Input Training Matters in L2 Syntactic Representation Entrenchment: Evidence from a Follow-Up ERP Study

Abstract

The usage-based theory highlights the important role of linguistic input in language acquisition, and assumes that syntactic representations could be entrenched through usage or exposure. In the present study, we used the event-related potential technique to investigate the long-term effect of input training on second language (L2) syntactic representations entrenchment, using English subject-verb agreement structures as the stimuli. Results showed that 3 months after the training of the specific subject-verb agreement structures, a significant P600 was observed in the key region (the verb) of the sentences with syntactic violations in the experimental group, but not in the control group. This indicates that linguistic input training contributes to syntactic representations entrenchment, which can be sustained for a relatively long period, indicating a long-term effect of input training. The results suggest that linguistic input is a causal variable in L2 online syntactic processing, supporting the usage-based theory.

http://bit.ly/2S6ZNy5

Exploring the Justifications for Selecting a Drop Landing Task to Assess Injury Biomechanics: A Narrative Review and Analysis of Landings Performed by Female Netball Players

Abstract

When assessing biomechanics in a laboratory setting, task selection is critical to the production of accurate and meaningful data. The injury biomechanics of landing is commonly investigated in a laboratory setting using a drop landing task. However, why this task is so frequently chosen is unclear. Therefore, this narrative review aimed to (1) identify the justification/s provided within the published literature as to why a drop landing task was selected to investigate the injury biomechanics of landing in sport and (2) use current research evidence, supplemented by a new set of biomechanical data, to evaluate whether the justifications are supported. To achieve this, a comprehensive literature search using Scopus, PubMed, and SPORTDiscus online databases was conducted for studies that had collected biomechanical data relating to sport injuries using a drop landing task. In addition, kinematic and kinetic data were collected from female netball players during drop landings and maximum-effort countermovement jumps from the ground to grab a suspended ball. The literature search returned a total of 149 articles that were reviewed to determine the justification for selecting a drop landing task. Of these, 54% provided no explicit justification to explain why a drop landing task was chosen, and 15% stated it was selected because it had been used in previous research. Other reasons included that the drop landing provides high experimental control (16%), is a functional sports task (11%), and is a dynamic task (6%). Evidence in the literature suggests that the biomechanical data produced with drop landings may not be as externally valid as more sport-specific tasks. Biomechanical data showed that the drop landing may not control center of mass fall height any better than maximum-effort countermovement jumps from the ground. Further, the frequently used step-off technique to initiate drop landings resulted in kinematic and kinetic asymmetries between lower limbs, which would otherwise be symmetrical when performing a countermovement jump from the ground. Researchers should consider the limitations of a drop landing task and endeavor to improve the laboratory tasks used to collect biomechanical data to examine the injury biomechanics of landing.

http://bit.ly/2WirBPb

Research progress and application prospect of anaerobic biological phosphorus removal

Abstract

Anaerobic biological phosphorus removal has proposed a new direction for the removal of phosphorus from wastewater, and the discovery of phosphate reduction makes people have a more comprehensive understanding of microbial phosphorus cycling. Here, from the perspective of thermodynamics, the bioreduction reaction of phosphate was analyzed and its mechanism was discussed. The research progress of phosphate reduction and the application prospects of anaerobic biological phosphorus removal from wastewater were introduced, pointing out the situation and guiding the further research in this field.

http://bit.ly/2S5wID9

Pharmacokinetics of elbasvir and grazoprevir in subjects with end-stage renal disease or severe renal impairment

Abstract

Purpose

To describe the phase 1 and population pharmacokinetic investigations that support dosing recommendations for elbasvir/grazoprevir (EBR/GZR) in hepatitis C virus-infected people with advanced chronic kidney disease.

Methods

This was an open-label, two-part, multiple-dose trial (MK-5172 PN050; NCT01937975) in 24 non–HCV-infected participants with end-stage renal disease (ESRD) or severe renal impairment who received once-daily EBR 50 mg and GZR 100 mg for 10 days. Population pharmacokinetic analyses from the phase 3 C-SURFER study (PN052, NCT02092350) were also conducted.

Results

When comparing haemodialysis (HD) and non-HD days in participants with ESRD, geometric mean ratios (GMRs) (90% confidence intervals [CIs]) for EBR and GZR AUC_0–24 were 1.14 (1.08–1.21) and 0.97 (0.87–1.09). When comparing ESRD and healthy participants, GMRs (90% CIs) for EBR and GZR AUC_0–24 were 0.99 (0.75–1.30) and 0.83 (0.56–1.22) on HD days, and 0.86 (0.65–1.14) and 0.85 (0.58–1.25) on non-HD days. GMRs (90% CIs) for AUC_0–24 in participants with severe renal impairment relative to healthy controls were 1.65 (1.09–2.49) for GZR and 1.86 (1.38–2.51) for EBR. In population modelling of data from C-SURFER, absolute geometric means of steady-state EBR AUC_0–24 were 2.78 and 3.07 μM*h (HD and non-HD recipients) and GZR AUC_0–24 were 1.80 and 2.34 μM*h (HD and non-HD recipients).

Conclusions

EBR/GZR represents an important treatment option for HCV infection in people with severe renal impairment and those with ESRD. No dosage adjustment of EBR/GZR is required in people with any degree of renal impairment, including those receiving dialysis.

http://bit.ly/2RPOOKc

Sudden unexpected death in Parkinson’s disease: why do neuroscientists still ignore this condition?

http://bit.ly/2B4EB1V

The clinical and imaging features of hypertrophic pachymeningitis: a clinical analysis on 22 patients

Abstract

Objective

To explore the clinical and imaging features of patients with hypertrophic cranial pachymeningitis (HCP).

Methods

A retrospective study was performed on 22 patients with HCP diagnosed at the Affiliated Hospital of Xuzhou Medical University from February 2014 to September 2017.

Results

A headache was present as an initial symptom in 18 patients. The headache was associated with the loss of vision (2 cases), facial pain (1 case), and unsteady walking (1 case). Other symptoms included cranial nerve dysfunction (15 cases), cerebellar ataxia (4 cases), and sinus thrombosis (3 cases). In the laboratory tests, 7 patients showed an increased number of white blood cells, higher levels of C-reaction protein (CRP), and erythrocyte sedimentation rate (ESR). An elevated level of immunoglobulin G4 (IgG4) and the presence of the anti-neutrophil cytoplasmic antibody (ANCA) were found in 3 and 2 patients respectively. There were 17 patients who had abnormalities in their cerebrospinal fluid (CSF) on lumbar puncture. On magnetic resonance imaging (MRI), a local or generalized thickening was observed in the cerebral falx, the tentorium of the cerebellum, the fronto-parietal lobe, the occipito-parietal lobe, and the dura of skull base. A dural biopsy obtained in one case showed a variety of inflammatory changes. An immunohistochemical analysis revealed the positivity of CD138, IgG, and IgG4 in some cells. All 22 patients had a good response to corticosteroids.

Conclusion

HCP mainly leads to a headache and the paralysis of multiple cranial nerves. A biopsy and MRI are often required and serve as the basis for the diagnosis and effective therapy.

http://bit.ly/2TbWAuv

Off-label use of tamoxifen in a Chinese tertiary care hospital

Abstract

Background Tamoxifen is an estrogen receptor modulator used for the treatment of breast cancer; however, currently, it is used in many off-label indications. Objective To investigate the prevalence of tamoxifen off-label prescribing and explore available scientific evidence that supports those uses in outpatients. Setting Xiamen maternity and child health care hospital in Xiamen city of China. Method All the prescriptions of outpatients receiving tamoxifen were exported from an electronic prescribing system during a 1-year period. Tamoxifen use was then classified as either on- or off-label according to the criteria we established previously, and the details of the off-label prescriptions were collected. Logistic regression was applied to explore predictive variables. Evidence search was limited to Up-To-Date, the Micromedex database and PubMed. Main outcome measure The rate of off-label use, risk factors identified by logistic regression and evidence exhibition. Results A total of 75% of all the prescriptions available were classified as off-label use. Hyperplasia of the breast was the most frequently prescribed off-label indication. According to the analysis of logistic regression, male patients, patients less than 34 years old, and physicians with a higher professional title were more likely associated with off-label prescribing. After a search in Up-To-Date, the Micromedex database and PubMed, only male infertility, atypical hyperplasia, mastodynia, peripheral precocious puberty and gynecomastia were found to have strong evidence supporting the use of tamoxifen off-label (22.75%). Conclusion Although the off-label use of tamoxifen was common in our hospital, there was a relative shortage of evidence available supporting those uses.

http://bit.ly/2FLRrpT

Polypharmacy in older patients at primary care units in Brazil

Abstract

Background Despite extensive studies of polypharmacy in older patients, no consensus regarding the definition of this practice exists in the literature. Several studies have defined polypharmacy as problematic when considering only the numbers of medications used by patients. Objective This study aimed to assess the prevalence of polypharmacy prescribing by comparing two different definitions (quantitative and qualitative) and evaluating factors associated with this practice in older patients. Setting Twenty-three basic health units. Method A cross-sectional study involving 386 older adults who received a prescription after a medical consultation. Multivariate analyses were conducted using a Poisson regression with robust variance. Main outcome measure The main outcome measures included patients with a prescription of five or more medications (quantitative polypharmacy) and those with a prescription of five or more medications including at least one drug considered potentially inappropriate for older adults (qualitative polypharmacy). Results The frequency of quantitative polypharmacy was 20.5%. The results of an adjusted analysis showed that the frequency of quantitative polypharmacy was associated with a higher number of self-reported morbidities and the prescription of potentially inappropriate drugs. The prevalence of qualitative polypharmacy was 10.4%, and after adjustment, this outcome remained significantly associated with the presence of three or more self-reported morbidities. Conclusions The presence of multiple comorbidities was identified as the main factor associated with the prescription of both quantitative and qualitative polypharmacy.

http://bit.ly/2FYD2py

Nifuroxazide induces apoptosis, inhibits cell migration and invasion in osteosarcoma

Summary

Osteosarcoma is the most common primary malignancy of bone and characterized by an appendicular primary tumor with a high rate of metastasis to the lungs. Unfortunately, there is no effective strategy to treat osteosarcoma in current clinical practice. In this study, the anticancer effects and potential mechanisms of nifuroxazide, an oral nitrofuran antibiotic, on two osteosarcoma cell lines were investigated. The results of the antiproliferative activity in vitro showed that nifuroxazide inhibited cell proliferation of UMR106 and MG63 cells in a dose- and time-dependent manner. Interestingly, nifuroxazide showed low toxicity to non-tumor cells (HEK 293 T). In addition, ROS-mitochondrial mediated apoptosis was observed after treatment of nifuroxazide. Moreover, nifuroxazide could significantly inhibit osteosarcoma cells migration and invasion via p-Stat3, MMP-2 and MMP-9 mediated signaling pathway. Taken together, our results suggested that nifuroxazide could be a promising agent for osteosarcoma treatment by inhibiting cell proliferation, inducing cell apoptosis and impairing cell migration and invasion.

http://bit.ly/2MtUinN

Low-dose rituximab as induction therapy for ANCA-associated vasculitis

Abstract

Administration of four once-weekly doses of 375 mg/m² rituximab (RTX) is commonly used as remission induction therapy for ANCA-associated vasculitis (AAV). Low-dose RTX has been recently shown to produce closely similar results to conventional treatments in other autoimmune diseases. However, the therapeutic potential of this approach in AAV remains largely unknown. Here, we analyzed the efficacy and tolerability of high- and low-dose regimens of RTX in patients with AAV. We retrospectively examined AAV patients who met the classification algorithm of Watts et al. from 2006 to 2016. Patients were divided into high- (HD) and low-dose (LD) RTX groups. HD-RTX was the original regimen while LD-RTX consisted of two once-weekly doses of 375 mg/m². Cumulative complete remission (CR) rates for 1 year were compared, and serial changes in peripheral B cell counts and serious adverse events were monitored. Apart from a higher percentage of elderly patients in the LD group (p < 0.01), the 17 patients with HD-RTX and 11 patients with LD-RTX showed no significant differences in clinical characteristics, including Birmingham Vasculitis Activity Score (BVAS), Vasculitis Damage Index (VDI), and the initial dose of glucocorticoid. On 1-year observation, cumulative CR rates did not significantly differ (p = 0.20). Further, peripheral B cell counts and incidence of serious adverse events also did not differ. Cumulative CR rate did not significantly differ between LD and HD groups. Further study is warranted to confirm these results.

http://bit.ly/2HwzdKC

Blocking C/EBP β protects vascular endothelial cells from injury induced by intermittent hypoxia

Abstract

Background

Intermittent hypoxia (IH) can damage endothelial cells and lead to apoptosis in obstructive sleep apnea-hypopnea syndrome (OSAHS). Hypoxia induces apoptosis in endothelial cells via upregulation of endothelin-1 (ET-1) and hypoxia inducible factor-1 alpha (HIF-1α) plays a key role in the hypoxic stress response.

Purpose

We investigated an approach to diminish the negative effect of HIF-1α while maintaining its protective effect.

Methods

Human umbilical vein endothelial cells (HUVECs) were subjected to sustained hypoxia (SH) or IH for 24 h, and the responses of HIF-1α, CCAAT/enhancer binding protein beta (C/EBP β), and endothelin-1 (ET-1) were assessed by western blotting. A luciferase reporter system was employed to verify the potential binding site (transcription factor binding site, TFBS) for C/EBP β in the ET-1 promoter. The specificity of regulation of ET-1 by HIF-1α via C/EBP β was evaluated by a lentiviral system. The effects of silencing of C/EBP β on IH-induced apoptosis, vascular endothelial growth factor (VEGF) protein levels, proliferation, and in vitro tube formation were studied.

Results

We found that IH significantly increased HIF-1α, C/EBP β, and ET-1 in HUVECs. Knockdown of HIF-1α or C/EBP β inhibited the upregulation of ET-1 induced by IH. Blocking C/EBP β impaired IH-induced apoptosis but did not affect VEGF expression, proliferation, or in vitro tube formation. C/EBP β was shown to mediate increased ET-1 transcription by HIF-1α through the TFBS, 5′-GTTGCCTGTTG-3′, in ET-1 promoter.

Conclusion

Silencing of C/EBP β can suppress apoptosis but does not affect the protective role of HIF-1α in the hypoxic stress response.

http://bit.ly/2RQFupt

Characteristics of N 2 O Emission in Distilled Water and Activated Sludge Mixture

Abstract

To investigate the emission characteristics of the dissolved N₂O in distilled water and activated sludge mixture, the total volume mass transfer coefficients of N₂O in distilled water and activated sludge mixture were determined by batch experiments. The results indicated a difference between emission processes of N₂O in distilled water and activated sludge mixture. At different initial N₂O concentrations, the total volume mass transfer coefficients of N₂O in distilled water were relatively stable, while the total volume mass transfer coefficients of N₂O in activated sludge mixture increased with increasing initial N₂O concentrations, due to endogenous denitrification by microorganisms in the mixture. Since N₂O was reduced and consumed by heterotrophic bacteria in activated sludge, biochemical reactions were involved in the transfer process of N₂O escaping from the mixture to the atmosphere. Therefore, use of distilled water was suggested to determine the total volume mass transfer coefficient in experiments calculating N₂O emission rates for biological nitrogen removal processes.

http://bit.ly/2TbL16z

The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model

Summary

Obtustatin, isolated from the Levantine Viper snake venom (Macrovipera lebetina obtusa -MLO), is the shortest known monomeric disintegrin shown to specifically inhibit the binding of the α1β1 integrin to collagen IV. Its oncostatic effect is due to the inhibition of angiogenesis, likely through α1β1 integrin inhibition in endothelial cells. To explore the therapeutic potential of obtustatin, we studied its effect in S-180 sarcoma-bearing mice model in vivo as well as in human dermal microvascular endothelial cells (HMVEC-D) in vitro, and tested anti-angiogenic activity in vivo using the chick embryo chorioallantoic membrane assay (CAM assay). Our in vivo results show that obtustatin inhibits tumour growth by 33%. The expression of vascular endothelial growth factor (VEGF) increased after treatment with obtustatin, but the level of expression of caspase 8 did not change. In addition, our results demonstrate that obtustatin inhibits FGF2-induced angiogenesis in the CAM assay. Our in vitro results show that obtustatin does not exhibit cytotoxic activity in HMVEC-D cells in comparison to in vivo results. Thus, our findings disclose that obtustatin might be a potential candidate for the treatment of sarcoma in vivo with low toxicity.

http://bit.ly/2FUXnfD

Impact of Diabetes Mellitus on Human Mesenchymal Stromal Cell Biology and Functionality: Implications for Autologous Transplantation

Abstract

Multipotent mesenchymal stem/stromal cells (MSCs) have regenerative and immunomodulatory properties to restore and repair injured tissues, making them attractive candidates for cell-based therapies. Experimental and clinical evidence has demonstrated the effectiveness of MSC transplantation in managing diabetes mellitus (DM). Autologous MSCs are assumed to be favorable because patient-derived cells are readily available and do not entail sustained immunosuppressive therapy. DM is associated with hyperglycemia, oxidative stress and altered immune responses and inflammation. It may thus alter the biological characteristics and therapeutic qualities of human MSCs (hMSCs). Several studies have explored the effect of DM or the diabetic microenvironment on the engraftment and efficacy of transplanted MSCs, which are determined by proliferation, differentiation, senescence, angiogenesis supportive effect, migration, anti-oxidative capacity and immunomodulatory properties. This review aims to present the available data on how DM impacts MSC biology and functionality and identify future perspectives for autologous MSC-based therapy in diabetics.

http://bit.ly/2MvT63r

Performance and calibration of the algorithm ASSIGN in predicting cardiovascular disease in Italian patients with psoriatic arthritis

Abstract

The increased cardiovascular (CV) risk is one of the major challenges in the management of patients with psoriatic arthritis (PsA). Recently, EULAR suggested to adapt the already available CV risk algorithms with a 1.5 multiplication factor in all the patients with rheumatoid arthritis (RA), but it is still uncertain if this adaptation could also be applied to patients with PsA. This study aims to evaluate the performance and calibration of the CV risk algorithm ASSIGN and its adaptations for RA (ASSIGN-RA) and according to EULAR recommendations in a cohort of patients with PsA (ASSIGN*1.5). Prospectively, collected data from two Italian cohorts has been analyzed. The discriminatory ability for CV risk prediction was assessed using the areas under the ROC curves. Calibration between predicted and observed events was assessed by Hosmer-Lemeshow (HL) test and calibration plots. For each algorithm, sensitivity and specificity were calculated for low- to high-risk cut-off (20%). One hundred fifty-five patients were enrolled with an observation of 1550 patient/years. Area under the ROC were 0.8179 (95% CI 0.72014 to 0.91558) for ASSIGN, 0.8160 (95% CI 0.71661 to 0.91529) for ASSIGN-RA, and 0.8179 (95% CI 0.72014 to 0.91558) for ASSIGN*1.5. HL tests did not demonstrate poor model fit for none of the algorithms. Discriminative ability and calibration were not improved by adaptation of the algorithms according to EULAR recommendations. Up to 20% of CV events occurred in patients at "low risk". No difference in performance has been observed between ASSIGN, Progetto CUORE, and QRISK2. ASSIGN could represent a useful tool in predicting CV risk in patients with PsA. Adaptation for RA or according to EULAR recommendations did not show any further improvement in performance and calibration.

http://bit.ly/2S3wlJo

Identification and characterization of an antimicrobial peptide, lysozyme, from Suncus murinus

Abstract

Lysozyme is one of the most prominent antimicrobial peptides and has been identified from many mammalian species. However, this enzyme has not been studied in the order Insectivora, which includes the most primitive placental mammals. Here, we done the lysozyme cDNA from Suncus murinus (referred to as suncus, its laboratory name) and compare the predicted amino acid sequence to those from other mammalian species. Quantitative PCR analysis revealed a relatively higher expression of this gene in the spleen and gastrointestinal tract of suncus. The lysozyme-immunopositive (ip) cells were found mainly in the red pulp of the spleen and in the mucosa of the whole small intestine, including the follicle-associated epithelium and subepithelial dome of Peyer's patches. The lysozyme-ip cells in the small intestine were mostly distributed in the intestinal crypt, although lysozyme-expressing cells were found not only in the crypt but also in the villi. On the other hand, only a few lysozyme-ip cells were found in the villi and some granules showing intense fluorescence were located toward the lumen. As reported for other mammals, Ki67-ip cells were localized in the crypt and did not co-localize with the lysozyme-ip cells. Moreover, fasting induced a decrease in the mRNA levels of lysozyme in the intestine of suncus. In conclusion, we firstly identified the lysozyme mRNA sequence, clarified expression profile of lysozyme transcripts in suncus and found a unique distribution of lysozyme-producing cells in the suncus intestine.

http://bit.ly/2FPNjoS

The relationship between ventilator-associated pneumonia and chronic obstructive pulmonary disease: what is the current evidence?

Abstract

Chronic obstructive pulmonary disease (COPD) affects approximately 65 million people from which > 25% will require intensive care unit (ICU) admission. Ventilator-associated pneumonia (VAP) is the commonest ICU infection and results in increased morbidity/mortality and costs. The literature on the interaction between COPD and VAP is scarce and controversial. The project aimed to search the literature in order to address the following: (i) Is COPD a risk factor for VAP development? (ii) Does COPD impact the outcome of patients with VAP? (iii) Does VAP development impact the outcome of COPD patients? (iv) Does COPD impact the aetiology of VAP? Current evidence on the topic is controversial. Regarding the impact of VAP on COPD patients, the majority of the existing limited number of studies suggests that VAP development results in higher mortality and longer duration of mechanical ventilation and ICU stay. Also, the majority of the studies exploring the impact of COPD on VAP outcomes suggest that COPD is independently associated with a decrease in survival, although the number of such studies is limited. Regarding the aetiology, Pseudomonas aeruginosa is the most frequent pathogen in VAP patients with COPD. Noteworthy, one study suggests that P. aeruginosa is higher in COPD patients even in the early-onset VAP subgroup. This manuscript provides a comprehensive overview of the available literature on the interaction between COPD and VAP, highlighting the differences and limitations that may have led to controversial results, and it may act as a platform for further research with important clinical implications.

http://bit.ly/2B51PVE

Use of MALDI-TOF mass spectrometry to detect nosocomial outbreaks of Serratia marcescens and Citrobacter freundii

Abstract

MALDI-TOF mass spectrometry (MS) may be used as a rapid typing method for nosocomial pathogens. Here, we evaluated MALDI-TOF MS for discrimination of hospital outbreak-related clusters of Serratia marcescens and carbapenemase-producing Citrobacter freundii. Thirty-three S. marcescens isolates collected from neonatal intensive care unit (NICU) patients, and 23 C. freundii isolates including VIM-positive isolates from a hospital colonization outbreak were measured by Vitek MS. Consensus spectra of each isolate were clustered using SARAMIS software. Genotyping was performed by whole-genome sequencing (WGS). First, a set of 21 S. marcescens isolates from 2014 with seven genotypes including three monoclonal clusters was used for the evaluation of MALDI-TOF typing. MS clustering was largely in agreement with genotyping results when the similarity cut-off for clonal identity was set on 90%. MALDI-TOF cluster analysis was then investigated for the surveillance of S. marcescens in the NICU in 2017 and demonstrated the introduction of new strains into the hospital and nosocomial transmissions. MS analysis of the C. freundii outbreak in 2016 revealed a monoclonal cluster of VIM-positive isolates and the separation of epidemiologically non-related VIM-positive and negative isolates. Two additional VIM-positive Citrobacter isolates from food samples were closely related to the large monoclonal cluster. WGS confirmed the MS results. MALDI-TOF MS may be used as a first-line typing tool for S. marcescens and C. freundii to detect transmission events in the hospital because isolates of an identical WGS type were grouped into the same MS cluster.

http://bit.ly/2T894Du

Gas-Phase Ion/Ion Chemistry as a Probe for the Presence of Carboxylate Groups in Polypeptide Cations

Abstract

The reactivity of 1-hydroxybenzoyl triazole (HOBt) esters with the carboxylate functionality present in peptides is demonstrated in the gas phase with a doubly deprotonated dianion. The reaction forms an anhydride linkage at the carboxylate site. Upon ion trap collisional-induced dissociation (CID) of the modified peptide, the resulting spectrum shows a nominal loss of the mass of the reagent and a water molecule. Analogous phenomenology was also noted for model peptide cations that likely contain zwitterionic/salt-bridged motifs in reactions with a negatively charged HOBt ester. Control experiments indicate that a carboxylate group is the likely reactive site, rather than other possible nucleophilic sites present in the peptide. These observations suggest that HOBt ester chemistry may be used as a chemical probe for the presence and location of carboxylate groups in net positively charged polypeptide ions. As an illustration, deprotonated sulfobenzoyl HOBt was reacted with the [M+7H]⁷⁺ ion of ubiquitin. The ion was shown to react with the reagent and CID of the covalent reaction product yielded an abundant [M+6H-H₂O]⁶⁺ ion. Comparison of the CID product ion spectrum of this ion with that of the water loss product generated from CID of the unmodified [M+6H]⁶⁺ ion revealed the glutamic acid at residue 64 as a reactive site, suggesting that it is present in the deprotonated form.

Graphical Abstract

ᅟ

http://bit.ly/2CHI9Yc

Computational Removal of Undesired Mass Spectral Features Possessing Repeat Units via a Kendrick Mass Filter

Abstract

Polymers are a common component of chemical background which complicates data analysis and can impair interpretation. Undesired chemical background cannot always be addressed via pre-analytical methods, chromatography, or existing data processing methods. The Kendrick mass filter (KMF) is presented for the computational removal of undesired signals present in MS¹ spectra. The KMF is analogous to mass defect filtering but utilizes homology information via Kendrick mass scaling in combination with chromatographic retention time and the number of observed signals. The KMF is intended to assist in situations in which current data processing methods to remove background, e.g., blank subtraction, are either not possible or effective. The major parameters affecting KMF were investigated using PEG 400 and NIST standard reference material 1950 (metabolites in human plasma). Further exploration of the KMF performance was tested using an extract of a swab known to contain polymers. An illustrative real-world example of skin analysis with polymeric signal is discussed. The KMF is also able to provide a high-level view of the compositionality of data regarding the presence of signals with repeat units and indicate the presence of different polymers.

Graphical Abstract

ᅟ

http://bit.ly/2RKKImo

Quantifying SIMS of Organic Mixtures and Depth Profiles—Characterizing Matrix Effects of Fragment Ions

Abstract

Sets of matrix factors, Ξ, are reported for the first time for secondary ions in secondary ion mass spectrometry for several binary organic systems. These show the interplay of the effects of ion velocity, fragment chemistry, and the secondary ion point of origin. Matrix factors are reported for negative ions for Irganox 1010 with FMOC or Irganox 1098 and, for both positive and negative ions, with Ir(ppy)2(acac). For Irganox 1010/FMOC, the Ξ values for Irganox 1010 fall with m/z, whereas those for FMOC rise. For m/z < 250, Ξ scales very approximately with (m/z)^0.5, supporting a dependence on the ion velocity at low mass. Low-mass ions generally have low matrix factors but |Ξ| may still exceed 0.5 for m/z < 50. Analysis of ion sequences with addition or loss of a hydrogen atom shows that the Ξ values for Irganox 1010 and FMOC ions change by − 0.026 and 0.24 per hydrogen atom, respectively, arising from the changing charge transfer rate constant. This effect adds to that of velocity and may be associated with the nine times more hydrogen atoms in the Irganox 1010 molecule than in FMOC. For Irganox 1098/Irganox 1010, the molecular similarity leads to small |Ξ|, except for the pseudo molecular ions where the behavior follows Irganox 1010/FMOC. For Ir(ppy)2(acac)/Irganox 1010, the positive secondary ions show twice the matrix effects of negative ions. These data provide the first overall assessment of matrix factors in organic mixtures necessary for improved understanding for quantification and the precise localization of species.

Graphical Abstract

ᅟ

http://bit.ly/2CG8G88

Screw fixation of ACPHT acetabular fractures offers sufficient biomechanical stability when compared to standard buttress plate fixation

Abstract

Background

Geriatric acetabular fractures require fixation with sufficient primary stability to allow for immediate full-weight bearing. Minimally-invasive procedures would be desirable in order to keep perioperative morbidity low. The purpose of this study was to compare the biomechanical strength of lag screw-only fixation of anterior column posterior hemi-transverse (ACPHT) acetabular fractures to standard anatomical plate fixation.

Methods

Standardized ACPHT fractures were created in fourth generation synthetic pelvis models and stabilized by either an anatomical buttress plate (n = 4) or by a screw-only construct (n = 4). In a validated setup, a cyclic loading protocol was applied with increasing axial force (3200 cycles, 175 N to 2250 N). Construct survival, acetabular fracture motion, and mode of failure were assessed.

Results

The median number of cycles needed until failure of the construct occurred was 2304 cycles (range, 2020 to 2675) in the plate fixation group and 3200 cycles (range, 3101 to 3200) for the screw fixation constructs (p = .003). With regard to energy absorbed until failure, the plate fixation group resisted to 1.57 × 10⁶ N*cycles (range, 1.21 × 10⁶ to 2.14 × 10⁶) and the screw fixation group to 3.17 × 10⁶ N*cycles (range, 2.92 × 10⁶ to 3.17 × 10⁶; p = .001). All plate fixation specimens failed with a break-out of the posterior-column screw in the quadrilateral wing of the anatomical plate within a maximum load of 1750 N while the screw fixation constructs all survived loading of at least 2100 N. Acetabular fracture gap motion, acetabular rim angle, and medial femoral head subluxation as measures of fracture displacement were all not different between the two groups (p > 0.1).

Conclusions

In this in vitro biomechanical study, screw-only fixation of an ACPHT acetabular fracture resulted in at least as good construct survival as seen for standard buttress plate fixation. Both methods resisted sufficiently to forces that would be expected under physiologic conditions.

http://bit.ly/2S33ViO

Rehabilitation and management outcomes of musculoskeletal injuries in a major referral hospital in Ghana

Abstract

Background

The devastating impact of musculoskeletal injury (MSI) on human lives, the economy, and health services cannot be overemphasised. This has ignited discussion at international fora, as countries have been exhorted to prioritise management of MSI in order to maintain a healthy society. In the Ghanaian context, the knowledge base management of MSI is very low, which has provided the impetus to explore the management of MSI and the rehabilitation systems at a tertiary hospital in Ghana.

Methods

The study was a retrospective cross-sectional study, using the consecutive sampling method to recruit patients who were discharged after admission at the accident and emergency unit, as well as patients undergoing orthopaedic review, at the St. Joseph's Orthopaedic Hospital in Koforidua over a six-month period.

Results

A total of 269 musculoskeletal injury patients were recruited for the study. Half of the participants (51%) had had surgery in addition to pain medication. The overall mean recovery days were 26.81 ± 33.94 days, and the average disability days spent in the hospital were estimated at 16.54 ± 27.97 days. Individuals reported financial constraints as a major challenge to their full participation in rehabilitation.

Conclusion

The findings of this study have implications for policymaking in Ghana. Particularly, the need to improve health facilities to enable MSI patients to seek treatment is highlighted. Also, the need to train health professionals who will be able to administer appropriate medication for MSI patients is discussed extensively.

http://bit.ly/2HvM9k4

Dynamic Detection of Thrombolysis in Embolic Stroke Rats by Synchrotron Radiation Angiography

Abstract

A rodent model of embolic middle cerebral artery occlusion is used to mimic cerebral embolism in clinical patients. Thrombolytic therapy is the effective treatment for this ischemic injury. However, it is difficult to detect thrombolysis dynamically in living animals. Synchrotron radiation angiography may provide a novel approach to directly monitor the thrombolytic process and assess collateral circulation after embolic stroke. Thirty-six adult Sprague-Dawley rats underwent the embolic stroke model procedure and were then treated with tissue plasminogen activator. The angiographic images were obtained in vivo by synchrotron radiation angiography. Synchrotron radiation angiography confirmed the successful establishment of occlusion and detected the thrombolysis process after the thrombolytic treatment. The time of thrombolytic recanalization was unstable during embolic stroke. The infarct volume increased as the recanalization time was delayed from 2 to 6 h (p < 0.05). The collateral circulation of the internal carotid artery to the ophthalmic artery, the olfactory artery to the ophthalmic artery, and the posterior cerebral artery to the middle cerebral artery opened after embolic stroke and manifested different opening rates (59%, 24%, and 75%, respectively) in the rats. The opening of the collateral circulation from the posterior cerebral artery to the middle cerebral artery alleviated infarction in rats with successful thrombolysis (p < 0.05). The cerebral vessels of the circle of Willis narrowed after thrombolysis (p < 0.05). Synchrotron radiation angiography provided a unique tool to dynamically detect and assess the thrombolysis process and the collateral circulation during thrombolytic therapy.

http://bit.ly/2Ul6xpN

Anti-Inflammatory and Neuroprotective Effects of DIPOPA (N,N-Diisopropyl-2-Oxopropanamide), an Ethyl Pyruvate Bioisoster, in the Postischemic Brain

Abstract

Ethyl pyruvate (EP) is a simple aliphatic ester of pyruvic acid and has been shown to have protective properties, which have been attributed to its anti-inflammatory, anti-oxidative, and anti-apoptotic functions. In an effort to develop better derivatives of EP, we previously synthesized DEOPA (N,N-diethyl-2-oxopropanamide, a novel isoster of EP) which has greater neuroprotective effects than EP, probably due to its anti-inflammatory and anti-excitotoxic effects. In the present study, we synthesized 3 DEOPA derivatives, in which its diethylamino group was substituted with diisopropylamino, dipropylamino, or diisobutylamino groups. Among them, DIPOPA (N,N-diisopropyl-2-oxopropanamide) containing diisopropylamino group had a greater neuroprotective effect than DEOPA or EP when administered intravenously to a rat middle cerebral artery occlusion (MCAO) model at 9 h after MCAO. Furthermore, DIPOPA had a wider therapeutic window than DEOPA and a marked reduction of infarct volume was accompanied by greater neurological and behavioral improvements. In particular, DIPOPA exerted robust anti-inflammatory effects, as evidenced by marked suppressions of microglia activation and neutrophil infiltration in the MCAO model, in microglial cells, and in neutrophil–endothelial cocultures at lower concentration, and did so more effectively than DEOPA. In particular, DIPOPA remarkably suppressed neutrophil infiltration into brain parenchyma, and this effect was attributed to the expressional inhibitions of cell adhesion molecules in neutrophils of brain parenchyma and in circulating neutrophils via NF-κB inhibition. Together, these results indicate the robust neuroprotective effects of DIPOPA are attributable to its anti-inflammatory effects and suggest that DIPOPA offers a potential therapeutic means of ameliorating cerebral ischemic injury and other inflammation-related pathologies.

http://bit.ly/2RPvA7w

Trichosporon fermentans biomass flocculation from soybean oil refinery wastewater using bioflocculant produced from Paecilomyces sp. M2-1

Abstract

The soybean oil refinery (SOR) wastewater contains a high concentration of chemical oxygen demand (COD) and lipid, so the direct emissions of SOR wastewater will result in environmental pollution and waste of resources. Oleaginous yeast Trichosporon fermentans can consume organic materials in SOR wastewater to synthesize microbial oil, which achieves the purpose of SOR wastewater resource utilization. The effective harvesting technology of oleaginous yeasts can improve the utilization efficiency. In this study, Paecilomyces sp. M2-1 with high flocculating activity was isolated. The flocculants produced by M2-1 (MBF2-1) include 75% (w/w) polysaccharides, rely on cations, and display the flocculation percentage of above 77% in the range of pH 2–11. Especially under alkaline conditions, the flocculation percentage can be kept above 97%. The results of scanning electron microscope observation and zeta potential measurements suggested that the bridging, net trapping, and sweeping were the main flocculation mechanism of MBF2-1. MBF2-1 could flocculate T. fermentans that was used to reduce the organic matter in SOR wastewater and to produce microbial oil. Under the optimum conditions, the flocculation percentage of MBF2-1 against T. fermentans from SOR wastewater can reach 95%. Fatty acid content percent in microbial oil from T. fermentans was not almost affected by flocculation of MBF2-1. Moreover, MBF2-1 can further remove 55% and 53% of COD and oil content in the fermented SOR wastewater, respectively. The properties and high flocculating percentage displayed by MBF2-1 indicated its potential application prospect in oleaginous yeast harvest and food industry wastewater treatment.

http://bit.ly/2FXH1Ti

Association between alcohol consumption and mammographic density: a hospital-based cross-sectional study

Abstract

Background

Mammographic density (MD), the proportion of radiological dense breast, has been reported to be a strong risk factor for breast cancer in many studies. Epidemiological evidence indicates that alcohol consumption increases the risk of breast cancer. In Western countries, a positive association between alcohol consumption and MD has been reported.

Methods

To investigate the effect of alcohol consumption on MD, we conducted a cross-sectional analysis of healthy women enrolled in a breast cancer screening program at the Ebina Health Service Center, Japan, in 2012, comprising 477 premenopausal women and 308 postmenopausal women. Alcohol consumption was assessed using a self-report questionnaire. Unconditional logistic regression was applied to calculate the odds ratio (OR) and 95% confidence intervals (CI) while adjusting for confounders.

Results

The study included 497 women with high breast density (HD group) and 288 women with low breast density (LD group). In all women, multivariate analysis revealed that the OR for HD was significantly increased among women with the highest alcohol intake (≥ 140 g/week of ethanol) compared with abstainers (OR 2.1, 95% CI 1.2–3.9 p = 0.01). The linear trend with increasing alcohol consumption was statistically significant (p = 0.009).

Conclusion

MD was positively associated with alcohol consumption in Japanese women.

http://bit.ly/2B40puA

Effect of respiratory motion on cardiac defect contrast in myocardial perfusion SPECT: a physical phantom study

Abstract

Objective

Correction for respiratory motion in myocardial perfusion imaging requires sorting of emission data into respiratory windows where the intra-window motion is assumed to be negligible. However, it is unclear how much intra-window motion is acceptable. The aim of this study was to determine an optimal value of intra-window residual motion.

Methods

A custom-designed cardiac phantom was created and imaged with a standard dual-detector SPECT/CT system using Tc-99m as the radionuclide. Projection images were generated from the list-mode data simulating respiratory motion blur of several magnitudes from 0 (stationary phantom) to 20 mm. Cardiac defect contrasts in six anatomically different locations, as well as myocardial perfusion of apex, anterior, inferior, septal and lateral walls, were measured at each motion magnitude. Stationary phantom data were compared to motion-blurred data. Two physicians viewed the images and evaluated differences in cardiac defect visibility and myocardial perfusion.

Results

Significant associations were observed between myocardial perfusion in the anterior and inferior walls and respiratory motion. Defect contrasts were found to decline as a function of motion, but the magnitude of the decline depended on the location and shape of the defect. Defects located near the cardiac apex lost contrast more rapidly than those located on the anterior, inferior, septal and lateral wall. The contrast decreased by less than 5% at every location when the motion magnitude was 2 mm or less. According to a visual evaluation, there were differences in myocardial perfusion if the magnitude of the motion was greater than 1 mm, and there were differences in the visibility of the cardiac defect if the magnitude of the motion was greater than 9 mm.

Conclusions

Intra-window respiratory motion should be limited to 2 mm to effectively correct for respiratory motion blur in myocardial perfusion SPECT.

http://bit.ly/2S4woo7

Knowledge-based automatic extraction of multi-structured light stripes

Abstract

To achieve automatic processing of the multi-structured light stripe images, we need to extract many stripes automatically in a short time. However, due to the complexity and diversity of its work, the related research progress is very slow. Therefore, we first use the Radon transformation and grayscale transform enhancement to eliminate noise in images. Then, a new and adaptive feature model is created based on the knowledge of stripes distribution. The distribution of the stripes is matched by the model, and then the target stripe regions are picked up to realize the extraction of the stripes. In the actual verification, the qualified rate of the detection is basically over 80%, and the detection time is controlled at about 2 s. The automatic extraction of target stripes effectively avoids the tedious work that workers need to do it manually, and it is of great significance for the application of multi-structured light detection technology.

http://bit.ly/2CLaf4A

Bacteriophage-host arm race: an update on the mechanism of phage resistance in bacteria and revenge of the phage with the perspective for phage therapy

Abstract

Due to a constant attack by phage, bacteria in the environment have evolved diverse mechanisms to defend themselves. Several reviews on phage resistance mechanisms have been published elsewhere. Thanks to the advancement of molecular techniques, several new phage resistance mechanisms were recently identified. For the practical phage therapy, the emergence of phage-resistant bacteria could be an obstacle. However, unlike antibiotic, phages could evolve a mechanism to counter-adapt against phage-resistant bacteria. In this review, we summarized the most recent studies of the phage-bacteria arm race with the perspective of future applications of phages as antimicrobial agents.

http://bit.ly/2FOX7PY

Expression analysis of long non-coding RNAs and their target genes in multiple sclerosis patients

Abstract

Multiple sclerosis (MS) is a progressive chronic autoimmune-mediated disease. Recently, long non-coding RNAs (lncRNAs) are characterized to participate in the adjustment of immune responses. Here, we evaluated the expression levels of GSTT1-AS1 and IFNG-AS1 lncRNAs and their targets (TNF and IFNG, respectively) in Iranian MS patients.

In this case-control study, 50 relapsing-remitting MS patients and 50 healthy subjects were recruited. Expressions of GSTT1-AS1 and IFNG-AS1 lncRNAs, as well as TNF and IFNG genes, were assessed in their peripheral blood samples by SYBR Green-based Real-time quantitative PCR.

Expression levels of GSTT1-AS1 and IFNG-AS1 lncRNAs were both significantly downregulated (p values 0.032 and 0.013, respectively). On the other hand, the expression of TNF and IFNG showed increased levels, however, did not reach statistical significance after our analysis (p > 0.05). Spearman correlation analysis showed that GSTT1-AS1 had a significant positive moderate correlation with IFNG-AS1 (r = 0.541, p < 0.0001), IFNG (r = 0.329, p = 0.001), and TNF (r = 0.204, p = 0.041). Also, IFNG-AS1 revealed the same correlation with IFNG (r = 0.475, p < 0.0001) as well as TNF (r = 0.399, p < 0.0001). Furthermore, GSTT1-AS1 (r = 0.313, p = 0.027) and (IFNG r = 0.478, p < 0.0001) demonstrated a significant positive correlation with age at onset.

Briefly, the current study provided for the first time dysregulation of GSTT1-AS1 and IFNG-AS lncRNAs network in MS, which highlights the significant role of epigenetic pathways in this autoimmune disorder. Larger sample size and further investigation assays could shed light on the underlying mechanisms in this area of science.

http://bit.ly/2Hw9pOZ

Functional outcome of surgically treated U-shaped sacral fractures: experience from 41 cases

Abstract

Purpose

To delineate the changes in functional outcomes of surgically treated U-shaped sacral fractures.

Methods

Forty-one patients with U-shaped sacral fractures were followed for a mean of 4.1 years after surgery. Impairment of lower extremities was assessed via a modified Gibbons score. Urinary function was assessed with a structured interview and residual urine volume. Sexual and bowel functions, as well as patient-reported health, were evaluated using a structured interview, and pain was evaluated with the visual analog scale. Comparisons of data at different time points were conducted with a mixed model, and Z-scores of the SF-36 questionnaire were calculated.

Results

Forty patients reported pain at 1 year and demonstrated no change at 2 years (p = 0.24). Thirty-six of 39 eligible patients had neurological deficits involving the lower extremities at baseline and demonstrated improvement at 1 year (p = 0.0002) but not between years 1 and 2 (p = 0.47). Twenty-three of 38 eligible patients had impaired bladder function, and 13 of 35 eligible patients had impaired bowel function at 3 months. Urinary function was worse at 2 years than at 1 year (p = 0.02). Sexual dysfunction was common, and patient-reported health was significantly worse than that of the normal population.

Conclusions

Neurological function in the lower extremities of patients with U-shaped sacral fractures improved after surgery; however, bowel and sexual functions did not change, and urinary function deteriorated over time. The majority of impairments appear to be permanent if still present at 1 year after surgery.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

http://bit.ly/2sHkBOo

Can objective functional impairment in lumbar degenerative disease be reliably assessed at home using the five-repetition sit-to-stand test? A prospective study

Abstract

Purpose

Objective functional tests like the five-repetition sit-to-stand test (5R-STS) can supplement an objective dimension to conventional patient-reported outcome measures. The reliability of unsupervised obtainment of 5R-STS performance is currently unknown.

Methods

We included patients with degenerative pathologies of the lumbar spine. Patients performed the 5R-STS during the initial clinical visit (supervised), as well as at home after instruction by a physiotherapist. At home, patients were first timed by a relative (unsupervised) and subsequently produced a video recording of themselves performing the 5R-STS for digital measurement (telesupervised). Two raters independently assessed the recordings.

Results

One hundred and twenty-one patients were recruited, of which 100 were eligible. Eighty-eight reported unsupervised results. Sixty-four returned recordings, of which 61 were ratable. Both unsupervised (r: 0.94, 95% CI 0.91–0.96, p < 0.001) and telesupervised (r: 0.90, 95% CI 0.83–0.94, p < 0.001) measurements demonstrated excellent correlation with clinical test times. Patients did not perform more slowly at home (p > 0.05). The interrater agreement for digital judgement of the telesupervised recording was excellent (ICC: 0.996, 95% CI 0.993–0.998, p < 0.001). We confirmed convergent validity with self-reported disability, back pain, and quality of life (all p < 0.05), but not with leg pain (p = 0.189).

Conclusions

Unsupervised at-home assessment using the 5R-STS is highly reliable. There does not appear to be a specific need for patients to return for a supervised 5R-STS follow-up. Rather, instructions can be provided, and the test performed and rated by a partner or family member at home. This is logistically and economically advantageous for patients, clinicians, and researchers.

Trial registry number

ClinicalTrials.gov Identifier: NCT03321357.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

http://bit.ly/2MsbdHD

Failure to maintain segmental lordosis during TLIF for one-level degenerative spondylolisthesis negatively affects clinical outcome 5 years postoperatively: a prospective cohort of 57 patients

Abstract

Purpose

The present study aimed to determine whether obtaining adequate lumbar (LL) or segmental (SL) lordosis during instrumented TLIF for one-level degenerative spondylolisthesis affects midterm clinical outcome.

Methods

The study was designed as a prospective one, including 57 patients who underwent single-level TLIF surgery for degenerative spondylolisthesis. Patients were analyzed globally with additional subgroup analysis according to pelvic incidence (PI). Radiographic analysis of spinopelvic sagittal parameters was conducted pre- and postoperatively. Clinical examination including ODI score was performed preoperatively, 1 and 5 years postoperatively.

Results

Significant improvement in ODI scores at 1 and 5 years postoperatively (p < 0.001) was demonstrated. There was a significant correlation between anterior shift of SVA and failure to improve SL (p = 0.046). Moreover, anterior SVA shift correlated with increased values of ODI score both 1 and 5 years postoperatively. In low-PI group, failure to correct LL correlated with high ODI scores 5 years postoperatively (r = − 0.499, p = 0.005).

Conclusions

Failure to correct segmental lordosis during surgery for one-level degenerative spondylolisthesis resulted in anterior displacement of the center of gravity, which in turn correlated with unfavorable clinical outcome 1 and 5 years postoperatively. In patients with low PI, failure to maintain lumbar lordosis correlated with unfavorable clinical outcome 5 years after surgery.

Level of evidence

II.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

http://bit.ly/2sIYHKu

Comparison of changes in lean body mass with a strength- versus muscle endurance-based resistance training program

Abstract

Purpose

The aim of this study was to compare the effects of resistance training (RT) with an emphasis on either muscular strength-type RT or muscular endurance-type RT on measures of body composition.

Methods

Twenty-five resistance-trained men (age 28.4 ± 6.4 years; body mass 75.9 ± 8.4 kg; height 176.9 ± 7.5 cm) were randomly assigned to either a strength-type RT group that performed three sets of 6–8 repetition maximum (RM) with 3-min rest (n = 10), an endurance-type RT group that performed three sets of 20–25 RM with a 60-s rest interval (n = 10), or a control group (n = 5, CG). All groups completed each set until muscular failure and were supervised to follow a hyperenergetic diet (39 kcal·kg⁻¹·day⁻¹). Body composition changes were measured by dual-energy X-ray absorptiometry.

Results

After 8 weeks, we found significant increases in total body mass (0.9 [0.3–1.5] kg; p < 0.05; ES = < 0.2) and lean body mass (LBM) (1.3 [0.5–2.2] kg; p < 0.05; ES = 0.31) only in the strength-type RT group; however, no significant interactions were noted between groups.

Conclusions

Although only strength-type RT showed statistically significant increases in LBM from baseline, no between-group differences were noted for any body composition outcome. These findings suggest that LBM gains in resistance trained are not significantly influenced by the type of training stimulus over an 8-week training period.

http://bit.ly/2FUukc2

Deep sequencing reveals specific bacterial signatures in the subgingival microbiota of healthy subjects

Abstract

Objectives

This study aimed to define the comprehensive bacterial flora of the healthy oral cavity by identifying and comparing bacterial species in different subgingival sites using 454 sequencing of 16S rRNA genes.

Materials and methods

Subgingival plaque samples were taken from six target teeth (central incisor, first premolar, and first molar in both the maxilla and mandible) of 10 periodontally healthy patients. Bacterial DNA was extracted and next-generation sequencing of 16S rRNA genes was performed.

Results

Bacterial composition in phylum level was similar for all sites within the same individual irrespective of tooth location. Unweighted UniFrac distance values of microbiome also showed that average distance was significantly larger between subjects than between tooth locations of the same subjects.

Conclusions

The present results clarify the lack of effect of tooth location in the healthy subgingival microbiota. Results may suggest that any subgingival site can demonstrate similar subject-specific microbiota.

Clinical relevance

This investigation offers a better understanding of the uniqueness of the oral microbiome. The present study will facilitate sampling in future subgingival microbiological studies.

http://bit.ly/2DxfvdK

Implementation of multiplex PCR diagnostics for gastrointestinal pathogens linked to increase of notified Shiga toxin-producing Escherichia coli cases in Norway, 2007–2017

Abstract

The aim of this study was to investigate implementation of multiplex PCR assays (broad screening PCR) on the distribution and characteristics of notified Shiga toxin-producing Escherichia coli (STEC) cases in Norway, 2007–2017. We described STEC cases notified to the Norwegian Surveillance System for Communicable Diseases (MSIS), 2007–2017 and categorised cases as high-virulent, low-virulent or unclassifiable STEC infections based on guidelines for follow-up of STEC cases. We conducted descriptive analysis and time series analysis allowing for trends and seasonality, and calculated adjusted incidence rate ratios (aIRR) using negative binomial regression for laboratories with and without broad screening PCR. A total of 1458 STEC cases were notified to MSIS (2007–2017), median age 21 years, 51% female. Cases were categorised as having 475 (33%) high-virulent, 652 (45%) low-virulent, and 331 (23%) unclassifiable STEC infections. We observed a higher increasing monthly trend in cases (aIRR = 1.020; 95% CI 1.016–1.024) notified from laboratories with broad screening PCR (n = 4) compared to laboratories (n = 17) without (aIRR = 1.011; 95% CI 1.007–1.014). Notification of low-virulent STEC infections increased from laboratories with broad screening PCR. The increase in notified STEC cases was prominent in cases categorised with a low-virulent STEC infection and largely attributable to unselective screening methods. We recommend NIPH to maintain differentiated control measures for STEC cases to avoid follow-up of low-virulent STEC infections. We recommend microbiological laboratories in Norway to consider a more cost-effective broad screening PCR strategy that enables differentiation of high-virulent STEC infections.

http://bit.ly/2MuL2jB

Macrolide prescription in Dutch children: compliance with guidelines

Abstract

For reasons of antibiotic resistance and side effects, macrolides should be prescribed with care in the pediatric population. We evaluated the adherence to Dutch guidelines of macrolide prescription in children and estimated the risk of Mycoplasma pneumoniae–associated pneumonia based on Fischer's decision tree. In this retrospective study, we included children aged 0–18 years who were treated with azithromycin or clarithromycin for pulmonary disease in four settings from general practice to hospital ward for (1) the prescriptions not in accordance with the guideline of the Dutch Association of Pediatrics and (2) the risk of M. pneumoniae in patients with community-acquired pneumonia (CAP) according to Fischer's decision tree. The latter suggests that children older than three years with a fever lasting more than two days are at high risk for M. pneumoniae and that it is therefore justified to treat them with macrolides. In total, 189 macrolide prescriptions from 2015 until 2017 were analyzed: 139 children used macrolides for a pulmonary indication (75%); 18% (n = 25) of the prescriptions were not in accordance with Dutch guidelines. Only 9.1% of patients with CAP were classified as having a high risk of M. pneumoniae according to Fischer's decision tree. A significant proportion of macrolide prescriptions for Dutch children with a pulmonary disease appears not to be in accordance with the guidelines. Most patients with CAP treated with a macrolide actually had a low risk of having M. pneumoniae according to Fischer's decision tree. Both observations suggest overuse of macrolides in children.

http://bit.ly/2sSqvMV

Persistent Candidemia in adults: underlying causes and clinical significance in the antifungal stewardship era

Abstract

To investigate the causes and the clinical significance of persistent candidemia (PC) in adults diagnosed in a tertiary hospital with an active antifungal stewardship program. Retrospective cohort including all adults with candidemia from 2010 to 2018. PC was defined as any positive follow-up blood culture (BC) obtained ≥ 5 days from the first BCs yielding the same Candida species. PC was detected in 35/255 (13.7%) patients. There were no differences regarding antifungal adequacy in PC vs. non-PC (94.3% vs. 82.3%, p = 0.084) and primary source control (63.3% vs. 76.4%, p = 0.172) at the time of the follow-up BCs. The average time until source control (2 [0–37] vs. 2 days [0–44], p = 0.311) or adequate antifungal treatment (2 [0–26] vs. 2 days [− 2–10], p = 0.748) was similar. Patients with PC had more non-ocular complications (31.4% vs. 10.5%, p = 0.002). No impact on 30-day mortality was observed (31.4% vs. 22.3%, p = 0.238). The only independent factor associated with PC was to have a previously undetected site of infection [OR 4.28, 95%CI (1.77–10.34), p = 0.001]. Persistent candidemia was not associated with inadequate or delayed therapeutic management, nor higher 30-day mortality rates. Timely screening and control of unexpected infection sources are encouraged to shorten hospitalization and improve patient care.

http://bit.ly/2MvQHWg

Limited awareness of the effective timing of HIV post-exposure prophylaxis among people with high-risk exposure to HIV

Abstract

The effectiveness of post-exposure prophylaxis (PEP), a major strategy in the battle against HIV, depends on awareness of this modality and its proper timing among high-risk groups. While general awareness of PEP is improving, recently estimated to be 36–47% among men who have sex with men (MSM), PEP implementation remains disappointingly low and may be driven by limited awareness of effective PEP timing window. The level of detailed understanding of PEP timing and effectiveness among populations at risk has not been prospectively assessed to date. We prospectively evaluated, for the first time, actionable awareness regarding effective timing of PEP among a large cohort of individuals tested for HIV following unprotected sexual intercourse. Four hundred participants were assessed between December 2014 and February 2016. Overall awareness of the option of PEP was 60% and was significantly higher among male members of the LGBTQ community (75·5% as compared to 52·6% among heterosexual males) and those undergoing past HIV testing (67·1%). However, only 24% of individuals at risk were aware as to the proper timing of effective PEP treatment, thereby leading, in the majority of cases, to missing the window of opportunity for PEP treatment. This study highlights the lack of knowledge as to the specific requirements needed for effective PEP timing. Expanded advertising, better targeting of the heterosexual population, training of family physicians in the field of gender, sexuality, and LGBTQ medicine, may improve effective PEP availability, thereby reducing HIV transmission.

http://bit.ly/2sN5EKw

Challenges in diagnosing Zika—experiences from a reference laboratory n a non-endemic setting

Abstract

Diagnosing a patient with Zika infection is not always straightforward. Here, we aim to describe our data collected from December 2015 to December 2017 and discuss the implemented algorithm and diagnostic challenges we encountered. At the National Reference Center for Arboviruses at the Institute of Tropical Medicine, Antwerp, Belgium (ITM), a commercial Zika virus (ZIKV) enzyme-linked immunosorbent assay (ELISA) detecting immunoglobulin (Ig) M and IgG, a commercial ZIKV immunofluorescence assay (IFA) detecting IgM, and an in-house Zika virus neutralization test (VNT) were implemented. For molecular detection of ZIKV, an in-house and a commercial real-time RT-PCR were applied. An algorithm, adapted from the European Centre for Disease Control and Prevention (ECDC), was implemented. Between December 2015 and December 2017, we tested 6417 patients for ZIKV. Of those, according to ECDC criteria, 127 (2.0%) were classified as a confirmed Zika infection of which 39 by RT-PCR (0.6%), 15 (0.2%) as a probable Zika infection, 73 (1.1%) as undefined, and 65 (1.0%) as false positive reactions. Main challenges were the brief window for detection of IgM, cross-reactivity of antibodies with other flaviviruses and malaria, and low VNT titers in the acute phase. In RT-PCR negative samples, classification of ZIKV infection as recent or past proved difficult, when IgM was negative. The majority of patients could be classified according to ECDC criteria, though 1.1% of patients remained "undefined" and 1.0% were ELISA false positive reactions. Complementary IFA IgM was of added value to increase IgM detection rates. Improved serological assays and more longitudinal data on antibody kinetics are needed.

http://bit.ly/2MuL5vE

The possible zoonotic diseases transferring from pig to human in Vietnam

Abstract

Southeast Asia is considered one of worldwide hotspots consisting many distinct zoonotic infections. With optimal condition for the development of various pathogens, Vietnam is facing serious risks of zoonotic diseases. Besides, more than 50% Vietnamese people settle in rustic areas and earn their livings through small-scale animal breeding. It is possible that zoonotic diseases can be easily spread to the population by close contact with the infected animals, their infected residues, contaminated water, soil, or other possible means of transmission. In fact, zoonotic infections—transmissible infections between vertebrate animals and humans—cover a wide range of diseases with distinctive clinical and epidemiological highlights. With insufficient understanding and swift alteration in toxicity of the pathogens, these infections have gained more concerns due to sophisticated routes of transmission and harmful threats to humans. Recently emerging viral diseases exerted potential dangers to human beings, which required many countries to impose immediate actions to prevent any complications. Vietnam has recorded several cases of zoonotic diseases, especially pig-related illnesses; however, the studies on these diseases in this country remain limited. This work aims to highlight the zoonotic diseases transferring from pigs to humans and discuss risk factors of these diseases in Vietnam.

http://bit.ly/2sH9GEo

The role of therapy with aminoglycoside in the outcomes of kidney transplant recipients infected with polymyxin- and carbapenem-resistant Enterobacteriaceae

Abstract

Kidney transplant recipients are at risk for infections due to carbapenem-resistant Enterobacteriaceae (CRE). Polymyxin-resistant CRE (PR-CRE) infections are especially difficult to treat. The aim of this study was to characterize PR-CRE infections among kidney transplant recipients and identify risk factors for treatment failure. This retrospective cohort study involved all kidney transplant recipients with PR-CRE infection between 2013 and 2017 at our center. Minimal inhibitory concentrations for polymyxin B were determined by broth microdilution. Carbapenem-resistant genes (bla_KPC, bla_NDM, and bla_OXA-48), aminoglycoside-resistance genes, and polymyxin-resistant gene mcr-1 were identified by polymerase chain reaction. All but one of the 47PR-CRE infections identified were due to Klebsiella pneumoniae. The most common type of infection (in 54.3%) was urinary tract infection (UTI). Monotherapy was used in 10 cases. Combined treatment regimens included double-carbapenem therapy in 19 cases, oral fosfomycin in 19, and amikacin in 13. Treatment failure occurred in 21 cases (45.7%). Clinical success was achieved 78.9% of patients who used aminoglycosides versus 37.0% of those who not used this drug (p = 0.007). Multivariate analysis showed diabetes mellitus to be a risk factor for treatment failure; amikacin use and UTI were found to be protective. Nine strains were RmtB producers. Although aminoglycosides constitute an important therapeutic option for PR-CRE infection, the emergence of aminoglycoside resistance could have a major impact on the management of CRE infection.

http://bit.ly/2MrV5G5

Short- versus long-course therapy in gram-negative bacilli bloodstream infections

Abstract

Bacteremia due to gram-negative bacilli (GNB) is one of the most frequent causes of admission and prolongation of hospital stay. Nevertheless, optimal duration of antibiotic treatment is not clearly established. We designed an observational, prospective study of a cohort of adult patients with uncomplicated GNB bacteremia. They were classified according to the duration of treatment in short (7–10 days) or long (> 10 days) course. Mortality and bacteremia recurrence rate were evaluated, and propensity score for receiving short-course treatment was calculated. A total of 395 patients met eligibility criteria including 232 and 163 who received long- and short-course therapy, respectively. Median age was 71 years, 215 (54.4% male) and 51% had a urinary source. Thirty-day mortality was 12%. In multivariate analysis by logistic regression stratified according to propensity score quartile for receiving short-course therapy showed no association of duration of treatment with 30-day mortality or 90-day recurrence rate. Based on the results observed in our cohort, short-course therapy could be as safe and effective as longer courses.

http://bit.ly/2sMfNYc

Clinical outcome of pharmacist-led prospective audit with intervention and feedback after expansion from patients using specific antibiotics to those using whole injectable antibiotics

Abstract

Prospective audit with intervention and feedback (PAF) and preauthorisation of antimicrobials are core strategies for antimicrobial stewardship (AS). PAF participants were expanded from patients using specific antibiotics to those using whole injectable antibiotics to evaluate clinical outcome. From January 2016 to December 2016, PAF was performed in patients using specific antibiotics (period 1) and from January 2017 to December 2017, PAF was performed in patients using whole injectable antibiotics (period 2). PAF was implemented for 5 days every week by pharmacists involved in infectious diseases chemotherapy. In total, 11,571 and 11,103 patients used antibiotic injections during periods 1 and 2, respectively. No significant difference in mortality within 30 days from the initial use of injection antibiotics was observed. The average duration of hospitalisation was significantly shorter during period 2 among patients using antibiotics; however, this was not significantly different from that of patients not receiving antibiotics. The average duration of therapy for intravenous antibiotics was significantly shorter during period 2 than during period 1. The ratio of methicillin-resistant Staphylococcus aureus (MRSA) to S. aureus was significantly low during period 2. The duration of intravenous antibiotic therapy for Escherichia coli bacteraemia during period 2 decreased significantly. De-escalation and appropriate antimicrobial treatment rates at specific doses during period 2 increased significantly. Expansion of patients eligible for PAF from patients using specific antibiotics to patients using whole injectable antibiotics shortened hospital stays, suppressed drug resistance, and promoted the appropriate use of antibiotics.

http://bit.ly/2MtcdLy

Anatomy Pathology

 Annals of Diagnostic Pathology

The frequency of <em>NOTCH1</em> variants in T-acute lymphoblastic leukemia/lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma among Jordanian patients

Publication date: Available online 24 January 2019Source: Annals of Diagnostic PathologyAuthor(s): Nezeen Z. Abualhaj, Zain Dardas, Belal Azab, Dema Ali, Maher A. Sughayer, Tariq N. Aladily, Mamoun AhramAbstractThe transmembrane receptor NOTCH1 is thought to be associated with the development and progression of T-acute lymphoblastic leukemia (T-ALL)/T-lymphoblastic lymphoma (T-LBL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The current study aimed to characterize NOTCH1...

Annals of Diagnostic Pathology

4h

Mark above section as read

 Pathology International

Combined hepatocellular‐cholangiocarcinoma with angiosarcomatoid change: A case report with immunohistochemical study

Sarcomatoid combined hepatocellular‐cholangiocarcinoma (cHCC‐CCA) is a rare condition, with only 16 cases reported to date; however, there have been no reports of hepatic sarcomatoid carcinoma with angiosarcomatous features. Here, we report a rare case of cHCC‐CCA with angiosarcomatoid changes in a 77‐year‐old man. The tumor was biphasic with malignant epithelial and mesenchymal components. Histologically, the epithelial component was concordant with classical type cHCC‐CCA. The mesenchymal component...

Pathology International

1d

Intravascular large B‐cell lymphoma involving large blood vessels, three autopsy cases

Although intravascular large B‐cell lymphoma (IVLBCL) is an extranodal lymphoma characterized by the selective growth of lymphoma cells within the lumina of small vessels, we here report three autopsy cases of IVLBCL characterized by the proliferation within large blood vessels. These three cases were diagnosed as IVLBCL of the bone marrow or skin biopsy. Two cases died suddenly before treatment, whereas the other died during treatment. Autopsies showed a large embolus of dense lymphoma cells extending...

Pathology International

1d

Mark above section as read

 Cells Tissues Organs

Whey Protein Complexes with Green Tea Polyphenols: Antimicrobial, Osteoblast-Stimulatory, and Antioxidant Activities

Polyphenols are known for their antimicrobial activity, whilst both polyphenols and the globular protein β-lactoglobulin (bLG) are suggested to have antioxidant properties and promote cell proliferation. These are potentially useful properties for a tissue-engineered construct, though it is unknown if they are retained when both compounds are used in combination. In this study, a range of different microbes and an osteoblast-like cell line (human fetal osteoblast, hFOB) were used to assess the combined...

Cells Tissues Organs

2h

Two Web Resources Linking Major Human Embryology Collections Worldwide

Human embryology is a core subject for medicine and current research. While animal models of development now have significant online resources available, the vast majority of human embryonic material is locked up in historic collections. When accessed today, these collections are still contributing to our understanding of human development. This paper describes two online resources for studying human development that are unlocking these invaluable collections and providing related human developmental...

Cells Tissues Organs

1d

Mark above section as read

 Case Reports in Pathology

A Rare Case of Fibrous Hamartoma of Infancy: A Clinicopathological Diagnosis at a Tertiary Hospital, Eastern Nepal

Background. Fibrous hamartoma of infancy is a rare soft tissue lesion of infants and young children with characteristic triphasic morphology. Case Description. An 18-month-old female child was presented with complaints of swelling over right leg shin since birth. On examination, a lump of size 7x3 cm was identified which was mobile and nontender. Local excision was performed and tissue sent for histopathological examination. On gross examination, a globular, capsulated, firm to hard tissue had cut...

Case Reports in Pathology

1d

Mark above section as read

 Cancer Cytopathology

The prevalence and surgical outcomes of Hurthle cell lesions in FNAs of the thyroid: A multi‐institutional study in 6 Asian countries

Background Hurthle cell‐rich nodules (HCNs) encompass non‐neoplastic to malignant lesions. There is paucity of literature on the frequency distribution of HCNs among Bethesda categories, histologic follow‐up, risk of malignancy (ROM), and risk of neoplasia (RON). The objective of this retrospective, multi‐institutional study was to determine the prevalence of the cytologic diagnostic category and surgical outcomes of patients with HCN. Methods Nine tertiary health centers representing 6 Asian...

Cancer Cytopathology

1d

Negative predictive value and sensitivity of urine cytology prior to implementation of The Paris System for Reporting Urinary Cytology

Background Urinary tract cytology (UTCy) is used for screening urothelial carcinoma (UC) and it must have a high negative predictive value (NPV) to be an effective test. To the authors' knowledge, the literature regarding the NPV of UTCy provides little information regarding the risk of malignancy, especially for patients with high‐grade urothelial carcinoma (HGUC). Methods Patients with negative UTCy specimens were identified in the pathology files at the study institution for the years 2012...

Cancer Cytopathology

1d

The value of cytology in the management of patients with pancreatic cysts

Cancer Cytopathology

1d