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Objective: To evaluate mortality for Alzheimer's Disease (AD) in Italy over more than three decades (1980–2015) and discuss the possible role of general and specific contributing factors. Methods: Mortality data were extracted by the Italian National Institute of Statistics: crude mortality rates were computed for sex and age, considering the whole country and its five main geographical sub-areas. Rates were standardized in two ways: directly (annual mortality rates AMRs) and indirectly (standardized mortality rates, SMRs). SMRs were then used to evaluate geographical differences; to study mortality trend, AMRs and joinpoint linear regression analysis were used. Results: Considering the entire period and the whole country, mortality rates were similar for females and males and for geographical regions, with the exception of the older age groups where mortality for AD in females slightly prevailed. In these older patients, a steep increase of mortality was seen starting from the current century. The increase in male mortality mirrored the national trend in North-West and Central Italy, but not in North-East, South, and the Islands, where it did not surge until the mid to late 1990s. Conclusions: the general increase of mortality is in line with international data and it reflects the increasing prevalence of the disease, likely due to increasing longevity, and to improvements in diagnostic accuracy. In addition, the accuracy of death certificate compilation could account for both geographical and temporal differences. Currently available drugs for AD do not seem to have an impact on mortality rates. [ABSTRACT FROM AUTHOR]

Self-Rated Health (SRH) is currently one of the most popular indicators of population health. Studies show that SRH has a strong association with physical functioning, well-being, and mortality across a variety of populations and ages. Despite its wide use, the different elements that act and interact when an individual assesses their own health are still not clear. To date, only one study has focused on the process of self-assessment of health among the oldest-old individuals. The aim of this paper is to explore direct and indirect effects of socioeconomic status, presence of disease, functional health, and emotional health on the good self-assessment of health among Italian nonagenarians. By applying Structural Equation Modelling (SEM) on Mugello Study data, we find a strong direct effect of both emotional and functional health on SRH, confirming their key roles in the process of self-assessment of health among the oldest-old individuals. Furthermore, we find indirect effects of socioeconomic status, presence of disease, and functional health on SRH. This is in line with existing literature on younger adults and elderly people. [ABSTRACT FROM AUTHOR]

Objective: Achieving remission in severe asthma holds paramount importance in elevating patient quality of life and reducing both individual and societal burdens associated with this chronic condition. This study centers on identifying pivotal patient-relevant endpoints through standardized, reproducible methods, while also developing a patient-centric definition of remission, essential for effective disease management. Methods: A discrete choice experiment (DCE) was conducted to assess patients' perceptions on the four primary criteria for defining severe asthma remission, as outlined by the SANI survey. Additionally, it investigated the correlation between these perceptions and improvements in the doctor-patient therapeutic alliance during treatment decision-making. Results: 249 patients (70% aged between 31–60, 59% women and 82% without other pathologies requiring corticosteroids) prioritize the use of oral corticosteroids (OCS, 48%) and the Asthma Control Test (ACT, 27%) in defining their condition, ranking these above lung function and exacerbations. This preference for OCS stems from its direct role in treatment, tangible tracking, immediate symptom relief, and being a concrete measure of disease severity compared to the less predictable and quantifiable exacerbations. Conclusions: This study explores severe asthma remission from patients' perspectives using clinician-evaluated parameters. The DCE revealed that most patients highly value OCS and the ACT, prefer moderate improvement, and avoid cortisone cycles. No definitive preference was found for lung function status. Integrating patient-reported information with professional insights is crucial for effective management and future research. Personalized treatment plans focusing on patient preferences, adherence, and alternative therapies aim to achieve remission and enhance quality of life. [ABSTRACT FROM AUTHOR]

Applying the Delphi method, this study aims at characterizing the perceptions and needs of physicians, individuals with hemophilia, and their caregivers in relation to the management of routine visits during regular follow-ups. A single structured questionnaire, prepared by an advisory board, was administered to 139 participants, comprising hemophilia treaters, patients and caregivers, during the period from May to June 2023. Agreement (defined following the Delphi method as developed by RAND Corporation) was reached on several topics. The Principal Component Analysis methods identified the four most relevant areas where consensus was reached among the interviewees, underscoring the necessity for in-depth discussions during routine visits: (1) medical aspects related to symptoms, life-limitations, pain, etc.; (2) non-medical related aspects (ambitions, lifestyle, network, etc.); (3) logistical-organizational aspects (home–hospital distance, alternative modalities of communication); and (4) visit duration and telemedicine integration. The results of both the Delphi and Principal Component Analysis underline that the care of individuals with hemophilia extends beyond merely prescribing drugs or treatment regimens. Instead, it necessitates consideration of numerous variables from both therapeutic and non-therapeutic domains, all of which are deemed important for the holistic management of the individuals. As a result, these aspects are routinely discussed and addressed during visits. [ABSTRACT FROM AUTHOR]

Background: On December 2017 the Italian Parliament approved law n. 219/2017 "Provisions for informed consent and advance directives" regarding challenging legal and bioethical issues related to healthcare decisions and end-of life choices. The law promotes the person's autonomy as a right and provides for the centrality of the individual in every scenario of health care by mean of three tools: informed consent, shared care planning and advance directives. Few years after the approval of the law, we conducted a survey among physicians working in four health care facilities specific for the care of people suffering from psychiatric disorders, cognitive disorders and dementia located in the North of Italy aiming to investigate their perceived knowledge and training need, attitudes regarding law n. 219/2017 provisions, and practices of implementation of the law. Methods: A semi-structured questionnaire was developed on an online platform. The invitation to participate in the survey was sent by email to the potential participants. Information was collected by means of the online platform (Google Forms) which allows to export data in a spreadsheet (Windows Excel) to perform basic statistical analysis (frequency distributions, bar chart representation). Results: Twenty-five out of sixty physicians participated in the survey. None of the respondents value their knowledge of the law as very good, 10 good, 13 neither poor nor good, 1 poor and 1 very poor. All the respondents want to learn more about the law (21 yes and 4 absolutely yes). The majority of respondents agrees with the content of the law as a whole (3 absolutely agree, 13 agree), and on each provision. The question on the clarity of the concept of capacity in the law received mixed answers and this impacted on the physicians' opinion regarding the legitimacy in principle for our groups of patients to realize shared care planning and write advance directives. Thirteen physicians neither introduced the theme of shared care planning nor arranged for shared care planning and the main reason for this was that no patient was in a clinical situation to require it. When shared care planning is realized, a variability in terms of type and number of meetings, mode of tracking and communication is registered. Conclusions: Our survey results indicate a need for more clarity regarding the interpretation and implementation of the law in the patient groups under study. There are in particular two related areas that deserve further discussion: (1) the question of whether these patient groups are in principle legitimized by the law to realize shared care planning or write advance directives; (2) the notion of capacity required by the law and how this notion can be declined in real-life situations. [ABSTRACT FROM AUTHOR]

Virtual reality (VR) applications are pervasive of everyday life, as in working, medical, and entertainment scenarios. There is yet no solution to cybersickness (CS), a disabling vestibular syndrome with nausea, dizziness, and general discomfort that most of VR users undergo, which results from an integration mismatch among visual, proprioceptive, and vestibular information. In a double-blind, controlled trial, we propose an innovative treatment for CS, consisting of online oscillatory imperceptible neuromodulation with transcranial alternating current stimulation (tACS) at 10 Hz, biophysically modelled to reach the vestibular cortex bilaterally. tACS significantly reduced CS nausea in 37 healthy subjects during a VR rollercoaster experience. The effect was frequency-dependent and placebo-insensitive. Subjective benefits were paralleled by galvanic skin response modulation in 25 subjects, addressing neurovegetative activity. Besides confirming the role of transcranially delivered oscillations in physiologically tuning the vestibular system function (and dysfunction), results open a new way to facilitate the use of VR in different scenarios and possibly to help treating also other vestibular dysfunctions. [ABSTRACT FROM AUTHOR]

Objectives: Fatigue in multiple sclerosis (MS) is a frequent and invalidating symptom, which can be relieved by non-invasive neuromodulation, which presents only negligible side effects. A 5-day transcranial direct-current stimulation, 15 min per day, anodically targeting the somatosensory representation of the whole body against a larger occipital cathode was efficacious against MS fatigue (fatigue relief in multiple sclerosis, Faremus treatment). The present proof-of-concept study tested the working hypothesis that Faremus S1 neuromodulation modifies the homology of the dominant and non-dominant corticospinal (CST) circuit recruitment. Methods: CST homology was assessed via the Fréchet distance between the morphologies of motor potentials (MEPs) evoked by transcranial magnetic stimulation in the homologous left- and right-hand muscles of 10 fatigued MS patients before and after Faremus. Results: In the absence of any change in MEP features either as differences between the two body sides or as an effect of the treatment, Faremus changed in physiological direction the CST's homology. Faremus effects on homology were more evident than recruitment changes within the dominant and non-dominant sides. Conclusions: The Faremus-related CST changes extend the relevance of the balance between hemispheric homologs to the homology between body sides. With this work, we contribute to the development of new network-sensitive measures that can provide new insights into the mechanisms of neuronal functional patterning underlying relevant symptoms. [ABSTRACT FROM AUTHOR]

Objectives: The homology of hemispheric cortical areas plays a crucial role in brain functionality. Here, we extend this concept to the homology of the dominant and non-dominant hemi-bodies, investigating the relationship of the two corticospinal tracts (CSTs). The evoked responses provide an estimate of the number of in-phase recruitments via their amplitude as a suitable indicator of the neuronal projections' integrity. An innovative concept derived from experience in the somatosensory system is that their morphology reflects the recruitment pattern of the whole circuit. Methods: CST homology was assessed via the Fréchet distance between the morphologies of motor-evoked potentials (MEPs) using a transcranial magnetic stimulation (TMS) in the homologous left- and right-hand first dorsal interosseous muscles of 40 healthy volunteers (HVs). We tested the working hypothesis that the inter-side Fréchet distance was higher than the two intra-side distances. Results: In addition to a clear confirmation of the working hypothesis (p < 0.0001 for both hemi-bodies) verified in all single subjects, we observed that the intra-side Fréchet distance was higher for the dominant than the non-dominant one. Interhemispheric morphology similarity increased with right-handedness prevalence (p = 0.004). Conclusions: The newly introduced measure of circuit recruitment patterning represents a potential benchmark for the evaluation of inter-lateral mechanisms expressing the relationship between homologous hemilateral structures subtending learning and suggests that variability in recruitment patterning physiologically increases in circuits expressing greater functionality. [ABSTRACT FROM AUTHOR]

Orally administered direct-acting antivirals (DAAs) have dramatically changed the possibility of curing HCV (hepatitis C virus) infection, with the two principal HCV regimens based on the combination of glecaprevir + pibrentasvir (GLE-PIB) and sofosbuvir + velpatasvir (SOF-VEL). A combination of drugs containing NS3/4A protease inhibitors, as well as the fact that almost all HCV patients can be treated at present, may expose patients to a higher rate of drug–drug interactions (DDIs). The hepatitis C treatment recommendations from the EASL (European Association for the Study of the Liver) state that, prior to starting treatment with a DAA, a detailed drug history should be taken; yet, the decision on managing the potential DDIs is not always clear. For this reason, a group of Italian cardiologists and hepatologists promoted a survey among colleagues to assess the controversial issues when treating patients with chronic hepatitis C taking concomitant cardiovascular drugs, aiming to reach a consensus on the best practice to apply when treating a patient with chronic hepatitis C who is taking concomitant drugs for cardiovascular diseases. Two consecutive questionnaires were proposed between June and July 2022 to a qualitative Expert Panel (EP) of 14 gastroenterologists, infectologists, hepatologists, and internists, with statistical analyses performed on 100% of the responses for both questionnaires. Agreement among experts was assessed following the Delphi method as developed by the RAND Corporation. The interviewed experts consider DDIs a critical clinical problem to be evaluated in HCV patients. Therefore, dose changes, drug substitution, and discontinuation of concomitant cardiovascular drugs should be discouraged, even if planned for a relatively short period. Since oral DAAs have different DDIs profiles, hepatologists should prefer the antiviral DAA combination presenting the lowest instance of potential interactions. [ABSTRACT FROM AUTHOR]

Background: On December 2017 the Italian Parliament approved law n. 219/2017 "Provisions for informed consent and advance directives" regarding challenging legal and bioethical issues related to healthcare decisions and end-of-life choices. The law does not contain an explicit reference to Ethics Committees (ECs), but they could still play a role in implementing the law.Methods: A questionnaire-based survey was performed among the ECs of the Italian Institute for Research and Care belonging to the Network of neuroscience and neurorehabilitation, with the aim of (1) knowing whether the ECs participated and, if so, how in the process of implementation of law n. 219/2017 in the referring institutes; (2) investigating the point of view of the ECs regarding their possible involvement in the process; (3) exploring the contribution ECs can provide to give effective implementation to the law principles and provisions.Results: Seventeen ECs out of thirty took part in the survey; the characteristics of the responding and non-responding committees are similar, so the responding ECs can be regarded as representative of all ECs in the Network. Nine ECs did not discuss the law in anyway: the main reason for this is that the referring institutions (6) and the health care professionals (3) did not ask for an EC intervention. Nevertheless, the large majority of the ECs believe that their involvement in the implementation of the law as a whole is appropriate (8) or absolutely appropriate (6), while 3 of them are neutral. No EC believes that the involvement is inappropriate. The aspect of the law on which the 14 ECs converge in considering the EC involvement appropriate/absolutely appropriate is the one related to the health facilities obligation to guarantee the full and proper implementation of the principles of the law.Conclusions: Our survey confirms that ECs believe they can play a role in the implementation of law n. 219/2017, although this does not entirely correspond to what the committees have actually done in reality. This role could be better exercised by ECs specifically established for clinical practice, which would have a composition, functioning and a mandate better suited to the purpose. This supports the call for a national regulation of ECs for clinical practice. [ABSTRACT FROM AUTHOR]

In healthy women, the cervicovaginal microbiota is characterized by the predominance of Lactobacillus spp., whereas the overgrowth of anaerobic bacteria leads to dysbiosis, known to increase the risk of acquiring genital infections like Chlamydia trachomatis. In the last decade, a growing body of research has investigated the composition of the cervicovaginal microbiota associated with chlamydial infection via 16s rDNA sequencing, with contrasting results. A systematic review and a meta-analysis, performed on the alpha-diversity indices, were conducted to summarize the scientific evidence on the cervicovaginal microbiota composition in C. trachomatis infection. Databases PubMed, Scopus and Web of Science were searched with the following strategy: "Chlamydia trachomatis" AND "micro*". The diversity indices considered for the meta-analysis were Operational Taxonomic Unit (OTU) number, Chao1, phylogenetic diversity whole tree, Shannon's, Pielou's and Simpson's diversity indexes. The search yielded 425 abstracts for initial review, of which 16 met the inclusion criteria. The results suggested that the cervicovaginal microbiota in C. trachomatis-positive women was characterized by Lactobacillus iners dominance, or by a diverse mix of facultative or strict anaerobes. The meta-analysis, instead, did not show any difference in the microbial biodiversity between Chlamydia-positive and healthy women. Additional research is clearly required to deepen our knowledge on the interplay between the resident microflora and C. trachomatis in the genital microenvironment. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea syndrome (OSAS) is an under-recognized clinical condition and is correlated with sleepiness and impaired cognitive function. Objectives: The primary aim of this systematic review, developed within the Sleep@OSA project, was to determine the correlations of obstructive sleep apnea syndrome, daytime sleepiness and sleep-disordered breathing with the risk of car accidents in adult working populations; a secondary aim was to analyze the epidemiologic data with a gender-based approach to identify differences between women and men in the data and in associated risk factors. Methods: Clinical trials and studies reporting data on the frequency of car accidents involving adult working population with daytime sleepiness and/or OSAS compared with a control group of participants were included. Literature searches of free text and MeSH terms were performed using PubMed, Google Scholar, the Cochrane Library and Scopus from 1952 to 3 May 2021. Results and Conclusions: The search strategy identified 2138 potential articles. Of these, 49 papers were included in the qualitative synthesis, and 30 were included in the meta-analysis. Compared with controls, the odds of car accidents were found to be more than double in subjects with OSAS (OR = 2.36; 95% CI 1.92–2.91; p < 0.001), with a similar risk between commercial motor vehicle drivers (OR = 2.80; 95% CI 1.82–4.31) and noncommercial motor vehicle drivers (OR = 2.32; 95% CI 1.84–2.34). No significant correlation was found between sleepiness and car crashes, but subjects with sleep-disordered breathing were at increased risk of car accidents (OR = 1.81; 95% CI 1.42–2.31; p < 0.001). To our surprise, although epidemiological studies on the risk of road accidents in the adult population with OSAS and daytime sleepiness are currently very abundant, specific data on the female population are not available. [ABSTRACT FROM AUTHOR]

Hypoparathyroidism is the only endocrine deficiency for which hormone replacement therapy is not the standard of care. Although conventional treatments may control hypocalcaemia, other complications such as hyperphosphatemia, kidney stones, peripheral calcifications, and bone disease remain unmet needs. This meta‐analysis (PROSPERO registration number CRD42019126881) aims to evaluate and compare the efficacy and safety of PTH1−34 and PTH1−84 in restoring calcium metabolism in chronic hypoparathyroidism. EMBASE, PubMed, and CENTRAL databases were searched for randomized clinical trials or prospective studies published between January 1996 and March 2021. English‐language trials reporting data on replacement with PTH1−34 or PTH1−84 in chronic hypoparathyroidism were selected. Three authors extracted outcomes, one author performed quality control, all assessed the risk of biases. Overall, data from 25 studies on 588 patients were analyzed. PTH therapy had a neutral effect on calcium levels, while lowering serum phosphate (−0.21 mmol/L; 95% confidence interval [CI], −0.31 to −0.11 mmol/L; p < 0.001) and urinary calcium excretion (−1.21 mmol/24 h; 95% CI, −2.03 to −0.41 mmol/24 h; p = 0.003). Calcium phosphate product decreased under PTH1−84 therapy only. Both treatments enabled a significant reduction in calcium and calcitriol supplementation. PTH therapy increased bone turnover markers and lumbar spine mineral density. Quality of life improved and there was no difference in the safety profile between PTH and conventionally treated patients. Results for most outcomes were similar for the two treatments. Limitations of the study included considerable population overlap between the reports, incomplete data, and heterogeneity in the protocol design. In conclusion, the meta‐analysis of data from the largest collection to date of hypoparathyroid patients shows that PTH therapy is safe, well‐tolerated, and effective in normalizing serum phosphate and urinary calcium excretion, as well as enabling a reduction in calcium and vitamin D use and improving quality of life. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Cyclic GMP–phosphodiesterase type 5 (PDE5) inhibition has been shown to counteract maladaptive cardiac changes triggered by diabetes in some but not all studies. We performed a single-center, 20-week, double-blind, randomized, placebo-controlled trial (NCT01803828) to assess sex differences in cardiac remodeling after PDE5 inhibition in patients with diabetic cardiomyopathy. A total of 122 men and women (45 to 80 years) with long-duration (>3 years) and well-controlled type 2 diabetes mellitus (T2DM; HbA1c < 86 mmol/mol) were selected according to echocardiographic signs of cardiac remodeling. Patients were randomly assigned (1:1) to placebo or oral tadalafil (20 mg, once daily). The primary outcome was to evaluate sex differences in cardiac torsion change. Secondary outcomes were changes in cardiovascular, metabolic, immune, and renal function. At 20 weeks, the treatment-by-sex interaction documented an improvement in cardiac torsion (−3.40°, −5.96; −0.84, P = 0.011) and fiber shortening (−1.19%, −2.24; −0.14, P = 0.027) in men but not women. The primary outcome could not be explained by differences in cGMP concentrations or tadalafil pharmacodynamics. In both sexes, tadalafil improved hsa-miR-199-5p expression, biomarkers of cardiovascular remodeling, albuminuria, renal artery resistive index, and circulating Klotho concentrations. Immune cell profiling revealed an improvement in low-grade chronic inflammation: Classic CD14++CD16− monocytes reduced, and Tie2+ monocytes increased. Nine patients (14.5%) had minor adverse reactions after tadalafil administration. Continuous PDE5 inhibition could offer a strategy to target cardiorenal complications of T2DM, with sex- and tissue-specific responses. Further studies are needed to confirm Klotho and hsa-miR-199-5p as markers for T2DM complications. Conditional cardioprotection: Phosphodiesterase 5 (PDE5) inhibition has been shown to have inconsistent cardioprotective effects. Here, Pofi et al. conducted a small phase 4 trial to assess sex differences in cardiac remodeling in patients with diabetes and diabetic cardiomyopathy treated with the PDE5 inhibitor tadalafil. They observed an improvement in cardiac shortening and torsion in men but not women, whereas circulating has-miR-199-5p was reduced and Klotho increased with treatment in both sexes. Certain populations of monocytes were also altered with treatment. Results highlight the importance of considering sex-specific differences in treatment response. [ABSTRACT FROM AUTHOR]

Background: It has been estimated that the incidence of chronic hepatitis C virus (HCV) will not decline over the next 10 years despite the improved efficacy of antiviral therapy because most patients remain undiagnosed and/or untreated. This study aimed to investigate the opinion of relevant target populations on the practicability, effectiveness and best modalities of the test-and-treat approach in the fight against HCV in Italy.Methods: A survey was delivered to patients with HCV from the general population, patients from drug addiction services, hospital physicians and healthcare providers for drug addiction services.Results: For both hospital clinicians and SerD HCPs, tolerability is shown as the most important feature of a suitable treatment. Time to treatment (the time from first contact to initiation of treatment) is deemed important to the success of the strategy by all actors. While a tolerable treatment was the main characteristic in a preferred care pathway for general patients, subjects from drug addiction services indicated that a complete Meet-Test-Treat pathway is delivered within the habitual care center as a main preference. This is also important for SerD HCPs who are a strong reference for their patients; hospital clinicians were less aware of the importance of the patient-HCP relationship in this process.Conclusion: The health system is bound to implement suitable pathways to facilitate HCV eradication. A Meet-Test-Treat program within the drug addiction services may provide good compliance from subjects mainly concerned with virus transmission. [ABSTRACT FROM AUTHOR]

Background: Early and affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer's disease (AD) is a major scientific challenge. Objective: To investigate the neurophysiological hallmarks of sensorimotor cortex function in aMCI under the hypothesis that some may represent the plastic rearrangements induced by neurodegeneration, hence predictors of future conversion to AD. We sought to determine (1) whether the sensorimotor network shows peculiar alterations in patients with aMCI and (2) if sensorimotor network alterations predict long-term disease progression at the individual level. Methods: We studied several transcranial magnetic stimulation (TMS)-electroencephalogram (EEG) parameters of the sensorimotor cortex in a group of patients with aMCI and followed them for 6 years. We then identified aMCI who clinically converted to AD [prodromal to AD-MCI (pAD-MCI)] and those who remained cognitively stable [non-prodromal to AD-MCI (npAD-MCI)]. Results: Patients with aMCI showed reduced motor cortex (M1) excitability and disrupted EEG synchronization [decreased intertrial coherence (ITC)] in alpha, beta and gamma frequency bands compared to the control subjects. The degree of alteration in M1 excitability and alpha ITC was comparable between pAD-MCI and npAD-MCI. Importantly, beta and gamma ITC impairment in the stimulated M1 was greater in pAD-MCI than npAD-MCI. Furthermore, an additional parameter related to the waveform shape of scalp signals, reflecting time-specific alterations in global TMS-induced activity [stability of the dipolar activity (sDA)], discriminated npAD-MCI from MCI who will convert to AD. Discussion: The above mentioned specific cortical changes, reflecting deficit of synchronization within the cortico-basal ganglia-thalamo-cortical loop in aMCI, may reflect the pathological processes underlying AD. These changes could be tested in larger cohorts as neurophysiological biomarkers of AD. [ABSTRACT FROM AUTHOR]

Introduction: The short forms of MacArthur-Bates Communicative Development Inventories (MB-CDI) are widely used for assessing communicative and linguistic development in infants and toddlers. Italian norms for the Words and Gestures (WG) and Words and Sentences (WS) short forms overlap between 18 and 24 months. Objective: To evaluate the agreement between these two forms. Methods: Parents of 104 children aged 18–24 months filled in both questionnaires. Results: The two questionnaires showed high agreement in measuring expressive vocabulary size and the percentile of lexical production and good agreement in identifying children at-risk for language delay (75% of the cases were accurately identified). Both short forms include a list of 100 words and a set of questions investigating potential risk factors for communication and language disorders. Ten children with an expressive vocabulary <10th percentile were compared to 10 with typical language development. Scores for children <10th percentile were significantly lower than their peers, in addition to scores of lexical comprehension, gesture-word, and 2-word combinations, and phonological accuracy, imitation of new words, and decontextualized use of language. Conclusions: Short forms of the Italian MB-CDI can be used interchangeably for evaluating lexical production, but each one offers different quantitative and qualitative information on the behaviours related to language acquisition. [ABSTRACT FROM AUTHOR]

The increasing number and quality of randomized controlled trials (RCTs) employing transcranial direct current stimulation (tDCS) denote the rising awareness of neuroscientific community about its electroceutical potential and opening to include these treatments in the framework of medical therapies under the indications of the international authorities. The purpose of this quantitative review is to estimate the recommendation strength applying the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria and PICO (population, intervention, comparison, outcome) model values for effective tDCS treatments on no-structural diseases, and to provide an estimate of Sham effect for future RCTs. Applying GRADE evaluation pathway, we searched in literature the tDCS-based RCTs in psychophysical diseases displaying a major involvement of brain electrical activity imbalances. Three independent authors agreed on Class 1 RCTs (18 studies) and meta-analyses were carried out using a random-effects model for pathologies sub-selected based on PICO and systemic involvement criteria. The meta-analysis integrated with extensive evidence of negligible side effects and low-cost, easy-to-use procedures, indicated that tDCS treatments for depression and fatigue in Multiple Sclerosis ranked between moderately and highly recommendable. For these interventions we reported the PICO variables, with left vs. right dorsolateral prefrontal target for 30 min/10 days against depression and bilateral somatosensory vs occipital target for 15 min/5 days against MS fatigue. An across-diseases meta-analysis devoted to the Sham effect provided references for power analysis in future tDCS RCTs on these clinical conditions. High-quality indications support tDCS as a promising tool to build electroceutical treatments against diseases involving neurodynamics alterations. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis, the leading cause of bacterial sexually transmitted diseases in developed countries, with around 127 million new cases per year, is mainly responsible for urethritis and cervicitis in women, and urethritis and epididymitis in men. Most C. trachomatis infections remain asymptomatic (>50%) and, hence, untreated, leading to severe reproductive complications in both women and men, like infertility. Therefore, the detection of C. trachomatis as well as the antimicrobial susceptibility testing becomes a priority, and, along the years, several methods have been recommended, like cell culture and direct immunofluorescence (DFA) on cell cultures. Herein, we described the application of In-Cell Western assay (ICW) via Odyssey CLx as a fast, more accessible, and high-throughput platform for the quantification of C. trachomatis and the screening of anti-chlamydial drugs. As a first step, we set up a standard curve by infecting cell monolayers with 2-fold serial dilutions of C. trachomatis Elementary Body (EB) suspension. Then, different unknown C. trachomatis EB suspensions were quantified and the chlamydial susceptibility testing to erythromycin was performed, using the DFA as comparison. Our results showed a very high concordance between these two assays, as evidenced by the enumeration of chlamydial IFUs as well as the determination of erythromycin Minimum Inhibitory Concentration (MIC). In conclusion, the ICW assay may be a promising candidate as an accurate and accessible methodology for C. trachomatis antimicrobial susceptibility testing. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to evaluate clinical, radiographic and laboratory results of ceramic-on-metal (CoM) (hybrid hard bearing) in total hip arthroplasty (THA), associated with a short stem implant. Methods: From a cohort of 37 patients suffering from primary or secondary hip osteoarthritis who underwent THA using CoM bearing, 19 were suitable for this study. All procedures were performed by the same surgeon using a posterior-lateral approach. All patients were compared clinically using the Harris Hip Score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS), 12-item Short Form Health Survey (SF12F/M), and radiographically (offset, CD angle, limb length discrepancy, cup inclination and anteversion, subsidence, osseointegration, heterotopic ossification). Blood samples were collected in order to evaluate chromium (Cr) and cobalt (Co) ions level. Radiographic evaluations were carried out by 3 different blinded surgeons. A statistical analysis was performed. Results: At a mean follow-up of 97 (73–125) months all implanted stems were well-positioned and osseointegrated. Clear improvements were observed for clinical scores comparing preoperative and postoperative values. Radiographic evaluation showed a good ability to restore proper articular geometry. Cr ion analysis revealed values below the safety threshold except for 1 case. Serum levels of Co were below the threshold in all patients. There was a statistically significant correlation only between Cr metal ions and length of follow-up. Conclusions: CoM bearing has proven to be reliable and safe at a mean 8-year follow-up for patients in whom the components were correctly implanted. The rise of blood metal ions was minimal and involved neither systemic or local toxicity nor influenced clinical results. [ABSTRACT FROM AUTHOR]

Parent-mediated intervention is widely used for pre-schoolers with autism spectrum disorder (ASD). Previous studies indicate small-to-moderate effects on social communication skills, but with a wide heterogeneity that requires further research. In this randomized controlled trial (RCT), cooperative parent-mediated therapy (CPMT) an individual parent coaching program for young children with ASD was administered to preschool children with ASD. All children received the same low-intensity psychosocial intervention (LPI) delivered in community settings, to evaluate the potential additional benefit of CPMT. Thirty-four participants with ASD (7 females; 27 males; aged 2, 6, 11 years) and their parents were included in the trial. The primary blinded outcome was social communication skills, assessed using the ADOS-G social communication algorithm score (ADOS-G SC). Secondary outcomes included ASD symptom severity, parent-rated language abilities and emotional/behavioral problems, and self-reported caregiver stress. Evaluations were made at baseline and post-treatment (at 6 months) by an independent multidisciplinary team. Results documented that CPMT showed an additional benefit on LPI with significant improvements of the primary blinded outcome, socio-communication skills, and of some secondary outcomes such as ASD symptom severity, emotional problems and parental stress related to parent–child dysfunctional interaction. No additional benefit was found for language abilities. Findings of our RCT show that CPMT provide an additional significant short-term treatment benefit on ASD core symptoms, when compared with active control group receiving only LPI. [ABSTRACT FROM AUTHOR]

Strokes causing similar lesions and clinical states can be followed by diverse regains of neurological functions, indicating that the clinical recovery can depend on individual modulating factors. A promising line to disclose these factors, to finally open new therapeutic strategies, is to search for individual indices of recovery prognosis. Here, we pursued on strengthening the value of acute phase electrophysiological biomarkers for poststroke functional recovery in a wide group of patients. We enrolled 120 patients affected by a monohemispheric stroke within the middle cerebral artery territory (70 left and 50 right damages) and collected the NIH stroke scale (NIHSS) score in the acute phase (T0, median 4 days) and chronic follow-up (T1, median 6 months). At T0, we executed electrophysiological noninvasive assessment (19-channel electroencephalography (EEG) or 28 channels per side magnetoencephalography (MEG)) of brain activity at rest by means of band powers in the contra- and ipsilesional hemispheres (CLH, ILH) or the homologous area symmetry (HArS). Low-band (2-6 Hz) HArS entered the regression model for predicting the stabilized clinical state (p<0.001), with bilateral impairment correlated with a poor outcome. Present data strengthen the fact that low-band impairment of homologous ipsi- and contralesional hemispheric regions in the acute stroke indicate a negative prognosis of clinical recovery. [ABSTRACT FROM AUTHOR]

Introduction and Aims: People who inject drugs (PWID) constitute the largest reservoir of hepatitis C virus (HCV). Although effective medications are available and access to care is universal in Italy, the proportion of PWID receiving appropriate care remains low.Design and Methods: To identify the major barriers for PWID to HCV treatment we surveyed a large sample of practitioners working in outpatient addiction centres (SerDs). The survey was conducted in two stages and involved 30.3% of SerDs operating in Italy. In the first, SerD physicians completed a questionnaire designed with a Delphi structure. In the second, SerD practitioners completed a targeted questionnaire to identify barriers to four SerD services in HCV management: screening, referral, treatment and harm reduction.Results: The first-stage questionnaire, in which a Delphi and RAND-UCLA method was used, revealed a lack of agreement among the physicians about barriers to health care. The more detailed second-stage questionnaire indicated the barriers to delivering specific SerD services. As regarded the delivery of all four services, the major reasons for treating <50% of patients were: physician and nurse understaffing, technical, economic and logistic issues. In contrast, the practitioners who responded that they follow protocol recommendations often deliver all four services to >50% of patients.Discussion and Conclusions: HCV treatment remains out of reach for many PWID attending a drug treatment centre in Italy. To meet the World Health Organisation (WHO) target, there is a need to increase economic, technical and staff support at treatment centres using the protocols and the universal health care already in place. [ABSTRACT FROM AUTHOR]

Objective: To clarify whether the clinical response after the first 2 cycles with Onabotulinumtoxin A can accurately predict the long‐term response. Background: Onabotulinumtoxin‐A (OBT‐A) is an approved preventive treatment option for chronic migraine (CM). Nowadays, it remains to be clarified if the treatment has to be prolonged for at least an entire year (4 injections every 3 months – ie, quarterly, as proposed in the PREEMPT trials) or it can be halted after the second or third injection if not clinically effective. Design and Methods: We conducted a multicenter observational cohort study based on real‐life data on the usage of OBT‐A in CM patients from 2 Italian headache centers, Roma Campus Bio‐Medico and Milano Besta, adopting the whole 4‐injections protocol. We performed a retrospective analysis of medical records of consecutive patients treated in the 2 centers. The main statistical analysis aimed to evaluate longitudinal measures related to headache (monthly headache frequency, monthly number of analgesic drugs, MIDAS). We hypothesized from our clinical practice with OBT‐A that only 2 cycles of treatment were not enough to actually define the non‐responder status to botulinum toxin A and that probably a longer time of treatment is needed to get the condition of long‐term (delayed) responder. Results: We considered 115 patients from the 2 centers: 53 in Roma and 62 in Milano. Regarding the main analysis, a clear improvement in each measure was obtained at the 6 months assessment and maintained up to 12 months. Comparing patients with <30% and ≥30% reduction in headache frequency between T0 and T2 or T4 (respectively, "Non‐Responders" and "Responders"), we found that the agreement between the classification Responders/Non‐Responders at T2 and T4 was not very high (79/104 = 76.0%, with a "moderate" Cohen's Kappa of 0.51), suggesting that the status at T4 is not fully predictable by the status at T2 (λ = 0.47). Responders for headache frequency at T4 were 54.8%. Among Responders at T2, Responders at T4 were 47/62 = 75.8% (95% CI: 64.5%, 85.5%), while among Non‐Responders at T2, Responders at T4 were 10/42 = 23.8% (95% CI: 11.9%, 38.1%). Similarly, even when considering the 50% reduction in painkillers consumption or in MIDAS total score between T0 and T2 as possible prognostic factors, the changes occurring at T4 are not strongly predictable by those at T2. Conclusions: A ≥30% reduction in headache frequency at T2 cut‐off is not adequate in predicting a late response to treatment: more than a quarter of excluded patients would miss a clinical improvement with an ongoing treatment, while in a similar percentage of Responders the treatment would lose efficacy. Results from our real‐life study suggest that we possibly have to postpone the definition of Responder/Non‐Responder to OBT‐A at least after 1 year of treatment (4 cycles). [ABSTRACT FROM AUTHOR]

One of the most popular and widely used parent report instruments for assessing early language acquisition is the MacArthur-Bates Communicative Development Inventories (MB-CDI). This study compares normative data of the Italian Words and Sentences complete form (WS-CF) and short form (WS-SF). The samples included 752 children for the WS-CF and 816 children for the WS-SF designed for children aged 18–36 months. The concordance between WS-SF and WS-CF is analyzed in a subgroup of 65 children. The results revealed strong correlations between WS-CF and WS-SF in both lexical and grammar skills as well as strong relationship between lexical and grammar skills. There was a high percentage agreement (97%) between the two forms for scores below the 10th percentile, suggesting that the two forms may be used interchangeably in order to describe vocabulary and grammatical development. [ABSTRACT FROM AUTHOR]

Aims: Several drug classes are now available to achieve a satisfactory metabolic control in patients with type 2 diabetes (T2DM), but patients' preferences may differ.Methods: In a discrete-choice experiment, we tested T2DM patients' preferences for recent antidiabetic drugs, in the event that their treatment might require intensification. The following attributes were considered: (a) route of administration; (b) type of delivery; (c) timing; (d) risk of adverse events; (e) effects on body weight. Twenty-two possible scenarios were built, transferred into 192 paired choices and proposed to 491 cases naïve to injectable treatments and 171 treated by GLP-1 receptor agonists (GLP-1RAs). Analyses were performed by descriptive statistics and random effects logit regression model.Results: Preferences according to dosing frequency, risk of nausea and urinary tract infections (UTls) were similar across groups, age, sex and BMI. Administration route and delivery type accounted for 1/3 of relative importance; the risk of UTIs, nausea and dosing frequency for ≈ 20% each, and weight loss for only 6%. Two significant interactions emerged (p < 0.01): type of delivery × group, and weight change × BMI class. Irrespective of previous treatment, the three preferred choices were injectable, coupled with weekly dosing and a ready-to-use device (first two choices). In a regression model, being naïve or non-naïve changed the ranking of preferences (p < 0.001), and the order was systematically shifted towards injectable medications in non-naïve subjects.Conclusion: Easy-to-deliver, injectable treatment is preferred in T2DM, independently of treatment history, and previous experience with GLP-1RAs strengthens patients' willingness to accept injectable drugs. [ABSTRACT FROM AUTHOR]

Oxidative status may play a role in chronic inflammation and neurodegeneration which are considered critical etiopathogenetic factors in Multiple Sclerosis (MS), both in the early phase of the disease and in the progressive one. The aim of this study is to explore oxidative status related to iron metabolism in peripheral blood of stable Relapsing-Remitting MS with low disability. We studied 60 Relapsing-Remitting MS patients (age 37.2 ± 9.06, EDSS median 1.0), and 40 healthy controls (age 40.3 ± 10.86). We measured total hydroperoxides (dROMs test) and Total Antioxidant Status (TAS), along with the iron metabolism biomarkers: Iron (Fe), ferritin (Ferr), transferrin (Tf), transferrin saturation (Tfsat), and ceruloplasmin (Cp) panel biomarkers [concentration (iCp) and enzymatic activity (eCp), copper (Cu), ceruloplasmin specific activity (eCp:iCp), copper to ceruloplasmin ratio (Cu:Cp), non-ceruloplasmin copper (nCp-Cu)]. We computed also the Cp:Tf ratio as an index of oxidative stress related to iron metabolism. We found lower TAS levels in MS patients than in healthy controls (CTRL) and normal reference level and higher dROMs and Cp:Tf ratio in MS than in healthy controls. Cp and Cu were higher in MS while biomarkers of iron metabolism were not different between patients and controls. Both in controls and MS, dROMs correlated with iCp (CTRL r = 0.821, p < 0.001; MS r = 0.775 p < 0.001) and eCp (CTRL r = 0.734, p < 0.001; MS r = 0.820 p < 0.001). Moreover, only in MS group iCp correlated negatively with Tfsat (r = -0.257, p = 0.047). Dividing MS patients in "untreated" group and "treated" group, we found a significant difference in Fe values [ F (2, 97) = 10.136, p < 0.001]; in particular "MS untreated" showed higher mean values (mean = 114.5, SD = 39.37 μg/dL) than CTRL (mean 78.6, SD = 27.55 μg/dL p = 0.001) and "MS treated" (mean = 72.4, SD = 38.08 μg/dL; p < 0.001). Moreover, "MS untreated" showed significantly higher values of Cp:Tf (mean = 10.19, SD = 1.77∗10-2; p = 0.015), than CTRL (mean = 9.03, SD = 1.46 ∗10-2). These results suggest that chronic oxidative stress is relevant also in the remitting phase of the disease in patients with low disability and short disease duration. Therefore, treatment with antioxidants may be beneficial also in the early stage of the disease to preserve neuronal reserve. [ABSTRACT FROM AUTHOR]

Objectives. It has been already confirmed that retinal neurodegeneration has a predictive value in the development of microvascular alterations in diabetic retinopathy. However, no data are available on the association between neuroretinal dysfunction and peripheral motor unit loss. Our study, therefore, was aimed at investigating the hypothesis that retinal neurodegeneration could be considered an early marker of diabetic peripheral neuropathy (DPN). Methods. 20 T1DM patients with no symptoms/signs of peripheral polyneuropathy, without DR or with very mild nonproliferative DR, and 14 healthy controls (C) age- and gender-matched were enrolled. The following electrophysiological tests were performed: standard nerve conduction studies (NCS) and incremental motor unit number estimation (MUNE) from the abductor hallux (AH) and abductor digiti minimi (ADM). Neuroretinal function was studied by multifocal electroretinogram (MfERG) recordings, measuring response amplitude density (RAD) and implicit time (IT) from rings and sectors of superior (S)/inferior (I)/temporal (T)/nasal (N) macular sectors up to 10 degrees of foveal eccentricity. Results. MfERG RADs from rings and sectors were significantly reduced in T1DM (p<0.05) vs. C. ADM MUNE and AH MUNE were significantly decreased in T1DM (p=0.039 and p<0.0001, respectively) vs. C. A positive correlation between mean MfERG RADs from the central 5 degrees of the four (S, I, T, and N) macular sectors and lower limb motor unit number (r=0.50, p=0.041; r=0.64, p=0.005; r=0.64, p=0.006; and r=0.61, p=0.010, respectively) was observed in T1DM patients. No abnormalities of NCS were found in any subject. Conclusions. The motor unit loss on the one hand and neuroretinal dysfunction on the other hand are already present in T1DM patients without DPN. The relationship between neuroretinal dysfunction and motor unit decline supports the hypothesis that neuroretina may represent a potential “window” to track the early neurogenic damage in diabetes. [ABSTRACT FROM AUTHOR]

Objective: Mild cognitive impairment (MCI) is a condition intermediate between physiological brain aging and dementia. Amnesic-MCI (aMCI) subjects progress to dementia (typically to Alzheimer-Dementia = AD) at an annual rate which is 20 times higher than that of cognitively intact elderly. The present study aims to investigate whether EEG network Small World properties (SW) combined with Apo-E genotyping, could reliably discriminate aMCI subjects who will convert to AD after approximately a year.Methods: 145 aMCI subjects were divided into two sub-groups and, according to the clinical follow-up, were classified as Converted to AD (C-MCI, 71) or Stable (S-MCI, 74).Results: Results showed significant differences in SW in delta, alpha1, alpha2, beta2, gamma bands, with C-MCI in the baseline similar to AD. Receiver Operating Characteristic(ROC) curve, based on a first-order polynomial regression of SW, showed 57% sensitivity, 66% specificity and 61% accuracy(area under the curve: AUC=0.64). In 97 out of 145 MCI, Apo-E allele testing was also available. Combining this genetic risk factor with Small Word EEG, results showed: 96.7% sensitivity, 86% specificity and 91.7% accuracy(AUC=0.97). Moreover, using only the Small World values in these 97 subjects, the ROC showed an AUC of 0.63; the resulting classifier presented 50% sensitivity, 69% specificity and 59.6% accuracy. When different types of EEG analysis (power density spectrum) were tested, the accuracy levels were lower (68.86%).Interpretation: Concluding, this innovative EEG analysis, in combination with a genetic test (both low-cost and widely available), could evaluate on an individual basis with great precision the risk of MCI progression. This evaluation could then be used to screen large populations and quickly identify aMCI in a prodromal stage of dementia. Ann Neurol 2018 Ann Neurol 2018;84:302-314. [ABSTRACT FROM AUTHOR]

The population of industrialized nations is progressively aging, with Italy having one of the most elderly populations in the world. Natural aging may be associated with physical and cognitive impairments, often straining public resources. The present study aims to investigate the influence of gender on wellness of the nonagenarians. We evaluated quality of life among nonagenarians living in the Mugello area, an Italian location with a large population of individuals > 90 years, using the Health Survey Scoring SF-12. The 15-item Geriatric Depression Scale and Basic and Instrumental Activity of Daily Living scales were also assessed. The Mini-Mental State Examination was used to evaluate the cognitive status. In the current survey, women outnumbered men 2.7:1 confirming their higher longevity. However, on the basis of SF-12 scores, nonagenarian women felt worse than men, both physically (mean: women = 41.8 vs men = 44.4, p = 0.004) and mentally (mean: women = 46.7 vs men =48.5, p = 0.034), and their depression rates were higher: considering a General Depression Scale score ≥ 5 as a possible depression status; 37.5% of men reported depression vs. 48.5% of women (p = 0.021). Significant differences were observed also in daily activities, both basic (median: woman = 3 vs men = 5, p < 0.001) and instrumental (median woman = 1 vs me = 3, p < 0.001). Despite prior reports showing that women perform better than men in aging, our study confirms data reported in most national and European surveys: women live longer than men, but with poorer quality of life. The current study confirms the phenomenon known as the "male-female health-survival paradox." [ABSTRACT FROM AUTHOR]

In this paper, we pose the following working hypothesis: in humans, transcranial electric stimulation (tES) with a time course that mimics the endogenous activity of its target is capable of altering the target's excitability. In our case, the target was the primary motor cortex (Ml). We identified the endogenous neurodynamics of hand Ml's subgroups of pyramidal neuronal pools in each of our subjects by applying Functional Source Separation (FSS) to their EEG recordings. We then tested whether the corticospinal excitability of the hand representation under the above described stimulation, which we named transcranial individual neurodynamics stimulation (tIDS), was higher than in the absence of stimulation (baseline). As a check, we compared tIDS with the most efficient noninvasive facilitatory corticospinal tES known so far, which is 20 Hz transcranial alternating current stimulation (tACS).Thecontrol conditions were as follows: (1) sham, (2) transcranial random noise stimulation (tRNS) in the same frequency range as tIDS (1-250 Hz), and (3) a low current tIDS (tlDSlow). Corticospinal excitability was measured with motor-evoked potentials under transcranial magnetic stimulation. The mean motor-evoked potential amplitude increase was 31% of the baseline during tIDS (p < 0.001), and it was 15% during tACS (p = 0.096). tRNS, tIDSlow, and sham induced no effects. Whereas tACS did not produce an enhancement in any subject at the individual level, tIDS was successful in producing an enhancement in 8 of the 16 subjects. The results of the present proof-of-principle study showed that proper exploitation of local neurodynamics can enhance the efficacy of personalized tES. [ABSTRACT FROM AUTHOR]

Management of medication overuse headache (MOH) requires abrupt suspension of overused drugs either alone or in association with a detoxification protocol to prevent withdrawal. However, there is no consensus about which suspension strategy is the most effective. Moreover, reliable data about the possible mid-term effect of detoxification are not available. The objective of this study was to evaluate whether a bridge therapy consisting of a 5-day i.v. infusion of methylprednisolone and diazepam determines a significant reduction in headache frequency and drug assumption during the detoxification protocol (day 5) and in the first 3 months in patients with MOH. We conducted a retrospective non-randomized before-and-after study comparing patients with MOH undergoing a bridge therapy protocol (5-day infusion of methylprednisolone, diazepam) with those who refused the treatment and were only recommended to suspend overused painkillers. Both groups started a prophylactic treatment and were followed-up for 3 months. At day 5, 82% of our patients were headache-free; moreover, 48% of the patients did not take any painkiller during the 5-day treatment. Three months after, the intervention group showed a greater reduction of monthly headache days (9.4 vs 3.0) and drugs (19.7 vs 6.5), a greater rate of patients with a ≥ 50% reduction of monthly headaches (p = 0.019) and symptomatic drug consumption (p = 0.000), than the control group. The methylprednisolone and diazepam detoxification protocol reduced headache attacks and drug assumption immediately and in the first 3 months after the intervention, concurring to improve the effect of a new prophylactic therapy. [ABSTRACT FROM AUTHOR]

Aims: Recent studies have identified neuroretinal abnormalities in persons affected by diabetes mellitus, before the onset of microvascular alterations. However, the role of glycemic variability (GV) on early retinal neurodegeneration is still not clarified. Methods: To explore the relationship between glycemic control and neuroretinal characteristics, 37 persons with Type 1 diabetes mellitus (Type 1 DM) divided into two groups with no signs (noRD) and with mild non-proliferative diabetic retinopathy (NPDR) compared to 13 healthy control participants ( C) were recruited. All persons underwent an optical coherence tomography with automatic segmentation of all neuroretinal layers. Measurements of mean of nasal ( N)/temporal ( T)/superior ( S)/inferior ( I) macular quadrants for individual layer were also calculated. Metabolic control was evaluated by glycated hemoglobin (HbA1c), and indexes of GV were calculated from continuous glucose monitoring. Results: The difference among the three groups in terms of RNFL thickness was significantly dependent on quadrant ( F(6;132) = 2.315; p = 0.037). This interaction was due to a specific difference in RNFL-N thickness, where both Type 1 DM groups showed a similar reduction versus C (−3.9 for noDR and −4.9 for NPDR), without any relevant difference between them (−1.0). Inner nuclear layer (INL) was increased in all quadrants in the two Type 1 DM groups compared to C (mean difference = 7.73; 95% CI: 0.32-15.14, p = 0.043; mean difference = 7.74; 95% CI: 0.33-15.15, p = 0.043, respectively). A negative correlation between RNFL-N and low blood glucose index ( r = −0.382, p = 0.034) and positive correlation between INL and continuous overall net glycemic action −1, −2, −4 h ( r = 0.40, p = 0.025; r = 0.39, p = 0.031; r = 0.41, p = 0.021, respectively) were observed in Type 1 DM patients. The triglycerides were positively and significantly correlated to INL ( r = 0.48, p = 0.011), in Type 1 DM subjects. GV and triglycerides resulted both independent predictors of increased INL thickness. No correlation was found with HbA1c. Conclusions: Early structural damage of neuroretina in persons with Type 1 DM patients is related to glucose fluctuations. GV should be addressed, even in the presence of a good metabolic control. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction involves 40-65 % of multiple sclerosis (MS) patients. It can be detected in all MS phenotypes from the early stages of the disease, and it tends to progress over time. Minimal Assessment of Cognitive Function in MS (MACFIMS) has been proved to be the most sensitive and comprehensive battery available for MS cognitive assessment in the English population. In Italy, MACFIMS applicability is limited in everyday clinical practice since the overall validity of this battery in the Italian MS population has never been demonstrated. The aim of this study was to translate/cross-culturally adapt and validate an Italian version of the MACFIMS. A total of 130 MS patients and 60 healthy controls (HCs) were enrolled and evaluated with an Italian version of the MACFIMS. All tests discriminated MS patients from HCs; according to the literature, approximately more than half of MS patients (70.8 %) exhibit cognitive impairment. Principal component analysis showed four distinct components: visual-spatial memory/processing speed, working memory, executive functions and verbal memory. Our study is the first to validate an Italian version of the MACFIMS. Several aspects of validity have been demonstrated: criterion and, partially, construct. Future work will investigate the longitudinal course of neuropsychological dysfunction in Italian MS patients using these measures. [ABSTRACT FROM AUTHOR]

Several studies have shown that, in spite of the fact that motor symptoms manifest late in the course of Alzheimer's disease (AD), neuropathological progression in the motor cortex parallels that in other brain areas generally considered more specific targets of the neurodegenerative process. It has been suggested that motor cortex excitability is enhanced in AD from the early stages, and that this is related to disease's severity and progression. To investigate the neurophysiological hallmarks of motor cortex functionality in early AD we combined transcranial magnetic stimulation (TMS) with electroencephalography (EEG). We demonstrated that in mild AD the sensorimotor system is hyperexcitable, despite the lack of clinically evident motor manifestations. This phenomenon causes a stronger response to stimulation in a specific time window, possibly due to locally acting reinforcing circuits, while network activity and connectivity is reduced. These changes could be interpreted as a compensatory mechanism allowing for the preservation of sensorimotor programming and execution over a long period of time, regardless of the disease's progression. Hum Brain Mapp 37:2083-2096, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Meta-analyses demonstrate copper involvement in Alzheimer's disease (AD), and the systemic ceruloplasmin status in relation to copper is an emerging issue. To deepen this matter, we evaluated levels of ceruloplasmin concentration, ceruloplasmin activity, ceruloplasmin specific activity (eCp/iCp), copper, non-ceruloplasmin copper iron, transferrin, the ceruloplasmin/transferrin ratio, and the APOE genotype in a sample of 84 AD patients and 58 healthy volunteers. From the univariate logistic analyses we found that ceruloplasmin concentration, eCp/iCp, copper, transferrin, the ceruloplasmin/transferrin ratio, and the APOE genotype were significantly associated with the probability of AD. In the multivariable logistic regression analysis, we selected the best subset of biological predictors by the forward stepwise procedure. The analysis showed a decrease of the risk of having AD for eCp/iCp (p = 0.001) and an increase of this risk for non-ceruloplasmin copper (p = 0.008), age (p = 0.001), and APOE-ɛ4 allele (p <  0.001). The estimated model showed a good power in discriminating AD patients from healthy controls (area under curve: 88% ; sensitivity: 66% ; specificity 93%). These data strength the breakdown of copper homeostasis and propose eCp/iCp as a reliable marker of ceruloplasmin status. [ABSTRACT FROM AUTHOR]

Objective: ERCC1 (excision repair cross-complementation group 1) expression predicts survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation. In order to evaluate the predictive role in the adjuvant setting, we investigated ERCC1 expression in radically resected HNSCC patients who underwent surgery and cisplatin chemoradiation. Methods: ERCC1 expression levels were determined by immunohistochemistry in primary tumor tissues from 48 patients with stage III-IV cancers. The median follow-up was 38.5 months (range: 5-121). Results: High ERCC1 expression was observed in 36 (75%) patients. Univariate analysis showed that patients with high levels of ERCC1 had significantly worse disease-free survival and overall survival (OS) than patients with low levels (HR = 7.15; 95% CI, 1.68-30.35; p = 0.008 and HR = 9.90; 95% CI, 1.33-73.96; p = 0.025, respectively). In the multivariate analysis, high ERCC1 expression (HR = 7.36; 95% CI, 1.72-31.4; p = 0.007) together with high-risk category (HR = 2.69; 95% CI, 1.01-7.18; p = 0.048) were the best predictors for relapse. High ERCC1 expression was the only unfavorable independent determinant for OS (HR = 9.53; 95% CI, 1.27-71.35; p = 0.028). Conclusions: This investigation suggests that ERCC1 expression might be useful to predict prognosis in radically resected HNSCC patients treated with surgery and chemoradiation. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Rationale: We recently reported on the efficacy of a personalized transcranial direct current stimulation (tDCS) treatment in reducing multiple sclerosis (MS) fatigue. The result supports the notion that interventions targeted at modifying abnormal excitability within the sensorimotor network could represent valid non-pharmacological treatments. Objective: The present work aimed at assessing whether the mentioned intervention also induces changes in the excitability of sensorimotor cortical areas. Method: Two separate groups of fatigued MS patients were given a 5-day tDCS treatments targeting, respectively, the whole body somatosensory areas (S1wb) and the hand sensorimotor areas (SM1hand). The study had a double blind, sham-controlled, randomized, cross-over (Real vs. Sham) design. Before and after each treatment, we measured fatigue levels (by the modified fatigue impact scale, mFIS), motor evoked potentials (MEPs) in response to transcranial magnetic stimulation and somatosensory evoked potentials (SEPs) in response to median nerve stimulation. We took MEPs and SEPs as measures of the excitability of the primary motor area (M1) and the primary somatosensory area (S1), respectively. Results: The Real S1wb treatment produced a 27% reduction of the mFIS baseline level, while the SM1hand treatment showed no difference between Real and Sham stimulations. M1 excitability increased on average 6% of the baseline in the S1wb group and 40% in the SM1hand group. Observed SEP changes were not significant and we found no association between M1 excitability changes and mFIS decrease. Conclusion: The tDCS treatment was more effective against MS fatigue when the electrode was focused on the bilateral whole body somatosensory area. Changes in S1 and M1 excitability did not correlate with symptoms amelioration. Significance: The neuromodulation treatment that proved effective against MS fatigue induced only minor variations of the motor cortex excitability, not enough to explain the beneficial effects of the intervention. [ABSTRACT FROM AUTHOR]

Aim: To examine whether the results at 4 years of age of the developmental questionnaire QS4-G can predict the outcome of cognitive, neuropsychological and academic abilities 4-6 years later. The QS4-G is a validated parental questionnaire designed for the screening and surveillance of the neuropsychological and behavioural developmental status of 4-year-olds (93 questions).Methods: Longitudinal prospective study on a subsample of the QS4-G validation original sample was conducted. According to previous results, the sample was divided into two groups: 'at risk' and 'not at risk'. Sensitivity, specificity, accuracy and likelihood ratios were assessed and referred to outcomes.Results: Thirty-five children were classified as 'not at risk' and 16 as 'at risk'. There were significant associations between past QS4-G score and cognitive, neuropsychological and academic abilities 4-6 years later. With the same cut-off identified at the first cross-sectional study, sensitivity and specificity for difficulties in cognitive development were 90% and 83% while in the neuropsychological abilities 62% and 90%, respectively. A lower predictive validity was found for difficulties in academic abilities (sensitivity 43%, specificity 86%). QS4-G specific area scores showed significant correlations with related academic tests at follow-up (rho range: 0.404-0.565, P < 0.005).Conclusions: QS4-G shows good predictive validity for cognitive development and neuropsychological abilities. The risk of false negatives for academic abilities can be reduced by analysing the specific area results of QS4-G, which show good correlations with related tests at follow-up. [ABSTRACT FROM AUTHOR]

Aim To examine whether the results at 4 years of age of the developmental questionnaire QS4-G can predict the outcome of cognitive, neuropsychological and academic abilities 4-6 years later. The QS4-G is a validated parental questionnaire designed for the screening and surveillance of the neuropsychological and behavioural developmental status of 4-year-olds (93 questions). Methods Longitudinal prospective study on a subsample of the QS4-G validation original sample was conducted. According to previous results, the sample was divided into two groups: 'at risk' and 'not at risk'. Sensitivity, specificity, accuracy and likelihood ratios were assessed and referred to outcomes. Results Thirty-five children were classified as 'not at risk' and 16 as 'at risk'. There were significant associations between past QS4-G score and cognitive, neuropsychological and academic abilities 4-6 years later. With the same cut-off identified at the first cross-sectional study, sensitivity and specificity for difficulties in cognitive development were 90% and 83% while in the neuropsychological abilities 62% and 90%, respectively. A lower predictive validity was found for difficulties in academic abilities (sensitivity 43%, specificity 86%). QS4-G specific area scores showed significant correlations with related academic tests at follow-up (rho range: 0.404-0.565, P < 0.005). Conclusions QS4-G shows good predictive validity for cognitive development and neuropsychological abilities. The risk of false negatives for academic abilities can be reduced by analysing the specific area results of QS4-G, which show good correlations with related tests at follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Transcranial electric stimulations (tES) with amplitude-modulated currents are promising tools to enhance neuromodulation effects. It is essential to select the correct cortical targets and inhibitory/excitatory protocols to reverse changes in specific networks. We aimed at assessing the dependence of cortical excitability changes on the current amplitude of 20 Hz transcranial alternating current stimulation (tACS) over the bilateral primary motor cortex. Methods: We chose two amplitude ranges of the stimulations, around 25 μA/cm2 and 63 μA/cm2 from peak to peak, with three values (at steps of about 2.5%) around each, to generate, respectively, inhibitory and excitatory effects of the primary motor cortex. We checked such changes online through transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs). Results: Cortical excitability changes depended upon current density (p = 0.001). Low current densities decreased MEP amplitudes (inhibition) while high current densities increased them (excitation). Conclusions: tACS targeting bilateral homologous cortical areas can induce online inhibition or excitation as a function of the current density. [ABSTRACT FROM AUTHOR]

Background: Over time, exposure to cerebrovascular risk factors and carotid artery disease may cause multiple asymptomatic brain cortical and subcortical microinfarcts, which are commonly found at brain autopsy. So far, lack of convenient neuroimaging tools limited the investigation of grey matter ischemic damage in vivo. We applied the Double Inversion Recovery (DIR) sequence to explore the impact of carotid artery disease on intracortical ischemic lesion load in vivo, taking into account the impact of demographic characteristics and vascular risk factors. Methods: DIR was acquired in 62 patients with common cerebrovascular risk factors stratified in three groups according to carotid artery disease severity. Intracortical lesions scored on DIR (DIRlns) were classified by vascular territory, lobe and hemisphere. White matter hyperintensities (WMHs) volume was also quantified on Fluid Attenuated Inversion Recovery sequence (FLAIR). Results: Among demographic characteristics and cerebrovascular risk variables explored, General Linear Model indicated that age and carotid artery disease were significantly associated to DIRlns. After correcting for age, DIRlns load was found to be significantly dependent on carotid artery stenosis severity (F(2, 58) = 5.56, p = 0.006). A linear positive correlation between DIRlns and WMHs was found after correcting for age (p = 0.003). Conclusions: Carotid disease severity is associated with DIRlns accrual. Microembolism and impaired cerebral hemodynamics may act as physiopathological mechanisms underlying cortical ischemic damage. The role of other factors, such as small vessel disease and the possible interaction with carotid disease, remains to be further explored. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]