Pilot study of 10-year absolute fracture risk assessment tool (FRAX®) introduction into the structure of undegraduate practical training "physician assistant” course

Background: high fracture rates throughout the Eastern Europe and Central Asia region have been reported. Major fractures rate increasing, primary care physicians need to be aware of risk assessment and prevention tools. Aims: The aim of this pilot study was to assess main issues of FRAX tool introduction into undergraduate medical education. Material and methods: Russian version of the IOF approved presentation on FRAX application procedure, results assessment and interpretation as well as Russian Association for Osteoporosis clinical guidelines and reference to www.osteoporoz.ru site have been provided to 248 undergraduate medical students. To increase osteoporosis related issues study motivation the students were asked to apply the Russian version of on-line FRAX calculator to assess risk fracture in their close relatives of appropriate age. Also the students were asked to create a FRAX assessment based patient management program. Results: 207 FRAX assessment reports were received as feedback. Derived intervention threshold was reached in 41 cases (19.8%), while in 45 reports (21.7%) body mass index (BMI) value was mistaken for a 10-year fracture risk. There were 123 cases of the students parents assessments. These subjects appeared to be quite young (median 48, range 42 62) and relatively healthy to report no fracture risk factors. The students grandparents or great-grandparents (68 cases) were assessed on rare occasions due to lack of information or absence of personal contacts between students and their relatives. The students reported appreciable difficulties in decision making. Lifestyle and diet modification were not included in 165 of recommendations, while calcium and vitamin D prescriptions were severely biased by TV advertising. The students reported that it was quite difficult for them to give the patients recommendations regarding the choice of drug and administration timeframe. Conclusion: pilot study of FRAX introduction into undergraduate medical education helped to ascertain several gaps in teaching of osteoporosis diagnosis, prevention and treatment to be covered during undergraduate medical educatio

Boron Influence on Defect Structure and Properties of Lithium Niobate Crystals

Defect structure of nominally pure lithium niobate crystals grown from a boron doped charge have been studied by Raman and optical spectroscopy, laser conoscopy, and photoinduced light scattering. An influence of boron dopant on optical uniformity, photoelectrical fields values, and band gap have been also studied by these methods in LiNbO3 crystals. Despite a high concentration of boron in the charge (up to 2 mol%), content in the crystal does not exceed 10−4 wt%. We have calculated that boron incorporates only into tetrahedral voids of crystal structure as a part of groups [BO3]3−, which changes O–O bonds lengths in O6 octahedra. At this oxygen–metal clusters MeO6 (Me: Li, Nb) change their polarizability. The clusters determine optically nonlinear and ferroelectric properties of a crystal. Chemical interactions in the system Li2O–Nb2O5–B2O3 have been considered. Boron, being an active element, structures lithium niobate melt, which significantly influences defect structure and physical properties of a crystal grown from such a melt. At the same time, amount of defects NbLi and concentration of OH groups in LiNbO3:B is close to that in stoichiometric crystals; photorefractive effect, optical, and compositional uniformity on the contrary is higher

Healthcare- and Community-Associated Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA) and Fatal Pneumonia with Pediatric Deaths in Krasnoyarsk, Siberian Russia: Unique MRSA's Multiple Virulence Factors, Genome, and Stepwise Evolution

<div><p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a common multidrug-resistant (MDR) pathogen. We herein discussed MRSA and its infections in Krasnoyarsk, Siberian Russia between 2007 and 2011. The incidence of MRSA in 3,662 subjects was 22.0% and 2.9% for healthcare- and community-associated MRSA (HA- and CA-MRSA), respectively. The 15-day mortality rates for MRSA hospital- and community-acquired pneumonia (HAP and CAP) were 6.5% and 50%, respectively. MRSA CAP cases included pediatric deaths; of the MRSA pneumonia episodes available, ≥27.3% were associated with bacteremia. Most cases of HA-MRSA examined exhibited ST239/<i>spa</i>3(t037)/SCC<i>mec</i>III.1.1.2 (designated as ST239_Kras), while all CA-MRSA cases examined were ST8/<i>spa</i>1(t008)/SCC<i>mec</i>IV.3.1.1(IVc) (designated as ST8_Kras). ST239_Kras and ST8_Kras strongly expressed cytolytic peptide (phenol-soluble modulin α, PSMα; and δ-hemolysin, Hld) genes, similar to CA-MRSA. ST239_Kras pneumonia may have been attributed to a unique set of multiple virulence factors (MVFs): toxic shock syndrome toxin-1 (TSST-1), elevated PSMα/Hld expression, α-hemolysin, the staphylococcal enterotoxin SEK/SEQ, the immune evasion factor SCIN/SAK, and collagen adhesin. Regarding ST8_Kras, SEA was included in MVFs, some of which were common to ST239_Kras. The ST239_Kras (strain OC3) genome contained: a completely unique phage, φSa7-like (W), with no <i>att</i> repetition; <i>S</i>. <i>aureus</i> pathogenicity island SaPI2R, the first TSST-1 gene-positive (<i>tst</i>⁺) SaPI in the ST239 lineage; and a super copy of IS<i>256</i> (≥22 copies/genome). ST239_Kras carried the Brazilian SCC<i>mec</i>III.1.1.2 and United Kingdom-type <i>tst</i>. ST239_Kras and ST8_Kras were MDR, with the same levofloxacin resistance mutations; small, but transmissible chloramphenicol resistance plasmids spread widely enough to not be ignored. These results suggest that novel MDR and MVF⁺ HA- and CA-MRSA (ST239_Kras and ST8_Kras) emerged in Siberian Russia (Krasnoyarsk) associated with fatal pneumonia, and also with ST239_Kras, a new (Siberian Russian) clade of the ST239 lineage, which was created through stepwise evolution during its potential transmission route of Brazil-Europe-Russia/Krasnoyarsk, thereby selective advantages from unique MVFs and the MDR.</p></div

Analysis of the <i>tst</i>⁺ SaPI (SaPI2R) structure and <i>tst</i> nucleotide and deduced amino acid sequences of the ST239_Kras strain OC3.

<p>In A, the integration site (<i>att</i>) and <i>att</i> sequences of SaPI2R of the ST239_Kras strain OC3 are shown. In B, the SaPI2R structure was compared with those of <i>tst</i>^- SaPI (ATCC25923) and <i>tst</i>⁺ SaPI2 (RN3984). Homologous regions between SaPI structures are shaded with color. Genes: <i>tst</i>, toxic shock syndrome toxin-1 gene; <i>eta</i>, <i>S</i>. <i>hyicus</i> exfoliatin A gene; <i>ter</i>, terminase gene (which cleaves multimeric DNA); <i>rep</i>, replication initiator gene; <i>int</i>, the integrase gene. In C, the nucleotide sequences of <i>tst</i>⁺ SaPIs and <i>tst</i>^- SaPI (ATCC25923) were analyzed for phylogenetic diversity. In D-a, the nucleotide sequences of the <i>tst</i> genes were analyzed for phylogenetic diversity. In this figure, each GenBank record year is also shown. In D-b, the deduced amino acid sequences of the <i>tst</i> gene products were analyzed for phylogenetic diversity. The origin (reported source) of each isolate is indicated by the color of the isolate name: red, Russia; yellow, United Kingdom (UK); blue, United States (USA); dark red, Korea; light blue, Argentine; purple, Japan; green, those for animal isolates. In C and D, the scale bar represents substitutions per single-nucleotide polymorphism site. In E, the representative <i>tst</i> gene sequences were compared with the reference sequences (of pRN6100). Arrows indicate the positions of the nucleotide and amino acid changes for the representative <i>tst</i> genes. At the bottom of the figure (green), different amino acids from the amino acid sequences of purified TSST-1 (MN8; GenBank accession number EFH95768) and the deduced amino acid sequence of the <i>tst</i> gene (pRN6100) are indicated in red letters.</p

Genome information for the ST239_Kras strain OC3, in comparison with the ST239 MRSA strain TW20.

<p>The ST239_Kras OC3 genome contigs (including filled contigs and complete structures; total 2.91-Mb) were mapped on the 3,043,210-bp TW20 genome (GenBank accession number FN433596); in the figure, the two genome structures were drawn as two circles on a common genome map, outside OC3 and inside TW20. Genome information included staphylococcal cassette chromosome <i>mec</i> (SCC<i>mec</i>), other drug resistance structures (such as a transposon, Tn, plasmid-related structure, and gene mutations), characteristic virulence genes, phages, <i>S</i>. <i>aureus</i> pathogenicity islands (SaPIs), genomic islands (νSa), and characteristic insertion sequences (ISs). SCC<i>mec</i>: SCC<i>mec</i>IIIA (in OC3), SCC<i>mec</i>III.1.1.2; SCC<i>mec</i>III (in TW20), SCC<i>mec</i>III.1.1.1 connected to SCC<i>Hg</i>. Drug resistance (gene mutations): Lvx^r, levofloxacin resistance; Rif^r, rifampicin resistance; Su^r, sulfamethoxazole resistance. Virulence genes (region): <i>tst</i>, toxic shock syndrome toxin-1 gene; <i>hld</i>, δ-hemolysin gene; <i>cna</i>, collagen adhesin gene; <i>spa</i>, protein A gene; <i>psmα</i>, phenol-soluble modulin (PSM) gene; <i>hla</i>, α-hemolysin (α-toxin) gene; IEC, immune evasion cluster. The CC30 and CC8 genome sections are from Holden <i>et al</i>. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128017#pone.0128017.ref019" target="_blank">19</a>], and the genetic element IEC<i>6013</i> is from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128017#pone.0128017.ref060" target="_blank">60</a>]. The plasmid pOC3 (2,908 bp; contig 75) of strain OC3 is not shown in the figure. The location of pSK41-related structure (with two IS<i>431</i> repeats at both ends) currently remains uncertain.</p

SCC<i>mec</i>III.1.1.2 structure of the ST239_Kras strain OC3, in comparison with the three structures: SCC<i>Hg</i>/SCC<i>mec</i>III.1.1.1 of the strain TW20, SCC<i>mec</i>III.1.1.2 of the strain HU25, and SCC<i>mec</i>III.1.1.4 of the strain 16K.

<p>Isolation of ST239 strains: OC3, Krasnoyarsk; TW20, London; HU25, Brazil; 16K, Vladivostok. Homologous regions are shaded in each comparison. In A, when compared with SCC<i>Hg</i>/SCC<i>mec</i>III.1.1.1 (of TW20), SCC<i>mec</i>III.1.1.2 (of OC3 and HU25) lacked the middle IS<i>431②</i>-IS<i>431</i>④ region. The J3 region of SCC<i>mec</i>III.1.1.2 corresponded to the bulk of SCC<i>Hg</i>. SCC<i>mec</i>III.1.1.4 (of 16K) lacked SCC<i>Hg</i>. In B, the primer set Hgreg (F)/attM (R) detected <i>attM</i>, and the primer set Hgreg (F)/rec2/4 (R) identified recombination between IS<i>431</i> copies ② and ④.</p

Pulsed-field gel electrophoresis (PFGE) analysis (right and left) and plasmid carriage patterns (center) of MRSA strains isolated in Krasnoyarsk.

<p>The MRSA strains shown are those described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128017#pone.0128017.t002" target="_blank">Table 2</a>. Group A (A1 and A2) and group B are described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128017#pone.0128017.t003" target="_blank">Table 3</a>. The color of the strain name indicates fatal pneumonia (red), possible sepsis (brown), and carrier cases (green). Of the cases of fatal pneumonia, OC3, OC8C, OC11, OC76 were from hospital-acquired pneumonia (HAP), while OC8, OC22, OC23, and OC59 were from community-acquired pneumonia (CAP). Of the carrier cases, OC14C and OC52 were from hospital workers and OC217 was from a student.</p

Structure of a phage φSa7-like (W) of the ST239_Kras strain OC3.

<p>φSa7-like (W) was compared with φSa7 of the strain Newman for the phage structure, the integration site (<i>att</i>) sequence, and integration site. Homologous regions are shaded in the comparison. The figure at the lower right side indicates each integration site on the <i>S</i>. <i>aureus</i> chromosome. The target huNaDC-1 sequence of φSa7-like (W), shown at the top of the figure (in blue and purple), was also present in the huNaDC-1 gene of other <i>S</i>. <i>aureus</i> strains.</p