A novel angiographic method to estimate arterial blood flow rates using contrast reflux: Effect of injection parameters.

BACKGROUND: Contrast reflux, which is the retrograde movement of contrast against flow direction, is commonly observed during angiography. Despite a vast body of literature on angiography, the hemodynamic factors affecting contrast reflux have not been studied. Numerous methods have been developed to extract flow from angiography, but the reliability of these methods is not yet sufficient to be of routine clinical use. PURPOSE: To evaluate the effect of baseline blood flow rates and injection conditions on the extent of contrast reflux. To estimate arterial flow rates based on measurement of contrast reflux length. MATERIALS AND METHODS: Iodinated contrast was injected into an idealized tube as well as a physiologically accurate model of the cervico-cerebral vasculature. A total of 194 high-speed angiograms were acquired under varying "blood" flow rates and injection conditions (catheter size, injection rate, and injection time). The length of contrast reflux was compared to the input variables and to dimensionless fluid dynamics parameters at the catheter-tip. Arterial blood flow rates were estimated using contrast reflux length as well as a traditional transit-time method and compared to measured flow rates. RESULTS: Contrast reflux lengths were significantly affected by contrast injection rate (p < 0.0001), baseline blood flow rate (p = 0.0004), and catheter size (p = 0.04), but not by contrast injection time (p = 0.4). Reflux lengths were found to be correlated to dimensionless fluid dynamics parameters by an exponential function (R2  = 0.6-0.99). When considering the entire dataset in unison, flow estimation errors with the reflux-length method (39% ± 33%) were significantly higher (p = 0.003) than the transit-time method (33% ± 36%). However, when subgrouped by catheter, the error with the reflux-length method was substantially reduced and was significantly lower (14% ± 14%, p < 0.0001) than the transit-time method. CONCLUSION: Results show correlations between contrast reflux length and baseline hemodynamic parameters that have not been reported previously. Clinically relevant blood flow rate estimation is feasible by simple measurement of reflux length. In vivo and clinical studies are required to confirm these correlations and to refine the methodology of estimating blood flow by reflux.

Choice of injection time of conscious sedation and its impact on pain control in colonoscopy.

Purpose: The aim of this study was to identify the effect of different injection times on pain during colonoscopy procedure. Methods: In this retrospective study, the data of patients who underwent colonoscopy from June 2020 to September 2020 were assessed to investigate the effect of different injection time of sedative drugs (midazolam and dezocine). The primary endpoint was evaluating the pain intensity of the patients using visual analogue scale (VAS) immediately after colonoscopy . Results: A total of 152 patients were eligible for this study. Of them, 76 received midazolam and dezocine injection 1 min prior to the colonoscopy procedure (the 1 Min group) and the other 76 patients received the injection 3 min prior to the procedure (the 3 Min group). The vital signs of all patients were stable except for one patient who was diagnosed with inflammatory bowel disease in the 3 Min group. A transient drop in blood pressure for this patient was observed during colonoscopy but returned to normal after general treatment. The two groups had similar rates of cecal intubation (84.21% vs. 90.97%, P = 0.22), addition of sedative drugs during procedure (2.63% vs. 5.26%, P = 0.68), and adequate bowel preparation (Boston Bowel Preparation Scale ≥6, 61.84% vs. 61.84%, P = 1.0). However, patients in the 3 Min group had significantly lower VAS than those in the 1 Min group [0 (0, 1) vs. 1 (0, 2), P = 0.041]. Conclusion: The timing of drug injection during conscious sedation may affect pain control during colonoscopy, with 3 min prior to the procedure showing lower VAS.

A live yeast supplementation to gestating ewes improves bioactive molecule composition in colostrum with no impact on its bacterial composition and beneficially affects immune status of the offspring.

Colostrum quality is of paramount importance in the management of optimal ruminant growth and infectious disease prevention in early life. Live yeast supplementation effect during the last month of gestation was evaluated on ewes' colostrum composition. Two groups of ewes (n = 14) carrying twin lambs were constituted and twins were separated into groups (mothered or artificially fed) 12 h after birth. Nutrient, oligosaccharides (OS), IgG and lactoferrin concentrations were measured over 72 h after lambing, and bacterial community was described in colostrum collected at parturition (T0). Immune passive transfer was evaluated through IgG measurement in lamb serum. In both groups, colostral nutrient, OS concentrations and IgG concentrations in colostrum and lamb serum decreased over time (P < 0⋅01), except for lactose, which slightly increased (P < 0⋅001), and lactoferrin, which remained stable. Bacterial population was stable over time with high relative abundances of Aerococcaceae, Corynebacteriaceae, Moraxellaceae and Staphylococcaceae in T0 colostrum. No effect of supplementation was observed in nutrient and lactoferrin concentrations. In supplemented ewes, the level of colostral IgG was higher at T0 and a higher level of serum IgG was observed in lambs born from supplemented mothers and artificially fed, while no effect of supplementation was observed in the mothered lamb groups. Using a metabolomic approach, we showed that supplementation affected OS composition with significantly higher levels of colostral Neu-5Gc compounds up to 5 h after birth. No effect of supplementation was observed on bacterial composition. Our data suggest that live yeast supplementation offsets the negative impact of early separation and incomplete colostrum feeding in neonate lambs.

Use of ultra high performance liquid chromatography with high resolution mass spectrometry to analyze urinary metabolome alterations following acute kidney injury in post-cardiac surgery patients.

BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) can increase the mortality and morbidity, and the incidence of chronic kidney disease, in critically ill survivors. The purpose of this research was to investigate possible links between urinary metabolic changes and cardiac surgery-associated AKI. METHODS: Using ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry, non-targeted metabolomics was performed on urinary samples collected from groups of patients with cardiac surgery-associated AKI at different time points, including Before_AKI (uninjured kidney), AKI_Day1 (injured kidney) and AKI_Day14 (recovered kidney) groups. The data among the three groups were analyzed by combining multivariate and univariate statistical methods, and urine metabolites related to AKI in patients after cardiac surgery were screened. Altered metabolic pathways associated with cardiac surgery-induced AKI were identified by examining the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: The secreted urinary metabolome of the injured kidney can be well separated from the urine metabolomes of uninjured or recovered patients using multivariate and univariate statistical analyses. However, urine samples from the AKI_Day14 and Before_AKI groups cannot be distinguished using either of the two statistical analyses. Nearly 4000 urinary metabolites were identified through bioinformatics methods at Annotation Levels 1-4. Several of these differential metabolites may also perform essential biological functions. Differential analysis of the urinary metabolome among groups was also performed to provide potential prognostic indicators and changes in signalling pathways. Compared with the uninjured kidney group, the patients with cardiac surgery-associated AKI displayed dramatic changes in renal metabolism, including sulphur metabolism and amino acid metabolism. CONCLUSIONS: Urinary metabolite disorder was observed in patients with cardiac surgery-associated AKI due to ischaemia and medical treatment, and the recovered patients' kidneys were able to return to normal. This work provides data on urine metabolite markers and essential resources for further research on AKI.

Drug Formulation Impact on Prefilled Syringe Functionality and Autoinjector Performance.

Given the surging interest in developing prefilled syringe and autoinjector combination products, investment in an early compatibility assessment is critical to prevent unwarranted drug/container closure interactions and avoid potential reformulation during late stages of drug development. In addition to the standard evaluation of drug stability, it is important to consider container closure functionality and overall device performance changes over time because of drug-container closure component interaction. This study elucidated the mechanisms that cause changes in syringe glide force over time and the impact on the injection duration. It was an expansion of the previous work, which indicated that drug formulation variables such as formulation excipients and pH affect syringe functionality over time. The current study described an investigative process for troubleshooting prolonged and variable autoinjector injection time caused by an increased syringe glide force variability over time. This increase in glide force variability stems from two root causes, namely plunger dimensional variation and syringe silicone oil change over time. The results demonstrated (a) the underlying factors of silicone oil change in the presence of drug formulation matrices, (b) accelerated stability of syringe glide force as a good indicator of long-term, real-time stability, and (c) that buffer matrix-filled syringes can be used to predict the syringe functionality and stability of drug product-filled syringes. Based on the experimental findings of a variety of orthogonal characterization techniques including contact angle, interfacial tension, and calculation of Hansen solubility parameters, it is proposed that silicone oil change is caused by formulation excipients and a complex set of phenomena summarized as "wet, wash, and delube" processes.

An Improved Boosting to Amplify Signal with Isobaric Labeling (iBASIL) Strategy for Precise Quantitative Single-cell Proteomics.

Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept of using boosting/carrier channels in isobaric labeling to increase the sensitivity in MS detection has also been increasingly used for quantitative proteomic analysis of small-sized samples including single cells. However, the full potential of such boosting/carrier approaches has not been significantly explored, nor has the resulting quantitation quality been carefully evaluated. Herein, we have further evaluated and optimized our recent boosting to amplify signal with isobaric labeling (BASIL) approach, originally developed for quantifying phosphorylation in small number of cells, for highly effective analysis of proteins in single cells. This improved BASIL (iBASIL) approach enables reliable quantitative single-cell proteomics analysis with greater proteome coverage by carefully controlling the boosting-to-sample ratio (e.g. in general <100×) and optimizing MS automatic gain control (AGC) and ion injection time settings in MS/MS analysis (e.g. 5E5 and 300 ms, respectively, which is significantly higher than that used in typical bulk analysis). By coupling with a nanodroplet-based single cell preparation (nanoPOTS) platform, iBASIL enabled identification of ∼2500 proteins and precise quantification of ∼1500 proteins in the analysis of 104 FACS-isolated single cells, with the resulting protein profiles robustly clustering the cells from three different acute myeloid leukemia cell lines. This study highlights the importance of carefully evaluating and optimizing the boosting ratios and MS data acquisition conditions for achieving robust, comprehensive proteomic analysis of single cells.

Comparing the Effectiveness of Doing Intra-uterine Insemination 36 and 42 Hours After Human Chorionic Gonadotropin (HCG) Injection on Pregnancy Rate: A Randomized Clinical Trial.

Objective: Intrauterine insemination (IUI) is an assisted conception technique that involves the deposition of a processed semen sample in the upper uterine cavity, overcoming natural barriers to sperm ascent in the female reproductive tract. Hence, we compared the results of doing intra-uterine insemination 36 and 42 hours after human chorionic gonadotropin (hCG) hormone injection to achieve clinical and chemical pregnancy rates. Materials and methods: One hundred and sixty infertile women with unexplained infertility participated in this clinical trial. They were divided into two groups: those who underwent IUI 36 hours after hCG injection (control group), and those who underwent IUI 42 hours after hCG injection (case group). Statistical analyses were done using IBM-SPSS 25.0. and Chi-square test were used for data analysis. Results: The percentages of clinical and chemical pregnancies were significantly higher in the 42h group compared to the other group (P = 0.038 vs. P = 0.009, respectively). There was no significant difference regarding frequency of abortion, twin and ectopic pregnancies between the two groups (P > 0.05). Conclusion: Doing IUI 42 hours after hCG injection can significantly increase chances of fertility compared to doing it 36 hours after hCG injection.

Complementary and Alternative Medicine Usage and Its Determinant Factors Among Infertile Men in Iran.

Objective: This study aimed to assess the use of some Complementary and Alternative Medicine (CAM) techniques in infertile men. Materials and methods: This cross-sectional study was conducted on 102 infertile men referred to the only center of infertility in Kerman, Iran using convenience sampling. Data were collected using a two-part researcher-made questionnaire and analyzed using descriptive and analytical statistics (chi-square test and logistic regression) with SPSS 16. Results: According to the present study, 72.5% of subjects used at least one of the CAM methods in the past year. Among them 28.4% of the subjects have used one CAM technique, 13.7% have used two techniques, 8.8% have used three techniques, 9.8% have used four techniques, and 11.8% have used more than four techniques since the last year. None of the socio-demographic characteristics had significant association with being the user of complementary and alternative medicines. Conclusion: The results showed that almost three quarters of the infertile men used CAM indicating a high prevalence of CAM usage among them.

Optimization and Modeling of Quadrupole Orbitrap Parameters for Sensitive Analysis toward Single-Cell Proteomics.

Single-cell proteomics represents a field of extremely sensitive proteomic analysis, owing to the minute amount of yet complex proteins in a single cell. Without amplification potential as of nucleic acids, single-cell mass spectrometry (MS) analysis demands special instrumentation running with optimized parameters to maximize the sensitivity and throughput for comprehensive proteomic discovery. To facilitate such analysis, we here investigated two factors critical to peptide sequencing and protein detection in shotgun proteomics, i.e. precursor ion isolation window (IW) and maximum precursor ion injection time (ITmax), on an ultrahigh-field quadrupole Orbitrap (Q-Exactive HF). Counterintuitive to the frequently used proteomic parameters for bulk samples (>100 ng), our experimental data and subsequent modeling suggested a universally optimal IW of 4.0 Th for sample quantity ranging from 100 ng to 1 ng, and a sample-quantity dependent ITmax of more than 250 ms for 1-ng samples. Compared with the benchmark condition of IW = 2.0 Th and ITmax = 50 ms, our optimization generated up to 300% increase to the detected protein groups for 1-ng samples. The additionally identified proteins allowed deeper penetration of proteome for better revealing crucial cellular functions such as signaling and cell adhesion. We hope this effort can prompt single-cell and trace proteomic analysis and enable a rational selection of MS parameters.

The effects of l-DOPA and sulpiride on growth hormone secretion at different injection times in Holstein steers.

The effects of l-DOPA, a precursor of dopamine (DA), and sulpiride, a D2 -type DA receptor blocker, on growth hormone (GH) and prolactin (PRL) secretion were investigated in steers. Eight Holstein steers (212.8 ± 7.8 kg body weight) were used. Lighting conditions were 12:12 L:D (lights on: 06.00-18.00 hours). Blood samplings were performed during the daytime (11.00-15.00 hours) and nighttime (23.00-03.00 hours). Intravenous injections of drugs or saline were performed at 12.00 hour for the daytime and 00.00 hour for the nighttime, respectively. Plasma GH and PRL concentrations were determined by radioimmunoassay. l-DOPA did not alter the GH secretion when it was injected at 12.00 hour (spontaneous GH level at its peak). On the other hand, l-DOPA increased GH secretion at 00.00 hour (GH level at its trough). Injection of sulpiride suppressed GH secretion at 12.00 hour but did not affect GH levels at 00.00 hour. l-DOPA inhibited and sulpiride stimulated PRL release during both periods. These results suggest that dopaminergic neurons have stimulatory action on GH secretion and inhibitory action on PRL secretion in cattle. In addition, injection time should be considered to evaluate the exact effects on GH secretion due to its ultradian rhythm of GH secretion in cattle.

The Effect of Extended Injection of Subcutaneous Heparin on Pain Intensity and Bruising Incidence.

BACKGROUND: Reducing patients' pain is one of the main goals of providing clinical services, which requires nursing skill. As a simple technique, increasing the duration of subcutaneous heparin injection may affect the intensity of pain and bruising. OBJECTIVE: The aim of this study was to assess the effect of increasing the heparin injection time on pain intensity and bruising associated with subcutaneous injection. METHODS: The present quasi-experimental study consisted of 86 patients, admitted to our hospital, who were treated with subcutaneous heparin injection. A McGill pain intensity questionnaire was used to measure pain severity in a purposive sampling. All of the subjects received subcutaneous heparin twice for 10 seconds. They also were injected twice with heparin infusion, although it was for 30 seconds this time. The interval between the two injections was 24 h, and the intensity of the pain was measured after each injection. The Pearson correlation coefficient was measured, and analysis of variance (ANOVA) and the t-test were used to analyze the data. RESULTS: Eighty patients received heparin. The body mass indexes were reported as 52 (60%) and 34 (40%) for subjects within the age range of 18.5-24.9 and 25-29.9, respectively. Regarding the mean of pain intensity, there was a significant difference between the 10 and 30 s injections (p < 0.05). Additionally, there was a significant difference in bruising rates between the two methods 48 and 72 h after injection (p < 0.05). The ANOVA test showed a significant association between gender and bruising (p = 0.001). CONCLUSION: According to the results, by elevating the duration of heparin injection, the severity of pain was reduced, and, therefore, the patients felt more comfortable. TRIAL REGISTRATION: The trial was registered at the Thai Clinical Trials Registry (TCTR) with the TCTR identification of TCTR20160221001. FUNDING: This research was supported by the research cluster grant (88186-25/01/89) from Mashhad University of Medical Sciences, Mashhad, Iran. The authors received no financial support for the authorship and/or publication of this article.

Sodium hyaluronate injection immediately versus 2 weeks after arthroscopic debridement for knee osteoarthritis / 中国组织工程研究

BACKGROUND:Sodium hyaluronate injection after arthroscopic debridement of knee osteoarthritis can reduce postoperative pain and improve joint function, but there is a controversy on the time for the hyaluronate injection after arthroscopic debridement of knee osteoarthritis. OBJECTIVE:To observe the time of hyaluronate injection after arthroscopic debridement of knee osteoarthritis, and to compare recent rehabilitation effect of knee sodium hyaluronate injection for knee function after arthroscopic debridement of knee osteoarthritis between injection just after knee arthroscopy and injection 2 weeks after knee arthroscopy. METHODS:The clinical data of 100 knee osteoarthritis patients undergoing sodium hyaluronate injection immediately and 2 weeks after arthroscopic debridement were analyzed with prospective randomized control ed trial method, and the preoperative visual analog scale score, Lysholm score, 6 weeks postoperative visual analog scale score, 3 months postoperative visual analog scale score, and 3 months postoperative Lysholm score were recorded. The effects of recently rehabilitation of knee joint after surgery in two groups were compared. RESULTS AND CONCLUSION:There was no significant difference in postoperative visual analog scale score between immediate injection group (6.52±2.38) and 2 weeks postoperative injection group (6.54±2.37). The preoperative Lysholm score in the immediate injection group (43.44±16.18) was lower than that in the 2 weeks postoperative injection group (51.12±16.3). The 6 weeks postoperative visual analog scale score in the immediate injection group (3.2±2.46) was significantly higher than that in the 2 weeks postoperative injection group (5.1±2.68). The 3 months postoperative visual analog scale score/Lysholm score in the immediate injection group (2.72±2.70)/(80.58±15.63) were significantly higher than those in the 2 weeks postoperative injection group (4.72±3.07)/(64.96±21.68). The results indicate that sodium hyaluronate injection immediately after arthroscopic debridement of knee osteoarthritis is more favorable for recent rehabilitation.