Reduction In Clearance Research Articles

The emerging role of neutrophil extracellular traps in endometritis.

Endometritis is a kind of common obstetric disease in women, usually caused by various pathogenic bacteria. Neutrophil infiltration is one of the most important pathological features of endometritis. Neutrophils can reach the uterine cavity through the endometrium, and make early response to the infection caused by the pathogen. Neutrophil extracellular traps (NETs), a meshwork of chromatin fibers extruded by neutrophils, have a role in entrapping microbial pathogens. It has been confirmed that NETs have a strong antibacterial effect and play crucial roles in the occurrence and development of various diseases. However, while killing pathogenic bacteria, excessive NETs formation may cause immune damage to the body. NETs are present in endometrium of female domestic animals in different physiological periods, especially post-mating, postpartum and in the presence of lesions, especially in endometritis. Meanwhile, NETs and its products might contribute to a reduction in physical clearance and persistent endometritis. In brief, NETs is a double-edged sword and it may play a different role in the development of endometritis, which may be beneficial or harmful, and its specific mechanism needs further study. Here we provide an overview of the role of NETs in the development of endometritis and the regulatory role of selenium on NETs formation and endometritis.

Evaluation of Chronic Kidney Disease Risk Factors after Radical Nephrectomy

Intraoperative hypotension (IOH) and loss of blood during radical nephrectomy (RN) cause postoperative clinically significant renal dysfunction, which after 12 months can cause a reduction in serum creatinine clearance of <60 mL/min. We conducted a prospective study of 93 adult patients in which we investigated the risk factors for developing chronic kidney disease (CKD) after RN. Forty-six (49.5%) patients had CKD, and of them, 43 patients had acute kidney injury (AKI) 48 h after surgery. Sixty-six (73.1%) of the postoperative AKI patients had CKD upstage. With each 1 mL estimated blood loss during RN (OR 1.01, p < 0.001), IOH was evaluated as the main risk factor of postoperative CKD development (OR 1.09, p < 0.01). Dunn’s t-test revealed that only clinically significant AKI had a main effect (g = −1.08, p < 0.0001) on renal function 1 year after RN. A higher preoperative estimated glomerular filtration rate (eGFR), OR 0.89, p = 0.02, and contralateral kidney CT volume (OR 0.97, p = 0.04) had a clinically significantly decreased risk of postoperative CKD. Risk factors of AKI with CKD upstage were a small contralateral kidney CT volume (OR 46.70), NLR > 3.5 (OR 1.42), higher primary eGFR (OR 1.13) and longer IOH (OR 1.05), and for all of these, p < 0.03. A half of all patients after RN are at increased risk of CKD. Longer IOH and increased blood loss during RN are significant risk factors for CKD. Clinically significant postoperative AKI is related with a developed risk for postoperative eGFR decline and the presence of CKD 12 months after RN, and can be predicted by NLR > 3.5. A higher preoperative eGFR and contralateral kidney CT volume reduces the risk of postoperative CKD.

Loss of aquaporin-4 results in glymphatic system dysfunction via brain-wide interstitial fluid stagnation.

The glymphatic system is a fluid transport network of cerebrospinal fluid (CSF) entering the brain along arterial perivascular spaces, exchanging with interstitial fluid (ISF), ultimately establishing directional clearance of interstitial solutes. CSF transport is facilitated by the expression of aquaporin-4 (AQP4) water channels on the perivascular endfeet of astrocytes. Mice with genetic deletion of AQP4 (AQP4 KO) exhibit abnormalities in the brain structure and molecular water transport. Yet, no studies have systematically examined how these abnormalities in structure and water transport correlate with glymphatic function. Here, we used high-resolution 3D magnetic resonance (MR) non-contrast cisternography, diffusion-weighted MR imaging (MR-DWI) along with intravoxel-incoherent motion (IVIM) DWI, while evaluating glymphatic function using a standard dynamic contrast-enhanced MR imaging to better understand how water transport and glymphatic function is disrupted after genetic deletion of AQP4. AQP4 KO mice had larger interstitial spaces and total brain volumes resulting in higher water content and reduced CSF space volumes, despite similar CSF production rates and vascular density compared to wildtype mice. The larger interstitial fluid volume likely resulted in increased slow but not fast MR diffusion measures and coincided with reduced glymphatic influx. This markedly altered brain fluid transport in AQP4 KO mice may result from a reduction in glymphatic clearance, leading to enlargement and stagnation of fluid in the interstitial space. Overall, diffusion MR is a useful tool to evaluate glymphatic function and may serve as valuable translational biomarker to study glymphatics in human disease.

Data analysis and fault-finding case study of a 660 MW steam turbine generator set in a power station,

TG2 is a GE 660 MW steam turbine generator unit at Hartlepool power station in North East of England. The unit consists of an HP turbine, an IP turbine and three LP turbines coupled with an alternator and an exciter. Although the unit was previously operating normally and within the established ISO standards, recent reports indicated excessive loading on the barring gear and instances of the barring gear becoming stuck. EDF Energy's central technical organization conducted a comprehensive analysis of the vibration data, including online, barring, run up, and run down data, to determine the root cause of the overloading. The data analysis revealed that the generator NDE bearing (bearing 12) showed signs of tilting, reducing the clearance between the shaft and the bearing and causing friction. This friction was determined to be the cause of the overloading of the barring gear. The generator operates in a pressurized hydrogen environment and changes in pressure during operation and shutdown had a ratcheting effect on the bearing tilt and clearance reduction. The EDF Energy engineering team responded promptly and professionally, documenting the issue, raising awareness among operations, and implementing a recovery plan.

Ameliorative effect of lycopene alone and in combination with co-enzyme Q10 in streptozotocin-induced diabetic nephropathy in experimental rats

Diabetic nephropathy (DN) has become an utmost reason for long-standing renal dysfunction and end-stage renal disease globally. Oxidative stress induced by persistent hyperglycemia is considered a fundamental element in the evolution of DN. The goal of this research was to discover the outcome of appendages of natural antioxidants such as lycopene and co-enzyme Q10 (CoQ10) in DN rats and to observe the preventive effects in DN. A diabetes model was developed in a Wistar strain of male rats (200–250 g) by subcutaneous injection of streptozotocin (55 mg/kg). Development of nephropathy was assessed by renal function tests including blood glucose, creatinine, albumin, total protein, total bilirubin, uric acid, total cholesterol, triglycerides, and CRP level. Oxidative stress markers such as LPO and GSH content and activity of membrane-bound Na+/K+ ATPases were measured in kidney homogenate. Renal damage was assessed by performing a histopathological analysis. DN rats showed a significant elevation in creatinine, albumin, total protein, total bilirubin, uric acid, total cholesterol, triglycerides, CRP, and LPO levels whereas a significant reduction in creatinine clearance and GSH level. Treatment with antioxidants such as lycopene (5 mg/kg/p.o.) and CoQ10 (10 mg/kg/p.o.) along with their combination for 4 weeks notably altered the level of renal function biomarkers and oxidative stress markers. These antioxidants and their combination also protected the kidney from abnormal morphological changes. The present findings suggest that the combined administration of lycopene and CoQ10, which are antioxidants, exhibits synergistic effects in mitigating renal injury by reducing hyperglycemia, oxidative stress markers, and histopathological alterations.

The peri-olfactory pathway: an "e-scent-ial" route for cerebrospinal fluid clearance?

The peri-olfactory pathway: an "e-scent-ial" route for cerebrospinal fluid clearance?

Temporal changes in the microglial proteome of male and female mice after a diffuse brain injury using label-free quantitative proteomics.

Traumatic brain injury (TBI) triggers neuroinflammatory cascades mediated by microglia, which promotes tissue repair in the short-term. These cascades may exacerbate TBI-induced tissue damage and symptoms in the months to years post-injury. However, the progression of the microglial function across time post-injury and whether this differs between biological sexes is not well understood. In this study, we examined the microglial proteome at 3-, 7-, or 28-days after a midline fluid percussion injury (mFPI) in male and female mice using label-free quantitative proteomics. Data are available via ProteomeXchange with identifier PXD033628. We identified a reduction in microglial proteins involved with clearance of neuronal debris via phagocytosis at 3- and 7-days post-injury. At 28 days post-injury, pro-inflammatory proteins were decreased and anti-inflammatory proteins were increased in microglia. These results indicate a reduction in microglial clearance of neuronal debris in the days post-injury with a shift to anti-inflammatory function by 28 days following TBI. The changes in the microglial proteome that occurred across time post-injury did not differ between biological sexes. However, we did identify an increase in microglial proteins related to pro-inflammation and phagocytosis as well as insulin and estrogen signaling in males compared with female mice that occurred with or without a brain injury. Although the microglial response was similar between males and females up to 28 days following TBI, biological sex differences in the microglial proteome, regardless of TBI, has implications for the efficacy of treatment strategies targeting the microglial response post-injury.

Respiratory viruses in stable bronchiectasis: A multicenter evaluation in Northern Italy

Bronchiectasis is a chronic respiratory disease defined by the radiological appearance of abnormal bronchial dilations in association with a clinical syndrome of cough, daily sputum production and frequent exacerbations [1]. Chronic infection with different bacteria plays a crucial role in the vicious cycle of bronchiectasis characterized by a persistent local inflammation, a worsening of bronchial anatomy and a reduction of the mucociliary clearance [2,3]. While a possible pathogenic role in bronchiectasis has been also identified for other pathogens, evidence on viral infection is still scarce [4,5].

Seasonal variation of lupus nephritis in a cohort of Egyptian patients

IntroductionSystemic lupus erythematosus is an autoimmune multisystem disease; renal affection is one of its most common manifestations. The effect of environmental factors on lupus nephritis flares is not fully understood.MethodsThis is a retrospective study that included 200 patients with lupus nephritis flares. All patients had confirmed diagnosis of lupus nephritis on histopathological examination. Lupus nephritis flares were defined by either (1) nephritic flare: defined as increased proteinuria or serum creatinine concentration; abnormal urinary sediment or a reduction in creatinine clearance, or (2) proteinuria flare defined as persistent increase in proteinuria > 0.5–1.0 g/day after achieving complete remission; doubling to > 1 g/day after achieving partial remission. The time of renal flare (month of the year) was recorded to determine the effect of seasonal variation on lupus nephritis flares.ResultsThe median age for the patients was 33 years (IQR = 13); 92% of patients were females. The median duration of lupus was 7 years (IQR = 6). The median serum creatinine was 1.4 mg/dl, median serum urea level was 32, and median UPCR was 2.4 gm/dl. The highest incidence of flares occurred in June (14%) and July (12.5%) (p = 0.003).ConclusionSeasonal pattern of LN flare was observed in our study in Egyptian cohort of patients, with most flares observed during meteorological summertime. Larger studies are needed to confirm this seasonal pattern.Key Points• Flares of lupus nephritis are common in patients with systemic lupus erythromatosus.• A seasonal pattern of flares of lupus nephritis was observed in our study. This seasonal pattern has been observed by previous studies in variable ethnicities and variable climatic circumstances.

Moderate hyperuricaemia ameliorated kidney damage in a low-renin model of experimental renal insufficiency.

Uric acid has promoted renal fibrosis and inflammation in experimental studies, but some studies have shown nephroprotective effects due to alleviated oxidative stress. We studied the influence of experimental hyperuricaemia in surgically 5/6 nephrectomized rats. Three weeks after subtotal nephrectomy or sham operation, the rats were allocated to control diet or 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Then blood, urine and tissue samples were taken, and renal morphology and oxidative stress were examined. Inflammation and fibrosis were evaluated using immunohistochemistry and real-time PCR (RT-PCR). Remnant kidney rats ingesting normal or oxonic acid diet presented with ~60% reduction of creatinine clearance and suppressed plasma renin activity. Oxonic acid diet increased plasma uric acid levels by >80 μmol/L. In remnant kidney rats, moderate hyperuricaemia decreased glomerulosclerosis, tubulointerstitial damage and kidney mast cell count, without influencing the fibrosis marker collagen I messenger RNA (mRNA) content. In both sham-operated and 5/6 nephrectomized rats, the mast cell product 11-epi-prostaglandin-F2α excretion to the urine and kidney tissue cyclooxygenase-2 (COX-2) levels were decreased. To conclude, hyperuricaemic remnant kidney rats displayed improved kidney morphology and reduced markers of oxidative stress and inflammation. Thus, moderately elevated plasma uric acid had beneficial effects on the kidney in this low-renin model of experimental renal insufficiency.

Insulin Clearance in Health and Disease.

Insulin action is impaired in type 2 diabetes. The functions of the hormone are an integrated product of insulin secretion from pancreatic β-cells and insulin clearance by receptor-mediated endocytosis and degradation, mostly in liver (hepatocytes) and, to a lower extent, in extrahepatic peripheral tissues. Substantial evidence indicates that genetic or acquired abnormalities of insulin secretion or action predispose to type 2 diabetes. In recent years, along with the discovery of the molecular foundation of receptor-mediated insulin clearance, such as through the membrane glycoprotein CEACAM1, a consensus has begun to emerge that reduction of insulin clearance contributes to the disease process. In this review, we consider the evidence suggesting a pathogenic role for reduced insulin clearance in insulin resistance, obesity, hepatic steatosis, and type 2 diabetes.

Effect of deuteration on the single dose pharmacokinetic properties and postoperative analgesic activity of methadone

Although methadone is effective in the management of acute pain, the complexity of its absorption-distribution-metabolism-excretion profile limits its use as an opioid of choice for perioperative analgesia. Because deuteration is known to improve the pharmacokinetic, pharmacodynamic and toxicological properties of some drugs, here we characterized the single dose pharmacokinetic properties and post-operative analgesic efficacy of d9-methadone.The pharmacokinetic profiles of d9-methadone and methadone administered intravenously to CD-1 male mice revealed that deuteration leads to a 5.7- and 4.4-fold increase in the area under the time-concentration curve and maximum concentration in plasma, respectively, as well as reduction in clearance (0.9 ± 0.3 L/h/kg vs 4.7 ± 0.8 L/h/kg). The lower brain-to-plasma ratio of d9-methadone compared to that of methadone (0.35 ± 0.12 vs 2.05 ± 0.62) suggested that deuteration decreases the transfer of the drug across the blood-brain barrier. The estimated LD50 value for a single intravenous dose of d9-methadone was 2.1-fold higher than that for methadone. Moreover, d9-methadone outperformed methadone in the efficacy against postoperative pain by primarily activating peripheral opioid receptors. Collectively, these data suggest that the replacement of three hydrogen atoms in three methyl groups of methadone altered its pharmacokinetic properties, improved safety, and enhanced its analgesic efficacy.

Minimizing Misalignment Effects in Finite Length Journal Bearings

This paper focuses on a method to reduce the detrimental effects that occur due to the misalignment in journal bearings by approaching it with the more complete model of a finite length bearing. Such a drawback is quite common in industrial applications, and it is generally accepted that misalignment causes a significant thinning in the film thickness in the area that is close to the bearing edges. Therefore, removing a certain volume of material from the inner surface of the bearing (bushing) over a distance that is at the bearing edges provides an additional clearance to compensate for the clearance reduction that is due to misalignment. A numerical solution that is used in this work is based on the finite difference method where the Reynolds boundary conditions are considered in the solution scheme, thereby, using an iterative procedure to identify the cavitation zone. A three-dimensional misalignment model is incorporated in the solution in order to provide a more realistic presentation of the deviations and errors that there are in comparison with the ideal aligned case. It has been found in the present work that the edge modification increases the thickness of the lubricant layer considerably and reduces the pressure spikes that are associated with the presence of misalignment. The suggested design also reduces the coefficient of friction in comparison with that of the misaligned case. Furthermore, this method helps in reducing the asymmetry of the hydrodynamic pressure field that results from the misalignment. This method enables the operation of journal bearings over a wider range of misalignment levels without sacrificing the load-carrying capacity of the bearing by maintaining a relatively thicker layer of lubricant at the critical positions that are not so due to the effects of misalignment.

In vitro evaluation of the impact of Covid-19 therapeutic agents on the hydrolysis of the antiviral prodrug remdesivir

Remdesivir (RDV, Veklury®) is an FDA-approved prodrug for the treatment of hospitalized patients with COVID-19. Recent in vitro studies have indicated that human carboxylesterase 1 (CES1) is the major metabolic enzyme catalyzing RDV activation. COVID-19 treatment for hospitalized patients typically also involves a number of antibiotics and anti-inflammatory drugs. Further, individuals who are carriers of a CES1 variant (polymorphism in exon 4 codon 143 [G143E]) may experience impairment in their ability to metabolize therapeutic agents which are CES1 substrates. The present study assessed the potential influence of nine therapeutic agents (hydroxychloroquine, ivermectin, erythromycin, clarithromycin, roxithromycin, trimethoprim, ciprofloxacin, vancomycin, and dexamethasone) commonly used in treating COVID-19 and 5 known CES1 inhibitors on the metabolism of RDV. Additionally, we further analyzed the mechanism of inhibition of cannabidiol (CBD), as well as the impact of the G143E polymorphism on RDV metabolism. An in vitro S9 fraction incubation method and in vitro to in vivo pharmacokinetic scaling were utilized. None of the nine therapeutic agents evaluated produced significant inhibition of RDV hydrolysis; CBD was found to inhibit RDV hydrolysis by a mixed type of competitive and noncompetitive partial inhibition mechanism. In vitro to in vivo modeling suggested a possible reduction of RDV clearance and increase of AUC when coadministration with CBD. The same scaling method also suggested a potentially lower clearance and higher AUC in the presence of the G143E variant. In conclusion, a potential CES1-mediated DDI between RDV and the nine assessed medications appears unlikely. However, a potential CES1-mediated DDI between RDV and CBD may be possible with sufficient exposure to the cannabinoid. Patients carrying the CES1 G143E variant may exhibit a slower biotransformation and clearance of RDV. Further clinical studies would be required to evaluate and characterize the clinical significance of a CBD-RDV interaction.

Regulation of Insulin Clearance by Non-Esterified Fatty Acids

Insulin stores lipid in adipocytes and prevents lipolysis and the release of non-esterified fatty acids (NEFA). Excessive release of NEFA during sustained energy supply and increase in abdominal adiposity trigger systemic insulin resistance, including in the liver, a major site of insulin clearance. This causes a reduction in insulin clearance as a compensatory mechanism to insulin resistance in obesity. On the other hand, reduced insulin clearance in the liver can cause chronic hyperinsulinemia, followed by downregulation of insulin receptor and insulin resistance. Delineating the cause–effect relationship between reduced insulin clearance and insulin resistance has been complicated by the fact that insulin action and clearance are mechanistically linked to insulin binding to its receptors. This review discusses how NEFA mobilization contributes to the reciprocal relationship between insulin resistance and reduced hepatic insulin clearance, and how this may be implicated in the pathogenesis of non-alcoholic fatty liver disease.

COVID-19 and renal involvement: a prospective cohort study assessing the impact of mild SARS-CoV-2 infection on the kidney function of young healthy males

PurposeCOVID-19 frequently affects the kidneys with symptoms ranging from mild proteinuria to progressive acute kidney injury. This prospective study aimed to assess the short- and long-term impact of asymptomatic and mild COVID-19 on the renal function of healthy young adults, and to determine the correlation between viral load and kidney function among these patients.MethodsThis was a prospective cohort study conducted over a period of 6 months. Patients were followed-up at baseline, and then after 3 and 6 months, respectively. Real-time PCR cycle threshold (CT) was used to determine the viral load and disease activity. Patients were classified into two groups with either asymptomatic COVID-19 or mild pneumonia. The assessment parameters were variables that could directly or indirectly relate to the renal function.ResultsA total of 48 patients were included and evaluated. The majority of patients (62.5%) had asymptomatic COVID-19 disease. Patients with mild pneumonia had significantly higher serum creatinine (SCr) at the time of COVID-19 diagnosis (beta = 12.836, 95% CI = 2.405–23.268, P = 0.019), after 3 months (beta = 14.345, 95% CI = 1.149–27.542, P = 0.035), and after 6 months (beta = 14.100, 95% CI = 0.730–27.470, P = 0.040) compared to asymptomatic patients. Mild pneumonia was also significantly associated with lower serum albumin level at the time of COVID-19 diagnosis (beta = – 6.317, 95% CI = – 9.448–− 3.185, P < 0.001).ConclusionMild COVID-19 is associated with mild renal involvement without AKI. Changes in the renal function appear to be related to reduced creatinine clearance and possible albumin leakage in the acute phase of the disease. The reduction in creatinine clearance is not predicted by viral load, and it appears to be a long-term effect of the disease that can last for at least 6 months.

Dysregulated miRNAs in Progression and Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive degeneration of neurons due to the accumulation of amyloid-β peptide (Aβ) and hyper-phosphorylation of tau protein in the neuronal milieu leading to increased oxidative stress and apoptosis. Numerous factors contribute towards the progression of AD, including miRNA, which are 22-24 nucleotides long sequence which acts as critical regulators of cellular processes by binding to 3' UTR of mRNA, regulating its expression post-transcriptionally. This review aims to determine the miRNA with the most significant dysregulation in the brain and cerebrospinal fluid (CSF) of human patients. A systemized inclusion/exclusion criterion has been utilized based on selected keywords followed by screening of those articles to conclude a list of 8 highly dysregulated miRNAs based on the fold change of AD vs control patients, which could be used in clinical testing as these miRNAs play central role in the pathophysiology of AD. Furthermore, a network study of highly dysregulated miRNA estimated the association of these miRNA in the mediation of Aβ generation and aggregation, inhibition of autophagy, reduction of Aβ clearance, microglial and astrocytic activation, neuro-inflammation, tau hyper-phosphorylation, and synaptic loss.

The Impact of Suboptimal 25-Hydroxyvitamin D Levels and Cholecalciferol Replacement on the Pharmacokinetics of Oral Midazolam in Control Subjects and Patients With Chronic Kidney Disease.

The aim of this study was to investigate the impact of suboptimal 25-hydroxyvitamin D (25-VitD) and cholecalciferol (VitD3 ) supplementation on the pharmacokinetics of oral midazolam (MDZ) in control subjects and subjects with chronic kidney disease (CKD). Subjects with CKD (n=14) and controls (n=5) with suboptimal 25-VitD levels (<30ng/mL) were enrolled in a 2-phase study. In phase 1 (suboptimal), subjects were administered a single oral dose of VitD3 (5000IU) and MDZ (2mg). In phase 2 (replete) subjects who achieved 25-VitD repletion after receiving up to 16 weeks of daily cholecalciferol were given the identical single oral doses of VitD3 and MDZ as in phase 1. Concentrations of MDZ and metabolites, 1'-hydroxymidazolam (1'-OHMDZ), and 1'-OHMDZ glucuronide (1'-OHMDZ-G) were measured by liquid chromatography-tandem mass spectrometry and pharmacokinetic analysis was performed. Under suboptimal 25-VitD, reductions in MDZ clearance and renal clearance of 47% and 87%, respectively, and a 72% reduction in renal clearance of 1'-OHMDZ-G were observed in CKD vs controls. In phase 1 versus phase 2, MDZ clearance increased in all control subjects, with a median (interquartile range) increase of 10.5 (0.62-16.7)L/h. No changes in MDZ pharmacokinetics were observed in subjects with CKD between phases 1 and 2. The effects of 25-VitD repletion on MDZ disposition was largely observed in subjects without kidney disease. Impaired MDZ metabolism and/or excretion alterations due to CKD in a suboptimal 25-VitD state may not be reversed by cholecalciferol therapy. Suboptimal 25-VitD may augment the reductions in MDZ and 1'-OHMDZ-G clearance values observed in patients with CKD.

A Comparison of Ivermectin and Non Ivermectin Based Regimen for COVID-19 in Abuja: Effects on Virus Clearance, Days-to-discharge and Mortality

Aim: To compare outcomes from ivermectin (IVM) - and non-ivermectin (NIVM)-based treatments for COVID-19 in Abuja, Nigeria.&#x0D; Methods: Sixty-one consecutive virology-proven cases were recruited and managed with IVM-based regimes. A subsequent cohort of 26 patients was treated with NIVM due to physician preference, with varying combinations of lopinavir/ritonavir (Alluvia), remdesivir, azithromycin, and enoxapramin. All patients received zinc sulfate, vitamin C and supportive therapy. Propensity matching was carried out as indicated, and Repeat Measures Analysis of Variance (RMANOVA) allowing for time*treatment interaction was carried out for time dependent variables, deriving Likelihood Ratio (LR) and P values.&#x0D; Main Outcome Measures: Change in cycle threshold (viral load) over time, positivity status by day 5, improvement in clinical status using myalgia scores, days to discharge (DTD), change in SpO2 and death.&#x0D; Results: IVM was associated with a greater and faster reduction in viral clearance (LR=64.2 p&lt; 0.0001 for the N gene): 31% and 95% were negative by days 5 and 14, respectively, versus 0% on NIVM. The mean DTD on IVM was 8.8 days versus 19.4 days, p&lt; 0.0001. IVM proved significantly superior for Myalgia scores, LR= 23.45, P=0.0007. The mortality rate was 0/61 (0%) in IVM but 4/26 (15.3%) in NIVM. Three of the 4 deaths were in females, and 2 had been vaccinated, one fully. The SP02% increased significantly more on IVM (p &lt; 0.0001 RMANOVA) than the NIVM group. C-reactive protein and D-dimer levels dropped significantly more sharply during IVM (P= 0.0068, 0.063), suggesting anti-inflammatory and antifibrinolytic activity.&#x0D; Conclusions: The IVM-based regimen caused earlier discharge from treatment and reduced mortality, in addition to clinical and laboratory improvements. Vaccination did not protect some patients from SARS-CoV-2 breakthrough infection and mortality.

Research on the influence of thermal expansion of steel shaft on dynamic characteristics of full ceramic bearing-rotor system

Bearing as the core components of high-grade CNC machine tools, with the constant change of internal clearance of bearing wear increasingly aggravated, spindle rotation accuracy reduced. In this paper, the idea of control variable method is used to explore the dynamic change of bearing clearance from different speeds and different radial loads. Starting with the dynamic model of bearing vibration, the theoretical model of rolling bearing with five degrees of freedom is established in this paper. The interaction force between steel shaft and ceramic bearing inner ring is calculated by Runge-Kutta method with elastic wall thickness ring theory, and the reduction of radial clearance of bearing is obtained. Therefore, a dynamic model of ceramic bearing considering the extrusion force of ceramic bearing inner ring is proposed. At the same time, the vibration test of steel shaft-all-ceramic bearing is designed and carried out. The test results show that under the same load, the higher the rotating speed, the shorter the time for the bearing-rotor system to reach temperature stability, and the root mean square of ceramic bearing-rotor system is obviously reduced. At the same speed, the greater the load, the more obvious the root mean square increase of the bearing-rotor system.