•We evaluated the performance of the Roche Elecsys IL6 assay on the Cobas analyser.•IL6 levels and inflammatory markers of 52 cases and 144 controls were compared.•IL6 in patients with COVID-like ...respiratory symptoms were higher than controls.•IL6 > 75 pg/mL was superior to other inflammatory markers in predicting ICU admission.•In some cases, IL6 rises earlier than the other inflammatory markers.
We evaluated the Roche Elecsys IL6 assay on the Cobas immunoassay analyser.
Serum IL6 of 144 controls were compared to 52 samples from patients with COVID-like respiratory symptoms (17 SARS-CoV-2 RT-PCR positive); 25 of these were from the intensive care unit (ICU). We compared the IL6 levels to C-reactive protein (CRP) and procalcitonin (PCT) levels in all cases.
The IL6 assay had coefficient-of-variation (CV) of 2.3 % (34.1 pg/mL) and 2.5 % (222.5 pg/mL), a limit of quantitation <1.6 pg/mL, and was linear from 1.6 to 4948 pg/mL. There was a significant difference in IL6 values between patients with COVID-like respiratory symptoms versus controls (p < 0.001). ROC analysis showed that IL6 > 6.4 pg/mL identified symptomatic cases (AUC 0.94, sensitivity 88.2 %, specificity 97.2 %). There was a significant difference between the IL6 of symptomatic ICU/non-ICU cases (median IL6 228 vs 11 pg/mL, p < 0.0001); ROC analysis showed IL6 > 75 pg/mL (sensitivity 76.0 %, specificity 88.9 %) was superior to CRP and PCT in predicting ICU admission (AUC: IL6 0.83, CRP 0.71, PCT 0.82).
The performance of Elecsys IL6 assay is in keeping with the manufacturer’s claims. IL6 > 6.4 pg/mL differentiates healthy from suspected COVID-19 cases and appears to be raised earlier than the other inflammatory markers in some cases. IL6 > 75 pg/mL was a good predictor of ICU admission.
The role of laminar flow (LAF) is contradictory with several studies failing to replicate risk reduction. The 2016 World Health Organization guidelines identified this lack of good comparative ...studies.
To analyse the use of LAF and the incidence of prosthetic joint infections (PJIs) in Asian patients undergoing total knee replacement (TKR).
Patients who underwent standard cemented posterior-stabilized TKR from 2004 to 2014 were reviewed from a prospectively collected single-surgeon database. Revision, traumatic and/or inflammatory cases were excluded. The type of airflow used was identified. The technique and surgical protocol for all procedures were similar. Tourniquets and inserted drains were routinely used. Patellar resurfacing was not performed. Patients were followed up at the outpatient clinics at regular intervals up to two years. At each visit, the patient was assessed for the occurrence of PJI.
Of the 1028 procedures, 453 (44.1%) were performed in an LAF operating theatre (OT) whereas 575 (55.9%) were performed in a non-LAF OT. There were no significant differences between the two groups in terms of age, gender, or side of procedure. The overall incidence of PJI was 0.6% (N = 6). Three (50%) occurred in an LAF OT whereas three (50%) occurred in a non-LAF OT. This was not statistically significant.
Laminar flow systems are costly to procure and maintain. With modern aseptic techniques, patient optimization, and use of prophylactic antibiotics, laminar flow does not appear to further reduce risk of PJI in Asian patients after TKR.
Chloroplast retrograde signaling networks are vital for chloroplast biogenesis, operation, and signaling, including excess light and drought stress signaling. To date, retrograde signaling has been ...considered in the context of land plant adaptation, but not regarding the origin and evolution of signaling cascades linking chloroplast function to stomatal regulation. We show that key elements of the chloroplast retrograde signaling process, the nucleotide phosphatase (SAL1) and 3′-phosphoadenosine-5′-phosphate (PAP) metabolism, evolved in streptophyte algae—the algal ancestors of land plants. We discover an early evolution of SAL1-PAP chloroplast retrograde signaling in stomatal regulation based on conserved gene and protein structure, function, and enzyme activity and transit peptides of SAL1s in species including flowering plants, the fern Ceratopteris richardii, and the moss Physcomitrella patens. Moreover, we demonstrate that PAP regulates stomatal closure via secondary messengers and ion transport in guard cells of these diverse lineages. The origin of stomata facilitated gas exchange in the earliest land plants. Our findings suggest that the conquest of land by plants was enabled by rapid response to drought stress through the deployment of an ancestral SAL1-PAP signaling pathway, intersecting with the core abscisic acid signaling in stomatal guard cells.
Metastatic cancer cells acquire energy-intensive processes including increased invasiveness and chemoresistance. However, how the energy demand is met and the molecular drivers that coordinate an ...increase in cellular metabolic activity to drive epithelial-mesenchymal transition (EMT), the first step of metastasis, remain unclear. Using different in vitro and in vivo EMT models with clinical patient's samples, we showed that EMT is an energy-demanding process fueled by glucose metabolism-derived adenosine triphosphate (ATP). We identified angiopoietin-like 4 (ANGPTL4) as a key player that coordinates an increase in cellular energy flux crucial for EMT via an ANGPTL4/14-3-3γ signaling axis. This augmented cellular metabolic activity enhanced metastasis. ANGPTL4 knockdown suppresses an adenylate energy charge elevation, delaying EMT. Using an in vivo dual-inducible EMT model, we found that ANGPTL4 deficiency reduces cancer metastasis to the lung and liver. Unbiased kinase inhibitor screens and Ingenuity Pathway Analysis revealed that ANGPTL4 regulates the expression of 14-3-3γ adaptor protein via the phosphatidylinositol-3-kinase/AKT and mitogen-activated protein kinase signaling pathways that culminate to activation of transcription factors, CREB, cFOS and STAT3. Using a different mode of action, as compared with protein kinases, the ANGPTL4/14-3-3γ signaling axis consolidated cellular bioenergetics and stabilized critical EMT proteins to coordinate energy demand and enhanced EMT competency and metastasis, through interaction with specific phosphorylation signals on target proteins.
The SINgapore GERiatric intervention study to reduce cognitive decline and physical frailty (SINGER) randomised controlled trial (RCT) uses a multidomain lifestyle interventions approach, shown to be ...effective by the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial, to delay cognitive decline.
To investigate the efficacy and safety of the SINGER multidomain lifestyle interventions in older adults at risk for dementia to delay cognitive decline.
1200 participants between 60-77 years old, with Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score ≥6, fulfilling at least one of the following LIBRA index for diet, cognitive activity, physical activity and a Montreal Cognitive Assessment (MoCA) score ≥18, ≤27 points, will be recruited across Singapore.
SINGER is a 2-year multi-site RCT consisting of multidomain interventions: dietary advice, exercise, cognitive training, and vascular risk factors management. Participants will be randomised into either the Self-Guided Intervention (SGI; general lifestyle and health information and resources) or Structured Lifestyle Intervention (SLI) group. The SLI comprises diet training (6 group and 3 individual sessions over 12 months); exercise (supervised: 1-hour twice weekly for 6 months, unsupervised: 2-3/week for the rest of the study duration); cognitive sessions (15-30 minutes/session, 3/week for 6 months, together with 10 workshops in 24 months). Vascular management takes place every 3-6 months or otherwise as specified by study physicians. The primary outcome is global cognition measured using the modified Neuropsychological Battery assessing performance in various domains, such as episodic memory, executive function and processing speed. Secondary outcome measures include: domain-specific cognition and function, imaging evidence of brain and retinal changes, incidence and progression of chronic diseases, blood biomarkers, quality of life, mental health and cost-benefit analysis.
SINGER is part of the Worldwide-FINGERS international network, which is at the forefront of harmonizing approaches to effective non-pharmacological interventions in delaying cognitive decline in older adults at risk of dementia. By establishing the efficacy of multidomain interventions in preventing cognitive decline, SINGER aims to implement the findings into public health and clinical practices by informing policy makers, and guiding the design of community- and individual-level health promotion initiatives.
The prognostic significance of focal and diffuse myocardial fibrosis in patients with cardiovascular risk factors is unclear.
REMODEL (Response of the Myocardium to Hypertrophic Conditions in the ...Adult Population) is an observational cohort of asymptomatic patients with essential hypertension. All participants underwent cardiovascular magnetic resonance to assess for myocardial fibrosis: nonischemic late gadolinium enhancement (LGE), native myocardial T1, postcontrast myocardial T1, extracellular volume fraction including/excluding LGE regions, interstitial volume (extracellular volume×myocardial volume), and interstitial/myocyte ratio. Primary outcome was a composite of first occurrence acute coronary syndrome, heart failure hospitalization, strokes, and cardiovascular mortality. Patients were recruited from February 2016 and followed until June 2021.
Of the 786 patients with hypertension (58±11 years; 39% women; systolic blood pressure, 130±14 mm Hg), 145 (18%) had nonischemic LGE. Patients with nonischemic LGE were more likely to be men, have diabetes, be current smokers, and have higher blood pressure (
<0.05 for all). Compared with those without LGE, patients with nonischemic LGE had greater left ventricular mass (66±22 versus 49±9 g/m
;
<0.001), worse multidirectional strain (
<0.001 for all measures), and elevated circulating markers of myocardial wall stress and myocardial injury, adjusted for potential confounders. Twenty-four patients had primary outcome over 39 (30-50) months of follow-up. Of all the cardiovascular magnetic resonance markers of myocardial fibrosis assessed, only nonischemic LGE (hazard ratio, 6.69 95% CI, 2.54-17.60;
<0.001) and indexed interstitial volume (hazard ratio, 1.11 95% CI, 1.04-1.19;
=0.002) demonstrated independent association with primary outcome.
In patients with hypertension, myocardial fibrosis on cardiovascular magnetic resonance is associated with adverse cardiac remodeling and outcomes.
We convert a linearly polarized Gaussian beam into a radially polarized doughnut beam with an eight-segment spirally varying retarder (SVR) at wavelength of 808 nm. The SVR is designed based on the ...linear birefringence of alpha-barium borate (alpha-BBO) crystal and fabricated using a dry etching process. Radially polarized light of high purity (> 96% at far-field distribution) was generated experimentally using the segmented SVR positioned between two quarter waveplates with orthogonal slow axes. The emergent polarization can be switched between radially and azimuthally polarized cylindrical vector beams with a pair of half-wave plates.
Outbreaks of gastroenteritis associated with the consumption of raw imported half-shelled frozen oysters occurred in Singapore between 16 Dec 2003 and 04 Jan 2004. A total of 305 cases were reported ...with clinical symptoms of diarrhoea (94%), abdominal cramps (72%), vomiting (69%) and fever (54%). The median incubation period was 30.8
h and the duration of illness was 2–3 days. The overall relative risk of oyster consumption was 14.1 (95% CI: 8.3–24.0,
P<0.001). Stool and oyster samples tested negative for common bacterial pathogens, including
Vibrio parahaemolyticus. However, stool samples were positive for the presence of Norovirus group II RNA via RT PCR while oyster samples indicated the presence of Norovirus particles by electron microscopy. The clinical and epidemiological features were suggestive of Norovirus gastroenteritis and were subsequently confirmed by laboratory tests of stools and implicated oysters. Steps have been taken to ensure that food outlets do not thaw frozen oysters and serve them raw.
Abstract
Funding Acknowledgements
Type of funding sources: None.
Introduction
Current ESC dyslipidemia guidelines recommend lowering LDL targets to 1.4mmol/L (55mg/dL) for very high risk ...individuals. Lipid levels of newborns may provide insights into physiologic levels at the time of birth. There is limited data on cord blood lipids/lipoprotein levels in Asian populations. This study aims to describe cord blood lipid levels in a multi-ethnic Asian population.
Methods
We analyzed 563 (F = 275) anonymized residual cord serum samples for the measurement of cholesterol, triglycerides, dLDL and HDL on the Cobas c702 autoanalyzer and cLDL after exclusion of outliers (Tukey). Following tests for Gaussian distribution (Shapiro-Wilk) all data were log transformed. Gender differences were assessed by Mann-Whitney U test. dLDL was compared with cLDL (Passing-Bablok regression, Wilcoxon’s test, Bland-Altman plot). Statistical calculations were performed using MedCalc v20 (MedCalc software, Ostend, Belgium).
Results
There was no gender difference for cord cholesterol (p = 0.1781) and cLDL (p = 0.6186) and their values were: cholesterol (range:0.78-3.09mmol/L; mean:1.486; reference interval:0.92-2.42) and cLDL (range:0.19-1.85mmol/L; mean:0.60 ; reference interval:0.27-1.21). dLDL was higher in females (p = 0.0388) (range:0.17-1.84mmol/L; median:0.54; IQR:0.37,0.71; reference interval:0.22-1.26; 99th percentile 1.42) compared to males (range:0.16-1.19mmol/L; median:0.49; IQR:0.36,0.62; reference interval:0.21-0.98; 99th percentile 1.13). Cord dLDL values were significantly lower (p < 0.001) than cLDL; the difference (Bland-Altman) between dLDL and cLDL ranged from -0.2062-0.0141 mmol/L (mean -0.0960). Passing-Bablok regression analysis showed cLDL = 1.0465dLDL + 0.0695 with a correlation coefficient (Spearman) of 0.963 (p < 0.0001). Female triglycerides were lower (p < 0.0001) range:0.11-0.82mmol/L; median:0.24; IQR:0.19,0.31; reference interval:0.11-0.64 than males range:0.11-0.85mmol/L; median:0.28; IQR:0.21,0.38; reference interval:0.13-0.66. HDL was higher in females range:0.40-1.62mmol/L; median:0.75; IQR:0.62,0.93; reference interval:0.44-1.34 than males range:0.33-1.29mmol/L; median:0.69; IQR:0.58,0.86; reference interval:0.43-1.16 (p = 0.005).
Conclusion
Contemporary cord blood lipid/lipoprotein values have been derived for our local multi-ethnic Asian population. Directly measured LDL, shows ESC guideline LDL targets are not lower than cord dLDL levels at the 99th percentile. However cLDL overestimates cord dLDL in this cohort of subjects.
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