A relationship between gut microbiome and central nervous system (CNS), have been suggested. The human microbiome may have an influence on brain's development, thus implying that dysbiosis may ...contribute in the etiology and progression of some neurological/neuropsychiatric disorders. The objective of this systematic review was to identify evidence on the characterization and potential distinctive traits of the microbiome of children with neurodevelopmental disorders, as compared to healthy children.
The review was performed following the methodology described in the Cochrane handbook for systematic reviews, and was reported based on the PRISMA statement for reporting systematic reviews and meta-analyses. All literature published up to April 2019 was retrieved searching the databases PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews. Only observational studies, published in English and reporting data on the characterization of the microbiome in humans aged 0-18 years with a neurodevelopmental disorder were included. Neurodevelopmental disorders were categorized according to the definition included in the Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5).
Bibliographic searches yielded 9,237 records. One study was identified through other data sources. A total of 16 studies were selected based on their relevance and pertinence to the topic of the review, and were then applied the predefined inclusion and exclusion criteria. A total of 10 case-control studies met the inclusion criteria, and were thus included in the qualitative analysis and applied the NOS score. Two studies reported data on the gut microbiome of children with ADHD, while 8 reported data on either the gut (
= 6) or the oral microbiome (
= 2) of children with ASD.
All the 10 studies included in this review showed a high heterogeneity in terms of sample size, gender, clinical issues, and type of controls. This high heterogeneity, along with the small sample size of the included studies, strongly limited the external validity of results. The quality assessment performed using the NOS score showed an overall low to moderate methodological quality of the included studies. To better clarify the potential role of microbiome in patients with neurodevelopmental disorders, further high-quality observational (specifically cohort) studies are needed.
The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to ...assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD.
The scope of practice of the osteopathic profession in Italy is underreported. The first part of the present study investigated the Italian osteopaths' profile, focusing on the socio-demographic ...information and geographical distribution together with the main characteristics of their education. The OPERA-IT study highlighted that the majority of respondents declared to work as sole practitioners (58.4%), while the remaining declared to work as part of a team. Since teamwork and networking are recognized as fundamental aspects of healthcare, the present study aims to compare the osteopathic practice, diagnostic and treatment modalities of osteopaths who work as a sole practitioner and osteopaths who work as part of a team to highlight possible differences. Moreover, patients' characteristics will be presented. The OPERA-IT study population was chosen to provide a representative sample. A web campaign was set up to inform the Italian osteopaths before the beginning of the study. The OPERA IT study used a previously tested questionnaire. The questionnaire was translated into Italian following the World Health Organization recommendation. The questionnaire was composed of 57 items grouped in five sections, namely: socio-demographics, osteopathic education and training, working profile, organization, and management of the clinical practice and patient profile. The survey was delivered online through a dedicated platform. The survey was completed by 4,816 individuals. Osteopaths who work as sole practitioners represented the majority of the sample (n = 2814; 58.4%). Osteopaths who work as part of a team declared to collaborate mostly with physiotherapists (n = 1121; 23.3%), physicians with speciality (n = 1040; 21.6%), and other osteopaths (n = 943; 19.6%). The two groups showed heterogeneous characteristics. Significative differences were observed in all the factors, namely: geographical distribution, age, gender, training, working contract and working place, daily consultations and time for each consultation, fees, and the average waiting period to book an appointment. The principal component analysis supported a ten-component model and explained 80.5% of the total variance. The analysis showed that osteopaths working as sole practitioners have an increased probability (OR = 0.91; CI 95%: 0.88-0.94; p<0.01) of using systemic diagnostic and treatment techniques and have distinct clinical features with higher probability (OR = 0.92; 0.88-0.96; p<0.01) of spending less time with patients, being paid less but treating a higher number of patients per week. The most represented patients' age groups were 41-64 years old (n = 4452; 92.4%) and 21-40 years old (n = 4291; 89.1%). Similarly, the most reported new patients' age groups were 41-64 years old (n = 4221; 87.7%) and 21-40 years old (n = 3364; 69.9%). The most common presenting complaints were back pain, neck pain, cervical radiculopathy, sciatica, shoulder pain, and headaches. Osteopathic practice in Italy seems to be characterised by interprofessional collaboration, mostly with physiotherapists. Our results highlighted two different profiles in terms of sociodemographic characteristics and work modalities between osteopaths who work as sole practitioners and those who work as part of a team. Although according to the respondents, people of all ages consult Italian osteopaths, the majority of patients are adults. Most of them have been referred to osteopathy by other patients or acquaintances. Patients seek osteopathic care mostly for musculoskeletal related complaints.
Introduction
The aim is to test whether adding a simple physical test such as walking speed (WS) to the neuropsychological assessment increases the predictive ability to detect dementia.
Methods
The ...2546 dementia‐free people from the SNAC‐K study were grouped into four profiles: (1) healthy profile; (2) isolated cognitive impairment, no dementia (CIND, scoring 1.5 standard deviation below age‐specific means on ≥1 cognitive domains); (3) isolated slow WS (<0.8 m/s); (4) CIND+ slow WS. The hazard of dementia (Cox regression), the positive and negative predictive values (PPV, NPV), and the area under the curve (AUC) were estimated.
Results
Participants with CIND +slow WS demonstrated the highest hazard of dementia (3.4; 95% confidence interval CI: 2.5–4.8). The AUC increased from 0.69 for isolated CIND to 0.83 for CIND+ slow WS. Such an increase was due to the improvement of the PPV, the NPV remaining optimal.
Discussion
Adding WS to the cognitive assessment dramatically increases the diagnostic accuracy of prodromal dementia.
Pontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging ...features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes.
We performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for
rearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters.
A genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was
, which accounted for nearly half cases (45%) and was mutated in females and occasionally in males. The European founder mutation p.Ala307Ser in
and pathogenic variants in
accounted for 18% and 9% of cases, respectively.
,
and
were mutated in single patients. We were able to confirm only few previously reported associations, including jitteriness and clonus with
and lower motor neuron signs with
. When considering multiple features simultaneously, a clear association with a phenotypic cluster only emerged for
.
represents the major PCH causative gene in Italy. Phenotypic variability associated with the most common genetic causes of PCH is wider than previously thought, with marked overlap between
and
-associated disorders.
Objective
In this prospective, controlled, monocentric study, we described the clinical and neuroimaging 12-month follow-up of two parallel cohorts of subjects with idiopathic normal pressure ...hydrocephalus (iNPH), who did or did not undergo lumboperitoneal shunt (LPS).
Methods
We recruited 78 iNPH patients. At baseline, subjects underwent clinical and neuropsychological assessments, 3 T magnetic resonance imaging (MRI), and tap test. After baseline, 44 patients (LPS group) opted for LPS implantation, whereas 34 subjects (control group) declined surgery. Both cohorts were then followed up for 12 months through scheduled clinical and neuropsychological evaluations every 6 months. 3 T MRI was repeated at 12-month follow-up.
Results
Gait, balance, and urinary continence improved in the LPS group, without significant influence on cognitive functions. Conversely, gait and urinary continence worsened in the control group. No preoperative MRI parameter was significant outcome predictor after LPS. Of relevance, in responders to LPS, we found postoperative reduction of periventricular white matter (PWM) hyperintensities, which were instead increased in the control group.
Conclusions
LPS is safe and effective in iNPH. An early surgical treatment is desirable to prevent clinical worsening. Post-surgery decrease of PWM hyperintensities may be a useful MRI marker surrogate for clinical effectiveness of LPS.
The relationship between cancer and dementia is triggering growing research interest. Several preclinical studies have provided the biological rationale for the repurposing of specific anticancer ...agents in Alzheimer's disease (AD), and a growing number of research protocols are testing their efficacy and safety/tolerability in patients with AD.
The aim of the present systematic review was to provide an overview on the repurposing of approved anticancer drugs in clinical trials for AD by considering both ongoing and completed research protocols in all phases. In parallel, a systematic literature review was conducted on PubMed, ISI Web, and the Cochrane Library to identify published clinical studies on repurposed anticancer agents in AD.
Based on a structured search on the ClinicalTrials.gov and the EudraCT databases, we identified 13 clinical trials testing 11 different approved anticancer agents (five tyrosine kinase inhibitors, two retinoid X receptor agonists, two immunomodulatory agents, one histone deacetylase inhibitor, and one monoclonal antibody) in the AD continuum. The systematic literature search led to the identification of five published studies (one phase I, three phase II, and one phase IIb/III) reporting the effects of antitumoral treatments in patients with mild cognitive impairment or AD dementia. The clinical findings and the methodological characteristics of these studies are described and discussed.
Anticancer agents are triggering growing interest in the context of repurposed therapies in AD. Several clinical trials are underway, and data are expected to be available in the near future. To date, data emerging from published clinical studies are controversial. The promising results emerging from preclinical studies and identified research protocols should be confirmed and extended by larger, adequately designed, and high-quality clinical trials.
Leisure activities, particularly exercise, play a protective role against dementia in healthy people, but it is unknown if this protective effect could be generalized to subjects with mild cognitive ...impairment (MCI).
To investigate the influence of leisure activities on the risk of progression of MCI to dementia.
176 MCI subjects attending a memory clinic underwent a standardized lifestyle questionnaire between October 2007 and May 2010. Social, cognitive, and physical scores were derived based on the assiduity of interpersonal contacts and on the frequency of participation in individual leisure activities. Subjects were requested to return every 12 months for dementia surveillance. The outcome measure was the risk of dementia associated with social, cognitive, and physical scores.
Over a median follow-up time of 2.59 year, 92 (52.2%) MCI subjects developed dementia. Subjects with physical scores in the highest third had a lower risk (HR 0.44; 95% CI 0.23-0.85) of dementia compared with those in the lowest third. No association was found between cognitive or social scores and the risk of dementia.
To our knowledge, this is the first prospective clinical study which demonstrates that high levels of participation in physical leisure activities are associated with reduced risk of dementia in subjects with MCI. In line with findings coming from community-based studies on healthy elderly, our finding suggests that the protective role of exercise against the development of dementia can be generalized to MCI subjects seen in clinical practice. Clinicians should encourage MCI subjects to participate in physical leisure activities.
The Italian Dementia National Plan Di Fiandra, Teresa; Canevelli, Marco; Di Pucchio, Alessandra ...
Annali dell'Istituto superiore di sanità,
12/2015, Letnik:
51, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The Italian Dementia National Plan was formulated in October 2014 by the Italian Ministry of Health in close cooperation with the regions, the National Institute of Health and the three major ...national associations of patients and carers. The main purpose of this strategy was to provide directive indications for promoting and improving interventions in the dementia field, not limiting to specialist and therapeutic actions, but particularly focusing on the support of patients and families throughout the pathways of care. Four main objectives are indicated: 1) promote health- and social-care interventions and policies; 2) create/strengthen the integrated network of services for dementia based on an integrated approach; 3) implement strategies for promoting appropriateness and quality of care; and 4) improve the quality of life of persons with dementia and their families by supporting empowerment and stigma reduction. These objectives and the pertaining actions are described in the present paper.
Background: Dysphagia is common after stroke, requiring exclusive enteral feeding in 20% of patients. Recovery of oral feeding is associated with increased quality of life, better functional ...outcomes, and decreased mortality rates. However, evidence is heterogeneous and not conclusive on which factors are predictive of oral feeding recovery for stroke patients in rehabilitation units. Aim: To investigate predictors of complete oral feeding recovery. Design: Retrospective study. Setting: Intensive inpatient rehabilitation hospital. Population: Poststroke dysphagic individuals with enteral feeding. Methods: Retrospective chart review of demographic, clinical, rehabilitation, and swallowing factors. Univariate analysis and multivariate regression analysis were used to compare variables between the oral feeding recovery group and the enteral feeding group at discharge. Results: One hundred thirty-nine patients were included in the analysis. A total of 61.9% of the sample population resumed complete oral intake at discharge. There were statistically significant differences between the 2 groups in Functional Independence Measure cognitive score, clinical swallow evaluation, and instrumental swallow evaluation at admittance, and dysphagia rehabilitation. Multiple logistic regression analysis identified the absence of aspiration signs with liquids associated with a higher probability of the resumption of complete oral feeding (odds ratio OR 3.57; 95% confidence interval CI 1.07-11.89). Age between 73 and 79 years (OR .96; 95% CI .01-.58), the presence of aspiration and/or penetration (OR .22; 95% CI .07-.72), and the presence of residue (OR .14; 95%CI .04-.43) during fiberoptic endoscopic evaluation of swallowing presented lower probability of returning to complete oral feeding. Conclusion: Several demographic and swallowing characteristics predicted oral feeding recovery. Absence of dysphagia signs documented on fiberoptic endoscopic evaluation of swallowing was the strongest predictor of complete oral feeding resumption.
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