Virus-specific antibodies are crucial for protective immunity against SARS-CoV-2. Assessing functional antibodies through conventional or pseudotyped virus neutralisation tests (pVNT) requires high ...biosafety levels. Alternatively, the virus-free surrogate virus neutralisation test (sVNT) quantifies antibodies interfering with spike binding to angiotensin-converting enzyme 2. We evaluated secreted nanoluciferase-tagged spike protein fragments as diagnostic antigens in the sVNT in a vaccination cohort. Initially, spike fragments were tested in a capture enzyme immunoassay (EIA), identifying the receptor binding domain (RBD) as the optimal diagnostic antigen. The sensitivity of the in-house sVNT applying the nanoluciferase-labelled RBD equalled or surpassed that of a commercial sVNT (
, GenScript Diagnostics) and an in-house pVNT four weeks after the first vaccination (98% vs. 94% and 72%, respectively), reaching 100% in all assays four weeks after the second and third vaccinations. When testing serum reactivity with Omicron BA.1 spike, the sVNT and pVNT displayed superior discrimination between wild-type- and variant-specific serum reactivity compared to a capture EIA. This was most pronounced after the first and second vaccinations, with the third vaccination resulting in robust, cross-reactive BA.1 construct detection. In conclusion, utilising nanoluciferase-labelled antigens permits the quantification of SARS-CoV-2-specific inhibitory antibodies. Designed as flexible modular systems, the assays can be readily adjusted for monitoring vaccine efficacy.
Pulmonary complications, including infections, are highly prevalent in patients after hematopoietic cell transplantation with chronic graft-vs-host disease. These comorbid diseases can make the ...diagnosis of early lung graft-vs-host disease (bronchiolitis obliterans syndrome) challenging. A quantitative method to differentiate among these pulmonary diseases can address diagnostic challenges and facilitate earlier and more targeted therapy.
We conducted a single-center study of 66 patients with CT chest scans analyzed with a quantitative imaging tool known as parametric response mapping. Parametric response mapping results were correlated with pulmonary function tests and clinical characteristics. Five parametric response mapping metrics were applied to K-means clustering and support vector machine models to distinguish among posttransplantation lung complications solely from quantitative output.
Compared with parametric response mapping, spirometry showed a moderate correlation with radiographic air trapping, and total lung capacity and residual volume showed a strong correlation with radiographic lung volumes. K-means clustering analysis distinguished four unique clusters. Clusters 2 and 3 represented obstructive physiology (encompassing 81% of patients with bronchiolitis obliterans syndrome) in increasing severity (percentage air trapping 15.6% and 43.0%, respectively). Cluster 1 was dominated by normal lung, and cluster 4 was characterized by patients with parenchymal opacities. A support vector machine algorithm differentiated bronchiolitis obliterans syndrome with a specificity of 88%, sensitivity of 83%, accuracy of 86%, and an area under the receiver operating characteristic curve of 0.85.
Our machine learning models offer a quantitative approach for the identification of bronchiolitis obliterans syndrome vs other lung diseases, including late pulmonary complications after hematopoietic cell transplantation.
Although a large number of adult women worldwide are affected by lipedema, the physiologic conditions triggering onset and progression of this chronic disease remain enigmatic. In the present study, ...a descriptive epidemiologic situation of postoperative lipedema patients is presented.
The authors developed an online survey questionnaire for lipedema patients in Germany. The survey was conducted on 209 female patients who had been diagnosed with lipedema and had undergone tumescent liposuction.
Most of the participants (average age, 38.5 years) had noticed a first manifestation of the disease at the age of 16. It took a mean of 15 years to accomplish diagnosis. Liposuction led to a significant reduction of pain, swelling, tenderness, and easy bruising as confirmed by the majority of patients. Hypothyroidism n = 75 (35.9 percent) and depression n = 48 (23.0 percent) occurred at a frequency far beyond the average prevalence in the German population. The prevalence of diabetes type 1 n = 3 (1.4 percent), and diabetes type 2 n = 2 (1 percent) was particularly low among the respondents. Forty-seven of the lipedema patients (approximately 22.5 percent) suffered from a diagnosed migraine. Following liposuction, the frequency and/or intensity of migraine attacks became markedly reduced, as stated by 32 patients (68.1 percent).
Quality of life increases significantly after surgery with a reduction of pain and swelling and decreased tendency to easy bruising. The high prevalence of hypothyroidism in lipedema patients could be related to the frequently observed lipedema-associated obesity. The low prevalence of diabetes, dyslipidemia, and hypertension appears to be a specific characteristic distinguishing lipedema from lifestyle-induced obesity.
Rising demand for food and bioenergy makes it imperative to breed for increased crop yield. Vegetative plant growth could be driven by resource acquisition or developmental programs. Metabolite ...profiling in 94 Arabidopsis accessions revealed that biomass correlates negatively with many metabolites, especially starch. Starch accumulates in the light and is degraded at night to provide a sustained supply of carbon for growth. Multivariate analysis revealed that starch is an integrator of the overall metabolic response. We hypothesized that this reflects variation in a regulatory network that balances growth with the carbon supply. Transcript profiling in 21 accessions revealed coordinated changes of transcripts of more than 70 carbon-regulated genes and identified 2 genes (myo-inositol-1-phosphate synthase, a Kelch-domain protein) whose transcripts correlate with biomass. The impact of allelic variation at these 2 loci was shown by association mapping, identifying them as candidate lead genes with the potential to increase biomass production.
Building upon the successes of Countdown to 2015, Countdown to 2030 aims to support the monitoring and measurement of women's, children's, and adolescents' health in the 81 countries that account for ...95% of maternal and 90% of all child deaths worldwide. To achieve the Sustainable Development Goals by 2030, the rate of decline in prevalence of maternal and child mortality, stillbirths, and stunting among children younger than 5 years of age needs to accelerate considerably compared with progress since 2000. Such accelerations are only possible with a rapid scale-up of effective interventions to all population groups within countries (particularly in countries with the highest mortality and in those affected by conflict), supported by improvements in underlying socioeconomic conditions, including women's empowerment. Three main conclusions emerge from our analysis of intervention coverage, equity, and drivers of reproductive, maternal, newborn, and child health (RMNCH) in the 81 Countdown countries. First, even though strong progress was made in the coverage of many essential RMNCH interventions during the past decade, many countries are still a long way from universal coverage for most essential interventions. Furthermore, a growing body of evidence suggests that available services in many countries are of poor quality, limiting the potential effect on RMNCH outcomes. Second, within-country inequalities in intervention coverage are reducing in most countries (and are now almost non-existent in a few countries), but the pace is too slow. Third, health-sector (eg, weak country health systems) and non-health-sector drivers (eg, conflict settings) are major impediments to delivering high-quality services to all populations. Although more data for RMNCH interventions are available now, major data gaps still preclude the use of evidence to drive decision making and accountability. Countdown to 2030 is investing in improvements in measurement in several areas, such as quality of care and effective coverage, nutrition programmes, adolescent health, early childhood development, and evidence for conflict settings, and is prioritising its regional networks to enhance local analytic capacity and evidence for RMNCH.
In the last years, cognitive impairment was emphasized to be a prominent long‐term sequelae of sepsis. The level of cognitive impairment is comparable with that in mild cognitive impairment (MCI) ...patients. Whether sepsis survivors also show a comparable brain atrophy is still unclear. For the analysis of brain atrophy, a novel method named brain age gap estimation (BrainAGE) was used. In this analysis approach, an algorithm identifies age‐specific atrophy across the whole brain and calculates a BrainAGE score in years. In case of accelerated brain atrophy, the BrainAGE score is increased in comparison to the healthy age reference group, indicating a difference in estimated chronological age. 20 survivors of severe sepsis (longer than 2 years post sepsis) with persistent cognitive deficits were investigated with a battery of neuropsychological tests. Their MRI images were compared to an age‐ and sex‐matched control group. Sepsis survivors showed a significant higher BrainAGE score of 4.5 years compared to healthy controls. We also found a close relationship between the BrainAGE score and severity of cognitive impairment (a higher BrainAGE score was associated with more severe cognitive impairment). Consequently, sepsis survivors with persistent cognitive impairment showed an accelerated brain ageing, which was closely associated with the severity of cognitive impairment (similar to MCI patients).
Brain Age Gap Estimation (BrainAGE) is an algorithm which identifies age‐specific atrophy across the whole brain. Sepsis survivors with persistent cognitive deficits showed a significant higher BrainAGE score of 4.5 years compared to healthy controls which could indicate an accelerated brain atrophy. There was also a close relationship between the BrainAGE score and severity of cognitive impairment (a higher BrainAGE score was associated with more severe cognitive impairment).
There is only limited knowledge about chronic pain conditions resulting from critical care. Experimental and clinical data suggest a close relationship between inflammation and pain perception. Since ...sepsis is the most severe form of systemic inflammation, the primary objective was to evaluate chronic pain states and functional impairment of septic and nonseptic patients 6 months after discharge from ICU. Second, we aimed to obtain the total prevalence and characteristics of chronic ICU-related pain.
Case-control study.
Observational study in long-term survivors of mixed surgical and medical ICUs.
Septic and nonseptic survivors of critical care (n = 207) and healthy controls (n = 46).
None.
We collected comprehensive information on patients' past and present pain 6 months after ICU discharge by means of the German pain questionnaire. Pain intensity levels and pain interference ratings were compared between septic and nonseptic patients and healthy controls. We found no differences in prevalence, severity, and interference of pain between septic and nonseptic patients. However, both patient groups differed significantly from controls. In secondary analysis, a third of all patients reported chronic clinically relevant pain associated with the ICU stay 6 months after ICU discharge. Half of these patients experienced chronic pain conditions before ICU admission and reported additional sources of pain. Most important, 16% of all patients had no preexisting pain condition and now experience chronic ICU-related pain. The majority of patients with chronic ICU-related pain reported a high degree of disabling pain, limiting daily activities.
A high percentage of former ICU patients develop chronic pain conditions associated with critical care. These patients differ significantly from control data in terms of pain intensity and show high levels of interference with pain. The presence of sepsis per se seems to play a marginal role for the development of chronic ICU-related pain.
Enzyme activity is determined by various different mechanisms, including posttranslational modifications and allosteric regulation. Allosteric activators are often metabolites but other molecules ...serve similar functions. So far, examples of long non-coding RNAs (lncRNAs) acting as allosteric activators of enzyme activity are missing. Here, we describe the function of mitolnc in cardiomyocytes, a nuclear encoded long non-coding RNA, located in mitochondria and directly interacting with the branched-chain ketoacid dehydrogenase (BCKDH) complex to increase its activity. The BCKDH complex is critical for branched-chain amino acid catabolism (BCAAs). Inactivation of mitolnc in mice reduces BCKDH complex activity, resulting in accumulation of BCAAs in the heart and cardiac hypertrophy via enhanced mTOR signaling. We found that mitolnc allosterically activates the BCKDH complex, independent of phosphorylation. Mitolnc-mediated regulation of the BCKDH complex constitutes an important additional layer to regulate the BCKDH complex in a tissue-specific manner, evading direct coupling of BCAA metabolism to ACLY-dependent lipogenesis.
Arabidopsis was grown in a 12, 8, 4 or 3 h photoperiod to investigate how metabolism and growth adjust to a decreased carbon supply. There was a progressive increase in the rate of starch synthesis, ...decrease in the rate of starch degradation, decrease of malate and fumarate, decrease of the protein content and decrease of the relative growth rate. Carbohydrate and amino acids levels at the end of the night did not change. Activities of enzymes involved in photosynthesis, starch and sucrose synthesis and inorganic nitrogen assimilation remained high, whereas five of eight enzymes from glycolysis and organic acid metabolism showed a significant decrease of activity on a protein basis. Glutamate dehydrogenase activity increased. In a 2 h photoperiod, the total protein content and most enzyme activities decreased strongly, starch synthesis was inhibited, and sugars and amino acids levels rose at the end of the night and growth was completely inhibited. The rate of starch degradation correlated with the protein content and the relative growth rate across all the photoperiod treatments. It is discussed how a close coordination of starch turnover, the protein content and growth allows Arabidopsis to avoid carbon starvation, even in very short photoperiods.
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