Sociodemographic profile, health-related behaviours and experiences of healthcare access in Italian transgender and gender diverse adult population.

PURPOSE: Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population. METHODS: A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP). RESULTS: TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p < 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p < 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity. CONCLUSIONS: Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.

Conspiracy mentality and health-related behaviour during the COVID-19 pandemic: a multiwave survey in Italy.

OBJECTIVES: This study aimed to (1) explore the changes in conspiracy mentality across the four waves of the COVID-19 pandemic; (2) assess the relationship between conspirative mentality and psychological/behavioural variables; (3) identify the predictors of conspirative mentality; and (4) explore the effect of conspirative mentality on COVID-19 protective behaviour. STUDY DESIGN: This was a multiwave survey. METHODS: A total of 10,013 Italian individuals, aged 18-70 years, were assessed across the four waves (from January to May 2021) through online survey. We collected information about the sociodemographic characteristics of participants, personal experiences of COVID-19 infection, trust, COVID-19 protective behaviours, COVID-19 risk perception, arousal, auto-efficacy, resilience and well-being. Conspiracy mentality was assessed with the Conspiracy Mentality Questionnaire. The statistical analyses included exploratory factorial analyses, Pearson correlations and multiple linear regressions. RESULTS: The conspiracy mentality score during the COVID-19 pandemic was medium-high (mean 59.0 on a 0-100 scale) and slightly increased from 58.2 to 59.9 across months, in parallel with a slight decrease in trust in health institutions and scientific informational sources. Individuals aged >35 years, poorly educated and particularly scared about their financial situation were at risk of showing higher levels of conspirative mentality. Higher levels of conspirative mentality were risk factors for low levels of COVID-19 protective behaviours. CONCLUSIONS: Clear and effective communication may improve trust in health institutions and informational sources, decrease conspirative theories and increase compliance with protective behaviour.

Risk factors affecting quality of life in a group of Italian children with asthma.

The measure of Quality of Life (QoL) has become one of the most important criteria used to assess the impact of chronic illness, such as asthma, on the patient’s daily life, in adults and children alike. The objective of our open observational study was to measure the QoL and analyze several factors that potentially affect QoL, such as symptoms and functional respiratory parameters, in a cohort of children with asthma. One hundred and twenty-seven children with asthma, 6 to 14 years of age, living in the city of Rome, were enrolled as outpatients. They were subjected to Skin Prick Tests (SPT), underwent spirometry and filled out the Pediatric Asthma Quality of Life Questionnaire (PAQLQ). One hundred and eleven children were diagnosed with intermittent asthma, 12 (10%) with mild asthma, and four with moderate persistent asthma. Ninety-six children had a positive SPT. The mean total score of QoL, obtained from the questionnaire, was 5.4 (∓1.2 SD). Two QoL groups were created. Children with total QoL score <5.5 were included in the “Lower QoL” score group while children with total QoL score ≥ 5.5 were included in the “Higher QoL” score group. Children in the Higher group and their mothers had a higher mean age, suffered from fewer asthma exacerbations during the year preceding the study, and showed a higher mean value of forced expiratory volume (FEV1) compared to the children in the Lower category. Using Logistic regression we identified the main factors that may affect QoL as FEV1, symptoms in the previous year and mother’s age. QoL is correlated with the frequency of asthma exacerbations and FEV1 values. Furthermore, our research shows that a significant impairment of QoL may also occur in patients with normal lung function, pointing out the importance of evaluating QoL in all children with asthma.

The contribution of environmental pollutants to the risk of autism and other neurodevelopmental disorders: A systematic review of case-control studies.

Exposure to environmental pollutants, such as metals, pesticides, and air pollutants during early life, is a risk factor for neurodevelopmental disorders (NDDs), including Autism Spectrum Disorder (ASD). Our systematic review aimed to select and summarize more recent case-control studies that examined the association between prenatal and early postnatal exposure to environmental pollutants and NDDs. We searched five databases (Web of Science, PubMed, Embase, Scopus, Ovid), screened 2261 records, and included 24 eligible case-control studies. Meta-analyses were conducted on subgroups of at least three studies that shared both the outcome and the exposure. A noteworthy discovery from this literature review is the existence of non-linear or non-monotonic dose-response relationships between the exposure to certain metals and the risk of ASD. The meta-analysis revealed a significant association between exposure to particular matter (PM)10 during the first year of life and the risk of ASD. Overall, studies included in our systematic review indicate that exposure to several pollutants within the first three years of life was significantly associated with the risk of NDDs.

Dual vs. triple antithrombotic treatment after percutaneous coronary intervention in patients with non-valvular atrial fibrillation: a meta-analysis on current evidence.

OBJECTIVE: Combination and duration of antithrombotic therapy in order to prevent both stent thrombosis and thromboembolic complications after coronary artery stenting (PCI) in non-valvular atrial fibrillation (AF) is still debated. This uncertainty can be attributed mainly to the fact that the reference trials were open-label and not adequately powered in order to reach a definitive conclusion on ischemic endpoints (i.e., stent thrombosis). On these grounds, data from real-life studies could support evidence on dual antithrombotic treatment (DAT) safety (bleeding risk) and efficacy (stent thrombosis prevention). The aim of the meta-analysis is to investigate in both randomized controlled trials (RCTs) and observational studies (Obs) the risks and/or benefits related to DAT vs. triple antithrombotic treatment (TAT) regimens in patients affected by AF undergoing PCI. MATERIALS AND METHODS: RCTs and Obs were retrieved through PubMed database. The risk ratio with 95% confidence interval was used to compare the primary and the safety endpoints. RESULTS: Meta-analysis demonstrated no significant differences between DAT vs. TAT for mortality. However, a two-fold higher mortality rate was registered in Obs than in RCTs. The Obs did not confirm the expected significant reduction in bleeding risk shown by the RCTs; however, the bleeding rates in Obs were more than three-fold those of RCTs. In Obs, a significant greater risk for stent thrombosis was observed in DAT than in TAT. CONCLUSIONS: The safety and efficacy outcomes observed in RCTs are unrealistic with respect to the current clinical practice. So, more evidence is needed to have more exhaustive guidelines based on RCTs with homogeneous designs and protocols that should mimic real-life population and practice.

Rapid maxillary expansion in children with Obstructive Sleep Apnoea Syndrome (OSAS).

AIM: to evaluate the effects of rapid maxillary expansion (RME) in a group of OSAS preschool children. MATERIALS AND METHODS: Lateral cephalograms of 15 OSAS children (8 boys and 7 girls, age mean ± SD: 5.94 ± 1.64 years) were analysed at the start of treatment with RME (T0). All subjects were revaluated after a mean period of 1.57 ± 0.58 years (T1). At this time the sample was divided into 2 groups according to the change in the respiratory disturbance index (RDI): an improved group (I: 8 subjects) and a stationary/worsened group (SW: 7 subjects). Differences between I and SW children with respect to values of cephalometric variables at T0 and to variations between T0 and T1 were evaluated using Mann-Whitney U test. Differences between T0 and T1 values in the overall group of children and separately in I and SW groups were assessed using Wilcoxon test. RESULTS: At the start of treatment, the I group was characterised by more retrognathic jaws with lower values of SNA (p=0.055) and SNB (p=0.020) and higher age values (p=0.093) when compared to SW group. After treatment, the I group showed an increase in SNA and SNB angle significantly higher than SW group (p=0.004 and p=0.003, respectively). On the contrary, I and SW groups did not differ as for variation in the skeletal divergency and in the total facial height. CONCLUSION: OSAS preschool children with retrognathic jaws could benefit from RME treatment.

Meta-analyses on intra-aortic balloon pump in cardiogenic shock complicating acute myocardial infarction may provide biased results.

OBJECTIVE: Intra-aortic balloon pump (IABP) is the device most commonly investigated in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). Recently meta-analyses on this topic showed opposite results: some complied with the actual guideline recommendations, while others did not, due to the presence of bias. We investigated the reasons for the discrepancy among meta-analyses and strategies employed to avoid the potential source of bias. MATERIALS AND METHODS: Scientific databases were searched for meta-analyses of IABP support in AMI complicated by CS. The presence of clinical diversity, methodological diversity and statistical heterogeneity were analyzed. When we found clinical or methodological diversity, we reanalyzed the data by comparing the patients selected for homogeneous groups. When the fixed effect model was employed despite the presence of statistical heterogeneity, the meta-analysis was repeated adopting the random effect model, with the same estimator used in the original meta-analysis. RESULTS: Twelve meta-analysis were selected. Six meta-analyses of randomized controlled trials (RCTs) were inconclusive because underpowered to detect the IABP effect. Five included RCTs and observational studies (Obs) and one only Obs. Some meta-analyses on RCTs and Obs had biased results due to presence of clinical and/or methodological diversity. The reanalysis of data reallocated for homogeneous groups was no more in contrast with guidelines recommendations. CONCLUSIONS: Meta-analyses performed without controlling for clinical and/or methodological diversity, represent a confounding message against a good clinical practice. The reanalysis of data demonstrates the validity of the current guidelines recommendations in addressing clinical decision making in providing IABP support in AMI complicated by CS.

The pathogenesis of the white matter abnormalities in phenylketonuria. A multimodal 3.0 tesla MRI and magnetic resonance spectroscopy (1H MRS) study.

OBJECTIVE: To gain insights into the nature and pathogenesis of white matter (WM) abnormalities in PKU. METHODS: Thirty-two patients with phenylalanine hydroxylase deficiency (21 with early and 11 with late diagnosis and treatment) and 30 healthy controls underwent an integrated clinical, neuroimaging (3.0 T MRI, diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI)) and neurochemical (1H MRS) investigation. RESULTS: All patients had white matter abnormalities on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) scans; parietal white was consistently affected, followed by occipital, frontal and temporal white matter. T1-weighted hypointense alterations were also found in 8 of 32 patients. DWI hyperintense areas overlapped with those detected on T2W/FLAIR. The apparent diffusion coefficient (ADC) was reduced and correlated inversely with severity of white matter involvement. Fractional anisotropy index, eigenvalues lambda(min), lambda(middle), lambda(max) obtained from DTI data, and the principal brain metabolites assessed by 1H MRS (except brain phenylalanine (Phe)) were normal. Brain Phe peak was detected in all but two subjects. Brain and blood Phe were strictly associated. Blood Phe at the diagnosis, patient's age, and concurrent brain Phe independently influence white matter alteration (as expressed by conventional MRI or ADC values). CONCLUSIONS: (a) MRI abnormalities in phenylketonuria are the result of a distinctive alteration of white matter suggesting the intracellular accumulation of a hydrophilic metabolite, which leaves unaffected white matter architecture and structure. (b) White matter abnormalities do not seem to reflect the mechanisms involved in the derangement of mental development in PKU. (c) Our data do not support the usefulness of conventional brain MRI examination in the clinical monitoring of phenylketonuria patients.

Citalopram amplifies the influence of living conditions on mood in depressed patients enrolled in the STAR*D study.

Selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed antidepressant drugs, have a variable and incomplete efficacy. In order to better understand SSRI action, we explored the hypothesis that SSRIs do not affect mood per se but amplify the influence of the living conditions on mood. To this aim, we exploited the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) data set, selected a subpopulation of 591 patients with an overlapping clinical history and analyzed treatment outcome according to dosage -20 or 40 mg per day of citalopram. We found that sociodemographic characteristics affected treatment response in the same direction in the two dose groups, but these effects reached statistical significance only in the 40 mg per day dose group. In the latter, higher improvement rate was associated with having a working employment status (P=0.0219), longer education (P=0.0053), high income (P=0.01) or a private insurance (P=0.0031), and the higher remission rate was associated with having a working employment status (P=0.0326) or longer education (P=0.0484). Moreover, the magnitude of the effect of the sociodemographic characteristics on mood, measured as the percent of patients showing a positive outcome when exposed to favorable living conditions, was much greater-up to 37-fold-in the 40 compared to the 20 mg per day dose group. Overall, our results indicate that citalopram amplifies the influence of the living conditions on mood in a dose-dependent manner. These findings provide a potential explanation for the variable efficacy of SSRIs and might lead to the development of personalized strategies aimed at enhancing their efficacy.

Testing practices and spread of HIV among sexual partners of HIV-positive haemophiliacs in Italy. Gruppo Italiano Coagulopatie Congenite.

OBJECTIVES: To evaluate rates and predictors of testing and HIV positivity among the sexual partners of Italian HIV-positive haemophiliacs. METHODS: Our index cases were 602 sexually active HIV-positive haemophiliacs (aged 18 years or more) enrolled in the Italian Registry of Haemophilia. Data on the demographic and clinical status of the haemophiliacs, whether their partners had undergone HIV testing, and the results of these tests were collected. RESULTS: To date, 205 (34.1%) partners of HIV-positive haemophiliacs have been tested for HIV, of whom 27 (13.2%) were seropositive. On univariate analysis, haemophiliacs who were unmarried, younger, and asymptomatic were less likely to have partners who had been tested for HIV (P << 0.001). On multivariate analysis, unmarried status [odds ratio (OR), 8.4; 95% confidence interval (CI), 5.4-13.1; P << 0.001] and younger age (OR, 1.9; 95% CI, 1.1-3.2) again predicted a higher rate of non-tested partners. There was no association between the demographic and medical characteristics of HIV-seropositive haemophiliacs and the risk of HIV positivity among their sexual partners. CONCLUSION: This study demonstrates that a high proportion of sexual partners of HIV-positive haemophiliacs have not yet been tested for HIV. The single most important predictor of not being tested was the marital status of the index case. These results emphasize the need to strengthen prevention programmes aimed at minimizing the risk of heterosexual HIV transmission, particularly among younger unmarried haemophiliacs.

Progression to AIDS among Italian HIV-seropositive haemophiliacs. Italian Group.

To investigate the interval between HIV-1 infection and the development of clinical AIDS among Italian patients with congenital coagulation disorders, a national cohort study was undertaken in 1988. Information was collected both retrospectively and prospectively on 499 HIV-1-positive patients enrolled in an ongoing national registry of patients with congenital coagulation disorders. Two methods were used to estimate each patient's seroconversion date: the mid-point between the last negative (either known or estimated) and the first positive test, and the median under a Weibull distribution, which was assumed to fit seroconversion data. The two methods of estimating the seroconversion time yielded similar results. The actuarial incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 12.8% (95% confidence interval = 9.7-15.9) over 7 years for Italian haemophiliacs. Progression appears to be slow in the first 5 years after the infection, and to rise steadily thereafter. A strong association between faster progression and older age at seroconversion was found. Zidovudine-treated individuals seem to have a slower progression than untreated individuals, after controlling for CD4, but there was no association between progression and type and severity of the congenital disorder.

Survival after AIDS among Italian haemophiliacs with HIV infection. The Italian Group on Congenital Coagulopathies.

OBJECTIVES: To estimate survival trends for persons with haemophilia and HIV/AIDS. DESIGN AND METHODS: Survival analysis conducted among the cohort of HIV-positive haemophiliacs with AIDS at the Italian Haemophilia Registry. Kaplan-Meier method was used to estimate survival times, stratifying for demographic and clinical covariates. Cox proportional hazards model was applied in order to identify factors independently associated with survival. RESULTS: Median survival from the first AIDS diagnosis to death was estimated to be 17.0 months for 176 individuals with AIDS. Median survival after AIDS diagnosis increased from 12.0 months in December 1983-December 1988 to 17.0 months in January 1989-May 1990 and to 25.0 months in June 1990-December 1991. Median survival times were significantly (P < 0.001) lower for individuals diagnosed with non-infective AIDS indicator diseases (lymphoma, AIDS-associated neurological disease, Kaposi's sarcoma, wasting syndrome: 4.0 months), in comparison with haemophiliacs diagnosed with Pneumocystis carinii pneumonia (PCP; 18.0 months) or other infections (35.0 months). Antiretroviral treatment after AIDS diagnosis was associated with a longer survival than that estimated for individuals with no treatment after AIDS; the same was true for PCP prophylaxis. Younger age at HIV seroconversion and at AIDS diagnosis were associated with a longer survival. Multivariate analysis showed that factors independently associated with survival were type of AIDS indicator disease and antiretroviral administration after AIDS diagnosis. CONCLUSIONS: This study indicates an increasing survival from AIDS diagnosis to death over time, also as a result of the introduction of antiretroviral therapy. Survival trends are similar to those reported among homosexual men and intravenous drug users with AIDS, suggesting a similar access to the health-care system for individuals with AIDS. Survival studies may improve our understanding of the natural history of HIV infection and may indicate the impact of preventive measures.

Clinical factors associated with progression to AIDS in the Italian cohort of HIV-positive hemophiliacs. G.I.C.C. Gruppo Italiano Coagulopatie Congenite.

This study updates estimates of the cumulative incidence of AIDS among Italian patients with congenital coagulation disorders (mostly hemophiliacs), and elucidates the role of age at seroconversion, type and amount of replacement therapy, and HBV co-infection in progression. Information was collected both retrospectively and prospectively on 767 HIV-1 positive patients enrolled in the on-going national registry of patients with congenital coagulation disorders. The seroconversion date was estimated as the median point of each patient's seroconversion interval, under a Weibull distribution applied to the overall interval. The independence of factors associated to faster progression was assessed by multivariate analysis. The cumulative incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 17.0% (95% CI = 14.1-19.9%) over an 8-year period for Italian hemophiliacs. Patients with age greater than or equal to 35 years exhibited the highest cumulative incidence of AIDS over the same time period, 32.5% (95% CI = 22.2-42.8%). Factor IX recipients (i.e. severe B hemophiliacs) had higher cumulative incidence of AIDS (23.3% vs 14.2%, p = 0.01) than factor VIII recipients (i.e. severe A hemophiliacs), as did severe A hemophiliacs on less-than-20,000 IU/yearly of plasma-derived clotting factor concentrates, as opposed to A hemophiliacs using an average of more than 20,000 IU (18.8% vs 10.9%, p = 0.02). No statistically significant difference in progression was observed between HBsAg-positive vs HBsAg-negative hemophiliacs (10.5% vs 16.4%, p = 0.10). Virological, immunological or both reasons can account for such findings, and should be investigated from the laboratory standpoint.

Epidemiology of hemophilia and of HIV infection in Italy. GICC. Gruppo Italiano Coagulopatie Congenite.

To evaluate the incidence and prevalence of hemophilia in Italy and the impact of HIV infection on the Italian hemophiliac population, data from a computerized national registry of patients from 95% of the hemophilia care centers in Italy were analyzed. A total of 4643 patients were included in the registry. The prevalence of hemophilia A was 8.2 per 100,000 males, with no significant regional differences; for hemophilia B the corresponding figure was 1.5 per 100,000. Temporal trends in hemophilia incidence suggest that the diagnosis of mild and moderate hemophilia has improved. The overall HIV prevalence was 26% and was significantly (p < 0.001) higher in patients with hemophilia B (47.1%) compared to those with hemophilia A (26.8%) or other diseases (16.5%). The highest rate of HIV seropositivity was among patients 20-29 years of age. The annual amount of clotting factor concentrates received was significantly (p < 0.001) higher in HIV seropositive patients than in those who were seronegative. Antibody testing was never performed on 10.1% of severely affected patients. The number of patients in the Italian registry was similar to the number that would have been expected based on prevalence estimates from other countries. In comparison with other countries, the prevalence of HIV infection recorded in Italy was lower in persons with hemophilia A, but higher in those with hemophilia B. Our study demonstrates the usefulness of a registry in delineating the epidemiology of hemophilia and in studying risk factors for HIV infection. It also underlines the need for continuing surveillance of this population.

Collateral flow prevents unintentional myocardial ischemia during antegrade cardioplegia in patients undergoing coronary artery bypass grafting.

OBJECTIVE: We evaluated, in the prevention of perioperative unintentional myocardial ischemia, the role of coronary collateral flow in patients with left anterior descending coronary artery stenosis or occlusion who underwent elective coronary artery bypass grafting. METHODS: Coronary lesions and collaterals were assessed by coronary angiography in 21 patients. Anteroseptal myocardial viability was evaluated by dobutamine echocardiography. Antegrade perfusion of cardioplegic solution was assessed by myocardial contrast echocardiography. Time-intensity curves were generated from the anteroseptal region. Twelve parameters were measured and averaged in the following four groups of patients: those with stenosis of the left anterior descending artery and poor collaterals; those with stenosis of the left anterior descending artery and good collaterals; those with occlusion of the left anterior descending artery and good collaterals; and those with occlusion of the left anterior descending artery and poor collaterals. RESULTS: Time-intensity curves were significantly different in patients with stenosis versus occlusion of the left anterior descending artery (p < 0.005); multiple comparisons with Bonferroni's correction showed that this difference was mainly a result of the impact of collateral circulation (p < 0.01). However, the role of collaterals was nonsignificant within the groups with stenosis and occlusion of the left anterior descending artery. Patients with occlusion of the left anterior descending artery and good collaterals had perfusion parameters similar to those of patients with stenosis of the left anterior descending artery (p = not significant), except for the ascending slope and time to peak values (p < 0.05 and p < 0.01, respectively), which reflected a higher flow resistance in the collateral circulation. Regional systolic function after coronary artery bypass grafting was depressed in patients with poor collaterals and poor perfusion of cardioplegic solution, as compared with findings in other subgroups. CONCLUSIONS: Incomplete myocardial protection may impair the early recovery of function after coronary artery bypass grafting.

Risk factors of incomplete distribution of cardioplegic solution during coronary artery grafting.

Myocardial distribution of cardioplegic solution infused by combined antegrade/retrograde routes was assessed with myocardial contrast echocardiography in 18 patients with chronic stable angina and three-vessel disease undergoing elective coronary artery bypass grafting. Overall myocardial opacification was significantly greater in retrograde than in antegrade cardioplegia (77.7% +/- 13.4% versus 59.1% +/- 15.7%; p = 0.0009). The difference was affected by collateral circulation, as pointed out by the significant interaction between coronary collateral circulation and percent of myocardial opacification after antegrade and retrograde cardioplegia (p = 0.002). When we performed multiple comparisons, in patients with good collaterals the opacification difference between antegrade and retrograde cardioplegia was not statistically significant (66.4% +/- 10.2% versus 76.0% +/- 15.2%; p = not significant), whereas in patients with poor collaterals myocardial opacification during retrograde cardioplegia was significantly greater (44.3% +/- 15.0% versus 81.2% +/- 9.0%; p < 0.02). During antegrade cardioplegia, patients with poor collaterals showed a lower degree of myocardial opacification than patients with good collaterals (44.3% +/- 15.0% versus 66.4% +/- 10.2%; p < 0.01). Our results show that retrograde cardioplegia in patients undergoing elective coronary artery bypass grafting offers no advantage over antegrade cardioplegia when collateral circulation is well developed. On the other hand, conventional aortic root infusion may not provide adequate myocardial protection in the subset of patients with significantly narrowed or occluded coronary arteries and poor collaterals.

Elevated novelty seeking and peculiar d-amphetamine sensitization in periadolescent mice compared with adult mice.

Novelty seeking as well as amphetamine sensitization were studied in adult (postnatal day "PND" > 60) and periadolescent (PND 3343) mice treated with saline or amphetamine (2 or 10 mg/kg once per day) for 3 days in a familiar environment. After a 48-hr wash-out period, mice were challenged with either saline or amphetamine (2 mg/kg) in the same environment. When given a choice, animals showed a preference for a novel environment, an effect more marked in periadolescents. Acute amphetamine strongly increased novelty seeking in adults, whereas it had an opposite effect in periadolescents. Adult mice in the chronic amphetamine 2 group showed a conditioned preference for the drug-paired compartment, whereas an aversion characterized adult mice in the amphetamine 10 group. Periadolescents in the latter group exhibited a greater sensitization of the locomotor response, but did not show the compulsive licking typical of adults. This appears to be a useful model to study psychobiological risk factors involved in vulnerability to addiction during human adolescence.

d-amphetamine conditioned place preference in developing mice: relations with changes in activity and stereotypies.

Conditioned place preference (CPP) with both visual and tactile cues, hyperactivity, and stereotypies produced by d-amphetamine (1-10 mg/kg ip, single dose) were studied in CD-1 mice at 2, 3, and 4 weeks from birth. CPP was shown from the youngest age onward in female mice and from 3 weeks in male mice. Hyperactivity was much more pronounced in postweanlings (3 and 4 weeks) than in preweanlings. Stereotypies (at 3.3 and 10 mg/kg) occurred from the youngest age and tended to peak at 3 weeks. Stereotypies may indicate a sickness experience or "poor welfare" (G.J. Mason, 1991; A. Wall, R.E. Hinson, E. Schmidt, C. Johnston, & A. Streather, 1990) due to an aversive component of amphetamine's action. Therefore, the delayed development of fully fledged amphetamine CPP, relative to cocaine CPP (G. Laviola, G. Dell'Omo, E. Alleva, & G. Bignami, 1992), may be due to an age-dependent diminution of the positive hedonic value of the former drug by negative effects that are minimal or absent in the case of the latter drug.

Limited changes of mouse maternal care after prenatal oxazepam: dissociation from pup-related stimulus perception.

There is evidence that activity at the GABA/benzodiazepine receptor complex in specific brain areas might be enhanced during rodent motherhood. We tested the hypothesis that the manipulation of this neurochemical system by prenatal benzodiazepine exposure affects typical behavioral responses of lactating mouse dams. Outbred CD-1 mouse fetuses were administered either oxazepam (OX, 15 mg/kg) or vehicle twice a day on embryonic days 12-16 and fostered at birth to untreated dams. Female offspring were subsequently mated at the young adult stage. In a first experiment, the behavioural repertoire of the two groups of lactating females was scored (single 10-min session) from postpartum days 3 to 18. When compared with VEH dams, OX females showed a shorter duration of pup-sniffing at 7-10 days and enhanced crouching behaviour when pups had reached the age of 14-18 days. In addition, OX-treated dams used more cotton for nest construction than the controls. The two female groups were differentiated only in the presence of their offspring. In a second experiment aimed at investigating possible OX-induced changes in pup-stimulus perception, the same lactating females were challenged in sequence on postpartum day 8 with three different patterns of pup-related cues consisting of: three 8-day-old live male pups (LP), three same-age dead pups DP, or three dead pups accompanied by pre-recorded ultrasounds (DPU). In the absence of carry-over effects of prenatal dam treatment, LP stimuli elicited a higher frequency of sniffing and digging than the others, whereas the level of licking, and grooming was reduced. In conclusion, the present results indicate that the slight alteration in maternal care resulting from prenatal OX treatment can be dissociated from changes in pup-related stimulus perception.

Chronic treatment with MIF-1 prevents the painful stimuli threshold elevation induced by neonatal handling in mice.

Chronic postnatal stressful handling results in a hyposensitivity to thermal nociceptive stimuli. This phenomenon is strongly affected by manipulations of the opioid system. In the present experiment, we report that chronic treatment with MIF-1 during the neonatal period prevents the behavioral alterations induced by handling while it is completely ineffective if injected acutely before antinociceptive testing by the tail flick test at 45 days of life.