Migraine with aura: which patients are most at risk of stroke?

The complex association between migraine (M) and ischemic stroke (IS) is discussed. Epidemiological studies and meta-analyses show that M with aura (MA) and not M without aura, doubles the risk of IS. The risk is higher for female gender, young age and higher headache attacks frequency. Smoking habit and oral contraceptives, especially if associated, increase stroke risk. The underlying pathogenetic mechanisms are not completely understood, but it is hypothesized that a particular brain susceptibility to cortical spread depression could explain the association between MA and IS. The absolute risk of IS in migraineurs is relatively low and an antithrombotic primary prevention is not indicated, but it is mandatory to investigate and treat associated risk factors for IS and, in young MA women, consider only progestinic oral contraceptives, if needed, and smoking cessation.

Deterioration of bio-based polylactic acid plastic teabags under environmental conditions and their associated effects on earthworms.

In response to the plastic waste crisis, teabag producers have substituted the petrochemical-plastic content of their products with bio-based, biodegradable polymers such as polylactic acid (PLA). Despite widespread use, the degradation rate of PLA/PLA-blended materials in natural soil and their effects on soil biota are poorly understood. This study examined the percentage mass deterioration of teabags with differing cellulose:PLA compositions following burial (-10 cm depth) in an arable field margin for 7-months, using a suite of analytical techniques, such as size exclusion chromatography, 1H nuclear magnetic resonance, dynamic scanning calorimetry, and scanning electron microscopy. The effect of 28-d exposure to teabag discs at environmentally relevant concentrations (0.02 %, 0.04 % and 0.07 % w/w) on the survival, growth and reproduction (OECD TG 222 protocol) of the key soil detritivore Eisenia fetida was assessed in laboratory trials. After 7-month burial, Tbag-A (2.4:1 blend) and Tbag-B (3.5:1 cellulose:PLA blend) lost 66 ± 5 % and 78 ± 4 % of their total mass, primarily attributed to degradation of cellulose as identified by FTIR spectroscopy and a reduction in the cellulose:PLA mass ratio, while Tbag-C (PLA) remained unchanged. There were clear treatment and dose-specific effects on the growth and reproductive output of E. fetida. At 0.07 % w/w of Tbag-A adult mortality marginally increased (15 %) and both the quantity of egg cocoons and the average mass of juveniles also increased, while at concentrations ≥0.04 % w/w of Tbag-C, the quantity of cocoons was suppressed. Adverse effects are comparable to those reported for non-biodegradable petrochemical-based plastic, demonstrating that bio-based PLA does not offer a more 'environmentally friendly' alternative. Our study emphasises the necessity to better understand the environmental fate and ecotoxicity of PLA/PLA-blends to ensure interventions developed through the UN Plastic Pollution Treaty to use alternatives and substitutes to conventional plastics do not result in unintended negative consequences.

MR Imaging Signs of Gadolinium Retention Are Not Associated with Long-Term Motor and Cognitive Outcomes in Multiple Sclerosis.

BACKGROUND AND PURPOSE: The long-term impact of gadolinium retention in the dentate nuclei of patients undergoing administration of seriate gadolinium-based contrast agents is still widely unexplored. The aim of this study was to evaluate the impact of gadolinium retention on motor and cognitive disability in patients with MS during long-term follow-up. MATERIALS AND METHODS: In this retrospective study, clinical data were obtained from patients with MS followed in a single center from 2013 to 2022 at different time points. These included the Expanded Disability Status Scale score to evaluate motor impairment and the Brief International Cognitive Assessment for MS battery to investigate cognitive performances and their respective changes with time. The association with qualitative and quantitative MR imaging signs of gadolinium retention (namely, the presence of dentate nuclei T1-weighted hyperintensity and changes in longitudinal relaxation R1 maps, respectively) was probed using different General Linear Models and regression analyses. RESULTS: No significant differences in motor or cognitive symptoms emerged between patients showing dentate nuclei hyperintensity and those without visible changes on T1WIs (P = .14 and 0.92, respectively). When we tested possible relationships between quantitative dentate nuclei R1 values and both motor and cognitive symptoms, separately, the regression models including demographic, clinical, and MR imaging features explained 40.5% and 16.5% of the variance, respectively, without any significant effect of dentate nuclei R1 values (P = .21 and 0.30, respectively). CONCLUSIONS: Our findings suggest that gadolinium retention in the brains of patients with MS is not associated with long-term motor or cognitive outcomes.

FLT3-targeted therapy restores GATA1 pathway function in NPM1/FLT3-ITD mutated acute myeloid leukaemia.

One-third of newly diagnosed adult acute myeloid leukaemia (AML) carry FLT3 mutations, which frequently occur together with nucleophosmin (NPM1) mutations and are associated with worse prognosis. FLT3 inhibitors are widely used in clinics with limitations due to drug resistance. AML cells carrying FLT3 mutations in both mouse models and patients present low expression of GATA1, a gene involved in haematopoietic changes preceding AML. Here, we show that FLT3 inhibition induces cellular responses and restores the GATA1 pathway and functions in NPM1/FLT3-ITD mutated AML, thus providing a new mechanism of action for this drug.

Towards the integration of ecophysiology with fisheries stock assessment for conservation policy and evaluating the status of the Mediterranean Sea.

Recent European Union (EU) regulations have been introduced to discourage the capture of undersized specimens with the aim of reducing the bycatch mortality imposed by commercial fisheries. We argue that we still lack accurate data regarding basic information required to properly implement these regulations for most Mediterranean ecosystems, including the true mortality imposed by fisheries, escape rates from fishing gears and the capability of specimens to survive following discard. We suggest that additional reliance on physiological biomarkers could assist in all aspects of the data collection required to support implementation of the EU discard ban (aka landing obligation), particularly in determining which species should receive special dispensation from this policy. Ideally, this new approach, here termed the 'Fisheries Environmental and Physiological Stress Analysis' (FEPSA), would become an important step for any fish stock assessment within the ecosystem approach to fisheries management and the recognition of Good Environmental Status, as established by the EU in the Marine Strategy Framework Directive (2008/56/EC). In particular, the main goal of FEPSA would be applying the study of physiological stressors to exploited stocks to estimate the so-called collateral fishing mortality, which includes the mortality experienced by fish that escape after interacting with fishing gears or that are discarded, with some degree of injury or physiological stress. The approach outlined here, which is described for bottom trawls but adaptable to any other type of fishing gear, is not a trivial undertaking but is a requirement for collecting the data required by recent EU fisheries policies. While we agree that the threats to marine biodiversity posed by fishing and associated discard practices require strong policy interventions, we emphasize that the research programs needed to support such initiatives, including the landing obligation, should be given equal priority. This is particularly true for Mediterranean fisheries, which are at a complex intersection of jurisdictional boundaries, numerous additional ecosystem threats including widespread pollution, thermal variation and hypoxia, and are historically understudied as compared to fisheries and species in more northern climates.

Olfactory function and cognition in relapsing-remitting and secondary-progressive multiple sclerosis.

BACKGROUND: Both cognition and olfaction are impaired in multiple sclerosis (MS). However, little is known about the relationship between smell identification ability and measures of cognitive function in this disease. OBJECTIVE: To assess olfactory function in MS and to evaluate its relationship with cognitive and physical disability. METHODS: Fifty-five MS patients and 20 healthy controls (HCs) were tested. The University of Pennsylvania smell identification test (UPSIT) was administered to assess olfactory function. Cognitive function was tested using the symbol digit modalities test (SDMT), California verbal learning test-II (CVLT II), brief visuospatial memory test (BVMT), paced auditory serial addition test (PASAT), and controlled oral word association test (COWAT). Fatigue and depressive symptoms were evaluated using the Modified Fatigue Impact Scale and the Beck Depression Inventory II, respectively. RESULTS: MS patients had lower UPSIT scores than those of the HCs (28.76 ±â€¯5.48 vs 31.7 ±â€¯2.18, p = 0.02), with secondary-progressive and cognitively impaired MS patients showing the greatest impairment. Scores on the SDMT, CVLTII, BVMT and COWAT were related to the olfactory test scores. CONCLUSION: We confirm that olfactory function is impaired in MS, particularly in progressive phenotypes, and show, for the first time, that such dysfunction is related to a broad range of cognitive measures. Our data suggest that olfactory dysfunction might be considered as an indirect measure of MS severity. Longitudinal studies are needed to confirm this possibility.

Detection of bovine Deltapapillomavirus DNA in peripheral blood of healthy sheep (Ovis aries).

Blood samples from 65 sheep were tested for the presence of bovine Deltapapillomavirus (δPVs) DNA. The sheep were divided into three groups. Sheep in groups 1 and 2 were from Sardinia and Campania, respectively, and were in contact with cattle and grazed on lands contaminated with bracken fern. Sheep in Group 3 lived in closed pens and had no contact with cattle. These sheep were fed hay that did not contain bracken fern. Bovine δPV E5 DNA was detected in blood from 24 of 27 (89%) sheep in Group 1. A single bovine δPV type was detected in the blood from nine (33%) sheep, including the detection of bovine δPV-1 DNA in four sheep, bovine δPV-2 in four and δPV-13 in one sheep. Two δPV types were detected in 33% of the sheep, and three bovine δPV types were detected in 22% of the sheep. Bovine δPVs were detected in 17 of 20 (85%) sheep from Group 2. The detection rate by a single δPV type was 40% with just δPV-1 DNA amplified from two, just δPV-2 DNA from four, and just δPV-13 DNA from two sheep. Two and three δPVs were detected in 30% and 15%, respectively. All sequenced amplicons showed a 100% identity with papillomaviral E5 DNA deposited in GenBank. Bovine δPV-14 DNA sequences were not detected from any sheep. No bovine δPV DNA was revealed in blood samples from sheep in Group 3. The detection of bovine δPV DNA in the blood of sheep means that sheep may be able to be infected by these PVs. This suggests that bovine δPVs could potentially be a previously unrecognized cause of disease in sheep. Furthermore, it is possible that sheep could act as a reservoir for these viruses.

Electroclinical evolution in ring chromosome 20 epilepsy syndrome: a case with severe phenotypic features followed for 25 years.

Intractable epilepsy and peculiar EEG patterns characterize ring chromosome 20 syndrome [r(20)], while dysmorphic features, mental retardation and behavioural disturbances are widely variable. The clinical evolution of r(20) over time is not well defined as relatively few cases have been reported. Here we describe a patient with severe clinical features followed for a 25-year period. The patient was subjected to clinical, psychometric and EEG evaluation twice a year from the age of 21 years. Cytogenetic studies, using chromosome analysis and fluorescence in situ hybridization (FISH) and several immunological investigations were performed. Ring chromosome 20 was found in 50% of examined metaphases with the deletion of subtelomeric regions 20p and 20q. Our patient presented with marked dysmorphic features, severe mental retardation, tetraparesis, dysarthria and intractable epilepsy with onset during the first year of life. During follow up, EEG findings and clinical features progressively worsened: a progressive disorganization of background EEG activity occurred and mental and motor impairment evolved. The severity of clinical expression depended on the extent of chromosomal deletion and on the haploinsufficiency of other important related genetic loci due to ring instability. The progressive worsening of both clinical and EEG features over a long period, which has also been reported by other authors, further characterized this syndrome.

Two-year surveillance on fluconazole susceptibility of Candida spp isolates in a general and university hospital in Rome.

Fluconazole susceptibility was tested in 385 clinical yeast isolates (285 Candida albicans, 38 C. glabrata, 31 C. tropicalis, 31 other Candida subsp.) using the agar disk diffusion test. Yeasts were collected from specimens obtained from outpatients (69) and inpatients (intensive care unit: 79 isolates, major burn unit: 31 isolates, hematology ward: 45 isolates, gynecology ward: 67 isolates, other wards: 94 isolates). Three hundred and fifty-six (92%) yeast isolates showed to be susceptible, 18 (5%) were susceptible dose-dependent, and 10 (3%) were resistant to fluconazole. Of the resistant group, 3 isolates were C.albicans, while seven were Candida non-albicans (2 C. rugosa, 2 C. humicola, 1 C. tropicalis, 1 C. ciferrii, 1 C. glabrata). The disk-diffusion method was easy to perform and there were no difficulties in the interpretation of inhibition zone diameters. Fluconazole maintained a good activity against Candida spp despite its extensive use for the prophylaxis and treatment of fungal infections.

The use of sulodexide in the treatment of peripheral vasculopathy accompanying metabolic diseases. Controlled study in hyperlipidemic and diabetic subjects.

Thirty vasculopathic subjects with hyperlipoproteinemia (18) and/or diabetes (22) underwent a clinical double-blind study in order to evaluate the effect of sulodexide on lipid and hemorheologic parameters. The experimental design consisted of a first 20-day i.m. therapeutic period with either sulodexide (300 Lipasemic Units twice daily via intramuscular route) or placebo and the following 70 days with the active compound for both groups at the same posology. Results obtained demonstrated that sulodexide yields a hypotriglyceridemic effect on type IV hyperlipoproteinemia and hypofibrinogenic effect, as well. Moreover, this compound exerted a beneficial effect on HDL Cholesterol levels and on the antithrombin III activity by increasing both parameters significantly. Signs and symptoms were alleviated, particularly in the most severe cases of peripheral vascular disease. Insignificant and slight changes were observed at the end of treatments as regards the efficacy of the two administration routes, the i.m. one being more efficacious on lipid parameters and faster acting. No side effects or intolerance were observed during the different periods of the trial.

Three pathways between the sacroiliac joint and neural structures.

BACKGROUND AND PURPOSE: Despite ongoing clinical suspicion regarding the relationship between sacroiliac joint (SIJ) dysfunction and lower extremity symptoms, there is a paucity of scientific literature addressing this topic. The purpose of this study was to describe patterns of contrast extravasation during SIJ arthrography and postarthrography CT in patients with lower back pain and to determine whether there are pathways of communication between the SIJ and nearby neural structures. METHODS: Fluoroscopically guided SIJ arthrography was performed on 76 SIJs. After the injection of contrast medium, anteroposterior, lateral, and oblique radiographs as well as 5-mm contiguous axial and direct coronal CT images were obtained. Contrast extravasation patterns were recorded for each joint. These observations included a search for contrast extravasation from the SIJ that contacted nearby lumbosacral nerve roots or structures of the plexus. RESULTS: Sixty-one percent of all joints studied revealed one of five contrast extravasation patterns. Three of these observed patterns show a pathway of communication between the SIJ and nearby neural structures. These included posterior extravasation into the dorsal sacral foramina, superior recess extravasation at the sacral alar level to the fifth lumbar epiradicular sheath, and ventral extravasation to the lumbosacral plexus. CONCLUSION: Three pathways between the SIJ and neural structures exist.

Specific impairment of BAER's in Friedreich's ataxia. Auditory evoked responses in clinical evaluation and differential diagnosis.

We have investigated brainstem and cortical auditory responses (BAERs and CAERs) in 16 cases of Friedreich's ataxia (FA) and have compared the findings with those obtained in 2 cases of familial spastic paraplegia (FSP), in 5 cases of Charcot-Marie-Tooth disease (CMTD), and in 6 cases of atypical FA of uncertain classification. BAERs could not be elicited in 11 FA patients and constantly disappeared at a higher intensity threshold than in normal subjects in the remaining 5 patients. BAERs were normal or only slightly abnormal in FSP and CMTD patients. CAERs were normal in all 29 patients. BAERs tended to disappear with the progression of FA and BAER thresholds were correlated with the Inherited Ataxias Clinical Rating Scale score, which is an index of the severity of illness. BAERs contributed to the diagnosis, or exclusion of FA in patients with an atypical picture. It is suggested that in FA myelinated fibers in the spiral ganglion are partially affected, resulting in the decrease of wave amplitude such as occurs for peripheral sensory potentials.

Severe systemic allergic reaction induced by accidental skin contact with cow milk in a 16-year-old boy. A case report.

The symptoms of food allergy are rarely induced by skin contact. A 16-year-old boy was referred to our Allergology Centre after an episode of systemic symptoms triggered by accidental skin contact with a drop of cow milk (CM) dripped from a sandwich containing fresh cheese. The patient had been allergic to CM from the age of 24 months and had experienced several episodes of urticaria-angioedema after the ingestion of tiny or "hidden" amounts of CM proteins. In vivo and in vitro diagnostic procedures showed intense sensitisation to all CM proteins (1/100 dilutions of allergenic extracts produced large wheals, and class 4 specific IgE antibodies. Total IgE antibodies were elevate (770.0 UI/). A moderate degree of bronchial hyperresponsiveness was found (PC20 metacholine: 3.90 milligrams). This case report suggests that patients with a high degree of sensitisation to CM proteins should be alert to the danger of skin contact and should beware of "hidden" CM allergens.

Bioptically demonstrated Lafora disease without EPM2A mutation: a clinical and neurophysiological study of two sisters.

Lafora disease (LD) is an autosomal recessive inherited form of progressive myoclonic epilepsy with dementia and ataxia, usually presenting in the second decade of life and inexorably progressing until death. Neuropathological hallmarks are Lafora bodies, intracytoplasmic inclusions that can be found in neurons and in other tissues. LD gene (EPM2A), mapping on chromosome 6, encodes for a tyrosine phosphatase protein called laforin. However, up to 20% cases of LD are not genetically linked to chromosome 6. We report two sisters affected from bioptically diagnosed LD but without evidence of EPM2A mutation. Although familial cases of LD are already reported in literature, our observation leads to some considerations on clinical-electrophysiological evolution as well as to remark the genetic heterogeneity of this condition. In addition, we report the good effect of the Levetiracetam for the treatment of myoclonus in these patients, also demonstrated by the electrophysiological findings.

Residual reading capability in a patient with alexia without agraphia.

A case of pure alexia due to an ischemic lesion of the occipital temporal region is described. Written words could be matched but not read. Immediate memory span for graphemes was defective. The reading defect probably depends on the inability to modify the written word "globally"; the phonological process was intact, but the memory disturbance impeded reading. The dissociation is explained by the preservation of word forms, which are linked to the semantic stage. Non-written stimuli trigger a "meaning" which evokes the word form and so the written word is recognized even though it cannot be read.

Incidence and complexity of ventricular ectopy during Holter monitoring in patients with exercise-induced myocardial ischemia and normal or mildly reduced left ventricular function.

We aimed to assess the relationship between frequent and complex ventricular ectopy by continuous electrocardigraphic 24-hours Holter monitoring in patients with coronary artery disease and inducible ischemia during exercise procedures. We investigated 609 consecutive patients. They were referred for chest pain (28% with a previous myocardial infarction, older than 6 months). In all population patients radionuclide ventriculography showed a global normal or mildly reduced left ventricular function (ejection fraction > 45%). All patients showed exercise-induced myocardial ischemia (ST depression) and exercise thallium-201 reversible defects. During Holter monitoring, in study population, divided according to incidence of premature ventricular complexes (PVC), we found a higher prevalence of complex ventricular arrhythmias (CVA) (bigeminy, couplets, ventricular tachycardia, multiformity) in patients with high incidence of PVC. The relationship between frequent and complex ventricular ectopy has been observed also during ischemic ST shifts occuring during 24-hours monitoring. In contrast, the R on T phenomenon was not related to incidence of PVC. Therefore, in patients with exercise-induced myocardial ischemia and global normal or mildly reduced left ventricular function there is a relationship between frequent and complex ventricular ectopy, as previously suggested in CAD patients with depressed left ventricular function.

The Fortin finger test: an indicator of sacroiliac pain.

Simple and reliable diagnostic aids need to be available for clinicians to consider sacroiliac joint dysfunction in the differential diagnosis of low back pain. The Fortin finger test was used as a means to identify patients with low back pain and sacroiliac joint dysfunction. Provocation-positive sacroiliac joint injections were used to ratify or refute the applicability of this new clinical sign for identification of patients with sacroiliac joint dysfunction. Sixteen subjects were chosen from 54 consecutive patients by using the Fortin finger test. All 16 patients subsequently had provocation-positive joint injections validating sacroiliac joint abnormalities. A subset of 10 individuals underwent additional evaluation to exclude the possibility of confounding discogenic or posterior joint pain sources. All 10 patients had no indication of either discogenic or zygapophyseal joint pain generators. These results indicate that positive findings of the Fortin finger test, a simple diagnostic measure, successfully identifies patients with sacroiliac joint dysfunction.

[Clinical efficacy of picotamide]. / Efficacia clinica della picotamide.

The effects of picotamide (300 mg b.i.d.) for secondary prevention of cerebral ischemia were compared with the effects of low-dosage aspirin (300 mg/die). Out of the 87 randomized patients, 47 completed a six month period of treatment: 29 patients in the picotamide (group P) with a mean period of 14.5 months, 18 in the aspirin group (group A) with a mean period of 15.2 months. Both showed reduced incidence of further cerebral ischemic episodes in comparison with non treated patients (literature data). Using intention-to-treat analysis, the recurrence of ischemic events (including TIA) was 5.8% in group P and 14.3% in group A. Explanatory analysis yielded similar results: 10.3% of patients in group P and 27.8% in group A had recurrence of cerebral ischemic eposides. Evaluating as endpoints only RIND and stroke, the incidence was 10.3% in group P and 16.7% in group A. In conclusion, picotamide was more effective than aspirin; however the difference was not statistically significant due to the small number of patients. The drug was well tolerated and only two patients dropped out because of side effects. Picotamide did not alter laboratory tests significantly.

[Effect of the chronic treatment with L-acetylcarnitine in Down's syndrome]. / Effetti del trattamento cronico con L-acetilcarnitina nella sindrome di Down.

Neuropsychologic tests were performed in subjects with Down syndrome in order to assess the effect of a 90-day treatment with L-acetyl-carnitine (LAC). Findings were evaluated statistically (Wilcoxon test) and compared to three further groups of subjects: untreated Down syndrome, mental deficiency due to other cases treated and not treated with LAC (Mann-Whitney U-test). Treated Down syndrome patients showed statistically significant improvements of visual memory and attention both in absolute terms and in comparison with the other groups. No improvement was found in mentally deficient non-Down subjects, so that the favourable effect of LAC appears to be specific for Down patients. In view of the analogies of the pathology and neurochemistry between Down syndrome and Alzheimer degenerative deficiency (deficit of cholinergic transmission) it is suggested that the action of LAC in these pathologies is related to its direct and indirect cholinomimetic effect.