Human peopling of Italian intramontane basins: The early Middle Pleistocene site of Pagliare di Sassa (L’Aquila, central Italy)

Multidisciplinary investigations at Pagliare di Sassa (L’Aquila, central Italy) suggest that the local succession accumulated from the late Early to the early Middle Pleistocene in a lacustrine environment. In the upper part, clastic sediments are part of an alluvial fan prograding into the lake, grading to a braided fluvial system. The pollen record confirms that a significant glacial phase occurred just before the onset of the Jaramillo inversion. These data, coupled with evidence from the nearby but earlier Madonna della Strada sequence, allow reconstruction of part of the environmental evolution of L’Aquila basin before the Jaramillo Subchron. The mammal species of Pagliare di Sassa include Stephanorhinus hundsheimensis, mostly of open environments, already present at Madonna della Strada. The faunal turnover characterizing the Early to Middle Pleistocene transition is indicated by the appearances of taxa typical of the Italian early to middle Galerian faunas, such as Praemegaceros verticornis, together with Megaloceros savini. The occurrence of Mimomys savini together with Microtus ex gr. Microtus hintonigregaloides suggests that this assemblage is earlier than the Isernia La Pineta fauna. A flint implement and a fragmentary herbivore femur with impact scars probably linked to human activity give evidence of the human peopling of intramontane basins of the Apennine chain since the early Middle Pleistocene.Published170-1782.2. Laboratorio di paleomagnetismoJCR Journalrestricte

Multi-proxy analysis suggests Late Pleistocene affinities of human skeletal remains attributed to Balzi Rossi

In two publications from 1967 and 1971, M. Masali described human skeletal remains presumed to have been found in the Balzi Rossi caves (Ventimiglia, Italy), based on a signed note dated to 1908. Since then, the remains - dubbed "Conio's Finds" and preserved at the University of Torino - had not been further studied. We performed a multidisciplinary investigation aimed at clarifying the geographical and chronological attribution of these specimens. Collagen extraction for AMS dating was unsuccessful, but we obtained two direct dates on the best- preserved crania via 231Pa/235U direct gamma-ray spectrometry (10,500±2,000 years BP and 12,500±2,500 years BP). We analyzed the metrics and morphology of the crania and femora by comparing them with samples belonging to the Upper Paleolithic, Mesolithic, and Neolithic periods, and evidenced that the "Conio's Finds" are morphologically more compatible with a Late Pleistocene rather than Holocene attribution. We analyzed the literature regarding the history of excavations at Balzi Rossi, and we propose that - if any credence should be given to the note accompanying the material - the remains may have been found in front of Grotta dei Fanciulli or Grotta del Caviglione, in the redeposited soil dug up during the installation of lime kilns carried out between the late 18th and the early 19th centuries. These hypotheses may be tested in the future by comparing the speleothem deposited on one of the crania and the remaining deposit at the site

Skp2B Overexpression Alters a Prohibitin-p53 Axis and the Transcription of PAPP-A, the Protease of Insulin-Like Growth Factor Binding Protein 4

We previously reported that the degradation of prohibitin by the SCF(Skp2B) ubiquitin ligase results in a defect in the activity of p53. We also reported that MMTV-Skp2B transgenic mice develop mammary gland tumors that are characterized by an increased proteolytic cleavage of the insulin-like growth factor binding protein 4 (IGFBP-4), an inhibitor of IGF signaling. However, whether a link exists between a defect in p53 activity and proteolysis of IGFBP-4 was not established.We analyzed the levels of pregnancy-associated plasma protein A (PAPP-A), the protease of IGFBP-4, in MMTV-Skp2B transgenic mice and found that PAPP-A levels are elevated. Further, we found a p53 binding site in intron 1 of the PAPP-A gene and that both wild type and mutant p53 bind to this site. However, binding of wild type p53 results in the transcriptional repression of PAPP-A, while binding of mutant p53 results in the transcriptional activation of PAPP-A. Since MMTV-Skp2B mice express wild type p53 and yet show elevated levels of PAPP-A, at first, these observations appeared contradictory. However, further analysis revealed that the defect in p53 activity in Skp2B overexpressing cells does not only abolish the activity of wild type of p53 but actually mimics that of mutant p53. Our results suggest that in absence of prohibitin, the half-life of p53 is increased and like mutant p53, the conformation of p53 is denatured.These observations revealed a novel function of prohibitin as a chaperone of p53. Further, they suggest that binding of denatured p53 in intron 1 causes an enhancer effect and increases the transcription of PAPP-A. Therefore, these findings indicate that the defect in p53 function and the increased proteolysis of IGFBP-4, we had observed, represent two components of the same pathway, which contributes to the oncogenic function of Skp2B

Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women with Preconception Immunity (CHILd Study)

Background: Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population. Methods: The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing. Results: Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was. 19% (95% confidence interval [CI]:. 11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7-32.2; P =. 037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P =. 003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled. Conclusions: Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV. Clinical trials registration: www.clinicaltrials.gov (NCT03973359)

Cetaceans in the Mediterranean Sea. Encounter rate, dominant species, and diversity hotspots

We investigated the presence and diversity of cetaceans in the Mediterranean Sea, analysing the data collected by 32 different research units, over a period of 15 years (2004–2018), and shared on the common web-GIS platform named Intercet. We used the encounter rate, the species prevalence, and the Shannon diversity index as parameters for data analysis. The results show that cetacean diversity, in the context of the Mediterranean basin, is generally quite low when compared with the eastern Atlantic, as few species, namely the striped dolphin, the bottlenose dolphin, the fin whale, and the sperm whale, dominate over all the others. However, some areas, such as the Alboran Sea or the north-western Mediterranean Sea, which includes the Pelagos Sanctuary (the Specially Protected Area of Mediterranean Interest located in the northern portion of the western basin), show higher levels of diversity and should be considered hotspots to be preserved. Primary production and seabed profile seem to be the two main drivers influencing the presence and distribution of cetaceans, with the highest levels of diversity observed in areas characterized by high levels of primary production and high bathymetric variability and gradient. This collective work underlines the importance of data sharing to deepen our knowledge on marine fauna at the scale of the whole Mediterranean Sea and encourages greater efforts in the networking process, also to accomplish the requirements of the Marine Strategy Framework Directive, with particular reference to Descriptor 1: biological diversity is maintained

Role of Fibronectin in the Adhesion of Acinetobacter baumannii to Host Cells

Adhesion to host cells is an initial and important step in Acinetobacter baumannii pathogenesis. However, there is relatively little information on the mechanisms by which A. baumannii binds to and interacts with host cells. Adherence to extracellular matrix proteins, such as fibronectin, affords pathogens with a mechanism to invade epithelial cells. Here, we found that A. baumannii adheres more avidly to immobilized fibronectin than to control protein. Free fibronectin used as a competitor resulted in dose-dependent decreased binding of A. baumannii to fibronectin. Three outer membrane preparations (OMPs) were identified as fibronectin binding proteins (FBPs): OMPA, TonB-dependent copper receptor, and 34 kDa OMP. Moreover, we demonstrated that fibronectin inhibition and neutralization by specific antibody prevented significantly the adhesion of A. baumannii to human lung epithelial cells (A549 cells). Similarly, A. baumannii OMPA neutralization by specific antibody decreased significantly the adhesion of A. baumannii to A549 cells. These data indicate that FBPs are key adhesins that mediate binding of A. baumannii to human lung epithelial cells through interaction with fibronectin on the surface of these host cells

Relationship between low Ankle-Brachial Index and rapid renal function decline in patients with atrial fibrillation: A prospective multicentre cohort study

OBJECTIVE: To investigate the relationship between Ankle-Brachial Index (ABI) and renal function progression in patients with atrial fibrillation (AF). DESIGN: Observational prospective multicentre cohort study. SETTING:Atherothrombosis Center of I Clinica Medica of 'Sapienza' University of Rome; Department of Medical and Surgical Sciences of University Magna Græcia of Catanzaro; Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study. PARTICIPANTS: 897 AF patients on treatment with vitamin K antagonists. MAIN OUTCOME MEASURES: The relationship between basal ABI and renal function progression, assessed by the estimated Glomerular Filtration Rate (eGFR) calculated with the CKD-EPI formula at baseline and after 2 years of follow-up. The rapid decline in eGFR, defined as a decline in eGFR >5 mL/min/1.73 m(2)/year, and incident eGFR<60 mL/min/1.73 m(2) were primary and secondary end points, respectively. RESULTS: Mean age was 71.8±9.0 years and 41.8% were women. Low ABI (ie, ≤0.90) was present in 194 (21.6%) patients. Baseline median eGFR was 72.7 mL/min/1.73 m(2), and 28.7% patients had an eGFR60 mL/min/1.73 m(2), 153 (23.9%) had a reduction of the eGFR <60 mL/min/1.73 m(2). ABI ≤0.90 was also an independent predictor for incident eGFR<60 mL/min/1.73 m(2) (HR 1.851, 95% CI 1.205 to 2.845, p=0.005). CONCLUSIONS: In patients with AF, an ABI ≤0.90 is independently associated with a rapid decline in renal function and incident eGFR<60 mL/min/1.73 m(2). ABI measurement may help identify patients with AF at risk of renal function deterioration

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81&nbsp;years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

The challenge of habitat modelling for threatened low density species using heterogeneous data : the case of Cuvier’s beaked whales in the Mediterranean

We are grateful to the ACCOBAMS Secretariat for their support in this work, including a small grant for the analysis.The Mediterranean population of Cuvieŕs beaked whale (Ziphius cavirostris), a deep-diving cetacean, is genetically distinct from the Atlantic, and subject to a number of conservation threats, in particular underwater noise. It is also cryptic at the surface and relatively rare, so obtain robust knowledge on distribution and abundance presents unique challenges. Here we use multiplatform and multiyear survey data to analyse the distribution and abundance of this species across the Mediterranean Sea. We use a novel approach combining heterogeneous data gathered with different methods to obtain a single density index for the region. A total of 594,996 km of survey effort and 507 sightings of Cuvier’s beaked whales, from 1990 to 2016, were pooled together from 24 different sources. Data were divided into twelve major groups according to platform height, speed and sea state. Both availability bias and effective strip width were calculated from the sightings with available perpendicular distance data. This was extrapolated to the rest of the sightings for each of the twelve groups. Habitat preference models were fitted into a GAM framework using counts of groups as a response variable with the effective searched area as an offset. Depth, coefficient of variation of depth, longitude and marine regions (as defined by the International Hydrographic Organization) were identified as important predictors. Predicted abundance of groups per grid cell were multiplied by mean group size to obtain a prediction of the abundance of animals. A total abundance of 5799 (CV = 24.0%) animals was estimated for the whole Mediterranean basin. The Alborán Sea, Ligurian Sea, Hellenic Trench, southern Adriatic Sea and eastern Ionian Sea were identified as being the main hot spots in the region. It is important to urge that the relevant stakeholders incorporate this information in the planning and execution of high risk activities in these high-risk areas.PostprintPeer reviewe