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Background: Seizures, neurological deficits, bradycardia, and, in the worst cases, cardiac arrest may occur following incidental durotomy during routine lumbar endoscopy. Therefore, we set out to measure the intraoperative epidural pressure during lumbar endoscopic decompression surgery. Methods: We conducted a retrospective observational cohort study to obtain intraoperative epidural measurements with an epidural catheter-pressure transducer assembly through the spinal endoscope on 15 patients who underwent lumbar endoscopic decompression of symptomatic lumbar herniated discs and spinal stenosis. The endoscopic interlaminar technique was employed. Results: There were six (40.0%) female and nine (60.0%) male patients aged 49.0667 ± 11.31034, ranging from 36 to 72 years, with an average follow-up of 35.15 ± 12.48 months. Three of the fifteen patients had seizures with durotomy and one of these three had intracranial air on their postoperative brain CT. Another patient developed spinal headaches and diplopia on postoperative day one when her deteriorating neurological function was investigated with a brain computed tomography (CT) scan, showing an intraventricular hemorrhage consistent with a Fisher Grade IV subarachnoid hemorrhage. A CT angiogram did not show any abnormalities. Pressure recordings in the epidural space in nine patients ranged from 20 to 29 mm Hg with a mean of 24.33 mm Hg. Conclusion: Most incidental durotomies encountered during lumbar interlaminar endoscopy can be managed without formal repair and supportive care measures. The intradural spread of irrigation fluid and intraoperatively used drugs and air entrapment through an unrecognized durotomy should be suspected if patients deteriorate in the recovery room. Ascending paralysis may cause nausea, vomiting, upper and lower motor neuron symptoms, cranial nerve palsies, hypotension, bradycardia, and respiratory and cardiac arrest. The recovery team should be prepared to manage these complications.

Introduction: Sporadic Creutzfeldt-Jakob disease (sCJD) comprises multiple subtypes (MM1, MM2, MV1, MV2C, MV2K, VV1, and VV2) with distinct disease durations and spatiotemporal cascades of brain lesions. Our goal was to establish the ante mortem diagnosis of sCJD subtype, based on patient-specific estimates of the spatiotemporal cascade of lesions detected by diffusion-weighted magnetic resonance imaging (DWI). Methods: We included 488 patients with autopsy-confirmed diagnosis of sCJD subtype and 50 patients with exclusion of prion disease. We applied a discriminative event-based model (DEBM) to infer the spatiotemporal cascades of lesions, derived from the DWI scores of 12 brain regions assigned by three neuroradiologists. Based on the DEBM cascades and the prion protein genotype at codon 129, we developed and validated a novel algorithm for the diagnosis of the sCJD subtype. Results: Cascades of MM1, MM2, MV1, MV2C, and VV1 originated in the parietal cortex and, following subtype-specific orderings of propagation, went toward the striatum, thalamus, and cerebellum; conversely, VV2 and MV2K cascades showed a striatum-to-cortex propagation. The proposed algorithm achieved 76.5% balanced accuracy for the sCJD subtype diagnosis, with low rater dependency (differences in accuracy of ± 1% among neuroradiologists). Discussion: Ante mortem diagnosis of sCJD subtype is feasible with this novel data-driven approach, and it may be valuable for patient prognostication, stratification in targeted clinical trials, and future therapeutics. Highlights: Subtype diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is achievable with diffusion MRI. Cascades of diffusion MRI abnormalities in the brain are subtype-specific in sCJD. We proposed a diagnostic algorithm based on cascades of diffusion MRI abnormalities and demonstrated that it is accurate. Our method may aid early diagnosis, prognosis, stratification in clinical trials, and future therapeutics. The present approach is applicable to other neurodegenerative diseases, enhancing the differential diagnoses.

Spinal neurofibromatosis (SNF), a phenotypic subclass of neurofibromatosis 1 (NF1), is characterized by bilateral neurofibromas involving all spinal roots. In order to deepen the understanding of SNF’s clinical and genetic features, we identified 81 patients with SNF, 55 from unrelated families, and 26 belonging to 19 families with at least 1 member affected by SNF, and 106 NF1 patients aged >30 years without spinal tumors. A comprehensive NF1 mutation screening was performed using NGS panels, including NF1 and several RAS pathway genes. The main features of the SNF subjects were a higher number of internal neurofibromas (p < 0.001), nerve root swelling (p < 0.001), and subcutaneous neurofibromas (p = 0.03), while hyperpigmentation signs were significantly less frequent compared with the classical NF1-affected cohorts (p = 0.012). Fifteen patients underwent neurosurgical intervention. The histological findings revealed neurofibromas in 13 patients and ganglioneuromas in 2 patients. Phenotypic variability within SNF families was observed. The proportion of missense mutations was higher in the SNF cases than in the classical NF1 group (21.40% vs. 7.5%, p = 0.007), conferring an odds ratio (OR) of 3.34 (CI = 1.33–10.78). Two unrelated familial SNF cases harbored in trans double NF1 mutations that seemed to have a subclinical worsening effect on the clinical phenotype. Our study, with the largest series of SNF patients reported to date, better defines the clinical and genetic features of SNF, which could improve the management and genetic counseling of NF1.

It is commonly reported that maximizing surgical resection of contrast-enhancing regions in patients with glioblastoma improves overall survival. Efforts to achieve an improved rate of resection have included several tools: among those, the recent widespread of fluorophores. Sodium fluorescein is an unspecific, vascular dye which tends to accumulate in areas with an altered blood–brain barrier. In this retrospective analysis of patients prospectively enrolled in the FLUOCERTUM study, we aimed to assess the role of fluorescein-guided surgery on surgical radicality, survival, and morbidity. A retrospective review based on 93 consecutively and prospectively enrolled IDH wild-type glioblastoma patients (2016–2022) was performed; fluorescence characteristics, rate of resection, clinical outcome, and survival were analyzed. No side effect related to fluorescein occurred; all of the tumors presented a strong yellow-green enhancement and fluorescein was judged fundamental in distinguishing tumors from viable tissue in all cases. Gross total resection was achieved in 77 cases out of 93 patients (82.8%). After a mean follow-up time of 17.4 months (3–78 months), the median progression-free survival was 12 months, with a PFS-6 and PFS-12 of 94.2% and 50%, respectively, whereas median overall survival was estimated to be 16 months; survival at 6, 12, and 24 months was 91.8%, 72.3%, and 30.1%, respectively. Based on these results, we can assert that the fluorescein-guided technique is a safe and valuable method for patients harboring a newly diagnosed, untreated glioblastoma.

Neurofibromatosis type 2 is an autosomal dominant tumor-prone disorder mainly caused by NF2 point mutations or intragenic deletions. Few individuals with a complex phenotype and 22q12 microdeletions have been described. The 22q12 microdeletions’ pathogenic effects at the genetic and epigenetic levels are currently unknown. We here report on 22q12 microdeletions’ characterization in three NF2 patients with different phenotype complexities. A possible effect of the position was investigated by in silico analysis of 22q12 topologically associated domains (TADs) and regulatory elements, and by expression analysis of 12 genes flanking patients’ deletions. A 147 Kb microdeletion was identified in the patient with the mildest phenotype, while two large deletions of 561 Kb and 1.8 Mb were found in the other two patients, showing a more severe symptomatology. The last two patients displayed intellectual disability, possibly related to AP1B1 gene deletion. The microdeletions change from one to five TADs, and the 22q12 chromatin regulatory landscape, according to the altered expression levels of four deletion-flanking genes, including PIK3IP1, are likely associated with an early ischemic event occurring in the patient with the largest deletion. Our results suggest that the identification of the deletion extent can provide prognostic markers, predictive of NF2 phenotypes, and potential therapeutic targets, thus overall improving patient management.

INTRODUCTIONSingle-cell (SC) gene expression analysis is crucial to dissect the complex cellular heterogeneity of solid tumors, which is one of the main obstacles for the development of effective cancer treatments. Such tumors typically contain a mixture of cells with aberrant genomic and transcriptomic profiles affecting specific sub-populations that might have a pivotal role in cancer progression, whose identification eludes bulk RNA-sequencing approaches. We present scMuffin, an R package that enables the characterization of cell identity in solid tumors on the basis of multiple and complementary criteria applied on SC gene expression data.RESULTSscMuffin provides a series of functions to calculate several different qualitative and quantitative scores, such as: expression of marker sets for normal and tumor conditions, pathway activity, cell state trajectories, CNVs, chromatin state and proliferation state. Thus, scMuffin facilitates the combination of various evidences that can be used to distinguish normal and tumoral cells, define cell identities, cluster cells in different ways, link genomic aberrations to phenotypes and identify subtle differences between cell subtypes or cell states. As a proof-of-concept, we applied scMuffin to a public SC expression dataset of human high-grade gliomas, where we found that some chromosomal amplifications might underlie the invasive tumor phenotype and identified rare quiescent cells that may deserve further investigations as candidate cancer stem cells.CONCLUSIONSThe analyses offered by scMuffin and the results achieved in the case study show that our tool helps addressing the main challenges in the bioinformatics analysis of SC expression data from solid tumors.

To report the clinical presentation of the first Italian child affected by hypomyelinating leukodystrophy (HLD) associated with the recurrent variant p.Asp252Asn in theThe methods included clinical case description, neurophysiologic assessment, brain MRI, and whole-exome sequencing (WES).The child presented soon after birth with nystagmus and hyperkinetic movement disorder. Focal seizures appeared from 2 months of age and recurred at high frequency, despite several antiseizure medications, and focal epileptic status frequently required IV phenytoin. Control of seizures was achieved at the age of 8 months by the association of high doses of sodium blockers. Clinical picture worsened over time and was characterized by axial hypotonia, failure to thrive requiring gastrostomy, pyramidal sings, and severe secondary microcephaly. MRI performed at ages 2, 6, and 20 months showed diffuse supratentorial and subtentorial hypomyelination; multimodal evoked potentials showed increased latency. WES performed at 6 months of age identified the p.Asp252Asn de novo variant in theHyperkinetic movement disorders and seizures may be early symptoms of

The recent approval of disease-modifying therapies for spinal muscular atrophy (SMA) raised the need of alternative outcome measures to evaluate treatment efficacy. In this study, we investigated the potential of muscle quantitative MRI (qMRI) as a biomarker of disease progression in adult SMA3 patients during nusinersen treatment. Six adult SMA3 patients (age ranging from 19 to 65 years) underwent 2-point Dixon muscle qMRI at beginning of nusinersen treatment (T0) and after 14 months (T14) to evaluate the muscle fat fraction (FF) at thigh and leg levels; patients were clinically assessed at T0 and T14 with the Hammersmith Functional Rating Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM) and the 6-minute walk test (6MWT). At T0, vastus lateralis muscle displayed the highest mean FF (67.5%), while tibialis anterior was the most preserved one (mean FF = 35.2%). At T0, a slightly significant correlation of FF with HFMSE (p = 0.042) and disease duration (p = 0.042) at thigh level and only with HFMSE (p = 0.042) at leg level was found. At T14, no significant change of mean FF values at thigh and leg muscles was found compared to T0. Conversely, a statistically significant (p = 0.042) improvement of HFMSE was reported at T14. We observed no significant change of FF in thigh and leg muscles after 14 months of nusinersen therapy despite a significant clinical improvement of HFMSE. Further studies with longer follow-up and larger cohorts are needed to better investigate the role of qMRI as marker of disease progression in SMA patients.

The present study clinically and radiographically compares the outcome of implants inserted in maxillary sinuses augmented with concentrated growth factors (CGFs) or demineralized bovine bone matrix (DBBM) in a one-stage lateral approach. In 20 patients with a residual bone height of 1 to 4 mm, lateral sinus floor elevation was performed, using CGFs or DBBM as the sole grafting material, with simultaneous implant placement. Outcome variables were implant and prosthesis failures, complications, subjective satisfaction, and radiographic changes in marginal bone level (MBL) 12 months after surgery. The patients were consecutively recruited: 10 to the CGF group and 10 to the DBBM group. No implant failed in either group at 12 months postsurgery, and there were no complications. There was no statistically significant difference in MBL change between the CGF and DBBM groups (difference of -0.3 mm, favoring the CGF group; 95% confidence interval [CI]: -0.8 to 0.2; P = .18). There was no statistically significant difference in satisfaction (difference of 0.2, favoring the CGF group; 95% CI: -0.2 to 0.6; P = .29). Within the limitations of the present study, the lateral sinus floor elevation performed with the use of CGFs as the sole grafting material showed implant survival rates and marginal bone level changes comparable to DBBM grafting.

Background: Casually cauterizing the radicular magna during routine thoracic discectomy may have dire consequences. Methods: We performed a retrospective observational cohort study on patients scheduled for decompression of symptomatic thoracic herniated discs and spinal stenosis who underwent a preoperative computed tomography angiography (CTA) to assess the surgical risks by anatomically defining the foraminal entry level of the magna radicularis artery into the thoracic spinal cord and its relationship to the surgical level. Results: Fifteen patients aged 58.53 ± 19.57, ranging from 31 to 89 years, with an average follow-up of 30.13 ± 13.42 months, were enrolled in this observational cohort study. The mean preoperative VAS for axial back pain was VAS of 8.53 ± 2.06 and reduced to a postoperative VAS of 1.60 ± 0.92 (p < 0.0001) at the final follow-up. The Adamkiewicz was most frequently found at T10/11 (15.4%), T11/12 (23.1%), and T9/10 (30.8%). There were eight patients where the painful pathology was found far from the AKA foraminal entry-level (type 1), three patients with near location (type 2), and another four patients needing decompression at the foraminal (type 3) entry-level. In five of the fifteen patients, the magna radicularis entered the spinal canal on the ventral surface of the exiting nerve root through the neuroforamen at the surgical level requiring a change of surgical strategy to prevent injury to this important contributor to the spinal cord’s blood supply. Conclusions: The authors recommend stratifying patients according to the proximity of the magna radicularis artery to the compressive pathology with CTA to assess the surgical risk with targeted thoracic discectomy methods.

Background and ObjectivesHeterozygous mutations or deletions of theEBF3gene are known to cause a syndrome characterized by intellectual disability, neurodevelopmental disorders, facial dysmorphisms, hypotonia, and ataxia; the latter is quite common despite in most patients brain MRI is reported to be normal. Despite the predominant neurologic involvement ofEBF3-related syndrome, a systematic definition of neurologic, cognitive/behavioral, and neuroradiologic features is lacking.MethodsWe report on 6 patients (2 females and 4 males, age range 2–12 years), of whom 4 carrying a heterozygous point mutation of theEBF3gene and 2 with 10q26 deletion encompassing the gene, diagnosed at Carlo Besta Neurologic Institute of Milan, Italy. Clinical evaluation was performed by a pediatric neurologist and pediatric dysmorphologist; ataxia severity was rated by Scale for the Assessment and Rating of Ataxia (SARA); brain MRIs were reviewed by expert neuroradiologists; general quotient levels were obtained through standardized Griffiths Mental Development Scales. Patients carrying a 10q26.3 deletion were diagnosed by array-CGH, whereasEBF3variants were detected by whole exome sequencing.ResultsPhenotype was consistent in all patients, but with wide variability in severity. Developmental milestones were invariably delayed and resulted in an extremely variable cognitive impairment. All patients showed ataxic signs, as confirmed by SARA scores, often associated with hypotonia. Brain MRI revealed in all children a cerebellar malformation with vermis hypoplasia and a peculiar foliation anomaly characterized by a radial disposition of cerebellar folia (dandelion sign). Neurophysiologic examinations were unremarkable.DiscussionEBF3-related syndrome has been so far described as a neurodevelopmental condition with dysmorphic traits, with limited emphasis on the neurologic features; we highlight the predominant neurologic involvement of these patients, which can be explained at least in part by the underlying cerebellar malformation. We therefore propose thatEBF3-related syndrome should be classified and treated as a congenital, nonprogressive ataxia.

A 5-month-old patient was first evaluated for a hypotonic hyporeflexic syndrome; over years, the phenotype evolved to involve ataxia, developmental delay, and coarse facies. Brain MRI showed abnormal configuration of cerebellar folia, rearranged in radial shape (figure). Whole exome sequencing analysis revealed the c.512 G>A (p.G171D) de novo mutation in EBF3 . EBF3 gene function is crucial for neuronal migration during corticogenesis.1 Cerebellar foliation is complex: folia sprout from anchoring centers,2 whose distribution and number determine the shape of lobules and fissures; EBF3 mutations may disrupt this process, thus causing the peculiar cerebellar lobule appearance seen here.

Wave propagation in periodic locally resonant materials (LRM) is characterized by the presence of band-gaps occurring at relatively low frequencies which can be exploited for vibration attenuation or impact absorption. In this work we consider the dispersion properties of three-components cellular LRM endowed with 2D (cylindrical) or 3D periodicity. Modal analyses on the unit cell, with Bloch-Floquet periodicity conditions, are performed by the finite element methods. For cylindrical LRM, the limits of plane analyses, which consider uncoupled in-plane and out-of-plane modes, are highlighted. Several different geometries for the 3D unit cells are also proposed and their influence on the band-gap width is studied.

Background Recent comparative studies have brought to our attention how somatic mutation detection from next-generation sequencing data is still an open issue in bioinformatics, because different pipelines result in a low consensus. In this context, it is suggested to integrate results from multiple calling tools, but this operation is not trivial and the burden of merging, comparing, filtering and explaining the results demands appropriate software. Results We developed isma (integrative somatic mutation analysis), an R package for the integrative analysis of somatic mutations detected by multiple pipelines for matched tumor-normal samples. The package provides a series of functions to quantify the consensus, estimate the variability, underline outliers, integrate evidences from publicly available mutation catalogues and filter sites. We illustrate the capabilities of isma analysing breast cancer somatic mutations generated by The Cancer Genome Atlas (TCGA) using four pipelines. Conclusions Comparing different “points of view” on the same data, isma generates a unique mutation catalogue and a series of reports that underline common patterns, variability, as well as sites already catalogued by other studies (e.g. TCGA), so as to design and apply filtering strategies to screen more reliable sites. The package is available for non-commercial users at the URL https://www.itb.cnr.it/isma. Electronic supplementary material The online version of this article (10.1186/s12859-019-2701-0) contains supplementary material, which is available to authorized users.

To compare 100% deproteinised bovine bone matrix grafts (DBBM, test group) and 100% autogenous bone grafts (AB, control group) for lateral maxillary sinus floor elevation in a blinded, parallel-group, randomised clinical trial.Patients with 1 to 3 mm of residual bone height were randomised for sinus floor elevation with DBBM or AB grafts and simultaneous implant placement. The outcome variables were implant failure, complications, subjective satisfaction and radiographic peri-implant bone level 7 years after loading.A total of 20 patients (27 implants) were randomised to the test group and 20 (32 implants) to the control group. Ten patients from the test group and seven from the control group dropped out. Two implant failures occurred in the test group, whereas none were observed in the control group (P = 0.178). One complication occurred in the test group and two were recorded in the control group (P = 1.000). The radiographic peri-implant crestal bone level was 2.5 ± 1.3 mm in the test group and 0.9 ± 0.9 mm in the control group. The difference was 1.6 mm, favouring the control group (95% confidence interval 0.7-2.6; P = 0.002). The difference in vertical bone height was -0.4 mm, favouring the control group (95% confidence interval -1.9-1.1; P = 0.590). The difference in satisfaction measured using a visual analogue scale 7 years after loading was 0.0 mm (95% confidence interval -1.0-0.0; P = 0.639).Differences between treatments were found for crestal bone level, favouring the control group. No differences were observed for the other variables evaluated.

Objective Large interhemispheric cysts (IHC) with partial or complete agenesis of corpus callosum (ACC) constitute a heterogeneous group of rare disorders. Neurosurgical treatment, in the terms of if, when and how to operate, remains unclear Methods We performed a surgical literature review of series or reports of IHCs with callosal anomalies; we evaluated whether revision surgeries were necessary and considered the dimensional change in the cyst postoperatively and the developmental outcome. We also reported our experience with sfour patients treated by programmable cysto-peritoneal (CP) shunting. Patients’ clinical history, neuroradiological and neuropsychological performances were evaluated pre and post operatively. Results The review included 133 patients with surgically-treated IHCs. Although most authors are in agreement to perform surgery if the patients present signs of raised ICP and to not intervene in those completely asymptomatic, for other signs and symptoms the debate is still open; only few authors performed cognitive tests pre and post-operatively. Shunting procedures were successful in 60% of our reviewed cases and often lead to a major cyst collapse. Craniotomy achieves good results but is extremely invasive. Endoscopy is minimally invasive and our review demonstrated a success rate of 66%. However, endoscopy does not ensue a complete cyst collapse. Our series and review seem to suggest a possible link between parenchymal re-expansion and cognitive outcome. Conclusions Early and effective surgery seems to obtain a greater cerebral parenchyma re-expansion and long-term cognitive evolution. Endoscopy is safe and reliable, but more data is needed on the impact of uncomplete cyst collapse on neurocognitive outcome.

Background and purpose: Little is known about hypomyelinating leukodystrophies (HLDs) in adults. The aim of this study was to investigate HLD occurrence, clinical features, and etiology among undefined leukoencephalopathies in adulthood. Methods: We recruited the patients with cerebral hypomyelinating magnetic resonance imaging pattern (mild T2 hyperintensity with normal or near-normal T1 signal) from our cohort of 62 adult index cases with undefined leukoencephalopathies, reviewed their clinical features, and used a leukoencephalopathy-targeted next generation sequencing panel. Results: We identified 25/62 patients (~40%) with hypomyelination. Cardinal manifestations were spastic gait and varying degree of cognitive impairment. Etiology was determined in 44% (definite, 10/25; likely, 1/25). Specifically, we found pathogenic variants in the POLR3A (n=2), POLR1C (n=1), RARS1 (n=1), and TUBB4A (n=1) genes, which are typically associated with severe early-onset HLDs, and in the GJA1 gene (n=1), which is associated with oculodentodigital dysplasia. Duplication of a large chromosome X region encompassing PLP1 and a pathogenic GJC2 variant were found in two patients, both females, with early-onset HLDs persisting into adulthood. Finally, we found likely pathogenic variants in PEX3 (n=1) and PEX13 (n=1) and potentially relevant variants of unknown significance in TBCD (n=1), which are genes associated with severe, early-onset diseases with central hypomyelination/dysmyelination. Conclusions: A hypomyelinating pattern characterizes a relevant number of undefined leukoencephalopathies in adulthood. A comprehensive genetic screening allows definite diagnosis in about half of patients, and demonstrates the involvement of many disease-causing genes, including genes associated with severe early-onset HLDs, and genes causing peroxisome biogenesis disorders.

Among the attractive properties of metamaterials, the capability of focusing and localizing waves has recently attracted research interest to establish novel energy harvester configurations. In the same frame, in this work, we develop and optimize a system for concentrating mechanical energy carried by elastic anti-plane waves. The system, resembling a Fabry-P&eacute, rot interferometer, has two barriers composed of Locally Resonant Materials (LRMs) and separated by a homogeneous internal cavity. The attenuation properties of the LRMs allow for the localization of waves propagating at particular frequencies. With proper assumptions on the specific ternary LRMs, the separation of scales (between the considered wave lengths and the characteristic dimension of the employed unit cells) enables the use of a two-scale asymptotic technique for computing the effective behavior of the employed LRMs. This leads to a complete analytic description of the motion of the system. Here we report the results achieved by optimizing the geometry of the system for obtaining a maximum focusing of the incoming mechanical energy. The analytic results are then validated through numerical simulations.

Computational drug repositioning is of growing interest to academia and industry, for its ability to rapidly screen a huge number of candidates in silico (exploiting comprehensive drug datasets) together with reduced development cost and time. The potential of drug repositioning has not been fully evaluated yet for cystic fibrosis (CF), a disease mainly caused by deletion of Phe 508 (F508del) of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. F508del-CFTR is thus withheld in the endoplasmic reticulum and rapidly degraded by the ubiquitin/proteasome system. CF is still a fatal disease. Nowadays, it is treatable by some CFTR-rescuing drugs, but new-generation drugs with stronger therapeutic benefits and fewer side effects are still awaited. In this manuscript we report about the results of a pilot computational drug repositioning screening in search of F508del-CFTR-targeted drugs performed on AIFA library by means of a dedicated computational pipeline and surface plasmon resonance binding assay to experimentally validate the computational findings.

Alexander disease (ALXDRD) is a rare astrocytic leukodystrophy caused by GFAP mutations. The adult-onset (AO) variant is usually characterized by gradual onset of spastic ataxia and bulbar symptoms with slowly progressive course. We report two AO-ALXDRD cases with rapid worsening after minor head trauma. In one of them, the only post-traumatic neuroimaging change was revealed by diffusion tensor imaging study. Our observations support the link between head trauma and ALXDRD progression, and suggest that this progression may be ascribed to microstructural changes. Clinicians should inform ALXDRD patients to minimize the risk of head trauma.

The aim of this histologic, single-blind, parallel, randomized clinical trial was to compare vertical bone augmentation grafting with 100% autogenous bone (group AB) vs 50% deproteinized bovine bone matrix (DBBM)/50% autogenous bone (group BOAB) using the Fence Technique in a two-stage implant placement. A biopsy was performed in the regenerated area at implant insertion 6 months after the augmentation surgery. The results reflect a sample size of four patients treated per group. At implant placement, 6 months after grafting, no significant differences were evident in the histomorphometric comparisons, even if the percentage of residual graft was obviously greater in the BOAB group (P = .0314).

This paper aims to report and analyze the possibility of focusing the mechanical energy carried by anti-plane shear waves, localizing it inside a resonant cavity. The transmission through a pair of identical barriers, constituted by two-dimensional (2-D), two-phase Locally Resonant Metamaterials (LRMs) and separated by the cavity itself, is here considered. Elastic waves at frequencies inside the LRMs band-gap are subjected to an attenuation which can trap them inside the cavity, enhancing its motion and concentrating the related vibration energy. LRMs behavior is characterized by applying an asymptotic homogenization technique, able to explicitly compute their effective properties. The behavior of the studied system is then analytically analyzed with the goal of optimizing the geometry to enhance the energy concentration. An example is finally shown.

This study presents the histomorphometric results of the Wafer Technique, which is based on guided bone regeneration and onlay grafts for 3D bone augmentation. This two-stage technique utilizes autogenous cortical bone plates and collagen membranes, forming a barrier containing a mixture of deproteinized bovine bone matrix, autologous blood, and bone grafted from intraoral sites. Twelve patients were treated. At 6 months postsurgery, histologic analysis of the regenerated areas revealed the presence of compact newly formed bone with no sign of inflammation. The percentages of new bone and native bone (mineralized tissue) were 16.4% (95% CI: 9.5% to 23.2%) and 42.6% (95% CI: 28.2% to 57.0%), respectively. Twenty-five implants were placed. The procedure has been proven to be safe and reliable, and only one transient complication was observed.

Background and Methods Mutations in WDR45 cause β-propeller protein-associated neurodegeneration (BPAN), a type of neurodegeneration with brain iron accumulation (NBIA). We reviewed clinical and MRI findings in 4 patients with de novo WDR45 mutations. Results Psychomotor delay and movement disorders were present in all cases; early-onset epileptic encephalopathy was present in 3. In all cases, first MRI showed: prominent bilateral SN enlargement, bilateral dentate nuclei T2-hyperintensity, and corpus callosum thinning. Iron deposition in the SN and globus pallidus (GP) only became evident later. Diffuse cerebral atrophy was present in 3 cases. Conclusions In this series, SN swelling and dentate nucleus T2 hyperintensity were early signs of BPAN, later followed by progressive iron deposition in the SN and GP. When clinical suspicion is raised, MRI is crucial for identifying early features suggesting this type of NBIA.

Purpose: This cross-sectional study aims to identify the predictors of work-related difficulties in a sample of employed persons with multiple sclerosis as addressed with the Multiple Sclerosis Questionnaire for Job Difficulties. Materials and methods: Hierarchical linear regression analysis was conducted to identify predictors of work difficulties: predictors included demographic variables (age, formal education), disease duration and severity, perceived disability and psychological variables (cognitive dysfunction, depression and anxiety). The targets were the questionnaire’s overall score and its six subscales. Results: A total of 177 participants (108 females, aged 21–63) were recruited. Age, perceived disability and depression were direct and significant predictors of the questionnaire total score, and the final model explained 43.7% of its variation. The models built on the questionnaire’s subscales show that perceived disability and depression were direct and significant predictors of most of its subscales. Conclusions: Our results show that, among patients with multiple sclerosis, those who were older, with higher perceived disability and higher depression symptoms have more and more severe work-related difficulties. The Multiple Sclerosis Questionnaire for Job Difficulties can be fruitfully exploited to plan tailored actions to limit the likelihood of near-future job loss in persons of working age with multiple sclerosis.Implications for rehabilitationDifficulties with work are common among people with multiple sclerosis and are usually addressed in terms of unemployment or job loss. The Multiple Sclerosis Questionnaire for Job Difficulties is a disease-specific questionnaire developed to address the amount and severity of work-related difficulties.We found that work-related difficulties were associated to older age, higher perceived disability and depressive symptoms.Mental health issues and perceived disability should be consistently included in future research targeting work-related difficulties. Difficulties with work are common among people with multiple sclerosis and are usually addressed in terms of unemployment or job loss. The Multiple Sclerosis Questionnaire for Job Difficulties is a disease-specific questionnaire developed to address the amount and severity of work-related difficulties. We found that work-related difficulties were associated to older age, higher perceived disability and depressive symptoms. Mental health issues and perceived disability should be consistently included in future research targeting work-related difficulties.

Metamaterials are generally known for their waves attenuation capabilities. This behaviour, which is related to the microstructure composing these materials, can be due to a Bragg-type scattering mechanism or to local resonances. The objective here is to exploit the two phenomena for generating a system able to localize the energy carried by propagating elastic (or acoustic) waves. To this purpose, we employ a 1D lattice composed of a chain of mass-in-mass particles, connected by elastic springs. The lattice contains an internal defect that causes the energy localization. This configuration allows for a completely analytical description of the problem. Eventually, an extensive discussion on the interaction between the two attenuation mechanisms is also given.

This study presents a novel technique based on guided bone regeneration and onlay grafts for three-dimensional bone augmentation. This two-stage technique uses an autogenous cortical bone plate and collagen membranes to form a barrier containing a mixture of deproteinized bovine bone matrix, autologous blood, and bone grafted from intraoral sites. Five patients were treated. At 6 months postsurgery, a mean increase in bone volume of 1,062 mm³ was shown. Mean maximum linear augmentation was 3.65 mm. Histologic analysis of the regenerated areas revealed the presence of compact newly formed bone with no sign of inflammation. A total of 13 implants were placed. The patients were satisfied, and complications were not observed.