = 0.029) independent of clinical‐prognostic confounders. For each unit increase in the ∆ctDNA (concentration difference between the last follow‐up and baseline) there was a 24% increased risk of disease progression, irrespective of treatment type and stage at diagnosis (OR = 1.24, 95% CI = 1.03–1.49, p = 0.020, AUC = 0.93). Patients with reduction of ctDNA level from baseline to the last follow‐up had longer OS (HR = 0.14; 95% CI = 0.05–0.44, p = 0.001) and PFS (HR = 0.08; 95% CI = 0.03–0.27, p < 0.0001) compared to patients with increased ctDNA, including adjustment for confounding factors. Our findings suggest that variation of ctDNA over time during melanoma treatment reflects the clinical outcome and tumour response to therapy and might be helpful in clinical monitoring. [ABSTRACT FROM AUTHOR]

BACKGROUND: Biofortification of vegetables is an important innovation technique in the horticultural sector. Vegetables can be a vector of different minor elements that have beneficial effects on human health. Selenium (Se) is an important element for human nutrition and plays a significant role in defence mechanisms. The aim of this work was to investigate the effect of Se in the nutrient solutions on the crop biofortification ability, yield, and quality parameters of four baby leafy vegetables destined to the minimally processed industry. Experiments were performed on lamb's lettuce, lettuce, wild rocket, and spinach. These crops were cultivated in the floating systems with nutrient solution enriched with 0, 2.6, 3.9, and 5.2 μmol L−1 Se provided as sodium selenate. RESULTS: At harvest, Se concentrations, yield, nitrate concentration, sugars, and some mineral elements were measured. Data collected and analyses showed that yield, nitrate, sucrose, and reducing sugars were not affected by Se treatments, even if varied among species. Se concentrations linearly increased in leaves of different species by increasing the Se concentration in the nutrient solution. Rocket was the species with the highest accumulation ability and reached a concentration of 11 μg g−1 fresh weight Se in plants grown with 5.2 μmol L−1 Se. CONCLUSION: A floating system with Se‐enriched nutrient solution is an optimal controlled growing biofortification system for leafy vegetables. The accumulation ability decreased in different species in the order wild rocket, spinach, lettuce, and lamb's lettuce, highlighting a crop‐dependent behaviour and their attitude to biofortification. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Target‐capture approaches have facilitated a rapid growth in the field of phylogenomics but few probe sets exist for molluscs, an exceptionally rich phylum with unparalleled ecological and morphological diversity. We designed and tested the first universal probe set using Phyluce to capture ultraconserved elements (UCEs) and exon loci from the Subclass Caenogastropoda ‐ one of six major lineages of gastropods. The probe set consists of 29,441 probes designed to target 1142 UCE loci and 1933 exon loci (3075 total). In silico analyses of our probe set yielded an average of 2110 loci from genomes and 1389 loci from transcriptomes of diverse caenogastropods, from which an average of 1669 and 849 loci were retained respectively after screening to remove those that matched multiple contigs. Phylogenetic analyses of the loci extracted from transcriptomes produced well‐supported trees very similar to those published based on transcriptomic analyses. Phylogenetic relationships estimated from loci extracted from genomes recover similar phylogenetic relationships, and indicate that the loci targeted with this probe set are informative for resolving deep phylogenetic relationships. An in vitro analysis of the probe set with the Epitoniidae, a diverse caenogastropod family of uncertain affinity and with poorly resolved evolutionary relationships, recovered a total of 2850 loci. Although preliminary, the analysis of loci captured by our probe set for a small number of epitoniid taxa produced a well‐resolved tree indicating that this probe set is also able to resolve relationships at shallower hierarchical scales. Together, the in silico and in vitro analyses indicate that target‐capture enrichment with this probe set is a useful tool for reconstructing phylogenetic relationships across taxonomic levels and evolutionary time scales. [ABSTRACT FROM AUTHOR]

This article reports on two cases of successful treatment with tralokinumab in patients with atopic dermatitis (AD) and dupilumab-induced psoriasis. The first case involves a 75-year-old woman who experienced psoriatic lesions after receiving dupilumab treatment. Methotrexate was added to manage the psoriatic eruption, but it was discontinued due to side effects. Tralokinumab was then started, resulting in the resolution of both AD and psoriatic lesions. The second case involves an 18-year-old woman who also developed psoriasis while on dupilumab. Tralokinumab was started after topical steroids showed minimal improvement, leading to remission of the psoriatic lesions and maintenance of AD remission. The article suggests that tralokinumab may be a valid option for treating AD in patients with dupilumab-induced psoriasis. [Extracted from the article]

Background: Cerebrospinal fluid (CSF) is highly labile and delayed processing might alter results of analysis. Hypothesis/Objectives: To determine the effects of time and addition of autologous serum on cytological evaluation of CSF. Animals: Ten client‐owned adult horses requiring euthanasia. Methods: Prospective study. Serum and CSF were collected from each horse before and within 10 minutes after euthanasia. CSF samples were divided into 15 aliquots (2 mL each); 1 aliquot was submitted for routine CSF analysis within 60 minutes of collection. Four drops of autologous serum were added to 7 of the aliquots, and stored at 4°C (serum group); the remaining 7 samples were stored unaltered at 4°C (control group). Total nucleated cell count (TNCC) and cell morphology score were done at T4, T8, T12, T24, T48, T72, and T96 hours after collection. Protein concentration was measured in the control group at T0 and T96 hours. Results: The cell morphology scores were significantly different in the control group at T48 (median 2, range 0‐4), T72 (2, 0‐4), and T96 (3, 0‐4) in comparison to T0 (1). No change was observed in the serum group. TNCC remained stable over time in both groups. No statistically significant difference in CSF protein concentration was found between T0 and T96. Conclusions and Clinical Importance: The addition of autologous serum to an aliquot of CSF sample before shipping improves the preservation of cell morphology up to 96 hours after collection. [ABSTRACT FROM AUTHOR]

Introduction: CDKL5 deficiency disorder (CDD) is a rare neurodevelopmental condition, primarily affecting girls for which no cure currently exists. Neuronal morphogenesis and plasticity impairments as well as metabolic dysfunctions occur in CDD patients. The present study explored the potential therapeutic value for CDD of FRAX486, a brain‐penetrant molecule that was reported to selectively inhibit group I p21‐activated kinases (PAKs), serine/threonine kinases critically involved in the regulation of neuronal morphology and glucose homeostasis. Methods: The effects of treatment with FRAX486 on CDD‐related alterations were assessed in vitro (100 nM for 48 h) on primary hippocampal cultures from Cdkl5‐knockout male mice (Cdkl5‐KO) and in vivo (20 mg/Kg, s.c. for 5 days) on Cdkl5‐KO heterozygous females (Cdkl5‐Het). Results: The in vitro treatment with FRAX486 completely rescued the abnormal neuronal maturation and the number of PSD95‐positive puncta in Cdkl5‐KO mouse neurons. In vivo, FRAX486 normalized the general health status, the hyperactive profile and the fear learning defects of fully symptomatic Cdkl5‐Het mice. Systemically, FRAX486 treatment normalized the levels of reactive oxidizing species in the whole blood and the fasting‐induced hypoglycemia displayed by Cdkl5‐Het mice. In the hippocampus of Cdkl5‐Het mice, treatment with FRAX486 rescued spine maturation and PSD95 expression and restored the abnormal PAKs phosphorylation at sites which are critical for their activation (P‐PAK‐Ser144/141/139) or for the control cytoskeleton remodeling (P‐PAK1‐Thr212). Conclusions: Present results provide evidence that PAKs may represent innovative therapeutic targets for CDD. [ABSTRACT FROM AUTHOR]

New biomarkers indicating the abuse of drugs and alcohol are still of major interest for clinical and forensic sciences. The endogenous neurotransmitter and approved drug, gamma‐hydroxybutyric acid (GHB), is often illegally used for drug‐facilitated crimes by spiking GHB into alcoholic beverages. Analytical detection windows of only 6 h in blood and 12 h in urine are often too short to provide reliable proof of GHB ingestion. Therefore, new biomarkers are needed to prove exogenous GHB administration. Previously, amino acid GHB conjugates were discovered in an untargeted metabolomics screening and fatty acid esters with GHB were recently discussed as promising biomarkers to enlarge the analytical detection time windows. However, the development of analytical methods is still slowed down since reference compounds for targeted screenings are still missing. In this paper, we describe simple procedures for the rapid synthesis and purification of amino acid GHB conjugates as well as fatty acid esters, which can be adopted in analytical and clinical/forensic laboratories. Structural characterization data, together with IR, 1H‐nuclear magnetic resonance (NMR), 13C‐NMR, high‐resolution mass spectra (MS), and MS/MS spectra in positive and negative ionization mode are reported for all obtained GHB conjugates and GHB conjugate precursors. [ABSTRACT FROM AUTHOR]

Background and purpose: This study was undertaken to determine the diagnostic and prognostic value of a panel of serum biomarkers and to correlate their concentrations with several clinical parameters in a large cohort of patients with amyotrophic lateral sclerosis (ALS). Methods: One hundred forty‐three consecutive patients with ALS and a control cohort consisting of 70 patients with other neurodegenerative disorders (DEG), 70 patients with ALS mimic disorders (ALSmd), and 45 healthy controls (HC) were included. Serum neurofilament light chain (NfL), ubiquitin carboxyl‐terminal hydrolase isozyme L1 (UCHL1), glial fibrillary acidic protein (GFAP), and total tau protein levels were measured using ultrasensitive single molecule array. Results: NfL correlated with disease progression rate (p < 0.001) and with the measures of upper motor neuron burden (p < 0.001). NfL was higher in the ALS patients with classic and pyramidal phenotype. GFAP was raised in ALS with cognitive–behavioral impairment compared with ALS with normal cognition. NfL displayed the best diagnostic performance in discriminating ALS from HC (area under the curve [AUC] = 0.990), DEG (AUC = 0.946), and ALSmd (AUC = 0.850). UCHL1 performed well in distinguishing ALS from HC (AUC = 0.761), whereas it was not helpful in differentiating ALS from DEG and ALSmd. In multivariate analysis, NfL (p < 0.001) and UCHL1 (p = 0.038) were independent prognostic factors. Survival analysis combining NfL and UCHL1 effectively stratified patients with lower NfL levels (p < 0.001). Conclusions: NfL is a useful biomarker for the diagnosis of ALS and the strongest predictor of survival. UCHL1 is an independent prognostic factor helpful in stratifying survival in patients with low NfL levels, likely to have slowly progressive disease. GFAP reflects extramotor involvement, namely cognitive impairment or frontotemporal dementia. [ABSTRACT FROM AUTHOR]

Cerium exchange by microporous materials, such as zeolites, has important applications in different fields, for example, rare earth element recovery from waste or catalytic processes. This work investigated the Ce‐exchange capacity of zeolite L in three different cationic forms (the as‐synthesized K form and Na‐ and NH4‐exchanged ones) from a highly concentrated solution. Chemical analyses and structural investigations allowed determination of the mechanisms involved in the exchanges and give new insights into the interactions occurring between the cations and the zeolite framework. Different cation sites are involved: (i) K present in the original LTL in the cancrinite cage (site KB) cannot be exchanged; (ii) the cations in KD (in the 12‐membered ring channel) are always exchanged; while (iii) site KC (in the eight‐membered ring channel) is involved only when K+ is substituted by NH4+, thus promoting a higher exchange rate for NH4+ → K+ than for Na+ → K+. In the Ce‐exchanged samples, a new site occupied by Ce appears in the centre of the main channel, accompanied by an increase in the number of and a rearrangement of H2O molecules. In terms of Ce exchange, the three cationic forms behave similarly, from both the chemical and structural point of view (exchanged Ce ranges from 38 to 42% of the pristine cation amount). Beyond the intrinsic structural properties of the zeolite L framework, the Ce exchange seems thus also governed by the water coordination sphere of the cation. Complete Ce recovery from zeolite pores was achieved. [ABSTRACT FROM AUTHOR]

To understand the pathology of axonal degeneration and demyelination in peripheral neuropathy, histological investigations in different animal models that mimic some aspects of human peripheral neuropathy are needed. Thus, in the following section of this special issue, the main pathological features of experimental autoimmune neuritis, animal models of chemotherapy‐induced peripheral neuropath and of human inherited peripheral neuropathies (IPNs) will be illustrated. When possible, micrographs from animal models and selected human biopsy will be shown side by side. [ABSTRACT FROM AUTHOR]

Normal nerve architecture is basic to a complete understanding of nerve pathology. Here, normal components of the nerve are illustrated, including myelinated and non‐myelinated nerve fibres, stromal elements, and vascular components. These are relevant because the differential diagnosis of neuropathy depends on the pathological processes affecting axon, myelin, interstitial space, and blood vessels. Thus, we present a description of the general pathological characteristics for the diagnosis of peripheral nerve disorders. [ABSTRACT FROM AUTHOR]

Pregnancy is a delicate phase in woman's life that could become a risk factor for osteoporosis in pregnant women who do not meet recommended nutrient standards, especially for calcium and vitamin D. Mediterranean diet (MD) has been demonstrated to be beneficial for adequate nutrient intake. This article aims to evaluate the MD adherence and dietary calcium intake in a group of pregnant Italian women and to investigate how these are linked to each other and to fast glycemia at first trimester of pregnancy. Two hundred and seventy‐nine pregnant women were recruited at the gynecology units of two hospitals in Florence. Socio‐demographic, clinical information, and results of the first trimester blood sample analysis were collected. Two questionnaires, validated for evaluation of MD adherence and calcium intake, were administered to the pregnant women. Approximately 60% of the women had a high level of MD adherence, with a mean dietary calcium intake of 870.3 ± 335.3. In women with higher MD adherence level, fast glycemia resulted lower. Calcium intake was lower than Population Rate Intake for the Italian population (1,200 mg/daily) and was positively correlated to MD adherence score. The MD proved to be nutritious, as it was related to a higher calcium intake in this group of Italian women. [ABSTRACT FROM AUTHOR]

Mutations in Myelin Protein Zero (MPZ) cause CMT1B, the second leading cause of CMT1. Many of the >200 mutations cause neuropathy through a toxic gain of function by the mutant protein such as ER retention, activation of the Unfolded Protein Response (UPR) or disruption of myelin compaction. While there is extensive literature on the loss of function consequences of MPZ in heterozygous Mpz +/− null mice, there is little known of the consequences of MPZ haploinsufficiency in humans. We identified six patients from different families with p.Tyr68Ter or p.Asp104fs heterozygous mutations of MPZ that are predicted to cause a premature termination and nonsense mediated decay of the mutant allele. Five patients were evaluated in Milan and one in Iowa City; all should be haploinsufficient for MPZ. Patients were evaluated clinically and by electrophysiology. Sensory ataxia dominated the clinical presentation with only mild weakness present in five of the six patients. Symptoms presented in adulthood in all patients and only one individual had a CMTNSv2 >5. Deep tendon reflexes were absent in all patients. Patients with likely MPZ loss of function due to mutations that cause haplodeficiency in MPZ have a mild, predominantly large fiber sensory neuropathy that serves as a human equivalent to the neuropathy observed in heterozygous Mpz null mice. Successful therapeutic approaches in treating Mpz deficient mice may be candidates for trials in these and similar patients. [ABSTRACT FROM AUTHOR]

As coral populations decline worldwide in the face of ongoing environmental change, documenting their distribution, diversity and conservation status is now more imperative than ever. Accurate delimitation and identification of species is a critical first step. This task, however, is not trivial as morphological variation and slowly evolving molecular markers confound species identification. New approaches to species delimitation in corals are needed to overcome these challenges. Here, we test whether target enrichment of ultraconserved elements (UCEs) and exons can be used for delimiting species boundaries and population structure within species of corals by focusing on two octocoral genera, Alcyonium and Sinularia, as exemplary case studies. We designed an updated bait set (29,181 baits) to target‐capture 3,023 UCE and exon loci, recovering a mean of 1,910 ± 168 SD per sample with a mean length of 1,055 ± 208 bp. Similar numbers of loci were recovered from Sinularia (1,946 ± 227 SD) and Alcyonium (1,863 ± 177 SD). Species‐level phylogenies were highly supported for both genera. Clustering methods based on filtered single nucleotide polymorphisms delimited species and populations that are congruent with previous allozyme, DNA barcoding, reproductive and ecological data for Alcyonium, and offered further evidence of hybridization among species. For Sinularia, results were congruent with those obtained from a previous study using restriction site associated DNA sequencing. Both case studies demonstrate the utility of target‐enrichment of UCEs and exons to address a wide range of evolutionary and taxonomic questions across deep to shallow timescales in corals. [ABSTRACT FROM AUTHOR]

The peripheral nervous system may be involved at any stage in the course of several hematological diseases, the most common being monoclonal gammopathies (of undetermined significance or malignant) or lymphomas. The underlying pathogenic mechanisms are different and therapies aim at targeting the dangerous either B‐cell or plasma cell clones. Recently, high‐throughput technologies, and next‐generation sequencing have increased our knowledge of hematological diseases pathogenesis by the identification of somatic mutation affecting pivotal signaling pathways. Accordingly, new target therapies are used that may also be borrowed for treatment of neuropathies in hematological diseases. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons. Pre‐clinical studies drive the development of animal models that well mimic ALS disorder and enable both the dissection of disease processes and an early assessment of therapy efficacy. A comprehensive knowledge of neuronal and vascular lesions in the brain and spinal cord is an essential factor to understand the development of the disease. Spatial resolution and bidimensional imaging are important drawbacks limiting current neuroimaging tools, while neuropathology relies on protocols that may alter tissue chemistry and structure. In contrast, recent ex vivo studies in mice demonstrated that X‐ray phase‐contrast tomography enables study of the 3D distribution of both vasculature and neuronal networks, without sample sectioning or use of staining. Here we present our findings on ex vivo SOD1G93A ALS mice spinal cord at a micrometric scale. An unprecedented direct quantification of neuro‐vascular alterations at different stages of the disease is shown. [ABSTRACT FROM AUTHOR]

New onset of remitting seronegative symmetrical synovitis with pitting oedema and palmoplantar psoriasis flare-up after Sars-Cov-2 vaccination The scenario indicated a flare-up of palmar psoriasis associated with the onset of psoriatic arthritis with remitting seronegative symmetrical synovitis with pitting oedema (RS3PE). (b) Tenosynovitis of the digital extensor tendon. gl New onset or exacerbation of psoriatic disease following vaccinations, though rare, is reported in literature. [Extracted from the article]

In this study, we assessed the modifications over time of daily activities and quality of life (QoL) in 32 subjects with anti‐myelin‐glycoprotein (MAG) antibody neuropathy. A widespread panel including clinical scores and patient‐reported questionnaires, in compliance of the terms by the International Classification of Functioning, Disability, and Health (ICF) of the World Health Organization (WHO), was employed at enrollment (T0) and at follow‐up evaluation (T1) after a mean interval of 15.4 ± 5.7 months. The Sensory Modality Sum score (SMS) at four limbs showed a significant worsening over time (mean score 27.2 ± 3.9 at T0 vs 25.7 ± 3 at T1 at upper limbs, P = .03; 20.5 ± 4.8 at T0 vs 18.6 ± 5.9 at T1 at lower limbs, P = .04). The Visual Analogue Scale (VAS) for pain significantly worsened at upper limbs at T1 (mean values 0.84 ± 1.95 at T0 vs 1.78 ± 2.6 at T1, P = .03). All the other tests did not show significant differences between T0 and T1. In the subgroup who underwent rituximab (15/32 treated before T0, 3/32 patients treated between T0 and T1 with median interval of 1 year), no significant differences were observed between T0 and T1. Despite the quite long follow‐up, statistical significance was not achieved either for the limited number of patients or for the lack of sensitive outcome measures. In our cohort, the significant worsening of the SMS and VAS after a median of 14 months can be considered as a reliable expression of the natural history of the disease, and suggest that these scales might represent possible outcome measures in anti‐MAG antibody neuropathy. [ABSTRACT FROM AUTHOR]

Background: Borderline personality disorder (BPD) is a psychiatric condition associated with the impairment of the frontolimbic network. However, a growing body of studies suggests that brain dysfunction underling BPD could involve other brain areas. We explored the whole‐brain white matter (WM) organization in BPD patients to clarify the structural pattern underlying the disease and its relationship with clinical features. Methods: Fourteen BPD patients and 14 healthy controls underwent a multidimensional clinical assessment and diffusion tensor imaging acquisition. Measures of fractional anisotropy (FA) and mean, axial and radial (RD) diffusivity were collected, and alterations in the WM were assessed using the voxelwise approach, including substance and alcohol abuse as covariates. Voxelwise regression analysis was performed to identify associations between microstructural changes and clinical feature in BPD. Results: Group comparisons showed alterations only for FA and RD: FA decreased in the right posterior hemisphere, while RD increased bilaterally and widespread in anterior and posterior areas (p < 0.05, threshold‐free cluster enhancement corrected). Moreover, WM alterations of the corpus callosum were related to anxiety in BPD group. Discussion: Our data support the idea that structural alterations underling BPD also involve cortico‐cortical pathways, corticothalamic and corticostriatal tracts, suggesting that the frontolimbic model should be reinterpreted. © 2019 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In August 2007, October 2008 and September–October 2010, 241 Tucker trawl and plankton net tows were conducted at the surface to depths of 1377 m at six locations in the northern and eastern Gulf of Mexico (GOM) to document leptocephalus diversity and determine how assemblage structure, larval size, abundance and isotopic signatures differ across the region and with depth. Overall, 2696 leptocephali representing 59 distinct taxa from 10 families were collected. Five families accounted for 96% of the total catch with Congridae and Ophichthidae being the most abundant. The top four most abundant species composed 59% of the total catch and included: Ariosoma balearicum, Paraconger caudilimbatus, Rhynchoconger flavus and Ophichthus gomesii. Four anguilliform species not previously documented in the GOM as adults or leptocephali were collected in this study, including Monopenchelys acuta, Quassiremus ascensionis, Saurenchelys stylura and one leptocephalus only known from its larval stage, Leptocephalus proboscideus. Leptocephalus catches were significantly greater at night than during the day. Catches at night were concentrated in the upper 200 m of the water column and significantly declined with increasing depth. Leptocephali abundances and assemblages were significantly different between sites on the upper continental slope (c. 500 m depth) and sites on the middle to lower continental slope (c. 1500–2300 m). Sites on the lower continental slope had a mixture of deep‐sea demersal, bathypelagic and coastal species, whereas upper‐slope sites contained several numerically dominant species (e.g., A. balearicum, P. caudilimbatus) that probably spawn over the continental shelf and upper slope of the GOM. Standard lengths of the four dominant species differed between sites and years, indicating heterochronic reproduction and potential larval source pools within and outside of the GOM. Stable‐isotope analyses (δ13C and δ15N) conducted on 185 specimens from six families revealed that leptocephali had a wide range of isotopic values at the family and size‐class levels. Species in the families Muraenidae, Congridae and Ophichthidae had similar δ15N values compared with the broad range of δ15N values seen in the deep‐sea families Nemichthyidae, Nettastomatidae and Synaphobranchidae. Stable‐isotope values were variably related to length, with δ15N values being positively size correlated in ophichthids and δ13C values being negatively size correlated in A. balearicum and P. caudilimbatus. Results suggest that leptocephali feed in various water depths and masses, and on different components of POM, which could lead to niche partitioning. Ecological aspects of these important members of the plankton community provide insight into larval connectivity in the GOM as well as the early life history of Anguilliformes. [ABSTRACT FROM AUTHOR]

Background: Non‐cognitive deficits (e.g., sleep‐cycle and neuroendocrine alterations) are commonly observed in Alzheimer's disease (AD) and are suggestive of hypothalamic (HPT) dysfunctions (Ishii and Iadecola., 2015). However, studies on the HPT involvement in the early stages of the disease are limited. Here, we compared the volumes of HPT and its subunits in cognitively unimpaired (CU), mild cognitive impairment (MCI), and AD. Method: Twenty‐nine cognitively unimpaired (CU), 21 MCI, and 21 AD participants were enrolled and underwent 3T MRI and neuropsychological exams. 3D T1‐weighted images were processed using the standard FreeSurfer v7.2 pipeline, and the newly released tool for the automated segmentation of HPT and its subunits (Billot et al., 2020). After normalization to the total intracranial volume, whole and subunits HTP volumes were compared among groups using the Kruskall‐Wallis test with Dunn‐Bonferroni correction. Result: MCI and AD showed lower left (p<.001) and right (p =.013) whole HPT volume than CU. Furthermore, lower volumes were detected in both the hemisphere for the anterior (p<.011) and posterior (p<.001) subunits in AD, and for right anterior posterior (p =.025) and for the superior tubular (p =.045) subunits in MCI, as compared with CU. No HPT differences were observed between AD and MCI patients. Conclusion: Posterior HPT subunit atrophy was detectable since MCI stage and increased according to the disease progression. These results suggest a possible involvement of hypothalamus in early AD phases. [ABSTRACT FROM AUTHOR]

Background: Recent studies reported microstructural alterations in the locus coeruleus ‐ transentorhinal cortex (LC‐TEC) pathway in patients with Alzheimer's disease (AD) but data in subjects at risk of AD (i.e., cognitively intact APOEε4 carriers) are missing. In this study, we apply in‐vivo diffusion weighted images (DWI) to study the effect of APOEε4 on the LC‐TEC pathway in cognitively unimpaired subjects. Method: Forty‐five participants (14 APOEε4 carriers: age = 68±7 years, 45% females, MMSE score = 29±0.9; 31 non‐carriers: age = 68±6 years, 57% females, MMSE score = 30±0.6) underwent multimodal 3T MRI and multidomain neuropsychological exams. DWI were corrected for distortions with topup and eddy tools (part of FMRIB's Software Library – FSL). Microstructural measures as fractional anisotropy (FA), mean (MD), axial (AxD), and radial (RD) diffusivities maps were estimated using the FMRIB's Diffusion Toolbox (part of FSL) after the exclusion of cerebrospinal fluid voxels. Microstructural integrity of LC‐TEC was assessed using a thresholded probabilistic atlas non‐linearly warped on native maps with FNIRT (part of FSL). A Bonferroni multivariate generalized linear model, corrected for age and sex, was conducted to compare the diffusivity indexes between APOEε4 carriers and non‐carriers. Association with memory functioning (immediate and delayed recall) was also tested using Spearman's rank correlations test. Result: APOEε4 carriers and non‐carriers were comparable for cognitive performance (p>.246). Compared to non‐carriers, APOEε4 carriers showed lower FA (p = 0.048) and higher RD (p = 0.036) in the left LC‐TEC. In APOEε4 carriers, left RD negatively correlated with both immediate (rho = ‐0.808, p<0.001) and delayed (rho = ‐0.673, p = 0.025) memory recall. Conclusion: Microstructural alterations of the LC‐TEC pathway are detectable in subjects at‐risk for AD and correlate with lower memory performance. These preliminary results support the view that LC‐TEC impairment may play a role in AD pathophysiology since its early stages. [ABSTRACT FROM AUTHOR]

Background: The ε4 allele of the Apolipoprotein E gene (APOE) is a well‐established risk factor for Alzheimer's disease (AD), ε4 carriers showing earlier onset and more severe memory impairment than non‐carriers. Neuroimaging evidence suggests that APOEε4 may modulate neural activity in AD since early stages. The purpose of this study was to determine whether APOEε4 influences brain activity in the memory circuit in older cognitively unimpaired individuals. Method: Thirty cognitively unimpaired participants (n = 10 APOEε4 heterozygous carriers, age = 65± 5 years, 50% females, MMSE score = 29±1; n = 20 APOEε4 non‐carriers, age = 68±5 years, 35% females, MMSE score = 30±1) were recruited and underwent multidomain (i.e., memory, visuospatial abilities, language, attention) neuropsychological exams and functional MRI scan during an associative memory task, which consisted of two phases: (i) encoding of face‐name associations; (ii) recognition of the name associated to each face. Image preprocessing and voxel‐wise comparisons were conducted using the Statistical Parametric Mapping (SPM, v12). Clusters were considered significant at an uncorrected threshold of p<0.001. Result: Participants were comparable for demographic and cognitive features (p>0.10) and performed similarly on the in‐scanner face‐name association memory task (p>0.10). Compared to ε4 non‐carriers, carriers showed (i) greater activation during the encoding task in the left temporo‐occipital cortex/fusiform gyrus, (ii) greater activation during the recognition task in the middle temporal gyrus/temporo‐occipital cortex bilaterally and in the right cerebellum, and (iii) lower activation during the recognition task in the medial supplementary motor area. Conclusion: These preliminary results confirm that the APOE ε4 allele is associated with a different pattern of brain functional activity during an associative memory task in cognitively unimpaired older. Given the similar cognitive performance between groups, higher activation in temporo‐occipital regions might reflect a compensatory process in regions vulnerable to AD pathology. [ABSTRACT FROM AUTHOR]

We wish to thank Drs Aamir, Shah and Mansure for their valuable comments on our recently published report investigating an "integrated panel of neurochemical biomarkers to optimize diagnosis and prognosis in amyotrophic lateral sclerosis" (ALS) [[1]], and are glad to see that our article stimulates further discussion on the topic of novel biomarkers for motor neuron diseases. However, axonal degeneration is not an ALS-specific process, as it is shared by several neurodegenerative and neuromuscular diseases; hence, the development of more specific ALS biomarkers is urgently needed. [Extracted from the article]

Background: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behaviour but their small size hampers their manual segmentation in multicenter datasets. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors. We applied a new high‐resolution atlas in two independent cohorts of older and younger healthy adults. Method: Sixty‐four older (PharmaCog study; age range: 50‐78 years) and 67 younger subjects (CoRR consortium; age range: 18‐43 years) underwent repeated 3D‐T1 MRI at two different time points between 1 and 90 days. Amygdala and hippocampus segmentation was performed using FreeSurfer v6.0. Reliability of functional parcellations was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. Nuclei/subfields were considered as single structures and grouped into relevant subregions (for the amygdala, basolateral and the centromedial complexes; for the hippocampus, head, body, and tail subdivisions). Result: Differences in MRI site/vendor had a significant impact (p<.05) for the ε of few subfields/nuclei, while extensively impacted DICE of most structures. The effect on DICE was limited by the functional parcellation only in the younger cohort. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (|rs|>.43, p<.001). In line, nuclei larger than 200 mm3 and subfields larger than 300 mm3 (except for molecular layer) had the best test‐retest reproducibility (ε<5% and DICE>0.80). Conclusion: Our results support the use of volumetric measures derived automatically from larger amygdalar nuclei and hippocampal subfields as reliable measures in multisite longitudinal MRI studies. These measures could be useful for studies evaluating disease progression and treatment response. [ABSTRACT FROM AUTHOR]

Deep‐sea coral communities are key components of the Gulf of Mexico ecosystem and were adversely affected by the Deepwater Horizon (DWH) oil spill. Coral colonies exposed to oil and dispersant exhibited mortality, damage and physiological signatures of stress. Understanding how corals respond to oil and dispersant exposure at the molecular level is important to elucidate the sublethal effects of the DWH disaster and reveal broader patterns of coral stress responses. Gene expression profiles from RNAseq data were compared between corals at an impacted site and from a reference site. A total of 1,439 differentially expressed genes (≥twofold) were shared among impacted Paramuricea biscaya colonies. Genes involved in oxidative stress, immunity, wound repair, tissue regeneration and metabolism of xenobiotics were significantly differentially expressed in impacted corals. Enrichment among the overexpressed genes indicates the corals were enduring high metabolic demands associated with cellular stress responses and repair mechanisms. Underexpression of genes vital to toxin processing also suggests a diminished capacity to cope with environmental stressors. Our results provide evidence that deep‐sea corals exhibited genome‐wide cellular stress responses to oil and dispersant exposure and demonstrate the utility of next‐generation sequencing for monitoring anthropogenic impacts in deep waters. These analyses will facilitate the development of diagnostic markers for oil and dispersant exposure in deep‐sea invertebrates and inform future oil spill response efforts. [ABSTRACT FROM AUTHOR]

Peripheral nerve regeneration is regulated through the coordinated spatio‐temporal activation of multiple cellular pathways. In this work, an integrated proteomics and bioinformatics approach was employed to identify differentially expressed proteins at the injury‐site of rat sciatic nerve at 20 days after damage. By a label‐free liquid chromatography mass‐spectrometry (LC‐MS/MS) approach, we identified 201 differentially proteins that were assigned to specific canonical and disease and function pathways. These include proteins involved in cytoskeleton signaling and remodeling, acute phase response, and cellular metabolism. Metabolic proteins were significantly modulated after nerve injury to support a specific metabolic demand. In particular, we identified a group of proteins involved in lipid uptake and lipid storage metabolism. Immunofluorescent staining for acyl‐CoA diacylglycerol acyltransferase 1 (DGAT1) and DAGT2 expression provided evidence for the expression and localization of these two isoforms in Schwann cells at the injury site in the sciatic nerve. This further supports a specific local regulation of lipid metabolism in peripheral nerve after damage. [ABSTRACT FROM AUTHOR]

Abstract: Anthozoans (e.g., corals, anemones) are an ecologically important and diverse group of marine metazoans that occur from shallow to deep waters worldwide. However, our understanding of the evolutionary relationships among the ~7,500 species within this class is hindered by the lack of phylogenetically informative markers that can be reliably sequenced across a diversity of taxa. We designed and tested 16,306 RNA baits to capture 720 ultraconserved element loci and 1,071 exon loci. Library preparation and target enrichment were performed on 33 taxa from all orders within the class Anthozoa. Following Illumina sequencing and Trinity assembly, we recovered 1,774 of 1,791 targeted loci. The mean number of loci recovered from each species was 638 ± 222, with more loci recovered from octocorals (783 ± 138 loci) than hexacorals (475 ± 187 loci). Parsimony informative sites ranged from 26 to 49% for alignments at differing hierarchical taxonomic levels (e.g., Anthozoa, Octocorallia, Hexacorallia). The per cent of variable sites within each of three genera (Acropora, Alcyonium, and Sinularia) for which multiple species were sequenced ranged from 4.7% to 30%. Maximum‐likelihood analyses recovered highly resolved trees with topologies matching those supported by other studies, including the monophyly of the order Scleractinia. Our results demonstrate the utility of this target‐enrichment approach to resolve phylogenetic relationships from relatively old to recent divergences. Redesigning the baits with improved affinities to capture loci within each subclass will provide a valuable toolset to address systematic questions, further our understanding of the timing of diversifications and help resolve long‐standing controversial relationships in the class Anthozoa. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injury (SCI) is a damage to the spinal cord that results in loss or impaired motor and/or sensory function. SCI is a sudden and unexpected event characterized by high morbidity and mortality rate during both acute and chronic stages, and it can be devastating in human, social and economical terms. Despite significant progresses in the clinical management of SCI, there remain no effective treatments to improve neurological outcomes. Among experimental strategies, bioengineered scaffolds have the potential to support and guide injured axons contributing to neural repair. The major aim of this study was to investigate a novel composite type I collagen scaffold with micropatterned porosity in a rodent model of severe spinal cord injury. After segment resection of the thoracic spinal cord we implanted the scaffold in female Sprague-Dawley rats. Controls were injured without receiving implantation. Behavioral analysis of the locomotor performance was monitored up to 55 days postinjury. Two months after injury histopathological analysis were performed to evaluate the extent of scar and demyelination, the presence of connective tissue and axonal regrowth through the scaffold and to evaluate inflammatory cell infiltration at the injured site. We provided evidence that the new collagen scaffold was well integrated with the host tissue, slightly ameliorated locomotor function, and limited the robust recruitment of the inflammatory cells at the injury site during both the acute and chronic stage in spinal cord injured rats. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1040-1053, 2017. [ABSTRACT FROM AUTHOR]

Background: Tau PET positivity (T+) is recommended in Alzheimer's disease (AD) trials involving preclinical and prodromal AD. As unbiased cut‐offs are still lacking, we established and validated data‐driven T+ PET cut‐offs for AD. Method: Data were from ADNI (estimation cohort) and Geneva memory center (validation cohort). 18F‐Flortaucipir standardized uptake value ratios (SUVr) were computed for a global temporal meta‐ROI and for cortical regions corresponding to Braak‐based stages I‐VI in amyloid negative (Aβ−) cognitively normal (CN), Aβ+ CN, Aβ+ MCI and AD. For Tau PET data‐driven cut‐off estimation, Gaussian mixture model (GMM) was applied on the global and regional SUVr distributions in Aβ− CN and AD (n = 269). The GMM cut‐offs' performance was compared with published 18F‐Flortaucipir cut‐offs (Mattsson et al., 2017) by assessing the percentage of T+ subjects within each diagnostic group. Result: Cut‐offs were 1.36 for temporal meta‐ROI and ranged 1.20‐1.39 for stages. In the validation cohort, all Aβ− CN were tau negative (T−), while T+ percentage increased along the Aβ+ continuum (CN

Background: Locus coeruleus (LC) neurodegeneration has been documented in Alzheimer's disease (AD) and frontotemporal dementia (FTD). In AD, the LC may be the earliest site of tau pathology, which subsequently spreads to the entorhinal cortex (EC) through axonal pathways; in FTD, pathology might follow the opposite pattern, spreading from the frontal/temporal areas to the LC. In this study, we investigated in vivo the integrity of the LC‐EC pathway in AD and FTD and explored its association with cognition and neurodegeneration. Method: Twenty‐one AD, 20 behavioral variant FTD (bvFTD), and 20 age‐matched healthy controls (HC) underwent 3T MRI and neuropsychological exam assessing multiple cognitive domains. Fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AxD, RD) maps were calculated from diffusion weighted images using the FMRIB's Diffusion Toolbox (FSL). Microstructural integrity of the LC‐EC pathway was assessed using a probabilistic atlas on diffusivity maps warped to MNI space with FSL TBSS tool. Group differences in diffusivity measures were assessed using the Kruskal‐Wallis test. Associations between diffusivity changes, cognition, and neurodegeneration (hippocampal and amygdala volumes, EC and temporal/frontal/parietal/occipital lobes cortex thickness) were assessed using Spearman's rank correlation. All analyses were corrected for multiple comparisons. Result: Compared to HC, bvFTD showed higher MD, AxD and RD in the left and right LC‐EC (p<0.010 for all) and lower FA in the right LC‐EC (p=0.023), while AD showed higher RD in the left LC‐EC (p=0.012). Compared to AD, bvFTD showed lower FA, higher MD and RD (p<0.033 for all) in the right LC‐EC. Right MD and AxD were negatively associated with right EC thickness (p<0.004) in bvFTD. No association emerged between volumetric/thickness measures and microstructural changes in AD (p>0.050). No significant association emerged with cognitive measures in AD nor bvFTD (p>0.050). Conclusion: Our study suggests that the LC‐EC pathway is impaired in both bvFTD and AD, and that this damage is more prominent in bvFTD. Microstructural alterations in bvFTD might reflect axonal damage and demyelination secondary to medial temporal neurodegeneration. The less pronounced effect in AD together with the lack of associations with neurodegeneration suggest that LC‐EC microstructural damage may be a late event in the disease cascade. [ABSTRACT FROM AUTHOR]

Background and purpose Amyotrophic lateral sclerosis ( ALS) is a fatal neurodegenerative disease. Approximately 5%-10% of cases are familial ( FALS) and the remaining are sporadic ( SALS). To date FUS mutations are responsible for 4%-6% of familial cases as well as 0.7%-1.8% of sporadic cases. Methods The frequency of FUS mutations was investigated in an Italian cohort of 500 SALS and 40 FALS patients through direct sequencing of exons 5, 6, 13, 14 and 15. Results Eight FUS mutation carriers were identified in five SALS (1%) and three FALS (7.5%), five already known and three new mutations: a de novo mutation was identified in a sporadic subject as well as the co-presence of FUS/C9 ORF72 mutations in a FALS subject. The molecular and clinical details of the three patients harbouring a novel mutation (G245V, G509D and R491C) are presented here. Moreover the co-presence of the R491C mutation and C9 ORF72 pathological expansion was found according to the oligogenic disease model. Conclusions In conclusion our results revealed a higher frequency of FUS mutation carriers (7.5%) in FALS compared to literature data together with a higher presence of female gender. [ABSTRACT FROM AUTHOR]

ABSTRACT Giant cell tumor of bone (GCTb) represents 5% of bone tumors, and although considered benign, 5% metastasize to the lung. The expression of proteins directly or indirectly associated with osteolysis and tumor growth was studied on 163 samples of GCTb. Of these, 33 patients developed lung metastasis during follow-up. The impact of tumor-host interaction on clinical aspects was evaluated with the aim of finding specific markers for new biological therapies, thus improving clinical management of GCTb. Protein expression was evaluated by immunohistochemical analysis on Tissue Microarray. The majority of GCTb samples from patients with metastatic disease were strongly positive to RANKL and its receptor RANK as well as to CAII and MMP-2 and to pro-survival proteins NFIB and c-Fos. Kaplan-Meier analysis indicated a significant difference in metastasis free survival curves based on protein staining. Interestingly, the statistical correlation established a strong association between all variables studied with a higher τ coefficient for RANK/RANKL, RANK/NFIB, and RANKL/NFIB pairs. At multivariate analysis co-overexpression of NFIB, RANK and RANKL significantly increased the risk of metastasis with an odds ratio of 13.59 (95%CI 4.12-44.82; p < 0.0005). In conclusion, the interconnection between matrix remodeling and tumor cell activity may identify tumor-host endpoints for new biological treatments. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1205-1211, 2015. [ABSTRACT FROM AUTHOR]

This research on "America's Cup" grinders investigated the effects of a specific eight-week long-arm cranking ergometer (ACE) training on upper body (UB) aerobic fitness (ventilatory threshold – Tvent, respiratory compensation point- RCP, –oxygen uptake peak – O2peak) and high intensity working capacity. The training consisted of sessions carried out for 20–30 mins, three times per week, at an intensity between the UB-Tvent and UB-RCP, and replaced part of a typical lower limb aerobic training whilst maintaining the usual weekly schedule of callisthenics, resistance training and sailing. Seven sailors, including four grinders and three mastmen (age 30 ± 5.5 years, height 1.9 ± 0.04 m, body mass 102 ± 3.6 kg), were evaluated through both an ACE cardiopulmonary maximal exercise test (CPET) and an ACE all-out up to exhaustion exercise test, before and after the ACE training. UB aerobic fitness improved significantly: UB- O2peak increased from 4.29 ± 0.442 to 4.52 ± 0.522 l·min−1 (6.4 ± 3.66%), O2 at UB-Tvent from 2.42 ± 0.282 to 2.97 ± 0.328 l·min−1 (22.8 ± 5.09%) and O2 at UB-RCP from 3.25 ± 0.402 to 3.75 ± 0.352 l·min−1 (16.1 ± 10.83%). Peak power at the ACE CPET increased from 351 ± 27.5 to 387 ± 33.5 W (10.5 ± 6.93%). The all-out test total mechanical work increased from 28.9 ± 2.35 to 40.1 ± 3.76 kJ (72.1 ± 4.67%). In conclusion, a high intensity aerobic ACE training can be effective in improving grinding performance by increasing UB aerobic fitness and all-out working capacity. [ABSTRACT FROM AUTHOR]

Growing evidence has shown the promise of mesenchymal stromal cells ( MSCs) for the treatment of cutaneous wound healing. We have previously demonstrated that MSCs seeded on an artificial dermal matrix, Integra (Integra Lifesciences Corp., Plainsboro, NJ) enriched with platelet-rich plasma ( Ematrix) have enhanced proliferative potential in vitro as compared with those cultured on the scaffold alone. In this study, we extended the experimentation by evaluating the efficacy of the MSCs seeded scaffolds in the healing of skin wounds in an animal model in vivo. It was found that the presence of MSCs within the scaffolds greatly ameliorated the quality of regenerated skin, reduced collagen deposition, enhanced reepithelization, increased neo-angiogenesis, and promoted a greater return of hair follicles and sebaceous glands. The mechanisms involved in these beneficial effects were likely related to the ability of MSCs to release paracrine factors modulating the wound healing response. MSC-seeded scaffolds, in fact, up-regulated matrix metalloproteinase 9 expression in the extracellular matrix and enhanced the recruitment of endogenous progenitors during tissue repair. In conclusion, the results of this study provide evidence that the treatment with MSC-seeded scaffolds of cutaneous wounds contributes to the recreation of a suitable microenvironment for promoting tissue repair/regeneration at the implantation sites. [ABSTRACT FROM AUTHOR]

Although exercise therapy is considered part of the treatment of neuropathic patients, and somatosensory input is essential for motor learning, performance and neural plasticity, rehabilitation of patients with sensory ataxia has received little attention so far. The aim of this prospective pilot study was to explore the short- and medium-term efficacy of a 3-week intensive balance and treadmill exercise program in chronic ataxic neuropathy patients; 20 consecutive patients with leg overall disability sum score (ODSS-leg) ≥2, absent/mild motor signs, clinical and therapeutic stability ≥4 months were enrolled. Evaluations were done at baseline, at the end of treatment and at 3- and 6-month follow-up. Outcome measurements included: ODSS-leg, Berg balance scale, 6-min walk distance, and the functional independence measure (FIM) scale. The short-form-36 health status scale (SF-36) was used to measure health-related quality of life (HRQoL). ODSS-leg improved significantly compared with baseline, 3 weeks, 3 months (primary outcome), and 6 months follow-up. A significant improvement in all functional secondary outcome measurements and in some SF-36 subscales was also observed. This pilot study suggests that balance exercise is safe and well tolerated and might be effective in ameliorating disability and HRQoL in patients with chronic peripheral sensory ataxia. [ABSTRACT FROM AUTHOR]