An overview of Personalized Medicine landscape and policies in the European Union.

BACKGROUND: The spread of Personalized Medicine (PM) over the last decade defined a revolution in healthcare systems. PM is among the priorities of the European Commission's research agenda, which funded the IC2PerMed international project aiming to integrate China into the International Consortium of PM (ICPerMed). In the context of this project, we mapped the existing policies related to PM in the European Union (EU) and at the EU Member States (EU-MS) level. METHODS: PubMed, Google Scholar, Google, Microsoft and national and international institutions' official repositories were searched in order to identify documents on PM-related policies, programmes and action plans at the EU and EU-MS level, published up to December 2020. RESULTS: We identified 28 policies in the EU aimed at improving public health promoting and fostering PM implementation, through some actions including the standardization of good medical practice, use of big data and digital innovation, data sharing and cross-border interoperability, healthcare sustainability, disease prevention and patients'/citizens' engagement. We identified 23 policies at EU-MS level which, notwithstanding national differences, have a common focus, such as patient-tailored treatment and targeted prevention, education of healthcare workers, research and innovation, big data harmonization and healthcare system sustainability. CONCLUSIONS: The definition of an integrated regulatory framework is essential to turn PM into an opportunity for citizens and patients with the involvement of all the stakeholders. This work can provide a valuable tool for decision-makers to define common approaches, priorities for research, development and increase international collaboration, which could overcome the fragmented European scenario and align the future direction on PM.

Spatiotemporal distribution of a non-haematophagous bat community and rabies virus circulation: a proposal for urban rabies surveillance in Brazil.

In Brazil, rabies surveillance is based on monitoring domestic and wild animals, although the most prevalent lineage of the rabies virus (RABV) currently diagnosed in Brazil is associated with bats, particularly non-haematophagous bats. Disease control is based on the mass vaccination of dogs and cats. We used data collected by the passive surveillance system of the city of Campinas from 2011 to 2015, to describe the temporal and geographic distributions of the bat specimens and RABV and discuss the current rabies surveillance with the advent of the declaration of canine and feline rabies-free areas in Brazil. We described the species, locations and health statuses of the collected bat specimens. Moreover, all samples were submitted for RABV diagnosis. Then, we performed a time series decomposition for each bat family. Additionally, we determined the spatiotemporal relative risk for RABV infection using the ratio of the kernel-smoothed estimates of spatiotemporal densities of RABV-positive and RABV-negative bats. From the 2537 bat specimens, the most numerous family was Molossidae (72%), followed by Vespertilionidae (14%) and Phyllostomidae (13%). The bat families behaved differently in terms of seasonal and spatial patterns. The distribution of bats varied geographically in the urban environment, with Molossidae and Phyllostomidae being observed downtown and Vespertilionidae being observed in peripheral zones. Concurrently, a significant relative risk of RABV infection was observed downtown for Vespertilionidae and in peripheral zones for Molossidae. No RABV-positive sample clusters were observed. As a result of the official declaration of RABV-free areas in southern Brazil, mass dog and cat vaccinations are expected to halt in the near future. This stoppage would make most dog and cat populations susceptible to other RABV lineages, such as those maintained by non-haematophagous bats. In this scenario, all information available on bats and RABV distribution in urban areas is essential. Currently, few studies have been conducted. Some local health authorities, such as that in Campinas, are spontaneously basing their surveillance efforts on bat rabies, which is the alternative in reality scenario of increased susceptibility to bat-associated RABV that is developing in Brazil.

Evaluation of PCR in the diagnosis of canine leishmaniasis in two different epidemiological regions: Campinas (SP) and Teresina (PI), Brazil.

SUMMARY Using the polymerase chain reaction (PCR) test for diagnosis of canine leishmaniasis has greater sensitivity and specificity than culture and visualization of the parasite. This study compares PCR for the diagnosis of the genus and species of Leishmania with serological techniques used for the control of canine visceral leishmaniasis (CVL) in Brazil, considering two regions. We analysed peripheral blood samples collected from 195 dogs in the Campinas (SP) and Teresina (PI) regions. ELISA was performed as a serological method and PCR was performed using specific primers for the genus Leishmania spp. and the species Leishmania chagasi. In Campinas, a greater sensitivity of PCR (88.24%) (P = 0.0455) compared to Teresina (14.71%) (P < 0.0001) was observed, and an agreement was observed for Cohen's kappa index (0.9096). Both PCR and ELISA showed discordance for sensitivity (Campinas 100%, Teresina 21.74%), specificity (Campinas 30.77%, Teresina 100%), positive predictive value (Campinas 68.97%, Teresina 100%), negative predictive value (Campinas 100%, Teresina 37.94%) and Cohen's kappa index (0.1238). This study confirms the importance of PCR in analysis of the canine reservoir, and as an effective method for the detection of active and recent infection.

External Responsiveness of the Yo-Yo IR Test Level 1 in High-level Male Soccer Players.

The aim of this study was to assess the external responsiveness, construct validity and internal responsiveness of the Yo-Yo Intermittent Recovery test level 1 and its sub-maximal version in semi-professional players. Tests and friendly matches were performed during the preseason and regular season. The distance covered above 15 km·h(-1) was considered as an indicator of the physical match performance. Construct validity and external responsiveness were examined by correlations between test and physical match performance (preseason and regular season) and training-induced changes. Internal responsiveness was determined as Cohen's effect size, standardized response mean and signal-to-noise ratio. The physical match performance increased after training (34.8%). The Yo-Yo Intermittent Recovery test level 1 improved after training (40.2%), showed longitudinal (r=0.69) and construct validity (r=0.73 and 0.59, preseason and regular season) and had higher internal responsiveness compared to its sub-maximal version. The heart rate at the 6(th) minute in the sub-maximal version did not show longitudinal (r=-0.38) and construct validity (r=0.01 and -0.06, preseason and regular season) and did not significantly change after training (-0.3%). The rate of perceived exertion decreased in the sub-maximal version (- 29.8%). In conclusion, the Yo-Yo Intermittent Recovery test level 1 is valid and responsive, while the validity of its sub-maximal version is questionable.

Aerobic fitness and performance in elite female futsal players.

Despite its growing popularity, few studies have investigated specific physiological demands for elite female futsal. The aim of this study was to determine aerobic fitness in elite female futsal players using laboratory and field testing. Fourteen female futsal players from the Venezuelan National team (age =21.2±4.0 years; body mass =58.6±5.6 kg; height =161±5.0 cm) performed a progressive maximal treadmill test under laboratory conditions. Players also performed a progressive intermittent futsal-specific field test for endurance, the Futsal Intermittent Endurance Test (FIET), until volitional fatigue. Outcome variables were exercise heart rate (HR), VO2, post-exercise blood lactate concentrations ([La]b) and running speeds (km · h-1). During the treadmill test, VO2max, maximal aerobic speed (MAS), HR and peak [La]b were 45.3±5.6 ml · kg-1 · min-1, 12.5±1.77 km · h-1, 197±8 beats · min-1 and 11.3±1.4 mmol · l-1, respectively. The FIET total distance, peak running velocity, peak HR and [La]b were 1125.0±121.0 m, 15.2±0.5 km · h-1, 199±8 beats · min-1 and 12.5±2.2 mmol · l-1, respectively. The FIET distance and peak speed were strongly associated (r= 0.85-87, p < 0.0001) with VO2max and MAS, respectively. Peak HR and [La]b were not significantly different between tests. Elite female futsal players possess moderate aerobic fitness. Furthermore, the FIET can be considered as a valid field test to determine aerobic fitness in elite level female futsal players.

Anthropometric and physiological characteristics of Melanesian futsal players: a first approach to talent identification in Oceania.

This study assessed the anthropometric and physiological characteristics of elite Melanesian futsal players in order to determine the best performance predictors. Physiological parameters of performance were measured in 14 Melanesian (MEL-G, 24.4±4.4 yrs) and 8 Caucasian (NMEL-G, 22.9±4.9) elite futsal players, using tests of jump-and-reach (CMJ), agility (T-Test), repeated sprint ability (RSA), RSA with change-of-direction (RSA-COD), sprints with 5 m, 10 m, 15 m, and 30 m lap times, and aerobic fitness with the 30-15 intermittent fitness test (30-15 IFT). The anthropometric data revealed significantly lower height for MEL-G compared with NMEL-G: 1.73±0.05 and 1.80±0.08 m, respectively; P = 0.05. The CMJ was significantly higher for MEL-G than NMEL-G: 50.4±5.9 and 45.2±4.3 cm, respectively; P = 0.05. T-Test times were significantly lower for MEL-G than NMEL-G: 10.47±0.58 and 11.01±0.64 seconds, respectively; P = 0.05. MEL-G height was significantly related to CMJ (r = 0.706, P = 0.01), CMJpeakP (r = 0.709, P = 0.01) and T-Test (r = 0.589, P = 0.02). No significant between-group differences were observed for sprint tests or 30-15 IFT, including heart rate and estimated VO2max. Between groups, the percentage decrement (%Dec) in RSA-COD was significantly lower in MEL-G than NMEL-G (P = 0.05), although no significant difference was noted between RSA and RSA-COD. Within groups, no significant difference was observed between %Dec in RSA or RSA-COD; P = 0.697. This study presents specific anthropometric (significantly lower height) and physiological (significantly greater agility) reference values in Melanesians, which, taken together, might help coaches and physical fitness trainers to optimize elite futsal training and talent identification in Oceania.

Effect of the number of sprint repetitions on the variation of blood lactate concentration in repeated sprint sessions.

The aim of the present study was to examine the effect of number of sprint repetitions on the variation of blood lactate concentration (blood [La]) during different repeated-sprint sessions in order to find the appropriate number of sprint repetitions that properly simulates the physiological demands of team sport competitions. Twenty male team-sport players (age, 22.2 ± 2.9 years) performed several repeated-sprint sessions (RSS) consisting of 1, 2, 3, 4, 5, 9, or 10 repetitions of 30 m shuttle sprints (2 × 15 m) with 30 s recovery in between. The blood [La] was obtained after 3 min of recovery at the end of each RSS. The present study showed that for RSS of 3 sprints (RSS3) there was a high increase (p<0.001) in blood [La], which reached approximately fivefold resting values (9.4±1.7 mmol · l(-1)) and then remained unchanged for the RSS of 4 and 5 sprints (9.6±1.4 and 10.5±1.9 mmol · l(-1), p=0.96 and 0.26, respectively). After RSS9 and RSS10 blood [La] further significantly increased to 12.6 and 12.7 mmol · l(-1), p<0.001, respectively. No significant difference was found between RSS3, RSS4 and RSS5 for the percentage of sprint speed decrement (Sdec) (1.5±1.2; 2.0±1.1 and 2.6±1.4%, respectively). There was also no significant difference between RSS9 and RSS10 for Sdec (3.9±1.3% and 4.5±1.4%, respectively). In conclusion, the repeated-sprint protocol composed of 5 shuttle sprint repetitions is more representative of the blood lactate demands of the team sports game intensity.

Effect of plyometric training on sand versus grass on muscle soreness and jumping and sprinting ability in soccer players.

OBJECTIVE: The lower impact on the musculoskeletal system induced by plyometric exercise on sand compared to a firm surface might be useful to reduce the stress of intensified training periods or during rehabilitation from injury. The aim of this study was to compare the effects of plyometric training on sand versus a grass surface on muscle soreness, vertical jump height and sprinting ability. DESIGN: Parallel two-group, randomised, longitudinal (pretest-post-test) study. METHODS: After random allocation, 18 soccer players completed 4 weeks of plyometric training on grass (grass group) and 19 players on sand (sand group). Before and after plyometric training, 10 m and 20 m sprint time, squat jump (SJ), countermovement jump (CMJ), and eccentric utilization ratio (CMJ/SJ) were determined. Muscle soreness was measured using a Likert scale. RESULTS: No training surface x time interactions were found for sprint time (p>0.87), whereas a trend was found for SJ (p = 0.08), with both groups showing similar improvements (p<0.001). On the other hand, the grass group improved their CMJ (p = 0.033) and CMJ/SJ (p = 0.005) significantly (p<0.001) more than players in the sand group. In contrast, players in the sand group experienced less muscle soreness than those in the grass group (p<0.001). CONCLUSIONS: Plyometric training on sand improved both jumping and sprinting ability and induced less muscle soreness. A grass surface seems to be superior in enhancing CMJ performance while the sand surface showed a greater improvement in SJ. Therefore, plyometric training on different surfaces may be associated with different training-induced effects on some neuromuscular factors related to the efficiency of the stretch-shortening cycle.

Acute and Residual Soccer Match-Related Fatigue: A Systematic Review and Meta-analysis.

BACKGROUND: Understanding soccer players' match-related fatigue and recovery profiles likely helps with developing conditioning programs that increase team performance and reduce injuries and illnesses. In order to improve match recovery (the return-to-play process and ergogenic interventions) it is also pivotal to determine if match simulation protocols and actual match-play lead to similar responses. OBJECTIVES: (1) To thoroughly describe the development of fatigue during actual soccer match play and its recovery time course in terms of physiological, neuromuscular, technical, biochemical and perceptual responses, and (2) to determine similarities of recovery responses between actual competition (11 vs. 11) and match simulations. METHODS: A first screening phase consisted of a systematic search on PubMed (MEDLINE) and SportDiscus databases until March 2016. Inclusion criteria were: longitudinal study with soccer players; match or validated protocol; duration > 45 min; and published in English. RESULTS: A total of 77 eligible studies (n = 1105) were used to compute 1196 effect sizes (ES). Half-time assessments revealed small to large alterations in immunological parameters (e.g. leukocytes, ES = 1.9), a moderate decrement in insulin concentration (ES = - 0.9) and a small to moderate impairment in lower-limb muscle function (ES = - 0.5 to - 0.7) and physical performance measures (e.g. linear sprint, ES = - 0.3 to - 1.0). All the systematically analyzed fatigue-related markers were substantially altered at post-match. Hamstrings force production capacity (ES = - 0.7), physical performance (2-4%, ES = 0.3-0.5), creatine kinase (CK, ES = 0.4), well-being (ES = 0.2-0.4) and delayed onset muscle soreness (DOMS, ES = 0.6-1.3) remained substantially impaired at G + 72 h. Compared to simulation protocols, 11 vs. 11 match format (CK, ES = 1.8) induced a greater magnitude of change in muscle damage (i.e. CK, ES = 1.8 vs. 0.7), inflammatory (IL-6, ES = 2.6 vs. 1.1) and immunological markers and DOMS (ES = 1.5 vs. 0.7) than simulation protocols at post-assessments. Neuromuscular performances at post-match did not differ between protocols. CONCLUSION: While some parameters are fully recovered (e.g. hormonal and technical), our systematic review shows that a period of 72 h post-match play is not long enough to completely restore homeostatic balance (e.g. muscle damage, physical and well-being status). The extent of the recovery period post-soccer game cannot consist of a 'one size fits all approach'. Additionally, the 'real match' (11 vs. 11 format) likely induces greater magnitudes of perceptual (DOMS) and biochemical alterations (e.g. muscle damage), while neuromuscular alterations were essentially similar. Overall, coaches must adjust the structure and content of the training sessions during the 72-h post-match intervention to effectively manage the training load within this time-frame.

Heart Rate and Perceived Experience Differ Markedly for Children in Same- versus Mixed-Gender Soccer Played as Small- and Large-Sided Games.

This study examines heart rate (HR) and perceived experience during same- versus mixed-gender soccer played as small- (SSG) and large-sided (LSG) games. HR, rating of perceived exertion (RPE), and fun scores were determined in 134 pupils (50 girls, 84 boys) randomly assigned to same- and mixed-genders formats playing 2x15-min of SSG (2v2, 4v4) and LSG (12v12) in a random order (~50 m2/player). HR was lower (p≤0.03) for girls when playing together with boys than when playing alone (71±10 versus 77±7%HRmax), while being similar for boys playing mixed- or same-gender games (74±7 versus 77±4%HRmax). Boys perceived less fun when playing together with girls than when playing alone (4.4±2.3 versus 6.3±2.3, p<0.001). Irrespective of gender, higher (p<0.001) HRmean, %time>80%HRmax, and RPE were observed during 2v2 (78±9%HRmax, 43±33%, 5.5±2.5) and 4v4 (76±9%HRmax, 39±32%, 5.5±2.7) than during 12v12 (70±10%HRmax, 23±27%, 3.8±2.9). Cardiovascular strain was lower for girls when playing together with boys than when playing alone in LSG. SSG were more intense than LSG when girls played mixed-gender games and when boys played mixed- and same-gender games. When boys played mixed-gender games, SSG were considered more fun than LSG. Physical education teachers and coaches should consider gender and game format differences when using soccer.

The effect of match standard and referee experience on the objective and subjective match workload of English Premier League referees.

The aim of the present study was to examine the effect of match standard and referee experience on the objective and subjective workload of referees during English Premier League and Football League soccer matches. We also examined the relationship between heart rate (HR) and ratings of perceived exertion (RPE) for assessing match intensity in soccer referees. Heart rate responses were recorded using short-range telemetry and RPE scores were collected using a 10-point scale. Analysis revealed a significant relationship between mean match HR and match RPE scores (r=0.485, p<0.05, n=18). There were significant differences in match HR (Premier League 83.6+/-2.6% maximal HR (HRmax) versus Football League 81.5+/-2.2%HRmax, p<0.05) and match RPE scores (Premier League 7.8+/-0.8 versus Football League 6.9+/-0.8, p<0.05) between standards of competition. Referee experience had no effect on match HR and RPE responses to Premier League and Football League matches. The results of the present study demonstrate the validity of using HR and RPE as a measure of global match intensity in soccer referees. Referee experience had no effect on the referees' objective and subjective match workload assessments, whereas match intensity was correlated to competition standard. These findings have implications for fitness preparation and evaluation in soccer referees. When progressing to a higher level of competition, referees should ensure that appropriate levels of fitness are developed in order to enable them to cope with an increase in physical match demands.

The incidence of complications after caesarean section in 156 HIV-positive women.

OBJECTIVE: To investigate the risks of post-operative complications in HIV-positive mothers who undergo a caesarean section (CS) because the delivery cannot be safely accomplished by the vaginal route or to protect the infant from viral infection. DESIGN: In a multicentre study, we reviewed the incidence and type of post-operative complications in 156 HIV-positive women who underwent a CS. These results were compared with those observed in an equal number of HIV-uninfected women who matched for the indication requiring a caesarean delivery, the stage of labour, the integrity or rupture of membranes, and the use of antibiotic prophylaxis. SETTING: Seven teaching hospitals providing obstetrical care for mothers infected with HIV. RESULTS: We found that six HIV-infected mothers suffered a major complication (two cases of pneumonia, one pleural effusion, two severe anaemia and one sepsis) compared with only one HIV-negative woman who required blood transfusion after surgery. Minor complications like post-operative fever, endometritis, wound and urinary tract infections were significantly more frequent in HIV-positive women than controls. Multivariate analysis revealed that in HIV-infected women the only factor associated with a significant increase in the rate of complications was a CD4 lymphocyte count < 200 x 10(6)/l. CONCLUSIONS: The results of our study indicate that HIV-positive mothers are at an increased risk of post-operative complications when delivered by CS. The risk of post-operative complications is higher in HIV-infected women who are severely immunodepressed.

HIV-1 proviral DNA polymerase chain reaction detection in chorionic villi after exclusion of maternal contamination by variable number of tandem repeats analysis.

OBJECTIVE: The study of the placental HIV infection in cases of seropositive pregnant women after exclusion of maternal contamination of chorionic villi samples by variable number of tandem repeats (VNTR) analysis. METHODS: We studied 30 HIV-positive women: 17 terminated their pregnancy (11 in the first trimester and six in the second) and 13 delivered at term (one was a twin gestation). We selected chorionic villi and ruled out maternal contamination by VNTR analysis. DNA from chorionic villi and cord and maternal blood were tested for HIV by PCR. All infants underwent a paediatric follow-up. RESULTS: All maternal blood samples tested positive for HIV-1 by polymerase chain reaction. No maternal contamination was revealed and HIV was found in six out of 11 first trimester placentas, in all second trimester samples, and in 10 out of 14 at term. Cord blood tested positive in all second trimester cases and in seven out of 14 liveborns. In no case was HIV found in cord blood without infection of the corresponding placenta; conversely, three placentas tested positive but cord blood was negative. Two infants were HIV-positive, 11 were uninfected (one case was lost to follow-up). CONCLUSION: Our study indicates that HIV-1 can infect the placenta from first trimester onwards. HIV was found in two-thirds of our cord blood samples but it is possible that some viral DNA in cord blood may have come from infected placental cells. Additional studies are needed to assess the source of HIV in cord blood and the possible contribution of placental or maternal cells infected with HIV to vertical transmission of the virus.

Prenatal diagnosis after ART success: the role of early combined screening tests in counselling pregnant patients.

First-trimester Down syndrome screening may cause a higher false positive rate in pregnant patients who have undergone ART (assisted reproductive technologies). The aim of this paper is to contribute to this analysis with the second largest series of combined biophysical and biochemical tests in the first trimester of pregnancy after ART. One hundred and forty-two singleton successful ART pregnancies were selected for this study: 50 pregnancies induced by using in-vitro fertilization (IVF), and 92 using intracytoplasmic sperm injection (ICSI). Each patient was matched with three naturally conceived pregnancies based on maternal age and gestational age. Free beta-HCG and PAPP-A were measured on dried blood spots and converted to MoMs. Nuchal translucency (NT) was measured by certified operators. Mean maternal age was 33 +/- 4. NT, free beta-HCG and PAPP-A values of the control cases were not significantly different from local standards evaluated on 3043 cases. NT between ART pregnancies and matched controls was not significantly different. PAPP-A was reduced but not significantly lower in ART pregnancies. Free beta-HCG was the only analyte that resulted in significantly higher values in ART pregnancies (1.12 MoM) versus controls (0.99 MoM). No significant differences were found for biochemical values observed between ICSI and IVF patients. The screen positive rates observed in ART and control pregnancies were 5.5 per cent and 4.6 per cent respectively. NT measurements were not affected by ART pregnancies. Our results (non-significant lower values of PAPP-A and significantly higher free beta-HCG values) were consistent with other reported series. The increase in the screen positive rate determined by these biological variations was not greater than 0.9 per cent. This higher false positive rate has a negligible impact on counselling ART patients. The algorithm used to calculate the relative risk after the combined tests should not be changed until the detection rate of trisomies in ART pregnancies is not fully disclosed by larger series.

Aromatase inhibition blocks the activation and sexual differentiation of appetitive male sexual behavior in Japanese quail.

Two experiments investigated the role of estrogens in the activation and sexual differentiation of appetitive sexual behavior (ASB) in Japanese quail (Coturnix japonica) as measured by a learned social proximity response. Injection of the aromatase inhibitor R767 13 in castrated, testosterone (T)-treated male quail completely suppressed ASB, confirming that, like consummatory sexual behavior, ASB is mediated by T aromatization. ASB is not observed in female quail, even if they are treated with T as adults. The role of embryonic estrogens in the sexual differentiation of ASB was tested by blocking estrogen synthesis in ovo. Control male and T-treated female quail deprived of estrogens during embryonic life learned the social proximity response used to assess ASB, whereas control female quail did not, despite the presence of high T. Thus, ASB is demasculinized by the action of embryonic estrogens during ontogeny as is consummatory behavior.

Systemic and intracerebroventricular injections of vasotocin inhibit appetitive and consummatory components of male sexual behavior in Japanese quail.

The authors investigated the behavioral actions of vasotocin (VT) in castrated testosterone-treated male Japanese quail. The appetitive and consummatory components of sexual behavior as well as the occurrence frequency of crows were inhibited, in a dose-dependent manner, by injections of VT. The authors observed opposite effects after injection of the V1 receptor antagonist, dPTyr(Me)AVP. Lower doses of VT were more active after central than after systemic injection, and effects of systemic injections of VT were blocked by a central injection of dPTyr(Me)AVP. The behavioral inhibition was associated with a modified diuresis after systemic but not central injection. These results provide direct evidence that VT affects male sexual behavior in quail by a direct action on the brain independent of its peripheral action on diuresis.

Effects of testosterone on the synaptology of the medial preoptic nucleus of male Japanese quail.

The medial preoptic nucleus (POM) of male Japanese quail is a sexually dimorphic testosterone-dependent structure that plays a key role in the activation of male sexual behavior. Both the total volume of the nucleus and the size of the dorsolateral neurons are decreased in gonadectomized males. Immunocytochemical studies have revealed a complex pattern of innervation: immunopositive fibers for several neuropeptides and neurotransmitters have been detected in the POM; some of them (e.g. vasotocin-immunoreactive fibers) are sexually dimorphic and testosterone-dependent To understand the anatomical bases of these testosterone-dependent neurochemical changes, we performed an ultrastructural study of the POM neuropil in intact sexually mature, gonadectomized, or testosterone-treated gonadectomized males. A complex synaptic organization of the POM neuropil was observed in intact male quail reflecting the heterogeneity of the neurotransmitters and neuropeptides present in this nucleus. Changes in this organization were observed after the endocrine manipulations. The number of axosomatic synapses per cell body decreased after gonadectomy and was restored to the level observed in the intact group after the administration of testosterone. By contrast, no significant change was observed in the density of axodendritic and axospinal synapses after hormonal manipulations which suggests that the total number of synapses in the nucleus should be affected by testosterone (constant density in a changing total volume). The cross-sectional area of synaptic boutons was also decreased by castration and restored to intact level by testosterone. The action of testosterone on the activation of male copulatory behavior in gonadectomized birds is hence paralleled by an extensive rearrangement of neuropil in the POM.

Testosterone effects on the neuronal ultrastructure in the medial preoptic nucleus of male Japanese quail.

Dorsolateral neurons of the medial preoptic nucleus (POM) of male Japanese quail are sensitive to the plasma levels of testosterone: their volume and optical density in Nissl-stained sections increase in castrated birds treated with testosterone. The present study was performed on castrated male quail treated or not with Silastic implants filled with testosterone to describe the ultrastructural variations induced by testosterone in these neurons. Gonadally intact male birds were included as controls. The ultrastructure of neurons, taken from the dorsolateral portion of the POM, was dramatically affected by the endocrine manipulations. Quantitative evaluations demonstrated a significant decrease in castrated birds of the rough endoplasmic reticulum (RER), of free polyribosomes, of Golgi complexes, and of dense bodies; these changes paralleled the decrease in cell size. The cell size and the percentage of volume occupied by the intracellular organelles in castrated birds treated with testosterone were comparable to values observed in controls. These ultrastructural changes are similar to those observed in neuronal targets for other gonadal hormones, supporting the idea that testosterone stimulates the development of cytoplasmic structures involved in protein synthesis and secretion. In addition, exposure to testosterone affects the synaptic inputs to POM. These ultrastructural changes are presumably related to the physiological effects (e.g., activation of male sexual behavior) exerted by testosterone on this preoptic region.

Differential effects of D1 and D2 dopamine-receptor agonists and antagonists on appetitive and consummatory aspects of male sexual behavior in Japanese quail.

Pharmacological studies in Japanese quail based on behavioral tests with a variety of dopaminergic compounds suggest that the activation of D2 dopamine receptors inhibits, and the activation of D1 dopamine receptors enhances, appetitive and consummatory components of male sexual behavior. This hypothesis was tested by studying the behavioral effects of specific D1 and D2 dopaminergic-receptor agonists and antagonists in castrated male Japanese quail chronically treated with exogenous testosterone (subcutaneous Silastic implants). The effects of 5 compounds were tested: 1 D1 (SKF38393) and 2 D2 (PPHT and quinpirole) agonists, and 1 D1 (SCH23390) and 1 D2 (Spiperone) antagonist. All compounds were tested at a low and a high dose (0.1 and 1 mg/kg, respectively, for all drugs, except spiperone where the doses were 2 and 10 mg/kg). A consistent effect of all drugs on consummatory sexual behavior was observed: it was stimulated by the D1 agonist and the D2 antagonist, but inhibited by the D1 antagonist and the D2 agonists. Far fewer effects of the treatments were detected on the measures of appetitive behavior. Measures of appetitive behavior were decreased by the 2 D2 agonists, but not affected by the other treatments. These data suggest that male copulatory behavior in quail is stimulated by dopamine acting on D1 receptors, but inhibited by activation of the D2 receptor subtype. The partial dissociation observed between the effects of the same treatments on appetitive and consummatory aspects of sexual behavior also suggests that these 2 behavioral systems may be controlled by the action of dopamine on different neuronal systems.