Time Points T1 Research Articles

Alteration of Gut Microbiota Composition and Diversity in Acute and/or Chronic Graft-versus-Host Disease Following Hematopoietic Stem Cell Transplantation: A Prospective Cohort Study.

Changes in gut microbiome composition have been implicated in the pathogenesis of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our objective was to explore the microbial abundance in patients with GvHD after allo-HSCT. We conducted a single-center, prospective study in patients who underwent allo-HSCT and developed grade II or higher acute GvHD and/or moderate or severe chronic GvHD, to explore the microbial abundance of taxa at the phylum, family, genus, and species level, and we utilized alpha and beta diversity indices to further describe our findings. We collected fecal specimens at -2 to +2 (T1), +11 to +17 (T2), +25 to +30 (T3), +90 (T4), and +180 (T5) days to assess changes in gut microbiota, with day 0 being the day of allo-HSCT. We included 20 allo-HSCT recipients in the study. Compared with timepoint T1, at timepoint T4 we found a significant decrease in the abundance of Proteobacteria phylum (14.22% at T1 vs. 4.07% at T4, p = 0.01) and Enterobacteriaceae family (13.3% at T1 vs. <0.05% at T4, p < 0.05), as well as a significant increase in Enterococcus species (0.1% at T1 vs. 12.8% at T4, p < 0.05) in patients who developed acute GvHD. Regarding patients who developed chronic GvHD after allo-HSCT, there was a significant reduction in the abundance of Eurobactereaceae family (1.32% at T1 vs. 0.53% at T4, p < 0.05) and Roseruria genus (3.97% at T1 vs. 0.09% at T4, p < 0.05) at T4 compared with T1. Alpha and beta diversity analyses did not reveal a difference in the abundance of bacteria at the genus level in GvHD patients at T4 compared with T1. Our study reinforces results from previous studies regarding changes in gut microbiota in patients with acute GvHD and provides new data regarding the gut microbiome changes in chronic GvHD. Future studies will need to incorporate clinical parameters in their analyses to establish their association with specific changes in gut microbiota in patients with GvHD after allo-HSCT.

Extracorporeal membrane oxygenation aggravates platelet glycoprotein V shedding and δ-granule deficiency in COVID-19–associated acute respiratory distress syndrome

BackgroundExtracorporeal membrane oxygenation (ECMO) is a lifesaving therapy in patients with acute respiratory distress syndrome (ARDS). Hemostatic complications are frequently observed in patients on ECMO and limit the success of this therapy. Platelets are key mediators of hemostasis enabling activation, aggregation, and thrombus formation by coming in contact with exposed matrix proteins via their surface receptors such as glycoprotein (GP) VI or GPIb/V/IX. Recent research has elucidated a regulatory role of the GPV subunit. The cleaved soluble GPV (sGPV) ectodomain was identified to spatiotemporally control fibrin formation through complex formation with thrombin. ObjectivesWe aimed to decipher the impact of ECMO on platelet phenotype and function, including the role of GPV and plasmatic sGPV. MethodsWe recruited 36 patients with ARDS in the wake of COVID-19 pneumonia and performed a longitudinal comparison of platelet phenotype and function in non-ECMO (n = 23) vs ECMO (n = 13) compared with those of healthy controls. Patients were assessed at up to 3 time points (t1 = days 1-3; t2 = days 4-6; and t3 = days 7-14 after cannulation/study inclusion). ResultsAgonist-induced platelet activation was assessed by flow cytometry and revealed decreased GPIIb/IIIa activation and α-granule release in all ARDS patients. During ECMO treatment, agonist-induced δ-granule release continuously decreased, which was independently confirmed by electron microscopy and was associated with a prolonged in vitro bleeding time. GPV expression on the platelet surface markedly decreased in ECMO patients compared with that in non-ECMO patients. Plasma sGPV levels were increased in ECMO patients and were associated with poor outcome. ConclusionOur data demonstrate an ECMO-intrinsic platelet δ-granule deficiency and hemostatic dysfunction beyond the underlying ARDS.

Effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery

ObjectiveThis research aimed to ascertain the effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery.MethodsObese patients undergoing laparoscopic surgery under general anesthesia were separated into the control group (group C) and the dexmedetomidine group (group D) (n = 30). Patients in group D were infused with dexmedetomidine (1 μg/kg) intravenously for 10 min and then at a rate of 0.5 mg/kg h until 30 min before the end of the surgery, and those in group C were infused with an equal volume of saline. The surgery time points were divided into: before anesthesia induction (T0), 5 min after intubation (T1), 30 min after pneumoperitoneum (T2), 10 min after pneumoperitoneum release (T3), at the time of extubation (T4), 3 min after extubation (T5), and 24 h after surgery (T6). Arterial blood was collected for blood gas analysis to record arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2). Dynamic lung compliance (Cdyn), oxygenation index (OI), alveolar-arterial oxygen partial pressure difference (A-aDO2), and respiratory index (RI) were calculated. The time of surgery, anesthesia, CO2 pneumoperitoneum, eye-opening, and time from the end of surgery to extubation were recorded. Plasma IL-8 and IL-10 levels were measured from T0 to T6.ResultsThe time of surgery, anesthesia, CO2 pneumoperitoneum, eye-opening, and time from the end of surgery to extubation in group D were not statistically significant when compared with those in group C. Versus at the T1 time point, A-aDO2 and RI were higher and Cdyn and OI were lower in both groups at T2 and T3 time points. Versus group C, group D had higher Cdyn and OI and lower A-aDO2 and RI at T2 and T3 time points. Versus at the T0 time point, at each time point from T1 to T6, IL-8 and IL-10 levels were higher in both groups. Versus group C, group D had lower IL-8 and higher IL-10 levels at each time point from T1 to T6.ConclusionIn obese patients undergoing laparoscopic surgery under general anesthesia, the use of dexmedetomidine can improve the lung compliance and OI of the patients, inhibit the inflammatory response of the lungs of the patients and thus have a certain protective effect on the lung function.

The use of sodium caseinate in the freezing of sheep semen.

The aim of this study was to assess the addition of 2% sodium caseinate in a commercial egg yolk-based medium in frozen ovine semen. Eight Dorper males were used for the study. The ejaculate was divided into two portions and frozen without (G1) or with the addition of 2% sodium caseinate (G2). Kinetic parameters were evaluated using CASA (computer-assisted sperm analysis), and membrane and acrosome integrity as well as oxidative stress were assessed using flow cytometry. After thawing, a thermoresistance test was conducted at time points T0 and T90. For the fertility test, 100 ewes were inseminated with semen from two rams selected based on invitro parameters, one with good post-thaw quality (+70% total motility) and the other with low post-thaw quality (-55% total motility). For the fertility test, the females were divided into 4 groups for insemination: low-quality ram without caseinate (GBS = 25) and with caseinate (GBC = 25), and high-quality ram without caseinate (GAS = 25) and with caseinate (GAC = 25). Regarding the results of sperm kinetics, there was a statistically significant difference in the parameters of average path velocity (VAP) and curvilinear velocity (VCL) between the group frozen with BotuBov and the group with added caseinate. At time point T90, straight-line velocity maintained a trend (p < .06), with BotuBov® (BB group) being superior to caseinate this time, and in the linearity parameter, caseinate was superior to BotuBov®. Flow cytometry analysis showed no difference between any of the evaluated tests. In the fertility test, there was no statistically significant difference in the pregnancy rate between the BotuBOV® group (23%, 11/48) and the sodium caseinate group (BC group) (33%, 17/52), and no differences were observed in the male versus diluent interaction (p = .70). In conclusion, sodium caseinate supplementation did not influence sperm kinetic parameters and the fertility of sheep.

Can the dietary inorganic nitrate supplementation mitigate the vascular dysfunction in elderly with Alzheimer’s disease?

Aging and Alzheimer disease (AD) are both characterized by progressive reduction in nitric oxide bioavailability and endothelial function impairment. Promising studies on young healthy individuals underly the positive effect of dietary nitrate supplementation on endothelial function. However, the pharmacokinetics of the plasma nitrate and nitrite (PN) and the accompanying endothelial responsiveness following the oral nitrate ingestion in healthy elderly (HE) and patients with AD is not clear. Our hypothesis was that due to the reduction of nitric oxide bioavailability during aging and AD, an equal dose of oral nitrate (ON) would ameliorate the endothelial responsiveness more in the HE and even more in patients with AD in comparison to healthy young subjects (HY). Therefore, with the aim of investigating the pharmacokinetics of PN and the time-course endothelial responsiveness in response to a single dose ON, 10 HY (25±4 YRS), 10 HE (72±8 YRS) and 13 AD (73±7 YRS) were recruited. PN levels and endothelial responsiveness (single-passive leg movement (ΔPLM)) were measured in the recruited individuals prior to (T0) and hourly for 4 hours (T1, T2, T3, and T4) after: a) a single dose of ON; and b) a single dose of placebo. As expected at T0 both PN and ΔPLM were significantly reduced in the HE and even more reduced in the AD in comparison to the HY (all p&lt;0.001). No changes in PN nor ΔPLM were detected in any group following placebo intake. PN increased significantly in all three groups at T1 (p&lt;0.001) and constantly increased up to T4, but no differences were detected between time points T1 to T4 in any group. ΔPLM increased significantly in all three groups at T2, reaching highest values at T4 (p&lt;0.001). However, AD exhibited significantly lower ΔPLM values at any time point compared to HY (p&lt;0.0001) and HE (p&lt;0.001). Significant correlation between PN and ΔPLM was found (p&lt;0.001, R2=0.1654). Contrary to our hypothesis, the results of this study suggest that the PN pharmacokinetics following a single dose of ON is similar in HY, HE and AD. Moreover, the expected time-course amelioration of the endothelial responsiveness was reduced in the HE and even more reduced in the AD, suggesting that other factors, rather than the nitric oxide bioavailability, are playing a role in the age- and AD-related vascular dysfunction. Ricerca di Base 2017 - RBVR17XRSA - Effectiveness of exercise and nitrate supplementation on progression of dementia in patients with Alzheimer’s disease. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Effect of Preprocedural Low-Dose Ketamine for Pain and Anxiety in Patients during Thoracic Epidural Catheterization.

Background and Objectives: Thoracic epidural catheterization (TEC) can be both uncomfortable and fearful for patients when performed awake with the thought that the procedure may be painful. The aim of this study was to assess the effect of low-dose intravenous ketamine administration on pain and anxiety during the TEC procedure. Materials and Methods: Sixty patients were randomly divided into two groups to receive intravenous (IV) placebo (Group P) and IV low-dose (0.15 mg/kg) ketamine (LDK) (Group K) 3 min before the procedure in a double-blind manner. A visual analog scale (VAS) was used to measure anxiety (VAS-A) and pain (VAS-P) scores. Vital parameters were monitored before premedication (T1), 20 min after premedication (T2), during skin anesthesia (T3), during TEC (T4), and 5 min after TEC (T5). VAS-A values were recorded at T1, T3, T4, and T5 periods, and VAS-P levels were noted at T3, T4, and T5 periods. Results: During TEC (T4), both VAS-P and VAS-A were significantly lower in Group K (p < 0.001). The mean VAS-A value was 10.6 mm lower, and the mean VAS-P value was 9 mm lower in Group K than in Group P at the T4 time point. Additionally, the mean VAS-P value was 7.7 mm lower in Group K compared to Group P at the T3 time point (p < 0.001). Both groups showed a statistically significant difference in VAS-A measurements when compared at their respective time points (p < 0.001). However, only Group P demonstrated a statistically significant difference in VAS-P measurements (p < 0.001). VAS-P values remained stable in Group K. The number of patients who did not recall the procedure was significantly higher in Group K (p < 0.001). Furthermore, the number of patients who would consent to the same procedure in the future was significantly higher in Group K (p = 0.007). Conclusions: A preprocedural LDK (0.15 mg/kg) can effectively prevent anxiety and pain experienced by patients during the TEC procedure. Administration of LDK may provide a more comfortable procedure process without causing ketamine-induced side effects (hemodynamic, respiratory, and psychological).

In Pursuit of Optimal Quality: Cultivar-Specific Drying Approaches for Medicinal Cannabis.

A limited number of studies have examined how drying conditions affect the cannabinoid and terpene content in cannabis inflorescences. In the present study, we evaluated the potential of controlled atmosphere drying chambers for drying medicinal cannabis inflorescence. Controlled atmosphere drying chambers were found to reduce the drying and curing time by at least 60% compared to traditional drying methods, while preserving the volatile terpene content. On the other hand, inflorescences subjected to traditional drying were highly infested by Alternaria alternata and also revealed low infestation of Botrytis cinerea. In the high-THC chemovar ("240"), controlled N2 and atm drying conditions preserved THCA concentration as compared to the initial time point (t0). On the other hand, in the hybrid chemovar ("Gen12") all of the employed drying conditions preserved THCA and CBDA content. The optimal drying conditions for preserving monoterpenes and sesquiterpenes in both chemovars were C5O5 (5% CO2, 5% O2, and 90% N2) and pure N2, respectively. The results of this study suggest that each chemovar may require tailored drying conditions in order to preserve specific terpenes and cannabinoids. Controlled atmosphere drying chambers could offer a cost-effective, fast, and efficient drying method for preserving cannabinoids and terpenes during the drying process while reducing the risk of mold growth.

Accuracy, concurrent validity, and test-retest reliability of pressure-based insoles for gait measurement in chronic stroke patients.

Wearables are potentially valuable tools for understanding mobility behavior in individuals with neurological disorders and how it changes depending on health status, such as after rehabilitation. However, the accurate detection of gait events, which are crucial for the evaluation of gait performance and quality, is challenging due to highly individual-specific patterns that also vary greatly in movement and speed, especially after stroke. Therefore, the purpose of this study was to assess the accuracy, concurrent validity, and test-retest reliability of a commercially available insole system in the detection of gait events and the calculation of stance duration in individuals with chronic stroke. Pressure insole data were collected from 17 individuals with chronic stroke during two measurement blocks, each comprising three 10-min walking tests conducted in a clinical setting. The gait assessments were recorded with a video camera that served as a ground truth, and pressure insoles as an experimental system. We compared the number of gait events and stance durations between systems. Over all 3,820 gait events, 90.86% were correctly identified by the insole system. Recall values ranged from 0.994 to 1, with a precision of 1 for all measurements. The F1 score ranged from 0.997 to 1. Excellent absolute agreement (Intraclass correlation coefficient, ICC = 0.874) was observed for the calculation of the stance duration, with a slightly longer stance duration recorded by the insole system (difference of -0.01 s). Bland-Altmann analysis indicated limits of agreement of 0.33 s that were robust to changes in walking speed. This consistency makes the system well-suited for individuals post-stroke. The test-retest reliability between measurement timepoints T1 and T2 was excellent (ICC = 0.928). The mean difference in stance duration between T1 and T2 was 0.03 s. We conclude that the insole system is valid for use in a clinical setting to quantitatively assess continuous walking in individuals with stroke.

Histopathologic Changes after Yttrium-90 Radioembolization of Colorectal Liver Metastases: A Pilot Feasibility Study

PurposeTo evaluate the histopathologic changes and potential correlations of tumor absorbed dose (TAD) after yttrium-90 transarterial radioembolization (TARE) for colorectal liver metastases (CLMs). Materials and MethodsThis prospective pilot study assessed 12 patients with 13 CLMs through positron emission tomography (PET)/computed tomography (CT)–guided biopsies before, immediately after TARE (T0), and 3 weeks after TARE (T3). Subsequent sampling from the same location was enabled by fiducial placement. Biopsy samples were evaluated with hematoxylin and eosin, TUNEL, Ki67, OxPhos, caspase-3 (CC3), and pH2AX antibodies. Proliferation changes (Ki67) and double-strand DNA breaks (DSBs) were evaluated quantitatively. TAD was calculated on post-TARE PET/CT scan of the biopsy needle location at T0 and T3. ResultsMedian TAD at 3 weeks after TARE was 162 Gy (interquartile range (IQR), 92–211 Gy). DSBs decreased significantly from T0 (median, 77%; IQR, 75%–100%) to T3 (median, 14%; IQR, 0%–54%; P = .028). A decrease in Ki67 was also documented (median, 73%; IQR, 70%–80% at T0 vs median, 41%; IQR, 0%–66% at T3; P = .046). There was a strong positive correlation between TAD and DSBs at T0 (r[9] = 0.68) and a strong negative correlation at T3 (r[10] = −0.855; P = .042 and P = .002, respectively). There was a strong negative correlation between TAD and Ki67 at both T0 (r[9] = −0.733; P = .025) and T3 (r[10] = −0.681; P = .030). Tumors that exhibited caspase-3 activation (8/13, 62%) at either T0 or T3 time point were more likely to develop progression (7/8 [88%] vs 1/5 [20%]; P = .015). ConclusionsPost-TARE biopsy can be used to assess TAD and histopathologic changes. Significant decreases in DSBs and proliferation index were noted after TARE. Post-TARE CC3 activation deserves further exploration.

460 Changes in Lipid Profiles with Progression of Pregnancy in Black Women

OBJECTIVES/GOALS: Pregnant African American (Black women) have higher rates of adverse pregnancy outcomes compared to other races and routine monitoring of lipid levels is not currently in practice in prenatal care. We hypothesized that lipid profiles would show variation across pregnancy indicative of specific requirements during gestation and fetal development. METHODS/STUDY POPULATION: We used an untargeted lipidome analysis approach to investigate lipid metabolism with the progression of pregnancy. Pregnant Black women were recruited at prenatal clinics in Midwest (Metro Detroit, Michigan and Columbus, Ohio), women under 18 or above 45 years of age were not enrolled due to metabolic changes associated with these age groups. Women signed the consent forms and plasma samples were collected at 8-18 weeks at (T1), 22-29 weeks (T2) and 30-36 weeks (T3) of pregnancy. Samples from sixty-three women (mean age 27.41 ± 5.61 years) who had term birth (completed 37 weeks of pregnancy) were subjected to “shotgun” Orbitrap high resolution/ accurate mass spectrometry. Mixed-effects models were used to quantify systematic changes in relative lipid abundances over time using R lme4 and ggplot2 packages. RESULTS/ANTICIPATED RESULTS: Total lipids and some major lipid classes showed a significant increase with the progression of pregnancy. Phospholipids and glycerolipids exhibited a gradual increase throughout pregnancy, while sphingolipids and total sterol lipids displayed a more pronounced increase at the T3 timepoint. Acylcarnitines, hydroxy acylcarnitines and Lyso phospholipids levels significantly decrease from T1 to T3. One of the interesting finding was that non-esterified fatty acids decreased from T1 to T2 and increased again from T2 to T3, suggesting a possible role for these lipids during the later stages of pregnancy. The fatty acids showing this trend included key fatty acids- Linoleic Acid, Arachidonic Acid, Alpha-linolenic acid, Eicosapentaenoic acid, Docosapentaenoic acid, Docosahexaenoic acid. DISCUSSION/SIGNIFICANCE: Mapping lipid trends during pregnancy could lend support to a precision health approach to reduce perinatal health disparities among pregnant Black women. The findings from this study will be used to identify biomarkers and study associations with social and environmental factors responsible for adverse perinatal outcome in pregnant Black women.

Influence of intra-abdominal pressure on ventilatory mechanical power delivery and respiratory driving pressure during laparoscopic cholecystectomy: A prospective cohort study.

Pneumoperitoneum creation for laparoscopic surgery increases the intraabdominal pressure and causes alveolar atelectasis. We investigated the influence of an increase in intra-abdominal pressure (IAP) on ventilatory mechanical power (MP) delivery during pneumoperitoneum creation for laparoscopic cholecystectomy. In a prospective cohort design, we enrolled 42 patients undergoing laparoscopic cholecystectomy. During pneumoperitoneum creation, the IAP was sequentially raised to three predefined IAP levels (8, 11 and 14 mmHg), keeping identical ventilatory settings (timepoints T1, T2, and T3). After that, positive end-expiratory pressure (PEEP) was sequentially raised from 5 to 8 to 11 cmH2O (timepoint T4 and T5). The primary outcome included ventilatory MP delivery at each timepoint. Other variables included respiratory driving pressure (DP), airway resistance (AR), and respiratory compliance (RC). The MP increased linearly with a rise in IAP from T1 to T3 (r = 0.71, P < 0.001); the MP increased by 0.19 per unit rise in IAP (effect size 0.90, P < 0.001). A similar positive correlation was also observed between DP and IAP from T1 to T3 (r = 0.73, P < 0.001); the DP increased by 0.72 per unit rise in IAP (effect size 0.89, P < 0.001). The MP increased significantly on increasing PEEP from T3 to T5, while the DP decreased concomitantly (P < 0.001). The AR increased significantly from T1 to T3, while RC decreased concomitantly; vice-versa was observed at T4 and T5 (P < 0.001). The ventilatory MP delivery rises linearly with an increase in IAP. Targeting an IAP-guided MP level could be an attractive approach to minimize lung injury.

Plasmatic profiles of cytokines/chemokines, glial fibrillary acidic protein (GFAP) and MRI brain damage in neonates with hypoxic ischemic encephalopathy (HIE)

BackgroundPerinatal hypoxia triggers the release of cytokines and chemokines by neurons, astrocytes and microglia. In response to hypoxia–ischemia resting/ramified microglia proliferate and undergo activation, producing proinflammatory molecules. The brain damage extension seems to be related to both the severity of hypoxia and the balance between pro and anti-inflammatory response and can be explored with neuroimaging. AimsThe aim of this preliminary study was to explore possible relationships between plasma levels of inflammatory cytokines/chemokines and the severe brain damage detectable by Magnetic Resonance Imaging (MRI), performed during the hospitalization. MethodsIn 10 full terms neonates with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH), divided into cases and controls, according to MRI results, we measured and compared the plasma levels of CCL2/MCP-1, CXCL8, GFAP, IFN y, IL-10, IL-18, IL-6, CCL3, ENOLASE2, GM-CSF, IL-1b, IL-12p70, IL-33, TNFα, collected at four different time points during TH (24, 25–48, 49–72 h of life, and 7–10 days from birth). Five of enrolled babies had pathological brain MRI (cases) and 5 had a normal MRI examination (controls). Cytokines were measured by Magnetic Luminex Assay. MRI images were classified according to Barkovich’s score. ResultsMean levels of all cytokines and molecules at time T1 were not significantly different in the two groups. Comparing samples paired by day of collection, the greatest differences between cases and controls were found at times T2 and T3, during TH. At T4, levels tended to get closer again (except for IL-6, IL10 and IL18). Infants with worse MRI showed higher plasmatic GFAP levels than those with normal MRI, while their IL-18 was lower. The mean levels of CCL3MIP1alpha, GMCSF, IL1BETA overlapped throughout the observation period in both groups. ConclusionIn a small number of infants with worse brain MRI, we found higher levels of GFAP and of IL-10 at T4 and a trend toward low IL-18 levels than in infants with normal MRI, considered early biomarker of brain damage and a predictor of adverse outcome, respectively. The greatest, although not significant, difference between the levels of molecules was found in cases and controls at time points T2 and T3, during TH.

Detrimental effects of electromagnetic radiation emitted from cell phone on embryo morphokinetics and blastocyst viability in mice.

Electromagnetic radiation (EMR) has deleterious effects on sperm motility and viability, as well as oocyte membrane and organelle structure. The aim was to assess the effects of cell phone radiation on preimplantation embryo morphokinetics and blastocyst viability in mice. For superovulation, 20 female mice were treated with intraperitoneal (IP) injections of 10 IU pregnant mare's serum gonadotropin (Folligon® PMSG), followed by 10 IU of human chorionic gonadotropin (hCG) after 48 h. The zygotes (n = 150) from the control group were incubated for 4 days. The experimental zygotes (n = 150) were exposed to a cell phone emitting EMR with a frequency range 900-1800 MHz for 30 min on day 1. Then, all embryos were cultured in the time-lapse system and annotated based on time points from the 2-cell stage (t2) to hatched blastocyst (tHDyz), as well as abnormal cleavage patterns. Blastocyst viability was assessed using Hoechst and propidium iodide staining. Significant increases (P < 0.05) were observed in the cleavage division time points of t2, t8, t10, and t12 of the experimental group compared with the controls. In terms of blastocyst formation parameters, a delay in embryo development was observed in the experimental group compared with the controls. Data analysis of the time intervals between the two groups showed a significant difference in the s3 time interval (P < 0.05). Also, the rates of fragmentation, reverse cleavage, vacuole formation, and embryo arrest were significantly higher in the experimental group (P < 0.05). Furthermore, the cell survival rate in the experimental group was lower than the control group (P < 0.05). Exposure to EMR has detrimental consequences for preimplantation embryo development in mice. These effects can manifest as defects in the cleavage stage and impaired blastocyst formation, leading to lower cell viability.

Both coiling and clipping induce the time-dependent release of endogenous neuropeptide Y into serum.

The vaso- and psychoactive endogenous Neuropeptide Y (NPY) has repeatedly been shown to be excessively released after subarachnoid hemorrhage and in numerous psychiatric disorders. NPY is stored in sympathetic perivascular nerve fibers around the major cerebral arteries. This prospective study was designed to analyze the impact of microsurgical and endovascular manipulation of the cerebral vasculature versus cranio- and durotomy alone on the serum levels of NPY. 58 patients (drop-out n = 3; m:f = 26:29; mean age 52.0 ± 14.1 years) were prospectively enrolled. The vascular group underwent repair for unruptured intracranial aneurysms (UIA) of the anterior circulation [endovascular aneurysm occlusion (EV) n = 13; microsurgical clipping (MS) n = 17]; in the non-vascular group, 14 patients received microsurgical resection of a small-sized convexity meningioma (CM), and 11 patients with surgically treated degenerative lumbar spine disease (LD) served as control. Plasma was drawn (1) before treatment (t0), (2) periprocedurally (t1), (3) 6 h postprocedurally (t2), (4) 72 h postprocedurally (t3), and (5) at the 6-week follow-up (FU; t4) to determine the NPY levels via competitive enzyme immunoassay in duplicate serum samples. We statistically evaluated differences between groups by calculating one-way ANOVA and for changes along the time points using repeated measure ANOVA. Except for time point t0, the serum concentrations of NPY ranged significantly higher in the vascular than in the non-vascular group (p < 0.001), with a slight decrease in both vascular subgroups 6 h postprocedurally, followed by a gradual increase above baseline levels until FU. At t3, the EV subgroup showed significantly higher NPY levels (mean ± standard deviation) than the MS subgroup (0.569 ± 0.198 ng/mL vs. 0.415 ± 0.192 ng/mL, p = 0.0217). The highest NPY concentrations were measured in the EV subgroup at t1, t3, and t4, reaching a climax at FU (0.551 ± 0.304 ng/mL). Our study reveals a first insight into the short-term dynamics of the serum levels of endogenous NPY in neurosurgical and endovascular procedures, respectively: Direct manipulation within but also next to the major cerebral arteries induces an excessive release of NPY into the serum. Our findings raise the interesting question of the potential capacity of NPY in modulating the psycho-behavioral outcome of neurovascular patients.

Recovery and stress monitoring in elite ice hockey: A longitudinal pilot-study

Introduction&#x0D; Young athletes in high-level sports experience a greater risk for injury and illness during phases of increased training and competitive load. When recovery is too sparse under these circumstances, psychological and physical health problems could emerge. These are referred to as nonfunctional overreaching or overtraining syndrome, OTS (Daly et al., 2022; Jones et al., 2017; Kiely, 2018). OTS is typically characterized by a reduction in athletic performance that lasts for several weeks to months, accompanied with mood and sleep disturbances, feelings of depression, respiratory tract infections, weight loss, and other symptoms. The prevalence of this condition is high with approxymately 10-20 % of young adult and about 29 % of young athletes from various sports beeing affected (Matos et al., 2011). To our knowledge, no scientifically valid and reliable measurement system currently exists, which would allow the preventive, early diagnosis of overreaching states that might lead to OTS (Weakley et al., 2022). The aim of this study is to develop and evaluate a multiparameter measurement system to assess the recovery and stress state of high-level athletes.&#x0D; Methods&#x0D; Twenty-five male ice hockey players from the highest level Swiss leagues at their respective age group participated (i.e., National League, NL, n = 11, age = 24.8 ± 4.1 years and U20, n = 14, age = 18.5 ± 1.5 years). Over 5-10 weeks during the in-season (i.e., competition phase) measurements were performed on 10 separate days, either after 1 day of passive recovery (T1) or after a day with match/intensive training (T2). The measurement battery included counter movement jump (CMJ), heart rate variability (HRV), executive functions (EF), tympanic temperature (Temp), and Stress Recovery Short Scale (SRSS).&#x0D; Results&#x0D; Independent Student’s t-tests showed significant differences (p &lt; 0.05) between timepoints T1 and T2 for CMJ (peak power per body mass), HRV (sympathic and parasympatic indexes), and SRSS (recovery, stress, total score); but not for CMJ (jump height), EF and Temp.&#x0D; Discussion/Conclusion&#x0D; We conclude that various measurment parameters, including CMJ performance, HRV indices, and subjective ratings of recovery and stress could provide valuable feedback for athletes, coaches, and medical staff regarding a potential overreaching or OTS state.&#x0D; References&#x0D; Daly, E., Pearce, A. J., Esser, P., &amp; Ryan, L. (2022). Evaluating the relationship between neurological function, neuromuscular fatigue, and subjective performance measures in professional rugby union players. Frontiers in Sports and Active Living, 4, Article 1058326. https://doi.org/10.3389/fspor.2022.1058326&#x0D; Jones, C. M., Griffiths, P. C., &amp; Mellalieu, S. D. (2017). Training load and fatigue marker associations with injury and illness: A systematic review of longitudinal studies. Sports Medicine, 47(5), 943-974. https://doi.org/10.1007/s40279-016-0619-5&#x0D; Kiely, J. (2018). Periodization theory: Confronting an inconvenient truth. Sports Medicine, 48(4), 753-764. https://doi.org/10.1007/s40279-017-0823-y&#x0D; Matos, N. F., Winsley, R. J., &amp; Williams, C. A. (2011). Prevalence of nonfunctional overreaching/overtraining in young English athletes. Medicine &amp; Science in Sports &amp; Exercise, 43(7), 1287-1294. https://doi.org/10.1249/MSS.0b013e318207f87b&#x0D; Weakley, J., Halson, S. L., &amp; Mujika, I. (2022). Overtraining syndrome symptoms and diagnosis in athletes: Where is the research? A systematic review. International Journal of Sports Physiology and Performance, 17(5), 675-681. https://doi.org/10.1123/ijspp.2021-0448

Clinical utility of elective paediatric flexible bronchoscopy and impact on the quality of life: protocol for a single-centre, single-blind, randomised controlled trial

IntroductionElective flexible bronchoscopy (FB) is now widely available and standard practice for a variety of indications in children with respiratory conditions. However, there are no randomised controlled trials (RCTs) that...

Prospective study of complications and sequelae of glucocorticoid therapy in ANCA-associated vasculitis

ObjectiveGlucocorticoids (GC) are a cornerstone in treating antineutrophil cytoplasmic antibodies-associated vasculitides (AAV), however, they add to morbidity and mortality. To date, GC toxicity in AAV has rarely been systematically investigated.MethodsPatients...

13C-Metabolic flux analysis detected a hyperoxemia-induced reduction of tricarboxylic acid cycle metabolism in granulocytes during two models of porcine acute subdural hematoma and hemorrhagic shock.

Supplementation with increased inspired oxygen fractions has been suggested to alleviate the harmful effects of tissue hypoxia during hemorrhagic shock (HS) and traumatic brain injury. However, the utility of therapeutic hyperoxia in critical care is disputed to this day as controversial evidence is available regarding its efficacy. Furthermore, in contrast to its hypoxic counterpart, the effect of hyperoxia on the metabolism of circulating immune cells remains ambiguous. Both stimulating and detrimental effects are possible; the former by providing necessary oxygen supply, the latter by generation of excessive amounts of reactive oxygen species (ROS). To uncover the potential impact of increased oxygen fractions on circulating immune cells during intensive care, we have performed a 13C-metabolic flux analysis (MFA) on PBMCs and granulocytes isolated from two long-term, resuscitated models of combined acute subdural hematoma (ASDH) and HS in pigs with and without cardiovascular comorbidity. Swine underwent resuscitation after 2 h of ASDH and HS up to a maximum of 48 h after HS. Animals received normoxemia (PaO2 = 80 - 120 mmHg) or targeted hyperoxemia (PaO2 = 200 - 250 mmHg for 24 h after treatment initiation, thereafter PaO2 as in the control group). Blood was drawn at time points T1 = after instrumentation, T2 = 24 h post ASDH and HS, and T3 = 48h post ASDH and HS. PBMCs and granulocytes were isolated from whole blood to perform electron spin resonance spectroscopy, high resolution respirometry and 13C-MFA. For the latter, we utilized a parallel tracer approach with 1,2-13C2 glucose, U-13C glucose, and U-13C glutamine, which covered essential pathways of glucose and glutamine metabolism and supplied redundant data for robust Bayesian estimation. Gas chromatography-mass spectrometry further provided multiple fragments of metabolites which yielded additional labeling information. We obtained precise estimations of the fluxes, their joint credibility intervals, and their relations, and characterized common metabolic patterns with principal component analysis (PCA). 13C-MFA indicated a hyperoxia-mediated reduction in tricarboxylic acid (TCA) cycle activity in circulating granulocytes which encompassed fluxes of glutamine uptake, TCA cycle, and oxaloacetate/aspartate supply for biosynthetic processes. We further detected elevated superoxide levels in the swine strain characterized by a hypercholesterolemic phenotype. PCA revealed cell type-specific behavioral patterns of metabolic adaptation in response to ASDH and HS that acted irrespective of swine strains or treatment group. In a model of resuscitated porcine ASDH and HS, we saw that ventilation with increased inspiratory O2 concentrations (PaO2 = 200 - 250 mmHg for 24 h after treatment initiation) did not impact mitochondrial respiration of PBMCs or granulocytes. However, Bayesian 13C-MFA results indicated a reduction in TCA cycle activity in granulocytes compared to cells exposed to normoxemia in the same time period. This change in metabolism did not seem to affect granulocytes' ability to perform phagocytosis or produce superoxide radicals.

A Structured Training for Trans Anal Irrigation in Pediatric Patients Improves Outcomes and Reduce Failures: Results of an Interventional Multicenter Prospective Study

BackgroundContinence issues due to organic causes including previous colorectal surgery or neurological issues might benefit from Transanal irrigation (TAI) that proved to be highly effective but with a number of limitations including a relatively high discontinuation rates. Our study was aimed at evaluating the efficacy of an advanced protocol tailored to each patient to prevent dropout and increase satisfaction, independence, and quality of life. Materials and methodsThis was a prospective, interventional, multicenter, nonrandomized study involving children aged 4–18 years with bowel dysfunction unresponsive to conventional treatments who required TAI. TAI was performed in accordance to the best standards of care with a total irrigation volume that was determined based on low emission X-Ray barium enemas performed at the very beginning of the study. All patients underwent training and assessments of continence, patients’ perspectives and quality of life were performed at different timepoints from enrollment (T0) up to 6 months since TAI was introduced (T3). ResultsA total of 78 patients were enrolled. Male to female ratio was 1.4:1. Mean age at enrollment was 106.1 ± 42.8 months. Discontinuation was reported by 3 patients (3.8 %). Continence, satisfaction and a number of other outcome measures increased from baseline (T0) to the last visit (T3). In particular, mean Rintala total score increased linearly from 7.8 to 14.8 during the study period (T0 to T3 timepoints). On a multivariate analysis, the only parameter that proved to be inversely associated with continence as well as with other outcome measures was the use of laxatives at enrollment and during the study. ConclusionsThis study has demonstrated the high efficacy of this innovative patient-tailored TAI protocol across all assessed scores. Of note, given the negative impact of laxatives, our findings suggest limiting their use in this patient population to further increase the efficacy of the procedure.

Algorithms for predicting COVID outcome using ready-to-use laboratorial and clinical data.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging crisis affecting the public health system. The clinical features of COVID-19 can range from an asymptomatic state to acute respiratory syndrome and multiple organ dysfunction. Although some hematological and biochemical parameters are altered during moderate and severe COVID-19, there is still a lack of tools to combine these parameters to predict the clinical outcome of a patient with COVID-19. Thus, this study aimed at employing hematological and biochemical parameters of patients diagnosed with COVID-19 in order to build machine learning algorithms for predicting COVID mortality or survival. Patients included in the study had a diagnosis of SARS-CoV-2 infection confirmed by RT-PCR and biochemical and hematological measurements were performed in three different time points upon hospital admission. Among the parameters evaluated, the ones that stand out the most are the important features of the T1 time point (urea, lymphocytes, glucose, basophils and age), which could be possible biomarkers for the severity of COVID-19 patients. This study shows that urea is the parameter that best classifies patient severity and rises over time, making it a crucial analyte to be used in machine learning algorithms to predict patient outcome. In this study optimal and medically interpretable machine learning algorithms for outcome prediction are presented for each time point. It was found that urea is the most paramount variable for outcome prediction over all three time points. However, the order of importance of other variables changes for each time point, demonstrating the importance of a dynamic approach for an effective patient's outcome prediction. All in all, the use of machine learning algorithms can be a defining tool for laboratory monitoring and clinical outcome prediction, which may bring benefits to public health in future pandemics with newly emerging and reemerging SARS-CoV-2 variants of concern.