Evaluation of the Psychometric Properties of the Revised Piper Fatigue Scale in Patients with Multiple Sclerosis

Background: Fatigue is one of the most common symptoms in patients with multiple sclerosis (MS), and has a major impact on their quality of life. Measurement tools that assess the patient’s condition are commonly used in the neurological field, though diagnostic tools are currently unable to distinguish potential alternative causes of fatigue in individual patients. The Revised Piper Fatigue Scale (PFS-R) is a self-administered assessment scale that is internationally used for fatigue measurement. Aim: This study aimed to evaluate the reliability and validity of the Italian version of the PFS-R in patients with MS. Methods: Forty-one individuals were included in this study. Each participant in the study was given a dossier, in paper format, containing the informed consent form, a personal data sheet, the Fatigue Symptoms and Impacts Questionnaire in Relapsing Multiple Sclerosis (FSIQ-RMS), the Fatigue Severity Scale (FSS), and the PFS-R. Results: The PFS-R was found to have strong internal consistency, with a value of α equal to 0.977. Correlations between PFS-R, FSS, and FSIQ-RMS scores were analyzed using the Pearson correlation coefficient, and all scales showed statistically significant correlations. Conclusion: The PFS-R is a new self-administered tool to assess fatigue in patients with MS. It evaluates fatigue characteristics, difficulty in carrying out daily life activities, and how the individual feels as a result of this symptom. This tool was previously validated for use in cancer patients, which also allows us to make a comparison between different pathologies and rehabilitation treatments

Human Papilloma Virus Vaccination and Oropharyngeal Cancer: Knowledge, Perception and Attitude among Italian Pediatric Dentists

Background: Pediatric dentists could play a key role in the prevention of human papilloma virus (HPV)-related oropharyngeal cancer (OP-cancer). The aim of this study was to assess knowledge, perception, and attitude on HPV-related OP-cancer, HPV infection, and HPV vaccination among Italian pediatric dentists. Methods: A cross-sectional study was conducted. Pediatric dentists received, by email, a link to participate in the questionnaire online. The questionnaire comprised four parts: (i) demographic information, (ii) knowledge on HPV-related OP-cancer, HPV infection, and HPV vaccine, (iii–iiii) perceptions and attitude on HPV-related OP-cancer, HPV infection, and HPV vaccine. Data were statistically analyzed with Kruskal–Wallis and Mann–Whitney test and Pearson’s chi-square test. Results: A total of 271 pediatric dentists completed the questionnaire. Results showed a good overall knowledge; a positive perception of their role in HPV disease prevention; a good attitude in discussing sensitive topics; a need for acquiring more information about HPV’s connection to cancer, HPV infection, and HPV vaccine. Conclusions: Improving educational training programs, as well as informing about prevention of HPV-related OP-cancer, will place pediatric dentists in the front line of HPV diseases primary prevention

A 3D Fully Convolutional Neural Network With Top-Down Attention-Guided Refinement for Accurate and Robust Automatic Segmentation of Amygdala and Its Subnuclei

Recent advances in deep learning have improved the segmentation accuracy of subcortical brain structures, which would be useful in neuroimaging studies of many neurological disorders. However, most existing deep learning based approaches in neuroimaging do not investigate the specific difficulties that exist in segmenting extremely small but important brain regions such as the subnuclei of the amygdala. To tackle this challenging task, we developed a dual-branch dilated residual 3D fully convolutional network with parallel convolutions to extract more global context and alleviate the class imbalance issue by maintaining a small receptive field that is just the size of the regions of interest (ROIs). We also conduct multi-scale feature fusion in both parallel and series to compensate the potential information loss during convolutions, which has been shown to be important for small objects. The serial feature fusion enabled by residual connections is further enhanced by a proposed top-down attention-guided refinement unit, where the high-resolution low-level spatial details are selectively integrated to complement the high-level but coarse semantic information, enriching the final feature representations. As a result, the segmentations resulting from our method are more accurate both volumetrically and morphologically, compared with other deep learning based approaches. To the best of our knowledge, this work is the first deep learning-based approach that targets the subregions of the amygdala. We also demonstrated the feasibility of using a cycle-consistent generative adversarial network (CycleGAN) to harmonize multi-site MRI data, and show that our method generalizes well to challenging traumatic brain injury (TBI) datasets collected from multiple centers. This appears to be a promising strategy for image segmentation for multiple site studies and increased morphological variability from significant brain pathology

Sustainability in peptide chemistry: current synthesis and purification technologies and future challenges.

Developing greener synthesis processes is an inescapable necessity to transform the industrial landscape, mainly in the pharmaceutical sector, into a long-term, sustainable reality. In this context, the renaissance of peptides as medical treatments, and the enforcement of more stringent sustainability requirements by regulatory agencies, pushed chemists toward the introduction of sustainable processes to prepare highly pure, active pharmaceutical ingredients (APIs). Innovative upstream (synthesis) and downstream (purification) methodologies have been developed during the last 5 years with the introduction and optimization of several technologies in solid-phase peptide synthesis (SPPS), liquid-phase peptide synthesis (LPPS), chemoenzymatic peptide synthesis (CEPS), and chromatographic procedures. These innovations are also moving toward the introduction of continuous processes that represent one of the most important targets for iterative processes. This overview discusses the most recent efforts in making peptide chemistry greener. The extensive studies that were carried out on green solvents, reaction conditions, auxiliary reagents and purification technologies in the peptide segment can be useful to other fields of organic synthesi

Steps towards sustainable solid phase peptide synthesis: use and recovery ofN-octyl pyrrolidone

The investigation of new green biogenic pyrrolidinones as alternative solvents toN,N-dimethylformamide (DMF) for solid phase peptide synthesis (SPPS) led to the identification ofN-octyl pyrrolidone (NOP) as the best candidate. NOP showed good performances in terms of swelling, coupling efficiency and low isomerization generating peptides with very high purity. A mixture of NOP with 20% dimethyl carbonate (DMC) allowed a decrease in solvent viscosity, making the mixture suitable for the automated solid-phase protocol. Aib-enkephalin and linear octreotide were successfully used to test the methodologies. It is worth noting that NOP, DMC and the piperidine used in the deprotection step could be easily recovered by direct distillation from the process waste mixture. The process mass intensity (PMI), being reduced by 63-66%, achieved an outstanding value representing a clear step forward in achieving green SPPS

Evaluation of BAFF, APRIL and CD40L in ocrelizumab-treated pwMS and infectious risk

Simple Summary Since B cells have been linked to multiple sclerosis (MS) and its progression as well as T cells, the second-generation anti-CD20 recombinant humanized monoclonal antibody ocrelizumab has been approved for MS treatment. Although ocrelizumab efficiently depletes B cells in peripheral blood, some B cells and CD20 negative plasma cells persist in lymphatic organs, and their survival is regulated by the B-cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) system. Moreover, ocrelizumab may result in higher infectious risk. Herein, we investigated plasma BAFF, APRIL and CD40L levels and their relationship with infectious risk in ocrelizumab-treated people with (pw) MS at baseline, at 6 months and at 12 months after starting the treatment, comparing the above-mentioned findings with a control group. At baseline, plasma levels of all three cytokines were higher compared to the control group. In pwMS, the longitudinal assessment showed a significant increase in plasma BAFF levels and a significant reduction in plasma APRIL and CD40L. Moreover, when stratifying pwMS according to the onset of an infectious event during the 12-month follow-up period, significantly higher plasma BAFF levels were found at all time-points in the group with an infectious event than in the group without an infectious event. Hence, BAFF may have a role as a marker of immune dysfunction and infectious risk. Background: The anti-CD20 monoclonal antibody ocrelizumab has been widely employed in the treatment of people with multiple sclerosis (pwMS). However, its B-cell-depleting effect may induce a higher risk of infectious events and alterations in the secretion of B-cell-activating factors, such as BAFF, APRIL and CD40L. Methods: The aim of this study was to investigate plasma BAFF, APRIL and CD40L levels and their relationship with infectious risk in ocrelizumab-treated pwMS at baseline (T0), at 6 months (T6) and at 12 months (T12) after starting the treatment. As a control group, healthy donors (HD) were enrolled too. Results: A total of 38 pwMS and 26 HD were enrolled. At baseline, pwMS showed higher plasma BAFF (p < 0.0001), APRIL (p = 0.0223) and CD40L (p < 0.0001) levels compared to HD. Compared to T0, plasma BAFF levels were significantly increased at both T6 and T12 (p < 0.0001 and p < 0.0001, respectively). Whereas plasma APRIL and CD40L levels were decreased at T12 (p = 0.0003 and p < 0.0001, respectively). When stratifying pwMS according to the development of an infectious event during the 12-month follow-up period in two groups-with (14) and without an infectious event (24)-higher plasma BAFF levels were observed at all time-points; significantly, in the group with an infectious event compared to the group without an infectious event (T0: p < 0.0001, T6: p = 0.0056 and T12: p = 0.0400). Conclusions: BAFF may have a role as a marker of immune dysfunction and of infectious risk

Do demographic and clinical features and comorbidities affect the risk of spread to an additional body site in functional motor disorders?

The aim of this study is to assess changes in the body distribution and the semeiology of functional motor disorder (FMD) in patients who reported only one or more than one body site affected at FMD onset. Data were obtained from the Italian Registry of Functional Motor Disorders, which included patients with a diagnosis of clinically definite FMDs. The relationship between FMD features and spread to other body sites was estimated by multivariate Cox regression analysis. We identified 201 (49%) patients who reported only one body site affected at FMD onset and 209 (51%) who reported multiple body sites affected at onset. FMD spread from the initial site to another site in 43/201 (21.4%) patients over 5.7 ± 7.1 years in those with only one site affected at FMD onset; FMD spread to an another body site in 29/209 (13.8%) over 5.5 ± 6.5 years. The spread of FMD was associated with non-motor functional symptoms and psychiatric comorbidities only in the patients with one body site affected at FMD onset. Our findings provide novel insight into the natural history of FMD. The number of body sites affected at onset does not seem to have a consistent influence on the risk of spread. Furthermore, our findings suggest that psychiatric comorbidities and non-motor functional symptoms may predict the spread of FMD symptoms, at least in patients with one body site affected at onset

Sustained Na⁺/H⁺ exchanger activation promotes gliotransmitter release from reactive hippocampal astrocytes following oxygen-glucose deprivation

Hypoxia ischemia (HI)-related brain injury is the major cause of long-term morbidity in neonates. One characteristic hallmark of neonatal HI is the development of reactive astrogliosis in the hippocampus. However, the impact of reactive astrogliosis in hippocampal damage after neonatal HI is not fully understood. In the current study, we investigated the role of Na +/H+ exchanger isoform 1 (NHE1) protein in mouse reactive hippocampal astrocyte function in an in vitro ischemia model (oxygen/glucose deprivation and reoxygenation, OGD/REOX). 2 h OGD significantly increased NHE1 protein expression and NHE1-mediated H+ efflux in hippocampal astrocytes. NHE1 activity remained stimulated during 1-5 h REOX and returned to the basal level at 24 h REOX. NHE1 activation in hippocampal astrocytes resulted in intracellular Na+ and Ca2+ overload. The latter was mediated by reversal of Na+/Ca2+ exchange. Hippocampal astrocytes also exhibited a robust release of gliotransmitters (glutamate and pro-inflammatory cytokines IL-6 and TNFα) during 1-24 h REOX. Interestingly, inhibition of NHE1 activity with its potent inhibitor HOE 642 not only reduced Na+ overload but also gliotransmitter release from hippocampal astrocytes. The noncompetitive excitatory amino acid transporter inhibitor TBOA showed a similar effect on blocking the glutamate release. Taken together, we concluded that NHE1 plays an essential role in maintaining H + homeostasis in hippocampal astrocytes. Over-stimulation of NHE1 activity following in vitro ischemia disrupts Na+ and Ca2+ homeostasis, which reduces Na+-dependent glutamate uptake and promotes release of glutamate and cytokines from reactive astrocytes. Therefore, blocking sustained NHE1 activation in reactive astrocytes may provide neuroprotection following HI. © 2014 Cengiz et al

Do demographic and clinical features and comorbidities affect the risk of spread to an additional body site in functional motor disorders?

The aim of this study is to assess changes in the body distribution and the semeiology of functional motor disorder (FMD) in patients who reported only one or more than one body site affected at FMD onset. Data were obtained from the Italian Registry of Functional Motor Disorders, which included patients with a diagnosis of clinically definite FMDs. The relationship between FMD features and spread to other body sites was estimated by multivariate Cox regression analysis. We identified 201 (49%) patients who reported only one body site affected at FMD onset and 209 (51%) who reported multiple body sites affected at onset. FMD spread from the initial site to another site in 43/201 (21.4%) patients over 5.7 ± 7.1 years in those with only one site affected at FMD onset; FMD spread to an another body site in 29/209 (13.8%) over 5.5 ± 6.5 years. The spread of FMD was associated with non-motor functional symptoms and psychiatric comorbidities only in the patients with one body site affected at FMD onset. Our findings provide novel insight into the natural history of FMD. The number of body sites affected at onset does not seem to have a consistent influence on the risk of spread. Furthermore, our findings suggest that psychiatric comorbidities and non-motor functional symptoms may predict the spread of FMD symptoms, at least in patients with one body site affected at onset

Functional motor phenotypes: to lump or to split?

Introduction Functional motor disorders (FMDs) are usually categorized according to the predominant phenomenology; however, it is unclear whether this phenotypic classification mirrors the underlying pathophysiologic mechanisms. Objective To compare the characteristics of patients with different FMDs phenotypes and without co-morbid neurological disorders, aiming to answer the question of whether they represent different expressions of the same disorder or reflect distinct entities. Methods Consecutive outpatients with a clinically definite diagnosis of FMDs were included in the Italian registry of functional motor disorders (IRFMD), a multicenter data collection platform gathering several clinical and demographic variables. To the aim of the current work, data of patients with isolated FMDs were extracted. Results A total of 176 patients were included: 58 with weakness, 40 with tremor, 38 with dystonia, 23 with jerks/facial FMDs, and 17 with gait disorders. Patients with tremor and gait disorders were older than the others. Patients with functional weakness had more commonly an acute onset (87.9%) than patients with tremor and gait disorders, a shorter time lag from symptoms onset and FMDs diagnosis (2.9 ± 3.5 years) than patients with dystonia, and had more frequently associated functional sensory symptoms (51.7%) than patients with tremor, dystonia and gait disorders. Patients with dystonia complained more often of associated pain (47.4%) than patients with tremor. No other differences were noted between groups in terms of other variables including associated functional neurological symptoms, psychiatric comorbidities, and predisposing or precipitating factors. Conclusions Our data support the evidence of a large overlap between FMD phenotypes