Search

Background While advances in PAH-specific therapies have substantially improved survival, there is still an unmet need to improve long-term outcomes in PAH. Purpose The UNISUS study is the first head-to-head superiority study in PAH, comparing the time to morbidity or mortality (M/M) with macitentan 75 mg vs macitentan 10 mg in PAH patients. Methods UNISUS, an ongoing multicentre, prospective, double-blind (DB), adaptive, event-driven superiority study randomises PAH patients 1:1 to receive macitentan 75 mg or macitentan 10 mg, with a target enrolment of ∼900 patients. Efficacy and safety are continuously assessed by an independent data monitoring committee (IDMC), who advises on pre-specified adaptive changes in study conduct, including expansion of the study population. An independent clinical event committee adjudicates all M/M events. The initial population was restricted to patients in functional class (FC) II/III, aged 18–75 years and excluded those with portopulmonary hypertension (PoPH) and those who were PAH treatment-naïve or receiving a prostanoid analogue. Stable (≥3 months) background PAH-therapy may be maintained, except for endothelin receptor agonists (ERAs), which must be stopped the day before initiating study drug. The study is comprised of a screening period, a 4-week run-in period (if ERA treatment-naïve or on sub-optimal ERA dose), and an event-driven DB treatment period, followed by a 2-year open-label extension with macitentan 75 mg. Initiation of macitentan 75 mg occurs after a 4-week up-titration step with macitentan 37.5 mg (Figure 1). The primary endpoint is time to first on-treatment M/M event, defined as first of: all-cause death, PAH-related hospitalisation, or PAH-related disease progression (confirmed ≥15% decrease in 6-minute walk distance (6MWD) and either FC worsening or addition of PAH therapy). Other endpoints include change from baseline to Week 24 in 6MWD and PAH-SYMPACT symptom scores; time to PAH-related hospitalisation or death; time to all-cause death (may be supplemented with data from an external control arm derived from the CARE PAH study [NCT04955990]); and the safety and tolerability of the study drugs. Figure 2 shows planned assessments and sub-studies. To maximise patient retention, add-on PAH therapies are allowed after a M/M event and, for patients at risk of withdrawing and unable to attend visits, the investigator may consider options for reduced follow-up. Results After 60 patients had been exposed for ≥8 weeks, the IDMC reviewed unblinded safety/tolerability data and recommended to expand recruitment from the restricted population to the target population (i.e., including patients: with PoPH, in FC II–IV, from any PAH therapy background [including naïve], aged ≥18 years). Conclusion UNISUS is the first head-to-head superiority study in PAH; with over 200 patients enrolled, it is currently recruiting the target population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Actelion Pharmaceuticals Ltd., a Janssen pharmaceutical company of Johnson & Johnson.

Hyperhidrosis is a dermatological condition that causes psychosocial impairment and has a negative impact on patients’ quality of life. The epidemiology of hyperhidrosis is currently poorly understood. The aim of this study was to analyse comorbidities and treatments in 511 subjects with hyperhidrosis selected from the patient records of Oulu University Hospital. The mean age of patients with local hyperhidrosis was 27.9 years and the majority were female (62.7%). The most common anatomical site of symptoms in the youngest age group was the palms, whereas the axillae were a more common site in advanced age. Depression was a common comorbidity in both local (11.6%) and generalized hyperhidrosis (28.6%). Anxiety affected 12.7% of patients with generalized hyperhidrosis. In 36.8% of the patients with local hyperhidrosis there was a delay in diagnosis of more than 10 years. The most commonly used treatments included topical antiperspirants, iontophoresis and botulin toxin injections.

In this paper we form a general conservation law that unifies a class of physics field theories. For this we first introduce the notion of a general field as a formal sum differential forms on a Minkowski manifold. Thereafter, we employ the action principle to define the conservation law for such general fields. By construction, particular field notions of physics, such as electric field strength, stress, strain etc. become instances of the general field. Hence, the differential equations that constitute physics field theories become also instances of the general conservation law. Accordingly, the general field and the general conservation law together correspond to a large class of physics field models. The approach creates solid foundations for multi-physics analysis and is critical in developing software systems for scientific computing; the unifying structure shared by the class of field models makes it possible to implement software systems which are not restricted to finite lists of admissible problems., 18 pages

Background The purpose of the study was to evaluate in a sample of insulin-treated diabetic patients, with type 1 or type 2 diabetes, the psychometric characteristics of the Italian version of the DEPS-R scale, a diabetes-specific self-report questionnaire used to analyze disordered eating behaviors. Methods The study was performed on 211 consecutive insulin-treated diabetic patients attending two specialist centers. Lifetime prevalence of eating disorders (EDs) according to DSM-IV and DSM-5 criteria were assessed by means of the Module H of the Structured Clinical Interview for DSM IV Axis I Disorder and the Module H modified, according to DSM-5 criteria. The following questionnaires were administered: DEPS-R and the Eating Disorder Inventory – 3 (EDI-3). Test/retest reproducibility was assessed on a subgroup of 70 patients. The factorial structure, internal consistency, test-retest reliability and concurrent validity of DEPS-R were assessed. Results Overall, 21.8% of the sample met criteria for at least one DSM-5 diagnosis of ED. A “clinical risk” of ED was observed in 13.3% of the sample. Females displayed higher scores at DEPS-R, a higher percentage of at least one diagnosis of ED and a higher clinical risk for ED. A high level of reproducibility and homogeneity of the scale were revealed. A significant correlation was detected between DEPS-R and the 3 ED risk scales of EDI-3. Conclusions The data confirmed the overall reliability and validity of the scale. In view of the significance and implications of EDs in diabetic patients, it should be conducted a more extensive investigation of the phenomenon by means of evaluation instruments of demonstrated validity and reliability. Electronic supplementary material The online version of this article (doi:10.1186/s12888-017-1434-8) contains supplementary material, which is available to authorized users.

To save network resources, multicast transmissions are more and more adopted by the operators when the same content has to reach several destinations in parallel, such as in IPTV services, radio broadcast and video-clip streaming. Though, with respect to unicast transmissions, multicast sessions make the routing problem more complex with huge sets of trees to be evaluated. Additionally, since in the real world several multicast sessions occur simultaneously, the suitable trees for more sessions have to be found concurrently. This problem is addressed in this paper, which proposes the use of the genetic algorithms (GA) to reduce the number of solutions to be evaluated. Firstly, a heuristic procedure is employed to generate a set of possible trees for each session in isolation; secondly, the GA are applied to find the appropriate combination of the trees to comply with the bandwidth needs of the group of multicast sessions simultaneously. The goodness of each solution is assessed by means of an expression that weights both network bandwidth allocation and one-way delay. Some key parameters are also introduced that allow the operator to find the desired balance between quality of service and network resource utilization. Experimental results are provided to show the performance of the proposed algorithm compared with alternative solutions in terms of bandwidth utilization and transmission delay and to illustrate the influence of the selection and crossover procedures configuration.

Alpha-lipoic acid (alpha-LA) is an antioxidant used for the treatment of a variety of diseases, including liver cirrhosis, heavy metal poisoining, and diabetic polyneuropathy. In addition to its protective effect against oxidative stress, alpha-LA induces apoptosis in different cancer cells types. However, whether alpha-LA acid induces apoptosis of hepatoma cells is unknown. Herein, we investigated whether alpha-LA induces apoptosis in two different hepatoma cell lines FaO and HepG2. The results showed that alpha-LA inhibits the growth of both cell lines as indicated by the reduction in cell number, the reduced expression of cyclin A and the increased levels of the cyclin/CDKs inhibitors, p27(Kip1) and p21(Cip1). Cell cycle arrest was associated with cell loss, and DNA laddering indicative of apoptosis. Apoptosis was preceded by increased generation of reactive oxygen species, and associated with p53 activation, increased expression of Bax, release of cytochrome c from mitochondria, caspases activation, decreased levels of survivin, induction of pro-apoptotic signaling (i.e JNK) and inhibition of anti-apoptotic signaling (i.e. PKB/Akt) pathways. In conclusion, this study provides evidence that alpha-LA induces apoptosis in hepatoma cells, describes a possible sequence of molecular events underlying its lethal effect, and suggests that it may prove useful in liver cancer therapy.

Retinoids have been shown to exert an anticarcinogenic effect through suppression of the cell cycle, induction of apoptosis and/or differentiation. In rat liver, in particular, retinoic acid has been shown to inhibit regeneration after partial hepatectomy, most probably through repression of the expression of c-fos and c-jun. Surprisingly enough, in spite of the proposed therapeutic effects of all-trans retinoic acid (tRA) no data are available on its effect on normal adult liver. Here, we show that tRA administration in the diet (150 mg/kg) increased DNA synthesis in mouse liver, at 1 and 2 weeks, with a return to control values at 4 weeks (labelling index was 16.5, 8.3 and 3.3%, respectively, versus control values of 1.4, 1.3 and 2.5%). Increase in mitotic index paralleled that of bromodeoxyuridine incorporation. Kinetic studies showed that entry into S phase began between 24 and 48 h, with a peak between 96 and 120 h. Histological observation of the liver and biochemical evaluation of the levels of serum glutamate-pyruvate transaminases did not reveal any evidence of cell death demonstrating that increased DNA synthesis was not due to tRA-induced liver damage and regeneration, but rather the consequence of a direct mitogenic effect. In addition, analysis of total hepatic DNA content after a 7-day treatment showed a significant increase in tRA-fed mice compared with controls (21.11 mg/100 g body wt in tRA-fed mice versus 15.67 mg/100 g body wt of controls). Hepatocyte proliferation in tRA-fed mice was associated with increased hepatic levels of cyclin D1, E and A, and enhanced expression of the member of pRb family, p107. In conclusion, the results showed that tRA induces hepatocyte proliferation in the absence of cell death, similarly to other ligands of steroid/thyroid hormone nuclear receptor superfamily. The mitogenic effect of tRA cautions about its possible use for antitumoral purposes in liver carcinogenesis.

The aim of the study was to evaluate, in a representative sample of high school students, the psychometric characteristics of the Italian version of the CEBRACS scale (Rahal et al., 2011), a questionnaire investigating compensatory eating behaviors correlated with alcohol consumption. These behaviors are adopted to make up for calories consumed through the drinking of alcohol and/or to enhance the intoxicative effects of alcohol. Study participants were selected from an initial sample of 965 students. Out of the 965 youths originally recruited, 640 (376 males and 264 females) reported drinking alcohol over the previous 3 months, and were considered eligible for the purpose of the study. The following questionnaires were administered: CEBRACS, Alcohol Use Disorders Identification Test (AUDIT) (Saunders, 1993), and the Eating Disorder Inventory-3 (EDI-3) (Garner, 2004). Test/retest reproducibility was evaluated on a subgroup of 189 youths. The factorial structure, internal consistency, test–retest reliability and concurrent validity of CEBRACS were evaluated. Factor analysis of inter-item correlation indicated 5 factors as being better suited to describe data, with an estimated 68.85% variance: "Alcohol Effect, "Laxative Use", "Dietary Restraint and Exercise", "Diuretic Use", "Restriction and Vomiting". A high degree of reproducibility and homogeneity (ICC = 0.806; Cronbach's Alpha = 0.886) of the scale was detected. A significant correlation was revealed between CEBRACS, the three eating disorder risk scales comprised in EDI-3 and scores and clinical risk yielded by AUDIT. The overall reliability and validity of the CEBRACS scale was confirmed in an extensive sample of Italian students, highlighting a satisfactory construct validity, good internal consistency and good degree of reproducibility. In view of the relevance of the problem, associated with serious health risks, a more widespread investigation of the phenomenon should be conducted using evaluation tools of proven validity and reliability on both representative samples of the general population and clinical samples.

Aims This study aimed to compare the performance of Positive and Negative Syndrome Scale (PANSS) symptom severity criteria established by the Remission in Schizophrenia Working Group (RSWG) with criteria based on Clinical Global Impression (CGI) severity score. The 6-month duration criterion was not taken into consideration. Methods A convenience sample of 112 chronic psychotic outpatients was examined. Symptomatic remission was evaluated according to RSWG severity criterion and to a severity criterion indicated by the overall score obtained at CGI-Schizophrenia (CGI-SCH) rating scale (≤3) (CGI-S). Results Clinical remission rates of 50% and 49.1%, respectively, were given by RSWG and CGI-S, with a significant level of agreement between the two criteria in identifying remitted and non-remitted cases. Mean scores at CGI-SCH and PANSS scales were significantly higher among remitters, independent of the remission criteria adopted. Measures of cognitive functioning were largely independent of clinical remission evaluated according to both RSWG and CGI-S. When applying RSWG and CGI-S criteria, the rates of overall good functioning yielded by Personal and Social Performance scale (PSP) were 32.1% and 32.7%, respectively, while the mean scores at PSP scale differed significantly between remitted and non-remitted patients, independent of criteria adopted. The proportion of patients judged to be in a state of well-being on Social Well-Being Under Neuroleptics-Short Version scale (SWN-K) were, respectively, 66.1% and 74.5% among remitters according to RSWG and CGI-S; the mean scores at the SWN scale were significantly higher only among remitters according to CGI-S criteria. Conclusions CGI severity criteria may represent a valid and user-friendly alternative for use in identifying patients in remission, particularly in routine clinical practice.

Multiple logistic regression was used on serological data collected in the context of the Sardinian African swine fever (ASF) eradication program from pig farms in the province of Nuoro, Sardinia. The monthly percentage of ASFV-positive herds decreased significantly from October 1994 through March 1996 (P < 0.001). The farm-level risk of seropositivity to African swine fever virus (ASFV) was higher in free-range farms than in partial-confinement farms (odds ratios (OR) varied between 4.9 in October 1994, and 5.7 in March 1996, P < 0.001). The risk of infection for total-confinement farms was one-fifth of the risk for partial-confinement farms in October 1994 (OR = 0.2, P < 0.001), whereas in March 1996, the estimated OR was 0.57 and not significant (upper confidence limit = 1.1). The maintenance of ASFV in Sardinia was primarily associated with free-range pig farms. The natural logarithm of the number of pigs tested per visit in a farm was positively associated with the risk of herd seropositivity (OR = 2.6, P < 0.001).

Outcome of psychotic disorders, particularly schizophrenia and related disorders, seems to be associated, among a number of other factors, to the latency of treatment of irst episode (duration of untreated psychosis, DUP); indeed, outcome seems to be worse in subjects with a longer DUP. However, few studies addressed the topic of long term outcome and DUP as regard to cognitive functioning, though the latter plays a crucial role in explaining a significant proportion of disability both in non-affective and affective psychoses. The study aims to analyze relationships between DUP and cognitive functioning in a sample of chronic psychotic patients.We considered a unselected sample constituted by 82 chronic outpatients, 49 males (59,8%) e 33 females (40,2%), age range 20-74 yrs (mean age 46,59; s.d. 10,68 yrs); these patients were affected by schizofrenia (n=41, 50%), Bipolar Disorder type I, with psychotic mood congruent or uncongruent features (n=18, 22%,) and Schizoaffettive Disorder (n=23, 28%) according to DSMIVTR, with diagnosis confirmed by means of SCID-I. Patients underwent WAIS-R in order to evaluate cognitive functioning.A longer DUP (more than 3 months between onset of first clinically evident psychotic symptoms and first antipsychotic treatment) was associated with significantly lower scores in 9 out of 11 subtests of WAIS, weighted total score, IQ-verbal score, IQ-performance score and IQ-total score. A significant relationship between a longer DUP and lower cognitive performances was confirmed among schizophrenic and schizoaffective patients, although limited to some subtests.The study provides new evidence for a positive association between longer DUP and worse neurocognitive functioning, even in the long term.

Summary The retractor clitoridis muscle originates from the coccygeal vertebrae in the cow, ewe, goat and mare, and from the anal musculature in the sow. It terminates at the base of the clitoris. In all the species considered, a vegetative innervation was found. This was represented by isolated or grouped ganglion cells. Nervous sensitive supply was also present. This was represented by Pacinian, Pacinian-like and Golgi-Mazzoni's corpuscles, and by Krauses's end bulbs. A notable difference was found in the amount and type of these receptors. They were numerous in the sow, ewe and goat, and rare in the cow and mare. Additionally, in the sow, ewe and goat, all the above mentioned receptors were found, while, in the cow and mare, only Pacinian and Pacinian-like corpuscles occurred. The morphology of these receptors was described and hypotheses were made concerning their probable functional role.

A prospective study was undertaken to compare the efficacy of everolimus versus azathioprine or placebo in maintaining steroid-induced remission in active Crohn's disease (CD) and assess the safety and pharmacokinetics of everolimus.This was a randomized, double-blind, placebo-controlled, proof-of-concept study in adults with moderate-to-severe active CD. The patients received oral steroids for a rapid induction of remission plus everolimus 6 mg/day, azathioprine 2.5 mg/kg/day, or placebo as maintenance treatment. The main outcome measure was the treatment success, defined as a steroid-free remission by the end of month 3 and maintained until study cutoff without the use of prohibited efficacy treatments.Following an interim analysis, the study was terminated before enrollment was completed due to the lack of efficacy. The full intent-to-treat population comprised 138 patients. Only 96 patients who entered the studyor =7 months prior to data cutoff were included in the primary efficacy population. The treatment success was achieved in 13 of 38 everolimus patients, 22 of 36 azathioprine patients, and 8 of 22 placebo patients. Using the Kaplan-Meier estimates at month 7, the incidence of treatment success was 22.0% with everolimus group (95% confidence interval [CI] 6.7-37.3%, P= 0.610 vs placebo), 38.3% with azathioprine group (95% CI 20.6-55.9%, P= 0.500 vs placebo), and 28.8% with placebo group (95% CI 7.7-49.9%). The type and incidence of adverse events in the everolimus cohort were similar to those reported in the approved transplantation indications.The safety and tolerability of everolimus (6 mg/day) in patients with active CD were comparable to azathioprine. At this dose, everolimus is not more efficacious in achieving a steroid-free remission in active CD than the comparators.

Drunkorexia, limiting food intake before alcohol consumption, increases teenagers and young adults’ risk for negative alcohol-related health consequences.The purpose of the present study is to explore gender and age differences regarding weight management behaviors and alcohol consumption among 3004 students aged 13 to 24 years.The following questionnaires were administered: Eating Disorder Inventory-3 (EDI-3), Alcohol Use Disorders Identification Test (AUDIT) and Compensatory Eating and Behaviors in Response to Alcohol Consumption Scale (CEBRACS).EDI-3 showed that 11.3% of the sample met the threshold on the “Drive for Thinness” (DT) scale, 28.9% on the “Bulimia” (B) scale, 17.2% on the “Body Dissatisfaction” (BD) scale. Females presented a higher risk at DT, B and BD scales (P < 0.001), and the risk of bulimia was higher in those aged ≤ 16 years (P = 0.028). AUDIT revealed a greater clinical risk of alcohol-related problems in males (P < 0.001) and in those aged > 16 years (P < 0.001). Drunkorexia was found in 44% of the sample, without significant difference in relation to gender and age.Girls and younger students have more weight concerns, while boys and older students are at greater risk of alcohol use disorders. Therefore, no specific group should be considered risk-free with respect to drunkorexia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Optical flow is a biologically inspired computation that has been widely used for tracking the movement of objects in a scene. This paper presents its novel application to an autonomous robot that is required to follow a person in an everyday environment. This robot skill is implemented as one of many concurrent behaviours and it is integrated in a general architecture called ERASMUS-Expert based Robot Architecture for Sensing and Moving in Unknown Surroundings. The details of the method are described as well as its integration in ERASMUS. Experimental results, evaluating both the performance and the reliability of our approach, will also be provided.

A high percentage of individuals affected by eating disorders (ED) achieve incomplete recovery following treatment. In an attempt to improve treatment outcome, it is crucial that predictors of outcome are identified, and personalized care approaches established in line with new treatment targets, thus facilitating patient access to evidence-based treatments. Among the psychological factors proposed as predictors of outcome in ED, alexithymia is of outstanding interest. The objective of this paper is to undertake a systematic review of the literature relating to alexithymia, specifically in terms of the implications for treatment of ED. In particular, issues concerning the role of alexithymia as a predictor of outcome and as a factor to be taken into account in the choice of treatment will be addressed. The effect of treatments on alexithymia will also be considered. A search of all relevant literature published in English using PubMed, PsycINFO, and Scopus databases was carried out on the basis of the following keywords: alexithymia, anorexia nervosa, bulimia nervosa, eating disorders, and treatment; no time limits were imposed. Despite the clinical relevance of alexithymia, the number of studies published on the above cited aspects is somewhat limited, and these studies are largely heterogeneous and feature significant methodological weaknesses. Overall, data currently available mostly correlate higher levels of alexithymia with a less favorable outcome in ED. Accordingly, alexithymia is seen as a relevant treatment target with the aim of achieving recovery of these patients. Treatments focusing on improving alexithymic traits, and specifically those targeting emotions, seem to show greater efficacy, although alexithymia levels often remain high even after specific treatment. Further investigations are needed to overcome the methodological limitations of previous studies, to understand the actual impact of alexithymia on ED outcome, and to allow more precise implications for treatment to be drawn. Additional research should also be undertaken to specify which of the alexithymic dimensions are specifically relevant to the course and outcome of ED, and to identify treatment protocols producing a significantly greater efficacy in ED patients with relevant alexithymic traits.

The product of the MDR1 gene (P-gp) has been implicated in the transport of cholesterol from plasma membrane to endoplasmic reticulum for esterification. In previous studies on leukemia cell lines, we suggested that cholesterol esterification may regulate the rate of cell growth and that the MDR1 gene might be involved in this process by modulating intracellular cholesterol esters levels. To further investigate this matter, the rate of cell growth, cholesterol metabolism, expression of the MDR1 gene, and P-gp activity were compared in KB cell lines displaying differences in expression and function of P-gp (drug-sensitive phenotype versus MDR phenotype). The rate of cell growth correlated with cholesterol esterification in all KB cell lines, whereas the over-expression of MDR1 observed in the MDR cell lines was not always associated with an increased capacity of cells to esterify cholesterol. Two known inhibitors of P-gp activity, progesterone and verapamil, strongly inhibited both cholesterol esterification and cell proliferation in all KB cell lines, but they affected intracellular accumulation of labeled vinblastine only in MDR cell lines. These results further support a role for cholesterol esters in the regulation of cell growth and suggest that the P-gp expressed in MDR KB cells is not involved in the general process leading to cholesterol esterification.

The extracts of the aerial parts and tubers of Asphodelus microcarpus (Liliacee) were studied. The fatty acids, the sugars and some anthraquinone glycosides were determined by means of GC/FTIR, GC/MS and HPLC. The antimicrobial activity of essential oil of aerial parts against blastomycetes, Gram-positive and Gram-negative bacteria was evaluated.

Although primary hyperaldosteronism is an uncommon cause of hypertension, it is the most common form of renin-independent hypermineralocorticoidism. The plasma aldosterone concentration and PRA with orthostatic test and saline infusion test are very useful aids to make a diagnosis. In this case the inconsistency between hormonal data and morphologic images (TC and NMR) led us to a dilemma: it was a question of adrenal adenoma or hyperplasia? Because it was impossible to dose the 18-OH-corticosterone, we had to perform a iodocholesterol scintigraphy NP 59. To distinguish an hyperplasia as cause of this kind of hyperaldosteronism made us able to define a therapeutic program useful to hypertension control.

The 3-Acetylpyridine (3-AP) is a neurotoxic that determines a selective destruction of inferior olivary nucleus in the rat. However, in the other animals (mouse, rabbit, guinea-pig, quail and chicken) the effect could be less selective in the mentioned nucleus and constant in other areas of the central and peripheral nervous system. This investigation means to expand the study of these neurotoxic effects to the hamster, species not yet studied. The intraperitoneal administration of 3-AP, at a dosage of 65 mg/Kg, determines in this animal stridulous breathing, coughing and ataxy. Wide sites of the nervous system show, by microscopical observations, pictures of shrinking cells, vacuolization of the cytoplasm, reduction or loss of Nissl stain affinity and neuronal mutilation. The neurotoxic effects are mostly evident in the motor nuclei of the cerebral trunk and in the ventral horns of the spinal cord. However, the inferior olivary nucleus appears undamaged or sparely involved.

In this paper we describe the clinical and radiographic features of a spondylo-epi-methaphyseal dysplasia. Dyggve-Melchior-Clausen syndrome. In these two new cases, without severe mental retardation, we have highlighted the clinical and radiological findings, progression of the skeletal changes that have allowed us to make a diagnosis.

Proprioceptive innervation of the external anal sphincter muscle and the organization of the vegetative and sensitive nerve components of the internal and sphincter muscle have been studied in different mammals. The findings of typical muscle spindles in the external anal sphincter muscle were constant in the pig, frequent in the goat and cow, rare in the sheep and horse and absent in the roe and rabbit. In the pig, muscle spindles were observed in the entire extension of the muscle, while in the sheep, goat, cow and horse, the receptors were found only in the cranial portion of the muscle. In all the species studied, the internal anal sphincter muscle had numerous ganglion cells, isolated or grouped, and rare Pacinian, Pacinian-like, and Golgi-Mazzoni corpuscles. Their functional role has been hypothesized.

Introduction The duration of untreated psychosis (DUP) is the time between the onset of symptoms and first psychiatric drug treatment. A large number of studies show that this time stretch is largely variable and often very long, lasting several months or even years and is associated with a worse outcome. Materials and methods This retrospective study is based on an analysis of medical records, standardized format AMDP, used at the Psychiatric Clinic of the University of Cagliari. The sample consisted of 184 patients (M = 57.1%, F = 42.4%) with an history of a psychotic onset regardless of the diagnosis made. We have collected data on the duration of untreated psychosis (DUP), number of relapse, number of hospitalizations, number of suicide attempts, disease duration, have been considered as course and outcome variables. Conclusions The duration of untreated psychosis is associated with an increased number of hospitalizations during the course of the disease (p = 0.04) regardless the disease duration. Our study gives a further confirmation of the fact that early intervention in first psychotic episode is necessary to improve the course of psychiatric illness.

Introduction A number of studies of a possible relationship between duration of untreated illness (DUI) and various psychiatric disorders shown the possible role of DUI as negative prognostic factor in schizophrenia and psychotic disorders. On the other hand few data evaluate the role of DUI in the clinical outcome of major depressive disorder. Objectives Analyze the duration of untreated illness and evaluate long-term outcomes in major depressive disorder. Method Sample of 73 subjects (53F and 20M) with major depressive disorder according to DSM-IV-TR. We collected demographic, clinical and outcome data: age, sex, family history, age at onset of illness, age of first antidepressant treatment and dosage, possible comorbidity with other diagnoses and substance abuse, number of depressive episodes before and after treatment, number of hospitalizations and suicide attempts. Results Results show that the DUI is longer in the male than in the female sample (p = 0.049) and long DUI is related to an onset disorder at a younger age (p = 0.040) and with a longer duration of illness (p = 0.006). It was also demonstrated that the number of depressive episodes prior to the first antidepressant treatment is higher in the sample of patients with a longer DUI (p = 0.006). Discussion These results show that the duration of untreated illness is longer in the male sample; other results are consistent with previous studies and show a better outcome of depression in patients with a short duration of untreated illness.

Introduction As many studies suggest, schizophrenic spectrum disorders outcome is linked with the duration of untreated first-episode psychosis; the longer is the gap between the onset of the disease and the first medical treatement the worst is the outcome. Cognitive impairment is one of the major predictor of poor outcome. Objective We study if there is a correlation between a long duration of untreated first-episode psychosis and cognitive impairment in the long term outcome. Methods Our sample consisted of 41 subjects (27M and 14 F) with a mean age of 48.6 years (SD = 11.91) with a mean age of onset of 23.4 years (SD = 7.68) and a mean duration of illness of 22.1 years (SD = 14.8) who has been diagnosed schizophrenic according to DSM-IV TR through the SCID-I and evaluated with the Wechsler Adult Intelligence Scale (WAIS) to study neuro-cognitive profile. Results A long duration of untreated psychosis is associated with redution in the performance scale of association symbols to number (p = 0.04) and performance IQ (p = 0.04) regardless of the duration of illness. Conclusion This study confirms an association between long duration of untreated psychosis and cognitive deterioration. The reduced performance suggest a deficit in memory, attention and concentration, speed of performance, coordination,skill and non verbal ability in the sample with the longer DUI.

The pyramidal tract of the hedgehog has been investigated. The motor cerebral cortex was first located electrophysiologically and subsequently ablated. Ablation of the motor cortex did not apparently cause motor deficits. The cerebral hemisphere of the operated side, brain stem and spinal cord were removed for histological examination. The Nauta-Gygax and the horseradish peroxidase methods were employed to study the course and origin of the above mentioned tract. The pyramidal tract runs ipsilaterally in the cerebral peduncle, and does not go beyond the first cervical segments of the spinal cord (C3-C4); moreover, their fibers do not cross at spinal level. The close relation between this anatomical pathway and the olfactory bulb of the same side is also reported.

The retractor penis muscle originates from the vertebrae in pigs, horses, cattle and goats; it arises from the rectum in sheep. In all the species considered, sensitive innervation was found. This was represented by encapsulated receptors. Nervous vegetative supply, made up of isolated or assembled ganglion cells, was also present. Among the numerous sensory nerve endings found in pigs, goats and sheep were Pacinian, Pacinian-like, Golgi-Mazzoni corpuscles and Krause's end bulbs (genital corpuscles). Few Pacinian and Pacinian-like corpuscles were found in cattle and horses. A hypothesis on the probable functional role of the observed receptorial apparatus was formulated.

Multiple Pterygium Syndrome is a rare autosomal recessive disorder characterized by short stature, multiple pterygium, joint contractures, vertebral fusions and minor facial anomalies. Due to the extreme phenotypic variability of this syndrome many mild cases may be misdiagnosed or not recognized. The importance of an early diagnosis is to provide an adequate follow-up of these children in order to try to prevent many of the clinical problems they may encounter in their life-time.

In order to assess the extent of environmental pollution by Pb, Cd and Zn in the industrial area of Portoscuso (Southwestern Sardinia-Italy), anatomohistopathological, histochemical and chemical tests were carried out on the heart, liver, kidneys and bones of sheep slaughtered in the local abattoir. On microscopic examination, degenerative lesions were severe in liver and kidneys and slight in the heart; histochemical stainings clearly showed a notable presence of Zn, while spectrophotometric examination confirmed, besides Zn pollution, very high tissue concentrations of Pb and Cd. The Authors conclude that other trial observations over larger areas are necessary.

Previous investigations have ascertained, according to the results obtained by Bradley et al. (1980) in the sheep, that the laryngeal surface of the epiglottis of goat and bovine is always provided with numerous taste buds. These observations have verified in other ruminant species, as the moufflon and the buffalo, the validity of the above-named datum and have ascertained that it is always inconstant in the other animal species considered (wild boar, coypu). These taste buds show a typical structure (diameter of the outer taste pore varying from 2.7 to 4.2 micron, width of the chemoreceptors varying from 30 to 60 micron and length from 27.5 to 57.5 micron). Moreover, the normal structure of the above-named taste buds is also testified by the arrangement of their innervation and particularly by the integrity of the synaptic contacts. The results of the present research have permitted a critical and more severe examination of the probable functional role of those laryngeal receptors. In fact, in the ruminants they may protect the deep airways precluding to food particles the larynx in the phase of food regurgitation.

The origin and course of the collateral sesamoidean (suspensory navicular) ligament of the horse and ass and its attachment to the distal sesamoid bone were studied by means of dissection. Particular attention was given to the topographic relations between this ligament and the deep digital flexor tendon. Numerous sensitive nerve endings are present in this anatomical district. The free and encapsulated nerve endings, displayed by impregnating techniques, are mostly concentrated in the ligament tract connected to the above-named tendon and close to its attachment to the distal sesamoid angle. The nerve endings are identified as typical Pacini, Pacini-like and Golgi-Mazzoni corpuscles on account of their morphological features and are found isolated, grouped to form flower-sprays, lined up along the course of a single nerve fibre or grouped to originate poikilomorphous fibres.

The authors have studied the vegetative and sensitive somatic innervation of the retractor penis muscle in some domestic animals. This last component is constituted by encapsulated receptors classified as Pacini, Pacini-like, Golgi-Mazzoni's corpuscles and Krause's end bulbs (genital corpuscles). They have also emphasized the structural characteristics of the various types of nervous endings and their remarkable variability in the investigated animals. Finally, they have examined the probable functional role of these mechanicoreceptors.

The most developed and organized lamina running trough the biceps brachii muscle belly forms a well-marked tendinous intersection connecting the proximal tendon with the distal one. Moreover, the lacertus fibrosus arises from this lamina close to the distal tendon and blends with the fascia of the forearm and joins the extensor carpi radialis muscle. The nerve supply for the biceps tendinous intersection arises from the intramuscular rami of the musculo-cutaneous nerve, whereas the lacertus fibrosus is provided with some cutaneous rami of the same nerve. The biceps brachii tendinous intersection and lacertus fibrosus are provided with free and encapsulated nervous endings. The encapsulated corpuscles are represented by rare Pacini, Pacini-like and Ruffini receptors and by numerous Golgi tendon-organs. All these receptors have been studied by a topographical point of view and the role played by the proprioceptors in synchronizing shoulder, elbow and carpal joint movements both in the flexion and the extension of the limb, has been hypothesized.

A vegetative innervation is described for the first time in this district. On the contrary, the finding of Pacini and pacini-like corpuscles, of Golgi Mazzoni's receptors, of muscle spindles and Golgi's tendon-organs testifies the existence of a sensitive innervation in this anatomical territory. According to Karamanlidis free nervous endings are not present. All the above recorded receptors show the typical structure and can be found isolated, grouped to constitute flower-sprays, organized to form opposito-polar corpuscles or associated to originate pecilomorphic fibers. These two last findings are new for this investigated anatomical territory. Moreover, the authors have described in the ox the so-called composed corpuscles previously observed by Ottolenghi (1931) and Karamanlidis in the horse. Finally, it has been demonstrated, contrary to the data reported by Karamanlidis, that the muscle spindles located in the ligament are always supplied with a nervous annulo-spiral termination which is centrally placed in the equatorial region.

The episclera of horse and ass is provided, just like in the bovine, with both vegetative and sensitive somatic innervation. The former is constituted by isolated or grouped ganglionic cells located along the course of the nerve bundles. The sensitive nervous component consist, above all, of encapsulated receptors such as Pacini, Pacini-like and Golgi-Mazzoni corpuscles. Most of these are Pacini-like receptors which also show some structural features. In fact they are very small and supplied with a thin capsule and an undivided expansional axon.

We examined 102 pregnancies in 59 diabetic women by Department of Gynaecology and Obstetrics of Sassari University from 1974 to 1983, we evaluated pregnancy and labor proceeding, perinative morbidity and mortality. Our issues show a perinative mortality high yet (14.8%), not always comparable to severity of maternal diabetes, that's mainly due to insufficient number of controls undertaken from patients for their por medical education. Recently diabetic pregnant women have getting used to routine controls of metabolic balance, pregnancy evolution and fetal well-being through biochemical and biophysic monitoring; that allows to obtain an improvement of perinative mortality.

The various types of sensory nerve endings found in the peroneus tertius muscle in the ass and in the horse have been studied with Ruffini's gold chloride method. Free nerve endings have been described as well as encapsulated receptors. These corpuscles are classified as Pacini-like, Ruffini's terminations and also Golgi's tendon-organs. The authors have pointed out the morphology, topography and structural characteristics of the above named nervous terminations and have hypothesized that a probable functional relation existed between these nervous corpuscles and the considered tendinous structure.