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Photonic crystal based sensing technology is the latest technology for various bio-sensing applications. A 2D photonic crystal (PhC) hexagonal shaped ring resonator based biosensor is simulated and designed for the detection of bio-molecules such as glucose, bilirubin, urea and albumin in blood and urine over different concentration ranges. The biosensor structure is created using line and point defect in order to form a ring waveguide and a bus waveguide above the ring structure. If the concentration of bilirubin, glucose, albumin and urea in blood and urine is varied, the refractive index is varied, which in turn changes the output response of the sensor [1] . This principle can be used to identify the aberrant value range of the glucose, bilirubin, albumin and urea in blood and urine. Finite Difference Time Domain (FDTD) tool called Lumericals is used for the modeling and simulation of the biosensor. The resonant wavelength shift, sensitivity, Full-Width Half-Maximum (FWHM) and quality factor (Q-factor) for different concentrations of glucose, bilirubin, albumin and urea are observed and tabulated. The Q-factor obtained for the normal range of glucose, bilirubin, albumin and urea concentration in blood and urine is 310, sensitivity is 400 nm and the resonant wavelength is around 1518.8 nm with the efficiency of 86%.

The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants and breakthrough infections despite available coronavirus disease 2019 (COVID-19) vaccines calls for antiviral therapeutics. The application of soluble angiotensin converting enzyme 2 (ACE2) as a SARS-CoV-2 decoy that reduces cell bound ACE2-mediated virus entry is limited by a short plasma half-life. This work presents a recombinant human albumin ACE2 genetic fusion (rHA-ACE2) to increase the plasma half-life by an FcRn-driven cellular recycling mechanism, investigated using a wild type (WT) albumin sequence and sequence engineered with null FcRn binding (NB). Binding of rHA-ACE2 fusions to SARS-CoV-2 spike protein subdomain 1 (S1) was demonstrated (WT-ACE2 KD = 32.8 nM and NB-ACE2 KD = 31.7 nM) using Bio-Layer Interferometry and dose-dependent in vitro inhibition of host cell infection of pseudotyped viruses displaying surface SARS-CoV-2 spike (S) protein. FcRn-mediated in vitro recycling was translated to a five times greater plasma half-life of WT-ACE2 (t½ β = 13.5 h) than soluble ACE2 (t½ β = 2.8 h) in humanised FcRn/albumin double transgenic mice. The rHA-ACE2-based SARS-CoV-2 decoy system exhibiting FcRn-driven circulatory half-life extension introduced in this work offers the potential to expand and improve the anti-COVID-19 anti-viral drug armoury. Statement of significance: The COVID-19 pandemic has highlighted the need for rapid development of efficient antiviral therapeutics to combat SARS-CoV-2 and new mutants to lower morbidity and mortality in severe cases, and for people that are unable to receive a vaccine. Here we report a therapeutic albumin ACE2 fusion protein (rHA-ACE2), that can bind SARS-CoV-2 S protein decorated virus-like particles to inhibit viral infection, and exhibits extended in vivo half-life compared to ACE2 alone. Employing ACE2 as a binding decoy for the virus is expected to efficiently inhibit all SARS-CoV-2 mutants as they all rely on binding with endogenous ACE2 for viral cell entry and, therefore, rHA-ACE2 constitutes a versatile addition to the therapeutic arsenal for combatting COVID-19.

Objectives: To determine whether the early use of albumin after cardiac surgery in the first 24 hours in the intensive care unit (ICU) is associated with reduced mortality. Design: A single-center nonrandomized retrospective cohort study using the Medical Information Mart in Intensive Care IV database. Setting: A single cardiothoracic ICU in the United States during a period between 2008 to 2019. Participants: Patients undergoing valvular and/or cardiac bypass graft surgeries. Interventions: Albumin administered during the first 24 hours of the ICU admission. Measurements and Main Results: A total of 8,136 patients were included in this study, of whom 4,444 (54.6%) received albumin at any stage during the first 24 hours of ICU admission, and 69 (1.6%) of those patients died. The patient population exposed to albumin had higher comorbidities and illness severity compared to the no-albumin group. Patients exposed to albumin during the first 24 hours of ICU admission had a statistically significant reduction in mortality (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.48-0.97, p < 0.05) after adjustment for age, the Oxford Acute Severity of Illness Score, and the Charlson comorbidity index. A sensitivity analysis of patients who received albumin at any stage during ICU admission showed increased mortality (OR, 1.93; 95% CI, 1.26-3.07, p < 0.01). Patients exposed to albumin had a significant increase in adjusted ICU length of stay (LOS) (geometric mean ratio 1.09; 95% CI, 1.05-1.10, p = < 0.001) and hospital LOS (geometric mean ratio 1.08; 95% CI, 1.05-1.10, p < 0.001). Conclusions: Exposure to albumin in the first 24 hours after cardiac surgery is associated with a reduction in adjusted hospital mortality and an increase in both hospital and ICU lengths of stay.

Blighia sapida (B. sapida) K.D. Koenig (Family Sapindaceae) is a branchless straight bole approximately 15 m long. The study evaluated the antioxidant and anti-inflammatory activities of ethanol extract and fractions of B. sapida stem-bark using in vitro methods. Ethanol extract and its fractions were investigated for 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), total antioxidant capacity (TAC), and quantitative phenolic and flavonoid contents. Anti-inflammatory activity was evaluated using albumin denaturation and membrane stabilization assays. The extract and its fractions exhibited radical scavenging and anti-inflammatory properties. The ethyl acetate fraction possessed maximum phenolic and flavonoid contents (136.67 ± 1.55 gallic acid mg/g and 75.76 ± 4.03 quercetin equivalent mg/g, respectively). Antioxidant studies revealed that the ethyl acetate fraction displayed superior activity with an IC50 = 0.09 ± 0.03 mg/mL DPPH, and values of 146.96 ± 3.81 and 359.20 ± 4.98 for FRAP and TAC respectively. Furthermore, the anti-inflammatory activity was revealed by inhibition of heat-induced albumin denaturation and red blood cell membrane stabilization at concentrations of 200-1000 μg/mL and 50-250 μg/mL, respectively. The ethanol extract and fractions exhibited antioxidant and anti-inflammatory activities, with ethyl acetate fraction showing superior activity, which could be attributed to secondary metabolites, mainly phenolic compounds. Overall, the antioxidant and anti-inflammatory activities of B. sapida can be exploited by ethnomedicinal users.

In vitro Construction of the liver sinusoidal structure using artificial tissue is an important but worthwhile challenge, particularly for assessing the risk of diseases such as sinusoidal obstruction syndrome (SOS). Current models are unsuitable for evaluating the toxicity because of lacking sinusoidal capillary. In this study, we developed a vascularized hepatic tissue (VHT) using a unique tissue engineering technique, the cell assembled viscous tissue by sedimentation (CAViTs) method. The “viscous bodies” created using the CAViTs method exhibited significant self-assembly within 6 h after seeding, promoting cell-cell interaction. The level of albumin secreted by the VHT was four times higher than that of 2D-coculture and maintained for 1 month. The gene expression pattern of the VHT was closer to that of total human liver, compared with the 2D system. Quantitative evaluations of the vascular structure of VHT treated with two typical SOS-inducing compounds, monocrotaline and retrorsine, revealed higher sensitivity (IC50 = 40.35 µM), 19.92 times higher than the cell-viability assay. Thus, VHT represents an innovative in vitro model that mimics the vessel network structure and could become a useful tool for the early screening of compounds associated with a risk of vascular toxicity. Statement of Significance Mimicking sinusoidal structures in in vitro liver model is important to consider from the perspective of predicting hepatotoxicity such like sinusoidal obstruction syndrome (SOS). However, it was difficult to reconstruct the vascular structure within the hepatocyte-rich environment. In this study, we constructed a vascularized hepatic tissue in a high-throughput manner by a unique method using collagen and heparin, and evaluated its applicability to toxicity assessment. Vessel morphology analysis of the model treated by monocrotaline, which is a well-known SOS-inducing compound, could predict the toxicity with higher sensitivity. To the best of our knowledge, this is the first report to provide vascularized hepatic tissues using sinusoidal endothelial cells at least for demonstrating applicability to the evaluation of SOS induction risk.

To verify the role of lactate dehydrogenase to albumin (LDH/ALB) ratio as an independent prognostic factor for mortality due to the lower respiratory tract infection (LRTI) in the emergency department (ED).We reviewed the electronic medical records of patients who were admitted to the ED for the management of LRTI between January 2018 and December 2020. Initial vital signs, laboratory data, and patient severity scores in the ED were collected. The LDH/ALB ratio was compared to other albumin-based ratios (blood urea nitrogen to albumin ratio, C-reactive protein to albumin ratio, and lactate to albumin ratio) and severity scales (pneumonia severity index, modified early warning score, CURB-65 scores), which are being used as prognostic factors for in-hospital mortality. Multivariable logistic regression was performed to identify independent risk factors.The LDH/ALB ratio was higher in the non-survivor group than in the survivor group (median [interquartile range]: 217.6 [160.3;312.0] vs. 126.4 [100.3;165.1], p 0.001). In the comparison of the area under the receiver operating characteristic curve (AUC) for predicting in-hospital mortality, the AUC of the LDH/ALB ratio (0.808, 95% confidence interval: 0.757-0.842, p 0.001) was wider than other albumin-based ratios and severity scales, except the blood urea nitrogen to albumin ratio. In the multivariable logistic regression analysis, the LDH/ALB ratio independently affected in-hospital mortality.The LDH/ALB ratio may serve as an independent prognostic factor for in-hospital mortality in patients with LRTI.

Backround Guillain-Barré syndrome (GBS) is an immune-mediated disease that affects the peripheral nervous system and may occur after some bacterial-viral infections. Aim The aim of this study is to determine and compare the epidemiological, clinical and laboratory characteristics of the patients followed up in our clinic with the diagnosis of GBS in the 15 month periods before and after March 2020. At the same time, we aimed to examine the importance of these markers as prognostic indicators by investigating the relationship of D-dimer, CRP, albumin and transferrin levels with Hughes functional grading scale score (HFGSS). Material and Methods The medical files of the patients who were followed up with the diagnosis of GBS between December 2018 and May 2021 were retrospectively analyzed. The patients were divided into groups as pandemic, pre-pandemic, post-COVID-19 and non-COVID-19. Epidemiological and clinical characteristics of GBS patients and plasma D-dimer, serum albumin, CRP and transferrin levels were recorded. Results No significant difference was found between the pandemic and pre-pandemic periods in terms of age, gender, GBS subtype, seasonal distribution and treatment characteristics of GBS patients. PostCOVID-19 GBS patients had significantly higher HFGSS both at admission and at discharge (p

Kupffer cells are a key source of reactive oxygen species (ROS) and are implicated in the development of steatohepatitis and fibrosis in nonalcoholic steatohepatitis (NASH). We recently developed a polythiolated and mannosylated human serum albumin (SH-Man-HSA), a nano-antioxidant that targets Kupffer cells, in which the mannosyl units on albumin allows their specific uptake by Kupffer cells via the mannose receptor C type 1 (MRC1), and in which the polythiolation confers antioxidant activity. The aim of this study was to investigate the therapeutic potential of SH-Man-HSA in NASH model mice. In livers from mice and/or patients with NASH, we observed a reduced blood flow in the liver lobes and the down-regulation in MRC1 expression in Kupffer cells, and SH-Man-HSA alone failed to improve the pathological phenotype in NASH. However, the administration of a nitric oxide (NO) donor restored hepatic blood flow and increased the expression of the mannose receptor C type 2 (MRC2) instead of MRC1. Consequently, treatment with a combination of SH-Man-HSA and an NO donor improved oxidative stress-associated pathology. Finally, we developed a hybrid type of nano-antioxidant (SNO-Man-HSA) via the S-nitrosation of SH-Man-HSA. This nanomedicine efficiently delivered both NO and thiol groups to the liver, with a hepatoprotective effect that was comparable to the combination therapy of SH-Man-HSA and an NO donor. These findings suggest that SNO-Man-HSA has the potential for functioning as a novel nano-therapy for the treatment of NASH.

Introduction Patients with aspiration pneumonia (AP) exhibit higher mortality than those with non-AP. However, data regarding predictors of short-term prognosis in patients with community-acquired AP are limited. Methods Patients hospitalized with community-acquired pneumonia (CAP) were retrospectively classified into aspiration pneumonia (AP) and non-AP groups. The AP patients were further divided into nonsurvivors and survivors by 30-day mortality, and various clinical variables were compared between the groups. Results Of 1249 CAP patients, 254 (20.3%) were classified into the AP group, of whom 76 patients (29.9%) died within 30 days. CURB-65, pneumonia severity index (PSI), and Infectious Diseases Society of America/American Thoracic Society criteria for severe CAP (SCAP) showed only modest prognostic performance for the prediction of 30-day mortality (c-statistics, 0.635, 0.647, and 0.681, respectively). Along with the PSI and SCAP, Eastern Cooperative Oncology Group performance status (ECOG-PS) and blood biomarkers, including, N-terminal of prohormone brain natriuretic peptide (NT-proBNP) and albumin, were independent predictors of 30-day mortality. In models based on clinical prediction rules, including CURB-65, PSI, and SCAP, the addition of ECOG-PS further improved their c-statistics compared to the clinical prediction rules alone. In the four combinations based on SCAP, ECOG-PS, and two blood biomarkers (NT-proBNP and albumin), the c-statistics further increased to reach approximately 0.8. Conclusions CURB-65, PSI, and SCAP exhibited only modest discriminatory power in predicting the 30-day mortality of patients with community-acquired AP. The addition of performance status and blood biomarkers, including NT-proBNP and albumin, further increased prognostic performance, showing good predictive accuracy in the SCAP-based model.

Chronic kidney disease (CKD) is a global burden in the world. Low protein diet (LPD) recommendation is suggested in CKD patients to avoid or defer dialysis initiation and slow down CKD progression. However, nutritional imbalance and protein energy wasting represent key worries. The amino acid-based metabolic profile may provide a sensitive biomarker to evaluate CKD patients' nutrition status with LPD recommendations.We conducted a cross-sectional study in CKD stage 3-5 patients who had received LPD recommendation to evaluate the association between LPD and traditional markers (including plasma levels of albumin, pre-albumin, transferrin, total iron-binding capacity), inflammation markers (including peripheral leukocyte count and plasma levels of high-sensitivity C-reactive protein), body composition, muscle strength, and physical function, and novel nutrition markers (including amino acid-based metabolic profile) in CKD stage 3-5 patients.In our study CKD stage 3-5 patients with the total number of 73, the mean age was around 71 ± 10 years old. The mean daily protein intake (DPI) was around 0.9 ± 0.3 g/kg/day and 25 (34%) patients met the recommended goal of DPI0.8 g/kg/day. The mean daily calorie intake (DCI) was around 23 ± 6 kcal/kg/day, with only 11 (15%) patients met the recommend DCI with 30-35 kcal/kg/day. Compared to CKD patients with non-LPD, patients with LPD had significantly lower hemoglobin and albumin levels, shorter 6-min walking distance (6MWD), and lower leucine levels. Multivariable analysis found that lower hemoglobin and leucine levels, and shorter 6MWD were negatively and independently associated with LPD (all p 0.05). Then ROC curve analysis found that the optimal cut-off value of leucine plasma levels was 95.5 μM with 60% sensitivity and 71% specificity to predict those CKD patients with LPD with the area under the curve of 0.646 (95% CI: 0.512-0.780).LPD attainment was noted in 34% patients and most of CKD stage 3-5 patients (around 85%) had inadequate daily calorie intake although receiving standard dietary counseling routinely. A low protein diet and inadequate daily calorie intake in CKD patients were associated with shorter 6MWD, and lower hemoglobin and leucine levels. Plasma leucine levels lower than 95.5 μM may be a herald for muscle wasting and malnutrition in these CKD stage 3-5 patients with inadequate calorie intake.

Background and aims The clinical spectrum of the SARS-CoV-2 infection is very broad, ranging from asymptomatic infection to severe pneumonia. However, the majority of fatalities related to COVID-19 have involved old, frail and patients with comorbidities, such as obesity, groups that also have high rates of a poor nutritional status. To assess the impact on clinical outcomes of the coexistence of any degree of obesity and low albumin levels on admission among patients with COVID-19. Methods This is a sub-analysis of a former study where 75 patients admitted due to COVID-19 were evaluated cross-sectionally. In this analysis, patients were divided in two groups, according to the presence of obesity and albumin levels on admission lower than 3.5 g/dl. Results 11 out 75 patients evaluated (14.7%) had obesity and albumin levels lower than 3.5 g/dl. Patients with obesity and hypoalbuminemia were older than patients without these two conditions (65.3 ± 7.7 vs 54.2 ± 17 years; p = 0.01). CRP (141.4 ± 47.9 vs 70.1 ± 60.6 mg/l; p = 0.002), D-dimer (2677.3 ± 2358.3 vs 521.7 ± 480.3 ng/ml; p = 0.001), fibrinogen (765.9 ± 123.9 vs 613.5 ± 158gr/L; p = 0.007) ferritin levels (903.1 ± 493 vs 531.4 ± 418.9 mcg/l; p = 0.01) and procalcitonin (3.5 ± 0.6 vs 1.1 ± 0.7 ng/ml; p = 0.009) were significantly higher in the group with obesity and hypoalbuminemia. Among patients with low albumin and obesity, length of hospital was higher (21.9 ± 18.7 vs 10.5 ± 9.5 days; p = 0.004) and the proportion of subjects admitted to ICU was greater (81.8% vs 11.5%; p

Objective: To investigate the effect of lactate/albumin (L/A) ratio on survival to discharge in patients who have had out-of-hospital cardiac arrest (OHCA). Methods: We analyzed adult patients (aged ≥18 years) who were admitted to our hospital's emergency department (ED) due to OHCA between January 2018 and June 2020 and who achieved return of spontaneous circulation after successful resuscitation. Blood lactate and albumin concentrations were obtained within the first 10 min after admission to the ED. Patients were grouped according to clinical outcomes. The primary outcome was survival until hospital discharge. The groups were then statistically compared. Results: In this study, 235 OHCA patients were analyzed, 42 (17.9%) of whom had survived until discharge. The L/A ratio was higher in the non-survivor group than in the survivor group (2.0 (interquartile range: 1.4–2.8) vs 1.4 (0.9–1.9); P < 0.001). A low L/A ratio was significantly associated with survival at discharge (odds ratio: 2.55; 95% confidence interval (CI): 3.24–11.08; P < 0.001). In the prediction of survival to discharge, the area under the curve (AUC) for the L/A ratio (AUC: 0.823) was higher than that for lactate (AUC: 0.762) or albumin (AUC: 0.722) alone. Moreover, the predictive value of L/A ratio for survival to discharge might significantly improve when the cutoff value is higher than 1.62. Conclusion: The L/A ratio is more valuable than the lactate or albumin levels alone in predicting survival to discharge. Our findings indicate that a combination of these parameters might increase the predictability of survival to discharge in OHCA patients.

Background The formation of dental plaque and its involvement in the pathogenesis of periodontitis is a topic of intense interest given the high prevalence of periodontitis in humans. Even though calcium-based particles play an active role in both dental plaque formation and periodontitis, few publications describe the physical-chemical properties of these particles. Methods Saliva samples were collected from healthy volunteers. From these samples, saliva-derived particles were isolated and stained for calcium using calcein or Fluo-4. The salivary particles were also subjected to characterization by flow cytometry and immunoblotting. Internalization of calcein-labeled salivary particles by gingival epithelial cells was visualized by confocal microscopy. Results We found that calcium-based salivary particles from healthy volunteers varied greatly in size but were enriched in particles of sizes at or greater than 1.5 μm. Immunoblotting analysis of the salivary particles identified several proteins including albumin, fetuin-A, and statherin, which have been found in calcium phosphate particles from other tissues or are known to modulate calcium homeostasis in saliva. In addition, calcium particles were internalized by both gingival epithelial cells and monocyte-derived macrophages. Conclusion Salivary calcium particles were enriched in the micrometer range, internalized by gingival epithelial cells, and contain albumin, fetuin-A and statherin, regulators of particle formation. These characteristics of the calcium-based salivary particles and their biological activities provide a basis for further studies to understand the molecular basis for pathogenesis of periodontitis.

Background & Aims: Acute decompensation (AD) of cirrhosis is a heterogeneous clinical entity associated with moderate mortality. In some patients, this condition develops quickly into the more deadly acute-on-chronic liver failure (ACLF), in which other organs such as the kidneys or brain fail. The aim of this study was to characterize the blood lipidome in a large series of patients with cirrhosis and identify specific signatures associated with AD and ACLF development. Methods: Serum untargeted lipidomics was performed in 561 patients with AD (518 without and 43 with ACLF) (discovery cohort) and in 265 patients with AD (128 without and 137 with ACLF) in whom serum samples were available to perform repeated measurements during the 28-day follow-up (validation cohort). Analyses were also performed in 78 patients with AD included in a therapeutic albumin trial (43 patients with compensated cirrhosis and 29 healthy individuals). Results: The circulating lipid landscape associated with cirrhosis was characterized by a generalized suppression, which was more manifest during AD and in non-surviving patients. By computing discriminating accuracy and the variable importance projection score for each of the 223 annotated lipids, we identified a sphingomyelin fingerprint specific for AD of cirrhosis and a distinct cholesteryl ester and lysophosphatidylcholine finger-print for ACLF. Liver dysfunction and infections were the prin-cipal net contributors to these fingerprints, which were dynamic and interchangeable between patients with AD whose condition worsened to ACLF and those who improved. Notably, blood lysophosphatidylcholine levels increased in these patients after albumin therapy. Conclusions: Our findings provide insights into the lipid land-scape associated with decompensation of cirrhosis and ACLF progression and identify unique non-invasive diagnostic bio-markers of advanced cirrhosis. Lay summary: Analysis of lipids in blood from patients with advanced cirrhosis reveals a general suppression of their levels in the circulation of these patients. A specific group of lipids known as sphingomyelins are useful to distinguish between patients with compensated and decompensated cirrhosis. Another group of lipids designated cholesteryl esters further distinguishes patients with decompensated cirrhosis who are at risk of developing organ failures. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

Objective To determine biomarkers for impending fluid overload during intravenous fluid administration in a feline haemorrhage-resuscitation model. Study design Randomized crossover study. Animals A group of six domestic cats (mean age and weight: 21 months; 4.9 kg, respectively). Methods The cats underwent three treatments, 2 months apart. They were anaesthetized and instrumented to measure a range of physiological, blood gas, haematological and biochemical variables over time. Samples were taken during a health check, before haemorrhage, after haemorrhage and then at 30 minute intervals during fluid resuscitation and 24 hours later. The three treatments were: 1) control, sham haemorrhage and resuscitation; 2) lactated Ringer’s solution (LRS); and 3) 6% tetrastarch 130/0.4 (Vol) where the cats underwent a controlled haemorrhage then resuscitation by administering LRS and Vol at 60 and 20 mL kg–1 hour–1, respectively, for 120 minutes. Fluid overload was identified by nasal discharge and radiographic evidence. Biomarkers were variables that exceeded the reference interval for cats during treatment. Potential biomarkers were analysed using receiver operating characteristic curves (p Results Mean ± standard deviation total blood loss was 10.2 ± 2.3, 29.3 ± 9.0 and 29.1 ± 6.3 mL kg–1 for control, LRS and Vol, respectively. The total volume of LRS and Vol administered was 120 and 40 mL kg–1, respectively. Haematocrit, albumin, magnesium, chloride-to-sodium ratio and sodium-chloride difference were identified as potential biomarkers. These variables exceeded the reference intervals from 30 minutes of resuscitation onwards. A chloride-to-sodium ratio > 0.84 was the most sensitive (90%) and specific (75%) of all potential biomarkers. Conclusions and clinical relevance Changes in physiological variables, haematocrit and albumin were poor biomarkers of impending fluid overload compared with electrolytes. Finding the ideal biomarker to identify impending fluid overload of commonly used intravenous fluids should improve the safety of their administration in cats.

Background In the critical care environment, elevated albuminuria values show capacity to reflect illness severity and predict mortality and hence assessing albumin/creatinine ratio (ACR) at the bedside has potential clinical benefit Point-of-care (POC) analysers offer rapid results but may be less accurate then laboratory analysis. Methods Critically ill adult patients with a urinary catheter in situ had albumin, creatinine, and ACR measurements performed via laboratory and POC analysis. Data are presented as mean (standard deviation) or median [interquartile range]. Measurement agreement was assessed by Lin's concordance correlation coefficient, Bland Altman 95% limits of agreement, and classification by Cohen's kappa statistic. Results/Findings Albumin, creatinine, and ACR analysis was performed for 30 patients. Lin's correlation coefficient showed ‘substantial’ agreement for albumin and ACR and ‘almost perfect’ agreement for creatinine for POC vs laboratory analysis. POC vs laboratory analysis also showed poor agreement for identification of normal ACR (>1 mg/mmol) and mild urine ACR (1–3 mg/mmol) and ‘substantial’ agreement for moderately increased urine ACR (3–30 mg/mmol). Conclusions ACR POC values appear to provide an accurate and rapid method that has potential to provide an early indication of injury severity and mortality risk in the critically ill.

Development of ocular drug delivery system is one of the most technically challenging tasks, when compared with other routes of drug delivery. Eye (an intricate organ) is highly sophisticated and sensitive organ due to presence of various structurally differed anatomical layers, which many times limits the drug delivery approaches. Despite several limitations, many advancements have been made as evidence from various recent studies involving improvement of both residence time and permeation of the drug at the ocular region. In the last few decades, albumin(s) based ophthalmic products have been gained most attention to solve the major challenges associated with conventional ocular drug delivery systems. Interestingly, an albumin-based micro, nano, conjugates, and genetically fused target specific to ligand(s) formulation being exploited through many studies for successful ocular delivery of bioactives (mostly repurposed drugs). Past and current studies suggested that albumin(s) based ocular drug delivery system is multifunctional in nature and capable of extending both drug residence time and sustaining the release of drugs to deliver desired pharmacological outcomes. Despite wide applications, still complete progress made in albumin based ocular drug delivery is limited in literature and missing in market. So, herein we presented an overview to explore the key concepts of albumin-based nanocarrier(s) including strategies involved in the treatment of ocular disease, that have yet to be explored.

Poor nutritional status is common among patients undergoing lower extremity amputation (LEA). In this study, the association between preoperative hypoalbuminemia, a marker for malnutrition, and postoperative mortality in patients undergoing LEA was explored.Data on patients undergoing LEA between 2005 and 2017 were retrospectively analyzed from the prospectively collected American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into clinically relevant categories based on their serum albumin level (2.5, 2.5-3.39, ≥3.4 g/dl) and were further stratified according to amputation level. Operative death was compared across groups and multivariable logistic regression was performed to estimate risk-adjusted odds ratio (AOR).In 35,383 patients, the rate of 30-day postoperative mortality was 7.6% (n = 2693). Mortality rate was highest in patients with very low albumin levels (11%) as compared to low (6.8%) and normal levels (3.9%). On multivariable analysis, lower albumin levels emerged as a risk-adjusted independent predictor of mortality. After risk-adjustment, patients with very low albumin levels (AOR [95% CI]: 2.25 [1.969-2.56], P0.001) and low albumin levels (AOR [95% CI]: 1.42 [1.239-1.616], P0.001) had higher odds of mortality when compared to patients with normal albumin levels. On sensitivity analysis, a similar trend was seen in patients undergoing above knee amputation but not in patients undergoing minor amputations.In patients undergoing major LEA, hypoalbuminemia is associated with an increased risk of postoperative mortality in a dose response manner, specifically in above knee amputations. Monitoring and optimizing patients' nutritional status before surgery, when possible, may be warranted and should be further explored.

Developing new therapeutic strategies that damage tumour cells without harming normal tissues is among the primary obstacles in chemotherapy. In this study, a novel β-glucuronidase-sensitive albumin-binding prodrug was designed and synthesized to selectively deliver the drug SN38 to tumour sites and maximize its efficacy. After intravenous administration, the prodrug Mal-glu-SN38 covalently bound to plasma albumin through the Michael addition, enabling it to accumulate in the tumour and release SN38 when triggered by extracellular β-glucuronidase. Compared to irinotecan, Mal-glu-SN38 displayed a slower plasma clearance and increased drug exposure over time. Moreover, Mal-glu-SN38 caused an increase in tumour-site accumulation of both the albumin-prodrug conjugate and free SN38 released from albumin conjugate when compared with irinotecan. After administration of multiple doses, Mal-glu-SN38 also significantly delayed the tumour growth, resulting in an impressive reduction or even disappearance of tumours (67% of mice cured) without causing any observable side effects.

BACKGROUND The aim of this study was to investigate the secretion patterns of brain natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP) after traumatic brain injury (TBI) and to analyze the source of them in cerebrospinal fluid (CSF). MATERIALS AND METHODS We synchronously measured BNP and NT-proBNP concentrations in paired CSF and plasma samples from 22 moderate to severe TBI patients and 40 healthy control patients. The CSF and/or plasma ratio of albumin (QAlbumin) was calculated daily. The BNP and NT-proBNP levels of CSF and plasma were compared between TBI patients and control patients. RESULTS CSF BNP and NT-proBNP levels peaked on day 3 after injury, as did the plasma BNP and NT-proBNP levels. The CSF BNP and NT-proBNP levels in TBI patients were elevated from day 1, which was significantly higher than control group (P < 0.05 and P < 0.01, respectively). However, in plasma, only NT-proBNP levels were significantly higher than in the control group from day 2 (P < 0.05). In addition, QBNP, defined as CSF BNP concentration and/or plasma BNP concentration, was significantly higher in TBI patients than in the control group (P < 0.01). However, QAlbumin remained within ranges of a mild to moderate dysfunction of blood-brain-barrier in TBI patients. CONCLUSIONS CSF BNP concentrations are elevated and peak on day 3 after moderate to severe TBI. CSF BNP may originate from the brain and may be a potential biomarker of TBI.

Background Most Hepatocellular Carcinomas (HCCs) are diagnosed at an advanced stage. However, HCC early diagnosis is complicated by the coexistence of inflammation and cirrhosis. The unsatisfactory sensitivity and specificity of Alpha-fetoprotien (AFP) for screening of early-stage HCC paved the way for new novel biomarkers to complement AFP such as AFP-L3. The aim of this study was the Evaluation of alpha fetoprotein-L3 (AFP-L3) as earlier marker in diagnosis of hepatocellular carcinoma in Egyptian patients. This study was conducted on 80 patients categorized into 2 groups; group 2 (40 patients with chronic active hepatitis) and group 3 (40 patients with HCC). HCC diagnosis was done by clinical, triphasic CT and positive US for focal lesion, in addition to 20 healthy individuals as controls (group 1). Results The median range of AFP and AFP-L3 were highly statistically significant difference between HCC group and other groups [p

Background: Efficacy of Anthracycline derivative Doxorubicin (Dox) has been proven in several malignancies such as breast cancer, Hodgkin and non-Hodgkin lymphoma, acute leukemia, lung, thyroid and ovarian cancer. However its clinical usefulness is restricted due to its cardiotoxicity and nephrotoxicity. Rosa centifolia belongs to family Rosaceae and in Ayurveda it is claimed for use in renal disorders. The main phyto-constituents of the plant are terpenoids, glycosides, flavonoids, tannins, phenolic compounds, pro-antroocyanides, pectin and riboflavin. Objective: To investigate the ameliorative role of ethanolic extract of petals of R. centifolia in doxorubicin induced nephrotoxicity in rats. Materials and methods: Nephrotoxicity was produced by administration of doxorubicin (2.5 mg/kg b.w., i.p. alternate day) in six equal injections for two weeks to achieve a cumulative concentration of 15 mg/kg. Low (LERC - 100 mg/kg p.o.) and high (HERC - 200 mg/kg p.o.) dosees of ethanolic extract of petals of R. centifolia was administered as a pretreatment prior to doxorubicin administration. The general parameters such as body weight, food and water intake were measured throughout the study period. Serum biomarkers such as blood urea nitrogen (BUN), serum creatinine and albumin were measured before treatment and at the end of the experiments. Anti-oxidant enzymes such as glutathione (GSH), melonldehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) were monitored after the last dose. Nephrotoxicity was assessed through histopathological analysis. Results: The repeated administration of doxorubicin produces several morphological changes including reduction in the body weight as well as decreased food and water consumption. Serum biomarkers such as BUN, serum creatinine were increased and albumin concentration was decreased. The GSH, SOD and CAT concentrations were decreased, whereas MDA concentration was increased. Deteriorating changes in the histological architecture of kidney tissue were observed. In the LERC and HERC pretreated groups following changes were observed in dose dependent manner: increase in body weight, food and water intake (p

Summary Background Both modified Child-Pugh (MCP) and Albumin-bilirubin (ALBI) grade were reported that simpler, more objective and evidence-based alternative to the Child-Pugh (CP) class for assessing liver function. Aims To investigate whether the MCP and ALBI grade could better evaluate the liver reserve of Hepatocellular Carcinoma (HCC) patients treated with TACE (transcatheter arterial chemoembolization) than CP grade. Methods Three hundred seventy-six consecutive HCC patients treated with TACE between December 2007 and October 2011 were enrolled. The baseline characteristics and clinical information were collected. Homogeneity and discriminatory ability were compared between the MCP grade and ALBI class or CP grade. Results Compared with the CP and ALBI, the MCP grade had a higher predictive accuracy for overall survival (OS) in terms of homogeneity and discriminatory ability. Most of the HCC patients had CP class A disease (84.0%) at presentation, and within this CP class, although the ALBI grade revealed two clear and nonoverlapping groups, the MCP grade revealed three clearly different prognostic groups. Both in the ALBI grade 1 or ALBI grade 2 group, the MCP grade still showed a significant progressive decrease in OS from the smallest to the largest grades, but the CP class was unsatisfactory in stratifying these patients. Conclusions The stratification ability and prognostic predictive power of the MCP grade for HCC patients treated with TACE may be better than that of the ALBI grade or CP class.

Studies have demonstrated that low serum albumin levels are associated with a high postoperative complication rate after microvascular free flap reconstruction. The aim of this study was to investigate whether perioperative albumin supplementation reduced the postoperative complications of microvascular free flap reconstruction in oral and maxillofacial tumor resections.Patients who underwent microvascular free flap reconstruction during oral and maxillofacial tumor resections from January 2012 to December 2017 were enrolled in this retrospective study. The predictor variable was perioperative albumin supplementation. The primary outcome variables were surgery-associated postoperative complications, including local and systemic complications. The secondary outcome variables were the total duration of hospital stay, postoperative ICU admission rate, duration of ICU stay, and mortality during hospitalization.In total, 315 patients met the criteria. Patients with serum albumin supplementation showed a lower rate of surgery-associated local complications (6.5 vs 21.6%) with an adjusted odds ratio (OR) of 0.24 (95% confidence interval (CI), 0.12 to 0.49, P.001). The average postoperative hospital stay was significantly shortened for patients with albumin supplementation (12.56 ± 4.23 vs 15.34 ± 5.24 days, P.001). However, albumin supplementation had no effect on systemic complications.The results of this study suggest that perioperative albumin supplementation is associated with a decreased risk of local complications, shortened hospital stay, and decreased need for crystalloid infusion in patients who underwent oral and maxillofacial tumor resections with microvascular free flap reconstruction.

OBJECTIVE: To evaluate the haemodynamic effects of rapid fluid bolus therapy (FBT) (500 mL of 4% albumin over several minutes) versus combined FBT (rapid 200 mL FBT followed by a 300 mL infusion over 30 minutes). DESIGN: Single centre, prospective, before-and-after trial. SETTING: A tertiary intensive care unit in Australia. PARTICIPANTS: Fifty mechanically ventilated post-cardiac surgery patients. INTERVENTIONS: Rapid 4% albumin FBT versus combined FBT. MAIN OUTCOME MEASURES: We recorded haemodynamic parameters from before FBT to 30 minutes after FBT. A mean arterial pressure (MAP) response was defined by a MAP increase > 10%, and a cardiac index (CI) response was defined by a CI increase > 15%. RESULTS: Immediately after rapid FBT versus combined FBT, there was a CI response in 13 patients (52%) compared with five patients (20%) respectively (P = 0.038), and a MAP response in 11 patients (44%) in each group. However, from FBT administration to 30 minutes, there was a time and group interaction such that MAP was higher in the rapid FBT group (P = 0.003), as was the case for central venous pressure (P = 0.002) and mean pulmonary artery pressure (P < 0.001). Body temperature fell immediately and was lower with rapid FBT but became warmer than with combined FBT later (P < 0.001). At 30 minutes, a MAP response was seen in ten patients (40%) compared with nine patients (36%) (P < 0.99) and a CI response was present in eight patients (32%) compared with 11 patients (44%) (P = 0.56) in the rapid versus combined FBT groups respectively. CONCLUSION: Rapid FBT was superior to combined FBT in terms of mean MAP levels and immediate CI response. However, the number of MAP responders or CI responders was similar at 30 minutes.

Subcutaneously injected formulations have been developed for many biological products including monoclonal antibodies (mAbs). A knowledge gap nonetheless remains regarding the absorption and catabolism mechanisms and kinetics of a large molecule at the administration site. A multiscale pharmacokinetic (PK) model was thus developed by coupling multiphysics simulations of subcutaneous (SC) absorption kinetics with whole-body pharmacokinetic (PK) modeling, bridged by consideration of the presystemic clearance by the initial lymph. Our local absorption simulation of SC-injected albumin enabled the estimation of its presystemic clearance and led to the whole-body PK modeling of systemic exposure. The local absorption rate of albumin was found to be influential on the PK profile. Additionally, nineteen mAbs were explored via this multiscale simulation and modeling framework. The computational results suggest that stability propensities of the mAbs are correlated with the presystemic clearance, and electrostatic charges in the complementarity-determining region influence the local absorption rate. Still, this study underscores a critical need to experimentally determine various biophysical characteristics of a large molecule and the biomechanical properties of human skin tissues.

AIM: The manufacturers' recommended methods to calculate delivered activities in liver radioembolization are simplistic and only slightly personalized. Activity planning could also be based on a 99mTc-macroaggregated albumin SPECT/CT (MAA) using the partition model but its accuracy is controversial. This study evaluates the dose parameters in the normal liver and in the tumor compartments using MAA SPECT/CT (pre-therapeutic imaging) and 90Y TOF-PET/CT (post-therapy imaging). Finally, we propose a prescription of the activity as a function of the normal liver MAA distribution. METHOD: 66 procedures of RE (with resin microspheres) corresponding to 171 lesions were analyzed. Tumor to normal targeted liver uptake (T/NTL), tumor absorbed dose (TD) and whole normal liver absorbed (WNLD) were assessed with MAA and 90Y imaging. Secondly, activities were recalculated using the MAA distribution in the normal liver compartment to reach the maximal tolerable liver dose. These Activities were compared to activities defined with the BSA method. RESULTS: Compared to 90Y imaging, our study demonstrated an accurate estimation of the WNLD using MAA imaging (Pearson's R = 0.97, p < 0.001). On the contrary, significant variations were found for TD (R = 0.65, p < 0.001). The MAA T/NTL ratio has a 85% positive predictive value in identifying patients who will get a 90Y T/NTL ratio above 1.5. Moreover, activities calculated using the MAA distribution in the normal liver compartment were significantly higher to activities defined with the BSA method. CONCLUSION: Whole normal liver absorbed doses are accurately predicted with MAA imaging and could be used to optimize the activity planning.

Introduction Early prediction of patients' prognosis in the emergency department (ED) is important. Patients' conditions such as dehydration help predict prognosis. The ratio of serum blood urea nitrogen to creatinine (BUN/Cr ratio) and inferior vena cava (IVC) diameter is often used to determine dehydration. Also, serum albumin levels reflect nutritional conditions such as dehydration. In this study, we evaluated the performance of BUN/Cr ratio, IVC diameter ratio, and BUN/Albumin ratio as predictive markers for in-hospital mortality and ICU admission among various diseases in ED. Material and methods This retrospective cohort study utilized data from patients who had abdominal and pelvic computed tomography (APCT) performed at our institution from 2015 to 2018. The measurement of IVC diameter from computed tomography, the BUN/Cr ratio, and the BUN/Albumin ratio were calculated. Differences in the performance among the BUN/Cr ratio, the IVC diameter ratio, and the BUN/Albumin ratio for predicting outcomes were evaluated by the area under the receiver operating characteristic (AUROC) curve. Results A total of 914 patients were enrolled and 78 patients (8.5%) were admitted to the ICU, and 71 patients (7.8%) died during the clinical process. Multivariate logistic regression showed that only the BUN/Albumin ratio was a significant predictor of inhospital mortality and ICU admission. Conclusion Among dehydration markers the BUN/Albumin ratio is a simple and useful tool for predicting the outcomes of patients visiting the ED.

In recent years, human serum albumin (HSA) has been characterized as an ideal drug carrier in the cancer arena. Caveolin-1 (Cav-1) has been established as the principal structural protein of caveolae and, thus, critical for caveolae-mediated endocytosis. Cav-1 has been shown to be overexpressed in cancers of the lung and pancreas, among others. We found that Cav-1 expression plays a critical role in both HSA uptake and response to albumin-based chemotherapies. As such, developing a novel albumin-based chemotherapy that is more selective for tumors with high Cav-1 expression or high levels of caveolar-endocytosis could have significant implications in biomarker-directed therapy. Herein, we present the development of a novel and effective HSA-SN-38 conjugate (SSH20). We find that SSH20 uptake decreases significantly by immunofluorescence assays and western blotting after silencing of Cav-1 expression through RNA interference. Decreased drug sensitivity occurs in Cav-1-depleted cells using cytotoxicity assays. Importantly, we find significantly reduced sensitivity to SSH20 in Cav-1-silenced tumors compared to Cav-1-expressing tumors in vivo. Notably, we show that SSH20 is significantly more potent than irinotecan in vitro and in vivo. Together, we have developed a novel HSA-conjugated chemotherapy that is potent, effective, safe, and demonstrates improved efficacy in high Cav-1-expressing tumors., Graphical abstract, In this study, the authors have developed and established a novel albumin-SN-38 conjugate (SSH20) and tested it in pre-clinical models of pancreatic and lung cancer. The advantageous properties inherent to SN-38 conjugation to albumin and targeted delivery make SSH20 an attractive candidate for further preclinical and potential clinical study.

The haem group is a promising redox probe for the design of albumin-based voltammetric sensors. Among the endogenous ligands carried by human serum albumin (hSA), haem is characterised by a reversible redox behaviour and its binding kinetics strongly depend on hSA’s conformation, which, in turn, depends on the presence of other ligands. In this work, the potential applicability of haem, especially hemin, as a redox probe was first tested in a proof-of-concept study using perfluorooctanoic acid (PFOA) as model analyte. PFOA is known to bind hSA by occupying Sudlow’s I site (FA7) which is spatially related to the haem-binding site (FA1). The latter undergoes a conformational change, which is expected to affect hemin’s binding kinetics. To verify this hypothesis, hemin:albumin complexes in the presence/absence of PFOA were first screened by UV–Vis spectroscopy. Once the complex formation was verified, haem was further characterised via electrochemical methods to estimate its electron transfer kinetics. The hemin:albumin:PFOA system was studied in solution, with the aim of describing the multiple equilibria at stake and designing an electrochemical assay for PFOA monitoring. This latter could be integrated with protein-based bioremediation approaches for the treatment of per- and polyfluoroalkyl substances polluted waters. Overall, our preliminary results show how hemin can be applied as a redox probe in albumin-based voltammetric sensing strategies.

The liver performs many vital functions for the human body. It stores essential vitamins and minerals, such as iron and vitamins A, D, K, and B12. It synthesizes proteins, such as blood clotting factors, albumin, and glycogen, as well as cholesterol, carbohydrates, and triglycerides. Additionally, it acts as a detoxifier, metabolizing and helping to clear alcohol, drugs, and ammonia. Typical MR imaging protocols for liver imaging include T2-weighted, chemical shift imaging, and precontrast and postcontrast T1-weighted sequences. This article discussed MR imaging of diffuse liver diseases and their typical imaging findings.

Albumin is the most abundant protein in the plasma and has a regulatory role in the distribution of body fluids, acid-base physiology, and binding of essential components in the bloodstream. C-reactive protein (CRP) is produced by hepatocytes and is commonly used to assess inflammation. It was previously noted that acute-phase concentrations of proteins, such as CRP, tend to rise in inflammatory conditions, while albumin concentrations tend to decline. This study assessed the correlation between albumin levels and various inflammatory indices (CRP, WBC, PLT) of patients hospitalized at the Galilee Medical Center over a period of 3 months. The study population consisted of 4434 patients, ages 18-107 years (mean: 52 years), of whom 60% were female. A negative correlation between albumin and CRP levels (r = −0.311) was identified, as well as between albumin and white blood cells levels (r = −0.157). Positive correlations were found between albumin and platelets levels (r = 0.084), as well as between albumin and hemoglobin levels (r = 0.513). When considering the three largest departments, the strongest negative correlation between albumin and CRP was identified in the Internal Medicine departments. A linear regression analysis discovered a fairly minor effect of CRP on albumin levels, which only became apparent when CRP levels were extremely high (500 mg/L). The mechanisms underlying this negative correlation still need to be explored.

Photothermal-responsive (PTR) and anti-oxidative silk fibroin/dopamine nanoparticles (SD NPs) mediated by tyrosinase were produced, and decorated either by curcumin or albumin (BSA) to produce SD/curcumin or SD/BSA NPs as drug delivery vehicles, respectively. Both drug loaded NPs were further blended into SF solutions to produce SD films, as a depot-based drug delivery. The reaction mechanisms for producing new SD NPs were proposed. Anti-oxidative activities for SD NPs were examined by H2O2 scavenge capacities of NPs. NPs were not cytotoxic at concentration of 1000μg/mL. Moreover, heparin was coated to SD films to produce SDH films for temporary implants. Cumulative release profiles for drugs loaded SDH films showed fast releases and then sustained releases stages. Furthermore, the releases of curcumin in sustained stages for varying SD/curcumin NPs loaded into SDH films were dependent on amounts of NPs. BSA releases profiles for SD/BSA NPs loaded into SDH films were similar to those profiles for the films carried with SD/curcumin NPs but release periods of BSA were short. Degrees of PTR effects with irradiation of near infrared on the releases of two drugs loaded films were different. Blood clot at wound areas of rats with SDH films implantations was not found for 24 h study.

The number of patients with non-alcoholic steatohepatitis (NASH) and inflammatory bowel disease (IBD) is increasing. This study elucidates the effect of both NASH and IBD on hepatocellular carcinoma (HCC) using a mouse model combining NASH and IBD. The melanocortin 4 receptor-deficient (Mc4r-KO) mice were divided into four groups with or without a high-fat diet (HFD) and with or without dextran sulfate sodium (DSS) to induce colitis, and the differences in liver damage and occurrence of HCC were analyzed. In the HFD + DSS group, the body weight, liver weight/body weight ratio, and serum levels of albumin and alanine aminotransferase were significantly lower than those in the HFD group. We further found that steatosis was significantly lower and lobular inflammation was significantly higher in the HFD + DSS group than those in the HFD group, and that individual steatosis and lobular inflammation state in the HFD + DSS mice varied. We detected HCC only in the HFD + DSS group, and mice with severe steatosis and mild colitis were found to be at high risk of HCC. Presently, the prediction of HCC is very difficult. In some cases, severe colitis reverses the fat accumulation due to appetite loss. Our findings clearly showed that severe steatohepatitis and mild colitis are simultaneously essential for the occurrence of HCC in patients with NASH and IBD.

Resumen: Introducción: Estudios previos han demostrado una elevada mortalidad de los pacientes en tratamiento con hemodiálisis, aunque en pocos de ellos se analiza la supervivencia de los que reciben exclusivamente este tratamiento. Nuestro objetivo fue analizar la mortalidad de los pacientes que recibieron tratamiento con hemodiálisis. Métodos: Se analizó la cohorte de pacientes que iniciaron tratamiento sustitutivo entre los años 2010 y 2012 en la comunidad de Castilla-La Mancha y permanecieron en tratamiento con hemodiálisis. Se estudiaron las variables edad, sexo, enfermedad renal primaria, acceso vascular, hemoglobina, índice de Charlson y albúmina sérica al comienzo del tratamiento y se realizó un seguimiento hasta final de 2017. Resultados: La mortalidad fue del 63,4% a los 5 años y del 76% al final del periodo de seguimiento, sin diferencias entre varones y mujeres, y se relacionó con una mayor edad, el comienzo urgente o en aquellos con enfermedad renal reagudizada, la utilización de catéteres o una albúmina inferior a 3,5 g/dl. Conclusiones: La mortalidad en los pacientes que permanecen en diálisis es muy elevada y se asocia a factores no modificables como la edad pero también a otros que podemos prevenir o tratar, como el tipo de acceso vascular o el estado de nutrición al comienzo del tratamiento. Abstract: Introduction: Previous reports have shown very high mortality among hemodialyisis patients. Our goal was to analyze the mortality of patients in the Renal Registry of Patients who remained exclusively on hemodialysis treatment. Methods: The cohort of patients who started treatment in the community of Castilla-La Mancha between 2010 and 2012 and remained on hemodialysis treatment was analysed until the end of 2017. Age, sex, primary kidney disease, vascular access, hemoglobin, Charlson index and serum albumin were included. Results: Mortality rate was 63.4% after 5 years and 76% at the end of the study, with no difference between males and females, and was linked to an older age, urgent onset or in those with acute deterioration of chronic kidney disease, the use of catheters or albumin less than 3.5 g/dl. Conclusions: Mortality in patients who remain on hemodialysis is very high and is associated with non-modifiable factors such as age but also others that we can prevent or treat such as type of vascular access or nutrition status at the beginning of treatment.

Background and Aims The efficacy and safety of albumin infusion for treatment and prevention of overt hepatic encephalopathy (OHE) among cirrhosis patients remained controversial. We performed a systematic review and meta-analysis to evaluate the benefit of albumin infusion for the treatment and prevention of OHE. Methods We performed a systematic search of 4 electronic databases up to 31st January 2021. The primary outcome was the resolution of OHE. Secondary outcomes were inpatient mortality and albumin-associated adverse events. We assessed the pooled odds’ risk, pooled mean differences, 95% confidence interval and heterogeneity using Review Manager Version 5.3. Results A total of 12 studies (2,087 subjects) were identified. Among cirrhosis patients with OHE, albumin infusion was associated with a lower pooled risk of OHE (OR=0.43, 95%CI: 0.27, 0.68; I2=0%). Among patients without baseline OHE, albumin infusion was associated with a lower pooled risk of developing OHE (OR=0.53, 95%CI: 0.32, 0.86; I2=62%). Albumin infusion was associated with a lower pooled risk of inpatient mortality (OR=0.36, 95%CI: 0.21, 0.60; I2=0%). Conclusion Well-powered randomized trials are required to confirm the benefits of albumin infusion for the prevention and treatment of overt hepatic encephalopathy among decompensated cirrhosis patients.

Long-term storage of proteins at ambient temperature is required for applications in pharmaceutics and biotechnology. Lyophilization is a versatile approach for stabilizing proteins at ambient temperature, although its freezing and drying processes negatively affect the protein structure. In this study, we show a glass-like protein condensate (GLPC) as a new method for protein stabilization at ambient temperature. Various protein types, including immunoglobulin G, gamma globulin, albumin, and chymotrypsin, formed a glassy state during ultracentrifugation and natural drying, while proteins that tend to crystalize, such as hen egg-white lysozyme, did not. The GLPCs were characterized by a transparent solid state, similar to a dry glass ball. Importantly, the GLPCs were dissolved easily in saline solution at a physiological concentration, thereby retaining their native structures and functions. The GLPCs preserved their native structures even after 1 year of incubation at ambient temperature. These results provide a framework for the development of protein preservation methods at ambient temperature other than lyophilization.

*Çayır, Serkan ( Aksaray, Yazar ) *Kayabaşı, Serkan ( Aksaray, Yazar ), Introduction: Prognosis of sudden sensorineural hearing loss may be predicted using several parameters of laboratory blood analysis. Objective: To identify and investigate the most significant indicator parameters related to the poor prognosis of sudden sensorineural hearing loss. Methods: Eighty-eight patients were included, and three groups were constituted: non-recovery group with14 patients, recovery group with 33 patients and control group with 41 individuals. We compared fibrinogen-to-albumin ratio, C-reactive protein-to-albumin ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, white blood cell and hemoglobin of the groups. Then, we investigated the most significant indicator parameters related to the poor prognosis of sudden hearing loss. Results: The mean hemoglobin, mean platelet-lymphocyte ratio and median white blood cell values did not significantly differ among three groups (p = 0.36, p = 0.86 and p = 0.79, respectively). A significant difference of median fibrinogen-albumin ratio, C-reactive protein-albumin ratio, neutrophil-to-lymphocyte ratio was evident among three groups (p < 0.001, p = 0.003 and p = 0.002, respectively). Median fibrinogen-albumin ratio, C-reactive protein-albumin ratio and neutrophil-to-lymphocyte ratio values were significantly greater in the non-recovery group, compared with the controls (p < 0.001, p = 0.003 and p = 0.005, respectively). Median fibrinogen-to-albumin ratio, C-reactive protein-to-albumin ratio and neutrophil-to-lymphocyte ratio were significantly greater in the recovery group, compared with the controls (p < 0.001, p = 0.013 and p = 0.005, respectively). Moreover, the median fibrinogen-albumin ratio was significantly greater in the non-recovery group compared with the recovery group (p = 0.017). However, no statistically significant difference of median C-reactive protein-albumin ratio, neutrophil-to-lymphocyte was evident between the non-recovery and recovery groups (p = 0.15). Conclusion: Increased levels of fibrinogen-albumin ratio may be predictive for poor prognosis in patients with sudden sensorineural hearing loss.

In most cases, once nanoparticles (NPs) enter the blood, their surface is covered by biological molecules, especially proteins, forming a so-called protein corona (PC). As a result, what the cells of the body “see” is not the NPs as formulated by the chemists, but the PC. In this way, the PC can influence the effects of the NPs and even mask the desired effects of the NP components. While this can argue for trying to inhibit protein-nanomaterial interactions, encapsulating NPs in an endogenous PC may increase their clinical usefulness. In this review, we briefly introduce the concept of the PC, its formation and its effects on the behavior of NPs. We also discuss how to reduce the formation of PCs or exploit them to enhance NP functions. Studying the interactions between proteins and NPs will provide insights into their clinical activity in health and disease. Statement of significance The formation of protein corona (PC) will affect the operation of nanoparticles (NPs) in vivo. Since there are many proteins in the blood, it is impossible to completely overcome the formation of PC. Therefore, the use of PCs to deliver drug is the best choice. De-opsonins adsorbed on NPs can reduce macrophage phagocytosis and cytotoxicity of NPs, and prolong their circulation in blood. Albumin, apolipoprotein and transferrin are typical de-opsonins. In present review, we mainly discuss how to optimize the delivery of nanoparticles through the formation of albumin corona, transferrin corona and apolipoprotein corona in vivo or in vitro.

We aimed to investigate the role of neutrophil to lymphocyte ratio (NLR) and the C-Reactive Protein/Albumin Ratio (CAR), which are obtained from the first laboratory values of the elderly patients at admission to the emergency department (ED), in predicting in-hospital mortality.This retrospective observational study includes the patients aged 65 and above who applied to the emergency department for two months. The patients' neutrophil, lymphocyte, C-reactive protein (CRP), albumin, NLR and CAR values were recorded. Statistical analysis of NLR and CAR values was performed according to in-hospital mortality and ED outcome.784 patients were included in the statistical analysis of the study. Increased NLR (8.82 (4.16-16.63), 4.76 (2.62-8.56), p˂0.001) and increased CAR (21.39 (6.02-55.07), 4.82 (1.17-17.03), p 0.001) values were found to be statistically significant in the group with mortality compared to the group without mortality. Increased NLR (AUC: 0.642) and increased CAR (AUC: 0.723) were a predictor of in-hospital mortality. It was found that in-hospital mortality risk in patients with concurrent high NLR and CAR values (CAR˃12.3, NLR˃7.1) was 9.87 times more than the patients with concurrent low NLR and CAR values (CAR12.3, NLR 7.1). NLR and CAR values of the patients hospitalized in intensive care and service (NLR 7.21 (4.07-13.36), 5.77 (3.45-11.22); CAR 12.65 (2.79-36.8), 9.56 (1.74-33.97)) were found to be statistically significantly higher than those who were discharged (NLR 3.64 (2.26-7.02); CAR 2.88 (0.9-10.59)).According to our results, the concurrent high levels of NLR and CAR values were found to be more effective in predicting in-hospital mortality compared to a separate evaluation.

In microfluidics, the emerging field of microphysiological systems (MPS) is overcoming the challenge of physiological irrelevancy by animal models for drug discovery and development. Liver function is critically influenced by drugs owing to its role in drug metabolism and detoxification. Human serum albumin (HSA) is one of the most important secreted biomarkers which indicate normal liver function. A microfluidic albumin immunosensor was developed to be integrated with liver-on-a-chip MPS for continuous feedback over disease modeling and treatment. A gold-electrode based electrochemical immunosensor was established by anti-HSA antibody immobilization. The liver MPS was found to be efficient for live monitoring of disease modelling and drug treatment over the period of 6 days. The system emulated and analyzed real-time toxicity modeling with HSA sensing. The detection limit of integrated sensor was 1 μg/ml with successive reproducibility. The proposed sensor was also validated with metabolic biomarkers’ assays. Molecular assays supported the sensor monitoring and depicted liver injury and recovery. The liver MPS with combined albumin sensor chip may be a promising platform to mimic real-time drug assessment.

Cylindrospermopsin (CYN) has been involved in cases of poisoning in humans following ingestion. Studies have demonstrated that the kidney is the most affected organ. CYN exposure leads to low-molecular-weight proteinuria and increased excretions of the tubular enzymes in mice, suggesting the damage caused by CYN is mainly tubular. However, the mechanism involved in CYN nephrotoxicity remains unknown. Thus, in order to evaluate the effects of CYN exposure (0.1, 0.5 and 1.0 μg/mL) on tubular renal cells LLC-PK1 distinct mechanisms were analyzed by assessing cell death using flow cytometry, albumin uptake by fluorescence analysis, Na+/K+-ATPase activity by a colorimetric method, RT-qPCR of genes related to tubular transport and function as well as internalization of CYN by ELISA. In this study, CYN was found to induce necrosis in all concentrations. CYN also decreased albumin uptake as well as downregulated megalin and dab2 expression, both proteins involved in albumin endocytosis process. Moreover, CYN appears to be internalized by renal tubular cells through a receptor-mediated endocytosis. Finally, the present study demonstrates that CYN is responsible for disrupting tubular cell transport and function in LLC-PK1 cells.

The BBB is a protective entity that prevents external substances from reaching the CNS but it also hinders the delivery of drugs into the brain when they are needed. The main objective of this work was to improve a previously proposed in vitro cell-based model by using a more physiological cell line (hCMEC/D3) to predict the main pharmacokinetic parameters that describe the access and distribution of drugs in the CNS: Kpuu,brain, fu,plasma, fu,brain and Vu,brain. The hCMEC/D3 permeability of seven drugs was studied in transwell systems under different conditions (standard, modified with albumin and modified with brain homogenate). From the permeability coefficients of those experiments, the parameters mentioned above were calculated and four linear IVIVCs were established. The best ones were those that relate the in vitro and in vivo Vu,brain and fu,brain (r2 = 0.961 and r2 = 0.940) which represent the binding rate of a substance to the brain tissue, evidencing the importance of using brain homogenate to mimic brain tissue when an in vitro brain permeability assay is done. This methodology could be a high-throughput screening tool in drug development to select the CNS promising drugs in three different in vitro BBB models (hCMEC/D3, MDCK and MDCK-MDR1).

Mice are arguably the most important tool in the preclinical evaluation of liposomes; however, the effects of inter-strain physiological variabilities on in vivo performance of liposomes have been seriously overlooked. The present study validated that plasma proteins (PPs) and the capability of mononuclear phagocyte system (MPS) (typically expressed by phagocytosis rate, K) were mice strain-dependent. Physiological variabilities in PPs and the phagocytosis rate jointly contributed to the inter-strain inconsistency of pharmacokinetic (PK) profiles of liposomes. For the PPs sensitive liposomes (such as plain PEGylated liposomes and folic acid functionalized PEGylated liposomes), inter-strain variabilities in PK profiles could be calibrated using the corrected phagocytic rate (KC = K×(c × Ig)/(alb×apo)), where c, Ig, alb and apo were respective the total content of complement proteins, immunoglobulins, albumin and apolipoproteins. While for the PPs insensitive liposomes (e.g., cRGD functionalized liposomes), phagocytic rate could be directly used to calibrate inter-strain difference of liposome PK profiles. Our data also warn that the reciprocal interaction between payloads and organisms would be much more complicated than that between liposomes and organisms, thus independent investigation should be conducted for each individual therapeutic agent.

Made available in DSpace on 2021-06-25T15:05:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Oxidative stress (OS) has been strongly associated with postprandial lipemia (PPL) in humans, and still requires further investigation in dogs. However, since lipemia interferes with spectrophotometric determinations such as those used to assess OS, the present study investigated the effect of PPL on OS parameters of healthy dogs. Twenty dogs had lipemic postprandial samples compared to the average of two non-lipemic moments. Subsequently, PPL was simulated in vitro using a commercial lipid emulsion and twelve pools of non-lipemic serum of these dogs were used to simulate the minimum, median and maximum concentrations of triglycerides obtained during the lipemic state. Serum OS parameters were assessed using the antioxidants uric acid, albumin and total bilirubin; total antioxidant capacity (TAC); total oxidant capacity (TOC); and lipid peroxidation. In vivo PPL caused an increase in albumin, TAC-CUPRAC, TAC-FRAP, uric acid (p < 0.0001), TOC (p = 0.0012) and total bilirubin (p = 0.0245); reduction of TAC-ABTS (p = 0.0008); and did not alter the lipid peroxidation (p = 0.8983). In vitro, levels of albumin increased at the three lipemic concentrations (p < 0.0001), uric acid increased in the median and maximum levels (p < 0.0001), and total bilirubin concentration increased only at the maximum lipemic level (p = 0.0012). All lipemic levels tested increased TAC-ABTS (p = 0.0011) and TACFRAP (p < 0.0001). TAC-CUPRAC (p = 0.5002), TOC (p = 0.5938) and lipid peroxidation (p = 0.4235) were not affected by in vitro lipemia. In conclusion, both the in vivo postprandial state and in vitro simulated lipemia affect oxidative stress markers in dogs depending on the oxidative stress marker, and thus the postprandial state and/or lipemic samples should be avoided. Londrina State Univ UEL, Dept Prevent Vet Med, Londrina, Parana, Brazil Univ Ctr Integrated Fac Ourinhos Unifio, Roque Quagliato Vet Hosp, Ourinhos, SP, Brazil Sao Paulo State Univ, Coll Vet Med Aracatuba, Dept Clin Surg & Anim Reprod, Aracatuba, SP, Brazil Univ Ctr Integrated Fac Ourinhos Unifio, Dept Vet Med, Rodovia BR 153,Km 338, BR-19909100 Ourinhos, SP, Brazil Sao Paulo State Univ, Coll Vet Med Aracatuba, Dept Clin Surg & Anim Reprod, Aracatuba, SP, Brazil FAPESP: 2018/18220-0 FAPESP: 2018/16334-9

Objective To assess the impact of using corrected calcium versus total calcium on hypercalcemia case detection in hospitalized patients. Methods Patients hospitalized from June 2012 to June 2017 with a corrected calcium level of ≥10.5 mg/dL were identified by medical record review. One-year follow-up data through June 2018 were acquired. Albumin-corrected calcium level was calculated: (4 − albumin concentration in g/dL) × 0.8 + total serum calcium in mg/dL. Results A group of 1067 patients had a corrected calcium level of ≥10.5 mg/dL. The prevalence of hypercalcemia was 0.73% with total calcium and 1.09% with corrected calcium, respectively, with a 49% relative increase. Most patients (62%) had mild hypercalcemia (10.5-11.9 mg/dL); 3.7% had severe hypercalcemia (>14 mg/dL). With corrected calcium, the most common categories of hypercalcemia were malignancy (35.4%), hypercalcemia that was not further evaluated (31.1%), and hyperparathyroidism (22.4%). All patients in the unidentified category had albumin levels Conclusion Using albumin-corrected calcium resulted in an ∼50% increase in the detection of hypercalcemia cases. Although hypercalcemia resolved in majority of the undiagnosed cases at 1 year, a number of these remained abnormal. Detecting hypercalcemic disorders by correcting for low albumin level can help identify conditions such as hyperparathyroidism. Adding auto-calculated albumin-corrected calcium to routine laboratory tests could be a cost-effective intervention to improve the detection of hypercalcemic disorders.

Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus. The combination of insulin (Ins) with liraglutide (Lir) has a greater potential for preventing DN than monotherapy. However, the renal protective effect of the combined Ins/Lir therapy is largely compromised due to their short half-lives after subcutaneous injection. Herein, a glucose-responsive hydrogel was designed in situ forming the dynamic boronic esters bonds between phenylboronic acid-grafted γ-Polyglutamic acid (PBA-PGA) and konjac glucomannan (KGM). It was hypothesized that the KGM/PBA-PGA hydrogel as the delivery vehicle of Ins/Lir would enhance the combinational effect of the latter on preventing the DN progress. Scan electronic microscopy and rheological studies showed that KGM/PBA-PGA hydrogel displayed good glucose-responsive property. Besides, the glucose-sensitive release profile of either Ins or Lir from KGM/PBA-PGA hydrogel was uniformly displayed at hyperglycemic level. Furthermore, the preventive efficacy of KGM/PBA-PGA hydrogel incorporating insulin and liraglutide (Ins/Lir-H) on DN progress was evaluated on streptozotocin-induced rats with diabetic mellitus (DM). At 6 weeks after subcutaneous injection of Ins/Lir-H, not only the morphology of kidneys was obviously recovered as shown by ultrasonography, but also the renal hemodynamics was significantly improved. Meanwhile, the 24-h urinary protein and albumin/creatinine ratio were well modulated. Inflammation and fibrosis were also largely inhibited. Besides, the glomerular NPHS-2 was obviously elevated after treatment with Ins/Lir-H. The therapeutic mechanism of Ins/Lir-H was highly associated with the alleviation of oxidative stress and activation of autophagy. Conclusively, the better preventive effect of the combined Ins/Lir via KGM/PBA-PGA hydrogel on DN progress was demonstrated as compared with their mixed solution, suggesting KGM/PBA-PGA hydrogel might be a potential vehicle of Ins/Lir to combat the progression of DN.

Background Laboratory testing is commonly performed in patients with COVID-19. Each of the laboratory parameters has potential value for risk stratification and prediction of COVID-19 outcomes. This systematic review and meta-analysis aimed to evaluate the difference between these parameters in severe and nonsevere disease and to provide the optimal cutoff value for predicting severe disease. Method We performed a systematic literature search through electronic databases. The variables of interest were serum procalcitonin, albumin, C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) levels in each group of severity outcomes from COVID-19. Results There were a total of 4848 patients from 23 studies. Our meta-analysis suggest that patients with severe COVID-19 infections have higher procalcitonin, (mean difference 0.07; 95% CI 0.05–0.10; p, Highlights • Currently, the cut-off value for laboratory markers to differentiate severity of COVID-19 is still unclear. • Our study suggest serum procalcitonin, albumin, CRP, D-dimer, and LDH can assist in differentiating the severity of COVID-19. • Physicians should check these laboratory parameters in COVID-19 patients for predicting the outcome of the disease.