Automated point-of-care molecular assays have greatly shortened the turnaround time of respiratory virus testing. One of the major bottlenecks now lies at the specimen collection step, especially in ...a busy clinical setting. Saliva is a convenient specimen type that can be provided easily by adult patients. This study assessed the diagnostic validity, specimen collection time and cost associated with the use of saliva.
This was a prospective diagnostic validity study comparing the detection rate of respiratory viruses between saliva and nasopharyngeal aspirate (NPA) among adult hospitalized patients using Xpert® Xpress Flu/RSV. The cost and time associated with the collection of saliva and nasopharyngeal specimens were also estimated.
Between July and October 2017, 214 patients were recruited. The overall agreement between saliva and NPA was 93.3% (196/210, κ 0.851, 95% CI 0.776–0.926). There was no significant difference in the detection rate of respiratory viruses between saliva and NPA (32.9% (69/210) versus 35.7% (75/210); p 0.146). The overall sensitivity and specificity were 90.8% (81.9%–96.2%) and 100% (97.3%–100%), respectively, for saliva, and were 96.1% (88.9%–99.2%) and 98.5% (94.7%–99.8%), respectively, for NPA. The time and cost associated with the collection of saliva were 2.26-fold and 2.59-fold lower, respectively, than those of NPA.
Saliva specimens have high sensitivity and specificity in the detection of respiratory viruses by an automated multiplex Clinical Laboratory Improvement Amendments-waived point-of-care molecular assay when compared with those of NPA. The use of saliva also reduces the time and cost associated with specimen collection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To determine the viral epidemiology and clinical characteristics of patients with and without clinically apparent respiratory tract infection.
This prospective cohort study was conducted during the ...2018 winter influenza season. Adult patients with fever/respiratory symptoms (fever/RS group) were age- and sex-matched with patients without fever/RS (non-fever/RS group) in a 1:1 ratio. Respiratory viruses were tested using NxTAG™ Respiratory Pathogen Panel IVD, a commercially-available multiplex PCR panel.
A total of 214 acutely hospitalized patients were included in the final analysis, consisting of 107 with fever/RS (fever/RS group), and 107 age- and sex-matched patients without fever/RS (non-fever/RS group). Respiratory viruses were detected in 34.1% (73/214) of patients, and co-infection occurred in 7.9% (17/214) of patients. The incidence of respiratory virus was higher in the fever/RS group than in the non-fever/RS group (44.9% (48/107) versus 23.4% (25/107), p 0.001). Influenza B virus, enterovirus/rhinovirus and coronaviruses were detected more frequently in the fever/RS group, whereas parainfluenza virus 4B and adenovirus were detected more frequently in the non-fever/RS group. Among the non-fever/RS group, chest discomfort was more common among patients tested positive for respiratory viruses than those without respiratory virus detected (44% (11/25) versus 22% (18/82), p 0.04).
Respiratory viruses can be frequently detected among hospitalized patients without typical features of respiratory tract infection. These patients may be a source of nosocomial outbreaks.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The appropriate use of generic preference-based measures determines the accuracy of disease assessment and further decision on healthcare policy using quality adjusted life years. The discriminative ...capacity of different instruments would differ across disease groups. Our study was to examine the difference in utility scores for COPD patients measured by EQ-5D and SF-6D and to assist the choice of a proper instrument in this disease group.
Differences of mean utility scores of EQ-5D and SF-6D in groups defined by socio-demographic characteristics, comorbidities, health service utilisation and severity of illness were tested using Mann-Whitney test, t-test, Kruskal-Wallis test, Pearson's correlation coefficient and ANOVA, as appropriate. The discriminative properties of the two instruments were compared against indicators of quality of life using receiver operating characteristic curves. The statistical significance of the area under the curves (AUC) was tested by ANOVA and F-statistics used to compare the efficiency with which each instrument discriminated between disease severity groups.
Mean utility scores of EQ-5D and SF-6D were 0.644 and 0.629 respectively in the 154 subjects included in the analysis. EQ-5D scores were significantly higher than SF-6D in groups less severe and these differences corresponded to a minimally important difference of greater than 0.03 (p<0.001). EQ-5D and SF-6D scores were strongly correlated across the whole sample (r = 0.677, p<0.001) and in pre-defined groups (r>0.5 and p<0.05 for all correlation coefficients). AUCs were above 0.5 against the indicators of health-related quality of life for both instruments. F-ratios suggested SF-6D was more efficient in discriminating cases of different disease severity than EQ-5D.
Both EQ-5D and SF-6D appeared to be valid preference-based measures in Chinese COPD patients. SF-6D was more efficient in detecting differences among subgroups with differing health status. EQ-5D and SF-6D measured different things and might not be used interchangeably in COPD patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study seeks to determine the objective and subjective success rates of anterior palatoplasty and its variants for the treatment of obstructive sleep apnoea (OSA). A systematic review with two ...independent searches of Medline, PubMed, Cochrane Library and Evidence Based Medicine Reviews was performed to identify publications relevant to OSA and anterior palatoplasty. All relevant studies published before 30 June 2015 were included. Six studies were included in the systematic review. The numbers of patients in each paper ranged from 13 to 77 (total = 240), and mean age ranged from 21 to 51 years. Substantial and consistent improvement in polysomnography (PSG) outcomes were observed in patients after the anterior palatoplasty, with or without multilevel surgery. The results showed that the anterior palatoplasty technique provides significantly improvement in the post-operative Apnoea-Hypopnea Index. The mean pre-operative AHI (in the 6 papers) improved from 16.3 to 7.1, the snore visual analogue scale improved from 7.5 to 3.1 and the Epworth score reduced from 11.3 to 7.3 post-operatively. The overall pro-rated pooled success rate for all the patients was 72.5%, with a mean follow-up of 17.3 months. Anterior palatoplasty is an effective option in the management of patients with mild to moderate OSA.
Objectives
To investigate effects of platelet‐rich plasma on tendon cell proliferation and the underlying molecular mechanisms.
Materials and methods
Platelet‐rich plasma was prepared manually by ...two‐step centrifugation. Proliferation was evaluated in cultured rat tendon cells by the 3‐4,5‐dimethylthiazol‐2‐yl‐2,5‐diphenyltetrazolium bromide assay. Cell cycle progression was assessed by flow cytometry. Messenger RNA expression of proliferating cell nuclear antigen (PCNA), cyclin E1, A2 and B1, and cyclin‐dependent kinases (Cdks) 1 and 2 was assessed by real‐time polymerase chain reaction. Protein expression of the above cyclins and Cdks and of signal transducer and activator of transcription (Stat) 3 and p27 was evaluated by western blotting.
Results
Platelet‐rich plasma used in the present study had concentrations of platelets, TGF‐β1 and PDGF over 3‐fold higher than normal whole blood. Platelet‐rich plasma enhanced tendon cell proliferation (P = 0.008) by promoting G1/S phase transition in the cell cycle, and increased expression of PCNA, cyclin E1, A2 and B1, Cdks1 and 2, and phosphorylated Stat3, while inhibiting p27 expression.
Conclusions
Platelet‐rich plasma contains high concentrations of TGF‐β1 and PDGF that increase tendon cell proliferation by modulating Stat3/p27Kip1, which enhances expression of cyclin–Cdk complexes that promote cell cycle progression. These results provide molecular evidence for positive effects of platelet‐rich plasma on tendon cell proliferation, which can be useful in clinical applications of tendon injury.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Human epidermal growth factor receptor 2 (HER2)/Neu is overexpressed in 20-30% of breast cancers and associated with aggressive phenotypes and poor prognosis. For deciphering the role of HER2/Neu in ...breast cancer, mouse mammary tumor virus (MMTV)-Her2/neu transgenic mice that develop mammary tumors resembling human HER2-subtype breast cancer have been established. Several recent studies have revealed that HER2/Neu is overexpressed in and regulates self renewal of breast tumor-initiating cells (TICs). However, in the MMTV-Her2/neu transgenic mouse model, the identity of TICs remains elusive, despite previous studies showing supportive evidence for existence of TICs in Her2/neu-induced mammary tumors. Through systematic screening and characterization, we identified that surface markers CD49f, CD61 and ESA were aberrantly overexpressed in Her2-overexpressing mammary tumor cells. Analysis of these markers and CD24 detected anomalous expansion of the luminal progenitor population in preneoplastic mammary glands of Her2/neu transgenic mice, indicating that aberrant luminal progenitors originated in Her2-induced mammary tumors. The combined markers, CD49f and CD61, further delineated the CD49f(high)CD61(high)-sorted fraction as a TIC-enriched population, which displayed increased tumorsphere formation ability, enhanced tumorigenicity both in vitro and in vivo and drug resistance to pacitaxel and doxorubicin. Moreover, the TIC-enriched population manifested increased transforming growth factor-β (TGFβ) signaling and exhibited gene expression signatures of stemness, TGFβ signaling and epithelial-to-mesenchymal transition. Our findings that self-renewal and clonogenicity of TICs were suppressed by pharmacologically inhibiting the TGFβ signaling further indicate that the TGFβ pathway is vital for maintenance of the TIC population. Finally, we showed that the integrin-β3 (CD61) signaling pathway was required for sustaining active TGFβ signaling and self-renewal of TICs. We for the first time developed a technique to highly enrich TICs from mammary tumors of Her2/neu transgenic mice, unraveled their properties and identified the cooperative integrin-β3-TGFβ signaling axis as a potential therapeutic target for HER2-induced TICs.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The superheavy element with atomic number Z=117 was produced as an evaporation residue in the (48)Ca+(249)Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The ...radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-μs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope (294)117 and its decay products. A hitherto unknown α-decay branch in (270)Db (Z = 105) was observed, which populated the new isotope (266)Lr (Z = 103). The identification of the long-lived (T(1/2) = 1.0(-0.4)(+1.9) h) α-emitter (270)Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an "island of stability."
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Summary Background & aims B-vitamins and homocysteine may contribute to the development of gestational diabetes mellitus (GDM), but existing studies are inconsistent. We examined the cross-sectional ...associations of plasma folate, vitamins B6, B12, and homocysteine concentrations with GDM and glycemia in a sample of multi-ethnic Asian pregnant women. Methods Plasma concentrations of folate, vitamins B6, B12, homocysteine and glucose were measured at 26-weeks’ gestation in 913 pregnant women. GDM was diagnosed using the 1999 World Health Organization criteria. Associations were examined with linear or logistic regression, adjusted for confounders and stratified by ethnicity. Results Higher plasma folate was associated with higher 2-h glucose and higher odds of GDM 0.15 (0.02, 0.23) per 1-SD increment in folate, OR 1.29 (1.00, 1.60), mainly among Indian mothers. Higher plasma vitamin B12 and homocysteine were associated with lower fasting and 2-h glucose, and lower odds of GDM −0.04 (−0.07, −0.01) per 1-SD increment in B12 and −0.09 (−0.18, −0.003) respectively, OR: 0.81 (0.68, 0.97); −0.05 (−0.08, −0.02) per 1-SD increment in homocysteine and −0.12 (−0.21, −0.02) respectively, OR: 0.76 (0.62, 0.92). The highest odds of GDM were observed among women with combined vitamin B12 insufficiency and high folate concentration OR: 1.97 (1.05, 3.68). An association between higher vitamin B6 and higher 2-h glucose shifted towards null adjusting for other B-vitamins. Conclusions Higher maternal folate coupled with vitamin B12 insufficiency was associated with higher GDM risk. This finding has potential implications for antenatal supplement recommendations but will require confirmation in future studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background and Aims
Hypoxia is one of the central players in shaping the immune context of the tumor microenvironment (TME). However, the complex interplay between immune cell infiltrates within the ...hypoxic TME of HCC remains to be elucidated.
Approach and Results
We analyzed the immune landscapes of hypoxia‐low and hypoxia‐high tumor regions using cytometry by time of light, immunohistochemistry, and transcriptomic analyses. The mechanisms of immunosuppression in immune subsets of interest were further explored using in vitro hypoxia assays. Regulatory T cells (Tregs) and a number of immunosuppressive myeloid subsets, including M2 macrophages and human leukocyte antigen–DR isotype (HLA‐DRlo) type 2 conventional dendritic cell (cDC2), were found to be significantly enriched in hypoxia‐high tumor regions. On the other hand, the abundance of active granzyme Bhi PD‐1lo CD8+ T cells in hypoxia‐low tumor regions implied a relatively active immune landscape compared with hypoxia‐high regions. The up‐regulation of cancer‐associated genes in the tumor tissues and immunosuppressive genes in the tumor‐infiltrating leukocytes supported a highly pro‐tumorigenic network in hypoxic HCC. Chemokine genes such as CCL20 (C‐C motif chemokine ligand 20) and CXCL5 (C‐X‐C motif chemokine ligand 5) were associated with recruitment of both Tregs and HLA‐DRlo cDC2 to hypoxia‐high microenvironments. The interaction between Tregs and cDC2 under a hypoxic TME resulted in a loss of antigen‐presenting HLA‐DR on cDC2.
Conclusions
We uncovered the unique immunosuppressive landscapes and identified key immune subsets enriched in hypoxic HCC. In particular, we identified a potential Treg‐mediated immunosuppression through interaction with a cDC2 subset in HCC that could be exploited for immunotherapies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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