Development of a Metric for Predicting Brain Strain Responses Using Head Kinematics

Diffuse brain injuries are caused by excessive brain deformation generated primarily by rapid rotational head motion. Metrics that describe the severity of brain injury based on head motion often do not represent the governing physics of brain deformation, rendering them ineffective over a broad range of head impact conditions. This study develops a brain injury metric based on the response of a second-order mechanical system, and relates rotational head kinematics to strain-based brain injury metrics: maximum principal strain (MPS) and cumulative strain damage measure (CSDM). This new metric, universal brain injury criterion (UBrIC), is applicable over a broad range of kinematics encountered in automotive crash and sports. Efficacy of UBrIC was demonstrated by comparing it to MPS and CSDM predicted in 1600 head impacts using two different finite element (FE) brain models. Relative to existing metrics, UBrIC had the highest correlation with the FE models, and performed better in most impact conditions. While UBrIC provides a reliable measurement for brain injury assessment in a broad range of head impact conditions, and can inform helmet and countermeasure design, an injury risk function was not incorporated into its current formulation until validated strain-based risk functions can be developed and verified against human injury data.     

Insecticidal activity of essential oils from native medicinal plants of Central Argentina against the house fly, <Emphasis Type="Italic">Musca domestica</Emphasis> (L.)

The insecticidal activity of nine essential oils (EOs) against the house fly (Musca domestica) was evaluated by placing flies in a screw-cap glass jar holding a piece of EO-treated cotton yarn. The dose necessary to kill 50% of flies (LC₅₀) in 30 min was determined at 26?±?1°C. The EOs showed LC₅₀ values ranging from 0.5 to 46.9 mg/dm³. The EO from Minthostachys verticillata was the most potent insecticide (LC₅₀?=?0.5 mg/dm³) followed by EOs from Hedeoma multiflora (LC₅₀?=?1.3 mg/dm³) and Artemisia annua (LC₅₀?=?6.5 mg/dm³). The compositions of the nine EOs, obtained by hydrodistillation of medicinal herbs, were analyzed by gas chromatography/mass spectroscopy. These analyses showed that (4R)(+)-pulegone (69.70%), menthone (12.17%), and limonene (2.75%) were the principal components of M. verticillata EO. (4R)(+)-pulegone was also the main constituent (52.80%) of H. multiflora, while artemisia ketone (22.36%) and 1,8-cineole (16.67%) were the major constituents of A. annua EO. The terpene (4R)(+)-pulegone showed a lower toxicity (LC₅₀?=?1.7 mg/dm³) than M. verticillata or H. multiflora EOs. Dimethyl 2,2-dichlorovinyl phosphate, selected as a positive control, showed an LC₅₀ of 0.5 mg/dm³. EOs from M. verticillata and H. multiflora show promise as natural insecticides against houseflies.     

Synthesis of two potential NK<Subscript>1</Subscript>-receptor ligands using [1-<Superscript>11</Superscript>C]ethyl iodide and [1-<Superscript>11</Superscript>C]propyl iodide and initial PET-imaging

Background

The previously validated NK₁-receptor ligand [O-methyl-¹¹C]GR205171 binds with a high affinity to the NK₁-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK₁-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK₁-receptor ligands with chemical structures based on [O-methyl-¹¹C]GR205171.

Methods

[1-¹¹C]Ethyl and [1-¹¹C]propyl iodide with specific radioactivities of 90 GBq/μmol and 270 GBq/μmol, respectively, were used in the synthesis of [O-methyl-¹¹C]GR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained (2S,3S)-N-(1-(2- [1-¹¹C]ethoxy-5-(3-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)phenyl)ethyl)-2-phenylpiperidin-3-amine (I) and (2S,3S)-2-phenyl-N-(1-(2- [1-¹¹C]propoxy-5-(3-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)phenyl)ethyl)piperidin-3-amine (II) was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of [O-methyl-¹¹C]GR205171.

Results

All ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that (II) had no specific binding in striatum. Ligand (I) had moderate specific binding compared to the [O-methyl-¹¹C]GR205171. The ethyl analogue (I) displayed reversible binding characteristics contrary to the slow dissociation rate shown by [O-methyl-¹¹C]GR205171.

Conclusion

The propyl-analogue (II) cannot be used for detecting changes in NK₁-ligand levels, while further studies should be performed with the ethyl-analogue (I).

     

<Emphasis Type="Italic">Slc11a1</Emphasis> (<Emphasis Type="Italic">Nramp</Emphasis>-<Emphasis Type="Italic">1</Emphasis>) gene modulates immune-inflammation genes in macrophages during pristane-induced arthritis in mice

Objective and design

Pristane-induced arthritis (PIA) in AIRmax mice homozygous for Slc11a1 R and S alleles was used to characterize the influence of Slc11a1 gene polymorphism on immune responses during disease manifestation. Previous reports demonstrated that the presence of the Slc11a1 S allele increased the incidence and severity of PIA in AIRmax ^SS , suggesting that this gene could interact with inflammatory loci to modulate PIA. We investigated the effects of Slc11a1 alleles on the activation of phagocytes during PIA.

Treatment

Mice were injected intraperitoneally with two doses of 0.5 mL of mineral oil pristane at 60-day intervals. Arthritis development was accompanied for 180 days.

Results

AIRmax ^SS mice showed differential peritoneal macrophage gene expression profiles during PIA, with higher expression and production of H₂O₂, NO, IL-1β, IL-6, TNF-α, and several chemokines. The presence of the Slc11a1 R allele, on the other hand, diminished the intensity of macrophage activation, restricting arthritis development.

Conclusion

Our data demonstrated the fine-tuning roles of Slc11a1 alleles modulating macrophage activation, and consequent PIA susceptibility, in those mouse lines.

     

Mechanics of porcine coronary arteries<Emphasis Type="Italic">ex vivo</Emphasis> employing impedance planimetry: A new intravascular technique

Our objective was to evaluate methodological aspects of impedance planimetry, a new balloon catheter-based technique, for the investigation of coronary artery mechanical wall properties. We used a four ring-electrode electrical impedance measuring system that was located inside a balloon. Two of the electrodes were used for excitation and connected to a generator producing a constant alternating current of 250 mA at 5 kHz. The other two electrodes for detection were placed midway between the excitation electrodes. The balloon was distended with electrically conducting fluid through an infusion channel. The vessel cross-sectional area (CSA) was measured according to the field gradient principle by measuring the impedance of the fluid inside the balloon. Impedance planimetry was applied in the three major branches of the coronary arteries of seven extracted porcine hearts to assess luminal CSAs in response to internal pressurization. The biomechanical wall properties were evaluated by computing the strain [(r?r ₀)·r ₀ ^?1, wherer is the vessels inner radius computed as (CSA · π^?1)^½ andr ₀ is the radius of the vessel at a minimal distension pressure], the tension [(r·dP), wheredP is the transmural pressure difference], and the pressure elastic modulus (ΔP·r·Δr ^?1). We found thatin vitro testing demonstrated that impedance planimetry was accurate and reproducible. The technique has controllable sources of crror. Measurements were performed with consecutively increasing pressures in the range 1–25 kPa (8–188 mmHg, 0.01–0.25 atm). The CSAs increased nonlinearly and were significantly larger in the left anterior descendent coronary artery (LAD) (1 kPa, mean 5.0 mm²; 25 kPa, mean 21.8 mm²) than in both the left circumflex (Cx) (4.5–16.0 mm²) and the right coronary artery (RCA) (2.8–15.6 mm²) (analysis of variance,P<0.001 for both). The circumferential wall tension-strain relation showed exponential behavior. For a given strain, tension values for LAD were significantly lower than those of Cx (P<0.01). The pressure elastic modulus-strain relation also was exponential, and values for Cx were significantly lower than values for LAD (P<0.001) and RCA (P<0.05). Impedance planimetry was applied to the study of coronary artery biomechanicsex vivo. The LAD had the largest CSA, and the Cx was the least compliant. Methodological aspects of anin vivo introduction of the method require additional evaluation.     

Age has a Minimal Effect on the Impact Performance of Field-Used Bicycle Helmets

Helmet manufacturers recommend replacing a bicycle helmet after an impact or after anywhere from 2 to 10 years of use. The goal of this study was to quantify the effect of helmet age on peak headform acceleration during impact attenuation testing of field-used bicycle helmets. Helmets were acquired by donation from consumers and retail stores, and were included in the study if they were free of impact-related damage, had a legible manufacture date label, and were certified to at least one helmet standard. Helmets (n = 770) spanning 0–26 years old were drop tested to measure peak linear headform acceleration during impacts to the right and left front regions of the helmets at two impact speeds (3.0 and 6.2 m/s). General linear mixed models were used to assess the effect of age and three covariates (helmet style, size and certification impact speed) on peak acceleration. Overall, age was related to either no difference or a statistically significant but small increase (≤0.76 g/year of helmet age) in peak headform acceleration. Extrapolated across 20 years, age-related differences were less than both style- (traditional vs. BMX) and size-related differences. The age-related differences were also less than the variability observed between different helmets after accounting for style, size and certification effects. These findings mean that bicycle helmets (up to 26-year-old traditional helmets and 13-year-old BMX helmets) do not lose their ability to attenuate impacts with age; however, other helmet features that may change with age were not evaluated in this study.     

Distinct Early Inflammatory Events during Ear Tissue Regeneration in Mice Selected for High Inflammation Bearing S<Emphasis Type="Italic">lc11a1 R</Emphasis> and <Emphasis Type="Italic">S</Emphasis> Alleles

High inflammatory AIRmax mice homozygous for Slc11a1 R and S alleles were produced. AIRmax ^SS mice showed faster ear tissue regeneration than AIRmax ^RR mice, suggesting that the S allele favored tissue restoration. Here, we investigated the gene expression profiles and the inflammatory reactions of AIRmax ^RR and AIRmax ^SS mice during the initial phase of ear tissue regeneration. We observed superior levels of analysis of wound myeloperoxidase and edema in AIRmax ^SS mice, although similar cell influx was verified in both lines. Of the genes, 794 were up- and 674 down-regulated in AIRmax ^RR , while 735 genes were found to be up- and 1616 down-regulated in AIRmax ^SS mice 48 h after punch. Both mouse lines showed significant over-represented genes related to cell proliferation; however AIRmax ^SS displayed up-regulation of inflammatory response genes. Quantitative PCR experiments showed higher expressions of Tgfb1, Dap12 and Trem1 genes in AIRmax ^SS mice. These results indicate that Slc11a1 gene modulated the early inflammatory events of ear tissue regeneration.     

Development of <Emphasis Type="Italic">T</Emphasis><Subscript><Emphasis Type="Italic">m</Emphasis></Subscript>-shift genotyping method for detection of cat-derived <Emphasis Type="Italic">Giardia lamblia</Emphasis>

To develop T _m -shift genotyping method for detection of cat-derived Giardia lamblia, two sets of primers with two GC-rich tails of unequal length attached to their 5′-end were designed according to two SNPs (BG434 and BG170) of β-giardin (bg) gene, and specific PCR products were identified by inspection of a melting curve on real-time PCR thermocycler. A series of experiments on the stability, sensitivity, and accuracy of T _m -shift method was tested, and clinical samples were also detected. The results showed that two sets of primers based on SNP could distinguish accurately between assemblages A and F. Coefficient of variation of T _m values of assemblage A and F was 0.14 and 0.07% in BG434 and 0.10 and 0.11% in BG170, respectively. The lowest detection concentration was 4.52 × 10^?5 and 4.88 × 10^?5 ng/μL samples of assemblage A and F standard plasmids. The T _m -shift genotyping results of ten DNA samples from the cat-derived G. lamblia were consistent with their known genotypes. The detection rate of clinical samples by T _m -shift was higher than that by microscopy, and their genotyping results were in complete accordance with sequencing results. It is concluded that the T _m -shift genotyping method is rapid, specific, and sensitive and may provide a new technological mean for molecular detection and epidemiological investigation of the cat-derived G. lamblia.     

In vitro evaluation of the effectiveness of new water-stable cationic carbosilane dendrimers against <Emphasis Type="Italic">Acanthamoeba castellanii</Emphasis> UAH-T17c3 trophozoites

Acanthamoeba is one of the most common free-living amoebas which is widespread in the environment and can infect humans, causing diseases such as keratitis and encephalitis. In this paper we examine for the first time the amebicidal activity of the family of cationic dendrimers nG-[Si{(CH₂)₃N⁺(Me)(Et)(CH₂)₂NMe₃ ⁺}2I^?] _x (where n denotes the generations: zero (n?=?0, x?=?1), first (n?=?1, x?=?4), and second (n?=?2, x?=?8); for simplicity, they were named as 0G-CNN2, 1G-CNN8, and 2G-CNN16, respectively) against Acanthamoeba castellanii UAH-T17c3 trophozoites. In order to test the amebicidal activity, we cultured the strain A. castellanii UAH-T17c3 in PYG-Bactocasitone medium and later, we treated it with different concentrations of these dendrimers and monitored the effects and damage by optical count, flow cytometry, and scanning electron microscopy. The results showed that all the nanosystems assayed had a strong amebicidal activity. The dendrimer 1G-CNN8 was the most effective against the amoeba. In the morphology of treated throphozoites of A. castellanii UAH-T17c3 analyzed by light and scanning electron microscopy techniques, morphological changes were evident in amoeba cells, such as loss of pseudopodia, ectoplasm increase, roundness, and cellular lysis. Furthermore, flow cytometry results showed alterations in cell granularity, which was dose–time dependent. In conclusion, this family of cationic carbosilane dendrimers has a strong amebicidal activity against the trophozoites of A. castellanii UAH-T17c3 in vitro. They could potentially become new agents significant to the development of new amebicidal compounds for prevention and therapy of Acanthamoeba infections.     

Characterisation of VIM-2-producing <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> isolates from lower tract respiratory infections in a Spanish hospital

To analyse the antimicrobial phenotype, carbapenem mechanisms, integrons, virulence factors and molecular typing of 164 Pseudomonas aeruginosa isolates recovered from lower tract respiratory samples in a Spanish hospital (1 year) as well as the patients’ clinical data. Susceptibility testing to 12 antipseudomonal agents was determined by microdilution and metallo-beta-lactamase (MBL) phenotype by double disc method. The oprD gene was studied by PCR, sequencing and comparison with P. aeruginosa PAO1 sequence. Detection and characterisation of MBLs, class 1, 2 and 3 integrons, and virulence genes were studied by PCR and sequencing. The prevalence of carbapenem-resistant P. aeruginosa (CRPA) was 26.8%. MBL phenotype was detected in 52.3% CRPA, and all of them were disseminated throughout the intensive care unit. Most of the MBL-carrying patients presented respiratory disease, mechanical ventilation, tracheostomy, bacteraemia, ≥?30 hospitalisation days and previous treatment with carbapenems and/or ≥?3 different antimicrobial families. The bla_VIM-2 gene was the unique MBL encoding gene and was detected inside class 1 integrons. The class 1 integrons detected in 39 strains (23.8%) were associated with aminoglycosides (aadB, aadA1, aadA6, aacA4, aac(3)-I) and carbapenems resistance genes (bla_VIM-2). The aac(3)-I?+?aadA1 and bla_VIM-2 arrangements were the most prevalent ones. Thirty-one different PFGE patterns and 4 STs (ST175, ST235, ST253, ST973) were detected among the 39 intI1-positive isolates, being ST235 the most frequent. CRPA showed a great variety of alterations in oprD gene. The exoU⁺/exoS^? genotype was detected in 82.6% of bla_VIM-2-producing strains (ST235) and the exoU^?/exoS⁺ in the remaining 17.4% (ST973).     

The interplay between arms-only propelling efficiency,power output and speed in master swimmers

Purpose

To explore the interplay between arms-only propelling efficiency (η _p), mechanical power output (\(\dot W_{\text{tot}}\)) and swimming speed (V); these three parameters are indeed related through the following equation V ³ = 1/kη _p \(\dot W_{\text{tot}}\) (where k is the speed-specific drag; k = F/V ²); thus, the larger are η _p and \(\dot W_{\text{tot}}\) the larger is V. We furthermore wanted to test the hypothesis that a multiple linear regression between \(\dot W_{\text{tot}}\), η _p and V would have a stronger correlation coefficient than a linear regression between \(\dot W_{\text{tot}}\) and V alone.

Methods

To this aim we recruited 29 master swimmers (21 M/8F) who were asked to perform (1) an incremental protocol at the arm-ergometer (dry-land test) to determine \(\dot W_{\text{tot}}\) at \(\dot V\)O_2max (e.g. \(\dot V\) _max); (2) a maximal 200 m swim trial (with a pull buoy: arms only) during which V and η _p were determined.

Results

No relationship was found between \(\dot W_{\text{max}}\) and η _p (not necessarily the swimmers with the largest \(\dot W_{\text{max}}\) are those with the largest η _p and vice versa) whereas significant correlations were found between \(\dot W_{\text{max}}\) and V (R = 0.419, P = 0.024) and η _p and V (R = 0.741, P = 0.001); a multiple linear regression indicates that about 75 % of the variability of V can be explained by the variability of \(\dot W_{\text{max}}\) and η _p (R = 0.865, P < 0.001).

Conclusions

These findings indicate that η _p should be taken into consideration when the relationship between \(\dot W_{\text{max}}\) and V is investigated and that this allows to better explain the inter-subject variability in performance (swimming speed).

     

Open-Source Radiation Exposure Extraction Engine (RE3) with Patient-Specific Outlier Detection

We present an open-source, picture archiving and communication system (PACS)-integrated radiation exposure extraction engine (RE3) that provides study-, series-, and slice-specific data for automated monitoring of computed tomography (CT) radiation exposure. RE3 was built using open-source components and seamlessly integrates with the PACS. RE3 calculations of dose length product (DLP) from the Digital imaging and communications in medicine (DICOM) headers showed high agreement (R ²?=?0.99) with the vendor dose pages. For study-specific outlier detection, RE3 constructs robust, automatically updating multivariable regression models to predict DLP in the context of patient gender and age, scan length, water-equivalent diameter (D _w), and scanned body volume (SBV). As proof of concept, the model was trained on 811 CT chest, abdomen + pelvis (CAP) exams and 29 outliers were detected. The continuous variables used in the outlier detection model were scan length (R ² ?=?0.45), D _w (R ²?=?0.70), SBV (R ²?=?0.80), and age (R ²?=?0.01). The categorical variables were gender (male average 1182.7?±?26.3 and female 1047.1?±?26.9 mGy cm) and pediatric status (pediatric average 710.7?±?73.6 mGy cm and adult 1134.5?±?19.3 mGy cm).     

Isolation of <Emphasis Type="Italic">Lactobacillus acidophilus</Emphasis> and assessment for its antiviral effect against herpes simplex virus type II

The prevalence of diverse genital infections among women and their increasing resistance to antibiotics has motivated researchers to study the use of probiotics to prevent and treat them. Samples of vaginal discharge were collected from healthy married women. The types of lactobacilli present were identified by biochemical and molecular testing. The antiviral properties of a culture supernatant of wild species or strains of Lactobacillus acidophilus LA-5 on the standard strain of herpes simplex virus type 2 (HSV-2) was evaluated. L. acidophilus culture supernatant significantly decreased the amount of plaque produced by HSV-2 on cells. Similar results were obtained for the standard strain. The inhibitory effect of the wild L. acidophilus did not require the production of H₂O₂ or H⁺ ions of the standard strain or an acidic environment. L. acidophilus was able to control HSV-2 without producing H₂O₂ or H⁺ ions or acidifying the environment. The inhibitory property of virus is most likely related to production of active metabolites.     

Sensitive and specific assay for the simultaneous detection of <Emphasis Type="Italic">Mycoplasma genitalium</Emphasis> and macrolide resistance-associated mutations

Patients infected by Mycoplasma genitalium are often treated empirically with the macrolide azithromycin. Macrolide resistance is becoming quite common; empirical treatment is compromised. Sequencing was initially used to detected azithromycin resistance-associated mutations. As this was laborious, qPCRs have been developed for their detection. In the present study, we describe a fast, sensitive, and specific qPCR assay that enables routine testing of M. genitalium and macrolide resistance-associated mutations in a single assay. M. genitalium positive clinical samples were used to compare (i) the commonly used MgPa assay for the detection of M. genitalium infections (MgPa qPCR), (ii) a combined 23S rRNA gene PCR/sequencing assay (Mg23S qPCR/Sequencing) to identify macrolide resistance-associated mutations, and (iii) our newly developed probe-based melt curve qPCR for simultaneous detection of M. genitalium and macrolide resistance-associated mutations (Macrolide-R/MG ELITe MGB Kit, Elitech Bothel USA in short Mg Macrolide^R qPCR). Specificity of the qPCR was tested using urogenital samples that were tested positive for a range of other micro-organisms. M. genitalium was detected in 196/236 (83.1%) samples by the MgPa qPCR, versus 172/236 (72.9%) by the combined Mg23S qPCR/Sequencing, and 202/236 (85.6%) by the Mg Macrolide^R qPCR. The Mg Macrolide^R qPCR showed high concordance to the Mg23S qPCR/Sequencing assay (201 vs 202 could be genotyped, respectively) for the detection of the macrolide resistant mutations. None of the other urogenital pathogens were tested positive in the Mg Macrolide^R qPCR, indicating specificity. The Mg Macrolide^R qPCR is fast, sensitive, specific, and can easily be implemented in the routine diagnostics.     

Dendrimer-mediated delivery of <Emphasis Type="Italic">N</Emphasis>-acetyl cysteine to microglia in a mouse model of Rett syndrome

Background

Rett syndrome (RTT) is a pervasive developmental disorder that is progressive and has no effective cure. Immune dysregulation, oxidative stress, and excess glutamate in the brain mediated by glial dysfunction have been implicated in the pathogenesis and worsening of symptoms of RTT. In this study, we investigated a new nanotherapeutic approach to target glia for attenuation of brain inflammation/injury both in vitro and in vivo using a Mecp2-null mouse model of Rett syndrome.

Methods

To determine whether inflammation and immune dysregulation were potential targets for dendrimer-based therapeutics in RTT, we assessed the immune response of primary glial cells from Mecp2-null and wild-type (WT) mice to LPS. Using dendrimers that intrinsically target activated microglia and astrocytes, we studied N-acetyl cysteine (NAC) and dendrimer-conjugated N-acetyl cysteine (D-NAC) effects on inflammatory cytokines by PCR and multiplex assay in WT vs Mecp2-null glia. Since the cysteine-glutamate antiporter (Xc^?) is upregulated in Mecp2-null glia when compared to WT, the role of Xc^? in the uptake of NAC and l-cysteine into the cell was compared to that of D-NAC using BV2 cells in vitro. We then assessed the ability of D-NAC given systemically twice weekly to Mecp2-null mice to improve behavioral phenotype and lifespan.

Results

We demonstrated that the mixed glia derived from Mecp2-null mice have an exaggerated inflammatory and oxidative stress response to LPS stimulation when compared to WT glia. Expression of Xc^? was significantly upregulated in the Mecp2-null glia when compared to WT and was further increased in the presence of LPS stimulation. Unlike NAC, D-NAC bypasses the Xc^? for cell uptake, increasing intracellular GSH levels while preventing extracellular glutamate release and excitotoxicity. Systemically administered dendrimers were localized in microglia in Mecp2-null mice, but not in age-matched WT littermates. Treatment with D-NAC significantly improved behavioral outcomes in Mecp2-null mice, but not survival.

Conclusions

These results suggest that delivery of drugs using dendrimer nanodevices offers a potential strategy for targeting glia and modulating oxidative stress and immune responses in RTT.

     

Body Esteem Among Women with Multiple Sclerosis and its Relationship with Demographic,Clinical and Socio-Psychological Factors

Purpose

The principal aim of this study was to verify if specific socio-demographic, clinical, and socio-psychological factors are correlates of body esteem in women with multiple sclerosis (MS).

Methods

The study included 185 women with MS who completed the Body Esteem Scale (BES), Rosenberg Self-Esteem Scale (RSES), Multiple Sclerosis Impact Scale (MSIS-29), Brief Illness Perception Questionnaire (B-IPQ), Actually Received Support Scale (a part of the Berlin Social Support Scale), and Expanded Disability Status Scale (EDSS). The patients were recruited as a result of cooperation with the Multiple Sclerosis Rehabilitation Centre in Borne Sulinowo and Polish Society of Multiple Sclerosis. The demographic characteristics of the participants and their illness-related problems were determined with a self-report survey.

Results

A hierarchical multiple regression revealed that four factors, psychological condition (R ²?=?0.23, p?≤?0.001), received support (R ²?=?0.28, p?≤?0.001), personal control (R ²?=?0.30, p?≤?0.001), and physical condition (R ²?=?0.31, p?≤?0.001), were significant correlates of the general body esteem in our study group of women with MS. The model explained 31 % of variance in body esteem.

Conclusion

Positive body esteem, an important component of self-esteem in women with MS, is associated with better social support, overcoming negative illness-related appraisals and improvement of psychological well-being. Subjective perception of a negative impact of MS on one’s physical condition may be helpful in the identification of women with MS being at increased risk of decreased body esteem.

     

Characterization of carbapenem-resistant <Emphasis Type="Italic">Escherichia coli</Emphasis> and <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> from a healthcare region in Hong Kong

Carbapenem-resistant Enterobacteriaceae represents a major public health issue. This study investigated the clonality and resistance mechanisms of 92 carbapenem-resistant E. coli (n?=?21) and K. pneumoniae (n?=?71) isolates collected consecutively from clinical specimens and patients at high risk of carriage between 2010 and 2012 in a healthcare region in Hong Kong. Combined disk tests (CDTs) and the Carba NP test were used for phenotypic detection of carbapenemases. PCR assays were used to detect carbapenemase genes. All isolates were intermediate or resistant to at least one carbapenem. Nine (9.8 %) isolates were genotypic carbapenemase producers and included six K. pneumoniae (one ST1306/bla _IMP-4, one ST889/bla _IMP-4, two ST11/bla _KPC-2, one ST258/bla _KPC-2, one ST483/bla _NDM-1) and three E. coli (one ST131/bla _IMP-4, two ST744/ bla _NDM-1) isolates. All nine isolates carrying carbapenemase genes could be detected by the CDTs and the Carba NP test. PCR identified bla _CTX-M and bla _AmpC alone or in combination in 77.8 % (7/9) and 96.4 % (80/83) of the carbapenemase-producers and non-producers, respectively. Porin loss was detected in 22.2 % (2/9) and 59.0 % (49/83) of the carbapenemase-producers and non-producers, respectively. Overall, the E. coli clones were diverse (14 different STs), but 36.6 % (26/71) of the K. pneumoniae isolates belonged to ST11. In conclusion, the prevalence of carbapenemases among carbapenem-nonsusceptible E. coli and K. pneumoniae remained low in Hong Kong. Porin loss combined with AmpC and/or CTX-M type ESBL was the major mechanism of carbapenem resistance in the study population.     

Diversity of plasmids and Tn<Emphasis Type="Italic">1546</Emphasis>-type transposons among VanA <Emphasis Type="Italic">Enterococcus faecium</Emphasis> in Poland

The objective of this study was to investigate the antimicrobial resistance, Tn1546 transposon variability and plasmid diversity among Polish vancomycin-resistant Enterococcus faecium (VREfm) isolates of VanA phenotype in the context of their clonal structure. Two hundred sixteen clinical VREfm isolates collected between 1997 and 2010 were studied by antimicrobial susceptibility testing, MLST, MLVA and detection of IS16, esp _Efm, pilA, intA and plasmid-specific genes by PCR. Tn1546 structure was revealed by overlapping PCR and sequencing. Selected isolates were subjected to PFGE-S1 and Southern hybridization analyses. The vast majority of the isolates (95.8 %) belonged to lineages 17/18 (during the whole study period 1997–2010) and 78 (mostly in 2006–2010) of hospital-adapted meroclone of E. faecium. All isolates displayed a multi-drug resistance phenotype. Twenty-eight Tn1546 types (including 26 novel ones) were associated with eight different ISs (IS1216, IS1251, ISEfa4, ISEfa5, ISEfm2, ISEf1, IS3-like, ISEfm1-like). The vanA-determinant was typically located on plasmids, which most commonly carried rep2_pRE25, rep17_pRUM, rep18_pEF418, rep1_pIP501, ω-ε-ζ and axe-txe genes. VanA isolates from 1997–2005 to 2006–2010 differed in clonal composition, prevalence of gentamicin- and tetracycline-resistance and plasmidome. Our analysis revealed high complexity of Tn1546-type transposons and vanA-plasmids, and suggested that diverse genetic events, such as conjugation transfer, recombination, chromosomal integration and DNA mutations shaped the structure of these elements among Polish VREfm.     

Frequent <Emphasis Type="Italic">BRAF</Emphasis><Superscript><Emphasis Type="Italic">V600E</Emphasis></Superscript> and Absence of <Emphasis Type="Italic">TERT</Emphasis> Promoter Mutations Characterize Sporadic Pediatric Papillary Thyroid Carcinomas in Japan

Pediatric papillary thyroid carcinoma (PTC) has unique features but requires further genetic investigation. Moreover, there has been increasing concern about the risk for pediatric PTC in Japan after the Fukushima accident. This study aims to evaluate the frequencies of BRAF and TERT promoter mutations and to examine their significance in non-radiation-associated pediatric PTCs in Japan. We enrolled 81 pediatric PTC patients aged ≤20 years. The control group included 91 adult PTCs from patients >20 years old. BRAF and TERT mutations were analyzed by allele-specific-PCR and/or Sanger sequencing. Compared with adult PTCs, pediatric PTCs exhibited larger tumor size, more frequent lymph node metastasis, and less classical histology. The prevalence of BRAF ^V600E in pediatric PTCs was 54% and significantly lower than that in adults of 85%. In the pediatric PTCs, BRAF ^V600E was positively associated with older age, classical histology, and the lymph node metastasis but independent from other clinicopathological factors. TERT mutations were identified in 13% of adults and in none of the pediatric PTCs. In conclusion, pediatric PTCs are characterized by more advanced clinicopathological features, lower BRAF ^V600E frequency, and absence of TERT mutation. The BRAF ^V600E frequency in this study is similar to the reported BRAF ^V600E frequency in the ultrasonographically screened pediatric PTCs in Fukushima.     

Brain inflammation is accompanied by peripheral inflammation in <Emphasis Type="Italic">Cstb</Emphasis><Superscript><Emphasis Type="Italic">−/−</Emphasis></Superscript> mice,a model for progressive myoclonus epilepsy

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited childhood-onset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB) underlie EPM1. The CSTB-deficient (Cstb ^?/? ) mouse model recapitulates key features of EPM1, including myoclonic seizures. The mice show early microglial activation that precedes seizure onset and neuronal loss and leads to neuroinflammation. We here characterized the inflammatory phenotype of Cstb ^?/? mice in more detail. We found higher concentrations of chemokines and pro-inflammatory cytokines in the serum of Cstb ^?/? mice and higher CXCL13 expression in activated microglia in Cstb ^?/? compared to control mouse brains. The elevated chemokine levels were not accompanied by blood-brain barrier disruption, despite increased brain vascularization. Macrophages in the spleen and brain of Cstb ^?/? mice were predominantly pro-inflammatory. Taken together, these data show that CXCL13 expression is a hallmark of microglial activation in Cstb ^?/? mice and that the brain inflammation is linked to peripheral inflammatory changes, which might contribute to the disease pathology of EPM1.