Effects of time and temperature of storage on chemical and nutritional characteristics of raw milk for Provolone Valpadana PDO cheesemaking: a multivariate approach.

We evaluated the possibility of increasing the storage temperature of raw milk for Provolone Valpadana cheesemaking, to identify the most suitable conditions of time and temperature for a pre-maturation process. We used Principal Component Analysis (PCA) to analyze the overall effects of different storage conditions on chemical, nutritional and technological characteristics of the raw milk. Four different thermal storage cycles, two at fixed temperature/time (6 and 12°C for 60 h) and two with two-phase thermal cycle (10 and 12°C for 15 h, followed by refrigeration at 4°C for 45 h) were studied. Although a moderate heterogeneity among raw milks from the 11 producers of Provolone Valpadana cheese was observed, PCA revealed the critical aspects of the extreme storage conditions (60 h of refrigeration). Some samples resulted in anomalous behaviors, probably related to unexpected fermentation phenomena occurring with increasing storage temperature. The acidification and the increase in the contents of lactic acid, soluble calcium, and degree of retinol isomerization observed in the anomalous samples can compromise the technological functionality of milk. Conversely, the storage with a two-phase thermal cycle did not lead to variations in any measured characteristic, suggesting that mild refrigeration conditions (10 or 12°C for 15 h followed by 4°C for 45 h) could be a good compromise in favoring milk pre-maturation without altering its quality characteristics.

Different saccadic profile in bulbar versus spinal-onset amyotrophic lateral sclerosis.

Two clinical phenotypes characterize the onset of amyotrophic lateral sclerosis (ALS): the spinal variant, with symptoms beginning in the limbs, and the bulbar variant, affecting firstly speech and swallowing. The two variants show some distinct features in the histopathology, localization and prognosis, but to which extent they really differ clinically and pathologically remains to be clarified. Recent neuropathological and neuroimaging studies have suggested a broader spreading of the neurodegenerative process in ALS, extending beyond the motor areas, toward other cortical and deep grey matter regions, many of which are involved in visual processing and saccadic control. Indeed, a wide range of eye movement deficits have been reported in ALS, but they have never been used to distinguish the two ALS variants. Since quantifying eye movements is a very sensitive and specific method for the study of brain networks, we compared different saccadic and visual search behaviours across spinal ALS patients (n = 12), bulbar ALS patients (n = 6) and healthy control subjects (n = 13), along with cognitive and MRI measures, with the aim to define more accurately the two patients subgroups and possibly clarify a different underlying neural impairment. We found separate profiles of visually-guided saccades between spinal (short saccades) and bulbar (slow saccades) ALS, which could result from the pathologic involvement of different pathways. We suggest an early involvement of the parieto-collicular-cerebellar network in spinal ALS and the fronto-brainstem circuit in bulbar ALS. Overall, our data confirm the diagnostic value of the eye movements analysis in ALS and add new insight on the involved neural networks.

FOLR1 Gene Variation With Adult-Onset Cerebral Folate Deficiency and Stable Clinical and MRI Features up to 2 Years.

Objectives: The objective of this case report was to describe the first report of FOLR1 variants associated with adult-onset paucisymptomatic leukoencephalopathy associated with cerebral folate deficiency (CFD). Methods: Considering the patient's symptoms, a nonprogressive leukoencephalopathy was suspected. CSF 5-methyltetrahydrofolate levels were low (10 nmol/L, normal range 41-117). With no other identifiable causes, a genetic analysis was conducted, revealing a compound heterozygous FOLR1 variation (c.45G>T and c. 493+2T>C). Results: A 47-year-old man with a history of drug and alcohol abuse was admitted to the hospital for double vision and postural instability. MRI of the brain was performed, which showed bilateral leukoencephalopathy. Diffusion tensor imaging revealed a diffuse reduction in fractional anisotropy, suggesting microstructural changes. MRI of the brain and overall clinical picture were stable on subsequent serial examinations. Discussion: Scientific evidence supports the deleterious effect of c.45G>T and c.493+2T>C variations on the folate receptor-α (FRα) protein structure and function. The weakness of the expression and function of FRα without elimination of its function caused by specific compound heterozygous variations may explain the atypical features observed in our patient. Although rare, CFD should be considered in paucisymptomatic adult patients with stable diffuse MRI white matter changes.

Local and Distributed fMRI Changes Induced by 40 Hz Gamma tACS of the Bilateral Dorsolateral Prefrontal Cortex: A Pilot Study.

Over the past few years, the possibility of modulating fast brain oscillatory activity in the gamma (γ) band through transcranial alternating current stimulation (tACS) has been discussed in the context of both cognitive enhancement and therapeutic scenarios. However, the effects of tACS targeting regions outside the motor cortex, as well as its spatial specificity, are still unclear. Here, we present a concurrent tACS-fMRI block design study to characterize the impact of 40 Hz tACS applied over the left and right dorsolateral prefrontal cortex (DLPFC) in healthy subjects. Results suggest an increase in blood oxygenation level-dependent (BOLD) activity in the targeted bilateral DLPFCs, as well as in surrounding brain areas affected by stimulation according to biophysical modeling, i.e., the premotor cortex and anterior cingulate cortex (ACC). However, off-target effects were also observed, primarily involving the visual cortices, with further effects on the supplementary motor areas (SMA), left subgenual cingulate, and right superior temporal gyrus. The specificity of 40 Hz tACS over bilateral DLPFC and the possibility for network-level effects should be considered in future studies, especially in the context of recently promoted gamma-induction therapeutic protocols for neurodegenerative disorders.

Case report: A quantitative and qualitative diffusion tensor imaging (DTI) study in varicella zoster-related brachial plexopathy.

Diffusion tensor imaging (DTI) is considered feasible for the nerve plexuses' imaging and quantitative evaluation but its value in the clinical practice is still virtually unexplored. We present the DTI profile of a case of acute varicella-zoster virus (VZV)-related brachial plexopathy. A 72-year-old woman presented with left upper-limb segmental paresis involving the spinal metamers C6-C7, preceded by a painful dermatomal vesicular eruption in C5-T1 dermatomes. Clinical and electrophysiological findings and magnetic resonance imaging indicated a plexus involvement. DTI analysis showed decreased fractional anisotropy (FA) and an increase of all the other diffusivity indexes, i.e., mean, axial, and radial diffusivity. The mechanisms underlying DTI parameter differences between healthy and pathologic brachial plexus sides could be related to microstructural fiber damage. Water diffusion is affected within the nerve roots by increasing the diffusion distance, leading to increased diffusion perpendicular to the largest eigenvalue and therefore to decreased FA values The role of DTI in clinical practice has not been defined yet. Additional quantitative and qualitative DTI information could improve the assessment and follow-up of brachial plexopathy.

Chemometrics for the Identification of Nitrogen and Acid Compounds in Milk-Whey as By-Products from Crescenza and Grana Padano Type Cheese-Making.

Proteomics and metabolomics are analytic tools used in combination with bioinformatics to study proteins and metabolites which contribute to describing complex biological systems. The growing interest in research concerning the resolution of these systems has stimulated the development of sophisticated procedures and new applications. This paper introduces the evolution of statistical techniques for the treatment of data, suggesting the possibility to successfully characterize the milk-whey syneresis process by applying two-dimensional correlation analysis (2DCOR) to a series of CE electropherograms referring to milk-whey samples collected during cheese manufacturing. Two cheese-making processes to produce hard cheese (Grana type) and fresh cheese (Crescenza) were taken as models. The applied chemometric tools were shown to be useful for the treatment of data acquired in a systematically perturbed chemical system as a function of time.

Impact of network-targeted multichannel transcranial direct current stimulation on intrinsic and network-to-network functional connectivity.

Dynamics within and between functional resting-state networks have a crucial role in determining both healthy and pathological brain functioning in humans. The possibility to noninvasively interact and selectively modulate the activity of networks would open to relevant applications in neuroscience. Here we tested a novel approach for multichannel, network-targeted transcranial direct current stimulation (net-tDCS), optimized to increase excitability of the sensorimotor network (SMN) while inducing cathodal inhibitory modulation over prefrontal and parietal brain regions negatively correlated with the SMN. Using an MRI-compatible multichannel transcranial electrical stimulation (tES) device, 20 healthy participants underwent real and sham tDCS while at rest in the MRI scanner. Changes in functional connectivity (FC) during and after stimulation were evaluated, looking at the intrinsic FC of the SMN and the strength of the negative connectivity between SMN and the rest of the brain. Standard, bifocal tDCS targeting left motor cortex (electrode ~C3) and right frontopolar (~Fp2) regions was tested as a control condition in a separate sample of healthy subjects to investigate network specificity of multichannel stimulation effects. Net-tDCS induced greater FC increase over the SMN compared to bifocal tDCS, during and after stimulation. Moreover, exploratory analysis of the impact of net-tDCS on negatively correlated networks showed an increase in the negative connectivity between SMN and prefrontal/parietal areas targeted by cathodal stimulation both during and after real net-tDCS. Results suggest preliminary evidence of the possibility of manipulating distributed network connectivity patterns through net-tDCS, with potential relevance for the development of cognitive enhancement and therapeutic tES solutions.

Insights into Endothelin-3 and Multiple Sclerosis.

Endothelins are powerful vasoconstrictor peptides that play numerous other roles. Endothelin-1 (ET1) is the principal isoform produced by the endothelium in the human cardiovascular system. Endothelin-3 (ET3) and its rPptor affinity have been demonstrated to support neuronal repair mechanisms throughout life. In multiple sclerosis (MS), the role of vasoactive peptides are not well defined. Here we focus on ET3, specifically the plasma levels between MS patients and healthy subjects. Furthermore, we evaluated the changes in ET1 and ET3 plasma levels during different disease phases, the correlation between ET3 and cerebral circulation time, and the relationship between ET1 and ET3. In MS patients, the ET3 plasma levels were altered in a time-dependent manner. These results could support a putative role of ET3 in neuroprotection and/or neuroimmune modulation over time.

Improving Choroid Plexus Segmentation in the Healthy and Diseased Brain: Relevance for Tau-PET Imaging in Dementia.

Recent studies have revealed the possible role of choroid plexus (ChP) in Alzheimer's disease (AD). T1-weighted MRI is the modality of choice for the segmentation of ChP in humans. Manual segmentation is considered the gold-standard technique, but given its time-consuming nature, large-scale neuroimaging studies of ChP would be impossible. In this study, we introduce a lightweight segmentation algorithm based on the Gaussian Mixture Model (GMM). We compared its performance against manual segmentation as well as automated segmentation by Freesurfer in three separate datasets: 1) patients with structural MRIs enhanced with contrast (n = 19), 2) young healthy subjects (n = 20), and 3) patients with AD (n = 20). GMM outperformed Freesurfer and showed high similarity with manual segmentation. To further assess the algorithm's performance in large scale studies, we performed GMM segmentations in young healthy subjects from the Human Connectome Project (n = 1,067), as well as healthy controls, mild cognitive impairment (MCI), and AD patients from the Alzheimer's Disease Neuroimaging Initiative (n = 509). In both datasets, GMM segmented ChP more accurately than Freesurfer. To show the clinical importance of accurate ChP segmentation, total AV1451 (tau) PET binding to ChP was measured in 108 MCI and 32 AD patients. GMM was able to reveal the higher AV1451 binding to ChP in AD compared with MCI. Our results provide evidence for the utility of the GMM in accurately segmenting ChP and show its clinical relevance in AD. Future structural and functional studies of ChP will benefit from GMM's accurate segmentation.

Percutaneous Intervertebral Disc Coagulation Therapy (PDCT) by Plasma Light: Preliminary Data from the First Experience in Europe.

PURPOSE: To retrospectively assess safety and potential effectiveness of percutaneous intervertebral disc coagulation therapy (PDCT) using plasma thermal reaction for the treatment of lumbar and cervical disc hernias resistant to medical therapy. MATERIALS AND METHODS: Forty-four patients (age range 18-87 years, mean 52.7) with contained and extruded symptomatic lumbar (N = 48) and cervical (N = 6) disc hernias in the absence of free fragments causing radiculopathy without improvement after 6-week conservative therapy were enrolled. Pretreatment discography has been performed in every patient. Spine MRI was performed before the procedure and 4 months later, in order to check post-PDCT changes. Technical success was defined as correct placement of PDCT fiber; clinical outcomes were evaluated using visual analog scale (VAS) and the Oswestry Disability Index (ODI) before the procedure and after 4 months. RESULTS: A total of 54 levels have been treated with 98% technical success; in 12 patients (27%), the treatment was performed in two levels at the same time. All patients well tolerated the procedure; most patients (N = 39; 89%) had significant improvement in symptoms, with ODI score reduction from 47.61 ± 8.7 to 13.38 ± 9.4 (p < 0.001). The mean pre-PDCT VAS score was 7.47 ± 0.8. VAS score was decreased down to 1.36 ± 1.6 at final follow-up (p < 0.001). There were no cases of infection, nerve damage, or bleeding. CONCLUSIONS: PDCT can be an effective and safe for minimally invasive indirect decompression for cervical and lumbar hernia resistant to conservative treatment, particularly when patients are correctly selected.

Functional and Brain Activation Changes Following Specialized Upper-Limb Exercise in Parkinson's Disease.

For the management of Parkinson's disease (PD), the concept of forced exercise (FE) has drawn interest. In PD subjects, the FE executed with lower limbs has been shown to lessen symptoms and to promote brain adaptive changes. Our study is aimed to investigate the effect of an upper-limb exercise, conceptually comparable with the FE, in PD. Upper-limb exercise was achieved in a sitting position by using a specially designed device (Angel's Wings®). Clinical data, computerized dynamic posturography, magnetic resonance imaging (MRI) (resting-state MRI and arterial spin labeling), and neuropsychological tests were used before and after 2 months' exercise training. We found a significant long-lasting improvement in Unified Parkinson Disease Rating Scale (UPDRS)-III and cognitive scales, along with improvement in balance and postural control (better alignment of the gravity center and improvement in weight symmetry and in anticipatory motor strategies). Computerized dynamic posturography pointed out an enhanced central ability to integrate the vestibular signals with afferents from other sensory systems. Neuroimaging analyses after 2 months' exercise training showed, with respect to pretraining condition, many changes. An increase of the cerebral blood flow was evident in the left primary motor cortex (M1), left supplementary motor cortical area, and left cerebellar cortex. The bilateral globus pallidus showed an increased functional connectivity to the right central operculum, right posterior cingulate gyrus, and left sensorimotor cortex. Seed-to-voxel analysis demonstrated a functional connectivity between M1 and the left superior frontal gyrus. Left crus II showed strengthened connections with the left pre-rolandic area, left post-rolandic area, and left supramarginal area. These findings likely reflect compensatory mechanisms to the neuropathological hallmark of PD. Overall, our results show that this upper-limb exercise model, conceptually comparable with the FE already tested in the lower limbs, leads to a global improvement (involving non-exercised limbs) likely consistent with the functional changes observed in the central nervous system.

Prospective study of clinical, neurophysiological and urodynamic findings in multiple sclerosis patients undergoing percutaneous transluminal venous angioplasty.

OBJECTIVE: Verify whether Percutaneous Transluminal Angioplasty (PTA) may affect neural conduction properties in Multiple Sclerosis (MS) patients, thereby modifying patients' disability, with prospective neurophysiological, urodynamic, clinical and subjective well-being evaluations. METHODS: In 55 out of 72 consecutively screened MS patients, the following procedures were carried out before (T0), at 2-6 months (T1) and at 6-15 months (T2) after a diagnostic phlebography, eventually followed by the PTA intervention if chronic cerebrospinal venous insufficiency (CCSVI) was diagnosed: clinical/objective evaluation (Expanded Disability Status Scale, EDSS), ratings of subjective well-being, evaluation of urodynamic functions and multimodal EPs (visual, acoustic, upper and lower limbs somatosensory and motor evoked potentials). RESULTS: The number of dropouts was relatively high, and a complete set of neurophysiological and clinical data remained available for 37 patients (19 for urological investigations). The subjective well-being score significantly increased at T1 and returned close to basal values at T2, but their degree of objective disability did not change. Nevertheless, global EP-scores (indexing the impairment in conductivity of central pathways in multiple functional domains) significantly increased from T0 (7.9 ±â€¯6.0) to T1 (9.2 ±â€¯6.3) and from T0 to T2 (9.8 ±â€¯6.3), but not from T1 and T2 (p > 0.05). Neurogenic urological lower tract dysfunctions slightly increased throughout the study. CONCLUSIONS: The PTA intervention did not induce significant changes in disability in the present cohort of MS patients, in line with recent evidence of clinical inefficacy of this procedure. SIGNIFICANCE: Absence of multimodal neurophysiological and functional testing changes in the first 15 months following PTA suggests that conduction properties of neural pathways are unaffected by PTA. Current findings suggest that the short-lived (2-6 months), post-PTA, beneficial effect on subjective well-being measures experienced by MS patients is likely related to a placebo effect.

Stroke in Pregnancy and Review of Current Literature: Arterial Spin-Labeling MRI Can Identify the Presence and Intensity of Collateral Circle.

Diagnosis and treatment of acute ischemic stroke is challenging during pregnancy. We present a diagnostic strategy in a pregnant woman with suspect of acute stroke. We perform magnetic resonance with arterial spin labeling sequence, an X-ray and contrast medium safe perfusion technique. Arterial spin labeling can detects collateral vessels in patient with acute ischemic stroke. Demonstrating collateral vessels is relevant for better understanding prognosis and for improving the diagnostic assessment in pregnancy.

Impaired Cerebral Perfusion in Multiple Sclerosis: Relevance of Endothelial Factors.

Magnetic resonance imaging techniques measuring in vivo brain perfusion and integrity of the blood-brain barrier have developed rapidly in the past decade, resulting in a wide range of available methods. This review first discusses their principles, possible pitfalls, and potential for quantification and outlines clinical application in neurological disorders. Then, we focus on the endothelial cells of the blood-brain barrier, pointing out their contribution in regulating vascular tone by production of vasoactive substances. Finally, the role of these substances in brain hypoperfusion in multiple sclerosis is discussed.

Folates biosynthesis by Streptococcus thermophilus during growth in milk.

The ability of folate-producer strains of Streptococcus thermophilus to accumulate folates and the expression of two target genes (folK and folP), involved in the folate biosynthesis, were studied during milk fermentation. An over-expression of folK took place only in the early phase of growth, whereas folP was mainly expressed in the mid log-phase of growth and declined thereafter. The accumulation of total folates, which was quantified by a microbiological assay, was strain-dependent. Two major forms of folates, i.e. tetrahydrofolate (THF) and 5-methyl-tetrahydrofolate (5-Met-THF), were identified and quantified by HPLC. With respect to the level accumulated by a weak folate producer (St 383), used as calibrator in the expression experiments and as control in folate quantification in milk, the strains St 563 and St 399 produced 5-Met-THF in amounts significantly higher than THF. The possibility of using selected folate-producer S. thermophilus strains as functional cultures for a bio-fortification of dairy products is discussed.

Influence of Circulating Endothelin-1 and Asymmetric Dimethylarginine on Whole Brain Circulation Time in Multiple Sclerosis.

Blood-brain barrier (BBB) breakdown, inflammatory and immune cell activation, and chronic cerebral hypoperfusion are features of multiple sclerosis (MS). The aim is to determine the influence of endothelin-1 (ET1) and asymmetric dimethylarginine (ADMA) on cerebral circulation time (CCT) in patients with MS. In all, 64 patients with MS (39 relapsing-remitting [RR]-MS; 25 secondary progressive [SP]-MS subtype) and 37 controls (C) were studied. Cerebral circulation time was obtained by angiography. Plasmatic ET1 and ADMA were measured by enzyme-linked immunosorbent assay. Lesion load (LL) and brain volume (BV) were obtained by magnetic resonance imaging. Cerebral circulation time was correlated to ET1, ADMA, LL, BV, disease duration (DD), and Expanded Disability Status Scale (EDSS). In MS, both ET1 and ADMA were significantly higher than C (P < .0001); CCT was approximately 2 times lower than C (P < .0001) and significantly slower in SP than in RR-MS (P = .0215). Cerebral circulation time significantly correlated with ET1 in SP-MS (r = 0.38), whereas in RR-MS CCT significantly correlated with DD (r = 0.75). The LL, BV, and EDSS did not correlate with CCT. Endothelin-1 significantly influences CCT delay in SP-MS. Diversely, CCT in RR-MS is independent of ET1 and correlates significantly with DD. We conclude that in RR-MS, DD responds to neurovascular damage accumulation. It is supposed that high ET1 and ADMA levels stem from a protective response to early insults, aimed at opposing nitric oxide overproduction, whereas persistent pathological ET1 and ADMA levels translate into detrimental long-term effects, due to increased brain micro-vessel resistance.

Neuroimaging of Takayasu Arteritis in a Patient with Ulcerative Rectocolitis.

BACKGROUND: Takayasu arteritis (TA), also known as aortoarteritis and pulseless disease, is an autoimmune, idiopathic, large-vessel vasculitis that primarily affects the aorta and its major branches, the coronary arteries, and the pulmonary arteries. METHODS: This is a peculiar clinical and radiological pattern of TA in a young female Caucasian. Her medical history included diagnosis of ulcerative rectocolitis at the age of 14. Because of the occurrence of anemia and exacerbation of rectocolitis, she had started infliximab associated with low doses of cortisone and mesalazine. Three months before admission, therapy with infliximab was discontinued because of the onset of fever, sore throat, and the increase in the neck pain. Imaging is crucial to achieve a proper diagnosis and the main differential diagnosis of this setting is arterial dissection. Magnetic resonance angiography (MRA) and color Doppler sonography (CDS) have been able to demonstrate rare but possible arteriovenous fistula in TA patients. This is the first report on arteriovenous fistula of cervical venous plexus in TA patients. CONCLUSION: (1) TA has to be suspected in young woman with neck pain, even without neurological symptoms. (2) Magnetic resonance imaging and CDS can depict wall thickening and abnormal caliber in the involved vessels. (3) MRA and CDS are able to demonstrate rare but possible arteriovenous fistula in TA patients. (4) Rectocolitis therapy could be a trigger factor of wall vessel involvement.