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1.
Eur Ann Allergy Clin Immunol ; 53(4): 168-170, 2021 07.
Article in English | MEDLINE | ID: mdl-32347686

ABSTRACT

Summary: The clinical usefulness of two commercial peach extracts for SPT (by Lofarma SpA and ALK-Abellò, respectively) was compared in a multicenter study carried out in Italy. Peach allergic patients were tested with the two extracts in parallel and underwent the detection of IgE specific for all three peach allergens currently available (Pru p1, Pru p3, and Pru p4, respectively). The two extracts were almost identical in terms of sensitivity and specificity, being able to detect virtually all patients sensitized to stable peach allergens (lipid transfer protein (LTP) and, presumably, peamaclein) but scoring negative in patients exclusively sensitive to labile allergens (either PR-10 and/or profilin). Thus, the two extracts represent an excellent tool to carry out a preliminary component-resolved diagnosis of peach allergy at the first patient visit.


Subject(s)
Allergens/immunology , Antigens, Plant/immunology , Food Hypersensitivity/diagnosis , Plant Extracts , Plant Proteins/immunology , Prunus persica , Skin Tests/methods , Antigens, Plant/analysis , Carrier Proteins , Food Hypersensitivity/immunology , Humans , Immunoglobulin E , Plant Extracts/chemistry , Plant Extracts/immunology , Plant Proteins/analysis
2.
J Investig Allergol Clin Immunol ; 32(1): 40-47, 2021 02 21.
Article in English | MEDLINE | ID: mdl-32732184

ABSTRACT

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.


Subject(s)
Cupressus , Food Hypersensitivity , Allergens/adverse effects , Antigens, Plant/adverse effects , Cross Reactions , Food Hypersensitivity/epidemiology , Gibberellins , Humans , Immunoglobulin E , Plant Proteins/adverse effects , Pollen , Skin Tests/adverse effects
3.
Bioinformatics ; 36(11): 3393-3400, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32119073

ABSTRACT

MOTIVATION: Omics technologies have the potential to facilitate the discovery of new biomarkers. However, only few omics-derived biomarkers have been successfully translated into clinical applications to date. Feature selection is a crucial step in this process that identifies small sets of features with high predictive power. Models consisting of a limited number of features are not only more robust in analytical terms, but also ensure cost effectiveness and clinical translatability of new biomarker panels. Here we introduce GARBO, a novel multi-island adaptive genetic algorithm to simultaneously optimize accuracy and set size in omics-driven biomarker discovery problems. RESULTS: Compared to existing methods, GARBO enables the identification of biomarker sets that best optimize the trade-off between classification accuracy and number of biomarkers. We tested GARBO and six alternative selection methods with two high relevant topics in precision medicine: cancer patient stratification and drug sensitivity prediction. We found multivariate biomarker models from different omics data types such as mRNA, miRNA, copy number variation, mutation and DNA methylation. The top performing models were evaluated by using two different strategies: the Pareto-based selection, and the weighted sum between accuracy and set size (w = 0.5). Pareto-based preferences show the ability of the proposed algorithm to search minimal subsets of relevant features that can be used to model accurate random forest-based classification systems. Moreover, GARBO systematically identified, on larger omics data types, such as gene expression and DNA methylation, biomarker panels exhibiting higher classification accuracy or employing a number of features much lower than those discovered with other methods. These results were confirmed on independent datasets. AVAILABILITY AND IMPLEMENTATION: github.com/Greco-Lab/GARBO. CONTACT: dario.greco@tuni.fi. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
DNA Copy Number Variations , Neoplasms , Algorithms , Biomarkers , Humans , Neoplasms/genetics , Precision Medicine
4.
Allergol. immunopatol ; 47(3): 277-281, mayo-jun. 2019. tab
Article in English | IBECS | ID: ibc-186490

ABSTRACT

Introduction and objectives: The reproducibility of the adverse reaction increases the suggestiveness of a history of food allergy. However, the positive predictive value (PPV) of multiple adverse reaction episodes for the diagnosis of IgE-mediated food allergy is not known. This evaluation was the objective of our study. Patients and methods: We retrospectively studied 180 children with a history of non-anaphylactic adverse reactions after the ingestion of a food. All children had the prick test positive for the offending food and performed the oral food challenge (OFC) within 12 months after the last adverse reaction episode (ARE). We have evaluated whether increasing the number of ARE increased the probability that the OFC would be positive (failed). Results: 93 patients (52%) presented one ARE, 49 (27%) presented two ARE, 24 (13%) presented three ARE, 14 (8%) patients presented ≥ four ARE. The OFC was positive in 94/180 (52%). The outcome of the OFC was found to be positively correlated with the number of ARE (OR = 1.56; 95% CI = 1.16-2.09; p = 0.003). A PPV = 100% was observed with a number of ARE ≥ five. Conclusions: The number of ARE is an important predictor of the diagnosis of food allergy, although less than we would have imagined. The number of ARE could be used to increase the predictability of the diagnostic tests currently in use, to define clinical prediction rules alternative to OFC and easy to use in clinical practice


No disponible


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Anaphylaxis/diagnosis , Food Hypersensitivity/diagnosis , Anaphylaxis/epidemiology , Administration, Oral , Allergens/immunology , Food , Food Hypersensitivity/epidemiology , Immunization , Immunoglobulin E/metabolism , Italy/epidemiology , Predictive Value of Tests , Prognosis , Retrospective Studies
6.
Exp Aging Res ; 45(1): 41-56, 2019.
Article in English | MEDLINE | ID: mdl-30633644

ABSTRACT

Background/Study context: Posture and gait are complex sensorimotor functions affected by age. These difficulties are particularly apparent when performing cognitively demanding tasks. Characterizing the functional organization of brain networks involved in these associations remains a challenge because of the incompatibility of brain imagery techniques with gross body movements. The present study aimed at testing whether resting-state functional connectivity of sensorimotor networks is associated with posture and gait performance recorded offline, in young and older adults. METHODS: Young (n = 12, mean = 24.1 y/o) and older (n = 14, mean = 65.6 y/o) healthy adults were tested for stability of their posture and gait. Four hours later, anatomical and functional brain imaging data were collected with Magnetic Resonance Imaging (MRI). Bilateral precentral and postcentral gyri were used as seeds in a graph theory analysis focused on global and local efficiency. The possible association between these data and posture and gait performance was examined. RESULTS: Both samples presented similar sensorimotor graphs, but with different global and local efficiencies (small world properties). The association between the networks' graph measures and posture and gait performance also differed across groups: local efficiency was correlated with gait stability in challenging conditions in older adults, but not in young adults. CONCLUSION: This exploratory study suggests that combining analyses of functional networks and offline body movement may provide important information about motor function. In older adults, the association between graph properties of the sensorimotor network and gait performance in challenging conditions may be indicative of compensatory processes. Prospective studies involving more subjects with a larger age range are warranted.


Subject(s)
Aging/physiology , Aging/psychology , Gait/physiology , Nerve Net/growth & development , Nerve Net/physiology , Posture/physiology , Aged , Brain Mapping , Cognition/physiology , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Prospective Studies , Trail Making Test , Young Adult
7.
Clin Exp Immunol ; 195(3): 322-333, 2019 03.
Article in English | MEDLINE | ID: mdl-30472725

ABSTRACT

Behçet's syndrome (BS) is a complex disease with different organ involvement. The vascular one is the most intriguing, considering the existence of a specific group of patients suffering from recurrent vascular events involving the venous and, more rarely, the arterial vessels. Several clinical clues suggest the inflammatory nature of thrombosis in BS, especially of the venous involvement, thus BS is considered a model of inflammation-induced thrombosis. Unique among other inflammatory conditions, venous involvement (together with the arterial one) is currently treated with immunosuppressants, rather than with anti-coagulants. Although many in-vitro studies have suggested the different roles of the multiple players involved in clot formation, in-vivo models are crucial to study this process in a physiological context. At present, no clear mechanisms describing the pathophysiology of thrombo-inflammation in BS exist. Recently, we focused our attention on BS patients as a human in-vivo model of inflammation-induced thrombosis to investigate a new mechanism of clot formation. Indeed, fibrinogen displays a critical role not only in inflammatory processes, but also in clot formation, both in the fibrin network and in platelet aggregation. Reactive oxygen species (ROS)-derived modifications represent the main post-translational fibrinogen alterations responsible for structural and functional changes. Recent data have revealed that neutrophils (pivotal in the pathogenetic mechanisms leading to BS damage) promote fibrinogen oxidation and thrombus formation in BS. Altogether, these new findings may help understand the pathogenetic bases of inflammation-induced thrombosis and, more importantly, may suggest potential targets for innovative therapeutic approaches.


Subject(s)
Behcet Syndrome/complications , Inflammation/complications , Thrombosis/etiology , Fibrinogen/physiology , Humans , Immunosuppressive Agents/therapeutic use , Reactive Oxygen Species/metabolism , Thrombosis/drug therapy
8.
Allergol Immunopathol (Madr) ; 47(3): 277-281, 2019.
Article in English | MEDLINE | ID: mdl-30573320

ABSTRACT

INTRODUCTION AND OBJECTIVES: The reproducibility of the adverse reaction increases the suggestiveness of a history of food allergy. However, the positive predictive value (PPV) of multiple adverse reaction episodes for the diagnosis of IgE-mediated food allergy is not known. This evaluation was the objective of our study. PATIENTS AND METHODS: We retrospectively studied 180 children with a history of non-anaphylactic adverse reactions after the ingestion of a food. All children had the prick test positive for the offending food and performed the oral food challenge (OFC) within 12 months after the last adverse reaction episode (ARE). We have evaluated whether increasing the number of ARE increased the probability that the OFC would be positive (failed). RESULTS: 93 patients (52%) presented one ARE, 49 (27%) presented two ARE, 24 (13%) presented three ARE, 14 (8%) patients presented≥four ARE. The OFC was positive in 94/180 (52%). The outcome of the OFC was found to be positively correlated with the number of ARE (OR=1.56; 95% CI=1.16-2.09; p=0.003). A PPV=100% was observed with a number of ARE≥five. CONCLUSIONS: The number of ARE is an important predictor of the diagnosis of food allergy, although less than we would have imagined. The number of ARE could be used to increase the predictability of the diagnostic tests currently in use, to define clinical prediction rules alternative to OFC and easy to use in clinical practice.


Subject(s)
Anaphylaxis/diagnosis , Food Hypersensitivity/diagnosis , Administration, Oral , Allergens/immunology , Anaphylaxis/epidemiology , Child , Child, Preschool , Female , Food , Food Hypersensitivity/epidemiology , Humans , Immunization , Immunoglobulin E/metabolism , Infant , Infant, Newborn , Italy/epidemiology , Male , Predictive Value of Tests , Prognosis , Retrospective Studies
9.
Eur Arch Otorhinolaryngol ; 275(9): 2237-2243, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30088076

ABSTRACT

PURPOSE: To diagnose cholesteatoma when it is not visible through tympanic perforation, imaging techniques are necessary. Recently, the combination of computed tomography and magnetic resonance imaging has proven effective to diagnose middle ear cholesteatoma. In particular, diffusion weighted images have integrated the conventional imaging for the qualitative assessment of cholesteatoma. Accordingly, the aim of this study was to obtain a quantitative analysis of cholesteatoma calculating the apparent diffusion coefficient value. So, we investigated whether it could differentiate cholesteatoma from other inflammatory tissues both in a preoperative and in a postoperative study. METHODS: This study included 109 patients with clinical suspicion of primary or residual/recurrent cholesteatoma. All patients underwent preoperative computed tomography and magnetic resonance imaging with diffusion sequences before primary or second-look surgery to calculate the apparent diffusion coefficient value. RESULTS: We found that the apparent diffusion coefficient values of cholesteatoma were significantly lower than those of non cholesteatoma. In particular, the apparent diffusion coefficient median value of the cholesteatoma group (0.84 × 10- 3 mm2/s) differed from the inflammatory granulation tissue (2.21 × 10- 3 mm2/s) group (p < 2.2 × 10- 16). Furthermore, we modeled the probability of cholesteatoma by means of a logistic regression and we determined an optimal cut-off probability value of ~ 0.86 (specificity = 1.0, sensitivity = 0.97), corresponding to an apparent diffusion coefficient cut-off value of 1.37 × 10- 3 mm2/s. CONCLUSIONS: Our study has demonstrated that apparent diffusion coefficient values constitute a valuable quantitative parameter for preoperative differentiation of cholesteatomas from other middle ear inflammatory diseases and for postoperative diagnosis of recurrent/residual cholesteatomas.


Subject(s)
Cholesteatoma, Middle Ear/diagnostic imaging , Diffusion Magnetic Resonance Imaging , Granulation Tissue/diagnostic imaging , Adolescent , Adult , Aged , Child , Cholesteatoma, Middle Ear/surgery , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Tomography, X-Ray Computed , Young Adult
10.
J Appl Microbiol ; 125(5): 1444-1454, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29998560

ABSTRACT

AIMS: To characterize airborne virus-like particles isolated from two cheese production plants in order to reveal their complexity in terms of viral communities and microbial genes potentially mobilized by viruses. METHODS AND RESULTS: Airborne virus-like particles have been isolated from Grana Padano and Gorgonzola PDO cheese production plants and ripening cellars. A shotgun metagenomics analysis of the isolated viromes highlighted a high complexity of the viral communities both in terms of viral taxonomy and phage-host associations. Bacterial reads in each of the viromes were confirmed to be abundant and their taxonomy appeared to be associated with the environmental parameters and the technological processes that characterize the sampling area. Antibiotic resistance genes have been identified in each virome thus confirming that phages could be involved in the mobilization of antimicrobial resistances among bacterial populations. Interestingly human viruses were also identified even if the contamination source was not revealed. CONCLUSIONS: The environmental conditions, which are imposed by the technology of the dairy process, seam to shape the viral populations as a consequence of the adaptation of microbial taxa to those environments. The identification of sequences belonging to Legionella pneumophila and to the human papillomavirus, raised some considerations about the safety of cheese-ripening cellars. SIGNIFICANCE AND IMPACT OF THE STUDY: In conclusion, the analysis of the dairy airborne viromes, has revealed a high complexity of the viral communities even if the environments where the samples were collected were confined environments. Metagenomics of airborne viral population could be a promising monitoring tool for the biological characterization of dairy environments.


Subject(s)
Cheese/virology , Environmental Monitoring , Food-Processing Industry , Viruses/isolation & purification , Bacteria/genetics , Bacteriophages/genetics , Bacteriophages/isolation & purification , Drug Resistance, Microbial/genetics , Humans , Metagenomics/methods , Viruses/genetics
11.
New Microbes New Infect ; 21: 23-27, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29204282

ABSTRACT

We report the selection in a 15-year-old boy of a multidrug-resistant, extended-spectrum ß-lactamase (ESBL)-producing Aeromonas salmonicida after medicinal leech therapy that required an antibiotic prophylaxis based on piperacillin/tazobactam and cotrimoxazole. Whole genome sequencing of the strain indeed revealed 13 antibiotic resistance genes, including the ESBL CTX-M-3 and the unusual ß-lactamase SCO-1.

12.
Behav Brain Funct ; 13(1): 6, 2017 Apr 08.
Article in English | MEDLINE | ID: mdl-28390437

ABSTRACT

BACKGROUND: Spatial normalization of brain images, a prerequisite for voxel based morphometry analysis, may account for the large variability of the volumetric data in medication overuse headache (MOH); possibly because this disease concerns patients differing on both sex and age, and hence with different brain size and shape. METHODS: The present study aimed at providing a subject-based analysis of macrostructure using a native space volumes segmentation (Freesurfer), and microstructure using a region of interest (ROI: i.e. hippocampus) tractography approach in MOH patients. RESULTS: The results show that MOH patients had decreased volumes of left hemisphere temporal gyri (temporal superior, fusiform) and occipital middle gyrus, together with an increased volume of the left inferior (temporal) lateral ventricle. The left temporal volume was negatively correlated with depression score and medication dependence parameters. Seed-based tractography of the hippocampus revealed a decreased number of reconstructed fibers passing through the left hippocampus. CONCLUSION: To our knowledge, these alterations have not been described with methods involving brain normalization, and they indicate that left hemisphere temporal areas, including the hippocampus, may play a role in MOH pathophysiology. Trial registration number NCT00833209. Registered 29 January 2009.


Subject(s)
Headache Disorders, Secondary/diagnostic imaging , Adult , Brain/physiopathology , Female , Hippocampus/physiopathology , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Temporal Lobe/physiopathology
14.
Eur Ann Allergy Clin Immunol ; 49(1): 15-17, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28120601

ABSTRACT

Background. Hymenoptera stings are sometimes fatal in venom-allergic patients. Fatalities mostly occur in previously stung subjects, especially those with a history of systemic reactions, and could be avoided if patients were properly informed of the existence of a prevention strategy for insect stings, referred to an allergy follow-up and prescribed auto-injectable epinephrine and/or venom-specific immunotherapy (VIT). We sought to assess knowledge and awareness of Hymenoptera Venom Allergy (HVA) in a small sample of Emergency Physicians in our geographic area. Methods. An eight-point questionnaire on HVA was administered to Emergency Department physicians working in the six largest ED in Naples. Results. Twenty-seven physicians completed the questionnaire. Twenty/27 (74%) were unaware of the classification of Hymenoptera sting reactions, 11/27 (41%) were unaware of the existence of prevention strategies such as VIT, 18/27 (67%) did not refer HVA patients to a specialist follow up. One/27 (4%) prescribed auto-injectable epinephrine and 100% wish better information on the topic. Conclusions. In our survey we found a number of ED physicians whose knowledge of HVA, beyond the emergency treatment, is not satisfactory. A closer collaboration among ED physicians and allergists is urgently needed.


Subject(s)
Allergists , Arthropod Venoms/immunology , Hymenoptera/immunology , Physicians , Animals , Emergency Service, Hospital , Humans , Intersectoral Collaboration
15.
Clin Genet ; 91(1): 100-105, 2017 01.
Article in English | MEDLINE | ID: mdl-27311568

ABSTRACT

Intellectual disability (ID) is a major health problem in our society. Genetic causes of ID remain unknown because of its vast heterogeneity. Here we report two Finnish families and one Dutch family with affected individuals presenting with mild to moderate ID, neuropsychiatric symptoms and delayed speech development. By utilizing whole exome sequencing (WES), we identified a founder missense variant c.983T>C (p.Leu328Pro) in seven affected individuals from two Finnish consanguineous families and a deletion c.799_1034-429delinsTTATGA (p.Gln267fs) in one affected individual from a consanguineous Dutch family in the C12orf4 gene on chromosome 12. Both the variants co-segregated in the respective families as an autosomal recessive trait. Screening of the p.Leu328Pro variant showed enrichment in the North Eastern sub-isolate of Finland among anonymous local blood donors with a carrier frequency of 1:53, similar to other disease mutations with a founder effect in that region. To date, only one Arab family with a three affected individuals with a frameshift insertion variant in C12orf4 has been reported. In summary, we expand and establish the clinical and mutational spectrum of C12orf4 variants. Our findings implicate C12orf4 as a causative gene for autosomal recessive ID.


Subject(s)
Genetic Predisposition to Disease/genetics , Intellectual Disability/genetics , Intracellular Signaling Peptides and Proteins/genetics , Mutation , Aged , Amino Acid Sequence , Base Sequence , Child , Consanguinity , Exome/genetics , Family Health , Female , Finland , Founder Effect , Genes, Recessive , Genotype , Geography , Humans , Male , Netherlands , Pedigree , Sequence Analysis, DNA/methods , Sequence Homology, Amino Acid
19.
Eur Ann Allergy Clin Immunol ; 46(3): 116-8, 2014 May.
Article in English | MEDLINE | ID: mdl-24853571

ABSTRACT

In the treatment of respiratory allergies Sublingual Immunotherapy (SLIT) represents a valid alternative to Subcutaneous Immunotherapy (SCIT) for its better safety profile. We describe a case of acute severe asthma following the first maintenance dose of SLIT in a boy allergic to Parietaria pollen. At the initiation of therapy, the patient was in healthy condition and his asthma appeared to be under control. An ultra-rush induction had given no reaction. Despite the good safety profile of SLIT, clinicians should be aware of the risk of adverse effects when prescribing SLIT for respiratory allergies.


Subject(s)
Antigens, Plant/adverse effects , Asthma/chemically induced , Parietaria/immunology , Rhinitis, Allergic, Seasonal/therapy , Sublingual Immunotherapy/adverse effects , Vaccines/adverse effects , Acute Disease , Administration, Sublingual , Antigens, Plant/administration & dosage , Asthma/diagnosis , Asthma/immunology , Child , Drug Administration Schedule , Humans , Male , Rhinitis, Allergic, Seasonal/diagnosis , Rhinitis, Allergic, Seasonal/immunology , Risk Factors , Severity of Illness Index , Vaccines/administration & dosage
20.
Cephalalgia ; 34(8): 605-15, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24449748

ABSTRACT

BACKGROUND: Several imaging studies have identified localized anatomical and functional brain changes in medication-overuse headache (MOH). OBJECTIVE: The objective of this article is to evaluate whole-brain functional connectivity at rest together with voxel-based morphometry in MOH patients, in comparison with episodic migraine (EM) patients and healthy controls (HCs). METHODS: Anatomical MRI and resting-state functional MRI scans were obtained in MOH patients (n = 17 and 9, respectively), EM patients (n = 18 and 15, respectively) and HCs (n = 17 and 17). SPM8 was used to analyze voxel-based morphometry and seed (left precuneus) to voxel connectivity data in the whole brain. RESULTS: Functional connectivity at rest was altered in MOH patients. Connectivity was decreased between precuneus and regions of the default-mode network (frontal and parietal cortices), but increased between precuneus and hippocampal/temporal areas. These functional modifications were not accompanied by significant gross morphological changes. Furthermore, connectivity between precuneus and frontal areas in MOH was negatively correlated with migraine duration and positively correlated with self-evaluation of medication dependence. Gray matter volumes of frontal regions, precuneus and hippocampus were also negatively related to migraine duration. Functional connectivity within the default-mode network appeared to predict anxiety scores of MOH patients while gray matter volumes in this network predicted their depression scores. CONCLUSIONS: Our data suggest that MOH is associated with functional alterations within intrinsic brain networks rather than with macrostructural changes. They also support the view that dependence-related processes might play a prominent role in its development and maintenance.


Subject(s)
Brain Mapping/methods , Brain/drug effects , Brain/physiopathology , Headache Disorders, Secondary/physiopathology , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Migraine Disorders/physiopathology , Nerve Net/drug effects , Nerve Net/physiopathology , Substance-Related Disorders/physiopathology , Adult , Anxiety/physiopathology , Dominance, Cerebral/physiology , Female , Frontal Lobe/physiopathology , Gray Matter/physiopathology , Hippocampus/physiopathology , Humans , Male , Middle Aged , Parietal Lobe/physiopathology , Reference Values , Temporal Lobe/physiopathology
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