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Experimental and Clinical... Mar 2024Management of potential organ donors is crucial in the donation process, considering that hemodynamic instability is quite common. (Observational Study)
Observational Study
OBJECTIVES
Management of potential organ donors is crucial in the donation process, considering that hemodynamic instability is quite common.
MATERIALS AND METHODS
In the this single-center retrospective observational study, we analyzed 87 utilized brain death donors consecutively admitted to our intensive care unit from January 1, 2019, to December 31, 2022. We assessed the achievement of donor management goals during the observation period, and we also evaluated whether the achieve-ment of donor goals differed between younger and older donors (arbitrary age cutoff of 65 years).
RESULTS
In our series, mean age of donors was 67 ± 18 y, and organ-per-donor ratio was 2.3. The number of donor goals significantly increased during the 6-hour observation period (P < .001) and all donor goals were achieved in most donors (84/87) at the end of the observation period with no changes in the use and dose of vasoactive drugs. With respect to age, the number of donor goals was significantly higher in older donors at first evaluation, but goals significantly increased in both age subgroups of donors at the end of the 6-hour observation period.
CONCLUSIONS
Our data strongly suggested that a strict hemodynamic monitoring schedule allows the achievement of donor goals both in older and in younger brain death donors. We confirmed our previous findings that hemodynamic management in brain death donors is influenced by age. A strict hemodynamic monitoring schedule of brain death donors is useful to consistently achieve donor goals.
Topics: Humans; Brain Death; Retrospective Studies; Middle Aged; Male; Female; Tissue Donors; Aged; Time Factors; Age Factors; Hemodynamics; Adult; Aged, 80 and over; Donor Selection; Risk Factors
PubMed: 38695586
DOI: 10.6002/ect.2024.0030 -
MedRxiv : the Preprint Server For... Apr 2024Active cigarette smoking leads to increased CXCL5 production. CXCL5 mediates the immune response by attracting immune cells to areas of inflammation. Elevated CXCL5...
BACKGROUND
Active cigarette smoking leads to increased CXCL5 production. CXCL5 mediates the immune response by attracting immune cells to areas of inflammation. Elevated CXCL5 levels are associated with various inflammatory diseases and tumorigenesis. In addition, smoking is linked to an increase in the level of the cytokine CEACAM6 in the bloodstream of smokers. CEACAM6 is increased in pancreatic adenocarcinoma, breast cancer, non small cell lung cancer, gastric cancer, colon cancer and other cancers and promotes tumor progression, invasion, and metastasis. Although cytokine secretion in the innate immune response returns to nonsmoker levels after quitting smoking, the effects on the adaptive response appear to persist for years or decades due to epigenetic memory. As a result, epigenetic changes induced by smoking may contribute to long-lasting alterations in immune function, including elevated CXCL5 and CEACAM6. The effects of cannabis smoking might be similar.
METHODS
In the current study we used UK Biobank (UKB) data to assess the relationship of CXCL5, CEACAM6, and pulmonary function to cigarette and cannabis smoking. Our UK Biobank application was approved as UKB project 57245 (S.L., P.H.R.). Our analysis included all subjects with smoking and/or marijuana use data in the UK Biobank database. Circulating levels of CXCL5 and CEACAM6 were from UKB Olink data. Individual CXCL5 and CEACAM6 levels are NPX, Normalized Protein expression, Olink arbitrary unit in Log2 scale (Olink Proteomics AB, Uppsala, Sweden; http://www.olink.com).
RESULTS
Current smokers and past smokers had elevated circulating levels of CXCL5 and CECAM6. In multivariate analysis, current, past, or no smoking history was significantly related to CXCL5 level and CECAM6 levels, independent of the effects of age, sex. Frequency of cannabis use had a similar effect. In multivariate analysis, frequency of cannabis use was significantly related to CXCL5 level and CECAM6 levels, independent of the effects of age, sex, and years between last cannabis use and enrollment in study.
CONCLUSION
we can confirm a previous report of epigenetic changes induced by cigarette smoking that may contribute to long-lasting alterations in immune function related to CXCL5 and CEACAM6. In addition, we have found that these same long-lasting smoking alterations in immune function related to CXCL5 and CEACAM6 occur in cannabis smokers, possibly rendering them vulnerable to smoking-related tumors in later life.
PubMed: 38633792
DOI: 10.1101/2024.04.01.24305156 -
EBioMedicine May 2024Matrix metalloproteinases (MMPs) are implied in blood-brain barrier degradation and haemorrhagic transformation following ischaemic stroke, but their local relevance in...
MMP-9 release into collateral blood vessels before endovascular thrombectomy to assess the risk of major intracerebral haemorrhages and poor outcome for acute ischaemic stroke: a proof-of-concept study.
BACKGROUND
Matrix metalloproteinases (MMPs) are implied in blood-brain barrier degradation and haemorrhagic transformation following ischaemic stroke, but their local relevance in the hyperacute disease phase is unknown. We aimed to examine ultra-early MMP-9 and MMP-2 release into collateral blood vessels, and to assess its prognostic value before therapeutic recanalisation by endovascular thrombectomy (EVT).
METHODS
We report a cross-sectional proof-of-concept study including patients undergoing EVT for large-vessel ischaemic stroke at the University Hospital Würzburg, Germany. We obtained liquid biopsies from the collateral circulation before recanalisation, and systemic control samples. Laboratory workup included quantification of MMP-9 and MMP-2 plasma concentrations by cytometric bead array, immunohistochemical analyses of cellular MMP-9 and MMP-2 expression, and detection of proteolytic activity by gelatine zymography. The clinical impact of MMP concentrations was assessed by stratification according to intracranial haemorrhagic lesions on postinterventional computed tomography (Heidelberg Bleeding Classification, HBC) and early functional outcome (modified Rankin Scale, mRS). We used multivariable logistic regression, receiver-operating-characteristic (ROC) curves, and fixed-level estimates of test accuracy measures to study the prognostic value of MMP-9 concentrations.
FINDINGS
Between August 3, 2018, and September 16, 2021, 264 matched samples from 132 patients (86 [65.2%] women, 46 [34.8%] men, aged 40-94 years) were obtained. Median (interquartile range, IQR) MMP-9 (279.7 [IQR 126.4-569.6] vs 441 [IQR 223.4-731.5] ng/ml, p < 0.0001) but not MMP-2 concentrations were increased within collateral blood vessels. The median MMP-9 expression level of invading neutrophils was elevated (fluorescence intensity, arbitrary unit: 2276 [IQR 1007-5086] vs 3078 [IQR 1108-7963], p = 0.0018). Gelatine zymography experiments indicated the locally confined proteolytic activity of MMP-9 but not of MMP-2. Pretherapeutic MMP-9 release into stroke-affected brain regions predicted the degree of intracerebral haemorrhages and clinical stroke severity after recanalisation, and independently increased the odds of space-occupying parenchymal haematomas (HBC1c-3a) by 1.54 times, and the odds of severe disability or death (mRS ≥5 at hospital discharge) by 2.33 times per 1000 ng/ml increase. Excessive concentrations of MMP-9 indicated impending parenchymal haematomas and severe disability or death with high specificity.
INTERPRETATION
Measurement of MMP-9 within collateral blood vessels is feasible and identifies patients with stroke at risk of major intracerebral haemorrhages and poor outcome before therapeutic recanalisation by EVT, thereby providing evidence of the concept validity of ultra-early local stroke biomarkers.
FUNDING
This work was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) and the Interdisciplinary Centre for Clinical Research (IZKF) at the University of Würzburg.
Topics: Humans; Matrix Metalloproteinase 9; Male; Female; Thrombectomy; Aged; Cerebral Hemorrhage; Ischemic Stroke; Middle Aged; Endovascular Procedures; Prognosis; Aged, 80 and over; Matrix Metalloproteinase 2; Biomarkers; Treatment Outcome; Cross-Sectional Studies; ROC Curve; Collateral Circulation
PubMed: 38579365
DOI: 10.1016/j.ebiom.2024.105095 -
Cytotherapy Jul 2024The administration of human cell-processed therapeutic products (hCTPs) is associated with a risk of tumorigenesis due to the transformed cellular contaminants. To...
BACKGROUND AIMS
The administration of human cell-processed therapeutic products (hCTPs) is associated with a risk of tumorigenesis due to the transformed cellular contaminants. To mitigate this risk, these impurities should be detected using sensitive and validated assays. The digital soft agar colony formation (D-SAC) assay is an ultrasensitive in vitro test for detecting tumorigenic transformed cells in hCTPs.
METHODS
In this study, we first evaluated the colony formation efficiency (CFE) precision of tumorigenic reference cells in positive control samples according to a previously reported D-SAC assay protocol (Protocol I) from multiple laboratories. However, the CFE varied widely among laboratories. Thus, we improved and optimized the test protocol as Protocol II to reduce variability in the CFE of tumorigenic reference cells. Subsequently, the improved protocol was validated at multiple sites. Human mesenchymal stromal cells (hMSCs) were used as model cells, and positive control samples were prepared by spiking them with HeLa cells.
RESULTS
Based on the previously reported protocol, the CFE was estimated using an ultra-low concentration (0.0001%) of positive control samples in multiple plates. Next, we improved the protocol to reduce the CFE variability. Based on the CFE results, we estimated the sample size as the number of wells (Protocol II) and assessed the detectability of 0.0001% HeLa cells in hMSCs to validate the protocol at multiple sites. Using Protocol I yielded low CFEs (mean: 30%) and high variability between laboratories (reproducibility coefficient of variance [CV]: 72%). In contrast, Protocol II, which incorporated a relatively high concentration (0.002%) of HeLa cells in the positive control samples, resulted in higher CFE values (mean: 63%) and lower variability (reproducibility CV: 18%). Moreover, the sample sizes for testing were estimated as the number of wells per laboratory (314-570 wells) based on the laboratory-specific CFE (42-76%). Under these conditions, all laboratories achieved a detection limit of 0.0001% HeLa cells in hMSCs in a predetermined number of wells. Moreover, colony formation was not observed in the wells seeded with hMSCs alone.
CONCLUSIONS
The D-SAC assay is a highly sensitive and robust test for detecting malignant cells as impurities in hCTPs. In addition, optimal assay conditions were established to test tumorigenic impurities in hCTPs with high sensitivity and an arbitrary false negative rate.
Topics: Humans; HeLa Cells; Cell- and Tissue-Based Therapy; Mesenchymal Stem Cells; Cell Transformation, Neoplastic
PubMed: 38556961
DOI: 10.1016/j.jcyt.2024.03.005 -
Nature Human Behaviour Jun 2024A long-standing engineering ambition has been to design anthropomorphic bionic limbs: devices that look like and are controlled in the same way as the biological body...
A long-standing engineering ambition has been to design anthropomorphic bionic limbs: devices that look like and are controlled in the same way as the biological body (biomimetic). The untested assumption is that biomimetic motor control enhances device embodiment, learning, generalization and automaticity. To test this, we compared biomimetic and non-biomimetic control strategies for non-disabled participants when learning to control a wearable myoelectric bionic hand operated by an eight-channel electromyography pattern-recognition system. We compared motor learning across days and behavioural tasks for two training groups: biomimetic (mimicking the desired bionic hand gesture with biological hand) and arbitrary control (mapping an unrelated biological hand gesture with the desired bionic gesture). For both trained groups, training improved bionic limb control, reduced cognitive reliance and increased embodiment over the bionic hand. Biomimetic users had more intuitive and faster control early in training. Arbitrary users matched biomimetic performance later in training. Furthermore, arbitrary users showed increased generalization to a new control strategy. Collectively, our findings suggest that biomimetic and arbitrary control strategies provide different benefits. The optimal strategy is probably not strictly biomimetic, but rather a flexible strategy within the biomimetic-to-arbitrary spectrum, depending on the user, available training opportunities and user requirements.
Topics: Humans; Hand; Biomimetics; Bionics; Adult; Learning; Male; Female; Motor Skills; Young Adult; Electromyography
PubMed: 38499772
DOI: 10.1038/s41562-023-01811-6 -
PloS One 2024The Medical Subject Headings (MeSH) thesaurus is a controlled vocabulary developed by the U.S. National Library of Medicine (NLM) for classifying journal articles. It is...
The Medical Subject Headings (MeSH) thesaurus is a controlled vocabulary developed by the U.S. National Library of Medicine (NLM) for classifying journal articles. It is increasingly used by researchers studying medical innovation to classify text into disease areas and other categories. Although this process was once manual, human indexers are now assisted by algorithms that automate some of the indexing process. NLM has made one of their algorithms, the Medical Text Indexer (MTI), available to researchers. MTI can be used to easily assign MeSH descriptors to arbitrary text, including from document types other than publications. However, the reliability of extending MTI to other document types has not been studied directly. To assess this, we collected text from grants, patents, and drug indications, and compared MTI's classification to expert manual classification of the same documents. We examined MTI's recall (how often correct terms were identified) and found that MTI identified 78% of expert-classified MeSH descriptors for grants, 78% for patents, and 86% for drug indications. This high recall could be driven merely by excess suggestions (at an extreme, all diseases being assigned to a piece of text); therefore, we also examined precision (how often identified terms were correct) and found that most MTI outputs were also identified by expert manual classification: precision was 53% for grant text, 73% for patent text, and 64% for drug indications. Additionally, we found that recall and precision could be improved by (i) utilizing ranking scores provided by MTI, (ii) excluding long documents, and (iii) aggregating to higher MeSH categories. For simply detecting the presence of any disease, MTI showed > 94% recall and > 87% precision. Our overall assessment is that MTI is a potentially useful tool for researchers wishing to classify texts from a variety of sources into disease areas.
Topics: United States; Humans; Reproducibility of Results; Abstracting and Indexing; Medical Subject Headings; Algorithms; National Library of Medicine (U.S.)
PubMed: 38478542
DOI: 10.1371/journal.pone.0297526 -
Scientific Reports Mar 2024To examine the second-order coherence of light propagation of quantum states in arbitrary directions through dispersive non-Hermitian optical media, we considered two...
To examine the second-order coherence of light propagation of quantum states in arbitrary directions through dispersive non-Hermitian optical media, we considered two sets of non-Hermitian periodic structures that consist of gain/loss unit cells. We show that each batch can satisfy the parity-time symmetry conditions at a distinct frequency. We then varied the gain/loss strength in the stable electromagnetic regime to evaluate the transmittance of N-photon number states through each structure. The results show both sets preserve their antibunching characteristics under specific incident light conditions. Furthermore, s(p)-polarized light exhibits higher (lower) second-order coherence at larger incident angles. In addition, the antibunching features of the transmitted states degrade with an increase in the number of unit cells in multilayered structures for both polarizations.
PubMed: 38443472
DOI: 10.1038/s41598-024-55777-0 -
Nature Communications Feb 2024Current soft neural probes are still operated by bulky, rigid electronics mounted to a body, which deteriorate the integrity of the device to biological systems and...
Current soft neural probes are still operated by bulky, rigid electronics mounted to a body, which deteriorate the integrity of the device to biological systems and restrict the free behavior of a subject. We report a soft, conformable neural interface system that can monitor the single-unit activities of neurons with long-term stability. The system implements soft neural probes in the brain, and their subsidiary electronics which are directly printed on the cranial surface. The high-resolution printing of liquid metals forms soft neural probes with a cellular-scale diameter and adaptable lengths. Also, the printing of liquid metal-based circuits and interconnections along the curvature of the cranium enables the conformal integration of electronics to the body, and the cranial circuit delivers neural signals to a smartphone wirelessly. In the in-vivo studies using mice, the system demonstrates long-term recording (33 weeks) of neural activities in arbitrary brain regions. In T-maze behavioral tests, the system shows the behavior-induced activation of neurons in multiple brain regions.
Topics: Animals; Mice; Electronics; Neurons; Brain; Skull; Metals; Printing, Three-Dimensional
PubMed: 38413568
DOI: 10.1038/s41467-024-45768-0 -
The Lancet. Child & Adolescent Health Apr 2024Touch interventions such as massage and skin-to-skin contact relieve neonatal pain. The Parental touch trial (Petal) aimed to assess whether parental stroking of their... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Touch interventions such as massage and skin-to-skin contact relieve neonatal pain. The Parental touch trial (Petal) aimed to assess whether parental stroking of their baby before a clinically required heel lance, at a speed of approximately 3 cm/s to optimally activate C-tactile nerve fibres, provides effective pain relief.
METHODS
Petal is a multicentre, randomised, parallel-group interventional superiority trial conducted in the John Radcliffe Hospital (Oxford University Hospitals NHS Foundation Trust, Oxford, UK) and the Royal Devon and Exeter Hospital (Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK). Neonates without neurological abnormalities who were born at 35 weeks gestational age or more and required a blood test via a heel lance in the first week of life were randomly assigned (1:1) to receive parental touch for 10 s either before (intervention group) or after (control group) the clinically required heel lance. Randomisation was managed at the Oxford site using a web-based minimisation algorithm with allocation concealment. The primary outcome measure was the magnitude of noxious-evoked brain activity in response to the heel lance measured with electroencephalography (EEG). Secondary outcome measures were Premature Infant Pain Profile-Revised (PIPP-R) score, development of tachycardia, and parental anxiety score. For all outcomes, the per-protocol effect was estimated via complier average causal effect analysis on the full analysis set. The trial is registered on ISRCTN (ISRCTN14135962) and ClinicalTrials.gov (NCT04901611).
FINDINGS
Between Sept 1, 2021, and Feb 7, 2023, 159 parents were approached to participate in the study, and 112 neonates were included. 56 neonates were randomly assigned to the intervention group of parental stroking before the heel lance and 56 to the control group of parental stroking after the heel lance. The mean of the magnitude of the heel lance-evoked brain activity was 0·85 arbitrary units (a.u.; SD 0·70; n=39; a scaled magnitude of 1 a.u. represents the expected mean response to a heel lance in term-aged neonates) in the intervention group and 0·91 a.u. (SD 0·76; n=43) in the control group. Therefore, the primary outcome did not differ significantly between groups, with a mean difference of -0·11 a.u. (lower in intervention group; SD 0·77; 95% CI -0·42 to 0·20; p=0·38; n=82). No significant difference was observed across secondary outcomes. The PIPP-R difference in means was 1·10 (higher in intervention group, 95% CI -0·42 to 2·61; p=0·15; n=100); the odds ratio of becoming tachycardic was 2·08 (95% CI 0·46 to 9·46; p=0·34, n=105) in the intervention group with reference to the control group; and the difference in parental State-Trait Anxiety Inventory-State score was -0·44 (higher in control group; SD 6·85; 95% CI -2·91 to 2·02; p=0·72; n=106). One serious adverse event (desaturation) occurred in a neonate randomly assigned to the control group, which was not considered to be related to the study.
INTERPRETATION
Parental stroking delivered at an optimal speed to activate C-tactile fibres for a duration of 10 s before the painful procedure did not significantly change neonates' magnitude of pain-related brain activity, PIPP-R score, or development of tachycardia. The trial highlighted the challenge of translating an experimental researcher-led tactile intervention into a parent-led approach, and the value of involving parents in their baby's pain management.
FUNDING
Wellcome Trust and Bliss.
Topics: Humans; Infant, Newborn; Pain; Pain, Procedural; Tachycardia; Touch; United Kingdom
PubMed: 38373429
DOI: 10.1016/S2352-4642(23)00340-1 -
Heliyon Feb 2024The system or unit survives when strength is more significant than the stress enjoined. This procedure is usually used in many companies to test their product. The...
The system or unit survives when strength is more significant than the stress enjoined. This procedure is usually used in many companies to test their product. The reliability or the quality of the scheme or component is described by the parameters of stress-strength reliability ()) where denotes strength and indicates stress. In this article, we adopted the statistical inference of while the two arbitrary factors and are independent and approach the Lomax lifetime distribution with common scale parameters. Also, the strength and stress variables are subjected to a partial step-stress-quickened life experiment. The classical estimation and Bayes method create the point estimate of . Confidence intervals of are computed with asymptotic distribution, bootstrap technique, and Bayesian credible intervals. All results are evaluated and compared under an extensive simulation study. Finally, the lifetime data sets generated from the Lomax distribution are used to analyze the system's reliability by estimating .
PubMed: 38371973
DOI: 10.1016/j.heliyon.2024.e25802