Peripheral Distribution Research Articles

Scaling of nuclear numbers and their spatial arrangement in skeletal muscle cell size regulation.

Many cells display considerable functional plasticity and depend on the regulation of numerous organelles and macromolecules for their maintenance. In large cells, organelles also need to be carefully distributed to supply the cell with essential resources and regulate intracellular activities. Having multiple copies of the largest eukaryotic organelle, the nucleus, epitomizes the importance of scaling gene products to large cytoplasmic volumes in skeletal muscle fibers. Scaling of intracellular constituents within mammalian muscle fibers is, however, poorly understood, but according to the myonuclear domain hypothesis, a single nucleus supports a finite amount of cytoplasm and is thus postulated to act autonomously, causing the nuclear number to be commensurate with fiber volume. In addition, the orderly peripheral distribution of myonuclei is a hallmark of normal cell physiology, as nuclear mispositioning is associated with impaired muscle function. Because underlying structures of complex cell behaviors are commonly formalized by scaling laws and thus emphasize emerging principles of size regulation, the work presented herein offers more of a unified conceptual platform based on principles from physics, chemistry, geometry, and biology to explore cell size-dependent correlations of the largest mammalian cell by means of scaling.

Population Pharmacokinetic Modeling and Dose Optimization of Acetaminophen and its Metabolites Following Intravenous Infusion in Critically ill Adults.

Acetaminophen (paracetamol) is a ubiquitously administered drug in critically ill patients. Considering the dearth of literature, we evaluated the population pharmacokinetics of intravenous acetaminophen and its principal metabolites (sulfate and glucuronide) in this population. Critically ill adults receiving intravenous acetaminophen were included in the study. One to three blood samples were withdrawn per patient for the estimation of acetaminophen, and its metabolites (acetaminophen glucuronide and acetaminophen sulfate). High-performance liquid chromatography was used for measuring serum concentrations. We used nonlinear mixed-effect modeling for estimating the primary pharmacokinetic parameters of acetaminophen and its metabolites. The effect of covariates was evaluated followed by dose optimization using Monte Carlo simulation. Patient factors such as demographic information, liver and renal function tests were used as covariates in population pharmacokinetic analysis. The therapeutic range for serum acetaminophen concentration was considered to be 66-132μM, while 990μM was considered as the threshold for toxic concentration. Eighty-seven participants were recruited. A joint two-compartment acetaminophen pharmacokinetic model linked to glucuronide and sulfate metabolite compartments was used. The central and peripheral volume distributions were 7.87 and 8.87 L/70kg, respectively. Estimated clearance (CL) was 0.58L/h/70 kg, while intercompartmental clearance was 44.2L/h/70 kg. The glucuronide and sulfate metabolite CL were 22 and 94.7L/h/70 kg, respectively. Monte Carlo simulation showed that twice-daily administration of acetaminophen would result in a relatively higher proportion of patient population achieving and retaining serum concentrations in the therapeutic range, with reduced risk of concentrations remaining in the toxic range. A joint pharmacokinetic model for intravenous acetaminophen and its principal metabolites in a critically ill patient population has been developed. Acetaminophen CL in this patient population is reduced. We propose a reduction in the frequency of administration to reduce the risk of supra-therapeutic concentrations in this population.

Clozapine-loaded nanocapsules improve antipsychotic activity in rats: building a sequential PopPK/PD model to discriminate nanocarriers in the preformulation step.

We investigated the impact of nanoformulations on the dose-exposure-response relationship of clozapine (CZP), a low-solubility antipsychotic with serious adverse effects, using a popPK/PD approach. We evaluated the pharmacokinetics and PK/PD profiles of three coated polymeric CZP-loaded nanocapsules functionalized with polysorbate 80 (NCP80), polyethylene glycol (NCPEG), and chitosan (NCCS). Data on in vitro CZP release by dialysis bag, plasma pharmacokinetic profiles in male Wistar rats (n = 7/group, 5 mg kg-1, i.v.), and percentage of head movements in a stereotyped model (n = 7/group, 5 mg kg-1, i.p.) were integrated using a sequential model building approach (MonolixSuiteTM-2020R1-Simulation Plus). A base popPK model developed with CZP solution data collected after the i.v. administration of CZP was expanded to describe the changes in drug distribution caused by nanoencapsulation. Two additional compartments were inserted into the NCP80 and NCPEG models, and a third compartment was included in the NCCS model. The nanoencapsulation showed a decrease in the central volume of distribution for NCCS (V1NCpop = 0.21 mL), while for FCZP, NCP80, and NCPEG, it was ~1 mL. The peripheral distribution volume was higher for the nanoencapsulated groups (19.1 and 129.45 mL for NCCS and NCP80, respectively) than for FCZP. The popPK/PD model showed a formulation-dependent plasma IC50, with 20-, 50-, and 80-fold reductions compared to the CZP solution (NCP80, NCPEG, and NCCS, respectively). Our model discriminates the coatings and describes the peculiar PK and PD behavior of nanoencapsulated CZP, especially NCCS, making it an exciting tool for evaluating the preclinical performance of nanoparticles.

Effect and Mechanism of Sodium Butyrate on Neuronal Recovery and Prognosis in Diabetic Stroke.

Ischemic stroke is a cerebrovascular lesion caused by local ischemia and hypoxia. Diabetes mellitus (DM) is a chronic inflammatory disease that disturbs immune homeostasis and predisposes patients to ischemic stroke. The mechanism by which DM exacerbates stroke remains unclear, although it may involve disturbances in immune homeostasis. Regulatory T cells (Tregs) play a regulatory role in many diseases, but the mechanism of Tregs in diabetes complicated by stroke remains unclear. Sodium butyrate is a short-chain fatty acid that increases Treg levels. This study examined the role of sodium butyrate in the prognosis of neurological function in diabetic stroke and the mechanism by which Tregs are amplified in the bilateral cerebral hemispheres. We evaluated the brain infarct volume, observed 48-h neuronal injury and 28-day behavioral changes, and calculated the 28-day survival rate in mice. We also measured Treg levels in peripheral blood and brain tissue, recorded changes in the blood‒brain barrier and water channel proteins and neurotrophic changes in mice, measured cytokine levels and peripheral B-cell distribution in bilateral hemispheres and peripheral blood, and examined the polarization of microglia and the distribution of peripheral T-cell subpopulations in bilateral hemispheres. Diabetes significantly exacerbated the poor prognosis and neurological deficits in mice with stroke, and sodium butyrate significantly improved infarct volume, prognosis, and neurological function and showed different mechanisms in brain tissue and peripheral blood. The potential regulatory mechanism in brain tissue involved modulating Tregs/TGF-β/microglia to suppress neuroinflammation, while that in peripheral blood involved improving the systemic inflammatory response through Tregs/TGF-β/T cells.

Pulmonary CT angiography in the first wave of the COVID-19 pandemic: Comparison between patients with and without infection and with a pre-pandemic series

Background and aimsTo analyze the diagnostic performance of pulmonary CT angiography and to compare different D-dimer cutoffs for the diagnosis of acute pulmonary embolism in patients with and without SARS-CoV-2 infections. Materials and methodsWe retrospectively analysed all consecutive pulmonary CT angiography studies done for suspected pulmonary embolism in a tertiary hospital during two time periods: the first December 2020 through February 2021 and the second December 2017 through February 2018. D-dimer levels were obtained less than 24 h before the pulmonary CT angiography studies. We analysed the sensitivity, specificity, positive and negative predictive values, area under the receiver operating curve (AUC), and pattern of pulmonary embolism for six different values of D-dimer and the extent of the embolism. During the pandemic period, we also analysed whether the patients had COVID-19. ResultsAfter excluding 29 poor-quality studies, 492 studies were analysed; 352 of these were done during the pandemic, 180 in patients with COVID-19 and 172 in patients without COVID-19. The absolute frequency of pulmonary embolism diagnosed was higher during the pandemic period (34 cases during the prior period and 85 during the pandemic; 47 of these patients had COVID-19). No significant differences were found in comparing the AUCs for the D-dimer values. The optimum values calculated for the receiver operating characteristic curves differed between patients with COVID-19 (2200 mcg/l), without COVID-19 (4800 mcg/l), and diagnosed in the prepandemic period (3200 mcg/l). Peripheral distribution of the emboli was more common in patients with COVID-19 (72%) than in those without COVID-19 and than in those diagnosed before the pandemic [OR 6.6, 95% CI: 1.5–24.6, p < 0.05 when compared to central distribution]. ConclusionsThe number of CT angiography studies and the number of pulmonary embolisms diagnosed during the pandemic increased due to SARS-CoV-2 infection. The optimal d-dimer cutoffs and the distribution of the pulmonary embolisms differed between the groups of patients with and without COVID-19.

Quantification approaches for magnetic resonance imaging following intravenous gadolinium injection: A window into brain-wide glymphatic function.

The glymphatic system is a brain-wide network of perivascular pathways along which cerebrospinal fluid and interstitial fluid rapidly exchange, facilitating solute and waste clearance from the brain parenchyma. The characterization of this exchange process in humans has relied primarily upon serial magnetic resonance imaging following intrathecal gadolinium-based contrast agent injection. However, less invasive approaches are needed. Here, we administered a gadolinium-based contrast agent intravenously in eight healthy participants and acquired magnetic resonance imaging scans prior to and 30, 90, 180, and 360 min post contrast injection. Using a region-of-interest approach, we observed that peripheral tissues and blood vessels exhibited high enhancement at 30 min after contrast administration, likely reflecting vascular and peripheral interstitial distribution of the gadolinium-based contrast agent. Ventricular, grey matter and white matter enhancement peaked at 90 min, declining thereafter. Using k-means clustering, we identify distinct distribution volumes reflecting the leptomeningeal perivascular network, superficial grey matter and deep grey/white matter that exhibit a sequential enhancement pattern consistent with parenchymal contrast enhancement via the subarachnoid cerebrospinal fluid compartment. We also outline the importance of correcting for (otherwise automatic) autoscaling of signal intensities, which could potentially lead to misinterpretation of gadolinium-based contrast agent distribution kinetics. In summary, we visualize and quantify delayed tissue enhancement following intravenous administration of gadolinium-based contrast agent in healthy human participants.

Spectrum of CT-Scan Findings in Symptomatic and Asymptomatic Patients of SARS-CoV-2 Disease: An African Series

In this paper, we studied retrospectively the Chest CT-scan chest of 118 SARS-CoV-2 disease cases confirmed by Polymerase Chain Reaction (PCR). We identified and characterized the most common CT findings, and compared such findings in the asymptomatic patients with those patients that presented with findings in patients with mild form of the disease. Bilateral pulmonary parenchyma ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and a peripheral lung distribution were the most common CT findings. These were often associated with reticular and crazy paving pattern. Pleural and pericardial effusions were rare and mainly present in diffuse lung involvement. Most of our patient showed minimal lung involvement. There was no statistical significant difference in CT findings between asymptomatic patients and those with mild symptoms.

Tomographic behavior of pneumonia caused by SARS-CoV-2

From the first report of the respiratory disease caused by SARS-Cov-2 towards the end of 2019, in Wuhan, China, to June 8, 2020, 6,931,000 people had been affected in the world, and 113,619 in Mexico, where there is a lack of literature describing the tomographic behavior of this disease throughout its evolution and its correlation with patient clinical data. To identify, describe and classify the manifestations detected on chest computed tomography images of patients with pneumonia caused by SARS-CoV-2. Hospitalized patients with RT-PCR-confirmed SARS-CoV-2 infection and who underwent a plain chest tomography were included. The most common tomographic patterns were ground glass opacity, consolidation, cobblestone pattern and mixed pattern, with peripheral and subpleural distribution and bilateral involvement in up to 95 %. Subpleural bands that distorted the architecture were identified in up to 62 % of patients, with an average of seven days of evolution. The most common extrapulmonary finding was an increase in pulmonary artery transverse axis. Knowing the behavior of this type of pneumonia allows becoming familiarized with the characteristic tomographic patterns, in order to aid timely detection and treatment.

Leucine Repeat Rich Kinase 1 Controls Osteoclast Activity by Managing Lysosomal Trafficking and Secretion.

We previously demonstrated that mice with targeted deletion of the leucine repeat rich kinase 1 (Lrrk1) gene were osteopetrotic due to the failure of osteoclasts to resorb bone. To determine how LRRK1 regulates osteoclast activity, we examined the intracellular and extracellular acidification with an acidotropic probe, acridine orange, in live osteoclasts on bone slices. We examined lysosome distribution in osteoclasts by localization of LAMP-2, cathepsin K, and v-ATPase by immunofluorescent staining with specific antibodies. We found that both vertical and horizontal cross-sectional images of the wild-type (WT) osteoclasts showed orange-staining of the intracellular acidic vacuoles/lysosomes dispersed to the ruffled border. By contrast, the LRRK1 deficient osteoclasts exhibited fluorescent orange staining in the cytoplasm away from the extracellular lacunae because of an altered distribution of the acidic vacuoles/lysosomes. In addition, WT osteoclasts displayed a peripheral distribution of LAMP-2 positive lysosomes with a typical actin ring. The clustered F-actin constitutes a peripheral sealing zone and a ruffled border which was stretched out into a resorption pit. The LAMP-2 positive lysosomes were also distributed to the sealing zone, and the cell was associated with a resorption pit. By contrast, LRRK1-deficient osteoclasts showed diffused F-actin throughout the cytoplasm. The sealing zone was weak and not associated with a resorption pit. LAMP-2 positive lysosomes were also diffuse in the cytoplasm and were not distributed to the ruffled border. Although the LRRK1-deficient osteoclast expressed normal levels of cathepsin K and v-ATPase, the lysosomal-associated cathepsin K and v-ATPase were not accumulated at the ruffled border in Lrrk1 KO osteoclasts. Our data indicate that LRRK1 controls osteoclast activity by regulating lysosomal distribution, acid secretion, and protease exocytosis.

Numerical Simulation of an Indirect Contact Mobilized Thermal Energy Storage Container with Different Tube Bundle Layout and Fin Structure

The great development of energy storage technology and energy storage materials will make an important contribution to energy saving, reducing emissions and improving energy utilization efficiency. Mobile thermal energy storage (M-TES) technology finds a way to realize value for low-grade heat sources far beyond the demand side. In this paper, an indirect-contact M-TES container is studied using the computational fluid dynamics (CFD) method. By optimizing the heat exchange tube bundle layout and the installed fin structure of the shell and tube type M-TES container, a method of enhancing the charging and discharging efficiency is identified. The peripheral distribution mode of the heat exchanger tubes improves the efficiency of heat charging by 12.6% compared with the traditional uniform layout. The installation of the Y-shaped fins can improve the heat charging efficiency by 8.3%, better than straight fins. Compared with the horizontal installation of Y-shaped fins, the vertical installation of Y-shaped fins is preferred to improve the heat charging efficiency of the M-TES container.

Associations between Short-Term Air Pollution Exposure and the Peripheral Leukocyte Distribution in the Adult Male Population in Beijing, China.

The inflammatory effects of air pollution exposure may account for increased public health risk. However, evidence regarding the effects of air pollution on peripheral blood leukocytes in the population is inconsistent. We investigated the association between the short-term effects of ambient air pollution and the peripheral blood leukocyte distribution in adult men in Beijing, China. From January 2015 to December 2019, a total of 11,035 men aged 22-45 years in Beijing were included in the study. Their peripheral blood routine parameters were measured. The ambient pollution monitoring parameters (particulate matter ≤ 10 µm (PM10), PM2.5, nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3)) were collected daily. The potential association between ambient air pollution exposure and peripheral blood leukocyte count and classification was analyzed with generalized additive models (GAMs). After adjusting for confounding factors, PM2.5, PM10, SO2, NO2, O3, and CO were significantly correlated with changes to at least one peripheral leukocyte subtype. Short-term and cumulative air pollutant exposure dramatically increased the participants' peripheral blood neutrophil, lymphocyte, and monocyte numbers and decreased eosinophils and basophils. Our results demonstrated that air pollution induced inflammation in the participants. The peripheral leukocyte count and classification can be utilized to evaluate the inflammation induced by air pollution in the exposed male population.

Predictive Factors of Piperacillin Exposure and the Impact on Target Attainment after Continuous Infusion Administration to Critically Ill Patients

Critically ill patients undergo significant pathophysiological changes that affect antibiotic pharmacokinetics. Piperacillin/tazobactam administered by continuous infusion (CI) improves pharmacokinetic/pharmacodynamic (PK/PD) target attainment. This study aimed to characterize piperacillin PK after CI administration of piperacillin/tazobactam in critically ill adult patients with preserved renal function and to determine the empirical optimal dosing regimen. A total of 218 piperacillin concentrations from 106 patients were simultaneously analyzed through the population PK approach. A two-compartment linear model best described the data. Creatinine clearance (CLCR) estimated by CKD-EPI was the covariate, the most predictive factor of piperacillin clearance (CL) interindividual variability. The mean (relative standard error) parameter estimates for the final model were: CL: 12.0 L/h (6.03%); central and peripheral compartment distribution volumes: 20.7 L (8.94%) and 62.4 L (50.80%), respectively; intercompartmental clearance: 4.8 L/h (26.4%). For the PK/PD target of 100% fT>1×MIC, 12 g of piperacillin provide a probability of target attainment > 90% for MIC < 16 mg/L, regardless of CLCR, but higher doses are needed for MIC = 16 mg/L when CLCR > 100 mL/min. For 100% fT>4×MIC, the highest dose (24 g/24 h) was not sufficient to ensure adequate exposure, except for MICs of 1 and 4 mg/L. Our model can be used as a support tool for initial dose guidance and during therapeutic drug monitoring.

Variation of Chest Computed Tomographic Findings in Coronavirus Disease-19 (COVID-19) Positive Patients in a Tertiary Care Hospital, Bangladesh

Background: We aimed to report different patterns of chest computed tomographic (CT) findings in coronavirus disease-19 (COVID-19) infected patients in Bangladesh.&#x0D; Methods: This was a cross-sectional descriptive study of 200 consecutive reverse transcriptase polymerase chain reaction (RT-PCR) positive patients who underwent CT chest. Distribution, type of abnormal lung findings and Prevalence were recorded.&#x0D; Result: Among the total study cohort of 200 patients, 148(74 %) were males and 52 (26 %) were females with mean age of 53.9 ± 16.7 years (range 20–92 years). We observed lung parenchymal abnormalities in 125 (62.0 %) cases whereas 75 (37.5 %) RT-PCR positive cases had a normal chest CT. Common symptom was cough in 108 (54%), Only 18.0% of the patients were dyspneic. Among the patients with abnormal CT findings bilateral involvement was commonest 98/125 (78.4 %), multilobar (54.0 %) lung involvement with a predominant peripheral and posterior distribution was more commonly observed. With regards to the type of opacity, ground glass opacity (GGO) was the predominant abnormality found in 122/125 cases. Pure GGO was observed in 29 (23.2 %), most common pattern was GGO mixed with consolidation was noted in 52(41.6 %). GGO with crazy paving pattern was seen in 33 (26.4 %) and sub pleural linear and curvilinear lines were seen in 23(18.4%). Peri-lesional or intralesional segmental or subsegmental pulmonary vessel enlargement was observed in 36 (70.6 %) cases.&#x0D; Conclusion: In this study population, we found a high proportion of symptomatic laboratory-confirmed SARS-CoV-2 patients had positive chest CT findings. Patients with a positive CT showed typical findings of predominant GGOs in a bilateral and multilobar distribution with peripheral predilection.&#x0D; AKMMC J 2021; 12(1) : 38-44

Association of peripheral blood neutrophil-lymphocyte ratio (NLR) and red cell distribution width (RDW) with immune checkpoint inhibitors (ICIs) for metastatic urothelial carcinoma (mUC).

540 Background: Determining a benefit from ICIs radiographically may take months and may be confounded by pseudoprogression. The NLR &amp; RDW are readily accessible inflammatory markers from routine peripheral blood analysis and have been associated with outcomes in malignancies. We evaluated the association of early changes in NLR and RDW within 4 weeks after initiating ICI with any regression of tumor (ART) and overall survival (OS) in mUC. Methods: This study included de-identified data from Dana-Farber Cancer Institute in pts with mUC who were treated with ICIs from 2015 to 2020. Age, gender, setting (untreated vs. post-platinum), sites of metastasis (mets), performance status (PS), platelet count, RDW, and NLR at baseline and 3-4 weeks after initiating the ICI were collected. The primary objective was to assess the association of early increase in NLR by ≥1.0 from baseline or RDW at 3-4 weeks (as a continuous variable) post-ICI therapy with ART and OS. ART was assessed via subsequent imaging at any time point while on ICI. A multivariable logistic regression model and Cox proportional-hazards model were employed to identify the association of NLR changes with ART and OS, respectively, using backward selection. Results: A total of 330 pts were evaluable. The median age was 70 years, 72.1% (n = 298) were male and 69.4% (n= 227) received post-platinum ICI (remaining were platinum naïve). 46.5% (n = 146) experienced ART and the median OS was 13 months (11.14-16.14). An increase in NLR ≥ 1 in 3-4 weeks was associated with a lower rate of ART (OR: 0.41, 95% CI 0.24-0.70; p: 0.001) and worse OS (hazard ratio [HR]: 1.84, 95% CI 1.37-2.46; p &lt; 0.0001) on multivariable analysis (Table). Higher RDW values at 3-4 weeks were associated with worse OS (HR: 1.08, 95% CI 1.03-1.14; p: 0.0004) but were not associated with ART. Conclusions: In pts with mUC initiating ICI, an early increase in NLR ≥ 1 and higher RDW in 3-4 weeks were associated with poor outcomes. Early changes in these readily available variables may enable early modification or intensification of therapy to improve outcomes. External validation of these findings is warranted. [Table: see text]

Francisella tularensis Glyceraldehyde-3-Phosphate Dehydrogenase Is Relocalized during Intracellular Infection and Reveals Effect on Cytokine Gene Expression and Signaling.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is known for its multifunctionality in several pathogenic bacteria. Our previously reported data suggest that the GAPDH homologue of Francisella tularensis, GapA, might also be involved in other processes beyond metabolism. In the present study, we explored GapA's potential implication in pathogenic processes at the host cell level. Using immunoelectron microscopy, we demonstrated the localization of this bacterial protein inside infected macrophages and its peripheral distribution in bacterial cells increasing with infection time. A quantitative proteomic approach based on stable isotope labeling of amino acids in cell culture (SILAC) combined with pull-down assay enabled the identification of several of GapA's potential interacting partners within the host cell proteome. Two of these partners were further confirmed by alternative methods. We also investigated the impact of gapA deletion on the transcription of selected cytokine genes and the activation of the main signaling pathways. Our results show that ∆gapA-induced transcription of genes encoding several cytokines whose expressions were not affected in cells infected with a fully virulent wild-type strain. That might be caused, at least in part, by the detected differences in ERK/MAPK signaling activation. The experimental observations together demonstrate that the F. tularensis GAPDH homologue is directly implicated in multiple host cellular processes and, thereby, that it participates in several molecular mechanisms of pathogenesis.

Differences in clinical characteristics and chest CT findings between severe and critical H1N1 pneumonia.

Critical H1N1 pneumonia patients usually have one of the symptoms such as respiratory failure, septic shock, multiple organ dysfunction, or other need for intensive care management, which are associated with high risk of mortality. It is essential to differentiate the severity of H1N1 pneumonia and take corresponding target treatments. We aim to investigate the differences in clinical characteristics and chest computed tomography (CT) findings between severe and critical patients with H1N1 pneumonia. A total of 27 patients diagnosed with H1N1 pneumonia from October 2018 to March 2019 were retrospectively analyzed, and the differences in clinical manifestations, laboratory tests, and chest CT findings between the severe group (15 patients) and the critical group (12 patients) were compared. Frequency of dyspnea at rest was higher in critical group than that in severe group (P= 0.019). The neutrophil percentage was higher (P= 0.014) and the lymphocyte percentage was lower (P= 0.025) in critical compared with severe group. Bilateral lung involvement was the predominant pattern in both severe and critical patients, whereas the number of involved lobes in critical patients was more than that in severe patients (P= 0.024). Peripheral distribution was the predominant pattern in severe patients (40%), whereas more diffuse involvement of the lungs was observed in critical patients (83.30%). Ground-glass opacities and consolidation were the main CT findings in both groups, and prevalence of consolidation was higher in critical relative to severe group (83.30%). Compared with severe patients, those with critical H1N1 pneumonia were more likely to present with dyspnea at rest and decreased lymphocyte percentage. Chest CT showed that diffuse bilateral involvement and higher prevalence of consolidation are associated with critical outcomes.

Effect of peripheral nonuniform distribution of furnace heat flux on thermo-hydraulic characteristics and design of riser downcomer circuit of natural circulation boiler

The usual practice of design of riser tubes of natural circulation boilers is with an assumption of uniform furnace heat flux. Using the uniform diameter of riser tubes inside the furnace zone is also very common. The effect of peripheral nonuniform distribution of furnace heat flux on thermo-hydraulic characteristics and design of the riser downcomer circuit of a natural circulation boiler is presented here for the first time. As the riser tubes are exposed under substantially high heat flux, the tubes containing water-steam mixture are vulnerable and susceptible to overheating, particularly at high flux zone. From systematic analysis, it is proposed that using different diameters and the number of riser tubes at various sections can overcome the early occurrence of tube dry-out. An appropriate two-phase flow model is developed with flow regime mapping, tube wall temperature calculation, and identification of possible dry-out. The peripheral nonuniform distribution of furnace heat flux is implemented analytically in the model by introducing a distribution parameter estimated from the actual furnace data. Results reveal that with an average heat flux of 150 kW/m2, the dry-out occurs near a riser tube height of 44 m for a typical 210 MW capacity boiler. However, considering the nonuniform heat flux variation, the dry-out appears near a height of 32 m and 73 m for higher and lower heat flux zone, respectively. The present analysis shows that the implementation of larger size and lower size diameter of riser tubes, respectively, in higher and lower heat flux regions has a 9.45 % cost-benefit compared to the usual design practice with a consideration of uniform diameter tube and heat flux. The present work concludes that instead of using uniform tube diameter with average heat flux assumption, the use of different diameter of tubes in different heat flux zone not only avoid the early onset of possible dry-out but also has a cost-benefit.

Population pharmacokinetics and limited sampling strategies of polymyxin B in critically ill patients.

To characterize the pharmacokinetics (PK) of polymyxin B in Chinese critically ill patients. The factors significantly affecting PK parameters are identified, and a limited sampling strategy for therapeutic drug monitoring of polymyxin B is explored. Thirty patients (212 samples) were included in a population PK analysis. A limited sampling strategy was developed using Bayesian estimation, multiple linear regression and modified integral equations. Non-linear mixed-effects models were developed using Phoenix NLME software. A two-compartment population PK model was used to describe polymyxin B PK. Population estimates of the volumes of central compartment distribution (V) and peripheral compartment distribution (V2), central compartment clearance (CL) and intercompartmental clearance (Q) were 7.857 L, 12.668 L, 1.672 L/h and 7.009 L/h. Continuous renal replacement therapy (CRRT) significantly affected CL, and body weight significantly affected CL and Q. The AUC0-12h of polymyxin B in patients with CRRT was significantly lower than in patients without CRRT. CL and Q increased with increasing body weight. A limited sampling strategy was suggested using a two-sample scheme with plasma at 0.5h and 8h after the end of infusion (C0.5 and C8) for therapeutic drug monitoring in the clinic. A dosing regimen should be based on body weight and the application of CRRT. A two-sample strategy for therapeutic drug monitoring could facilitate individualized treatment with polymyxin B in critically ill patients.

Cutaneous α-Synuclein Signatures in Patients With Multiple System Atrophy and Parkinson Disease.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder caused by the abnormal accumulation of α-synuclein in the nervous system. Clinical features include autonomic and motor dysfunction, which overlap with those of Parkinson disease (PD), particularly at early disease stages. There is an unmet need for accurate diagnostic and prognostic biomarkers for MSA and, specifically, a critical need to distinguish MSA from other synucleinopathies, particularly PD. The purpose of the study was to develop a unique cutaneous pathologic signature of phosphorylated α-synuclein that could distinguish patients with MSA from patients with PD and healthy controls. We studied 31 patients with MSA and 54 patients with PD diagnosed according to current clinical consensus criteria. We also included 24 matched controls. All participants underwent neurologic examinations, autonomic testing, and skin biopsies at 3 locations. The density of intraepidermal, sudomotor, and pilomotor nerve fibers was measured. The deposition of phosphorylated α-synuclein was quantified. Results were compared with clinical rating assessments and autonomic function test results. Patients with PD had reduced nerve fiber densities compared with patients with MSA (p < 0.05, all fiber types). All patients with MSA and 51/54 with PD had evidence of phosphorylated α-synuclein in at least one skin biopsy. No phosphorylated α-synuclein was detected in controls. Patients with MSA had greater phosphorylated α-synuclein deposition (p < 0.0001) and more widespread peripheral distribution (p < 0.0001) than patients with PD. These results provided >90% sensitivity and specificity in distinguishing between the 2 disorders. α-synuclein is present in the peripheral autonomic nerves of patients with MSA and when combined with synuclein distribution accurately distinguishes MSA from PD. This study provides Class II evidence that measurement of phosphorylated α-synuclein in skin biopsies can differentiate patients with MSA from those with PD.

The Compatibility of Chest CT Scan with RT-PCR in Suspected COVID-19 Patients

Background: Thoracic CT scan plays a role in detecting and assessing the progression of COVID-19. It can evaluate the response to the therapy given. In diagnosis, the CT scan of the chest may complement the limitations of RT-PCR. Several recent studies have discussed the importance of CT scans in COVID-19 patients with false-negative RT-PCR results. The sensitivity of chest CT scan in the diagnosis of COVID-19 is reportedly around 98%. This study aimed to determine the compatibility of CT scan of the thorax with RT-PCR in suspected COVID-19 patients. Materials and methods: This research was conducted in the Radiology Department of the Wahidin Sudirohusodo Hospital Makassar from April to December 2020 with 350 patients. The method used was a 2x2 table diagnostic test. Results: The study included 188 male patients (53.7%) and 162 female patients (46.2%). The most common age group was 46–65 years (35.4%). The most common types of lesions were GGO (163 cases), consolidation (128 cases), and fibrosis (124 cases), mostly found in the inferior lobe with a predominantly peripheral or subpleural distribution. The sensitivity of the CT scan to the PCR examination was 86%, and the specificity was 91%. Conclusions: Thoracic CT scan was a good modality in establishing the diagnosis of COVID-19. CT scan of the chest with abnormalities could confirm the diagnosis in 88% of cases based on RT-PCR examination. It excluded the diagnosis in 91% based on the RT-PCR examination. The accuracy of the thoracic CT scan was 88% with RT-PCR as the reference value.