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.

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.

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.

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.

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.

[Serological diagnosis of systemic connective tissue inflammation; a new immunofluorescence method for demonstrating antinuclear antibodies]. / La diagnosi sierologica delle connettiviti sistemiche; un nuovo metodo d'immunofluorescenza per la dimostrazione di anticorpi antinucleari.

Two methods for the demonstration of antinuclear antibodies by means of indirect immunofluorescence were employed on 83 serum samples from 80 patients, with rat liver as the substrate. The first method (the classic ANA-test) uses cryostatic slices fixed in acetone; the second (ANA-Bp-test) is based on fixation of the substrate with Bouin's fluid and embedding in paraffin. The series was composed of 25 cases of lupus erythematosus (28 serum samples), 10 of rheumatoid arthritis, 1 of dermatomyositis, 8 of progressive systemic sclerosis, 4 of unclassifiable systemic connective tissues diseases, and 28 various internal and rheumatological forms. The undiluted sera that proved positive were subsequently tested for Ig typing and ANA titration. The ANA-Bp-test was found to be more sensitive, safer, more practical and less expensive than the ANA-test.

[Connective tissue diseases and HEp-2 antinuclear antibodies]. / Connettiviti e anticorpi antinucleari HEp-2.

Some characteristics of antinuclear antibodies that might be of use for diagnostic and/or prognostic purposed were studied using indirect immunofluorescence on HEp-2 cells in 55 cases of various types of connective tissue disease. For each nuclear (homogeneous, speckled, granular, dotted, pulverulent and centromeric) and nucleolar fluorescence pattern (homogeneous, conglutinated and dotted), the following parameters were observed; C3 fixing capacity, degree of antibody affinity and sensitivity to RNAse, DNAse and trypsin. The results were very interesting, especially in relation to the diagnosis of progressive systemic sclerosis and of the related subsets, but were insufficient for reliable, conclusive prognostic evaluation.

[Clinical significance of antinuclear antibodies in progressive systemic sclerosis]. / Significato clinico degli anticorpi antinucleari nella sclerosi sistemica progressiva.

Indirect immunofluorescence (IIF) was used to detect antinuclear antibodies (ANA) in 42 clinical cases. In each case cryostatic rat kidney slices and cultivated HEp-2 cells were used as substrates. Clinical diagnoses were as follow: Progressive Systemic Sclerosis (PSS) 25 cases, of which 8 were acrosclerotic, 8 diffuse, 5 CREST syndrome, 1 overlap PSS + Systemic Lupus Erythematosus (SLE) and 3 PSS + myopathy; Localised scleroderma (morphea): 3 cases; Mixed Connective Tissue Disease (MCTD): 3 cases; "Idiopathic" Raynaud's Disease (RD): 4 cases; Dermatomyositis (DM): 2 cases (1 paraneoplastic); SLE: 1 case; Unclassifiable Connective Tissue Disease (UCTD): 4 cases. The ANA-positive cases identified by the traditional technique were divided according to pattern into 4 categories: homogeneous, peripheral, speckled, nucleolar. In contrast those identified using HEp-2 cells were divided into 9 pattern groups: (nuclear type) centromere, fine speckled, coarse speckled, diffusely grainy, homogeneous: (nucleolar type) speckled, clumpy, homogeneous. The results demonstrated a higher general incidence of positivity with HEp-2 cells and confirmed the close connection between Anticentromere ANA and CREST syndrome. A similarly close connection was noted between MCTD and both nuclear diffusely grainy and nucleolar speckled patterns. A fairly clear connection was also noted between acrosclerotic or diffuse SSP and a fine speckled nuclear pattern. It is felt that ANA tests using IFI on HEp-2 cells should lead to significant progress in the field of diagnosis and prognosis and the study of PSS subsets.

[Immuno-histological findings on Sjögren's syndrome]. / Indagini immuno-istologiche nella sindrome di Sjögren.

Six cases of SS, 12 cases of SS in association with other diseases (AR, LES, MCTD, SSP) and 14 cases of various diseases with no clinical signs of SS (AR, UCTD, LES, MCTD, PM, cutaneous PAN, Scheuermann's disease, ankylosing spondylitis) have been examined. Examination of the patients included general clinical, stomatological and ophthalmological examinations, slit lamp and Schirmer I test, labial biopsy direct immunofluorescence on labial biopsy, indirect immunofluorescence on labial biopsy of a healthy subject scialography and salivary scintiscan. Various seroimmunological tests were also performed--in the hope of identifying LE, ANA, anti-ENA and anti-dsDNA factors. The results of these clinical, immunological, bioptic and instrumental tests were studied with a view to clarifying the diagnostic and nosographic problems of the syndrome. The diagnostic importance of immunological and instrumental tests is emphasized. Labial biopsy in particular also makes it possible to quantify the glandular lesion to some extent as well as providing other histological data regarding any associated disease. Nosographically, it is suggested that SS be definitively included among the connective tissue diseases in recognition of its polymorphism and variety of clinical forms which cover a wide range from definite SS, whether in pure form or associated with other diseases, to "subclinical" SS in systemic diseases.

[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.

[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.

[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.

[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.

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.

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.