Correlation of the Subjective Hip Value with Validated Patient-Reported Outcome Measurements for the Hip

Background: The subjective hip value (SHV) was developed as a patient-reported outcome measurement (PROM) that is easily and quickly performed and interpreted. The SHV is defined as a patient's subjective hip measurement tool expressed as a percentage of an entirely normal hip joint, which would score 100%. The hypothesis is that results of the subjective hip value correlate with the results of the modified Harris hip score and the International Hip Outcome Tool in patients with hip-related diseases. Methods: 302 patients completed the modified Harris hip score (mHHS), the International Hip Outcome Tool (iHot-33) as well as the SHV. The SHV consist of only one question: "What is the overall percent value of your hip if a completely normal hip represents 100%?". The patients were divided into five different groups depending on the diagnosis. Pearson correlation was used to evaluate the correlation between the different PROMs and linear regression analysis was used to calculate R2. Results: 302 complete datasets were available for evaluation. There was a high correlation between the SHV and the iHOT-33 (r = 0.847; r2 = 0.692, p < 0.001) and the mHHS (r = 0.832; r2 = 0.717, p < 0.001). The SHV showed a medium (r = 0.653) to high (r = 0.758) correlation with the mHHS and the iHOT-33 in all diagnosis groups. Conclusion: The SHV offers a useful adjunct to established hip outcome measurements, as it is easily and quickly performed and interpreted. The SHV reflects the view of the patient and is independent of the diagnosis. Further research with prospective studies is needed to test the psychometric properties of the score

The C-terminal α–α superhelix of Pat is required for mRNA decapping in metazoa

Pat proteins regulate the transition of mRNAs from a state that is translationally active to one that is repressed, committing targeted mRNAs to degradation. Pat proteins contain a conserved N-terminal sequence, a proline-rich region, a Mid domain and a C-terminal domain (Pat-C). We show that Pat-C is essential for the interaction with mRNA decapping factors (i.e. DCP2, EDC4 and LSm1–7), whereas the P-rich region and Mid domain have distinct functions in modulating these interactions. DCP2 and EDC4 binding is enhanced by the P-rich region and does not require LSm1–7. LSm1–7 binding is assisted by the Mid domain and is reduced by the P-rich region. Structural analysis revealed that Pat-C folds into an α–α superhelix, exposing conserved and basic residues on one side of the domain. This conserved and basic surface is required for RNA, DCP2, EDC4 and LSm1–7 binding. The multiplicity of interactions mediated by Pat-C suggests that certain of these interactions are mutually exclusive and, therefore, that Pat proteins switch decapping partners allowing transitions between sequential steps in the mRNA decapping pathway

Klinische, kontrollierte, prospektive Kohortenstudie zur Untersuchung der Effektivität einer azellulären dreidimensionalen Kollagenmatrix zur Verdickung der fazialen Mukosa nach Sofortimplantation

Connective tissue grafts have become a standard for compensating horizontal volume loss in immediate implant placement. The use of new biomaterials like acellular matrices may avoid the need to harvest autogenous grafts, yielding less postoperative morbidity. This randomized comparative study evaluated the clinical outcomes following extraction and immediate implant placement in conjunction with anorganic bovine bone mineral (ABBM) and the use of a porcine acellular dermal matrix (ADM) vs an autogenous connective tissue graft (CTG) in the anterior maxilla. Twenty patients (11 men, 9 women) with a mean age of 48.9 years (range: 21 to 72 years) were included in the study and randomly assigned to either the test (ADM) or control (CTG) group. They underwent tooth extraction and immediate implant placement together with ABBM for socket grafting and either ADM or CTG for soft tissue augmentation. Twelve months after implant placement, the cases were evaluated clinically and volumetrically. All implants achieved osseointegration and were restored. The average horizontal change of the ridge dimension at 1 year postsurgery was –0.55 ± 0.32 mm for the ADM group and –0.60 ± 0.49 mm for the CTG group. Patients of the ADM group reported significantly less postoperative pain. Using xenografts for hard and soft tissue augmentation in conjunction with immediate implant placement showed no difference in the volume change in comparison to an autogenous soft tissue graft, and showed significantly less postoperative morbidity. Int J Periodontics Restorative Dent 2022;42:381–390. doi: 10.11607/prd.563

Reconciling the Greenland ice-core and radiocarbon timescales through the Laschamp geomagnetic excursion

Cosmogenic radionuclides, such as 10Be and 14C, share a common production signal, with their formation in the Earth's upper atmosphere modulated by changes to the geomagnetic field, as well as variations in the intensity of the solar wind. Here, we use this common production signal to compare between the radiocarbon (IntCal) and Greenland ice-core (GICC05) timescales, utilising the most pronounced cosmogenic production peak of the last 100,000 years – that associated with the Laschamp geomagnetic excursion circa 41,000 years ago. We present 54 new 14C measurements from a peat core (‘TP-2005’) from Tenaghi Philippon, NE Greece, contiguously spanning between circa 47,300 and 39,600 cal. BP, demonstrating a distinctive tripartite structure in the build up to the principal Laschamp production maximum that is not present in the consensus IntCal13 calibration curve. This is the first time that a continuous, non-reservoir corrected 14C dataset has been generated over such a long time span for this, the oldest portion of the radiocarbon timescale. This period is critical for both palaeoenvironmental and archaeological applications, with the replacement of Neanderthals by anatomically modern humans in Europe around this time. By placing our Tenaghi Philippon 14C dataset on to the Hulu Cave U-series timescale of Cheng et al. (2018) via Bayesian statistical modelling, the comparison of TP-2005 14C with Greenland 10Be fluxes also implicitly relates the underlying U-series and GICC05 timescales themselves. This comparison suggests that whilst these two timescales are broadly coherent, the IntCal13 timescale contains erroneous structure circa 40,000 cal. BP

Comparative genomics of Mycoplasma feriruminatoris, a fast-growing pathogen of wild Caprinae.

Mycoplasma feriruminatoris is a fast-growing Mycoplasma species isolated from wild Caprinae and first described in 2013. M. feriruminatoris isolates have been associated with arthritis, kerato conjunctivitis, pneumonia and septicemia, but were also recovered from apparently healthy animals. To better understand what defines this species, we performed a genomic survey on 14 strains collected from free-ranging or zoo-housed animals between 1987 and 2017, mostly in Europe. The average chromosome size of the M. feriruminatoris strains was 1,040±0,024 kbp, with 24 % G+C and 852±31 CDS. The core genome and pan-genome of the M. feriruminatoris species contained 628 and 1312 protein families, respectively. The M. feriruminatoris strains displayed a relatively closed pan-genome, with many features and putative virulence factors shared with species from the M. mycoides cluster, including the MIB-MIP Ig cleavage system, a repertoire of DUF285 surface proteins and a complete biosynthetic pathway for galactan. M. feriruminatoris genomes were found to be mostly syntenic, although repertoires of mobile genetic elements, including Mycoplasma Integrative and Conjugative Elements, insertion sequences, and a single plasmid varied. Phylogenetic- and gene content analyses confirmed that M. feriruminatoris was closer to the M. mycoides cluster than to the ruminant species M. yeatsii and M. putrefaciens. Ancestral genome reconstruction showed that the emergence of the M. feriruminatoris species was associated with the gain of 17 gene families, some of which encode defence enzymes and surface proteins, and the loss of 25 others, some of which are involved in sugar transport and metabolism. This comparative study suggests that the M. mycoides cluster could be extended to include M. feriruminatoris. We also find evidence that the specific organization and structure of the DnaA boxes around the oriC of M. feriruminatoris may contribute to drive the remarkable fast growth of this minimal bacterium

Host Species Restriction of Middle East Respiratory Syndrome Coronavirus through Its Receptor, Dipeptidyl Peptidase 4

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and ferret cells enabled MERS-CoV replication, whereas expression of hamster or ferret DPP4 did not. Modeling the binding energies of MERS-CoV spike protein RBD to DPP4 of human (susceptible) or hamster (nonsusceptible) identified five amino acid residues involved in the DPP4-RBD interaction. Expression of hamster DPP4 containing the five human DPP4 amino acids rendered BHK cells susceptible to MERS-CoV, whereas expression of human DPP4 containing the five hamster DPP4 amino acids did not. Using the same approach, the potential of MERS-CoV to utilize the DPP4s of common Middle Eastern livestock was investigated. Modeling of the DPP4 and MERS-CoV RBD interaction predicted the ability of MERS-CoV to bind the DPP4s of camel, goat, cow, and sheep. Expression of the DPP4s of these species on BHK cells supported MERS-CoV replication. This suggests, together with the abundant DPP4 presence in the respiratory tract, that these species might be able to function as a MERS-CoV intermediate reservoir

Genomic Characterization and Antimicrobial Susceptibility of Dromedary-Associated Staphylococcaceae from the Horn of Africa.

Members of the Staphylococcaceae family, particularly those of the genus Staphylococcus, encompass important human and animal pathogens. We collected and characterized Staphylococcaceae strains from apparently healthy and diseased camels (n = 84) and cattle (n = 7) in Somalia and Kenya. We phenotypically characterized the strains, including their antimicrobial inhibitory concentrations. Then, we sequenced their genomes using long-read sequencing, closed their genomes, and subsequently compared and mapped their virulence- and resistance-associated gene pools. Genome-based phylogenetics revealed 13 known Staphylococcaceae and at least two novel species. East African strains of different species encompassed novel sequence types and phylogenetically distant clades. About one-third of the strains had non-wild-type MICs. They were resistant to at least one of the following antimicrobials: tetracycline, benzylpenicillin, oxacillin, erythromycin, clindamycin, trimethoprim, gentamicin, or streptomycin, encoded by tet(K), blaZ/blaARL, mecA/mecA1, msrA/mphC, salA, dfrG, aacA-aphD, and str, respectively. We identified the first methicillin- and multidrug-resistant camel S. epidermidis strain of sequence type (ST) 1136 in East Africa. The pool of virulence-encoding genes was largest in the S. aureus strains, as expected, although other rather commensal strains contained distinct virulence-encoding genes. We identified toxin-antitoxin (TA) systems such as the hicA/hicB and abiEii/abiEi families, reported here for the first time for certain species of Staphylococcaceae. All strains contained at least one intact prophage sequence, mainly belonging to the Siphoviridae family. We pinpointed potential horizontal gene transfers between camel and cattle strains and also across distinct Staphylococcaceae clades and species. IMPORTANCE Camels are a high value and crucial livestock species in arid and semiarid regions of Africa and gain importance giving the impact of climate change on traditional livestock species. Our current knowledge with respect to Staphylococcaceae infecting camels is very limited compared to that for other livestock species. Better knowledge will foster the development of specific diagnostic assays, guide promising antimicrobial treatment options, and inform about potential zoonotic risks. We characterized 84 Staphylococcaceae strains isolated from camels with respect to their antimicrobial resistance and virulence traits. We detected potentially novel Staphylococcus species, resistances to different classes of antimicrobials, and the first camel multidrug-resistant S. epidermidis strain of sequence type 1136

In utero undernutrition in male mice programs liver lipid metabolism in the second-generation offspring involving altered lxra DNA methylation

SummaryObesity and type 2 diabetes have a heritable component that is not attributable to genetic factors. Instead, epigenetic mechanisms may play a role. We have developed a mouse model of intrauterine growth restriction (IUGR) by in utero malnutrition. IUGR mice developed obesity and glucose intolerance with aging. Strikingly, offspring of IUGR male mice also developed glucose intolerance. Here, we show that in utero malnutrition of F1 males influenced the expression of lipogenic genes in livers of F2 mice, partly due to altered expression of Lxra. In turn, Lxra expression is attributed to altered DNA methylation of its 5′ UTR region. We found the same epigenetic signature in the sperm of their progenitors, F1 males. Our data indicate that in utero malnutrition results in epigenetic modifications in germ cells (F1) that are subsequently transmitted and maintained in somatic cells of the F2, thereby influencing health and disease risk of the offspring

Mapping of the DLQI scores to EQ-5D utility values using ordinal logistic regression

Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://crea tivecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Purpose: The Dermatology Life Quality Index (DLQI) and the European Quality of Life-5 Dimension (EQ-5D) are separate measures that may be used to gather health-related quality of life (HRQoL) information from patients. The EQ-5D is a generic measure from which health utility estimates can be derived, whereas the DLQI is a specialty-specific measure to assess HRQoL. To reduce the burden of multiple measures being administered and to enable a more disease-specific calculation of health utility estimates, we explored an established mathematical technique known as ordinal logistic regression (OLR) to develop an appropriate model to map DLQI data to EQ-5D-based health utility estimates. Methods: Retrospective data from 4010 patients were randomly divided five times into two groups for the derivation and testing of the mapping model. Split-half cross-validation was utilized resulting in a total of ten ordinal logistic regression models for each of the five EQ-5D dimensions against age, sex, and all ten items of the DLQI. Using Monte Carlo simulation, predicted health utility estimates were derived and compared against those observed. This method was repeated for both OLR and a previously tested mapping methodology based on linear regression. Results: The model was shown to be highly predictive and its repeated fitting demonstrated a stable model using OLR as well as linear regression. The mean differences between OLR-predicted health utility estimates and observed health utility estimates ranged from 0.0024 to 0.0239 across the ten modeling exercises, with an average overall difference of 0.0120 (a 1.6% underestimate, not of clinical importance). Conclusions: This modeling framework developed in this study will enable researchers to calculate EQ-5D health utility estimates from a specialty-specific study population, reducing patient and economic burden.Peer reviewedFinal Published versio

Diamond nano-pillar arrays for quantum microscopy of neuronal signals

Modern neuroscience is currently limited in its capacity to perform long term, wide-field measurements of neuron electromagnetics with nanoscale resolution. Quantum microscopy using the nitrogen vacancy centre (NV) can provide a potential solution to this problem with electric and magnetic field sensing at nano-scale resolution and good biocompatibility. However, the performance of existing NV sensing technology does not allow for studies of small mammalian neurons yet. In this paper, we propose a solution to this problem by engineering NV quantum sensors in diamond nanopillar arrays. The pillars improve light collection efficiency by guiding excitation/emission light, which improves sensitivity. More importantly, they also improve the size of the signal at the NV by removing screening charges as well as coordinating the neuron growth to the tips of the pillars where the NV is located. Here, we provide a growth study to demonstrate coordinated neuron growth as well as the first simulation of nano-scopic neuron electric and magnetic fields to assess the enhancement provided by the nanopillar geometry.Comment: 18 pages including supplementary and references, 12 figure