Here I discuss the study in this issue of
Genes & Development
by Youn et al. (pp. 737–751), which describes defined and diverse roles of primary cilia in molecularly distinct medulloblastoma ...subgroups, highlighting once again the importance of designing subgroup-specific therapeutic approaches for this tumor.
Since its first clinical description (on his son) by William James West (1793–1848) in 1841, and the definition of the classical triad of (1) infantile spasms; (2) hypsarrhythmia, and (3) ...developmental arrest or regression as “West syndrome”, new and relevant advances have been recorded in this uncommon disorder. New approaches include terminology of clinical spasms (e.g., infantile (IS) vs. epileptic spasms (ES)), variety of clinical and electroencephalographic (EEG) features (e.g., typical ictal phenomena without EEG abnormalities), burden of developmental delay, spectrum of associated genetic abnormalities, pathogenesis, treatment options, and related outcome and prognosis. Aside the classical manifestations, IS or ES may present with atypical electroclinical phenotypes (e.g., subtle spasms; modified hypsarrhythmia) and may have their onset outside infancy. An increasing number of genes, proteins, and signaling pathways play crucial roles in the pathogenesis. This condition is currently regarded as a spectrum of disorders: the so-called infantile spasm syndrome (ISs), in association with other causal factors, including structural, infectious, metabolic, syndromic, and immunologic events, all acting on a genetic predisposing background. Hormonal therapy and ketogenic diet are widely used also in combination with (classical and recent) pharmacological drugs. Biologically targeted and gene therapies are increasingly studied. The present narrative review searched in seven electronic databases (primary MeSH terms/keywords included West syndrome, infantile spasms and infantile spasms syndrome and were coupled to 25 secondary clinical, EEG, therapeutic, outcomes, and associated conditions terms) including MEDLINE, Embase, Cochrane Central, Web of Sciences, Pubmed, Scopus, and OMIM to highlight the past knowledge and more recent advances.
The CD-MUSIC model is able to successfully predict phosphate speciation on ferrihydrite nanoparticles under a wide range of conditions, pointing out that the dominant species are the bidentate ...surface complexes.
Ferrihydrite nanoparticles may dominate the ion binding properties of the natural oxide fraction present in soil and aquatic systems. A correct description of the adsorption properties of ferrihydrite nanoparticles may be useful for gaining a better insight into the adsorption processes in natural systems and at the same time will be essential for developing surface complexation models able to describe these processes. In the present study, phosphate speciation in ferrihydrite has been analyzed combining the available spectroscopic data and molecular information with modeling calculations. For this purpose, a new data set that analyzes the effect of pH and ionic strength on the phosphate adsorption onto ferrihydrite has been used. Description of the phosphate adsorption process onto ferrihydrite nanoparticles, for the entire pH and ionic strength range, has been made taking into account the presence of protonated and nonprotonated bidentate surface complexes. The presence of monodentate complexes, protonated and nonprotonated, was also analyzed, but no significant improvement in the description of the results was observed. The surface complexation constants obtained with the CD-MUSIC modeling calculations are comparable to the values found in the literature for phosphate surface complexes in goethite particles.
Abstract It is known that the olfactory dysfunction is involved in various neurological diseases, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, Huntington's disease and motor ...neuron disease. In particular, the ability to identify and discriminate the odors, as well as the odor threshold, can be altered in these disorders. These changes often occur as early manifestation of the pathology and they are not always diagnosed on time. The aim of this review is to summarize the major neurological diseases which are preceded or accompanied by olfactory dysfunction. In addition, new instrumental approaches, such as psychophysical testing, olfactory event-related potentials (OERPs) and functional magnetic resonance imaging (fMRI) measurements, supported by olfactometer for the stimuli delivery, and their combination in evaluation of olfactory function will be discussed. In particular, OERPs and fMRI might to be good candidates to become useful additional tools in clinical protocols for early diagnosis of neurological diseases.
M-mode ultrasonography has been used in the assessment of diaphragm kinetics. The sonographic diaphragmatic parameters can provide valuable information in the assessment and follow-up of patients ...with diaphragmatic dysfunction, during ventilation, and can potentially help to understand post-operative pulmonary dysfunction or weaning failure from ventilation. We conducted a systematic review of literature concerning the clinical applications of diaphragmatic ultrasound in children. The morphological and functional evaluation of the diaphragm by ultrasound technique is becoming an increasingly widespread practice in intensive, medical and surgery category. Our systematic review shows how diaphragmatic ultrasonography finds indication in different areas. It requires a standardization of parameters and normal measurement values.
Statins as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase are widely prescribed for hypercholesterolemia treatment. In the last years, statins have also been shown to exert ...immunomodulatory and anti-inflammatory effects which appear to be related to inhibition of isoprenylation of small GTP-binding proteins and, at least in part, independent of their cholesterol-lowering effects. These “pleiotropic” effects make statins an attractive treatment option for immune-mediated disorders such as multiple sclerosis. Studies in vitro and in experimental autoimmune encephalomyelitis animal model seem to support not only the efficacy of statins as immunomodulatory agents but also their potential neuroprotective properties, although the exact mechanism with which statins exert these effects has not yet been fully understood. The immunomodulatory, anti-inflammatory and neuroprotective properties of statins provided the incentive for several clinical trials in multiple sclerosis, in which they were tested not only as mono-therapy but also in combination with interferon-β. However, the attempt to translate the results of animal model studies in humans produced conflicting results. Further large, prospective, randomized, double-blind, placebo-controlled trials, designed to evaluate the long-term effects of statins alone or in add-on to other disease-modifying therapies, are needed to support their routine clinical use in multiple sclerosis.
Cerebrovascular malformations include a wide range of blood vessel disorders affecting brain vasculature. Neuroimaging differential diagnosis can result unspecific due to similar phenotypes of ...lesions and their deep localization. Next-generation sequencing (NGS) platforms simultaneously analyze several hundreds of genes and can be applied for molecular distinction of different phenotypes within the same disorder’s macro-area. We discuss about the main criticisms regarding molecular bases of cerebral cavernous malformations (CCM) and brain arteriovenous malformations (AVM), highlighting both common pathogenic aspects and genetic differences leading to lesion development. Many recent studies performed on human CCM and AVM tissues aim to detect genetic markers to better understand molecular bases and pathogenic mechanism, particularly for sporadic cases. Several genes involved in angiogenesis show different expression patterns between CCM and AVM, and these could represent a valid starting point to project a NGS panel to apply for differential cerebrovascular malformation diagnosis.
On March 2019 the World Health Organization declared Coronavirus disease (COVID-19) pandemic. Several recent reports disclose that the outcome of the infection is related to age, sex and can be ...influenced by underlying clinical conditions. Parkinson's disease (PD) and other parkinsonisms are the most common chronic disease which can cause, directly or indirectly, the patient to be more exposed to other diseases, mostly respiratory system's ones. Our primary outcome is to evaluate if PD patients are more susceptible than non-PD to take COVID-19 infection. Second, to detect if the infection course is worse in PD-COVID+ patients versus non-PD. This is a retrospective observational study on a cohort of 18 patients (13 PD- 5 non-PD), hospitalized in a Rehabilitative Unit during the occurrence of SARS-CoV2 epidemic outbreak. All patients performed laboratory tests, lung Computed Tomography (CT) and have been tested for COVID-19 thorough pharyngeal swab. PD and non-PD groups were comparable for age, gender and Hoehn and Yahr stage. Seventy-seven (77)% of PD and 60% of non-PD resulted positive for COVID-19. PD-COVID+ and PD-COVID- did not differ for age, disease duration and L-dopa daily dose. PD COVID-19+ subjects were mainly asymptomatic (50%) while non-PD ones were all symptomatic, mostly with respiratory difficulties. PD doesn't seem to be a risk factor to take SARS-COV2 infection, even if our study is related to a limited sample size. Our results, together with those of other recent studies, highlight the need to evaluate the actual susceptibility of patients with Parkinson's disease to develop COVID-19 disease, and how the infection may influence the risk of clinical worsening and increase of mortality.
The purpose of the study is to evaluate the use of the suprapectineal quadrilateral surface (QLS) plates associated with the anterior intrapelvic approach (AIP) to the acetabulum in the surgical ...treatment of acetabular fractures with anterior involvement.
We did a retrospective study of patients surgically treated with QLS plates and AIP for acetabular fractures with the involvement of the anterior column, between February 2018 and February 2020, in our Hospital. The following data were recorded: mechanism of injury, the pattern of fracture, presence of other associated injuries, the time before performing the surgery, surgical approach, position on operating table, time of surgery, intraoperative bleeding, hospitalization time, intraoperative and postoperative complications. Follow-ups were performed at 1, 3, 6, 12 months, then annually. The clinical-functional outcome was assessed with the Merle d'Aubigne Postel score (MAP) modified by Matta; while the radiological outcome with the Matta Radiological Scoring System (MRSS). A Chi-square test was utilized to examine associations between parametric variables.
We included 34 patients, mean age 62.1, with an average follow-up of 20.7 months. The most frequent traumatic mechanism was road trauma. There were 15 isolated anterior columns and 19 associated patterns. There were 5 cases of associated visceral injuries, and 10 cases of other associated skeletal fractures. All patients were in the supine position. The surgical approach used was the AIP in all cases, with the addition of the first window of the ilioinguinal approach in 16 cases and of the Kocher-Langenbeck approach in 2 cases. The average time before performing the surgery was 8.5 days. The mean time of the surgery and the mean length of stay after surgery were 227.9 min and 8.2 days, respectively. There weren't cases of intra-operative complications, while there were postoperative complications in 5 patients. The MRSS was judged anatomical in 26 cases, imperfect in 7 cases and poor in 1 case. The average MAP value was 15.2. We observed a significant relationship between the radiological outcome and the clinical outcome (p < 0.05).
The QLS plates in association with the AIP approach represent an effective treatment strategy for the treatment of acetabular fractures with anterior involvement.
In this work, we introduce Permutation Disalignment Index (PDI) as a novel nonlinear, amplitude independent, robust to noise metric of coupling strength between time series, with the aim of applying ...it to electroencephalographic (EEG) signals recorded longitudinally from Alzheimer's Disease (AD) and Mild Cognitive Impaired (MCI) patients. The goal is to indirectly estimate the connectivity between the cortical areas, through the quantification of the coupling strength between the corresponding EEG signals, in order to find a possible matching with the disease's progression.
PDI is first defined and tested on simulated interacting dynamic systems. PDI is then applied to real EEG recorded from 8 amnestic MCI subjects and 7 AD patients, who were longitudinally evaluated at time Formula: see text0 and 3 months later (time Formula: see text1). At time Formula: see text1, 5 out of 8 MCI patients were still diagnosed MCI (stable MCI) whereas the remaining 3 exhibited a conversion from MCI to AD (prodromal AD). PDI was compared to the Spectral Coherence and the Dissimilarity Index.
Limited to the size of the analyzed dataset, both Coherence and PDI resulted sensitive to the conversion from MCI to AD, even though only PDI resulted specific. In particular, the intrasubject variability study showed that the three patients who converted to AD exhibited a significantly (Formula: see text) increased PDI (reduced coupling strength) in delta and theta bands. As regards Coherence, even though it significantly decreased in the three converted patients, in delta and theta bands, such a behavior was also detectable in one stable MCI patient, in delta band, thus making Coherence not specific. From the Dissimilarity Index point of view, the converted MCI showed no peculiar behavior.
PDI significantly increased, in delta and theta bands, specifically in the MCI subjects who converted to AD. The increase of PDI reflects a reduced coupling strength among the brain areas, which is consistent with the expected connectivity reduction associated to AD progression.
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