Dual inhibitory action of trazodone on dorsal raphe serotonergic neurons through 5-HT1A receptor partial agonism and α1-adrenoceptor antagonism

Trazodone is an antidepressant drug with considerable affinity for 5-HT1A receptors and α1-adrenoceptors for which the drug is competitive agonist and antagonist, respectively. In this study, we used cell-attached or whole-cell patch-clamp recordings to characterize the effects of trazodone at somatodendritic 5-HT1A receptors (5-HT1AARs) and α1-adrenoceptors of serotonergic neurons in rodent dorsal raphe slices. To reveal the effects of trazodone at α1-adrenoceptors, the baseline firing of 5-HT neurons was facilitated by applying the selective α1-adrenoceptor agonist phenylephrine at various concentrations. In the absence of phenylephrine, trazodone (1-10 μM) concentration-dependently silenced neurons through activation of 5-HT1AARs. The effect was fully antagonized by the selective 5-HT1A receptor antagonist Way-100635. With 5-HT1A receptors blocked by Way-100635, trazodone (1-10 μM) concentration-dependently inhibited neuron firing facilitated by 1 μM phenylephrine. Parallel rightward shift of dose-response curves for trazodone recorded in higher phenylephrine concentrations (10-100 μM) indicated competitive antagonism at α1-adrenoceptors. Both effects of trazodone were also observed in slices from Tph2-/- mice that lack synthesis of brain serotonin, showing that the activation of 5-HT1AARs was not mediated by endogenous serotonin. In whole-cell recordings, trazodone activated 5-HT1AAR-coupled G protein-activated inwardly-rectifying (GIRK) channel conductance with weak partial agonist efficacy (~35%) compared to that of the full agonist 5-CT. Collectively our data show that trazodone, at concentrations relevant to its clinical effects, exerts weak partial agonism at 5-HT1AARs and disfacilitation of firing through α1-adrenoceptor antagonism. These two actions converge in inhibiting dorsal raphe serotonergic neuron activity, albeit with varying contribution depending on the intensity of α1-adrenoceptor stimulation

Transverse jointing in foreland fold-and-thrust belts: a remote sensing analysis in the eastern Pyrenees

Joint systems in the eastern portion of the Ebro Basin of the eastern Pyrenees enjoy near continuous exposure from the frontal portion of the belt up to the external portion of its associated foredeep. Utilizing orthophoto mosaics of these world-class exposures, we have manually digitized over 30 000 joints within a 16 km×50 km study area. The mapped traces exhibit orientations that are dominantly perpendicular to the trend of the belt (transverse) and, subordinately, parallel to the belt (longitudinal). In particular, joints systematically orient perpendicular to the trend of the belt both in the frontal folds and in the inner and central portion of the foredeep basin. Longitudinal joints occur rarely with a disordered spatial distribution, exhibiting null difference in abundance between the belt and the foredeep. Joint orientations in the external portion of the foredeep become less clustered, with adjacent areas dominated by either transverse or oblique joints. Our data indicate that joints in the studied area formed in the foredeep in response to a foredeep-parallel stretching, which becomes progressively less intense within the external portion of the foredeep. There, the minimum stress direction becomes more variable, providing evidence of the poor contribution of the forebulge-perpendicular stretching on stress organization

Geoelectrical Subsurface Characterization for Foundation Purposes in the College of Agricultural Sciences (CAS) Campus, Ebonyi State University, Abakaliki, Southeastern Nigeria

The study area is underlain by shales and volcanoclastics with subordinate lenses of sandstones and sandy limestone (Abakaliki Formation) of the Albian Asu River Group, southeastern Nigeria. Geophysical investigation was carried out at the College of Agricultural Sciences (CAS) Campus, Ebonyi State University (EBSU) to determine the structural competence of the subsurface geological strata for building construction and other foundation purposes, using vertical electrical sounding (VES) survey technique of the electrical resistivity method. From the result of the survey, two major zones have been established within the study area for building construction purposes. Zone A comprises of areas around the catholic church building, EBSU primary school up to the school of post graduate studies, while zone B  is made up of areas around the EBSU secondary school, proposed student centre up to the main entrance gate which led to the Ogoja road. Zone A has been recommended for bungalows and other forms of low rising buildings, while zone B has been recommended for storey buildings and other heavy engineering structures. Overburden thickness for the two zones ranges from 1.3 m to 2.7 m, and 0.6 m to 2.7 m for zones A and B respectively. The cracks on walls of the buildings within the campus have been attributed to either the inability of the engineers to dig the foundation to the required depth or the construction of heavier structures on very weak subsurface layers which triggered off movement. Keywords: Geoelectrical, Characterization, Foundation, Ebonyi State University, Nigeria

Nanotechnologies in Obstetrics and Cancer during Pregnancy: A Narrative Review

Nanotechnology, the art of engineering structures on a molecular level, offers the opportunity to implement new strategies for the diagnosis and management of pregnancy-related disorders. This review aims to summarize the current state of nanotechnology in obstetrics and cancer in pregnancy, focusing on existing and potential applications, and provides insights on safety and future directions. A systematic and comprehensive literature assessment was performed, querying the following databases: PubMed/Medline, Scopus, and Endbase. The databases were searched from their inception to 22 March 2022. Five independent reviewers screened the items and extracted those which were more pertinent within the scope of this review. Although nanotechnology has been on the bench for many years, most of the studies in obstetrics are preclinical. Ongoing research spans from the development of diagnostic tools, including optimized strategies to selectively confine contrast agents in the maternal bloodstream and approaches to improve diagnostics tests to be used in obstetrics, to the synthesis of innovative delivery nanosystems for therapeutic interventions. Using nanotechnology to achieve spatial and temporal control over the delivery of therapeutic agents (e.g., commonly used drugs, more recently defined formulations, or gene therapy-based approaches) offers significant advantages, including the possibility to target specific cells/tissues of interest (e.g., the maternal bloodstream, uterus wall, or fetal compartment). This characteristic of nanotechnology-driven therapy reduces side effects and the amount of therapeutic agent used. However, nanotoxicology appears to be a significant obstacle to adopting these technologies in clinical therapeutic praxis. Further research is needed in order to improve these techniques, as they have tremendous potential to improve the accuracy of the tests applied in clinical praxis. This review showed the increasing interest in nanotechnology applications in obstetrics disorders and pregnancy-related pathologies to improve the diagnostic algorithms, monitor pregnancy-related diseases, and implement new treatment strategies

Forebulge migration in the foreland basin system of the central-southern Apennine fold-thrust belt (Italy): New high-resolution Sr-isotope dating constraints

The Apennines are a retreating collisional belt where the foreland basin system, across large domains, is floored by a subaerial forebulge unconformity developed due to forebulge uplift and erosion. This unconformity is overlain by a diachronous sequence of three lithostratigraphic units made of (a) shallow-water carbonates, (b) hemipelagic marls and shales and (c) siliciclastic turbidites. Typically, the latter two have been interpreted regionally as the onset of syn-orogenic deposition in the foredeep depozone, whereas little attention has been given to the underlying unit. Accordingly, the rate of migration of the central-southern Apennine fold-thrust belt-foreland basin system has been constrained, so far, exclusively considering the age of the hemipelagites and turbidites, which largely post-date the onset of foredeep depozone. In this work, we provide new high-resolution ages obtained by strontium isotope stratigraphy applied to calcitic bivalve shells sampled at the base of the first syn-orogenic deposits overlying the Eocene-Cretaceous pre-orogenic substratum. Integration of our results with published data indicates progressive rejuvenation of the strata sealing the forebulge unconformity towards the outer portions of the fold-thrust belt. In particular, the age of the forebulge unconformity linearly scales with the pre-orogenic position of the analysed sites, pointing to an overall constant migration velocity of the forebulge wave in the last 25 Myr

Foreign bodies in the upper airways: the experience of two Italian hospitals

OBJECTIVE: To study the pattern of foreign bodies in the upper airways as emerging from the hospital records in the Bologna and Siena hospitals in Italy 1997-2002. METHODS: A retrospective review of hospital records was performed using a standardized protocol. All injuries with ICD9 (International Classification of Diseases, 9'h revision) codes ranging from 931 to 934 which occurred in children age 0-14 were considered for the database. RESULTS: One hundred ninety seven patients were included in the database with a diagnosis of Foreign Bodies (FB) over the study period, 78 with ICD931, 105 with ICD932, 12 with ICD933 and 2 with ICD934 discharge diagnosis. Of the 197 patients, 51.90% of the patients were males and the 48.10% were female. Median age was 4 (2, 6). At the moment of the injury, the child was eating (11%), playing (83%) or studying (4%) or cleaning ears (2%). The child was supervised by an adult in doing his/her activities at the moment of injury in the 84.2% of the cases. The child reached the hospital using always private transport (100%), never by using an emergency transport (0%). Most commonly, FB were extracted in ambulatory (95.4%), more rarely using an endoscopic procedure (4.1%), and never using surgery. Hospitalization was required in the 0.5% of cases (1). CONCLUSIONS: Our study showed the substantial epidemiological similarity of the Italian data with the experience of other center in the world. The burden of chocking was very limited in our country, as proven by the limited access to emergency and more invasive procedures. Nevertheless, some consideration can be made from the preventive point of view. Quite surprisingly, the majority of injuries occurred under the supervision of an adult in playing or recreational activities

Foreign bodies in the upper airways: the experience of two Italian hospitals

OBJECTIVE: To study the pattern of foreign bodies in the upper airways as emerging from the hospital records in the Bologna and Siena hospitals in Italy 1997-2002. METHODS: A retrospective review of hospital records was performed using a standardized protocol. All injuries with ICD9 (International Classification of Diseases, 9'h revision) codes ranging from 931 to 934 which occurred in children age 0-14 were considered for the database. RESULTS: One hundred ninety seven patients were included in the database with a diagnosis of Foreign Bodies (FB) over the study period, 78 with ICD931, 105 with ICD932, 12 with ICD933 and 2 with ICD934 discharge diagnosis. Of the 197 patients, 51.90% of the patients were males and the 48.10% were female. Median age was 4 (2, 6). At the moment of the injury, the child was eating (11%), playing (83%) or studying (4%) or cleaning ears (2%). The child was supervised by an adult in doing his/her activities at the moment of injury in the 84.2% of the cases. The child reached the hospital using always private transport (100%), never by using an emergency transport (0%). Most commonly, FB were extracted in ambulatory (95.4%), more rarely using an endoscopic procedure (4.1%), and never using surgery. Hospitalization was required in the 0.5% of cases (1). CONCLUSIONS: Our study showed the substantial epidemiological similarity of the Italian data with the experience of other center in the world. The burden of chocking was very limited in our country, as proven by the limited access to emergency and more invasive procedures. Nevertheless, some consideration can be made from the preventive point of view. Quite surprisingly, the majority of injuries occurred under the supervision of an adult in playing or recreational activities

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Contains reports on seven research projects.Lincoln Laboratory (Purchase Order DDL-B222