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Understanding the actual distribution of different Legionella species in water networks would help prevent outbreaks. Culture investigations followed by serological agglutination tests, with poly/monovalent antisera, still represent the gold standard for isolation and identification of Legionella strains. However, also MALDI-TOF and mip-gene sequencing are currently used. This study was conducted to genetically correlate strains of Legionella non pneumophila (L-np) isolated during environmental surveillance comparing different molecular techniques. Overall, 346 water samples were collected from the water system of four pavilions located in a hospital of the Apulia Region of Italy. Strains isolated from the samples were then identified by serological tests, MALDI-TOF, and mip-gene sequencing. Overall, 24.9% of water samples were positive for Legionella, among which the majority were Legionella pneumophila (Lpn) 1 (52.3%), followed by Lpn2-15 (20.9%), L-np (17.4%), Lpn1 + Lpn2-15 (7.1%), and L-np + Lpn1 (2.3%). Initially, L-np strains were identified as L. bozemanii by monovalent antiserum, while MALDI-TOF and mip-gene sequencing assigned them to L. anisa. More cold water than hot water samples were contaminated by L. anisa (p L. anisa strains. Eleven out of 14 strains identified in all four pavilions showed 100% of similarity upon PFGE analysis. RAPD, Rep-PCR, and SAU-PCR showed greater discriminative power than PFGE.

Purpose\ud The use of high-performance gradient systems (i.e., high gradient strength and/or high slew rate) for human MRI is limited by physiological effects (including the elicitation of magnetophosphenes and peripheral nerve stimulation (PNS)). These effects, in turn, depend on the interaction between time-varying magnetic fields and the body, and thus on the participant’s position with respect to the scanner’s isocenter. This study investigated the occurrence of magnetophosphenes and PNS when scanning participants on a high-gradient (300 mT/m) system, for different gradient amplitudes, ramp times, and participant positions.\ud \ud Methods\ud Using a whole-body 300 mT/m gradient MRI system, a cohort of participants was scanned with the head, heart, and prostate at magnet isocenter and a train of trapezoidal bipolar gradient pulses, with ramp times from 0.88 to 4.20 ms and gradient amplitudes from 60 to 300 mT/m. Reports of magnetophosphenes and incidental reports of PNS were obtained. A questionnaire was used to record any additional subjective effects.\ud \ud Results\ud Magnetophosphenes were strongly dependent on participant position in the scanner. 87% of participants reported the effect with the heart at isocenter, 33% with the head at isocenter, and only 7% with the prostate at isocenter. PNS was most widely reported by participants for the vertical gradient axis (67% of participants), and was the dominant physiological effect for ramp times below 2 ms.\ud \ud Conclusion\ud This study evaluates the probability of eliciting magnetophosphenes during whole-body imaging using an ultra-strong gradient MRI system. It provides empirical guidance on the use of high-performance gradient systems for whole-body human MRI.

(1) Background: Dural arteriovenous fistulas (DAVF) represent a rare acquired intracranial vascular malformation, with a variety of clinical signs and symptoms, which make their diagnosis difficult. Intracranial hemorrhage is one of the most serious clinical manifestations. In this paper the authors’ goal was to verify the accuracy and utility of contrast-enhanced brain CT angiography (CTA) for the identification and the characterization of dural arteriovenous fistulas (DAVFs) in patients who presented with brain hemorrhage compared to 3D digital subtraction angiography (3D DSA); (2) a retrospective study of 26 patients with DAVFs who presented with intracranial hemorrhage to our institution was performed. The information reviewed included clinical presentation, location and size of hemorrhage, brain CTA and 3D DSA findings; (3) results: 61% (16/26) of DAVFs were identified by CTA. The vast majority of patients were male (69%, 18/26) and the most common presenting symptom was sudden onset headache. All DAVFs had cortical venous drainage and about one-third were associated with a venous varix. The most common location was tentorial (73%, 19/26); (4) conclusions: CTA can represent a valid alternative diagnostic method to 3D DSA for the study of DAVF in the initial and preliminary diagnostic approach, especially in emergency situations. In fact, it represents a fast, inexpensive, non-invasive and above all, easily accessible and available diagnostic technique, unlike DSA or MRI, allowing to provide information necessary for the identification, classification and treatment planning of DAVFs.

The consumption of hot drinks dispensed from vending machines has become a common practice, both in workplaces and during free time. Every day, millions of bulk drinks are sold, but the quality of the products distributed may not always be guaranteed, as it is related to many factors such as the quality of the water, the raw materials used, and the effectiveness of the equipment’s cleaning system. The purpose of this study is to evaluate the hygienic-sanitary requirements of hot drinks and vending machine surfaces. The investigation highlighted the microbial contamination of both coffee and vending machine surfaces. Although the ”coffee break” is usually considered a moment of pleasure, apparently not subject to specific jurisdiction, the products dispensed can represent a health risk if the hygienic conditions are not fully respected. Therefore, official controls carried out by the Prevention Department represent a suitable way for evaluating and guaranteeing the hygienic-sanitary requirements, providing for corrective actions, when needed, to protect consumers.

Coastal habitats provide important ecosystem services, such as the maintenance of ecological sustainability, water quality regulation, nutrient recycling, and sandy beaches which are important areas for recreation and tourism. The quality of seawater is generally measured by determining the concentrations ofEscherichia coliand intestinal Enterococci, which might be affected by the persistent populations of these bacteria in sand. Sand might thus be a significant source of pathogen exposure to beachgoers. The quality of coastal recreational waters can also be affected by eutrophication, water discoloration, and harmful algal blooms, which pose additional human health risks. Here, we conducted a monitoring of the beaches quality along the Taranto Gulf by determining the concentrations of fecal indicator organisms, as well as other parameters that are not traditionally measured (physicochemical parameters,Pseudomonas aeruginosa, and harmful microalgae), in shallow seawater and sand sampled from three beaches. The concentrations of bacteria were determined using both standard microbiological methods and the IDEXX system. Our results demonstrate the utility of measuring a greater number of parameters in addition to those conventionally measured, as well as the importance of assessing the health risks posed by the sand matrix. Additional work is needed to develop rapid analytical techniques that could be used to monitor the microbiological parameters of solid matrices.

Healthcare-related infections are sustained by various bacteria and fungi. In recent years, various technologies have emerged for the sanitation of healthcare-related environments. This study evaluated the effectiveness of a no-touch disinfection system that aerosolizes 5% hydrogen peroxide and 10% ethyl alcohol. After selecting an environment, the Total Bacterial Count and the Total Fungal Count in the air and on a surface of the room were determined to evaluate the effectiveness of the aerosolization system. In addition, sterile stainless-steel plates inoculated with S. aureus, P. aeruginosa, and Aspergillus spp. isolated from hospitalized patients and reference strains were used to evaluate the effectiveness of the system. For each organism, three plates were used: A (cleaned), B (not cleaned), and C (control). The A plates were treated with non-ionic surfactant and the aerosolization system, the B plates were subjected to the aerosolization system, and the plates C were positioned outside the room that was sanitized. Following sanitization, air and surface sampling was conducted, after which, swabs were processed for bacterial and fungal enumeration. The results showed that the air sanitization system had good efficacy for both bacteria and fungi in the air and on stainless-steel plates, particularly for the A plates.

APOE-ε4 is a main genetic risk factor for developing late onset Alzheimer’s disease (LOAD) and is thought to interact adversely with other risk factors on the brain. However, evidence regarding the impact of APOE-ε4 on grey matter structure in asymptomatic individuals remains mixed. Much attention has been devoted to characterising APOE-ε4-related changes in the hippocampus, but LOAD pathology is known to spread through the whole of the Papez circuit including the limbic thalamus. Here, we tested the impact of APOE-ε4 and two other risk factors, a family history of dementia and obesity, on grey matter macro- and microstructure across the whole brain in 165 asymptomatic individuals (38–71 years). Microstructural properties of apparent neurite density and dispersion, free water, myelin and cell metabolism were assessed with Neurite Orientation Density and Dispersion (NODDI) and quantitative magnetization transfer (qMT) imaging. APOE-ε4 carriers relative to non-carriers had a lower macromolecular proton fraction (MPF) in the left thalamus. No risk effects were present for cortical thickness, subcortical volume, or NODDI indices. Reduced thalamic MPF may reflect inflammation-related tissue swelling and/or myelin loss in APOE-ε4. Future prospective studies should investigate the sensitivity and specificity of qMT-based MPF as a non-invasive biomarker for LOAD risk.

Purpose To compare technical success, clinical success, complications and radiation dose for percutaneous intradiscal ozone therapy in patients with lumbar disc herniation using fluoroscopic guidance versus conventional computed tomography (CT) guidance. Materials and methods Between March 2018and March 2021, 124consecutive percutaneous intradiscal ozone therapies wereperformedon111 patients with low back pain (LBP) and/or sciatic pain due to lumbar disc herniation, using fluoroscopic or conventional CT guidance, respectively in 53 and 58 herniated lumbar discs, with at least 1-month follow up. Dose area product (DAP) and dose length product (DLP) were recorded respectively for fluoroscopy and CT, and converted to effective dose (ED). Results Fluoroscopic and CT groups were similar in terms of patient age (p-value 0.39), patient weight (p-value 0.49) and pre-procedure Oswestry Disability Index (ODI, p-value 0.94). Technical success was achieved in all cases. Clinical success was obtained in 83.02% (44/53) patients in fluoroscopic group and 79.31% (46/58) in CT group. Mean DAP was 11.63Gy*cm2 (range 5.42–21.61). Mean DLP was 632.49mGy-cm (range 151.51–1699). ED was significantly lower in the fluoroscopic group compared toCT group (0.34 vs. 5.53mSv, p = 0.0119). No major complication was registered. Minor complications were observed in 4 cases (2 in fluoroscopic group; 2 in CT group). Conclusions Compared to conventional CT guidance, fluoroscopic guidance for percutaneous intradiscal ozone therapy in patients with lumbar disc herniation shows similar technical and clinical success rates, with lower radiation dose. This technique helps sparing dose exposure to patients.

As a complement to clinical disease surveillance, the monitoring of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in wastewater can be used as an early warning system for impending epidemics. This study investigated the dynamics of SARS-CoV-2 in untreated wastewater with respect to the trend of coronavirus disease 2019 (COVID-19) prevalence in Southern Italy. A total of 210 wastewater samples were collected between May and November 2020 from 15 Apulian wastewater treatment plants (WWTP). The samples were concentrated in accordance with the standard of World Health Organization (WHO, Geneva, Switzerland) procedure for Poliovirus sewage surveillance, and molecular analysis was undertaken with real-time reverse-transcription quantitative PCR (RT-(q) PCR). Viral ribonucleic acid (RNA) was found in 12.4% (26/210) of the samples. The virus concentration in the positive samples ranged from 8.8 × 102 to 6.5 × 104 genome copies/L. The receiver operating characteristic (ROC) curve modeling showed that at least 11 cases/100,000 inhabitants would occur after a wastewater sample was found to be positive for SARS-CoV-2 (sensitivity = 80%, specificity = 80.9%). To our knowledge, this is the first study in Italy that has applied wastewater-based epidemiology to predict COVID-19 prevalence. Further studies regarding methods that include all variables (meteorological phenomena, characteristics of the WWTP, etc.) affecting this type of wastewater surveillance data would be useful to improve data interpretation.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged in March 2020 in Italy, leading to the pandemic of coronavirus disease 2019 (COVID-19) that continues to cause high global morbidity and mortality in human populations. Numerous studies have focused on the spread and persistence of the virus in the hospital setting. New scientific evidence shows that SARS-CoV-2 is present in different community environments. Although aerosol is one of the main routes of transmission for SARS-CoV-2, indirect contact through virus-contaminated surfaces could also play a key role. The survival and persistence of SARS-CoV-2 on surfaces appear to be influenced by the characteristics of the material, temperature, and humidity. In this study, we investigated the presence of SARS-CoV-2 RNA on surfaces in 20 supermarkets throughout the Apulia region during the lockdown period. We collected a total of 300 swab samples from various surfaces including supermarket scales, trolley handles, refrigerator and freezer handles, and keyboards. In total, 13 (4.3%) surfaces were positive for SARS-CoV-2 RNA contamination, with shopping trolley handles being the most frequently contaminated. This study showed that contamination in public spaces can occur, so we remark the importance to adopt adequate preventive measures, including environment ventilation, careful surfaces sanitation, hand hygiene, and correct usage of masks, to reduce the likelihood of virus transmission.

Aging leads to gray and white matter decline but their causation remains unclear. We explored two classes of models of age and dementia risk related brain changes. The first class of models emphasises the importance of gray matter: age and risk-related processes cause neurodegeneration and this causes damage in associated white matter tracts. The second class of models reverses the direction of causation: aging and risk factors cause white matter damage and this leads to gray matter damage. We compared these models with linear mediation analysis and quantitative MRI indices (from diffusion, quantitative magnetization transfer and relaxometry imaging) of tissue properties in two limbic structures implicated in age-related memory decline: the hippocampus and the fornix in 166 asymptomatic individuals (aged 38-71 years). Aging was associated with apparent glia but not neurite density damage in the fornix and the hippocampus. Mediation analysis supported white matter damage causing gray matter decline; controlling for fornix glia damage, the correlations between age and hippocampal damage disappear, but not vice versa. Fornix and hippocampal differences were both associated with reductions in episodic memory performance. These results suggest that fornix white matter glia damage may cause hippocampal gray matter damage during age-dependent limbic decline.

Nowadays, increasing longevity associated with declining cerebral nervous system functions, suggests the need for continued development of new imaging contrast mechanisms to support the differential diagnosis of age-related decline. In our previous papers, we developed a new imaging contrast metrics derived from anomalous diffusion signal representation and obtained from diffusion-weighted (DW) data collected by varying diffusion gradient strengths. Recently, we highlighted that the new metrics, named γ-metrics, depended on the local inhomogeneity due to differences in magnetic susceptibility between tissues and diffusion compartments in young healthy subjects, thus providing information about myelin orientation and iron content within cerebral regions. The major structural modifications occurring in brain aging are myelinated fibers damage in nerve fibers and iron accumulation in gray matter nuclei. Therefore, we investigated the potential of γ-metrics in relation to other conventional diffusion metrics such as DTI, DKI and NODDI in detecting age-related structural changes in white matter (WM) and subcortical gray matter (scGM). DW-images were acquired in 32 healthy subjects, adults and elderly (age range 20–77 years) using 3.0T and 12 b-values up to 5000 s/mm2. Association between diffusion metrics and subjects’ age was assessed using linear regression. A decline in mean γ (Mγ) in the scGM and a complementary increase in radial γ (γ⊥) in frontal WM, genu of corpus callosum and anterior corona radiata with advancing age were found. We suggested that the increase in γ⊥ might reflect declined myelin density, and Mγ decrease might mirror iron accumulation. An increase in D// and a decrease in the orientation dispersion index (ODI) were associated with axonal loss in the pyramidal tracts, while their inverted trends within the thalamus were thought to be linked to reduced architectural complexity of nerve fibers. γ-metrics together with conventional diffusion-metrics can more comprehensively characterize the complex mechanisms underlining age-related changes than conventional diffusion techniques alone.

Globally, at the time of writing (20 March 2021), 121.759.109 confirmed COVID-19 cases have been reported to the WHO, including 2.690.731 deaths. Globally, on 18 March 2021, a total of 364.184.603 vaccine doses have been administered. In Italy, 3.306.711 confirmed COVID-19 cases with 103.855 deaths have been reported to WHO. In Italy, on 9 March 2021, a total of 6.634.450 vaccine doses have been administered. On 15 March 2021, Italian Medicines Agency (AIFA) decided to temporarily suspend the use of the AstraZeneca COVID-19 vaccine throughout the country as a precaution, pending the rulings of the European Medicines Agency (EMA). This decision was taken in line with similar measures adopted by other European countries due to the death of vaccinated people. On 18 March 2021, EMA’s safety committee concluded its preliminary review about thromboembolic events in people vaccinated with COVID-19 Vaccine AstraZeneca at its extraordinary meeting, confirming the benefits of the vaccine continue to outweigh the risk of side effects, however, the vaccine may be associated with very rare cases of blood clots associated with thrombocytopenia, i.e., low levels of blood platelets with or without bleeding, including rare cases of cerebral venous thrombosis (CVT). We report the case of a 54-year-old woman who developed disseminated intravascular coagulation (DIC) with multi-district thrombosis 12 days after the AstraZeneca COVID-19 vaccine administration. A brain computed tomography (CT) scan showed multiple subacute intra-axial hemorrhages in atypical locations, including the right frontal and the temporal lobes. A plain old balloon angioplasty (POBA) of the right coronary artery was performed, without stent implantation, with restoration of distal flow, but with persistence of extensive thrombosis of the vessel. A successive thorax angio-CT added the findings of multiple contrast filling defects with multi-vessel involvement: at the level of the left upper lobe segmental branches, of left interlobar artery, of the right middle lobe segmental branches and of the right interlobar artery. A brain magnetic resonance imaging (MRI) in the same day showed the presence of an acute basilar thrombosis associated with the superior sagittal sinus thrombosis. An abdomen angio-CT showed filling defects at the level of left portal branch and at the level of right suprahepatic vein. Bilaterally, it was adrenal hemorrhage and blood in the pelvis. An evaluation of coagulation factors did not show genetic alterations so as the nasopharyngeal swab ruled out a COVID-19 infection. The patient died after 5 days of hospitalization in intensive care.

White matter (WM) alterations have been identified as a relevant pathological feature of Huntington’s disease (HD). Increasing evidence suggests that WM changes in this disorder are due to alterations in myelin-associated biological processes. Multi-compartmental analysis of the complex gradient-echo MRI signal evolution in WM has been shown to quantify myelin in vivo, therefore pointing to the potential of this technique for the study of WM myelin changes in health and disease. This study first characterized the reproducibility of metrics derived from the complex multi-echo gradient-recalled echo (mGRE) signal across the corpus callosum in healthy participants, finding highest reproducibility in the posterior callosal segment. Subsequently, the same analysis pipeline was applied in this callosal region in a sample of premanifest HD patients (n = 19) and age, sex and education matched healthy controls (n = 21). In particular, we focused on two myelin-associated derivatives: i. the myelin water signal fraction (fm), a parameter dependent on myelin content; and ii. the difference in frequency between myelin and intra-axonal water pools (Δω), a parameter dependent on the ratio between the inner and the outer axonal radii. fm was found to be lower in HD patients (β = −0.13, p = 0.03), while Δω did not show a group effect. Performance in tests of working memory, executive function, social cognition and movement was also assessed, and a greater age-related decline in executive function was detected in HD patients (β = −0.06, p = 0.006), replicating previous evidence of executive dysfunction in HD. Finally, the correlation between fm, executive function, and proximity to disease onset was explored in patients, and a positive correlation between executive function and fm was detected (r = 0.542; p = 0.02). This study emphasises the potential of complex mGRE signal analysis for aiding understanding of HD pathogenesis and progression. Moreover, expanding on evidence from pathology and animal studies, it provides novel in vivo evidence supporting myelin breakdown as an early feature of HD.

Municipal solid waste (MSW) must be managed to reduce its impact on environmental matrices and population health as much as possible. In particular, the variables that influence the production, separate waste collection, and costs of MSW must be understood. Although many studies have shown that such factors are specific to an area, the awareness of these factors has created opportunities to implement operations to enable more effective and efficient MSW management services, and to specifically respond to the variables that have the most impact. The deep learning approaches used in this study are effective in achieving this goal and can be used in any other territorial context to ensure that the organizations that deal with these issues are more aware and create useful plans to promote the circular economy. Our findings indicate the important influence of number of rooms in a residential buildings and construction years on MSW production, the combination of services such as municipal collection centers and door-to-door service for separate MSW collection and the characteristics of the residential buildings in the municipalities on MSW management costs.

We provide a rich multi-contrast microstructural MRI dataset acquired on an ultra-strong gradient 3T Connectom MRI scanner comprising 5 repeated sets of MRI microstructural contrasts in 6 healthy human participants. The availability of data sets that support comprehensive simultaneous assessment of test-retest reliability of multiple microstructural contrasts (i.e., those derived from advanced diffusion, multi-component relaxometry and quantitative magnetisation transfer MRI) in the same population is extremely limited. This unique dataset is offered to the imaging community as a test-bed resource for conducting specialised analyses that may assist and inform their current and future research. The Microstructural Image Compilation with Repeated Acquisitions (MICRA) dataset includes raw data and computed microstructure maps derived from multi-shell and multi-direction encoded diffusion, multi-component relaxometry and quantitative magnetisation transfer acquisition protocols. Our data demonstrate high reproducibility of several microstructural MRI measures across scan sessions as shown by intra-class correlation coefficients and coefficients of variation. To illustrate a potential use of the MICRA dataset, we computed sample sizes required to provide sufficient statistical power a priori across different white matter pathways and microstructure measures for different statistical comparisons. We also demonstrate whole brain white matter voxel-wise repeatability in several microstructural maps. The MICRA dataset will be of benefit to researchers wishing to conduct similar reliability tests, power estimations or to evaluate the robustness of their own analysis pipelines.

The COVID-19 pandemic started in China in early December 2019, and quickly spread around the world. The epidemic gradually started in Italy at the end of February 2020, and by May 31, 2020, 232,664 cases and 33,340 deaths were confirmed. As a result of this pandemic, the Italian Ministerial Decree issued on March 11, 2020, enforced lockdown; therefore, many social, recreational, and cultural centers remained closed for months. In Apulia (southern Italy), all non-urgent hospital activities were suspended, and some wards were closed, with a consequent reduction in the use of the water network and the formation of stagnant water. This situation could enhance the risk of exposure of people to waterborne diseases, including legionellosis. The purpose of this study was to monitor the microbiological quality of the water network (coliforms, E. coli, Enterococci, P. aeruginosa, and Legionella) in three wards (A, B and C) of a large COVID-19 regional hospital, closed for three months due to the COVID-19 emergency. Our study revealed that all three wards' water network showed higher contamination by Legionella pneumophila sg 1 and sg 6 at T1 (after lockdown) compared to the period before the lockdown (T0). In particular, ward A at T1 showed a median value = 5600 CFU/L (range 0–91,000 CFU/L) vs T0, median value = 75 CFU/L (range 0–5000 CFU/L) (p-value = 0.014); ward B at T1 showed a median value = 200 CFU/L (range 0–4200 CFU/L) vs T0, median value = 0 CFU/L (range 0–300 CFU/L) (p-value = 0.016) and ward C at T1 showed a median value = 175 CFU/L (range 0–22,000 CFU/L) vs T0, median value = 0 CFU/L (range 0–340 CFU/L) (p-value, Highlights • Microbiological quality of the water network in a COVID-19 hospital was monitored. • The water network showed high contamination by L. pneumophila. • Coliforms and P.aeruginosa were detected in temporarily closed units.

Highlights • Gradient-echo data were acquired from premanifest HD patients in the callosum at 7 T. • Reproducibility of multi-compartment analysis across callosal areas was assessed. • Reduced myelin water signal fraction (fm) in HD patients suggested myelin breakdown. • Executive function correlated with callosal fm values in HD patients. • The reported approach may aid understanding of HD pathogenesis and progression., White matter (WM) alterations have been identified as a relevant pathological feature of Huntington’s disease (HD). Increasing evidence suggests that WM changes in this disorder are due to alterations in myelin‐associated biological processes. Multi-compartmental analysis of the complex gradient-echo MRI signal evolution in WM has been shown to quantify myelin in vivo, therefore pointing to the potential of this technique for the study of WM myelin changes in health and disease. This study first characterized the reproducibility of metrics derived from the complex multi-echo gradient-recalled echo (mGRE) signal across the corpus callosum in healthy participants, finding highest reproducibility in the posterior callosal segment. Subsequently, the same analysis pipeline was applied in this callosal region in a sample of premanifest HD patients (n = 19) and age, sex and education matched healthy controls (n = 21). In particular, we focused on two myelin-associated derivatives: i. the myelin water signal fraction (fm), a parameter dependent on myelin content; and ii. The difference in frequency between myelin and intra-axonal water pools (Δω), a parameter dependent on the ratio between the inner and the outer axonal radii. fm was found to be lower in HD patients (β = −0.13, p = 0.03), while Δω did not show a group effect. Performance in tests of working memory, executive function, social cognition and movement was also assessed, and a greater age-related decline in executive function was detected in HD patients (β = −0.06, p = 0.006), replicating previous evidence of executive dysfunction in HD. Finally, the correlation between fm, executive function, and proximity to disease onset was explored in patients, and a positive correlation between executive function and fm was detected (r = 0.542; p = 0.02). This study emphasises the potential of complex mGRE signal analysis for aiding understanding of HD pathogenesis and progression. Moreover, expanding on evidence from pathology and animal studies, it provides novel in vivo evidence supporting myelin breakdown as an early feature of HD.

APOE-e4 is a major genetic risk factor for late-onset Alzheimer’s disease that interacts with other risk factors, but the nature of such combined effects remains poorly understood. We quantified the impact of APOE-e4, family history (FH) of dementia, and obesity on white matter (WM) microstructure in 165 asymptomatic adults (38-71 years old) using quantitative magnetization transfer and neurite orientation dispersion and density imaging. Microstructural properties of the fornix, parahippocampal cingulum, and uncinate fasciculus were compared with those in motor and whole-brain WM regions. Widespread interaction effects between APOE, FH, and waist-hip ratio were found in the myelin-sensitive macromolecular proton fraction from quantitative magnetization transfer. Among individuals with the highest genetic risk (FH+ and APOE-e4), obesity was associated with reduced macromolecular proton fraction in the right parahippocampal cingulum, whereas no effects were present for those without FH. Risk effects on apparent myelin were moderated by hypertension and inflammation-related markers. These findings suggest that genetic risk modifies the impact of obesity on WM myelin consistent with neuroglia models of aging and late-onset Alzheimer's disease.

A family history (FH) of dementia,APOE-ε4 genotype, and obesity are major risk factors for developing Alzheimer’s disease but their combined effects on the brain and cognition remain elusive. We tested the hypothesis that these risk factors affect apparent white matter (WM) myelin and cognition including spatial navigation and processing speed in 166 asymptomatic individuals (38-71 years). Microstructure in temporal [fornix, parahippocampal cingulum, uncinate fasciculus], motor and whole-brain WM was assessed with myelin-sensitive indices from quantitative magnetization transfer [macromolecular proton fraction (MPF)] and axon density from diffusion imaging. Individuals with the highest genetic risk (FH+ andAPOE-ε4) compared to those with FH+ alone showed obesity-related reductions in MPF and axon density in the right parahippocampal cingulum. No effects were present for those without FH. Furthermore, FH modulated obesity-related effects on spatial navigation behaviour. In summary, an individual’s genetic dementia risk influenced the impact of obesity on WM myelin and cognition.

Magnetic resonance imaging (MRI) offers the possibility to non-invasively map the brain’s metabolic oxygen consumption (CMRO2), which is essential for understanding and monitoring neural function in both health and disease. However, in depth study of oxygen metabolism with MRI has so far been hindered by the lack of robust methods. One MRI method of mapping CMRO2 is based on the simultaneous acquisition of cerebral blood flow (CBF) and blood oxygen level dependent (BOLD) weighted images during respiratory modulation of both oxygen and carbon dioxide. Although this dual-calibrated methodology has shown promise in the research setting, current analysis methods are unstable in the presence of noise and/or are computationally demanding. In this paper, we present a machine learning implementation for the multi-parametric assessment of dual-calibrated fMRI data. The proposed method aims to address the issues of stability, accuracy, and computational overhead, removing significant barriers to the investigation of oxygen metabolism with MRI. The method utilizes a time-frequency transformation of the acquired perfusion and BOLD-weighted data, from which appropriate feature vectors are selected for training of machine learning regressors. The implemented machine learning methods are chosen for their robustness to noise and their ability to map complex non-linear relationships (such as those that exist between BOLD signal weighting and blood oxygenation). An extremely randomized trees (ET) regressor is used to estimate resting blood flow and a multi-layer perceptron (MLP) is used to estimate CMRO2 and the oxygen extraction fraction (OEF). Synthetic data with additive noise are used to train the regressors, with data simulated to cover a wide range of physiologically plausible parameters. The performance of the implemented analysis method is compared to published methods both in simulation and with in-vivo data (n=30). The proposed method is demonstrated to significantly reduce computation time, error, and proportional bias in both CMRO2 and OEF estimates. The introduction of the proposed analysis pipeline has the potential to not only increase the detectability of metabolic difference between groups of subjects, but may also allow for single subject examinations within a clinical context.

Legionella is the causative agent of Legionnaires' disease, a flu-like illness normally acquired following inhalation or aspiration of contaminated water aerosols. Our recent studies revealed that climatic parameters can increase the number of reported cases of community-acquired Legionnaires' disease. Here, we evaluated the presence of Legionella in water networks and the distribution of Legionnaires' disease cases associated with touristic-recreational facilities in the Apulia region (southern Italy) during the period 2001–2017 using geostatistical and climatic analyses. Geostatistical analysis data revealed that the area with the highest concentration of Legionella in water systems also had the greatest number of cases of Legionnaires' disease associated with touristic-recreational facilities. Climatic analysis showed that higher daily temperature excursion (difference between maximum and minimum temperature) on the day of sampling was more often associated with Legionella-positive samples than Legionella-negative samples. In addition, our data highlighted an increased risk of Legionnaires’ disease with increases in precipitation and average temperature and with decreases in daily temperature excursion (difference between maximum and minimum temperature over the course of 24 h in the days of incubation period of disease) and minimum temperature. Healthcare professionals should be aware of this phenomenon and be particularly vigilant for cases of community-acquired pneumonia during such climatic conditions and among the tourist population. The innovative geo-statistical approach used in this study could be applied in other contexts when evaluating the effects of climatic conditions on the incidence of Legionella infections.

Background. Recent evidence suggested that Action Observation Therapy (AOT), based on observation of actions followed by immediate reproduction, could be a useful rehabilitative strategy for promoting functional recovery of children affected by unilateral cerebral palsy (UCP). AOT most likely exploits properties of the parieto-premotor mirror neuron system (MNS). This is more intensely activated when participants observe actions belonging to their own motor repertoire. Objective. The aim of the present study was to investigate the issue of whether MNS of UCP children is better activated by actions performed by a paretic hand rather than a healthy one. Methods. Using functional magnetic resonance imaging, we assessed brain activation in a homogeneous group of 10 right UCP children compared with that of 10 right-handed typically developing (TD) children, during observation of grasping actions performed by a healthy or a paretic hand. Results. The results revealed a significant activation within the MNS in both UCP and TD children, more lateralized to the left hemisphere in the TD group. Most important, region of interest (ROI) analysis on parietal and premotor regions showed that, in UCP, the MNS was more strongly activated by observation of actions performed by the paretic hand, a motor model more similar to the observer’s motor repertoire. Conclusions. This study shows that children affected by spastic UCP exhibit enhanced activation of the MNS during observation of goal-directed actions performed by a pathological model with respect to a healthy one.

Late recovery of consciousness in vegetative state is considered as an exceptional outcome and has been reported prevalently in patients who suffered a traumatic brain injury. In these patients, the benefits of prolonging the rehabilitation, aimed at the recovery of autonomy in basic everyday activities, has been demonstrated. Here, we describe the application of an intensive multi-professional rehabilitation program carried out on a young female patient, with exceptionally late recovery of consciousness, specifically, after 7 years of vegetative state due to severe brain hemorrhage. Neuropsychological and functional assessment was conducted before and after the end of the rehabilitation program. In addition, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI)-based probabilistic tractography were performed. Two follow-up neuropsychological and functional assessments were also conducted 6 and 29 months after the conclusion of the program. Functional results showed an improvement, maintained over time, in walking with assistance, cognitive efficiency, visual acuity and visual field, dysarthria, and execution of activities of daily living. Moreover, functional and structural magnetic resonance imaging (MRI) data documented the existence of preserved neural networks involved in sensory, motor, and linguistic tasks, which in all likelihood support the recovery process. This report suggests the possibility of undertaking an intensive rehabilitation program in patients who remain for long periods in altered states of consciousness, in spite of early negative prognosis.

The internal state of others can be understood observing their actions or listening to their voice. While the neural bases of action style (vitality forms) have been investigated, there is no information on how we recognize others' internal state by listening to their speech. Here, using fMRI technique, we investigated the neural correlates of auditory vitality forms while participants listened to action verbs in three different conditions: human voice pronouncing the verbs in a rude and gentle way, robot voice pronouncing the same verbs without vitality forms, and a scrambled version of the same verbs pronounced by human voice. In agreement with previous studies on vitality forms encoding, we found specific activation of the central part of insula during listening to human voice conveying specific vitality forms. In addition, when listening both to human and robot voices there was an activation of the posterior part of the left inferior frontal gyrus and of the parieto-premotor circuit typically described to be activated during observation and execution of arm actions. Finally, the superior temporal gyrus was activated bilaterally in all three conditions. We conclude that, the central part of insula is a key region for vitality forms processing allowing the understanding of the vitality forms regardless of the modality by which they are conveyed.

Midlife obesity is a risk factor of late onset Alzheimer's disease (LOAD) but why this is the case remains unknown. As systemic inflammation is involved in both conditions, obesity-related neuroinflammation may contribute to damage in limbic structures important in LOAD. Here, we investigated the hypothesis that systemic inflammation would mediate central obesity related effects on limbic tissue microstructure in 166 asymptomatic individuals (38–71 years old). We employed MRI indices sensitive to myelin and neuroinflammation [macromolecular proton fraction (MPF) and kf] from quantitative magnetization transfer (qMT) together with indices from neurite orientation dispersion and density imaging (NODDI) to investigate the effects of central adiposity on the fornix, parahippocampal cingulum, uncinate fasciculus (compared with whole brain white matter and corticospinal tract) and the hippocampus. Central obesity was assessed with the Waist Hip Ratio (WHR) and abdominal visceral and subcutaneous fat area fractions (VFF, SFF), and systemic inflammation with blood plasma concentrations of leptin, adiponectin, C-reactive protein and interleukin 8. Men were significantly more centrally obese and had higher VFF than women. Individual differences in WHR and in VFF were negatively correlated with differences in fornix MPF and kf, but not with any differences in neurite microstructure. In women, age mediated the effects of VFF on fornix MPF and kf, whilst in men differences in the leptin and adiponectin ratio fully mediated the effect of WHR on fornix MPF. These results suggest that visceral fat related systemic inflammation may damage myelin-related properties of the fornix, a key limbic structure known to be involved in LOAD., Highlights • Central adiposity is linked to apparent myelin/inflammatory damage in the fornix. • Central adiposity is not linked to differences in apparent neurite microstructure. • Men were more centrally obese and had higher visceral fat fractions than women. • In women, age mediated the correlation between visceral fat and fornix myelin. • In men, adipokines mediated the correlation between WHR and fornix myelin.

Aging leads to gray and white matter decline but their causation remains unclear. We explored two broad classes of models of age and dementia risk related brain changes. The first class of models emphasises the importance of gray matter: age and risk-related processes cause neurodegeneration and this causes damage in associated white matter tracts. The second class of models reverses the direction of causation: aging and risk factors cause white matter damage and this leads to gray matter damage. We compared these models with linear mediation analysis and quantitative multi-modal MRI indices (from diffusion, quantitative magnetization transfer and relaxometry imaging) of tissue properties in two limbic structures implicated in age-related memory decline: the hippocampus and the fornix in 166 asymptomatic individuals (aged 38 - 71 years). Aging was associated with apparent glia but not axon density damage in the fornix. Mediation analysis unambiguously supported white matter damage causing gray matter decline; controlling for fornix glia damage, the correlation between age and hippocampal damage disappears, but not vice versa. Fornix and hippocampal tissue loss were both associated with reductions in episodic memory performance. The implications of these findings for neuroglia and neurodegenerative models of aging and late onset dementia are discussed.

Midlife obesity is a risk factor of late onset Alzheimer’s disease (LOAD) but why this is the case remains unknown. As systemic inflammation is involved in both conditions, one possibility is that obesity-related neuroinflammation may contribute to the development of LOAD. Neuroinflammation is closely linked to white matter myelin loss, and this can be measured in vivo with quantitative magnetization transfer (qMT) imaging. Here, we investigated whether differences in obesity measures, i.e., in Waist Hip Ratio (WHR), abdominal visceral and subcutaneous fat volume fractions and Body Mass Index (BMI), were associated with reductions in qMT indices of apparent myelin in temporal white matter pathways involved in LOAD (i.e., the fornix, the parahippocampal cingulum and the uncinate fasciculus compared with whole brain and cortico-spinal white matter) in 166 cognitively healthy individuals (38-71 years of age). Obesity-related effects on myelin-sensitive markers were contrasted with differences in apparent axon density from dual-shell diffusion Neurite Orientation Dispersion and Density Imaging (NODDI). Differences in WHR and in visceral fat volume fractions were negatively correlated with differences in qMT estimates of apparent myelin and tissue metabolism in the fornix but not with any other microstructural components. These correlations were not explained by demographic (age, sex, education), health (hypertension, alcohol consumption, sedentary lifestyle) or genetic (APOE genotype, family history of dementia) risk factors of LOAD. Furthermore, differences in the ratio of plasma concentrations of leptin and adiponectin were also positively correlated with differences in C-Reactive Protein concentrations, and contributed significantly to the correlations between central obesity and myelin-sensitive metrics in the fornix. These results are consistent with the view that visceral fat-related chronic inflammation may damage white matter myelin in limbic regions, known to be vulnerable to LOAD pathology.

Background: Recently, efforts have been made to combine complementary perspectives in the assessment of Alzheimer type dementia. Of particular interest is the definition of the fingerprints of an early stage of the disease known as Mild Cognitive Impairment or prodromal Alzheimer's Disease. Machine learning approaches have been shown to be extremely suitable for the implementation of such a combination. Methods: In the present pilot study we combined the machine learning approach with structural magnetic resonance imaging and cognitive test assessments to classify a small cohort of 11 healthy participants and 11 patients experiencing Mild Cognitive Impairment. Cognitive assessment included a battery of standardised tests and a battery of experimental visuospatial memory tests. Correct classification was achieved in 100% of the participants, suggesting that the combination of neuroimaging with more complex cognitive tests is suitable for early detection of Alzheimer Disease. Results: In particular, the results highlighted the importance of the experimental visuospatial memory test battery in the efficiency of classification, suggesting that the high-level brain computational framework underpinning the participant's performance in these ecological tests may represent a “natural filter” in the exploration of cognitive patterns of information able to identify early signs of the disease.

Background Regular breakfast consumption is associated with better health status and healthier food intake throughout the day, but this association is a complex interaction of several factors. Objective This study aimed to investigate the effect of nutritional and cognitive-perceived characteristics of breakfast on metabolic and behavioral variables related to food intake. Methods The study was a randomized, crossover, controlled trial, with 4 experimental conditions consisting of 3 iso-energetic breakfasts and 1 energy-free control meal. Breakfasts had similar nutritional profiles but differed for glycemic index (GI), glycemic load (GL), and perceived healthiness, satiety, palatability, or energy content. Fifteen healthy normal-weight men [means ± SDs; age: 24 ± 2 y; body mass index (BMI; kg/m2) 23.4 ± 1.6] underwent each experimental condition in random order during 4 different weeks, separated by ≥1-wk washout. On the third day of each intervention week, postprandial blood variables (with insulin as primary outcome), satiety ratings, and food intake during an ad libitum lunch consumed 4 h after breakfast (secondary outcomes) were measured for each experimental condition. Results A main effect of time, treatment, and time × treatment was found for postprandial insulin, glucose, and nonesterified fatty acids (P

Precise kinematics or body configuration cannot be recovered from visual input without disparity information. Yet, no imaging study has investigated the role of disparity on action observation. Here, we investigated the interaction between disparity and the main cues of biological motion, kinematics and configuration, in two fMRI experiments. Stimuli were presented as point‐light figures, depicting complex action sequences lasting 21 s. We hypothesized that interactions could occur at any of the three levels of the action observation network, comprising occipitotemporal, parietal and premotor cortex, with premotor cortex being the most likely location. The main effects of kinematics and configuration confirmed that the biological motion sequences activated all three levels of the action observation network, validating our approach. The interaction between configuration and disparity activated only premotor cortex, whereas interactions between kinematics and disparity occurred at all levels of the action observation network but were strongest at the premotor level. Control experiments demonstrated that these interactions could not be accounted for by low level motion in depth, task effects, spatial attention, or eye movements, including vergence. These results underscore the role of premotor cortex in action observation, and in imitating others or responding to their actions. Hum Brain Mapp 37:203–219, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.