Diaphragm ultrasonography is rapidly evolving in both critical care and research. Nevertheless, methodologically robust guidelines on its methodology and acquiring expertise do not, or only ...partially, exist. Therefore, we set out to provide consensus-based statements towards a universal measurement protocol for diaphragm ultrasonography and establish key areas for research.
To formulate a robust expert consensus statement, between November 2020 and May 2021, a two-round, anonymous and online survey-based Delphi study among experts in the field was performed. Based on the literature review, the following domains were chosen: "Anatomy and physiology", "Transducer Settings", "Ventilator Impact", "Learning and expertise", "Daily practice" and "Future directions". Agreement of ≥ 68% (≥ 10 panelists) was needed to reach consensus on a question.
Of 18 panelists invited, 14 agreed to participate in the survey. After two rounds, the survey included 117 questions of which 42 questions were designed to collect arguments and opinions and 75 questions aimed at reaching consensus. Of these, 46 (61%) consensus was reached. In both rounds, the response rate was 100%. Among others, there was agreement on measuring thickness between the pleura and peritoneum, using > 10% decrease in thickness as cut-off for atrophy and using 40 examinations as minimum training to use diaphragm ultrasonography in clinical practice. In addition, key areas for research were established.
This expert consensus statement presents the first set of consensus-based statements on diaphragm ultrasonography methodology. They serve to ensure high-quality and homogenous measurements in daily clinical practice and in research. In addition, important gaps in current knowledge and thereby key areas for research are established. Trial registration The study was pre-registered on the Open Science Framework with registration digital object identifier https://doi.org/10.17605/OSF.IO/HM8UG .
We examined the associations of GAD antibodies (GADA) and C-peptide (CP) with insulin initiation, glycemic responses, and severe hypoglycemia in type 2 diabetes (T2D).
In 5,230 Chinese patients ...(47.6% men) with T2D (mean ± SD age: 56.5 ± 13.9 years; median diabetes duration: 6 interquartile range 1, 12 years), enrolled consecutively in 1996-2012 and prospectively observed until 2019, we retrospectively measured fasting CP and GADA in stored serum and examined their associations with aforementioned outcomes.
At baseline, 28.6% (n = 1,494) had low CP (<200 pmol/L) and 4.9% (n = 257) had positive GADA (GADA+). In the low-CP group, 8.0% had GADA+, and, in the GADA+ group, 46.3% had low CP. The GADA+ group had an adjusted hazard ratio (aHR) of 1.46 (95% CI 1.15-1.84, P = 0.002) for insulin initiation versus the GADA- group, while the low-CP group had an aHR of 0.88 (0.77-1.00, P = 0.051) versus the high-CP group. Following insulin initiation, the GADA+ plus low-CP group had the largest decrements in HbA1c (-1.9% at month 6; -1.5% at month 12 vs. -1% in the other three groups). The aHR of severe hypoglycemia was 1.29 (95% CI 1.10-1.52, P = 0.002) in the low-CP group and 1.38 (95% CI 1.04-1.83, P = 0.024) in the GADA+ group.
There is considerable heterogeneity in autoimmunity and β-cell dysfunction in T2D with GADA+ and high CP associated with early insulin initiation, while GADA+ and low CP, increased the risk of severe hypoglycemia. Extended phenotyping is warranted to increase the precision of classification and treatment in T2D.
Self-assembling peptides are biomedical materials with unique structures that are formed in response to various environmental conditions. Governed by their physicochemical characteristics, the ...peptides can form a variety of structures with greater reactivity than conventional non-biological materials. The structural divergence of self-assembling peptides allows for various functional possibilities; when assembled, they can be used as scaffolds for cell and tissue regeneration, and vehicles for drug delivery, conferring controlled release, stability, and targeting, and avoiding side effects of drugs. These peptides can also be used as drugs themselves. In this review, we describe the basic structure and characteristics of self-assembling peptides and the various factors that affect the formation of peptide-based structures. We also summarize the applications of self-assembling peptides in the treatment of various diseases, including cancer. Furthermore, the in-cell self-assembly of peptides, termed reverse self-assembly, is discussed as a novel paradigm for self-assembling peptide-based nanovehicles and nanomedicines.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Sensitive, specific, yet multifunctional tattoo‐like electronics are ideal wearable systems for “any time, any where” health monitoring because they can virtually become parts of the human skin, ...offering a burdenless “unfeelable” wearing experience. A skin‐like, multifunctional electronic tattoo made entirely from gold using a standing enokitake‐mushroom‐like vertically aligned nanowire membrane in conjunction with a programmable local cracking technology is reported. Unlike previous multifunctional systems, only a single material type is needed for the integrated gold circuits involved in interconnects and multiplexed specific sensors, thereby avoiding the use of complex multimaterials interfaces. This is possiblebecause the programmable local cracking technology allows for the arbitrary fine‐tuning of the properties of elastic gold conductors from strain‐insensitive to highly strain‐sensitive simply by adjusting localized crack size, shape, and orientations—a capability impossible to achieve with previous bulk cracking technology. Furthermore, in‐plane integration of strain/pressure sensors, anisotropic orientation‐specific sensors, strain‐insensitive stretchable interconnects, temperature sensors, glucose sensors, and lactate sensors without the need of soldering or gluing are demonstrated. This strategy opens a new general route for the design of next‐generation wearable electronic tattoos.
A programmable local cracking technology is proposed for the fabrication of an in‐plane multisensing gold tattoo entirely based on a vertically aligned nanowire membrane. This strategy allows arbitrary fine‐tuning of the properties of elastic gold from stretchable conductors to highly sensitive pressure and strain sensors. By using this method, a multifunctional sensing system without the need of soldering or gluing is demonstrated.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
There are considerable challenges in directly targeting the mutant p53 protein, given the large heterogeneity of p53 mutations in the clinic. An alternative approach is to exploit the altered fitness ...of cells imposed by loss-of-wild-type p53. Here we identify niclosamide through a HTS screen for compounds selectively killing p53-deficient cells. Niclosamide impairs the growth of p53-deficient cells and of p53 mutant patient-derived ovarian xenografts. Metabolome profiling reveals that niclosamide induces mitochondrial uncoupling, which renders mutant p53 cells susceptible to mitochondrial-dependent apoptosis through preferential accumulation of arachidonic acid (AA), and represents a first-in-class inhibitor of p53 mutant tumors. Wild-type p53 evades the cytotoxicity by promoting the transcriptional induction of two key lipid oxygenation genes, ALOX5 and ALOX12B, which catalyzes the dioxygenation and breakdown of AA. Therefore, we propose a new paradigm for targeting cancers defective in the p53 pathway, by exploiting their vulnerability to niclosamide-induced mitochondrial uncoupling.
Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions ...in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.
Coronary computed tomographic angiography (coronary CT) is a non-invasive test for diagnosis of cardiac function. Coronary calcium scores determined by coronary CT are associated with cardiovascular ...risk factors. However, no studies have investigated the association between coronary calcium scores and cardiovascular complications after liver transplantation (LT). We therefore evaluated the utility of preoperative coronary calcium scores for predicting early postoperative cardiovascular complications in LT recipients.
Between 2010 and 2012, 443 LT recipients were analysed retrospectively. Preoperative cardiovascular assessments, including coronary CT, were performed. A coronary calcium score >400 was defined as a positive finding. Predictive factors of early postoperative cardiovascular complications were evaluated by univariate and multivariate analyses. Major cardiovascular complications occurring during a period of 1 month after LT were noted.
Of the 443 patients, 38 (8.6%) experienced one or more cardiovascular complications. Positive coronary CT findings were seen in 11 (2.5%) patients. In the multivariate analysis, a coronary calcium score >400 {odds ratio (OR)=4.62 95% confidence interval (CI): 1.14–18.72, P=0.032} and female sex OR=2.76 (1.37–5.57), P=0.005 were predictive of cardiovascular complications.
A preoperative coronary calcium score of >400 predicted cardiovascular complications occurring 1 month after LT, suggesting that preoperative evaluation of coronary calcium scores could help predict early postoperative cardiovascular complications in LT recipients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aims/hypothesis New genetic variants associated with susceptibility to type 2 diabetes mellitus have been discovered in recent genome-wide association (GWA) studies. The aim of the present study was ...to examine the association between these diabetogenic variants and gestational diabetes mellitus (GDM). Methods The study included 869 Korean women with GDM and 345 female and 287 male Korean non-diabetic controls. We genotyped the single nucleotide polymorphisms (SNPs) rs7756992 and rs7754840 in CDKAL1; rs564398, rs1333040, rs10757278 and rs10811661 in the CDKN2A-CDKN2B region; rs8050136 in FTO; rs1111875, rs5015480 and rs7923837 in HHEX; rs4402960 in IGF2BP2; and rs13266634 in SLC30A8. In addition, rs7903146 and rs12255372 in TCF7L2; rs5215 and rs5219 in KCNJ11; and rs3856806 and rs1801282 in PPARG were genotyped. The genotype frequencies in the GDM patients were compared with those in the non-diabetic controls. Results Compared with controls (men and women combined), GDM was associated with rs7756992 and rs7754840 (OR 1.55, 95% CI 1.34-1.79, p = 4.17 x 10⁻⁹) in CDKAL1; rs10811661 (OR 1.49, 95% CI 1.29-1.72, p = 1.05 x 10⁻⁷) in the CDKN2A-CDKN2B region; rs1111875 (OR 1.27, 95% CI 1.09-1.49, p = 0.003), rs5015480, and rs7923837 in HHEX; rs4402960 (OR 1.18, 95% CI 1.01-1.38, p = 0.03) in IGF2BP2; rs13266634 (OR 1.24, 95% CI 1.07-1.43, p = 0.005) in SLC30A8; and rs7903146 (OR 1.58, 95% CI 1.03-2.43, p = 0.038) in TCF7L2. The risk alleles of the SNPs rs7756992 and rs7754840 in CDKAL1; rs10811661 in the CDKN2A-CDKN2B region; and rs1111875, rs5015480 and rs7923837 in HHEX were associated with significant decreases in the insulin AUC during a 100 g OGTT performed at the time of diagnosis of GDM. Conclusions/interpretation Some of the type 2 diabetes-associated genetic variants that were discovered in the recent GWA studies are also associated with GDM in Koreans.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this study, planar anode‐supported solid oxide fuel cells (5 × 5 cm2) were fabricated with cathode segmentations and tested in a channel type setup. The in‐plane performance variation became ...significant with an increasing current density (fuel utilization), and impedance analysis on each segment indicated that the poor performance in the outlet region was due to gas conversion overpotential combined with gas concentration overpotential. Pt reference electrodes were embedded in the electrolyte layers of the segments so that the anode and cathode overpotential could be separated for each segment. It was found that the cathode overpotential was dominant for both segments, which suggested that the cathode overpotential determined the overall cell performance. On the other hand, the anode overpotential was responsible for the in‐plane performance variation. Post‐analysis revealed that the Ni anode was partially oxidized and its layer was delaminated in the outlet region. Thus, this study suggests that the anode overpotential related to gas conversion is a critical factor in determining Ni anode stability as well as overall cell performance in planar anode supported cells with a gas channel setup.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
ABSTRACT
Prevalence and antimicrobial resistance profiles of Salmonella serotypes isolated from 7 chicken meat brands produced by different integrated broiler operations in Korea were determined. In ...total, 210 samples were collected from retail supermarkets in Seoul, South Korea, and analyzed for the presence of Salmonella. Of 210 chicken meat samples, overall Salmonella prevalence was 22.4%. Salmonella Enteritidis was the dominant serovar, with an isolation rate of 57.4% from the Salmonella-positive chickens, followed by Salmonella Montevideo. Salmonella isolates frequently were resistant to various antibiotics, including 100% to erythromycin, 87% to cephalothin, 85% to nalidixic acid, and 70% to streptomycin. Of the 47 isolates, 41 (87.2%) isolates were resistant to 3 or more antibiotics. Moreover, the Salmonella profiles of each chicken meat brand were different by broiler operation. Brand A showed the highest prevalence of Salmonella (18 isolates, 60%), whereas brand G showed the lowest prevalence (one isolate, 3.3%). Eight among the 18 isolates of brand A were resistant to 11 antibiotics, whereas 5 of the 6 brand C isolates were resistant to only 2 antibiotics. This study demonstrates that a high proportion of chicken meat in Korea is contaminated with Salmonella and the prevalence and antimicrobial resistance patterns of Salmonella of chicken meat differ significantly according to the integrated broiler operation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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