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Medicine Dec 2022Noninvasive and simple indicators for diagnosing latent tuberculosis (TB) infection (LTBI) and tracking progression from latent infection to active TB infection are...
Noninvasive and simple indicators for diagnosing latent tuberculosis (TB) infection (LTBI) and tracking progression from latent infection to active TB infection are still desperately needed. The aim of this study was to screen and identify possible biomarkers for diagnosing LTBI and monitoring the progression from latent infection to active TB infection, as well as to investigate the underlying processes and functions. To assess changes in metabolite composition associated with active tuberculosis infection in humans, whole blood supernatants were collected from patients with LTBI, drug-susceptible TB patients, drug-resistant TB patients, and healthy controls. The metabolites in all serum samples were extracted by oscillatory, deproteinization, and then detected by liquid chromatography-tandem mass spectrometry/MS analysis. Normalization by Pareto-scaling method, the difference analysis was carried out by Metaboanalyst 4.0 software, and 1-way analysis of variance analysis among groups showed that P-value < 0.05 was regarded as a different metabolite. To clarify the dynamic changes and functions of differential metabolites with disease progression, and explore its significance and mechanism as a marker by further cluster analysis, functional enrichment analysis, and relative content change analysis of differential metabolites. 65 metabolites were substantially different in four groups. Differential metabolites such as Inosine and Prostaglandin E1 may be important blood indicators for diagnosing mycobacterium tuberculosis latent infection, which were all tightly connected to amino acid metabolism, Biosynthesis of various secondary metabolites, Nucleotide metabolism, Endocrine system, Immune system, Lipid metabolism, and Nervous system. This study screened and identified Inosine, 16, 16-dimethyl-6-keto Prostaglandin E1, Theophylline, and Cotinine as potential serum biomarkers for diagnosing latent TB infection, and Cotinine as potential biomarkers for monitoring disease progression from healthy population to LTBI and then to active TB including drug-resistant TB infection and sensitive TB infection. Furthermore, this research provides a preliminary experimental basis to further investigate the development of metabolomics-based diagnosis of LTBI and monitoring the progress from latent infection to active TB infection.
Topics: Humans; Alprostadil; Tuberculosis, Pulmonary; Latent Infection; Mass Spectrometry; Tuberculosis, Multidrug-Resistant; Disease Progression
PubMed: 36482536
DOI: 10.1097/MD.0000000000032153 -
European Heart Journal. Case Reports Nov 2022The severity of peripheral artery disease (PAD) is usually diagnosed by physiological assessments, such as the ankle brachial index (ABI) or peak systolic velocity (PSV)...
BACKGROUND
The severity of peripheral artery disease (PAD) is usually diagnosed by physiological assessments, such as the ankle brachial index (ABI) or peak systolic velocity (PSV) on ultrasonography. We examined peripheral fractional flow reserve (pFFR: distal mean pressure divided by proximal mean pressure) measured by a pressure wire and pressure gradient to diagnose PAD patients who do not have lowered ABI or high PSV on ultrasonography.
CASE SUMMARY
An 84-year-old woman with intermittent claudication in her left leg had severe calcification in the left common femoral artery (CFA) on angiography. The exercise-stress ABI of pre-endovascular therapy (EVT) was 1.05/0.98. In addition, the PSV of the left CFA on ultrasonography was 230 cm/s. However, the pFFR using papaverine and alprostadil in the left CFA was 0.86, which was a significant score. In addition, the systolic pressure gradient between the distal and proximal regions was >20 mmHg. We performed EVT for the lesion, and the pFFR improved to 0.96. The systolic pressure gradient was only 1 mmHg at the lesion.
DISCUSSION
Symptomatic PAD patients whose ABI or PSV on ultrasonography is insufficient for EVT could be diagnosed with ischaemia using a pressure gradient and pFFR.
PubMed: 36405536
DOI: 10.1093/ehjcr/ytac426 -
World Journal of Clinical Cases Nov 2022Apnea caused by retrobulbar anesthesia is a very rare but severe complication during ophthalmic surgery.
BACKGROUND
Apnea caused by retrobulbar anesthesia is a very rare but severe complication during ophthalmic surgery.
CASE SUMMARY
We report a rare case of apnea caused by retrobulbar anesthesia, and emergency resuscitation was used. A 74-year-old female patient was diagnosed with rhegmatogenous retinal detachment in the right eye and planned to undergo vitrectomy under retrobulbar anesthesia. After the retrobulbar anesthesia in her right eye, she became unconscious and apneic. It was suggested that she had developed brainstem anesthesia. Assisted ventilation was initiated. Atropine 0.5 mg, epinephrine 1 mg, ephedrine 30 mg, and lipid emulsion were given. Five minutes later, her consciousness and breathing gradually returned, but with uncertain light perception in her right eye. Alprostadil 20 µg was given, and after 2 h her visual acuity resumed to the preoperative level.
CONCLUSION
Brainstem anesthesia is a serious complication secondary to retrobulbar anesthesia. Medical staff should pay attention to the identification of brainstem anesthesia and be familiar with the emergency treatment for this complication.
PubMed: 36387800
DOI: 10.12998/wjcc.v10.i31.11646 -
European Journal of Radiology Dec 2022To investigate the diagnostic value of synthetic MRI combined MUSE DWI and 3D-pCASL in hippocampal sclerosis (HS).
PURPOSE
To investigate the diagnostic value of synthetic MRI combined MUSE DWI and 3D-pCASL in hippocampal sclerosis (HS).
METHOD
A total of 30 HS patients participated in the study. At the same time, 51 healthy volunteers were collected as the control group. All patients and healthy volunteers underwent epilepsy MR scanning protocol (including oblique coronal MAGiC, MUSE DWI, and axial 3D-pCASL) at 3.0 T MR scanner.The independent samples T test and Mann-Whitney U test were used to compare the differences of the apparent dispersion coefficient(ADC), cerebral blood flow(CBF) and quantitative parameters, including T1 relaxation time (T1), T2 relaxation time (T2), and proton density (PD) values, in the hippocampus of the affected side of HS and the contralateral and control groups, respectively. The diagnostic performance was evaluated using binary logistic regression analysis and area under the receiver operating characteristic (ROC) curves (AUC).
RESULTS
Significant statistical differences in T1, T2, CBF, and ADC values were observed between the affected hippocampus of HS patients and contralateral and control hippocampus (all P < 0.005). The T2 has higher discrimination abilities compared with other univariable parameters, with the AUC of 0.899. The combined T2, ADC and CBF model had the best diagnostic performance of HS in MTLE patients with AUC, sensitivity and specificity of 0.946, 86.67 %, 93.33 %, respectively.
CONCLUSIONS
Relaxometry parameters derived from synthetic MRI contributed to diagnosis of HS. The proposed approach combining T2, ADC and CBF showed a strong diagnostic capability.
Topics: Humans; Sclerosis; Alprostadil; Magnetic Resonance Imaging; Atrophy; Hippocampus
PubMed: 36327855
DOI: 10.1016/j.ejrad.2022.110571 -
Abdominal Radiology (New York) Feb 2023To compare four diffusion-weighted imaging (DWI) sequences for image quality, rectal contour, and lesion conspicuity, and to assess the difference in their...
Multiplexed sensitivity-encoding diffusion-weighted imaging (MUSE) in diffusion-weighted imaging for rectal MRI: a quantitative and qualitative analysis at multiple b-values.
PURPOSE
To compare four diffusion-weighted imaging (DWI) sequences for image quality, rectal contour, and lesion conspicuity, and to assess the difference in their signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC).
METHODS
In this retrospective study of 36 consecutive patients who underwent 3.0 T rectal MRI from January-June 2020, DWI was performed with single-shot echo planar imaging (ss-EPI) (b800 s/mm), multiplexed sensitivity encoding (MUSE) (b800 s/mm), MUSE (b1500 s/mm), and field-of-view optimized and constrained undistorted single-shot (FOCUS) (b1500 s/mm). Two radiologists independently scored image quality using a 5-point Likert scale. Inter-reader agreement was assessed using the weighted Cohen's к. SNR, CNR, and ADC measurements were compared using the paired t-test.
RESULTS
For both readers, MUSE b800 scored significantly higher for image quality, rectal contour, and lesion conspicuity compared to ss-EPI; MUSE b800 also scored significantly higher for image quality and rectal contour compared to all other sequences. Lesion conspicuity was equally superior for MUSE b800 and MUSE b1500 compared to the other two sequences. There was good to excellent inter-reader agreement for all qualitative features (к = 0.72-0.88). MUSE b800 had the highest SNR; MUSE b1500 had the highest CNR. A significant difference in ADC was observed between ss-EPI compared to the other sequences (p < 0.001) and between MUSE b800 and FOCUS. No significant difference in ADC was found between MUSE b1500 and FOCUS b1500.
CONCLUSION
MUSE b800 improved image quality over ss-EPI and both MUSE b800 and b1500 showed better tumor conspicuity compared to conventional ss-EPI.
Topics: Humans; Alprostadil; Retrospective Studies; Reproducibility of Results; Diffusion Magnetic Resonance Imaging; Rectum; Echo-Planar Imaging
PubMed: 36307596
DOI: 10.1007/s00261-022-03710-2 -
Frontiers in Immunology 2022Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multi-organ inflammation and defect, which is linked to many molecule mediators. Oxylipins as a...
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multi-organ inflammation and defect, which is linked to many molecule mediators. Oxylipins as a class of lipid mediator have not been broadly investigated in SLE. Here, we applied targeted mass spectrometry analysis to screen the alteration of oxylipins in serum of 98 SLE patients and 106 healthy controls. The correlation of oxylipins to lupus nephritis (LN) and SLE disease activity, and the biomarkers for SLE classification, were analyzed. Among 128 oxylipins analyzed, 92 were absolutely quantified and 26 were significantly changed. They were mainly generated from the metabolism of several polyunsaturated fatty acids, including arachidonic acid (AA), linoleic acid (LA), docosahexanoic acid (DHA), eicosapentanoic acid (EPA) and dihomo-γ-linolenic acid (DGLA). Several oxylipins, especially those produced from AA, showed different abundance between patients with and without lupus nephritis (LN). The DGLA metabolic activity and DGLA generated PGE1, were significantly associated with SLE disease activity. Random forest-based machine learning identified a 5-oxylipin combination as potential biomarker for SLE classification with high accuracy. Seven individual oxylipin biomarkers were also identified with good performance in distinguishing SLE patients from healthy controls (individual AUC > 0.7). Interestingly, the biomarkers for differentiating SLE patients from healthy controls are distinct from the oxylipins differentially expressed in LN patients non-LN patients. This study provides possibilities for the understanding of SLE characteristics and the development of new tools for SLE classification.
Topics: Humans; Lupus Nephritis; Oxylipins; 8,11,14-Eicosatrienoic Acid; Eicosapentaenoic Acid; Alprostadil; Lupus Erythematosus, Systemic; Biomarkers; Arachidonic Acids; Linoleic Acids
PubMed: 36275708
DOI: 10.3389/fimmu.2022.964901 -
Journal of Medical Economics 2022Leveraging the safety profile of the synthetic hygroscopic cervical dilator (SHCD), one potential way to reduce the burden-of-care provision in the labor-and-delivery...
Moving preinduction cervical ripening to a lower acuity inpatient setting using the synthetic hygroscopic cervical dilator: a cost-consequence analysis for the United States.
BACKGROUND
Leveraging the safety profile of the synthetic hygroscopic cervical dilator (SHCD), one potential way to reduce the burden-of-care provision in the labor-and-delivery unit without compromising safety is to introduce a low-acuity care room (ripening room) for patients undergoing cervical ripening as a part of labor induction at term.
METHODS
Implementing a ripening room using SHCDs was compared to scenarios using prostaglandins including a dinoprostone insert (PGE2 insert) or gel (PGE2 gel) and misoprostol given orally (oral PGE1) or vaginally (vaginal PGE1). A theoretical, cost-consequence model was developed to assess costs, staff time, and selected clinical outcomes related to cervical ripening. The model assessed a hypothetical cohort where patients remained in hospital from admission for induction of labor (IOL) to delivery, taking the US labor-and-delivery unit perspective. Model inputs were taken from structured searches of PubMed and ClinicalTrials.gov, published US guidance, and clinical practice. Results are presented as mean (95% credible interval [CrI]).
RESULTS
The ripening room using SHCDs cost US$3,210 and required 10.22 hours (h) of nurse time on average per patient. The cost difference to prostaglandins ranged from -$894 (-$2,269 to $398) for PGE2 gel to +$460 (-$1,467 to $1,539) for vaginal PGE1. Mean nurse time was shorter than all prostaglandins, with time savings ranging from -7.05 (-24.55 to 5.73) h for PGE2 insert to -0.97 (-14.69 to 9.59) h for vaginal PGE1. When outcomes of the probabilistic sensitivity analysis were ranked from 1 (best) to 5 (worst), the ripening room using SHCDs ranked 1.94 for costs and 1.97 for nurse time. In a nulliparous population, results improved for the ripening room using SHCDs relative to all prostaglandins.
CONCLUSION
In this theoretical study, implementing a ripening room using SHCDs resulted in the lowest time burden and the second lowest costs. The cheapest option for preinduction cervical ripening was vaginal misoprostol.
Topics: Pregnancy; Female; Humans; United States; Cervical Ripening; Misoprostol; Dinoprostone; Alprostadil; Inpatients; Oxytocics; Prostaglandins
PubMed: 36274625
DOI: 10.1080/13696998.2022.2136854 -
Scientific Reports Oct 2022Mesenchymal stem cells (MSCs) are increasingly used as regenerative therapies for patients in the preclinical and clinical phases of various diseases. However, the main...
Mesenchymal stem cells (MSCs) are increasingly used as regenerative therapies for patients in the preclinical and clinical phases of various diseases. However, the main limitations of such therapies include functional heterogeneity and the lack of appropriate quality control (QC) methods for functional screening of MSC lines; thus, clinical outcomes are inconsistent. Recently, machine learning (ML)-based methods, in conjunction with single-cell morphological profiling, have been proposed as alternatives to conventional in vitro/vivo assays that evaluate MSC functions. Such methods perform in silico analyses of MSC functions by training ML algorithms to find highly nonlinear connections between MSC functions and morphology. Although such approaches are promising, they are limited in that extensive, high-content single-cell imaging is required; moreover, manually identified morphological features cannot be generalized to other experimental settings. To address these limitations, we propose an end-to-end deep learning (DL) framework for functional screening of MSC lines using live-cell microscopic images of MSC populations. We quantitatively evaluate various convolutional neural network (CNN) models and demonstrate that our method accurately classifies in vitro MSC lines to high/low multilineage differentiating stress-enduring (MUSE) cells markers from multiple donors. A total of 6,120 cell images were obtained from 8 MSC lines, and they were classified into two groups according to MUSE cell markers analyzed by immunofluorescence staining and FACS. The optimized DenseNet121 model showed area under the curve (AUC) 0.975, accuracy 0.922, F1 0.922, sensitivity 0.905, specificity 0.942, positive predictive value 0.940, and negative predictive value 0.908. Therefore, our DL-based framework is a convenient high-throughput method that could serve as an effective QC strategy in future clinical biomanufacturing processes.
Topics: Humans; Deep Learning; High-Throughput Screening Assays; Alprostadil; Mesenchymal Stem Cells; Machine Learning
PubMed: 36266301
DOI: 10.1038/s41598-022-21653-y -
Scientific Reports Oct 2022Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic pluripotent-like stem cells that exhibit triploblastic differentiation and...
Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic pluripotent-like stem cells that exhibit triploblastic differentiation and self-renewability at the single-cell level, and are collectable as pluripotent surface marker SSEA-3(+) from the bone marrow (BM), peripheral blood, and organ connective tissues. SSEA-3(+) cells from human amniotic membrane mesenchymal stem cells (hAMSCs) were compared with hBM-Muse cells. Similar to hBM-Muse cells, hAMSC-SSEA-3(+) cells expressed pluripotency genes (OCT3/4, NANOG, and SOX2), differentiated into triploblastic cells from a single cell, self-renewed, and exhibited non-tumorigenicity. Notably, however, they exhibited unique characteristics not seen in hBM-Muse cells, including higher expression of genes related to germline- and extraembryonic cell-lineages compared with those in hBM-Muse cells in single-cell RNA-sequencing; and enhanced expression of markers relevant to germline- (PRDM14, TFAP2C, and NANOS3) and extraembryonic cell- (CDX2, GCM1, and ID2) lineages when induced by cytokine subsets, suggesting a broader differentiation potential similar to naïve pluripotent stem cells. t-SNE dimensionality reduction and Gene ontology analysis visualized hAMSC-SSEA-3(+) cells comprised a large undifferentiated subpopulation between epithelial- and mesenchymal-cell states and a small mesenchymal subpopulation expressing genes relevant to the placental formation. The AM is easily accessible by noninvasive approaches. These unique cells are a potentially interesting target naïve pluripotent stem cell-like resource without tumorigenicity.
Topics: Alprostadil; Amnion; Cell Differentiation; Cytokines; Female; Humans; Placenta; Pregnancy; RNA
PubMed: 36241699
DOI: 10.1038/s41598-022-22282-1 -
International Journal of Molecular... Sep 2022Progesterone and prostaglandin E1 are postulated to trigger the human sperm acrosome reaction (AR). However, their reported efficacy is very variable which likely, in...
Progesterone and prostaglandin E1 are postulated to trigger the human sperm acrosome reaction (AR). However, their reported efficacy is very variable which likely, in part, reflects the plethora of experimental conditions and methodologies used to detect this physiologically relevant event. The purpose of this study was to develop an assay for the robust induction and objective measurement of the complete AR. Sperm from healthy volunteers or patients undertaking IVF were treated with a variety of ligands (progesterone, prostaglandin E1 or NHCl, alone or in combinations). AR, motility and intracellular calcium measurements were measured using flow cytometry, computer-assisted sperm analysis (CASA) and fluorimetry, respectively. The AR was significantly increased by the simultaneous application of progesterone, prostaglandin E1 and NHCl, following an elevated and sustained intracellular calcium concentration. However, we observed notable inter- and intra-donor sample heterogeneity of the AR induction. When studying the patient samples, we found no relationship between the IVF fertilization rate and the AR. We conclude that progesterone and prostaglandin E1 alone do not significantly increase the percentage of live acrosome-reacted sperm. This assay has utility for drug discovery and sperm toxicology studies but is not predictive for IVF success.
Topics: Acrosome; Acrosome Reaction; Alprostadil; Calcium; Calcium, Dietary; Humans; Male; Progesterone; Semen; Sperm Motility; Spermatozoa
PubMed: 36232560
DOI: 10.3390/ijms231911253