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This project aims to test whether geometric morphometric (GM) and trabecular analyses may be useful tools in identifying talar characteristics related to hypochondroplasia. We quantified the external and internal talar morphology of an hypochondroplasic dwarf (T17) from Modena (northern Italy) dated to the 6th century AD. External talar morphology of T17 was compared with a broad sample of modern human tali (n = 159) using GM methods. Additionally, a subsample of these tali (n = 41) was used to investigate whole talar trabecular changes in T17. Our results show that GM and trabecular analyses identify a combination of traits linked to the dwarfing disorder of hypochondroplasia. These traits include decreased scaled talar dimensions compared to normal-sized individuals, presence of an accessory antero-lateral talar facet, high bone volume fraction and high anisotropy values throughout the entire talus. In our case study, hypochondroplasia does not appear to substantially modify external talar morphology probably due to the fast growth of the talus. We suggest that small talar dimensions are associated with hypochondroplasia. An antero-lateral talar facet may result from the talus and calcaneus coalition (i.e., talocalcaneal abnormal bridging) possibly related to an everted foot posture that was limited by overgrowth of the fibula. We suggest that high talar trabecular density and strut orientation provide insights into pathological development of the trabecular plates in T17. Finally, our study suggests that high talar trabecular density and strut orientation, and small talar dimensions, may be added as possible concomitant talar hallmarks for hypochondroplasia.

The tempo and mode of Homo sapiens dispersal in Eurasia and the demise of Neanderthals has sparked debate about the dynamics of Neanderthal extinction and its relationship to the arrival of H. sapiens. In Italy, the so-called ‘Transition’ from Neanderthals to H. sapiens is related to the Uluzzian technocomplex, i.e. the first archaeological evidence for modern human dispersal on the European continent. This paper illustrates the new chronology and stratigraphy of Uluzzo C, a rock shelter and Uluzzian key site located in the Uluzzo Bay in southern Italy, where excavations are ongoing, refining the cultural sequence known from previous excavations. Microstratigraphic investigation suggests that most of the deposit formed after dismantling of the vault of the rock shelter and due to wind input of loess deflated by the continental shelf. The occasional reactivation of the hydrology of the local karst system under more humid conditions further contributed to the formation of specific layers accumulating former Terra Rossa-type soil fragments. Superposed on sedimentary processes, strong bioturbation and the mobilization and recrystallization of calcite have been detected. Optically stimulated luminescence (OSL) ages from Uluzzo C Rock Shelter are congruent with previously published radiocarbon ages obtained on shell beads and tephrachronology from adjacent sites preserving the Uluzzian technocomplex such as Grotta del Cavallo, confirming the onset for the Uluzzian in the area to ca. 39.2–42.0 ka. The OSL chronology from Uluzzo C also provides a terminus post quem for the end of the Mousterian in the region, constraining the disappearance of the Neanderthals in that part of Italy to ≥46 ± 4 ka.

Bacterial drug resistance is one of the major challenges to present and future human health, as the continuous selection of multidrug resistant bacteria poses at serious risk the possibility to treat infectious diseases in the near future. One of the infection at higher risk to become incurable is tuberculosis, due to the few drugs available in the market against

none 6 no Teeth fusion is a developmental anomaly characterized by the union of two and, more rarely, three adjacent teeth. The fusion is caused by the physical pressure between two adjacent teeth during their development due to congenital, inherited, acquired or idiopathic factors. Nowadays, fused teeth occur with a frequency ratio between 0.1% and 1% in permanent dentition and 0.5% and 2.5% in primary dentition, and with an equal distribution between males and females. Fused teeth are a rare clinical finding, so there are not standardized clinical protocols and each case should be treated independently. This condition is rare in archaeological populations, likely due to taphonomic processes that cause the lack of information, as well as for the general low occurrence of the defect itself. In the European archaeological literature, there are no reports of two permanent fused teeth so far. Therefore, the present paper represents the first case study of two fused permanent incisors in the past Europe populations as this anomaly has been recognized in an adult man buried in the Longobard cemetery of Guidizzolo (VI–VII century A.D., northern Italy). open Collina F.; Conti S.; Menetti M.; Scheda L.; Sorrentino R.; Benazzi S. Collina F.; Conti S.; Menetti M.; Scheda L.; Sorrentino R.; Benazzi S.

Objective: The development of bipedalism is a very complex activity that contributes to shaping the anatomy of the foot. The talus, which starts ossifying in utero, may account for the developing stages from the late gestational phase onwards. Here, we explore the early development of the talus in both its internal and external morphology to broaden the knowledge of the anatomical changes that occur during early development.Materials and Methods: The sample consists of high-resolution microCT scans of 28 modern juvenile tali (from 36 prenatal weeks to 2 years), from a broad chronological range from the Late Roman period to the 20th century. We applied geometric morphometric and whole-bone trabecular analysis to investigate the early talar morphological changes.Results: In the youngest group (

[Objectives] During the middle-to-upper Paleolithic transition (50,000 and 40,000¿years ago), interaction between Neanderthals and Homo sapiens varied across Europe. In southern Italy, the association between Homo sapiens fossils and non-Mousterian material culture, as well as the mode and tempo of Neanderthal demise, are still vividly debated. In this research, we focus on the study of two human teeth by using 3D geometric morphometric approaches for a reliable taxonomical attribution as well as obtaining new radiometric dates on the archeological sequence., [Material and Methods] This work presents two lower deciduous molars uncovered at Roccia San Sebastiano (Mondragone-Caserta, Italy), stratigraphically associated with Mousterian (RSS1) and Uluzzian (RSS2) artifacts. To obtain a probabilistic attribution of the two RSS teeth to each reference taxa group composed of Neanderthals and Homo sapiens, we performed and compared the performance of three supervised learning algorithms (flexible discriminant analysis, multiadaptive regression splines, and random forest) on both crown and cervical outlines obtained by virtual morphometric methods. [Discussion] This site yields the most recent direct evidence for a Neanderthal presence in southern Italy and confirms a later shift to upper Paleolithic technology in southwestern Italy compared to the earliest Uluzzian evidence at Grotta del Cavallo (Puglia, Italy)., The authors are very grateful to the Municipality of Mondragone for supporting and funding the excavations. We also thank the Museo Civico Archeologico Biagio Greco, Mondragone, Caserta, Italy which provided funding, logistic support and welcomed the researcher since 1999 as well as an acknowledgement to the Soprintendenza Archeologia Belle Arti e Paesaggio di Salerno e Avellino, Benevento e Caserta. V.S. acknowledges funding from the Alon Fellowship. This study received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 724046 – SUCCESS, http://www.erc-success.eu); the radiocarbon dating was supported by the ERC-RESOLUTION grant agreement No 803147, https://site.unibo.it/resolution-erc/en);); the DNA analysis was funded by the European Research Council (grant agreement number 694707 to Svante Pääbo) and the Max Planck Society. We thank E. Essel, S. Nagel, B. Nickel, J. Richter, B. Schellbach and A. Weihmann for work in the ancient DNA lab; and M. Meyer and S. Pääbo for their input. Open Access Funding provided by Universita degli Studi di Bologna within the CRUI-CARE Agreement.

Fil: Drube, Hilton. Universidad Nacional de Catamarca. Facultad de Ciencias Exactas y Naturales; Argentina. Universidad Nacional de Santiago del Estero; Argentina

Neanderthal foot bone proportions and morphology are mostly indistinguishable from those of Homo sapiens, with the exception of several distinct Neanderthal features in the talus. The biomechanical implications of these distinct talar features remain contentious, fueling debate around the adaptive meaning of this distinctiveness. With the aim of clarifying this controversy, we test phylogenetic and behavioral factors as possible contributors, comparing tali of 10 Neanderthals and 81 H. sapiens (Upper Paleolithic and Holocene hunter-gatherers, agriculturalists, and postindustrial group) along with the Clark Howell talus (Omo, Ethiopia). Variation in external talar structures was assessed through geometric morphometric methods, while bone volume fraction and degree of anisotropy were quantified in a subsample (n = 45). Finally, covariation between point clouds of site-specific trabecular variables and surface landmark coordinates was assessed. Our results show that although Neanderthal talar external and internal morphologies were distinct from those of H. sapiens groups, shape did not significantly covary with either bone volume fraction or degree of anisotropy, suggesting limited covariation between external and internal talar structures. Neanderthal external talar morphology reflects ancestral retentions, along with various adaptations to high levels of mobility correlated to their presumably unshod hunter-gatherer lifestyle. This pairs with their high site-specific trabecular bone volume fraction and anisotropy, suggesting intense and consistently oriented locomotor loading, respectively. Relative to H.sapiens, Neanderthals exhibit differences in the talocrural joint that are potentially attributable to cultural and locomotor behavior dissimilarity, a talonavicular joint that mixes ancestral and functional traits, and a derived subtalar joint that suggests a predisposition for a pronated foot during stance phase. Overall, Neanderthal talar variation is attributable to mobility strategy and phylogenesis, while H. sapiens talar variation results from the same factors plus footwear. Our results suggest that greater Neanderthal body mass and/or higher mechanical stress uniquely led to their habitually pronated foot posture.

Objective To evaluate, via a multidisciplinary approach, a distinctive paleopathological condition believed to be fibrous dysplasia, found on a 19th/20th century skeleton from Certosa Monumental Cemetery, Bologna, Italy. Materials A skeletonized cranium and mandible recovered from an ossuary in 2014. Methods Pathological alterations were analysed by radiological examination, dental macrowear, histopathological and genetic analyses. Result The skeleton is believed to be an adult male. Differential diagnoses include Paget's disease, McCune-Albright syndrome, osteochondroma and osteosarcoma. The radiographic findings, along with the solitary nature of the lesions, are strong evidence for the diagnosis of fibrous dysplasia (FD). Genetic analysis further revealed a frequency of ˜1% of mutant alleles with the R201C substitution, one of the post-zygotic activating mutation frequently associated with FD. Conclusions The multi-analytical method employed suggests a diagnosis of monostotic form of FD. The diagnostic design incorporates multiple lines of evidence, including macroscopic, histopathological, and genetic analyses. Significance Through the use of a multi-analytic approach, robust diagnoses can be offered. This case serves as one of the oldest examples of FD from an historical context. The genetic mutation detected, associated with FD, has not been previously reported in historical/ancient samples.

The 4th century BC marks the main entrance of Celtic populations in northern Italy. Their arrival has been suggested based on the presence of Celtic customs in Etruscan mortuary contexts, yet up to now few bioarchaeological data have been examined to support or reject the arrival of these newcomers. Here we use strontium isotopes, non-metric dental traits and funerary patterns to unravel the biocultural structure of the necropolis of Monterenzio Vecchio (Bologna, Italy). Subsamples of our total sample of 38 individuals were analyzed based on different criteria characterizing the following analyses: 1) strontium isotope analysis to investigate migratory patterns and provenance; 2) non-metric dental traits to establish biological relationships between Monterenzio Vecchio, 13 Italian Iron age necropolises and three continental and non-continental Celtic necropolises; 3) grave goods which were statistically explored to detect possible patterns of cultural variability. The strontium isotopes results indicate the presence of local and non-local individuals, with some revealing patterns of mobility. The dental morphology reveals an affinity between Monterenzio Vecchio and Iron Age Italian samples. However, when the Monterenzio Vecchio sample is separated by isotopic results into locals and non-locals, the latter share affinity with the sample of non- continental Celts from Yorkshire (UK). Moreover, systematic analyses demonstrate that ethnic background does not retain measurable impact on the distribution of funerary elements. Our results confirm the migration of Celtic populations in Monterenzio as archaeologically hypothesized on the basis of the grave goods, followed by a high degree of cultural admixture between exogenous and endogenous traits. This contribution shows that combining different methods offers a more comprehensive perspective for the exploration of biocultural processes in past and present populations. European Commission Horizon 2020

The aim of this work was to evaluate cold atmospheric plasma bactericide activity towards biofilm formation on soft reline oral palatal obturators. Plasma was generated using two dielectric barrier discharge and tested against the oral biofilm formers Streptococcus mutans and Aggregatibacter actinomycetemcomitans. Relines were either plasma treated before being infected with 24 h biofilm, or infected with 90 min (early) or 24 h (mature) biofilm prior to be plasma treated for 30, 60, or 120 s. Bacteria numbers and viability were evaluated by Colonies Forming Units counts (CFU) and quantitative colorimetric metabolic 2,3-bis (2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenyl amino) carbonyl]-2H-tetrazolium hydroxide assay (XTT). cytocompatibility was assayed towards human primary fibroblasts and keratinocytes cultivated on plasma-treated specimens by colorimetric metabolic 3-(4,5-Dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay and light microscopy. Results demonstrated that both plasma sources were effective. Plasma treatment of sterile reline affected bacterial adhesion, reducing CFU number and viability by 2 logs and by 50%, in comparison with untreated controls (p < 0.05). Plasma efficacy was marked against early biofilm: after 120 s, CFUs were reduced by 3 logs, and viability decreased by about 60% (p < 0.05). Significant results were also observed for mature biofilm: CFUs and viability were reduced by approximately 2 logs and 40% (p < 0.05), after 120 s exposure. Lastly, MTT did not show any toxic effect on human cells. Thus, plasma could represent a very promising skill for soft reline shutters decontamination.

Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate-binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3-O-β-d-rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB-MDA-231, selected as representative for triple-negative breast cancer and (ii) MCF-7 used as a well-characterized model of HER2-negative breast cancer. To assess the cytocompatibility of rutin against non-cancer cells, primary human mammary fibroblasts were used as control and non-target cells. In MDA-MB-231 cells, 20 μM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p

Peri-implantitis is a severe condition affecting the success of transmucosal dental implants: tissue healing is severely limited by the inflammatory processes that come about to control homeostasis in the surrounding tissues. The main cause of peri-implantitis is bacterial biofilm infection; gingival fibroblasts play a pivotal role in regulating the inflammatory cascades. A new technology aimed at preventing bacterial colonization of titanium (Ti) implants, and enhancing the spread of gingival fibroblasts, is presented. Using electro-spinning, mirror-polished Ti disks were uniformly coated with keratin fibers obtained from discarded wool via sulfitolysis. The keratin-coated surfaces were then doped with silver (Ag) to introduce antibacterial properties, using different concentrations of silver nitrate as a precursor (0.01, 0.05 and 0.1 M). The resulting specimens were characterized in terms of morphology and chemical composition by FESEM, FTIR and XPS, revealing silver concentrations between 1.7 and 1.9%. Silver release into the medium was evaluated in the presence of cells (a-MEM) or bacteria (LB) by ICP; release was 0.2-1.4 mg l1 for a-MEM, and 10-40 mg l1 for LB. The antibacterial properties of the Ag-doped specimens were tested against a multidrug-resistant Staphylococcus aureus biofilm through morphology (FESEM) and metabolic assay (XTT); reduction in viability was significant (p o 0.05; 480% reduction within 72 h). Lastly, the cytocompatibility of the specimens was confirmed using human primary gingival fibroblasts, whose viability, spread and matrix deposition were found to be comparable to those of untreated Ti polished controls (p 4 0.05). Thus, Ag surface enrichment was effective in reducing viability and maturation of S. aureus biofilm, without compromising human cell viability. Moreover, cell spread was found to be very sensitive to keratin fiber stimulation. The strategy thus appears to be very promising to introduce surface features in line with the main requirements for transmucosal dental implants.

To evaluate OPN, MCM7, Ki-67, p53, Bcl-2 and 53BP1 presence, together with the abnormal adaptive CD4 and CD8 T-cell response markers expression in a series of oral lichen planus (OLP) affected patients and assess their combined contribution for a more objective disease classification.In this ex-vivo retrospective analysis, biopsy specimens from 28 adults with a clinical diagnosis of OLP at different progression degree (16 reticular, 2 plaque-like, 1 erosive and 9 mixed type) were collected. Sections were immunohistochemically investigated for the proinflammatory cytokine osteopontin (OPN), alpha-beta CD4 and CD8 positive T cells, DNA replication licensing factor (MCM7), proliferating cell marker (Ki-67), apoptotic and tumor antigen (p53), apoptosis modulator (Bcl-2) and cellular response regulator to double-strand breaks tumor suppressor p53-binding protein 1 expression. Statistical analysis revealed that 53BP1 is highly represented among the OLP study patients (p0.05). Moreover, on the basis of the quantification results of the highly expressed parameters, two illness categories with different severity were evidenced. The classification hypothesis was confirmed by i) OLP lesion persistence, ii) the development of oral severe lesions in the patients belonging to high grade activity OLP group (HGA-OLPs) and iii) the ascertainment of the same evidence both in the oral squamous cell tumor controls (OSCC) and in HGA-OLP cases.This study completes the scenario with respect to early detection, thanks to a more precise histological analysis, for rationalizing the clinical and histological findings toward a sharable international disease scoring system.

This paper contains original data supporting the antibacterial activities of Gallium (Ga3+)-doped pro-osteointegrative titanium alloys, obtained via Anodic Spark Deposition (ASD), as described in “The effect of silver or gallium doped titanium against the multidrug resistant Acinetobacter baumannii” (Cochis et al. 2016) [1].In this article we included an indirect cytocompatibility evaluation towards Saos2 human osteoblasts and extended the microbial evaluation of the Ga3+ enriched titanium surfaces against the biofilm former Escherichia coli and Staphylococcus epidermidis strains. Cell viability was assayed by the Alamar Blue test, while bacterial viability was evaluated by the metabolic colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Finally biofilm morphology was analyzed by Scanning Electron Microscopy (SEM). Data regarding Ga3+ activity were compared to Silver. Keywords: E. coli, S. epidermidis, Biofilm, Gallium, Silver, Titanium, Anodic Spark Deposition

Entheses have rarely been systematically studied in the field of human evolution. However, the investigation of their morphological variability (e.g., robusticity) could provide new insight into their evolutionary significance in the European Neanderthal populations. The aim of this work is to study the entheses and joint features of the lower limbs of El Sidrón Neanderthals (Spain; 49 ka), using standardized scoring methods developed on modern samples. Paleobiology, growth, and development of both juveniles and adults from El Sidrón are studied and compared with those of Krapina Neanderthals (Croatia, 130 ka) and extant humans. The morphological patterns of the gluteus maximus and vastus intermedius entheses in El Sidrón, Krapina, and modern humans differ from one another. Both Neanderthal groups show a definite enthesis design for the gluteus maximus, with little intrapopulation variability with respect to modern humans, who are characterized by a wider range of morphological variability. The gluteus maximus enthesis in the El Sidrón sample shows the osseous features of fibrous entheses, as in modern humans, whereas the Krapina sample shows the aspects of fibrocartilaginous ones. The morphology and anatomical pattern of this enthesis has already been established during growth in all three human groups. One of two and three of five adult femurs from El Sidrón and from Krapina, respectively, show the imprint of the vastus intermedius, which is absent among juveniles from those Neanderthal samples and in modern samples. The scant intrapopulation and the high interpopulation variability in the two Neanderthal samples is likely due to a long-term history of small, isolated populations with high levels of inbreeding, who also lived in different ecological conditions. The comparison of different anatomical entheseal patterns (fibrous vs. fibrocartilaginous) in the Neanderthals and modern humans provides additional elements in the discussion of their functional and genetic origin., This work is funded by the Spanish Ministry of Economy and Competitiveness: CGL2016-75109-P.

Background Despite vaccination and screening measures, anogenital cancer, mainly promoted by HPV16 oncoproteins, still represents the fourth tumor and the second cause of death among women. Cell replication fidelity is the result of the host DNA damage response (DDR). Unlike many DNA viruses that promote their life cycle through the DDR inactivation, HR-HPVs encourage cells proliferation despite the DDR turned on. Why and how it occurs has been only partially elucidated. During HPV16 infection, E6 links and degrades p53 via the binding to the E6AP LXXLL sequence; unfortunately, E6 direct role in the DDR response has not clearly identified yet. Similarly, E7 increases DDR by competing with E2F1-pRb interaction, thus leading to the inactivation of pRb, and promotion, E2F1 mediated, of DDR genes translation, by binding to the pRb-like proteins CBP/p300 and p107, that also harbour LXXLL sequence, and via the interaction and activation of several DDR proteins. Methods To gain information regarding E6 and E7 contribution in DDR activation, we produced an in vitro 3D HPV16-E6E7 infected epithelium, already consolidated study model for HPVs, and validated it by assessing H&E staining and BrdU, HPV16 DNA, E6E7 proteins and γH2A.X/53BP1 double-strand break (DSBs) sensors expression; then we made an immuno-colocalization of E6 and E7 with cyclin E2 and B1. Since 53BP1, like E6 and E7, also binds p53 and pRb, we supposed their possible direct binding. To explore this hypothesis, we performed a double immunofluorescence of E6 and E7 with 53BP1, a sequence analysis of 53BP1 within its BRCT2 domain and then an in situ PLA within CaSki, E6E7HPV16 NHEKs and the 3D model. Results The in vitro epithelium resembled the histology and the events typical of in vivo infected tissues. E6E7HPV16 were both expressed in basal and differentiated strata and induced H2A.X phosphorylation and 53BP1 increment into nuclear foci. After highlighting E6 and E7 co-expression with 53BP1 and a LKVLL sequence within the 53BP1 BRCT2 domain, we demonstrated the bindings via the PLA technique. Conclusions Our results reinforce E6 and E7 role in cellular function control providing potentially new insights into the activity of this tumor virus.

Chlorhexidine (CHX), one of the most effective drugs administered for periodontal treatment, presents collateral effects including toxicity when used for prolonged periods, here, we have evaluated the bactericidal potency and the cytocompatibility of Juniperus excelsa M. Bieb essential oil (EO) in comparison with 0.05% CHX. The EO was extracted from berries by hydrodistillation and components identified by gas chromatography and mass spectrometry. Bacterial inhibition halo analysis, quantitative cell viability 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenyl amino) carbonyl]-2H-tetrazolium hydroxide assay (XTT), and colony forming unit (CFU) count were evaluated against the two biofilm formers Aggregatibacter actinomycetemcomitans and Streptococcus mutans. Finally, cytocompatibility was assessed with human primary gingival fibroblasts (HGF) and mucosal keratinocytes (HK). The resulting EO was mainly composed of monoterpene hydrocarbons and oxygenated monoterpenes. An inhibition halo test demonstrated that both bacteria were sensitive to the EO, XTT analysis and CFU counts confirmed that 10-fold-diluted EO determined a statistically significant (p &lt, 0.05) reduction in bacteria count and viability towards both biofilm and planktonic forms in a comparable manner to those obtained with CHX. Moreover, EO displayed higher cytocompatibility than CHX (p &lt, 0.05). In conclusion, EO exhibited bactericidal activity similar to CHX, but a superior cytocompatibility, making it a promising antiseptic alternative to CHX.

Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate-binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3-O-β-d-rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB-MDA-231, selected as representative for triple-negative breast cancer and (ii) MCF-7 used as a well-characterized model of HER2-negative breast cancer. To assess the cytocompatibility of rutin against non-cancer cells, primary human mammary fibroblasts were used as control and non-target cells. In MDA-MB-231 cells, 20 μM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p 0.05) increased the anticancer activity of both chemotherapeutics, at 24-48-72 h, and decreased the activity of the adenosine triphosphate-binding cassette transporters, namely, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Flow cytometry analysis showed 20 μM and 50 μM rutin arrested cell cycle at G2/M and G0/G1 phases, respectively, significantly promoting cell apoptosis. Rutin, via non-selective inhibition of P-gp and BCRP pumps, efficiently reverses multidrug resistance and restores chemosensitivity to cyclophosphamide and cyclophosphamide of human chemoresistant, triple-negative breast cancer cells, successfully arresting cell cycle progression. Copyright © 2017 John WileySons, Ltd.

Periimplantitis and epithelial downgrowth are nowadays the main conditions associated to transmucosal dental implants. Gingival fibroblasts can play an important role in periimplantitis because they are the promoters of the inflammatory process and eventual tissue homeostasis and destruction. Moreover, the related inflammatory state is commonly driven also to counteract bacteria implants colonization. In the present research, a new technology based on mechanically produced nanogrooves (0.1-0.2mum) and keratin nanofibers deposited by electrospinning has been proposed in order to obtain titanium surfaces able to drive gingival fibroblasts alignment and proliferation without increasing bacterial adhesion. The prepared surfaces have been characterized for their morphology (FESEM), chemical composition (FTIR, XPS), surface charge (zeta potential) and wettability (contact angle). Afterwards, their performances in terms of cells (human primary gingival fibroblasts) and bacteria (Staphylococcus aureus) adhesion were compared to mirror-like polished titanium surfaces. Results revealed that gingival fibroblasts viability was not negatively affected by the applied surface roughness or by keratin nanofibers. On the opposite, cells adhesion and spread were strongly influenced by surface roughness revealing a significant cell orientation along the produced nanogrooves. However, the keratin influence was clearly predominant with respect to surface topography, thus leading to increased cells proliferation on the surfaces with nanofibers, disregarding the presence of the surfaces grooves. Moreover, nor nanogrooves nor keratin nanofibers increase bacterial biofilm adhesion in comparison with mirror polished surfaces. Thus, the present research represents a promising innovative strategy and technology for a surface modification finalized to match the main requirements for transmucosal dental implants.

Severe oral cancer might require patients to undergo surgical removal of soft tissues of the oral cavity; in order to replace these tissues, patients are required to wear removable oral palatal obturators, generally patient custom-made, as it is necessary to mold as much as possible the prosthesis to the lacking tissue. Among the large number of materials suitable for this purpose, soft reline holds a relevant position since it is easily moldable and possesses, thanks to its sponge-like return, the mechanical characteristics required to sustain the typical values of the compressive oral forces. Unfortunately, because of the sophistication of the raw material and the custom-made production process, soft reline oral palatal obturators are very expensive. Therefore, an eventual implant failure might be severely resource-(because of the implants cost) and time-(because of the long production process) consuming, prompting the desire for novel means for limiting implant failures, which are primarily caused by severe bacteria biofilm contaminations. Cold atmospheric plasma (CAP) processes represent a very promising strategy to decontaminate soft reline shutters, given its strong antibacterial potential, related to the killing activity of the several and synergic biologically active agents.

Randomized clinical trials have not shown long-term benefit of postmenopausal hormone replacement therapy (PHT) nor have they shown conclusively that the harmful consequences outweighs the benefits of the treatment. Rather, it is possible that an individualized hormone replacement therapy in questionably clinically healthy postmenopausal women may lead to different results than randomized trials. Design In this cross-sectional study we evaluated anthropometric parameters, body composition, serum lipids, blood pressure, heart rate variability (HRV) and neurocognitive functions in 39 healthy postmenopausal women PHT users or not users (n = 13, age 53.0 ± 3.3 and n = 26, age = 53.3 ± 5.0 SD, respectively) as well as in 27 younger controls (ages = 33.3 ± 7.1). Results Demographic parameters were similar in women PHT users and not users. Postmenopausal women showed a significantly increase of body mass index (BMI) as well as of waist circumference, compared to younger controls, but in PHT users the values of fat free mass were intermediate between the ones of not treated and younger women. The study of HRV showed a reduction in low frequency (LF) component (sympathetic modulation) during the day, and a reduction in high frequency (HF) component (parasympathetic modulation), particularly in postmenopausal women without PHT. PHT users were characterized by autonomic parameters intermediate between younger controls and age-matched women without PHT. Conclusions The impact of PHT on the age-dependent changes of anthropometric features and body composition seems to be modest but positive. Furthermore, PHT seems to play a positive role on the autonomic modulation of cardiac function, through a shift of LF / HF ratio values towards those of young controls.

Rarely have entheses been systematically utilized in the field of human evolution, but investigation of their morphological variability (robusticity) could provide new insights on their evolutionary meaning in the European Neandertal populations. The aim of this work is to study the entheses and joint features of the lower limbs of El Sidrón Neandertals (Spain; 49kyrs), utilizing scoring standardized methods developed on modern samples. Paleobiology, growth and development of both El Sidrón juveniles and adults are explored and compared with those of Krapina Neandertals (Croatia, 130 Kyrs) and European modern humans. The morphological patterns of the gluteus maximus and vastus intermedius entheses of El Sidrón, Krapina and modern humans are different from one another. Both Neandertal groups show a definite enthesis design for the gluteus maximus, with little intrapopulation variability with respect to modern humans, that display a wider range of morphological variability. The gluteus maximus enthesis of El Sidrón shows the osseous features of fibrous entheses, as in modern humans, while the Krapina sample shows the aspects of fibrocartilaginous ones. The morphology and anatomical pattern of this enthesis is already established during growth in all of the three human groups. One out of two and three out of five adult femurs of El Sidrón and Krapina, respectively, show the imprint of m. vastus intermedius, absent in their juvenile specimens and in the modern samples. The little intra-population and evident inter-population variability of the two Neandertal samples is likely due to long-term history of small, isolate populations with high levels of inbreeding also living in different ecological conditions. The comparison of different anatomical entheseal pattern (fibruous vs. fibrocartilagineous) of the Neandertals and modern humans opens new functional perspectives.

We present the results of a multi-disciplinary investigation on a deciduous human tooth (Pradis 1), recently recovered from the Epigravettian layers of the Grotte di Pradis archaeological site (Northeastern Italian Prealps). Pradis 1 is an exfoliated deciduous molar (Rdm2), lost during life by an 11—12-year-old child. A direct radiocarbon date provided an age of 13,088—12,897 cal BP (95% probability, IntCal20). Amelogenin peptides extracted from tooth enamel and analysed through LC¿MS/MS indicate that Pradis 1 likely belonged to a male. Time-resolved 87Sr/86Sr analyses by laser ablation mass spectrometry (LA-MC-ICPMS), combined with dental histology, were able to resolve his movements during the first year of life (i.e. the enamel mineralization interval). Specifically, the Sr isotope ratio of the tooth enamel differs from the local baseline value, suggesting that the child likely spent his first year of life far from Grotte di Pradis. Sr isotopes are also suggestive of a cyclical/seasonal mobility pattern exploited by the Epigravettian human group. The exploitation of Grotte di Pradis on a seasonal, i.e. summer, basis is also indicated by the faunal spectra. Indeed, the nearly 100% occurrence of marmot remains in the entire archaeozoological collection indicates the use of Pradis as a specialized marmot hunting or butchering site. This work represents the first direct assessment of sub-annual movements observed in an Epigravettian hunter-gatherer group from Northern Italy., The authors are grateful to Municipal Administration of Clauzetto, Pradis Cave Museum and the Superintendence for Archeology, Fine Arts and Landscape of Friuli Venezia Giulia for granting permission to study the tooth. This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (Grant Agreement no. 724046–SUCCESS awarded to S.B.; www.erc-success.eu and Grant Agreement no. 803147–RESOLUTION awarded to S.T.; https://site.unibo.it/resolution-erc/en) and by the MIUR FARE programme 2018 (FARE Ricerca in Italia: Framework per l'attrazione e il rafforzamento delle eccellenze—SAPIENS project to S.B.). A.N. is supported by a Marie Skłodowska-Curie Actions Individual Fellowship (grant number H2020-MSCA-IF-2018-842812-WEAN IT). E.Ba. is supported by EQUIPEX ASTER-CEREGE and ANR MARCARA and thanks Y. Fagault and T. Tuna for technical support. The Frankfurt Isotope & Element Research Center (FIERCE) is financially supported by the Wilhelm and Else Heraeus Foundation and by the Deutsche Forschungsgemeinschaft (DFG; INST 161/921-1 Forschungsgroßgeräte and INST 161/923-1 Forschungsgroßgeräte), which is gratefully acknowledged. This is FIERCE contribution No. 91. We acknowledge Elettra Sincrotrone Trieste for providing access to its laboratory facilities and the TomoLab staff for technical support. The authors deeply thank prof. Anna Cipriani for the use of geochemical facilities at UNIMORE (https://www.geochem.unimore.it/). Dr. Filippo Genovese is thanked for the help during LC-MS analyses. The ‘Fondazione Cassa di Risparmio di Modena’ is acknowledged for funding the UHPLC-ESI-Q Exactive system at the Centro Interdipartimentale Grandi Strumenti (CIGS), UNIMORE. Two anonymous reviewers are acknowledged for their constructive comments on our manuscript.

Morphology of hominid foot bones has received focused attention in paleoanthropological studies because of distinctive traits that are purportedly related to locomotor behaviors. In particular, the navicular is thought to preserve signatures of the medial longitudinal arch that uniquely characterizes the foot of Homo sapiens (among extant taxa), as well as distinctive morphological features that reflect habitual locomotor modes of hominids (great apes and humans). However, it is still debated what should be considered uniquely characteristic of human naviculars. This study reevaluates the distinctive traits of human naviculars that are presumably linked to locomotor behaviors by comparing naviculars of 21 Pongo, 35 Gorilla, 46 Pan and 221 H. sapiens accounting for different levels of mobility and subsistence strategies. Navicular shape was captured using a 3D template of 85 (semi)landmarks and analyzed through Geometric Morphometric methods. After Generalized Procrustes analysis, differences in shape coordinates were explored with Principal Component analysis and statistically evaluated with Procrustes ANOVA. Centroid size was used to investigate overall size differences and its contribution to shape variation (allometry). Navicular shape significantly differentiates Pongo, Gorilla, Pan, and H. sapiens. Alongside of size variation, it is possible to observe a subtle allometric effect that distinguishes H. sapiens from great apes. H. sapiens appears unique by showing a proximo-distally broader navicular body, a coronal displacement of cuneiform facets and a less medial-laterally elongated talar facet in respect to the navicular transversal length. We suggest that this morphology may reflect the presence of the medial longitudinal arch, therefore may be ultimately linked to our obligate bipedal locomotion. Human and non-human African great apes show a relative larger tuberosity than Pongo likely related to terrestrial locomotion. This preliminary contribution can be considered as a source for future studies aimed to investigate fossil hominin naviculars and their inferred locomotor behaviors.