The clinical, radiological, microbiological, and molecular profile of the skin-penetration site of transfemoral amputees treated with bone-anchored prostheses.

The breach of the skin barrier is a critical issue associated with the treatment of individuals with transfemoral amputation (TFA) using osseointegrated, percutaneous titanium implants. Thirty TFA patients scheduled for abutment exchange or removal were consecutively enrolled. The aims were to determine the macroscopic skin signs, the presence of bacteria and the gene expression in abutment-adherent cells and to conduct correlative and comparative analyses between the different parameters. Redness and a granulation ring were present in 47% of the patients. Bacteria were detected in 27/30 patients, commonly in the bone canal. Staphylococcus aureus, coagulase-negative staphylococci, streptococci, and Enterococcus faecalis were the most common. A positive correlation was found between TNF-α expression and the detection of S. aureus. Staphylococcus aureus together with other bacterial species revealed a positive relationship with MMP-8 expression. A negative correlation was demonstrated between the length of the residual femur bone and the detection of a granulation ring and E. faecalis. A positive correlation was revealed between fixture loosening and pain and the radiological detection of endosteal bone resorption. Fixture loosening was also correlated with the reduced expression of interleukin-10 and osteocalcin. It is concluded that several relationships exist between clinical, radiological, microbiological, and molecular assessments of the percutaneous area of TFAs. Further long term studies on larger patient cohorts are required to determine the precise cause-effect relationships and unravel the role of host-bacteria interactions in the skin, bone canal and on the abutment for the longevity of percutaneous implants as treatment of TFA. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 578-589, 2017

The Maglemosian skeleton from Koelbjerg, Denmark revisited: identifying sex and provenance

The Koelbjerg individual, dated c. 8500 cal BC, represents the earliest human skeletal remains described from Scandinavia. Based on ancient DNA, strontium isotope and statistical anthropological analyses the individual’s sex, haplogroup and geographical provenance are here analysed and discussed. In contrast to previous claims, our genetic and anthropological analyses show that this individual was a male. Additionally, the strontium isotope ratio of one of his first molars indicates that he most likely grew up locally

Effect of minor gallium addition on corrosion, passivity, and antibacterial behaviour of novel β-type Ti–Nb alloys

Metastable Ti–Nb alloys are promising bone-implant materials due to improved mechanical biofunctionality and biocompatibility. To overcome increasing bacterial infection risk, alloying with antibacterial elements is a promising strategy. This study investigates the effect of minor gallium (Ga) additions (4, 8 wt% Ga) to as-cast and solution-treated β-type Ti–45Nb-based alloy (96(Ti–45Nb)-4Ga, 92(Ti–45Nb)-8Ga (wt.%)) on corrosion and passive film properties, as well as cytocompatibility and antibacterial activity. The electrochemical properties were evaluated by potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and Mott-Schottky analyses in phosphate-buffered saline (PBS). X-ray photoelectron spectroscopy (XPS) was performed to analyze the chemical composition of passive films. Early adhesion and viability of macrophages and Staphylococcus aureus were assessed by nucleocounting and colony-forming unit counting, respectively. The results showed that high corrosion resistance and passive film properties of Ti–45Nb are retained and even slightly improved with Ga. EIS results revealed that Ga addition improves the passive film resistance. XPS measurements of 92(Ti–45Nb)-8Ga show that the passive film contains Ti-, Nb- and Ga-based oxides, implying the formation of mixed (Ti–Nb-Ga) oxides. In addition, marginal Ga ion release rate was detected under free corrosion conditions. Therefore, it can be assumed that Ga species may contribute to passive film formation on Ga-containing alloys. The 92(Ti–45Nb)-8Ga elicited an antibacterial effect against S. aureus compared to cp-Ti at 4 h. Moreover, Ga-containing alloys showed good cytocompatibility with THP-1 macrophages at 24 h. In conclusion, it was demonstrated that Ga additions to Ti–45Nb are beneficial to corrosion resistance and showed promising initial host and bacterial interactions

La composition corporelle des adolescentes. La mode et quelques répercussions cliniques

Les changements biologiques et psychologiques qui surviennent au moment de la croissance fragilisent l’enfant et peuvent favoriser des facteurs de risque durant cette période de maturation et dans sa future vie d’adulte. L’influence de la publicité et la pression sociale font naître, essentiellement chez les filles, un nouveau prototype corporel où l’extrême maigreur n’est plus l’exception comme c’était le cas dans les périodes précédentes. Pour détecter les possibles risques ou maladies causés par de telles modifications, 134 adolescentes de la ville de Madrid et de sa banlieue, âgées de 15 à 17 ans, ont été échantillonnées. Les participantes connaissaient les objectifs de l’étude et y ont participé volontairement avec le consentement parental. Deux sous-échantillons contrastés ont été comparés, en fonction de l’indice de masse corporelle (groupes au-dessous et au-dessus de la limite du dixième percentile somatique, soit IMC = 17). On constate une très basse ingestion de calories (900 Kcal/jours) pour les filles avec un IMC < 17, et une diminution de la proportion recommandée d’hydrates de carbone. On remarque également une prise alimentaire irrégulière et des comportements alimentaires à risque. La composition corporelle est modifiée par rapport aux normes habituelles chez la femme, ce qui pourrait être la cause de 77.7 % des aménorrhées et de l’androgénicité dans la distribution des graisses.The biological and psychological changes which occur during growth stages render children fragile, which can favour risk factors during the period of maturation as well as later on in adult life. The influence of advertising and social pressure is particularly strong in the case of girls, and a new prototype of body proportion has emerged in which extreme thinness is no longer the exception as it has been in previous periods. In order to detect the possible risks and diseases caused by such modifications, 134 adolescent girls in the city of Madrid and its outskirts, aged 15 to 17 years of age, were sampled. The participants understood the objectives of the study and participated voluntarily with parental consent. Two contrasting sub-samples were compared, according to the index of body mass (groups below and above the limit of the somatic tenth percentile, that is BMI = 17). A very low nutritional intake was observed (900 Kcal/day) for the girls with a BMI < 17, as well as a decrease in the recommended proportion of carbohydrates. Irregularity of food intake and risky food-related behaviours were noted. The body composition was modified in comparison to female body norms, which could be the cause of 77% of amenorrhoeas and of androgenicity in fat distribution

The Fennoscandian Shield deep terrestrial virosphere suggests slow motion 'boom and burst' cycles

The deep biosphere contains members from all three domains of life along with viruses. Here we investigate the deep terrestrial virosphere by sequencing community nucleic acids from three groundwaters of contrasting chemistries, origins, and ages. These viromes constitute a highly unique community compared to other environmental viromes and sequenced viral isolates. Viral host prediction suggests that many of the viruses are associated with Firmicutes and Patescibacteria, a superphylum lacking previously described active viruses. RNA transcript-based activity implies viral predation in the shallower marine water-fed groundwater, while the deeper and more oligotrophic waters appear to be in 'metabolic standby'. Viral encoded antibiotic production and resistance systems suggest competition and antagonistic interactions. The data demonstrate a viral community with a wide range of predicted hosts that mediates nutrient recycling to support a higher microbial turnover than previously anticipated. This suggests the presence of 'kill-the-winner' oscillations creating slow motion 'boom and burst' cycles. Karin Holmfeldt et al. sequence metagenomes and metatranscriptomes of viruses in deep groundwaters down to 448m below the surface. The results reveal ecological dynamics of viruses including slow motion 'boom and burst' cycles and a 'kill the winner' model potentially driven by viral predation

Heterologous adenovirus-vector/messenger RNA regimen is associated with improved severe acute respiratory syndrome coronavirus 2 humoral response in liver transplant recipients

Knowledge of the immunogenicity of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in liver transplant recipients (LTRs) is mainly limited to messenger RNA (mRNA)-based types. We aimed to evaluate the humoral response in LTRs and to address the use of different doses of mycophenolate (MMF) on the probability of developing anti-spike immunoglobulin G (IgG). In this prospective cohort study, SARS-CoV-2 anti-spike IgG, neutralizing antibodies (NAs), and nucleocapsid protein (N) were evaluated in LTRs and healthy volunteers 21–90 days after receiving the second vaccine dose of either ChAdOx1 (AstraZeneca), rAd26-rAd5 (Sputnik V), inactivated BBIBP-CorV (Sinopharm), or the heterologous combination rAd26/mRNA-1273 (Sputnik V/Moderna). We collected information regarding clinical data and vaccine side effects. After excluding three LTRs due to a positive N test, 120 LTRs and 27 controls were analyzed. No significant differences were found among groups. Overall, 24 (89%) controls and 74 (62%) LTRs were positive for anti-spike IgG (p = 0.007). Among LTRs, those immunized with rAd26/mRNA-1273 presented significantly higher positive serology and NAs when compared with the homologous regimens (91% vs. 55%, p = 0.001; and 1182 IU/ml vs. 446 IU/ml, p = 0.002; respectively). In the multivariate analysis, humoral response was significantly reduced in LTRs who received higher doses of MMF (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.03–0.3; p < 0.001) and with increased BMI (OR, 0.4; 95% CI, 0.2–0.7; p = 0.005); and it was significantly higher in those immunized with rAd26/mRNA-1273 (OR, 13.1; 95% CI, 2.3–72.9; p = 0.003). In LTRs anti-spike IgG concentrations showed a very good correlation with NA titers (R2 = 0.949; 95% CI, 0.919–0.967; p < 0.001). No serious adverse events were reported in either group. Conclusion: In LTRs, rAd26/mRNA-1273 was independently associated with higher antibody response. Future studies are necessary to evaluate whether combining different vaccine platforms and MMF reduction may lead to a better booster response.Fil: Mendizabal, Manuel. Universidad Austral; ArgentinaFil: Ducasa, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Benencio, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Anders, Margarita. Hospital Alemán; ArgentinaFil: Cairo, Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Barbero, Manuel. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Etcheves, Patricia. No especifíca;Fil: Alter, Adriana. Hospital Italiano; ArgentinaFil: Scarton, Giampaolo. No especifíca;Fil: Abraldes, Juan G.. University of Alberta; CanadáFil: Biglione, Mirna Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Mauro, Ezequiel. Hospital Italiano; Argentin

Population history, phylogeography, and conservation genetics of the last Neotropical mega-herbivore, the lowland tapir (Tapirus terrestris)

<p>Abstract</p> <p>Background</p> <p>Understanding the forces that shaped Neotropical diversity is central issue to explain tropical biodiversity and inform conservation action; yet few studies have examined large, widespread species. Lowland tapir (<it>Tapirus terrrestris</it>, Perissodactyla, Tapiridae) is the largest Neotropical herbivore whose ancestors arrived in South America during the Great American Biotic Interchange. A Pleistocene diversification is inferred for the genus <it>Tapirus </it>from the fossil record, but only two species survived the Pleistocene megafauna extinction. Here, we investigate the history of lowland tapir as revealed by variation at the mitochondrial gene Cytochrome <it>b</it>, compare it to the fossil data, and explore mechanisms that could have shaped the observed structure of current populations.</p> <p>Results</p> <p>Separate methodological approaches found mutually exclusive divergence times for lowland tapir, either in the late or in the early Pleistocene, although a late Pleistocene divergence is more in tune with the fossil record. Bayesian analysis favored mountain tapir (<it>T. pinchaque</it>) paraphyly in relation to lowland tapir over reciprocal monophyly, corroborating the inferences from the fossil data these species are sister taxa. A coalescent-based analysis rejected a null hypothesis of allopatric divergence, suggesting a complex history. Based on the geographic distribution of haplotypes we propose (<it>i</it>) a central role for western Amazonia in tapir diversification, with a key role of the ecological gradient along the transition between Andean subcloud forests and Amazon lowland forest, and (<it>ii</it>) that the Amazon river acted as an barrier to gene flow. Finally, the branching patterns and estimates based on nucleotide diversity indicate a population expansion after the Last Glacial Maximum.</p> <p>Conclusions</p> <p>This study is the first examining lowland tapir phylogeography. Climatic events at the end of the Pleistocene, parapatric speciation, divergence along the Andean foothill, and role of the Amazon river, have similarly shaped the history of other taxa. Nevertheless further work with additional samples and loci is needed to improve our initial assessment. From a conservation perspective, we did not find a correspondence between genetic structure in lowland tapir and ecogeographic regions proposed to define conservation priorities in the Neotropics. This discrepancy sheds doubt into this scheme's ability to generate effective conservation planning for vagile species.</p

Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping

Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases

‘Real-life’ experience with direct-acting antiviral agents for HCV after kidney transplant

Introductions and Objectives: The introduction of direct-acting antiviral (DAA) agents promises to change dramatically the management of hepatitis C in kidney transplant recipients, a patient group where the treatment of hepatitis C is historically challenging. The purpose of the current study was to assess (in a ‘real-life’ setting) the safety and efficacy of all-oral, interferon-free, direct-acting antiviral agents in kidney transplant recipients with HCV. Material and Methods: We performed a single-arm, multi-center study in a cohort (n = 95) of kidney transplant recipients who underwent antiviral therapy with DAAs. The primary end-point was sustained virologic response (SVR) (serum HCV RNA < 15 IU/mL, 12 weeks after treatment ended; SVR12). We recorded data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities. Results: Various regimens were adopted at the discretion of the treating physician: elbasvir/grazoprevir (n = 11), paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens ± ribavirin (n = 23), and sofosbuvirbased regimens ± ribavirin (n = 61). The SVR12 rate was 93.7% (89/95) (95% CI, 88%; 98%), according to intention-to-treat analysis; three patients without viral response (n = 3) were found. Ribavirin was administered in 8 (8.4%) allograft recipients. The frequency of drop-outs was 4.2% (4/95) (95% CI, 0.2%; 8.2%); these were related to arthralgia/myalgia (n = 2), fatigue (n = 1), and lowered estimated glomerular filtration rate (eGFR) (n = 1). There were no differences with regard to serum creatinine and eGFR before and after antiviral therapy and during follow-up in the whole cohort. The patient who interrupted antiviral treatment due to raised serum creatinine was on sofosbuvir/daclatasvir regimen; one of the four dropouts obtained SVR. Conclusions: All-oral, interferon-free therapy with DAAs for chronic HCV after kidney transplantation was effective and well-tolerated in a ‘real–life’ clinical setting. Identical results have been observed in patients with intact kidneys or advanced chronic kidney disease. Careful evaluation of kidney function over follow-up in kidney transplant recipients who received DAAs regimens is recommended. Clinical trials aimed to assess whether sustained viral response translates into improved patient/graft survival are under way