Clinical and advanced neurophysiology in the prognostic and diagnostic evaluation of disorders of consciousness: review of an IFCN-endorsed expert group.

The analysis of spontaneous EEG activity and evoked potentialsis a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). Thepast few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury,opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of bothconsolidated and investigational electrophysiological techniquesfor the prognostic and diagnostic assessment of DoC.We describe conventional clinical EEG approaches, then focus on evoked and event-related potentials, and finally we analyze the potential of novel research findings. In doing so, we (i) draw a distinction between acute, prolonged and chronic phases of DoC, (ii) attempt to relate both clinical and research findings to the underlying neuronal processes and (iii) discuss technical and conceptual caveats.The primary aim of this narrative review is to bridge the gap between standard and emerging electrophysiological measures for the detection and prediction of recovery of consciousness. The ultimate scope is to provide a reference and common ground for academic researchers active in the field of neurophysiology and clinicians engaged in intensive care unit and rehabilitation.

Compound heterozygosity for TNXB genetic variants in a mixed-breed dog with Ehlers-Danlos syndrome.

The Ehlers-Danlos syndromes (EDSs) are a heterogeneous group of inherited connective tissue disorders characterized by skin hyperextensibility, joint hypermobility and tissue fragility. Inherited disorders similar to human EDS have been reported in different mammalian species. In the present study, we investigated a female mixed-breed dog with clinical signs of EDS. Whole-genome sequencing of the affected dog revealed two missense variants in the TNXB gene, encoding the extracellular matrix protein tenascin XB. In humans, TNXB genetic variants cause classical-like EDS or the milder hypermobile EDS. The affected dog was heterozygous at both identified variants. Each variant allele was transmitted from one of the case's parents, consistent with compound heterozygosity. Although one of the variant alleles, XM_003431680.3:c.2012G>A, p.(Ser671Asn), was private to the family of the affected dog and absent from whole-genome sequencing data of 599 control dogs, the second variant allele, XM_003431680.3:c.2900G>A, p.(Gly967Asp), is present at a low frequency in the Chihuahua and Poodle population. Given that TNXB is a functional candidate gene for EDS, we suggest that compound heterozygosity for the identified TNXB variants may have caused the EDS-like phenotype in the affected dog. Chihuahuas and Poodles should be monitored for EDS cases, which might confirm the hypothesized pathogenic effect of the segregating TNXB variant.

A frameshift variant in the COL5A1 gene in a cat with Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) is a group of heritable connective tissue disorders caused by defective collagen synthesis or incorrect assembly of the collagen triple helical structure. EDS is characterised by joint hypermobility, skin hyperextensibility, abnormal scarring, poor wound healing and tissue friability. Human EDS may be caused by variants in several different genes including COL5A1, which encodes the collagen type V alpha 1 chain. For the present study we investigated a 1.5-year-old, spayed female, domestic shorthair cat with EDS. The affected cat showed multiple recurrent skin tears, hyperextensibility of the skin and joint abnormalities. We obtained whole genome sequencing data from the affected cat and searched for variants in candidate genes known to cause EDS. We detected a heterozygous single base-pair deletion in exon 43 of the COL5A1 gene, namely c.3420delG. The deletion was predicted to result in a frameshift and premature stop codon: p.(Leu1141SerfsTer134). Sanger sequencing confirmed that the variant was present in the affected cat and absent from 103 unaffected cats from different breeds. The variant was also absent from a Burmese cat with EDS. Based on knowledge about the functional impact of COL5A1 variants in other species, COL5A1:c.3420delG represents a compelling candidate causative variant for the observed EDS in the affected cat.

Comparing immediate-type food allergy in humans and companion animals-revealing unmet needs.

Adverse food reactions occur in human as well as veterinary patients. Systematic comparison may lead to improved recommendations for prevention and treatment in both. In this position paper, we summarize the current knowledge on immediate-type food allergy vs other food adverse reactions in companion animals, and compare this to the human situation. While the prevalence of food allergy in humans has been well studied for some allergens, this remains to be investigated for animal patients, where owner-reported as well as veterinarian-diagnosed food adverse reactions are on the increase. The characteristics of the disease in humans vs dogs, cats, and horses are most often caused by similar, but sometimes species-dependent different pathophysiological mechanisms, prompting the specific clinical symptoms, diagnoses, and treatments. Furthermore, little is known about the allergen molecules causative for type I food allergy in animals, which, like in human patients, could represent predictive biomarkers for risk evaluation. The definite diagnosis of food allergy relies-as in humans-on elimination diet and provocation tests. Besides allergen avoidance in daily practice, novel treatment options and tolerization strategies are underway. Taken together, numerous knowledge gaps were identified in veterinary food allergy, which need to be filled by systematic comparative studies.

Mismatch Negativity in essential tremor: role of age at onset in pre-attentive auditory discrimination.

OBJECTIVE: To investigate whether pre-attentive auditory discrimination is impaired in patients with essential tremor (ET) and to evaluate the role of age at onset in this function. METHODS: Seventeen non-demented patients with ET and seventeen age- and sex-matched healthy controls underwent an EEG recording during a classical auditory MMN paradigm. RESULTS: MMN latency was significantly prolonged in patients with elderly-onset ET (>65 years) (p=0.046), while no differences emerged in either latency or amplitude between young-onset ET patients and controls. CONCLUSIONS: This study represents a tentative indication of a dysfunction of auditory automatic change detection in elderly-onset ET patients, pointing to a selective attentive deficit in this subgroup of ET patients. SIGNIFICANCE: The delay in pre-attentive auditory discrimination, which affects elderly-onset ET patients alone, further supports the hypothesis that ET represents a heterogeneous family of diseases united by tremor; these diseases are characterized by cognitive differences that may range from a disturbance in a selective cognitive function, such as the automatic part of the orienting response, to more widespread and complex cognitive dysfunctions.

Attention in essential tremor: evidence from event-related potentials.

Clinically subtle executive dysfunctions have recently been described in essential tremor (ET), though the presence of attentional deficits is still unclear. We investigated the psychophysiological aspects of attention in ET, using event-related potentials (ERPs). Twenty-one non-demented patients with ET and 21 age- and sex-matched healthy controls underwent a psychophysiological evaluation. P300 components and the Contingent Negative Variation (CNV) were recorded. The latencies and amplitudes of the P3a and P3b subcomponents and CNV areas were evaluated. Possible correlations between clinical parameters and ERP data were investigated. P3a latency was significantly longer in the ET group (p < 0.05), while no differences emerged between patients and controls in P3b latency. No differences were observed between the two groups in the CNV parameters. ET patients display a difficulty in the response to novelty and in the recruitment of prefrontal attentive circuits, while the memory context-updating process appears to be spared. This selective cognitive dysfunction does not appear to interfere with the attentional set linked to the expectancy evaluated during a complex choice-reaction time task, which is preserved in ET. This multitask psychophysiological approach reveals the presence of a peculiar attentional deficit in patients with ET, thus expanding the clinical features of this disease.

Prevalence of canine methicillin resistant Staphylococcus pseudintermedius in a veterinary diagnostic laboratory in Italy.

The overall prevalence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) was 2% (10/590) among 590 canine specimens submitted to an Italian veterinary diagnostic laboratory during a two-month period, and 21% (10/48) among Staphylococcus intermedius group (SIG) isolates. All methicillin-resistant strains exhibited additional resistance to fluoroquinolones, gentamicin, lincosamides, tetracyclines, and potentiated sulfonamides, belonged predominantly to spa type t02 and harboured SCCmec type II-III cassette.

Diffusion tensor MRI-based estimation of the influence of brain tissue anisotropy on the effects of transcranial magnetic stimulation.

We evaluate and discuss the relevance of fiber anisotropy in estimating the effect of transcranial magnetic stimulation (TMS) on the human brain. Finite element simulations were carried out on a three-dimensional model of the head that included anisotropic conductivity information derived from diffusion tensor imaging (DTI). The results show that anisotropy has minor effects both on the position of the main locus of activation and on its intensity. It has considerably more effect on the spatial distribution of the induced electric field, yielding differences of the order of 10% of the maximum induced field. Moreover the area affected by magnetic stimulation is slightly larger when we include fiber anisotropy in the calculations than in an isotropic model. We also show that the induced field observed in the anisotropic model does not always align with the local fiber orientation but rather follows specific patterns of parallelity. These findings will help to improve the estimation of the areas involved in magnetic stimulation.

Cyclophosphamide Effect on the Epithelial Covering of Rats Fetuse's Tongue: A Morphometric Study / Efectos de la Ciclofosfamida en el Epitelio de Revestimiento de la Lengua de Fetos de Rata: Un Estudio Morfométrico

The present study has the aim to describe morphologically, morphometrically and stereologically some changes in the tongue epithelium of rat fetuses under the effect of cyclosphosphamide. This drug was used in a single 6mg/kg according to the body weight in the tenth ­ pregnancy day while the control group received equal dosage of saline solution by the same duct and in the same day of pregnancy. The fetuses were plunged into fixed solution of Bouin for five days and the heads of then were divided and blocked in paraffin. Histological sections of six-micrometer thickness were performed and then colored with hematoxilin and eosin. It was used morphometrical and stereological analysis after the morphological study. The data were submitted under the statistical non-parametric test of Mann-Whitney. The results showed that the cyclosposphamide usage effect during the rat pregnancy caused a delayed in the embryo fetal growing, a reduction in the placental weight as wells as in the umbilicus cord length. The covering epithelia in the tongue of the treated group showed some changes since there was an epithelial hyperplasia associated with a cell hypotrophy. The fetuses in this group were more premature than the ones in the control.

El estudio tiene como objetivo describir morfológica, morfométrica y estereológicamente algunos cambios en el epitelio de la lengua de fetos de rata bajo los efectos de la ciclofosfamida. Esta droga fue usada en una muestra única de 6mg/kg de acuerdo al peso del cuerpo, en el décimo día de preñez, mientras el grupo control recibió igual dosis de una solución salina, por la misma vía, en los mismos días de preñez. Los fetos fueron sumergidos en solución fijadora de Bouin, por cinco días y las cabezas de ellos fueron cortadas y colocadas en bloques de parafina. Secciones histológicas de 6 µm fueron teñidas con hematoxilina-eosina. Después del estudio morfológico se realizaron análisis morfométricos y estereológicos. Se utilizó el test estadístico no paramétrico de Mann-Whitney. Los resultados mostraron que el uso de la ciclofosfamida provoca efectos durante la preñez de la rata, causando un retardo en el crecimiento de los embriones, una reducción en el peso de las placentas como también, en la longitud del funículo umbilical. El epitelio de revestimiento de la lengua del grupo tratado, mostró algunos cambios desde una hiperplasia epitelial asociada con una hipotrofia celular. Los fetos del grupo tratado fueron más prematuros que los del grupo control.

Topological approach to neural complexity.

Considerable effort in modern statistical physics is devoted to the study of networked systems. One of the most important example of them is the brain, which creates and continuously develops complex networks of correlated dynamics. An important quantity which captures fundamental aspects of brain network organization is the neural complexity C(X) introduced by Tononi et al. [Proc. Natl. Acad. Sci. USA 91, 5033 (1994)]. This work addresses the dependence of this measure on the topological features of a network in the case of a Gaussian stationary process. Both analytical and numerical results show that the degree of complexity has a clear and simple meaning from a topological point of view. Moreover, the analytical result offers a straightforward and faster algorithm to compute the complexity of a graph than the standard one.

[Results of elective open surgery for juxtarenal aortic aneurysms]. / I risultati del trattamento elettivo in open surgery degli aneurismi juxtarenali dell'aorta.

Review of the most significant surveys (data base: Pub Med on September 2003) of elective open surgery for Juxtarenal aneurysms and personal results of 106 cases (9.3% of AAA consecutively operated in the last 11 yrs.) are reported. Mortality and morbidity are discussed related to: technique of aortic cross-clamping; protective measures on splanchnic and renal perfusion; risks from previous CAD and chronic renal failure. Over all, the main predictive factor is the accuracy of the selected technique, without any difference among different approaches, and the same results of infrarenal aneurysms can be obtained.

Combined surgical approach for carotid and coronary stenosis. Sixty-four patients and review of literature.

BACKGROUND: The proper role of combined carotid endarterectomy (CEA) and coronary bypass (CABG) is still controversial. We contribute to the discussion through the critical evaluation of 64 consecutive patients, whose data have been collected in a prospective way. METHODS: Between 1990 and 1999, 64 patients presenting a critical coronary disease (unemendable by PTA) associated with severe carotid stenosis (= or >70% if symptomatic, = or >80% if asymptomatic), underwent combined CEA-CABG. Cardiological symptoms were evident in 90.6% of cases. Thirty-five patients (54.7%) had a three-vessel coronaropathy, 18 (28.1%) a two-vessel disease and 11 (17.2%) severe stenosis of the common trunk; furthermore 7 patients (10.9%) had a low ejection fraction (<50%). A positive neurologic history was present in 22 (44%) patients. Thirty-four patients (55%) had a carotid stenosis >90%; a significant disease of the contralateral carotid axis was observed in 53% of cases: stenosis >50% in 30 patients and thrombosis in 4. CEA was performed with somato-sensorial evoked potential monitoring. RESULTS: The hospital mortality rate was 6.2% (4 patients). The cause of death was cardiac in 2 cases (1 early bypass thrombosis and 1 irreversible coronary spasm) and related to a multiorgan failure in 2. The neurologic morbidity rate was 0%. CONCLUSIONS: Our data highlight that in these high-risk patients the combined approach dramatically reduces the stroke risk although the mortality rate is still higher than that observed after CEA or CABG.

Suprarenal aortic cross-clamping in elective abdominal aortic aneurysm surgery.

INTRODUCTION: this retrospective study was undertaken to evaluate whether suprarenal aortic cross-clamping increased the perioperative mortality and morbidity as compared to infrarenal clamping, in order to create the rationale for a more extensive application of this apparently more traumatic manoeuvre. MATERIALS AND METHODS: in a series of 734 elective aortic substitutions for abdominal aneurysm (AA), performed consecutively from January 1992 to June 1999, aortic cross-clamping was performed at a suprarenal level in 56 juxtarenal aneurysms, i.e. aneurysms extending to the lower edge of the renal arteries (8%, Group 1), and at an infrarenal level in 634 subrenal aneurysms (92%, Group 2). When analysing preoperative data, the diameter of aneurysms was larger in Group 1 than in Group 2 (p<0. 005). No significant differences were found between the two groups as regards age, sex, postinfarction cardiomyopathy, chronic obstructive pulmonary disease, chronic renal insufficiency and ASA classification of operative risks. RESULTS: the average time of renal exclusion in the juxtarenal aneurysms was 20 min (range 12-35 min). There is no difference between the two groups as regards the time of aortic clamping (mean 50 vs. 60 min) or the need for homologous blood transfusion (7% vs. 11% of patients). Perioperative (30 days) mortality did not differ: 3.6% vs. 1.9% (n.s.); nor did the incidence of acute myocardial infarction (3.6% vs. 2.3%). Renal function deteriorated in 8 (14%) vs. 0 (0%) (p<0.001) and 1 patient (2%) required permanent dialysis, as compared to 0% in Group 2. The incidence of ischaemic colitis was also significantly higher in Group 1 (7%) than in Group 2 (2%, p<0.01). CONCLUSION: this data shows that suprarenal clamping, which is necessary for the radical treatment of juxtarenal aortic aneurysms, can be performed with a low risk.

[Carotid endarterectomy in patients with neurological non-side related (NSRS) symptoms]. / La endoarterectomia della carotide in pazienti con sintomi neurologici non lateralizzati (NSRS).

Out of 970 carotid endarterectomies (CE) performed for high-grade (> 80%) stenosis of the internal carotid artery (ICA) until 1995, 147 patients with neurological non side-related symptoms (NSRS) and without any cardiac, ocular or vestibular significant pathology have been evaluated, analyzing the medium and long-term functional results (mean follow-up 37.6 months) related to the morphological status of the ICA contralateral and the vertebral arteries. NSRS disappeared in 126 pts (85.71%): contralateral ICA was non-stenotic in 32 cases (25.39%), stenotic < 75% in 68 cases (53.96%), stenotic > 75% in 7 cases (5.55%) and occluded in 19 cases (15.09%); vertebral arteries were pathological in only 6 cases (4.75%), among which 4 were on the same side and 2 on the opposite side of CE. NSRS persisted in 20 pts (13.6%): contralateral ICA was non-stenotic in 5 cases (25%), with a stenosis < 75% in 11 cases (55%) and with stenosis > 75% in 4 cases (20%); vertebral obliterative lesions were 3 (15.78%), among which 1 on the same and 2 on the opposite side of CE. No one statistical comparison among the groups of cases obtained on the ground of the status of ICA and vertebral arteries were significant (p always > 0.05 at chi-square analysis). Authors' data confirmed that high grade stenoses of ICA can cause NSRS and that CE--always performed at the aim to prevent major neurological attacks--can relieve also these functional disorders in the most of cases, independently from the status of the contralateral ICA and the vertebral arteries.

[The treatment of bacterial infections of the lower respiratory tract in childhood. An open comparative study of sulbactam/ampicillin vs. ceftazidime]. / Trattamento delle infezioni batteriche delle basse vie respiratorie in età pediatrica. Studio aperto comparativo sulbactam/ampicillin vs ceftazidime.

Sixty children suffering from lower respiratory tract infections have been included into this study, respectively 30 (18 M + 12 F) in the sulbactam/ampicillin (S/A) group and 30 (20 M + 10 F) in the ceftazidime (CFT) group. Average age was 42.9 months +/- 34.4 in S/A group (range 6-120) and 48.7 +/- 42.1 (range 6-144) in CFT group. Both groups were similar as to sex, age, type and duration of the infection. Posology was 150 mg/kg/die for S/A and 50 mg/kg/die for CFT. The duration of treatment was 7.2 days +/- 2.2 (range 5-12) for S/A group and 6.4 days +/- 1.6 (range 5-12) for CFT group. At the end of the therapy clinical recovery has been obtained in all cases. A rapid defervescence and remission of symptoms at an identical rate has been recorded in both treatment groups. General and local tolerability was excellent in both treatment groups.

Immediate detection of postreconstructive ischaemia by intra-operative Doppler ankle pressure index monitoring during aortic reconstructions.

From March 1980 to February 1988, 368 aorto-iliac or aorto-femoral bilateral reconstructions were performed for aneurysmal or occlusive disease. In order to demonstrate early postreconstructive ischaemic complications, the intra-operative Doppler Ankle Pressure Index (API) was measured immediately before reconstruction (PRE), just after declamping (DEC) and 5, 15, 30 and 45 min thereafter. Each limb of the reconstruction (736) was considered individually and subdivided as follows: Group (A) 705 immediately successful (96% of limbs and 92% of patients); Group (B) 22 (3% of limbs and 5% of patients) in which, on the grounds of API data, an ischaemic complication was regarded as imminent and treated by graft revision or a peripheral thromboembolectomy (intra-operative corrections); Group (C) 9 (1% of limbs and 2% of patients) in which the diagnosis of ischaemic complications was made postoperatively when the patients underwent successful reoperation. All 736 reconstructions were patent and functional at discharge of the patient. By a retrospective analysis the intra-operative APIs were studied and the features (single or associated) suggesting an ischaemic complication examined. These were: (1) no flow at the time of declamping or its disappearance during the operation (10 cases, 1.25% of limbs) all detected and successfully corrected intra-operatively.(ABSTRACT TRUNCATED AT 250 WORDS)

[Surveillance of health status in an agrarian environment: proposal for a method. 2. Environmental data]. / La sorveglianza dello stato di salute in ambiente agricolo: proposta di un metodo. Nota II--Dati ambientali.

In this second note, the Authors consider the environment surrounding the farms to identify the agricultural practices affecting both the ecological bicycle and the health of the farm-hands. The risk factors in the farm are principally the use of agricultural chemicals (pesticides, fertilizers, nitroso-compounds, etc.) and quality of the irrigation and drinkable water. In the first phase of the survey a complete analysis of environment was carried out to: a. identify all sources of pollution such as industries, roads, etc. b. consider drinkable water supplies, wastewater disposal and hygienic conditions in houses. At the same time data were collected about the use of pesticides, fertilizers and other agricultural chemicals, the characteristics of irrigation water, the presence of animals, storehouses, garages, etc. In the second phase of the survey a quality analysis of drinkable and irrigation water was carried out; the presence of dangerous chemicals (amines, nitrosoamines, nitrites, nitrates) in the vegetable caused by agricultural practices was also verified. The results demonstrated a substantial good hygienic situation of the farms but a bad state of drinkable and irrigation waters. We have difficulty in finding out how much and how the pesticides were used; therefore it will be necessary to control these practices more carefully. The amount of nitrites and nitrates in vegetables was normal, while no amines and nitrosoamines were found. The results suggest that it will be necessary in the future both to estimate the pesticide residues on the vegetables and the amount of fertilizers in the soil, and to analyse the soil composition.

[Surveillance of health status in an agrarian environment: proposal for a method. 1. Epidemiological data]. / La sorveglianza dello stato di salute in ambiente agricolo: proposta di un metodo. Nota I--Dati epidemiologici.

In order to evaluate the risk of the exposure of the pesticides and N-nitroso compounds in the agricultural environment not only farm-hands have to be considered but also their families. So it is necessary to prepare survey methodologies to examine the state of health of all individuals who are exposed to same kind of risk (pesticides and nitroso compounds), even if in different ways and intensity. We have therefore chosen four farms situated on the same territory which cultivate vegetables. Three, of these farms, made wide use of pesticides and fertilizers, the fourth one was used as a "control farm" because it did not employ any chemicals. For every farm data about the neighbouring territory, the climate, the kind of cultivation, the pesticides and other employed chemicals were collected. Every subject (in all 25) residing in the farm was interviewed with a standard questionnaire about personal data, the duties performed on the farm, the way in which chemicals were used, their medical history as well as the life style. Samples of blood were drawn periodically in different seasons, over a two year period, to determine both nitrosoamine (NA) and the enzymes which reveal hepatic damage: Alkaline phosphatase (ALP), Leucinoaminopeptidase (LAP), Gamma-glutamyltransferase (GGT) and Acetylcholinesterase (Ach). We have observed that: a. the most frequent pathologies concern skin (16% of the people) and liver (12% of the people), which are favourite targets for agricultural chemicals though the serum enzymes did not show any important change; b. 8% of the subjects had acute pesticide poisoning; we therefore observed neither particular precautionary safety measures, nor a particular knowledge of acute and chronic toxic effects depending on the use of pesticides. So we suggest: 1) that the Sanitary Authorities control the state of health not only of the farm-hands but also of their families, if exposed to risk; this can be realized through the strict collaboration of the Occupational Physician and the Family doctor; 2) capillary action of health education regarding agricultural risks; 3) to increase research to find more sensitive and efficient biological indicators in order to evaluate the hazards of agricultural chemicals.

[Tooth extraction wound healing after administration of vitamin B6 (pyridoxine). Histological study in rats]. / Processo de reparo em feridas de extração dental após administração de vitamina B6 (piridoxina). Estudo histológico em ratos.

Male rats with 250 grs of weight were injected daily with 0.1 ml of B6 vitamin by peritoneal (way paths). The animal were sacrificed at three, seven, 10, 15 and 21 day after the upper incisor extraction. Its hemimaxila were retired and fixed in 10% formalin and after had been embedded in paraffin sections were cut with 6 micrometers pick. The analysis of the sections stained by hematoxylin and eosin when compared with the controls showed that: 1) the blood clot and fibrin net are substituted more rapidly by the granulation tissue; 2) granulation tissue is more plentiful, early and mature; 3) the bone tissue is more plentiful and mature.