A Novel Mutation in Lamin A/C Gene: Phenotype and Consequences on the Protein Structure and Flexibility

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Case Report: Modulation of Effective Connectivity in Brain Networks after Prosthodontic Tooth Loss Repair

INTRODUCTION. Recent neuroimaging studies suggest that dental loss replacements induce changes in neuroplasticity as well as in correlated connectivity between brain networks. However, as the typical temporal delay in detecting brain activity by neuroimaging cannot account for the influence one neural system exerts over another in a context of real activation (“effective” connectivity), it seems of interest to approach this dynamic aspect of brain networking in the time frame of milliseconds by exploiting electroencephalographic (EEG) data. MATERIAL AND METHODS. The present study describes one subject who received a new prosthodontic provisional implant in substitution for previous dental repairs. Two EEG sessions led with a portable device were recorded before and after positioning the new dental implant. By following MATLAB-EEGLAB processing supported by the plugins FIELDTRIP and SIFT, the independent component analysis (ICA) derived from EEG raw signals was rendered as current density fields and interpolated with the dipoles generated by each electrode for a dynamic study of the effective connectivity. One more recording session was undertaken six months after the placement of the final implant. RESULTS. Compared to the baseline, the new prosthodontic implant induced a novel modulation of the neuroplasticity in sensory-motor areas which was maintained following the definitive implant after six months, as revealed by changes in the effective connectivity from the basal strong enslavement of a single brain area over the others, to an equilibrate inter-related connectivity evenly distributed along the frontotemporal regions of both hemispheres. CONCLUSIONS. The rapid shift of the effective connectivity after positioning the new prosthodontic implant and its substantial stability after six months suggest the possibility that synaptic modifications, induced by novel sensory motor conditions, modulate the neuroplasticity and reshape the final dynamic frame of the interarea connectivity. Moreover, given the viability of the EEG practice, this approach could be of some interest in assessing the association between oral pathophysiology and neuronal networking

Gastro-intestinal parasites of pigs in Sardinia: a copromicroscopical investigation

This paper illustrates a copromicroscopical investigation carried out in Sardinia to update epidemiological data on diffusion of gastro-intestinal parasites in swine. Results obtained lead to suggest the employment of copromicroscopic exam to monitorate parasites diffusion in swine breedings in order to set up correct prophylactic and therapeutically intervents

An unusual delusion of duplication in a patient affected by Dementia with Lewy bodies

Background: Dementia with Lewy bodies (DLB) is the second most frequent diagnosis of progressive degenerative dementia in older people. Delusions are common features in DLB and, among them, Capgras syndrome represents the most frequent disturbance, characterized by the recurrent and transient belief that a familiar person, often a close family member or caregiver, has been replaced by an identical-looking imposter. However, other delusional conditions near to misidentification syndromes can occur in DLB patients and may represent a major psychiatric disorder, although rarely studied systematically. Case presentation: We reported on a female patient affected by DLB who presented with an unusual delusion of duplication. Referring to the female professional caregiver engaged by her relatives for her care, the patient constantly described the presence of two different female persons, with a disorder framed in the context of a delusion of duplication. A brain 99Tc-hexamethylpropyleneamineoxime SPECT was performed showing moderate hypoperfusion in both occipital lobes, and associated with marked decreased perfusion in parieto-fronto-temporal lobes bilaterally. Conclusions: An occipital hypoperfusion was identified, although in association with a marked global decrease of perfusion in the remaining lobes. The role of posterior lobes is certainly important in all misidentification syndromes where a natural dissociation between recognition and identification is present. Moreover, the concomitant presence of severe attentional and executive deficits evocative for a frontal syndrome and the marked global decrease of perfusion in the remaining lobes at the SPECT scan also suggest a possible dysfunction in an abnormal connectivity between anterior and posterior areas

Increase in 20–50 Hz (gamma frequencies) power spectrum and synchronization after chronic vagal nerve stimulation

Objective: Though vagus nerve stimulation (VNS) is an important option in pharmacoresistant epilepsy, its mechanism of action remains unclear. The observation that VNS desynchronised the EEG activity in animals suggested that this mechanism could be involved in VNS antiepileptic effects in humans. Indeed VNS decreases spiking bursts, whereas its effects on the EEG background remain uncertain. The objective of the present study is to investigate how VNS affects local and inter regional syncronization in different frequencies in pharmacoresistent partial epilepsy. Methods: Digital recordings acquired in 11 epileptic subjects 1 year and 1 week before VNS surgery were compared with that obtained 1 month and 1 year after VNS activation. Power spectrum and synchronization were then analyzed and compared with an epileptic group of 10 patients treated with AEDs only and with 9 non-epileptic patients. Results: VNS decreases the synchronization of theta frequencies (P!0.01), whereas it increases gamma power spectrum and synchronization (!0.001 and 0.01, respectively). Conclusions: The reduction of theta frequencies and the increase in power spectrum and synchronization of gamma bands can be related to VNS anticonvulsant mechanism. In addition, gamma modulation could also play a seizure-independent role in improving attentional performances. Significance: These results suggest that some antiepileptic mechanisms affected by VNS can be modulated by or be the reflection of EEG changes.2026-2036Pubblicat

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Lymphocyte subpopulations in blood and cerebrospinal fluid from patients with subacute sclerosing panencephalitis

Lymphocyte subpopulations in peripheral blood (PB) and cerebrospinal fluid (CSF) from 26 children affected with subacute sclerosing panencephalitis (SSPE) and from 13 controls with various neurological diseases without any immunological implication were examined for surface markers. SSPE patients were found to have significantly lower %s of E-rosette forming cells (RFC) (T lymphocytes) and of EA-RFC (TG lymphocytes, suppressor T cells) in both CSF and PB. No difference was found in EAC-RFC (B lymphocytes) either in CSF or PB. The low EA-RFC values can be explained by genetic factors, immune complexes or virus infection, and they could account for the hypersynthesis of oligoclonal immunoglobulins in the central nervous system. Longitudinal studies performed in 6 SSPE patients during isoprinosine therapy revealed a time-dependent decrement of the %s of E- and EA-RFC in CSF. It cannot be affirmed whether this is related to the disease or to the therapy.</br