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BACKGROUND: The coronavirus disease-19 (COVID-19) outbreak has been recently associated with lower hospitalization rates for acute coronary syndromes. Aim of the study was to investigate whether a similar behaviour is observed in admissions for urgent pacemaker implant. METHODS: This retrospective study included 1315 patients from 18 hospitals in Northern Italy with a high number of COVID-19 cases. Hospitalization rates for urgent pacemaker implant were compared between the following periods: 20 February to 20 April 2020 (case period); from 1 January to 19 February 2020 (intra-year control period); from 20 February to 20 April 2019 (inter-year control period). RESULTS: The incidence rate of urgent implants was 5.0/day in the case period, 6.0/day in the intra-year control period and 5.8/day in the inter-year control period. Incidence rate in the case period was significantly lower than both the intra-year [incidence rate ratio (IRR): 0.81, 95% CI 0.67-0.99, P = 0.040] and inter-year control periods (IRR: 0.79, 95% CI 0.66-0.95, P = 0.012); this reduction was highest after the national lockdown (IRR 0.68, 95% CI 0.52-0.91, P = 0.009). The prevalence of residents in rural areas undergoing urgent pacemaker implant was lower in the case period (36%) than in both the intra-year (47%, P = 0.03) and inter-year control periods (51%, P = 0.002). Elective pacemaker implants also decreased in the case period, with the incidence rate here being 3.5/day vs. 6.4/day in the intra-year (-45%) and 6.9/day in the inter-year period (-49%). CONCLUSION: Despite severe clinical patterns, the COVID-19 outbreak has negatively affected the population presentation to Emergency Departments for bradyarrhythmias requiring urgent pacemaker implant in Northern Italy. This mainly occurred after the national lockdown and concerned patients living in rural areas.

It is well recognized that both college and noncollege students are at-risk age groups for alcohol consumption. We investigated the alcohol consumption habits of undergraduate students with an emphasis on binge drinking. Participants (N = 809, 61.2% female) were freshmen attending courses at one of the main universities of southern Italy. They were asked to fill out a paper-and-pencil questionnaire that was administered between October 2017 and January 2018. Nearly 90% of the questioned students reported drinking alcohol during the 12 months before the survey. Among them, 31.4% of female students and 41.5% of male students engaged in binge drinking, mainly once a month; binge drinkers preferred highly alcoholic beverages during parties, underestimated the alcoholic content of their drinks, started drinking alcohol at a younger age than nonbinge drinkers, and drank weekly and between meals. Binge drinkers started smoking earlier than their peers, and a great number of them consumed illicit drugs. Moreover, 30.3% of female and 34.8% of male nonbinge drinkers declared that they consumed 6 or more units of alcohol in one occasion, making them unaware binge drinkers. Furthermore, approximately 50% of students recognized that alcohol consumption has effects similar to those induced by illicit drugs but only considered their peers' drinking behavior to be risky.This study highlights that most students involved in this survey expose themselves to a risky lifestyle by heavy drinking and, most alarmingly, that some of them are not even aware of that.

Current scientific consensus about the physiopathology in the progression from severe sepsis to septic shock and death focuses on myocardial contractile dysfunction. Nevertheless, objective parameters to establish a pathological correlate of a fatal outcome are lacking; then a cause of death due to sepsis can remain an unsolved problem. We first reviewed all death cases recorded at our institutions during the period from 2007 until 2015. Then, we conducted a retrospective study of a selected autopsy series of people who had received “sepsis” as cause of death. Two pathologists re-examined the heart sections while the most suitable myocardial sample for each case was stained for immunohistochemistry with antibodies targeted for specific inflammatory-related molecules. We used specific antibodies for the following markers: alpha-smooth muscle actin (alpha-SMA); fibronectin; matrix metallopeptidase 9 (MMP-9); intercellular adhesion molecule 1 (ICAM-1); caspase-3; lactoferrin (LF); cluster differentiation 15 (CD15). The statistical significance of differences was assessed using student’s t-test for unpaired data or non-parametric Mann–Whitney or Wilcoxon tests for skewed variables or one-way analysis of variance and post hoc Scheffe’s test for continuous variables and Pearson’s χ2-test for discrete variables. Linear regression analysis was used to determine the presence of a correlation between continuous variables. At our institutions, 2220 deaths have been recorded during the period study. Sepsis accounted as a cause of death for the 20% of total. We finally enrolled 56 cases; of these, only 20 were positive for microbiological analysis. At histological examination, clear inflammation was detectable in the 32% of cases; otherwise, immunohistochemical reaction showed a positive reaction for LF and CD15 in more than a half cases (56%). We still ignore all the underlying mechanisms of sepsis and all its pathophysiological connections with cardiac metabolism; in this sense, we aim to corroborate the diagnostic value of anti-LF and anti-CD15 staining for the post-mortem detection of myocardial inflammation.

Alcohol is recognized as one of four major risk factors for non-communicable diseases. Exposure to alcoholic beverages during the adolescence has been linked to increased heavier drinking habits: obviously, the age of alcohol initiation resulted an important determinant of alcohol dependence. The aim of this study is to analyze knowledge, attitudes and practices in alcohol habit of adolescent population.943 students from 13 schools (middle and upper secondary schools) of the Bari district were enrolled in the study: in each school one class for each age was randomly selected. The research was carried out by an anonymous, self-administered questionnaire which investigated alcohol consumption, knowledge of alcohol consumption of parents and knowledge of the law regulating alcohol consumption.34.8% (328) have never consumed alcoholic drinks while 65.2% (615) declare the use of alcohol; the average age of alcohol initiation was 12.2 years. 35.7% (329/921) of mothers and 36.6% (335/915) of fathers drink alcohol only on special occasions. 17.9% (168/939) considered that alcohol could be free sale at all while 16.4% (154/939) reported that sale is forbidden for children under 14.The higher prevalence of alcohol habits and the poor knowledge on alcohol law seemed to indicated the need of improving public health efforts in the prevention of alcohol consumption among Italian adolescents.

Hirsutism has negative impact on adolescent psychosocial development for both cosmetic and endocrine reasons. This study evaluated the effectiveness of a new intermittent, low-dose finasteride regimen consisting of 2.5 mg of drug given every 3 days (1 day of treatment, 2 days of drug withdrawal) for 6 months in girls with hirsutism by polycystic ovarian syndrome (PCOS) or idiopathic hirsutism (IH).Twenty-eight girls (15-19 y old) with hirsutism were randomly assigned to 2 treatment groups and treated for 6 months. Fourteen patients (7 with IH, 7 with PCOS) received finasteride; fourteen patients (7 with IH, 7 with PCOS) received placebo. Hirsutism score (HS), clinical, and hormonal effects were compared between the 2 groups.In patients treated with finasteride, the HS value at 6 months was 52.9% lower than that observed at baseline in girls with IH, and 52.8% lower in girls with PCOS (P.0001 for both). Similarly, the 3α-17 β-androstenediol glucuronide serum levels were decreased by 34.8% in patients with IH, and by 47.5% in patients with PCOS (P.0001, respectively). Finasteride treatment was well tolerated and did not alter values of BMI, serum levels of sexual hormones, metabolic parameters related to liver and kidney function as well as glycemic and lipidic asset.A low-dose of finasteride, given every 3 days, reduces the HS in young patients affected by PCOS or IH. Compared with conventional continuous finasteride administration, the intermittent low-dose regimen has similar efficacy with the advantage to be safer and less expensive.

Xanthium strumariumL. is a member of the Asteraceae commonly used in Cuba, mainly as diuretic. Some toxic properties of this plant have also been reported and, to date, very little is known about its genotoxic properties. The present work aims was to evaluate the potential cytotoxic and genotoxic risk of whole extract fromXanthium strumariumL. whole extract of aerial parts. No positive response was observed in a battery of fourSalmonella typhimuriumstrains, when exposed to concentrations up to 5 mg/plate, with and without mammalian metabolic activation (liver microsomal S9 fraction from Wistar rats). In CHO cells, high concentrations (25–100 μg/mL) revealed significant reduction in cell viability. Results from sister chromatid exchanges, chromosome aberrations, and comet assay showed thatX. strumariumextract is genotoxic at the highest concentration used, when clear cytotoxic effects were also observed. On the contrary, no increase in micronuclei frequency in bone marrow cells was observed when the extract was orally administered to mice (100, 500, and 2000 mg/Kg doses). The data presented here constitute the most complete study on the genotoxic potential ofX. strumariumL. and show that the extract can inducein vitroDNA damage at cytotoxic concentrations.

Introduction: Major depression is a worldwide problem and often remains undetected and untreated. Given the low rates of detection plus the need to intervene in a short time, it is important to identify factors which are likely to improve treatment outcomes. Methods: STIMA-D was designed to provide the profile of patients with major depression in Italy (focusing on pathway to care, patient characteristics, drug therapy and treatment outcomes). The patients enrolled (M/F, aged between 18 and 65) experienced single/multiple episodes of major depression (DSM-IV-TR). Patients with lifetime or current bipolar syndrome or other mental disorders were excluded. Results: 44 of the 50 invited centers sent data concerning 1 140 patients. The majority of patients were women. Among working individuals, 52.5% of them were absent from work due to depression in the previous 6 months. Recurrent episodes of major depression were very common and were associated with persistence of residual post-episodic symptoms, a family history of mood disorders and presence of anxiety. 59.6% of the patients were treated with monotherapy (SSRI or SNRI), while 19.2% of them were treated with SSRI plus SNRI. Only the 25.5% on monotherapy had a complete response compared to 12.4% of patients on dual therapy. Discussion: Poor outcomes in major depression have profound implications on patients’ quality of life and cost burden. New pharmacological approaches with novel modes of action are therefore urgently needed.

Earlier neuroimaging studies of motor function in schizophrenia have demonstrated reduced functional lateralization in the motor network during motor tasks. Here, we used event-related functional magnetic resonance imaging during a visually guided motor task in 18 clinically unaffected siblings of patients with schizophrenia and 24 matched controls to investigate if abnormal functional lateralization is related to genetic risk for this brain disorder. Whereas activity associated with motor task performance was mainly contralateral with only a marginal ipsilateral component in healthy participants, unaffected siblings had strong bilateral activity with significantly greater response in ipsilateral and contralateral premotor areas as well as in contralateral subcortical motor regions relative to controls. Reduced lateralization in siblings was also identified with a measure of laterality quotient. These findings suggest that abnormal functional lateralization of motor circuitry is related to genetic risk of schizophrenia.

The clinical presentation of Bordetella pertussis can overlap with that of respiratory syncytial virus (RSV), and coinfection does occur, but management differs.The prevalence of B. pertussis is2% among Emergency Department (ED) patients with bronchiolitis. Our secondary hypothesis was that the prevalence of Bordetella parapertussis is also2% among these patients.Nasal washings were obtained from children up to 18 months of age (inclusive) who presented to a county hospital ED with a clinical diagnosis of bronchiolitis. These washings were frozen to -70°C before testing for B. pertussis and B. parapertussis using species-specific real-time polymerase chain reaction (PCR) assays. The assays were optimized to target conserved regions within a complement gene and the CarB gene, respectively. A Bordetella spp. genus-specific real-time PCR assay was designed to detect the Bhur gene of B. pertussis, B. parapertussis, and B. bronchiseptica. RSV antigen detection was also performed.There were 227 patients enrolled. After exclusions, 204 remained in the analysis. RSV antigen testing was positive in 109/186 (59%) of the patients in whom it was performed. All samples were tested for B. pertussis. B. parapertussis testing could not be completed on 23 samples. No cases (0/204; 95% confidence interval [CI] 0-1.8%) tested positive for B. pertussis or B. parapertussis (0/181; 95% CI 0-2%).The prevalence of B. pertussis in children presenting to the ED with bronchiolitis was2%.

Punica granatum L. (Punicaceae) whole fruit extracts, have been used in Cuban traditional medicine as an effective drug for the treatment of respiratory diseases. This species showed interesting anti-viral activity, e.g. aqueous or hydroalcoholic extracts of whole fruits have proved highly active against the influenza virus. However, some toxic properties of this extract have also been reported and, to date, very little is known about its genotoxic properties. In the present study, the genotoxicity of a Punica granatum (pomegranate) whole fruit extract was assessed using different in vitro and in vivo assays that detect DNA damage at different expression levels. Results from reversion and gene-conversion test in microorganisms, sister chromatid exchanges, micronuclei and sperm-shape abnormality assays in mice, clearly showed that the hydroalcoholic extract of P. granatum whole fruits is genotoxic when tested both in vitro and in vivo.

Background Vitamin D (Vit D) is important for the regulation of reproductive physiology. In humans, maternal Vit D deficiency has been implicated in several reproductive- and pregnancy-related disorders. Very few data are available regarding the Vit D status in male partners of couples attempting pregnancy. This observational study (IRB Prot. N. 078/13) aimed to evaluate whether low Vit D serum levels in males might decrease the rate of successful conception in couples attempting pregnancy. Methods Male and female partners of infertile couples (n = 102) were classified into 2 GROUPS according to normal (≥30 ng/ml) or low (below 30 ng/ml) serum Vit D levels in male partners. Semen analysis was performed in each male participant based on the WHO reference criteria. The female partners of both groups were subjected to 3 consecutive cycles of gonadotropin-induced mono-ovulation. The main outcome measures included the clinical pregnancy rate, delivery per patient and per cycle, and miscarriage rate between the 2 groups evaluated at the end of the three-month period of the study. Results In male partners of both groups, standard semen analysis did not highlight substantial differences in sperm concentration, sperm progressive motility, or typical form. The pregnancy rates per patient and per cycle and delivery rates per patient and per cycle were all significantly higher (p

Premenstrual syndrome (PMS) might become severe enough to interfere with normal interpersonal relationships. This study was planned to assess whether administration of vitamin D (200,000 IU at first, followed by 25,000 IU every 2 weeks) for a 4-month period might lessen the appearance and the intensity of mood disorders associated with PMS in young girls with severe hypovitaminosis D. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: One hundred fifty-eight young girls (15-21 years old) with PMS-related severe symptoms of the emotional and cognitive domains and low serum 25-hydroxycholecalciferol (25-OH-D) levels (≤10 ng/mL) were randomly assigned to two treatment groups and treated for 4 months with vitamin D (group 1; n = 80) or placebo (group 2; n = 78). Clinical and hormonal effects were compared between the two groups.In patients from group 1, levels of vitamin D reached the normal range (35-60 ng/mL) after the first month and remained stable throughout the whole study. At the end of treatment, anxiety score decreased from 51 to 20 (P .001 vs baseline); irritability score declined from 130 to 70 (P .001 vs baseline). Crying easily and sadness decreased by a score of 41 and 51 to a score of 30 and 31, respectively (P .001). For disturbed relationships, the score decreased from 150 to 70 (P .001). Conversely, no appreciable changes were noted in symptom intensity from patients of group 2. The frequency of adverse events (nausea and constipation) was not different between participants of group 1 and group 2.On the basis of the present findings, vitamin D therapy can be proposed as a safe, effective, and convenient method for improving the quality of life in young women with severe hypovitaminosis D and concomitant mood disorders associated with PMS.

Aims/hypothesis. This study aimed to determine if the incidence of Type I (insulin-dependent) diabetes mellitus increased over time and if the time trend is attributable to linear trend, calendar period or birth cohort effects.¶Methods. This study was based on a cohort of subjects aged 0–29 years from 1984 to 1996, who resided in the province of Turin, Italy. Poisson regression models were used to estimate the effect of sex, age, calendar time and cohorts on incidence rates.¶Results. The mean incidence rate in the age group of 0 to 29 years was 7.78 of 100,000 person-years (95 % confidence interval: 7.26–8.32), with a lower risk in women than in men [rate ratio (RR): 0.76 (0.67–0.88)]. We found a trend of incidence increasing over time (annual increase of risk 2.25 % a year, 95 % CI 0.44–4.10). In Poisson regression analysis we found that the best model was the one with sex, age and a linear term attributable to either calendar period or cohort effects. The linear term corresponds to a RR of 1.12 (1.02–1.22, p = 0.015) for each 5-year age span.¶Conclusion/interpretation. We found that the time trend in this Mediterranean area was similar in magnitude to that reported in northern European countries. The increase was linear in pattern, each birth cohort and each calendar period showing a higher risk than the preceeding one with some evidence of two steep increases in the incidence of Type I diabetes centered on the years 1964 and 1984. We found that the incidence of diabetes increased in the 0 to 14 age group and also in the older age group of 15 to 29 years and that the age-period models were not statistically significantly better than the age-cohort models. [Diabetologia (2001) 44: 22–25]

Background Children of Sardinian heritage are at high risk of type 1 diabetes, whereas no data are available in young adults. Age at onset of type 1 diabetes could be associated with different relative weight of genetic susceptibility and environmental determinants in the pathogenesis of the disease. We test this hypothesis in subjects with Sardinian heritage 0‐29 years of age living in the city of Turin, a highly industrialized area in Northern Italy. Methods In all, 202 cases with onset of type 1 diabetes aged 0‐29 years during 1984‐1991 and 1010 controls randomly selected from residents of the city of Turin, frequency-matched by sex and year of birth to cases, were included in this study. Name and place of birth of parents were ascertained by postal inquiry and linkage with city population and census files. Social class was based on the highest educational level of parents abstracted from 1991 and 1981 census files. Results Differential effects on risk of type 1 diabetes of Sardinian heritage and social class in the age groups 0‐14 and 15‐29 years were found. In children with one and both Sardinian parents the odds ratios (OR) were 2.09 (95% CI : 0.85‐5.15) and 3.20 (95% CI : 0.75‐13.64); in young adults 0.81 (95% CI : 0.18‐3.64) and 1.95 (95% CI : 0.51‐7.40), respectively. In subjects with low social class the OR were 1.16 (95% CI : 0.68‐1.97) in children and 0.66 (95% CI : 0.41‐1.05) in young adults. Conclusions This study shows higher risk of type 1 diabetes in subjects of Sardinian heritage; higher risk in children than in young adults and a protective effect of low social class in young adults. These findings are consistent with the hypothesis of heterogeneity of type 1 diabetes by age at onset, with prevailing genetic effect in childhood and environmental determinants in adulthood.

Failure of intestinal anastomosis is a major complication following abdominal surgery. Biological materials have been introduced as reinforcement of abdominal wall hernia in contaminated setting. An innovative application of biological patch is its use as reinforcement of gastrointestinal anastomosis. The aim of study was to verify whether the bovine pericardium patch improves the healing of anastomosis, when in vivo wrapping the suture line of pig intestinal anastomosis, avoiding leakage in the event of deliberately incomplete suture. Forty-three pigs were randomly divided: Group 1 (control, n = 14): hand-sewn ileo-ileal and colo-colic anastomosis; Group 2 (n = 14): standard anastomosis wrapped by pericardium bovine patch; Group 3 (n = 1) and 4 (n = 14): one suture was deliberately incomplete and also wrapped by patch in the last one. Intraoperative evaluation, histological, biochemical, tensiometric and electrophysiological studies of intestinal specimens were performed at 48 h, 7 and 90 days after. In groups 2 and 4, no leak, stenosis, abscess, peritonitis, mesh displacement or shrinkage were found and adhesion rate decreased compared to control. Biochemical studies showed mitochondrial function improvement in colic wrapped anastomosis. Tensiometric evaluations suggested that the patch preserves the colic contractility similar to the controls. Electrophysiological results demonstrated that the patch also improves the mucosal function restoring almost normal transport properties. Use of pericardium bovine patch as reinforcement of intestinal anastomosis is safe and effective, significantly improving the healing process. Data of prevention of acute peritonitis and leakage in cases of iatrogenic perforation of anastomoses, covered with patch, is unpublished.

The aim of the paper was to perform a chronological assessment of the phenomenon of delayed rupture of the spleen, to assess the phenomenological order about the sub-capsular hematoma transformation to determine the causal relationship with trauma as hypothetical cause of death. 80 cases of blunt trauma with splenic capsular hematoma and subsequent rupture of the spleen were evaluated: 38 had an acute rupture of the spleen, 42 presented a break in days or weeks after the traumatic injury. Time between the traumatic event and delayed rupture of the spleen is within a range of time from one day to more than one month. Data recorded included age, sex, type of trauma, injury severity score, grade of splenic injury, associated intra-abdominal injuries, pathologic specimen evaluation. Immunohistochemical investigation of perisplenic hematoma or laceration was performed utilizing polyclonal antibodies anti-fibrinogen, CD61 and CD68, and showed structural chronological differences of sub-capsular hematoma. Expression of modification and organization of erythrocytes, fibrinogen, platelets and macrophages provides an informative picture of the progression of reparative phenomena associated with sub-capsular hematoma and subsequent delayed splenic rupture. Sub-capsular splenic hematoma dating, which we divided into 4 phases, is representing a task in both clinical practice and forensic pathology.

BackgroundDespite depressive disorders being very common there has been little research to guide primary care physicians on the choice of treatment for patients with mild to moderate depression.AimsTo evaluate the efficacy of interpersonal counselling compared with selective serotonin reuptake inhibitors (SSRIs), in primary care attenders with major depression and to identify moderators of treatment outcome.MethodA randomised controlled trial in nine centres (DEPICS, Australian New Zealand Clinical Trials Registry number: ACTRN12608000479303). The primary outcome was remission of the depressive episode (defined as a Hamilton Rating Scale for Depression score 7 at 2 months). Daily functioning was assessed using the Work and Social Adjustment Scale. Logistic regression models were used to identify moderators of treatment outcome.ResultsThe percentage of patients who achieved remission at 2 months was significantly higher in the interpersonal counselling group compared with the SSRI group (58.7% v. 45.1%, P = 0.021). Five moderators of treatment outcome were found: depression severity, functional impairment, anxiety comorbidity, previous depressive episodes and smoking habit.ConclusionsWe identified some patient characteristics predicting a differential outcome with pharmacological and psychological interventions. Should our results be confirmed in future studies, these characteristics will help clinicians to define criteria for first-line treatment of depression targeted to patients' characteristics.

The aim of the present study was to investigate the influence of prenatal exposure to carbon monoxide (CO) on vascular reactivity of rat resistance vessels, in different stages of neurogenesis. Both prenatally CO-exposed and control male Wistar pups (5–7, 9–11, 14–16, 20–22 days) were tested vs respective 60 day adult rats. The results showed that: (i) at 5–7 days of age, TTX caused a more marked inhibition of perivascular nerve stimulation (PNS)-evoked vasoconstriction in CO-exposed animals with respect to controls; (ii) the NO-related relaxant effect by ACh in CO-exposed group appeared earlier (5–7 days) than in control group (9–11 days); (iii) the contractile response evoked by ACh on resting tone disappeared earlier (after 14–16 days) than in control group (after 20–22 days). These observations suggested that CO-exposure might induce changes in nerve electrophysiological properties and might cause a precocious maturation of the NO-related enzymatic mechanism implicated in ACh-relaxation.

This study evaluated the usefulness of multidetector computed tomography (MDCT) in the postmortem diagnosis of death by drowning in fresh water by measuring the difference of blood density within the cardiac chambers. Twenty-two corpses including six cases of fresh-water drowning (group A) and 16 deaths by other causes (group B), among which were also different forms of mechanical asphyxia other than drowning, underwent MDCT and conventional autopsy. Blood density within the right and left heart chambers, the aorta and the pulmonary trunk was measured and values compared between groups and within each group between heart chambers. Blood density in all cardiac chambers was lower in group A than in group B. The difference was statistically significant within the left atrium and ventricle and was significantly lower in the left than in the right heart chambers in group A only. MDCT, together with conventional autopsy, may contribute to the diagnosis of drowning, by measuring blood density in the heart chambers.

The aim of the present study was to evaluate whether prenatal exposure to relatively low concentrations of carbon monoxide (CO) may alter the frequency of splenic cells either in young (15—21 days) or in aged rats (18 months). Wistar female rats were exposed to 75 and 150 ppm of CO from day 0 to day 20 of pregnancy, respectively.The results show that prenatal exposure to 150 ppm of CO significantly decreases the number of leucocyte common antigen (LCA±) cells in 21 day old male rats, whereas other cellular populations, such as macrophages, Major Histocompatibility (MHC) II cells, T and B lymphocytes display only a trend towards a reduction without achieving statistical significance. The alterations in LCA± cell frequency produced by gestational exposure to CO were reversible.These data further extend previous findings showing that rats prenatally exposed to moderate concentrations of CO exhibit subtle immunological changes in the absence of overt signs of toxicity.

Wistar female rats were exposed to relatively mild concentrations of carbon monoxide (CO) (75 and 150 p.p.m.) from day 0 to day 20 of pregnancy. The results show that splenic macrophage phagocytosis of Candida albicans was significantly decreased in 15 and 21 day old male rats exposed to CO (150 p.p.m.) during pregnancy. Moreover, splenic macrophage killing was significantly reduced in 15 day old male pups prenatally exposed to 75 and 150 ppm of CO. Prenatal CO (150 p.p.m.) significantly decreased splenic macrophage O2- release in both 15 and 21 day old pups. CO-induced alterations in the immune system were not observed in 60 day old rats. These findings indicate that gestational exposure to relatively mild concentrations of CO induces in rat offspring reversible immunological changes characterized by an altered splenic macrophage function.

The authors report a study of treated prevalence and incidence of schizophrenic and related functional psychoses in an area of northeastern Italy (Portogruaro), based on case-register data. Point, 1-year, and lifetime prevalence as well as incidence rates on the adult population for a broad ICD-9 diagnosis of schizophrenia are given. Data over an 8-year period show the incidence around .2/1000, point prevalence around 1.4, 1-year prevalence of 2.7, and lifetime prevalence around 5.2. The rates peak in the 45 to 64 age group on all measures of prevalence. The implications of these findings are discussed in the light of methodological issues in epidemiological studies of schizophrenia and comparisons are made with figures from other countries.

1. Prolonged administration of a benzodiazepine receptor antagonist, such as flumazenil (given to the mother at a dose of 3 mg/kg s.c. from day 14 to day 20 of gestation), produced subtle behavioral changes in rat pups. 2. Flumazenil treatment decreased the rate of ultrasonic vocalization in 15-day old male pups removed from their nest. 3. No significant changes in the locomotor activity of the flumazenil-treated group with respect to controls was found at the end of the second and fourth postnatal week. 4. These results suggest that late prenatal exposure to flumazenil induces in rat offspring behavioral changes characterized by decreased emotional responsiveness to environmental challenges.

The authors ascertained the prevalence of primary blepharospasm (BSP) in a community located in Puglia, a region in Southern Italy, by focusing on neurologists and ophthalmologists. The crude prevalence rates were 133 per million (95% CI, 61--153) for both focal and segmental BSP, 74 per million (95% CI, 24--173) for focal BSP, and 59 per million (95% CI, 16--151) for segmental BSP. Prevalence rate increased with age. Apraxia of eyelid opening and BSP coexisted in one third of cases.

Background Depression is a frequently observed and disabling condition in primary care, mainly treated by Primary Care Physicians with antidepressant drugs. Psychological interventions are recommended as first-line treatment by the most authoritative international guidelines but few evidences are available on their efficacy and effectiveness for mild depression. Methods/Design This multi-center randomized controlled trial was conducted in 9 Italian centres with the aim to compare the efficacy of Inter-Personal Counseling, a brief structured psychological intervention, to that of Selective Serotonin Reuptake Inhibitors. Patients with depressive symptoms referred by Primary Care Physicians to psychiatric consultation-liaison services were eligible for the study if they met the DSM-IV criteria for major depression, had a score ≥13 on the 21-item Hamilton Depression Rating Scale, and were at their first or second depressive episode. The primary outcome was remission of depressive symptoms at 2-months, defined as a HDRS score ≤ 7. Secondary outcome measures were improvement in global functioning and recurrence of depressive symptoms at 12-months. Patients who did not respond to Inter-Personal Counseling or Selective Serotonin Reuptake Inhibitors at 2-months received augmentation with the other treatment. Discussion This trial addresses some of the shortcomings of existing trials targeting major depression in primary care by evaluating the comparative efficacy of a brief psychological intervention that could be easily disseminated, by including a sample of patients with mild/moderate depression and by using different outcome measures. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12608000479303

Objective To evaluate whether the addition of finasteride (a 5〈-reductase inhibitor) to conventional protocol of ovarian stimulation with gonadotropin can improve ovarian follicular growth in polycystic ovary syndrome (PCOS) women who did not respond to previous stimulation with gonadotropin alone. Design Double-blind randomized study. Setting Outpatient in an academic research environment. Patient(s) Thirty-six PCOS patients in whom the previous multifollicular stimulation protocols with gonadotropin failed. Intervention(s) The patients were randomly assigned to two treatment groups: group 1 underwent ovarian stimulation with recombinant FSH (rFSH) plus finasteride, and group 2 received rFSH alone. When the dominant follicle reached a mean diameter of 18 mm, hCG was administered and finasteride withdrawn. Main Outcome Measure(s) Ovulation rate in women with PCOS. Result(s) Follicular growth and ovulation occurred in eight patients in group 1, whereas no cases were detected in group 2. Conclusion(s) This study confirms that hyperandrogenism interferes with follicular growth and suggests that administration of finasteride during ovarian stimulation with rFSH improves ovulation rate in selected hyperandrogenic anovulatory women.

Objective To evaluate the hypothesis that pretreatment with estrogens in women affected by premature ovarian failure (POF) may improve the results of ovarian stimulation. Design Double-blind, randomized, placebo-controlled study. Setting Outpatient department in an academic research environment. Patient(s) Fifty women with POF seeking pregnancy. Intervention(s) Before starting ovarian stimulation, group 1 received 0.05 mg ethinyl-E 2 (EE) three times a day for 2 weeks, while group 2 received placebo. Ovarian stimulation was carried out with recombinant FSH (r-βFSH), 200 IU/day/SC. Both EE and placebo were administered during ovarian stimulation. Human chorionic gonadotropin (10,000 IU/IM) was added when the follicle exceeded a mean diameter of 18 mm. Main Outcome Measure Rate of ovulation in women with POF. Result(s) Levels of FSH before stimulation were significantly lower in group 1 than in group 2. The rate of ovulation in group 1 (8/25; 32%) was significantly higher than in group 2 (0/25; 0%). Notably, induction of ovulation was successful only in patients whose FSH levels after EE treatment were ≤15 mIU/mL. Conclusion(s) Our data suggest that pretreatment with EE improves the success of rate of ovulation induction with exogenous gonadotropins in patients with POF. A threshold of FSH ≤15 mIU/mL should be achieved before starting ovarian stimulation.

Assessing biological age in the youth nearby legal age has always represented a stimulating issue for the Italian forensic scientist as far as he deals with matter of imputability and legal or illegal immigration of uncertain age subjects. Since any method of evaluation should of course be accurate, not invasive, reproducible and, as possible, easily exploitable, radiological investigation of age dependent features is the most appropriate instrument to the purpose. Dental development is slower and delayed compared with skeletal bone one, occurring according to a known, regular pattern from whose evaluation a biological age can be assessed with a reasonably restricted span for a certain radiological image. This is the assumption which inspired since 1941 (Schour e Massler) so many anthropologists and forensic and clinic odontologist in investigating biological age by the study of radiological dental morphology. Demirjian and Goldstein [New systems for dental maturity based on seven and four teeth, Ann. Hum. Biol. 3 (1976) 411–421] obtained no differences between two groups of subjects whose age was extimated by the evaluation of 14 teeth in one case and 7 teeth in another, the last being greatly simpler. Afterwards, Thorson (1991), Mincer et al. [The A.B.F.O. study of third molar development and its use as estimator of chronological age, J. Forensic Sci. 38 (1993) 379], Solari and Abramovitc [The accuracy and precision of third molar development as an indicator of chronological age in Hispanic, J. Forensic Sci. (3) (2002) 531–535] and then Prieto Carrero [Evaluation of Chronological Age Based on Third Molar Development in the Spanish Population, Atti del XIX Congresso IALM, Milano, 2003], developed a method based on the evaluation of the radiological development of the alone third molar, according to Demirjian's schematic definitions of crown and root formation. Eight stages of development of the third molar are defined from the time of mineralization appearance of the cusp tips up to complete closing of the apexes. In order to achieve grater precision in discriminating stages F and G, Solari added two stages (F1 and G1), determining 10 stages of maturation of root and crown. Prieto tested the accuracy and precision of this method by the evaluation of about 1300 orthopantomographs of juveniles and young Spanish adults of known age, divided for gender. We analyzed a total of 400 orthopantograms of young Spanish dental patients to evaluate the chronology of the right mandibular third molar development and to assess its correlation with the biological age of the tested. Biological age is attributed with a maximum standard deviation of 2.47 from the mean in the eight stages outline. The greatest limit of the method seems to be the operator experience in determining the dental stage of development. We think that age data coming from such evaluation method should be clearly explained to the magistrate in their true statistical significance and limits.

In a prospective randomized study 38 women with idiopathic hirsutism or polycystic ovary syndrome (PCOS) received 2.5 mg of finasteride every day or every 3 days. Intermittent low-dose administration of finasteride was as effective as continuous administration in reducing hirsutism score and was accompanied by a lower incidence of side effects.

Single-voxel proton magnetic resonance spectroscopy (1H-MRS), localised to the basal ganglia, was used to determine changes in metabolite levels in idiopathic spasmodic torticollis (IST). We examined nine patients and 13 healthy subjects. The mean values (+/- SD) of peak area ratios were: IST: N-acetyl-aspartate (NAA)/choline-containing compounds (Cho) 1.79 +/- 0.39, NAA/creatine and phosphocreatine compounds (Cr) 1.61 +/- 0.38, Cho/Cr 0.91 +/- 0.19; controls: NAA/Cho 2.07 +/- 0.35, NAA/ Cr 1.82 +/- 0.31, Cho/Cr 0.89 +/- 0.12. Statistical analysis showed that NAA/Cho and NAA/Cr were significantly lower in patients than in controls (P = 0.0304 and 0.0431, respectively). These results indicate a reduction in NAA, and suggest striatal involvement in the pathogenesis IST.

Objective: To compare the clinical efficacy of an original combined therapy with cyproterone acetate, 2 mg, and ethinylestradiol, 35 μg (Diane 35), plus finasteride (5 mg) for 2 weeks per month with that of Diane 35 alone in hirsute women. Design: Prospective randomized, single-blinded study. Setting: Outpatients in an academic research environment. Patient(s): Fifty women with idiopathic hirsutism (IH) or the polycystic ovary syndrome (PCOS). Intervention(s): Group 1 (n = 25) received Diane 35 alone and group 2 (n = 25) received Diane 35 plus finasteride. The latter drug was administered using a new therapeutic scheme: 14 consecutive days for each therapeutic cycle. Main Outcome Measure(s): Hormonal evaluation was done before beginning treatment and after 3 and 6 months of therapy. Hirsutism was graded at 3-month intervals. Result(s): The combination of Diane 35 plus finasteride for 14 days significantly decreased the hirsutism score after 3 months of therapy, while Diane 35 alone induced this effect after 6 months. Conclusion(s): Finasteride in combination with Diane 35 for 14 days is effective, well accepted, and safe in hirsute patients, as the amount of antiandrogenic drugs administered is much lower than that in conventional treatment.

In a case-control study, the authors found that arterial hypertension occurred more frequently among 115 patients with primary hemifacial spasm than among 115 neurologic controls matched for age (+/-5 years), sex, and referral center. The association was not confounded by education level, smoking history, diabetes, or other diseases (adjusted OR 2.64; 95% CI 1.3 to 5.33, p = 0.007). Hypertension was significantly associated with the outcome in the left-sided group (OR 4.0; 95% CI 1.4 to 11.5), but data concerning patients with right-sided spasm were inconclusive (OR 1.05; 95% CI 0.36 to 3.1). In our sample, hypertension either preceded or followed the onset of hemifacial spasm.

To analyze aggressive angiomyxoma hormone-dependency.Estroprogestinic receptor expression was studied by immunohistochemistry in 5 patients with aggressive angiomyxoma of the vulva.The immunohistochemical results confirm the positivity of angiomyxoma for estrogen and progesterone receptors.We hypothesized that the concomitant factor favoring neoplastic growth is a different genetic substrate specific in the female sex. Analysis of the data regarding the distribution of angiomyxomas in different age groups has strengthened this hypothesis suggesting that this tumor is correlated with complete maturity, in all probability hormonal. However it cannot be excluded that the tumor begins to develop at an early age, but since it has a slow growth rate, the phenomenon is delayed and is related to hormonal stimulation.

OBJECTIVE: In lean diabetic patients, the presentation of the disease does not allow one to easily distinguish between type 1 and type 2. Aims of this study were to describe clinical, immunological, and genetic features of lean newly diagnosed diabetic patients. RESEARCH DESIGN AND METHODS: A population-based cohort of 130 lean (BMI < 25 kg/m2) newly diagnosed patients, aged 30-54 years, was identified among residents of the province of Turin. Islet cell antibodies (ICAs), anti-GAD, fasting and glucagon-stimulated C-peptide values, and HLA DQA1-DQB1 susceptibility genotypes were assessed within 2 months of the diagnosis. RESULTS: A total of 45 (34.6%) and 29 (22.3%) patients were, respectively, ICA+ and anti-GAD+, with 15 (11.5%) having both antibodies. In 59 patients, ICAs and/or anti-GAD antibodies were detected, giving a high prevalence of autoimmunity (45.4%, 95% Cl 36.8-54.0); relative to patients without markers (n = 71), they were younger (40.8 +/- 7.5 vs. 45.0 +/- 6.5 years, P < 0.001) and showed lower values of fasting C-peptide (0.56 +/- 0.33 vs. 0.79 +/- 0.41 nmol/l, P < 0.001) and stimulated C-peptide (1.03 +/- 0.56 vs. 1.42 +/- 0.69 nmol/l, P < 0.001). The lowest stimulated C-peptide values were found in patients with both ICA and anti-GAD antibodies. Frequencies of adult-onset type 1 and type 2 diabetes were, respectively, 49.2 and 50.8%. Clinical and genetic features were not useful in the classification of patients. CONCLUSIONS: Almost 50% of lean young and middle-aged patients were ICA+ and/or anti-GAD+, suggesting a high prevalence of a slowly evolving form of type 1 diabetes. The evaluation at diagnosis of both beta-cell secretory capacity and markers of autoimmunity is recommended to provide a pathogenetic classification of the disease.

Single-volume proton magnetic resonance spectroscopy, localized to basal ganglia, was carried out in 10 patients with primary blepharospasm (PB) to assess the levels of N-acetyl aspartate (NAA), creatine-phosphocreatine, and choline-containing compounds. NAA was reduced significantly in patients compared with control subjects. This result suggests a striatal neuronal loss in PB.

So-called apraxia of eyelid opening (scAEO) has been described chiefly in the context of extrapyramidal disorders. We described 10 new patients with scAEO developing in the absence of any other CNS sign and reviewed the 11 cases with isolated scAEO reported in the literature. Combining our patients and those from the literature, peak age at onset was in the 6th decade and there was a female preponderance of 2:1. The characteristic inability to initiate lid elevation was frequently associated with failure to sustain lid elevation, thus suggesting that eyelid motor control may be abnormal in isolated scAEO. Antecedent events included ocular signs and symptoms consistent with diseases of eyes or face (4 cases in our series and 2 in the literature), chronic treatment with flunarizine (1 case), and family history of dystonia (1 case). Flunarizine discontinuation led to sustained remission of the eyelid disturbance. Overall, these clues suggest the involvement of the extrapyramidal system in the pathophysiology of isolated scAEO. Familial clustering of isolated scAEO in one of our patients may be in favor of a genetic contribution. In our series, botulinum toxin administration close to the pretarsal part of the orbicularis oculi muscle significantly improved scAEO in 8/10 cases, whereas orbital/preseptal injection had no effect. We conclude that the term ‘apraxia’ may not be the correct descriptive term even when the eyelid disturbance occurs without any other CNS disease.

To document the incidence of IDDM in the Province of Turin (Italy) in the 8-year period 1984-91 in children (0-14 years) and young adults (15-29 years), in relation to age, sex, monthly-seasonal variability, calendar year and urban/rural area, (all newly diagnosed cases (502) were ascertained through primary and secondary data sources and completeness of ascertainment estimated with the two sample capture-recapture method (99% in childhood and 95% in young adults). The independent effect of age, sex, calendar year, and urban/rural area was estimated with a Poisson regression model. Age-specific incidence rates were 8.42/100,000 (95% CI 7.37-9.62) and 6.72/100,000 (95% CI 5.96-7.58), respectively, in the age groups 0-14 and 15-29 years. Sex differences were evident in young adults, with an almost 1.5-fold increased risk in men (8.37/100,000, 95% CI 7.21-9.71 vs 5.00/100,000, CI 4.09-6.10). Seasonal trend was evident in childhood. Predictors of incidence rates were age, place of residence and interaction between sex and age; no temporal trend was detected. No significant differences were found in the two age-groups with respect to glycaemia, glycosuria, ketonuria, and fasting C-peptide levels. In conclusion, this study shows sex differences in IDDM risk in young adults; 55% of incident cases occurring in young adults; an independent contribution of urban/rural differences to IDDM risk; no temporal trend in 1984-91; a seasonal pattern of incidence in children; no significant differences in clinical presentation between age groups.

Wistar female rats were exposed to relatively mild concentrations of carbon monoxide (75 and 150 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to CO (150 ppm) significantly impairs the acquisition of a two-way active avoidance task in 3-month-old male rats as well as the acquisition and reacquisition of this schedule in 18-month-old animals subjected to six daily 20-trial sessions. These deficits do not seem to be attributable to alterations of a non-associative nature, as the intertrial activity and the escape response latencies in CO exposed animals were not significantly affected with respect to controls. These findings, showing that gestational exposure to CO induces in rat offspring permanent learning and memory impairment, confirm that the offspring of smoking mothers may be at considerably greater risk than current epidemiological studies on birthweight and neonatal mortality suggest.

A case of pure neurinoma of the retroperitoneal space developing in the pelvis is described. This tumor (phi max, 15 cm) responsible for intense compressive symptomatology involving the pelvic organs, was at first mistaken for a uterine fibroid. The ultimate diagnosis both of neurinoma as well as every other neoplasm originating in the retroperitoneum can sometimes be very hard to obtain. Those tumors can indeed be misdiagnosed for other more common conditions both clinically and instrumentally and the rarity of this particular localization adds further trouble to the matter.

Mammalian DNA topoisomerase II represents the cellular target of many antitumor drugs, such as epipodophyllotoxin VP-16 (etoposide). The mechanism by which VP-16 exerts its cytotoxic and antineoplastic actions has not yet been firmly established, although the unique correlation between sensitivity to ionizing radiation and to topoisomerase II inhibitors suggest the involvement of DNA double-strand breaks. In the present study we analyzed the chromosomal sensitivity of lymphoblastoid cell lines derived from ataxia telangiectasia (AT) patients to low concentrations of the drug. Our results indicate that AT derived cells are hypersensitive to the clastogenic activity of VP-16 either when the drug is present for the whole duration of the cell cycle or specifically in the G2 phase, confirming that the induction of DNA double strand breaks, to which AT cells seem typically sensitive, could have an important role in the biological activity of VP-16.

SynopsisService utilization measures from the psychiatric case registers for urban South-Verona and rural Portogruaro in North East Italy for the period 1983–9 were used to identify associations with socio-demographic variables from the 1981 census in schizophrenia and related disorders as well as in all diagnoses. The patterns of service use were broadly similar, except that Portogruaro has significantly more community contacts, and has about twice the treated incidence and prevalence of schizophrenia. The census data showed that unmarried and unemployed people were more likely to live alone in the urban than in the rural area. In South-Verona the most strongly associated predictor variables, both for schizophrenia and all diagnoses, are: living alone, unemployment, percentage of the total population who are dependents and the percentage who are divorced, separated or widowed. In contrast, in Portogruaro there were no consistent associations between census and service use variables. Stepwise multiple regression models using three census predictor variables accounted for over 85% of the variance in South-Verona utilization rates. The results indicate that the strongly predictive associations previously described in England hold in urban South-Verona, but not in rural Portogruaro, and may be related to the effect of cities in clustering seriously disabled psychiatric patients in areas of low-cost housing where they live in relative social isolation.

The present experiments were designed to investigate whether alterations of peripheral nervous system activity may be produced in male Wistar rats by prenatal exposure (from day 0 to day 20 of pregnancy) to relatively low levels of CO (75 and 150 ppm). The voltage clamp analysis of ionic currents recorded from sciatic nerve fibres showed that prenatal exposure to CO produced modifications of sodium current properties. In particular, in 40-day-old rats exposed to CO (75 and 150 ppm) during gestation, the inactivation kinetics of transient sodium current were significantly slowed. Analysis of the potential dependence of steady-state Na inactivation, h infinity (V), showed that the percentage of the maximum number of activable Na channels at the normal resting potential (-80 mV) was increased to approximately 85% in CO-exposed rats. Moreover, the voltage-current relationship showed a negative shift of sodium equilibrium potential in CO treated animals. In 270-day-old CO-exposed rats, parameters of sodium inactivation were not significantly modified; the reversal potential was still lower with respect to controls. The results indicate that prenatal exposure to mild CO concentrations produces reversible changes in sodium inactivation kinetics and on irreversible change in sodium equilibrium potential. These alterations could reflect CO influence on the rate of ion channel development.

Wistar female rats were exposed to relatively mild concentrations of carbon monoxide (75 and 150 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to CO (150 ppm) produced a significant reduction in the minimum frequency of ultrasonic calls emitted by rat pups removed from their nest. Moreover, a significant decrease in the responsiveness (rate of calling) to a challenge dose of diazepam (0.25 mg/kg) was found in male pups exposed to CO (150 ppm) during gestation. Prenatal CO (75 and 150 ppm) did not significantly affect locomotor activity or d -amphetamine-induced hyperactivity in both 14- and 21-day-old animals. Futhermore, adult male rats exposed to this chemical (150 ppm) during gestation exhibited significant alterations in the acquisition of an active avoidance task. CO-induced learning disruption does not seem to be linked to changes in the emotionality of animals. These findings suggest that gestational exposure to CO induces in rat offspring both short- and long-term behavioral changes characterized by altered ontogeny of emotional responsiveness to environmental challenges and by learning impairment.

The timing of developmental administration of psychotropic drugs affecting dopaminergic and GABAergic neurotransmission is crucial for the induction of specific neurobehavioral and neurochemical changes in rodents. Compensatory mechanisms occurring in response to a prolonged treatment with some neuroleptic and anxiolytic agents during development seem to be markedly different from those occurring in response to a prolonged administration in adult animals.

The results reported in this review show that prenatal and/or postnatal administration of benzodiazepines, at dose levels below those associated with overt signs of neurotoxicity, produces both short- and long-term alterations in rats. Most of these behavioral changes are characterized by altered activity patterns and emotional/motivational responsiveness to environmental challenges.

On day 15 of gestation, pregnant Sprague-Dawley rats were orally treated by gavage with 8 mg/kg of methyl mercury (MMC). At day 1 of postnatal life the levels of MMC in whole brain of exposed pups were found to be about 100 times higher than those of saline-exposed rats, while they were near to the control values at 21 days and practically normal at 60 days of age. Behavioral experiments showed that exposure to MMC in late gestation did not affect at any tested time (14, 21 and 60 days) locomotor activity or development of ultrasonic vocalization. An increased response to a challenge dose of amphetamine was, however, detected in MMC-exposed pups at day 14. This phenomenon was no longer evident at day 21 and 60 of age. In parallel, an increased density of dopamine receptors was found in the striatum at 14, but not at 21 and 60, days of age. From these data, we tentatively suggest that a high level of MMC induces a transient phenomenon of disuse-supersensitivity of the dopaminergic system. Moreover, further evidence that acute MMC exposure during prenatal life might induce permanent disturbances in learning and memory which could be partially related to a reduced functional activity of the glutamatergic system is provided.

The authors report the case of a young nun who came to their attention because of the simultaneous development of mammary and pelvic lymphoblastic lymphoma and acute leukemia showing aspects typical of nonendemic Burkitt's lymphoma. The rapid tumoral growth and the equally rapid spontaneous cell lysis led to severe renal insufficiency and metabolic acidosis which were ultimately the cause of death. Given the rareness of the clinical situation and the diagnostic problems involved, the authors examined the literature dealing with this subject.

Percutaneous arterial catheterization in angiographic studies and in regional chemotherapy of cancer offers several interesting features. The authors describe a method for catheterization of the hypogastric arteries and their branches in man. Until the present, the percutaneous selective catheterization of these vessels was considered impracticable because of the unfavorable angle of bifurcation, but the diagnostic and therapeutic results were satisfactory. This new procedure will introduce interesting hematochemical and hemodynamic studies in urology, gynecology, and obstetrics. No damage occurred in the 18 patient submitted to this procedure.

Restriction endonucleases (REs) are able to induce chromosomal aberrations in Chinese hamster ovary (CHO) cells. The G1 phase of the cell cycle seems to be especially sensitive for the induction of chromosomal aberrations by REs. The different capacities of REs to induce chromosomal aberrations are probably correlated with the number of recognition sites in the genome.