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1.
Sci Adv ; 10(28): eadg1421, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996019

RESUMO

Genomic mechanisms enhancing risk in males may contribute to sex bias in autism. The ubiquitin protein ligase E3A gene (Ube3a) affects cellular homeostasis via control of protein turnover and by acting as transcriptional coactivator with steroid hormone receptors. Overdosage of Ube3a via duplication or triplication of chromosomal region 15q11-13 causes 1 to 2% of autistic cases. Here, we test the hypothesis that increased dosage of Ube3a may influence autism-relevant phenotypes in a sex-biased manner. We show that mice with extra copies of Ube3a exhibit sex-biasing effects on brain connectomics and autism-relevant behaviors. These effects are associated with transcriptional dysregulation of autism-associated genes, as well as genes differentially expressed in 15q duplication and in autistic people. Increased Ube3a dosage also affects expression of genes on the X chromosome, genes influenced by sex steroid hormone, and genes sex-differentially regulated by transcription factors. These results suggest that Ube3a overdosage can contribute to sex bias in neurodevelopmental conditions via influence on sex-differential mechanisms.


Assuntos
Transtorno Autístico , Transcriptoma , Ubiquitina-Proteína Ligases , Animais , Masculino , Feminino , Transtorno Autístico/genética , Camundongos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Humanos , Comportamento Animal , Caracteres Sexuais , Encéfalo/metabolismo , Modelos Animais de Doenças , Predisposição Genética para Doença
2.
Artigo em Inglês | MEDLINE | ID: mdl-38836336

RESUMO

Background: Cognitive impairment is observed in up to 50% of patients with amyotrophic lateral sclerosis (ALS). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is an ALS-specific multi-domain screening tool. Few studies have examined the relationship between ECAS scores and [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) findings. Objective: To assess the relationship between ECAS scores and glucose metabolism patterns on [18F]FDG -PET images in ALS. Methods: We collected [18F]FDG-PET images from 65 patients with ALS and 39 healthy controls. ECAS scores were collected on all patients and we calculated the correlation to [18F]FDG-PET in order to investigate the potential links between cognition and glucose metabolism. Results: We observed hypometabolism in the frontal cortex, insula, and limbic system, together with hypermetabolism in the cerebellum in patients with ALS compared to controls. A lower ECAS total score was associated with lower glucose metabolism in the right orbitofrontal gyrus and higher glucose metabolism in lateral occipital, medial occipital, and cerebellar regions, among patients with ALS. Similar results, although less widespread, were observed in the analyses of ECAS ALS-specific scores. Conclusions: The metabolic patterns in [18F]FDG -PET show that changes in the glucose metabolism of corresponding areas are related to cognitive dysfunction in ALS, and can be detected using the ECAS.

3.
Nat Neurosci ; 27(7): 1318-1332, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38769153

RESUMO

Emotion recognition and the resulting responses are important for survival and social functioning. However, how socially derived information is processed for reliable emotion recognition is incompletely understood. Here, we reveal an evolutionarily conserved long-range inhibitory/excitatory brain network mediating these socio-cognitive processes. Anatomical tracing in mice revealed the existence of a subpopulation of somatostatin (SOM) GABAergic neurons projecting from the medial prefrontal cortex (mPFC) to the retrosplenial cortex (RSC). Through optogenetic manipulations and Ca2+ imaging fiber photometry in mice and functional imaging in humans, we demonstrate the specific participation of these long-range SOM projections from the mPFC to the RSC, and an excitatory feedback loop from the RSC to the mPFC, in emotion recognition. Notably, we show that mPFC-to-RSC SOM projections are dysfunctional in mouse models relevant to psychiatric vulnerability and can be targeted to rescue emotion recognition deficits in these mice. Our findings demonstrate a cortico-cortical circuit underlying emotion recognition.


Assuntos
Emoções , Córtex Pré-Frontal , Animais , Emoções/fisiologia , Córtex Pré-Frontal/fisiologia , Camundongos , Masculino , Humanos , Neurônios GABAérgicos/fisiologia , Vias Neurais/fisiologia , Somatostatina/metabolismo , Reconhecimento Psicológico/fisiologia , Camundongos Endogâmicos C57BL , Optogenética , Feminino , Giro do Cíngulo/fisiologia
5.
eNeuro ; 11(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38499355

RESUMO

Fueled by the recent and controversial brain-wide association studies in humans, the animal neuroimaging community has also begun questioning whether using larger sample sizes is necessary for ethical and effective scientific progress. In this opinion piece, we illustrate two opposing views on sample size extremes in MRI-based animal neuroimaging.


Assuntos
Imageamento por Ressonância Magnética , Neuroimagem , Animais , Humanos , Neuroimagem/métodos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem
6.
Ann Neurol ; 95(6): 1178-1192, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38466158

RESUMO

OBJECTIVE: To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography-confirmed RBD who eventually phenoconverted to overt alpha-synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non-phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion. RESULTS: Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD-converters from DLB-converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z-score cutoff of -1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of -1.0 at the most affected hemisphere putamen/caudate ratio characterized PD-converters. INTERPRETATION: Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease-modifying trials. ANN NEUROL 2024;95:1178-1192.


Assuntos
Dopamina , Doença por Corpos de Lewy , Aprendizado de Máquina , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Sinucleinopatias , Humanos , Transtorno do Comportamento do Sono REM/diagnóstico por imagem , Masculino , Feminino , Idoso , Sinucleinopatias/diagnóstico por imagem , Pessoa de Meia-Idade , Doença por Corpos de Lewy/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/complicações , Dopamina/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Terminações Pré-Sinápticas/metabolismo , Imageamento Dopaminérgico
7.
Commun Biol ; 6(1): 1238, 2023 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062107

RESUMO

Technical advances in neuroimaging, notably in fMRI, have allowed distributed patterns of functional connectivity to be mapped in the human brain with increasing spatiotemporal resolution. Recent years have seen a growing interest in extending this approach to rodents and non-human primates to understand the mechanism of fMRI connectivity and complement human investigations of the functional connectome. Here, we discuss current challenges and opportunities of fMRI connectivity mapping across species. We underscore the critical importance of physiologically decoding neuroimaging measures of brain (dys)connectivity via multiscale mechanistic investigations in animals. We next highlight a set of general principles governing the organization of mammalian connectivity networks across species. These include the presence of evolutionarily conserved network systems, a dominant cortical axis of functional connectivity, and a common repertoire of topographically conserved fMRI spatiotemporal modes. We finally describe emerging approaches allowing comparisons and extrapolations of fMRI connectivity findings across species. As neuroscientists gain access to increasingly sophisticated perturbational, computational and recording tools, cross-species fMRI offers novel opportunities to investigate the large-scale organization of the mammalian brain in health and disease.


Assuntos
Conectoma , Imageamento por Ressonância Magnética , Animais , Imageamento por Ressonância Magnética/métodos , Encéfalo/fisiologia , Conectoma/métodos , Primatas , Neuroimagem , Mamíferos
8.
Brain Sci ; 13(7)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37508982

RESUMO

According to the WHO (World Health Organization), Eye Movement Desensitization and Reprocessing (EMDR) is an elective therapy to treat people with post-traumatic stress disorders (PTSD). In line with the personalization of therapeutic strategies, through this pilot study, we assessed in people suffering from the effects of trauma the feasibility, safety, acceptance, and efficacy of EMDR enriched with sound stimulation (by administering neutral sounds synchronized with the guided bilateral alternating stimulation of the gaze) and musical reward (musical listening based on the patients' predisposition and personal tastes). Feasibility, quantified by the number of patients who completed the treatment, was excellent as this was the case in 12 out of the 12 enrolled people with psychological trauma. Safety and acceptance, assessed by self-compiled questionnaires, were excellent, with an absence of side effects and high satisfaction. Efficacy, quantified by the number of EMDR treatment sessions required to reach the optimal scores on the Subjective Units of Disturbance (SUD) and Validity of Cognition (VOC) scales typical of EMDR protocols, revealed an average duration of 8.5 (SD 1.2) sessions, which is well below the 12 sessions considered a standard EMDR treatment duration. EMDR+ appears to be a relevant personalization of EMDR, particularly in music-sensitive people, consolidating the therapeutic alliance through a multisensory communicative bond for trauma treatment.

9.
Front Psychol ; 14: 1120203, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37228335

RESUMO

Background: During the COVID-19 pandemic, psychological support was provided to healthcare workers in Nephrology and Dialysis Operative Unit of the Azienda Ospedaliera Bassini using an EMDR group protocol to decrease posttraumatic stress symptoms in the medium and long term. The aim of this study was to demonstrate the effectiveness of EMDR treatment to reduce post-traumatic stress symptoms at the end of the first pandemic wave and its progress over time in the subsequent phases of the health emergency. Methods: The sample of study consisted of 43 healthcare workers from the Nephrology and Dialysis Service who spontaneously decided to take part in the Brief EMDR treatment. Statistical analyses were carried out to compare the data collected with the IES-R, the Emotion Thermometer and the Post-Traumatic Growth Scale. The comparisons covered pre-treatment, post-treatment and follow-up. Results: The results show a significant clinical improvement in reducing PTSD symptoms following the Brief EMDR group treatment. The comparison between PRE and POST treatment (DELTA1) regarding the scores from IES-R and Emotion Thermometer, highlighted the important statistically change that occurred in terms of symptomatology reduction (p < 0.001). By comparing POST and FU (DELTA2), it was observed that all variables except avoidance show a significant weakening of the effect with time (p < 0.001), but the magnitude of this effect is much smaller than the improvement found in DELTA1. DELTA 3 analysis finally made it possible to highlight how the treatment effect is maintained almost intact at follow-up. In fact, the maintenance of a better situation at follow-up was observed, in the course of re-traumatization linked to the new wave, compared to the initial data (p < 0.001). Conclusion: The COVID-19 health emergency has significantly impacted hospital healthcare workers, leading to a high risk of developing PTSD symptoms. A psychological intervention aimed at the operators themselves is therefore of great importance.

10.
Artigo em Inglês | MEDLINE | ID: mdl-36755485

RESUMO

Objective: Amyotrophic lateral sclerosis (ALS) is a clinically heterogenous disease, typically presenting with focal motor weakness that eventually generalizes. Weather there is a correlation between focal motor weakness and metabolic alterations in specific areas of the brain has not been thoroughly explored. This study aims to systematically investigate this by using fluorodeoxyglucose-positron emission tomography (FDG-PET), including longitudinal imaging. Methods: This observational imaging study included 131 ALS patients diagnosed and examined with FDG-PET at the ALS Clinical Research Center at the Karolinska University Hospital in Stockholm, Sweden. Thirteen ALS patients had a second scan and were analyzed longitudinally. The findings were compared to 39 healthy controls examined at the University Medical Center of Gröningen, the Netherlands. Results: There was a general pattern of brain metabolic alterations consistent with previously reported findings in ALS, namely hypometabolism in frontal regions and hypermetabolism in posterior regions. A higher symptom burden was associated with increased hypometabolism and decreased hypermetabolism. However, there was no clear correlation between focal motor weakness and specific metabolic alterations, neither when analyzing focal motor weakness with concomitant upper motor neuron signs or when including all focal motor weakness. Longitudinal FDG-PET imaging showed inconsistent results with little correlation between progression of motor weakness and metabolic alterations. Conclusion: Our results support the disease model of ALS as a diffuse process since no clear correlation was seen between focal motor weakness and specific metabolic alterations. However, there is need for further research on a larger number of patients, particularly including longitudinal imaging.


Assuntos
Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/metabolismo , Fluordesoxiglucose F18/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Lobo Frontal
11.
Mol Psychiatry ; 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737483

RESUMO

Functional and structural connectivity alterations in short- and long-range projections have been reported across neurodevelopmental disorders (NDD). Interhemispheric callosal projection neurons (CPN) represent one of the major long-range projections in the brain, which are particularly important for higher-order cognitive function and flexibility. However, whether a causal relationship exists between interhemispheric connectivity alterations and cognitive deficits in NDD remains elusive. Here, we focused on CDKL5 Deficiency Disorder (CDD), a severe neurodevelopmental disorder caused by mutations in the X-linked Cyclin-dependent kinase-like 5 (CDKL5) gene. We found an increase in homotopic interhemispheric connectivity and functional hyperconnectivity across higher cognitive areas in adult male and female CDKL5-deficient mice by resting-state functional MRI (rs-fMRI) analysis. This was accompanied by an increase in the number of callosal synaptic inputs but decrease in local synaptic connectivity in the cingulate cortex of juvenile CDKL5-deficient mice, suggesting an impairment in excitatory synapse development and a differential role of CDKL5 across excitatory neuron subtypes. These deficits were associated with significant cognitive impairments in CDKL5 KO mice. Selective deletion of CDKL5 in the largest subtype of CPN likewise resulted in an increase of functional callosal inputs, without however significantly altering intracortical cingulate networks. Notably, such callosal-specific changes were sufficient to cause cognitive deficits. Finally, when CDKL5 was selectively re-expressed only in this CPN subtype, in otherwise CDKL5-deficient mice, it was sufficient to prevent the cognitive impairments of CDKL5 mutants. Together, these results reveal a novel role of CDKL5 by demonstrating that it is both necessary and sufficient for proper CPN connectivity and cognitive function and flexibility, and further validates a causal relationship between CPN dysfunction and cognitive impairment in a model of NDD.

12.
J Nucl Med ; 64(4): 508-514, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36732056

RESUMO

The impact of chemotherapy on brain functionality has been widely investigated from a clinical perspective, and there is a consensus on a significant impairment of multiple cognitive domains affecting cancer patients after treatment. Nuclear medicine offers a variety of biomarkers for evaluating possible effects of chemotherapy on the brain and for depicting brain changes after chemotherapy. This review summarizes the most relevant findings on brain imaging in patients undergoing chemotherapy for the most common oncologic diseases. The literature published to date offers exciting results on several radiolabeled compounds, from the more common imaging of glucose metabolism to neuroinflammation. This review also provides a general overview of the literature concerning clinical features and the physiopathologic basis of chemotherapy-related cognitive impairment.


Assuntos
Comprometimento Cognitivo Relacionado à Quimioterapia , Neoplasias , Medicina Nuclear , Humanos , Comprometimento Cognitivo Relacionado à Quimioterapia/metabolismo , Comprometimento Cognitivo Relacionado à Quimioterapia/patologia , Encéfalo/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Diagnóstico por Imagem
13.
J Clin Epidemiol ; 154: 97-107, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36403886

RESUMO

OBJECTIVES: To develop the Functional Risk Index for Dependence in Ambulation (FRIDA) score, a nomogram to predict individual risk of dependence in ambulation at discharge from postacute rehabilitation and validate its performance temporally and spatially. STUDY DESIGN AND SETTING: We analyzed the database of a multicenter prospective observational quality cohort study conducted from January 2012 to March 2016, including data from 8,796 consecutive inpatients who underwent rehabilitation after stroke, hip fracture, lower limb joint replacement, debility, and other neurologic, orthopedic, or miscellaneous conditions. RESULTS: A total of 3,026 patients (34.4%) were discharged dependent in ambulation. In the training set of 5,162 patients (58.7%), Lasso-regression selected advanced age, premorbid disability, and eight indicators of medical and functional adverse syndromes at baseline to establish the FRIDA score. At the temporal validation obtained on an external set of 3,234 patients (41.3%), meta-analyses showed that the FRIDA score had good and homogeneous discrimination (summary area under the curve 0.841, 95% confidence interval = 0.826-0.855, I2 = 0.00%) combined with accurate calibration (summary Log O/E ratio 0.017, 95% confidence interval -0.155 to 0.190). These performances remained stable at spatial validation obtained on 3,626 patients, with substantial heterogeneity of estimates across nine facilities. Decision curve analyses showed that a FRIDA score-supported strategy far outperformed the usual "treat all" approach in each impairment categories. CONCLUSION: The FRIDA score is a new clinically useful tool to predict an individual risk for dependence in ambulation at rehabilitation discharge in many different disabilities, and may also reflect well the case-mix composition of the rehabilitation facilities.


Assuntos
Fraturas do Quadril , Nomogramas , Humanos , Estudos Prospectivos , Estudos de Coortes , Caminhada
14.
Eur J Nucl Med Mol Imaging ; 50(3): 784-791, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36308536

RESUMO

PURPOSE: The identification of prognostic tools in amyotrophic lateral sclerosis (ALS) would improve the design of clinical trials, the management of patients, and life planning. We aimed to evaluate the accuracy of brain 2-[18F]fluoro-2-deoxy-D-glucose-positron-emission tomography (2-[18F]FDG-PET) as an independent predictor of survival in ALS. METHODS: A prospective cohort study enrolled 418 ALS patients, who underwent brain 2-[18F]FDG-PET at diagnosis and whose survival time was available. We discretized the survival time in a finite number of classes in a data-driven fashion by employing a k-means-like strategy. We identified "hot brain regions" with maximal power in discriminating survival classes, by evaluating the Laplacian scores in a class-aware fashion. We retained the top-m features for each class to train the classification systems (i.e., a support vector machine, SVM), using 10% of the ALS cohort as test set. RESULTS: Data were discretized in three survival profiles: 0-2 years, 2-5 years, and > 5 years. SVM resulted in an error rate < 20% for two out of three classes separately. As for class one, the discriminant clusters included left caudate body and anterior cingulate cortex. The most discriminant regions were bilateral cerebellar pyramid in class two, and right cerebellar dentate nucleus, and left cerebellar nodule in class three. CONCLUSION: Brain 2-[18F]FDG-PET along with artificial intelligence was able to predict with high accuracy the survival time range in our ALS cohort. Healthcare professionals can benefit from this prognostic tool for planning patients' management and follow-up. 2-[18F]FDG-PET represents a promising biomarker for individual patients' stratification in clinical trials. The lack of a multicentre external validation of the model warrants further studies to evaluate its generalization capability.


Assuntos
Esclerose Lateral Amiotrófica , Fluordesoxiglucose F18 , Humanos , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Estudos Prospectivos , Glucose , Inteligência Artificial , Tomografia por Emissão de Pósitrons/métodos , Encéfalo/diagnóstico por imagem
15.
J Neurol ; 270(2): 953-959, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36322237

RESUMO

BACKGROUND: MRI studies reported that ALS patients with bulbar and spinal onset showed focal cortical changes in corresponding regions of the motor homunculus. We evaluated the capability of brain 2-[18F]FDG-PET to disclose the metabolic features characterizing patients with pure bulbar or spinal motor impairment. METHODS: We classified as pure bulbar (PB) patients with bulbar onset and a normal score in the spinal items of the ALSFRS-R, and as pure spinal (PS) patients with spinal onset and a normal score in the bulbar items at the time of PET. Forty healthy controls (HC) were enrolled. We compared PB and PS, and each patient group with HC. Metabolic clusters showing a statistically significant difference between PB and PS were tested to evaluate their accuracy in discriminating the two groups. We performed a leave-one-out cross-validation (LOOCV) over the entire dataset. Four classifiers were considered: support vector machines (SVM), K-nearest neighbours, linear classifier, and decision tree. Then, we used a separate test set, including 10% of patients, with the remaining 90% composing the training set. RESULTS: We included 63 PB, 271 PS, and 40 HC. PB showed a relative hypometabolism compared to PS in bilateral precentral gyrus in the regions of the motor cortex involved in the control of bulbar function. SVM showed the best performance, resulting in the lowest error rate in both LOOCV (4.19%) and test set (9.09 ± 2.02%). CONCLUSIONS: Our data support the concept of the focality of ALS onset and the use of 2-[18F]FDG-PET as a biomarker for precision medicine-oriented clinical trials.


Assuntos
Esclerose Lateral Amiotrófica , Córtex Motor , Humanos , Fluordesoxiglucose F18 , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética
16.
Front Psychol ; 13: 969028, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312101

RESUMO

Residential nursing homes were particularly badly affected by the first wave of COVID-19, with large numbers of their frail person getting infected with COVID-19 and dying. The staff in these structures were catapulted into a reality very different from what they were used to. They had to adapt the way they used to take care of their patients in a very short space of time and in a scenario that was continually changing. In this manuscript we describe the subjective experience of staff in a number of Italian nursing homes during the first wave of the COVID-19 pandemic; and we report data showing the effectiveness of the Eye Movement Desensitization and Reprocessing (EMDR) treatment provided to support them during this Pandemic.

17.
Neurol Genet ; 8(6): e200033, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36313067

RESUMO

Background and Objectives: To characterize the clinical and cognitive behavioral phenotype and brain 18F-2-fluoro-2-deoxy-d-glucose-PET (18F-FDG-PET) metabolism of patients with amyotrophic lateral sclerosis (ALS) carrying the rs12608932 variant of the UNC13A gene. Methods: The study population included 1,409 patients with ALS without C9orf72, SOD1, TARDBP, and FUS mutations identified through a prospective epidemiologic ALS register. Control participants included 1,012 geographically matched, age-matched, and sex-matched participants. Clinical and cognitive differences between patients carrying the C/C rs12608932 genotype and those carrying the A/A + A/C genotype were assessed. A subset of patients underwent 18F-FDG-PET. Results: The C/C genotype was associated with an increased risk of ALS (odds ratio: 1.54, 95% confidence interval 1.18-2.01, p = 0.001). Patients with the C/C genotype were older, had more frequent bulbar onset, and manifested a higher rate of weight loss. In addition, they showed significantly reduced performance in the letter fluency test, fluency domain of Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and story-based empathy task (reflecting social cognition). Patients with the C/C genotype had a shorter survival (median survival time, C/C 2.25 years, interquartile range [IQR] 1.33-3.92; A/A + C/C: 2.90 years, IQR 1.74-5.41; p = 0.0001). In Cox multivariable analysis, C/C genotype resulted to be an independent prognostic factor. Finally, patients with a C/C genotype had a specific pattern of hypometabolism on brain 18F-FDG-PET extending to frontal and precentral areas of the right hemisphere. Discussion: C/C rs12608932 genotype of UNC13A is associated with a specific motor and cognitive/behavioral phenotype, which reflects on 18F-FDG-PET findings. Our observations highlight the importance of adding the rs12608932 variant in UNC13A to the ALS genetic panel to refine the individual prognostic prediction and reduce heterogeneity in clinical trials.

18.
Front Psychol ; 13: 964334, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160528

RESUMO

Aim: The Coronavirus 2019 (COVID-19) pandemic represents one of the most catastrophic events of recent times. Due to the hospitals' emergency situation, the population of healthcare workers was the most affected. Healthcare workers who were exposed to COVID-19 patients are most likely to develop psychological distress and post-traumatic stress disorder (PTSD). The present study aimed at investigating PTSD in a sample of Italian healthcare workers during this outbreak and to evaluate the effectiveness of the Eye Movement Desensitization and Reprocessing (EMDR) Therapy with this population. Methods: A total of 744 healthcare workers were included. 587 healthcare workers were treated with EMDR, while the other 157 were not treated. Participants were asked to provide sociodemographic information; the post-traumatic symptomatology was evaluated through Impact of Event Scale-Revised (IES-R) and to investigate the level of intensity of emotional activation was used The Emotion Thermometer (THERMO) at two time points (pre-post treatment). Results: The results obtained between EMDR treatment and non-EMDR treatment were evaluated on only 2 hospitals. Treatment group n = 68 vs. waitlist non-treatment group n = 157. All scores pre- and post-EMDR decreased significantly (p < 0.001) showing an evident effect of EMDR. The differences between pre- and post-treatment of the IES-R scores of subjects in which EMDR was performed as compared to the scores pre- and post-12 weeks of waiting list subjects in which it was not performed were significantly different (p < 0.001). Limitation: The emergency situation did not provide an opportunity to explore further aspects that would have been important for research. One limitation is the use and analysis of only two standardized tests. In addition, other psychopathologies were not investigated as outcome measures. A limitation is the comparison of subjects treated online and de visu. Although the protocol used was the same, the mode of intervention may have influenced the results. In addition, the effectiveness of EMDR treatment was only evaluated at two time points (pre-post) with no possibility of follow-up and the lack of a control group. Discussion/conclusion: The findings of the present study suggest that healthcare workers were at high risk of developing PTSD when confronted with COVID-19 outbreak and suggest the importance of psychological support during this humanitarian emergency.

19.
J Integr Neurosci ; 21(5): 143, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36137952

RESUMO

INTRODUCTION: The spread of the COVID-19 Pandemic led the Italian government to impose restrictive measures. Schools were closed and the organization of Distance Learning (DL) made adolescents face the psychological impact of the pandemic and the loss of their social life. OBJECTIVE: This research aimed to evaluate the psychological impact of the COVID-19 Pandemic and DL on students, attending two high schools in the Lodi area (Lombardy, Italy). METHOD: A questionnaire, composed of PSYCHO-COVID 19 and EMOTION THERMOMETER applied to DL, was administered anonymously through the Google Drive School platform, from May 5th to June 5th 2020. RESULTS: Analysis of the protocols revealed stress reactions in 35% of students (12% High, 7% Moderate, 16% Mild). Principal Components Analysis also revealed the presence of a "distress entity" characterized by anxiety, depressive and somatic symptoms (comparable to those of post-traumatic stress syndrome), with a greater impact on females. The analysis of data on DL showed that online teaching was experienced negatively, in an almost linear correlation, by those subjects who had expressed distress. CONCLUSIONS: The results suggest that the pandemic had a traumatic impact on adolescents, especially on girls; psychological distress negatively influenced individual experiences with DL. Appropriate psychotherapeutic interventions are needed to prevent the chronicization of stress reactions and to facilitate the adaptation of adolescents to possible rapid changes in educational management.


Assuntos
COVID-19 , Pandemias , Adolescente , Ansiedade , Feminino , Humanos , Pandemias/prevenção & controle , Distanciamento Físico , SARS-CoV-2
20.
Front Psychol ; 13: 964407, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003099

RESUMO

We report the results of a pilot study regarding the adaptation of the group eye movement desensitization and reprocessing (EMDR) protocol for the treatment online, for the management of trauma associated with the COVID-19 Pandemic in Italy. The target group were healthcare workers in a nursing home (Residenza sanitaria assistita, RSA) who decided to live and stay on site during the most acute phase of the Pandemic in order to protect the residents of the home. Scores for perceived post traumatic stress disorder (PTSD) symptoms and quality of emotional experience improved significantly following participation in the therapy programme. These preliminary results confirm the innovative potential of the EMDR protocol when used online on early intervention, to prevent the development of later psychological disturbances.

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