Clearance Rate Research Articles

Differential T-cell profiles determined by Hepatitis B surface antigen decrease among people with Human Immunodeficiency Virus /Hepatitis B Virus coinfection on treatment

BackgroundSeveral studies have reported that combination antiretroviral therapy (cART) enhances the hepatitis B surface antigen (HBsAg) clearance rate in Human Immunodeficiency Virus-1/Hepatitis B Virus (HIV/HBV) coinfected patients, yet the associated immunological characteristics remain unclear.MethodsGlobal and specific immune phenotypic profiles were examined in 48 patients with HIV/HBV coinfection before cART and at 1-year, and 3-year after cART using flow cytometry. In addition, 61 patients with HBV monoinfection were included for comparison.ResultsHBsAg response (sAg-R) was defined as > 0.5 log decrease within six months of cART initiation, and 16 patients achieved it. Patients with sAg-R (the sAg-R group) exhibited distinct immune phenotypes compared to those of HBsAg-retained patients (the sAg-NR group). Notably, patients with sAg-R had lower CD4+ T cell counts and a higher number of HBcAg-specific T cells. Further, the sAg-R group exhibited upregulation of HLA-DR, Ki67, and PD-1 in CD4+ T cells and heightened HLA-DR and T-bet in CD8+ T cells. However, the sAg-R group had fewer TEMRA cells but more TEM and Th17 cells than those in the sAg-NR group. Expression of various markers, including HLA-DR+CD4+, Ki67+CD4+, PD-1+CD4+, CD38+CD8+, HLA-DR+CD8+, TIM-3+CD8+, HBV-specific CD4+ T cell secreting IFN-γ and IL-2, and specific CD8+ T cell secreting IFN-γ and IL-2, correlated with HBsAg decrease.ConclusionThe decline in HBsAg levels during cART in HIV/HBV coinfection involves significant alterations in CD4+ and CD8+ T cells phenotypes, offering a novel perspective on a functional HBV cure.

Cryosurgery of eyelid actinic keratosis and the effect of adrenaline in local anesthetics - temperature mapping using IR thermography

ABSTRACT Purpose The efficacy of cryosurgery is believed to depend on the thaw time. The presence of adrenaline in local anesthetics affects blood perfusion, and may thus also affect the thaw time. The aim of the present study was to use IR thermography to monitor the tissue temperature during cryosurgery of actinic keratosis, and to assess the effect of adrenaline in local anesthetics. Methods Twelve patients with actinic keratosis in the periorbital region underwent cryosurgery. The temperature was continuously mapped using a high-precision IR camera and was also visually assessed by the surgeon. The results obtained when employing local anesthetics with and without adrenaline were compared. Results The temperature change during thawing showed a triphasic pattern. The thaw time was significantly longer when using an anesthetic with adrenaline. This was observed with both IR thermography and by visual observation. Conclusions The findings indicate that a longer freezing time may be needed when using a local anesthetic without adrenaline to achieve the same cryo-effect as when using a local anesthetic with adrenaline. A larger clinical trial is needed on the effects of using local anesthetics with and without adrenaline to treat actinic keratosis, for example, the clearance rate, before recommendations can be made concerning their use.

Transpulmonary Plasma Endothelin-1 Arterial:Venous Ratio Differentiates Survivors from Non-Survivors in Critically Ill Patients with COVID-19-Induced Acute Respiratory Distress Syndrome.

Endothelin-1 (ET-1) is a potent vasoconstrictor produced by endothelial cells and cleared from circulating blood mainly in the pulmonary vasculature. In a healthy pulmonary circulation, the rate of local production of ET-1 is less than its rate of clearance. In the present study, we aimed to investigate whether the abnormal pulmonary circulatory handling of ET-1 relates to poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS). To this end, central venous and systemic arterial ET-1 plasma levels were simultaneously measured on Days 1 and 3 following ICU admission in mechanically ventilated COVID-19 patients with ARDS (COVID-19 ARDS, N = 18). Central venous and systemic arterial ET-1 plasma levels were also measured in two distinct SARS-CoV-2-negative mechanically ventilated critically ill patient groups, matched for age, sex, and critical illness severity, with ARDS (non-COVID-19 ARDS, N = 14) or without ARDS (non-COVID-19 non-ARDS, N = 20). Upon ICU admission, COVID-19-induced ARDS patients had higher systemic arterial and central venous ET-1 levels compared to the non-COVID-19 ARDS and non-COVID-19 non-ARDS patients (p < 0.05), yet a normal systemic arterial:central venous (A:V) ET-1 ratio [0.63 (0.49-1.02)], suggesting that pulmonary ET-1 clearance is intact in these patients. On the other hand, the non-COVID-19 ARDS patients demonstrated abnormal ET-1 handling [A:V ET-1 ratio 1.06 (0.93-1.20)], while the non-COVID-19 non-ARDS group showed normal ET-1 handling [0.79 (0.52-1.11)]. On Day 3, the A:V ratio in all three groups was <1. When the COVID-19 ARDS patients were divided based on 28-day ICU mortality, while their systemic arterial and central venous levels did not differ, the A:V ET-1 ratio was statistically significantly higher upon ICU admission in the non-survivors [0.95 (0.78-1.34)] compared to the survivors [0.57 (0.48-0.92), p = 0.027]. Our results highlight the potential importance of ET-1 as both a biomarker and a therapeutic target in critically ill COVID-19 patients. The elevated A:V ET-1 ratio in non-survivors suggests that the early disruption of pulmonary ET-1 handling may be a key marker of poor prognosis.

Effects of ocean acidification on the interaction between calcifying oysters (Ostrea chilensis) and bioeroding sponges (Cliona sp.)

Ocean acidification can negatively affect a broad range of physiological processes in marine shelled molluscs. Marine bioeroding organisms could, in contrast, benefit from ocean acidification due to reduced energetic costs of bioerosion. Ocean acidification could thus exacerbate negative effects (e.g. reduced growth) of ocean acidification and shell borers on oysters. The aim of this study was to assess the impact of ocean acidification on the oyster Ostrea chilensis, the boring sponge Cliona sp., and their host-parasite relationship. We exposed three sets of organisms 1) O. chilensis, 2) Cliona sp., and 3) O. chilensis infested with Cliona sp. to pHT 8.03, 7.83, and 7.63. Reduced pH had no significant effect on calcification, respiration and clearance rate of uninfested O. chilensis. Low pH significantly reduced calcification leading to net dissolution of oyster shells at pHT 7.63 in sponge infested oysters. Net dissolution was likely caused by increased bioerosion by Cliona sp. at pHT 7.63. Additionally, declining pH and sponge infestation had a significant negative antagonistic effect (less negative than predicted additively) on clearance rate. This interaction suggests that sponge infested oysters increase clearance rates to cope with higher energy demand of increased shell repair resulting from higher boring activity of Cliona sp. at low seawater pH. O. chilensis body condition was unaffected by sponge infestation, pH, and the interaction of the two. The reduction in calcification rate suggests sponge infestation and ocean acidification together would exacerbate direct (reduced growth) and indirect (e.g., increased predation) negative effects on oyster health and survival. Our results indicate that ocean acidification by the end of the century could have severe consequences for marine molluscs with boring organisms.

24 Comparative Effectiveness of Normal Saline, Lactated Ringer’s Solution, and Isolyte on Rate of Lactate Clearance in Shock

24 Comparative Effectiveness of Normal Saline, Lactated Ringer’s Solution, and Isolyte on Rate of Lactate Clearance in Shock

Real-World Data on Brodalumab Treatment in Patients with Moderate-to-Severe Plaque Psoriasis: An Observational Study from the Czech Republic BIOREP Registry.

The aim of this observational, multicenter study was to assess the real-world use of brodalumab for the treatment of moderate-to-severe plaque psoriasis in patients in the Czech Republic, using data from the BIOREP registry. The study included 273 patients aged≥18years with moderate-to-severe psoriasis who received brodalumab. Endpoints were drug survival (time from treatment initiation to discontinuation), effectiveness [Psoriasis Area and Severity Index (PASI)], and health-related quality-of-life [Dermatology Life Quality Index (DLQI)]. Predicted drug survival probability was 92.4% [95% confidence interval (CI): 89.1, 95.7%] at 6months and 84.2% (95% CI 79.5, 89.1%) at 12months; this was maintained at 24months [80.4% (95% CI 74.5, 86.8%)]. Younger age, higher body mass index, and no previous biologic treatment were significantly associated with longer drug survival. Absolute PASI≤3 after 3months was achieved by 89.8% of patients; 92.4%, 77.8%, and 59.1% reached PASI 75, PASI 90, and PASI 100, respectively. After 12months, 96.5% of 141 patients had an absolute PASI≤3. The proportion of patients achieving DLQI 0/1 was 87.3% at 12months. This study demonstrated high and sustained drug survival with high rates of skin clearance and improved quality of life in patients with relatively severe disease treated with brodalumab. Improvements were observed as early as 3months post-treatment initiation and were sustained for up to 24months in a real-life setting.

Investigation of varying tip clearance gap and operating conditions on the fulfilment of low-speed axial flow fan

Abstract The present study aims to identify the suitable tip clearance and volumetric flow rates for low-speed axial flow fans. The performance of an axial fan depends on various parameters like fan speed, available tip clearance gap, volumetric flow rate, power consumption, and working fluid. Leakage flow occurring at a rotating component such as a blade and solid casing of a ducted axial fan is typically linked to losses and the potential emergence of a rotating stall. The numerical analysis for this study uses the Reynolds Averaged Navier–Stokes equations with the k-omega SST turbulence model to perform the steady-state simulations by varying tip gap and volumetric flow rate. The results proved that the optimum performance was obtained with a tip clearance gap of 1 mm, and maximum fan efficiency was achieved at a volumetric flow rate of 3.9–4.5 m3/s. The novelty of this proposed work is to enhance the efficiency of axial flow fans with circular arc-cambered aerofoils using optimum tip clearance and volumetric flow rate through steady-state simulations. This method can be used in turbomachinery to improve fan performance.

Azaspiracid-59 accumulation and transformation in mussels (Mytilus edulis) after feeding with Azadinium poporum (Dinophyceae)

Azaspiracid-59 (AZA-59) was detected in plankton in coastal waters of the Pacific Northwest USA. Given that bivalves metabolize and transform accumulated phycotoxins, a strain of Azadinium poporum isolated from the coast of Washington State that is a known producer of AZA-59 was used in a controlled feeding experiment with mussels (Mytilus edulis) to assess AZA-59 accumulation rates and transformation into shellfish metabolites. Mussels started feeding immediately after the addition of A. poporum. Mussels were generally healthy during the entire experimental exposure of 18 days with prevailingly high rates of clearance (ca 100 mL per mussel and hour) and ingestion. Mussel were extracted after different exposure times and were analyzed by liquid chromatography coupled with low- and high-resolution mass spectrometry. In the course of the experiment a number of putative AZA-59 metabolites were detected including hydroxyl and carboxy analogs that corresponded with previously reported mussel metabolites of AZA-1. A significant formation of 3-OH fatty acid acyl esters relative to free AZAs was observed through the time course of the study, with numerous fatty acid ester variants of AZA-59 confirmed. These results illustrate the potential for metabolism of AZA59 in shellfish and provide important information for local AZA monitoring and toxicity testing along the Northern Pacific US coast.

Preparation of decellularized bone graft material with supercritical carbon dioxide extraction technique.

To evaluate the immunogenicity and osteogenic ability of animal-derived bone graft material decellularized with supercritical carbon dioxide. Porcine femurs were randomly divided into two groups after preliminary treatment, and decellularized with conventional method (conventional control group) or supercritical carbon dioxide (experimental group). Clearance rate of galactose-α-1, 3-galactose (α-Gal) and residual DNA of the two groups were analyzed to assess the immunogenicity of the xenogenic materials. Clearance rate of α-Gal was determined by enzyme-linked immunosorbent assay and residual DNA was detected by fluorescence method. Nine SPF-grade male athymic nude mice of 6 weeks old were randomly divided into experimental group, conventional control group and positive control group. Samples were implanted over biceps femoris muscle of athymic nude mice, the explants were collected 4 weeks post implantation, hematoxylin and eosin (HE) staining and immunohistochemistry were applied to determine the osteogenic ability and bone tissue-associated protein expressions of the implants. The clearance rates of α-Gal antigen in the experimental group and the conventional control group were (99.09±0.26)% and (30.18±2.02)%, respectively (t=58.67, P<0.01). The residual DNA of the experimental group, the conventional control group and the positive control group were (13.49±0.07) ng/mg, (15.20±0.21) ng/mg and (14.70±0.17) ng/mg, the residual DNA in the experimental group was significantly lower than that in the conventional control group (t=－13.41, P<0.01) and the positive control group (t=－11.30, P<0.01). HE staining showed that multiple bone formation centers with active osteogenesis and rich bone marrow were observed in experimental group 4 weeks after implantation, only a small number of bone formation centers were observed in the conventional control group and the positive control group, with no obvious osteoblasts present. Immunohistochemistry results indicated that the expressions of alkaline phosphatase, Runt-related transcription factor 2, typeⅠcollagen and osteocalcin in the experimental group showed an increasing trend compared with those in the conventional control group and the positive control group. Compared with clinically used demineralized bone matrix and bone graft material decellularized with conventional method, bone graft material decellularized with supercritical carbon dioxide exhibits lower immunogenicity and better osteogenic ability.

Caffeic acid-mediated photodynamic multifunctional hyaluronic acid-gallic acid hydrogels with instant and enduring bactericidal potency accelerate bacterial infected wound healing

The emergence of drug-resistant bacteria poses significant challenges in wound treatment. Antimicrobial photodynamic therapy has emerged as an effective approach to eliminating bacteria by inducing oxidative stress without causing drug resistance. Here, we developed a natural hyaluronic acid (HA)-gallic acid (GA) conjugation-based hydrogel combined with herbal photosensitizer-caffeic acid (CA), which exhibits self-healing ability, shape adaptability, biodegradability, and robust tissue adhesion. Under exposure to 400 nm light, caffeic acid acts as a photosensitizer, generating reactive oxygen species and oxidative damage to bacterial cell membranes. Furthermore, the presence of GA and CA displayed a continuous inhibitory effect on bacterial growth, along with antioxidant properties that promote wound healing even after the cessation of light exposure. The antibacterial mechanism of the HA-GA/CA hydrogel against MRSA, S. aureus, and E. coli was investigated through various assays measuring ATP levels, Zeta potential, hydroxyl radicals (·OH) generated by light irradiation, and biofilm clearance rate. Additionally, hydrogel's application in treating MRSA-infected wounds in mice under light irradiation demonstrated rapid wound-healing effects and biocompatibility. Overall, HA-GA/CA hydrogel provides a sustainable, antibiotic-free alternative for treating MRSA-infected wounds.

Subacute Toxicity and Pharmacokinetic Evaluation of the Synthetic Cannabinoid 4F-MDMB-BUTINACA in Rats: A Forensic and Toxicological Perspective

Background: 4-MDMB-BUTINACA, a next-generation synthetic cannabinoid, presents significant public health and forensic challenges due to its evolving nature and potential toxicity. Methods: This study evaluates the subacute toxic effects and pharmacokinetics of 4−Fluoro MDMB−BUTINACA (4F-MDMB-BUTINACA) in adult male albino rats, administered orally for seven days at doses of 1 mg/kg, 5 mg/kg, and 15 mg/kg. The hematological, biochemical, and histopathological parameters were assessed and compared to controls. Results: The pharmacokinetics were determined using GC–MS/MS with a positive chemical ionization and granisetron as an internal standard. A histological analysis revealed inflammatory cell aggregation, congestion, hemorrhage, edema, and fibrosis in various tissues, with renal examinations showing tubule degradation, glomerular atrophy, Bowman’s space expansion, edema, and hemorrhage. The liver exhibited cellular infiltration, while cardiac muscle fibers showed myocardial fiber degradation and inflammatory cell aggregation. Biochemical assays indicated significant alterations (p &lt; 0.05) in the serum levels of AST, ALT, ALP, GGT, total protein, albumin, triglycerides, urea, MCHC, MCV, RDW, platelets, neutrophils, eosinophils, and basophils compared to the controls. Conclusions: The validated bioanalytical method revealed rapid absorption of 4F-MDMB-BUTINACA, with a plasma half-life of 2.371 h, a volume of distribution of 2272.85 L, and a plasma clearance rate of 664.241 L/h. In conclusion, 4F-MDMB-BUTINACA is a highly toxic synthetic cannabinoid, particularly affecting the liver, kidneys, and heart.

Effect of microwave-puffed on Auricularia auricula polysaccharide and probiotic fermentation on its biotransformation and quality characteristics during storage period

In this study, probiotics with superior fermentation performance were screened, and the mixed-bacteria fermentation was carried out with Auricularia auricula treated with microwave-puffed process as fermentation substrate, and the changes in nutritional quality under different storage conditions were investigated. The results showed that the acid and bile salt resistance of Lactiplantibacillus plantarum 21,801 and 21,805 reached 95 % and 75 % respectively, and the intestinal adhesion was superior; microwave puffing treatment had the highest retention rate of A. auricula polysaccharides and the lowest loss of polyphenols, and no effect on soluble protein. Mixed bacterial fermentation significantly increased the total polyphenols and total flavonoids of A. auricula (p < 0.05), and the DPPH and ABTS radical scavenging reached 48.31 % and 73.21 % respectively. Furthermore, the viable counts, DPPH radical scavenging, color, and sensory quality of fermented A. auricula remained stable when stored at 4 °C. In contrast, when stored at 25 °C for 7 days, the taste was unfavorable, undesirable odor and spoilage occurred; by 21 days, DPPH clearance rate dropped below 40 % and color changed significantly (△E > 2). In conclusion, the probiotic mixed fermentation and storage conditions had a significant effect on the biometabolic transformation of macromolecules and other substances in A. auricula.

Does tilt-retrograde intrarenal surgery enhance stone clearance and offer better surgical ergonomics in patients with renal calculi? A prospective randomized control study

Introduction: Retrograde intrarenal surgery (RIRS) is the standard treatment for renal calculi. Direct visualization and fragmentation are its major advantages. The variable stone clearance rates and the ergonomic challenges faced by urologists are a few limitations. Table tilt enhances stone clearance and improves surgical ergonomics by facilitating better access to stones and reducing procedural strain. Subjects and Methods: In this prospective study, patients with intrarenal calculi were randomized into standard lithotomy RIRS (S-RIRS) and table-tilted RIRS (T-RIRS) groups. Specified table tilts were suggested for each of the stone locations. The outcomes with regard to stone clearance, operative and lasing time, and ergonomics were studied. Results: About 100 patients were studied, with 50 in each group. The overall operating time and lasing time in the T-RIRS group were less than that in the S-RIRS group (P &lt; 0.001). The complication rates were the same in both groups. Most surgeons felt that the surgical ergonomics was better in the T-RIRS group (P &lt; 0.001). When stone-free status was analyzed, seven patients in the S-RIRS group and one in the T-RIRS group had residual stones. The mean Borg category-ratio 10 (CR-10) scores in the S-RIRS and T-RIRS groups were 4.18 and 2.20, respectively (P &lt; 0.001). Conclusions: This is the first study to document the distinct advantages of T-RIRS and its benefits on surgical ergonomics. T-RIRS resulted in significantly shorter operative and lasing times, particularly for stones in lower calyces. Surgical ergonomics, assessed by the Borg CR-10 scale, were significantly better in the T-RIRS group. T-RIRS should become a standard of care for patients undergoing RIRS.

Probability of early infection extinction depends linearly on the virus clearance rate.

We provide an in silico study of stochastic viral infection extinction from a pharmacokinetical viewpoint. Our work considers a non-specific antiviral drug that increases the virus clearance rate, and we investigate the effect of this drug on early infection extinction. Infection extinction data are generated by a hybrid multiscale framework that applies both continuous and discrete mathematical approaches. The central result of our paper is the observation, analysis and explanation of a linear relationship between the virus clearance rate and the probability of early infection extinction. The derivation behind this simple relationship is given by merging different mathematical toolboxes.

One-Stage Intraoperative ERCP combined with Laparoscopic Cholecystectomy Versus Two-Stage Preoperative ERCP Followed by Laparoscopic Cholecystectomy in the Management of Gallbladder with Common Bile Duct Stones: A Meta-analysis.

Concomitant gallbladder and common bile duct (CBD) stones, known as cholecystocholedocholithiasis, are clinically prevalent. There is currently no consensus on sequential versus simultaneous management approaches, and, if simultaneous, which approach to adopt. This meta-analysis evaluates the safety and efficacy of one-stage laparoscopic cholecystectomy (LC) with intraoperative endoscopic retrograde cholangiopancreatography (ERCP) versus two-stage ERCP followed by LC for treating concomitant gallbladder and CBD stones. A comprehensive literature search was conducted in five databases, PubMed, Embase, Web of Science, VIP, and Wanfang, for all randomized controlled trials (RCTs), cohort and retrospective studies published up to February 2024. Data extraction was performed independently by two reviewers. The primary outcomes were CBD stone clearance rate and postoperative complications morbidity. Secondary outcomes included conversion to other procedures and length of hospital stay. Statistical analyses were performed using R (v.4.3.2) with weighted mean differences and odds ratios (ORs) calculated for continuous and dichotomous variables, respectively, with 95% confidence intervals (CIs). A total of 17 studies involving 2120 patients have been included, with 898 patients receiving single-stage and 1222 patients undergoing two-stage treatment. Of these studies, 9 were RCTs and 8 were retrospective cohort study. The one-stage group demonstrated superior outcomes in terms of CBD stone clearance (OR=2.07, p=0.0004), overall morbidity (OR=0.35, p<0.0001), post-operative pancreatitis (OR=0.49, p=0.006), conversion to other procedures (OR=0.38, p=0.0006), and length of hospital stay (MD=- 2.6456, 95% CI -3.5776; -1.7136, p<0.0001). No significant differences were observed in post-operative cholangitis (OR=0.44, p=0.12), post-operative bleeding (OR=0.76, p=0.47), or bile leakage (OR=1.28, p=0.54). For patients with concomitant gallbladder and CBD stones, the one-stage approach combining ERCP and LC appears safer and more effective, with advantages including higher stone clearance rates, reduced postoperative complications (particularly pancreatitis), shorter hospital stays, fewer residual stones, and decreased need for additional procedures. However, additional high-quality clinical trials are needed to establish the optimal treatment approach for various patient scenarios.

Glucagon Clearance Is Decreased in Chronic Kidney Disease but Preserved in Liver Cirrhosis.

It is not completely clear which organs are responsible for glucagon elimination in humans, and disturbances in the elimination of glucagon could contribute to the hyperglucagonemia observed in chronic liver disease and chronic kidney disease (CKD). Here, we evaluated kinetics and metabolic effects of exogenous glucagon in individuals with stage 4 CKD (n =16), individuals with Child-Pugh A-C cirrhosis (n = 16) and matched control individuals (n = 16), before, during and after a 60-minute glucagon infusion (4 ng/kg/min). Individuals with CKD exhibited a significantly lower mean metabolic clearance rate of glucagon (14.0 [95% CI 12.2;15.7] mL/kg/min) both compared to individuals with cirrhosis (19.7 [18.1;21.3] mL/kg/min, P < 0.001) and to control individuals (20.4 [18.1;22.7] mL/kg/min, P < 0.001). Glucagon half-life was significantly prolonged in the CKD group (7.5 [6.9;8.2] minutes) compared to individuals with cirrhosis (5.7 [5.2;6.3] minutes, P = 0.002) and control individuals (5.7 [5.2;6.3] minutes, P < 0.001). No difference in the effects of exogenous glucagon on plasma glucose, amino acids, or triglycerides was observed between groups. In conclusion, chronic kidney disease, but not liver cirrhosis leads to a significant reduction in glucagon clearance, supporting the kidneys as a primary site for human glucagon elimination.

Relative Uptake of Tomato Carotenoids by In Vitro Intestinal and Prostate Cancer Cells

BackgroundConsumption of tomatoes and tomato carotenoids is associated with a reduced risk of prostate cancer. Prostate tissue accumulates tomato carotenoids, including lycopene, β-carotene, and phytoene. Phytoene accumulation is relatively greater in the prostate than that of lycopene, but the metabolic determinants of tissue carotenoid profiles are poorly understood. ObjectivesThe purpose of this study was to determine if differences in stability, cellular uptake, and clearance of phytoene compared with lycopene or β-carotene by prostate and intestinal cells may explain differences in observed tissue carotenoid profiles. MethodsGene and protein expression for carotenoid metabolism in prostate cell lines were analyzed by qRT-PCR and Western blot, respectively. Uptake, efflux, and clearance of phytoene, lycopene, or β-carotene by prostate cell (LNCaP, RWPE-1, and PC-3) and absorptive enterocyte (Caco-2) cultures were compared. The effect of scavenger receptor class B member 1 (SCARB1) inhibition on carotenoid uptake by LNCaP, RWPE-1, and Caco-2 cells was tested. ResultsSCARB1 was expressed across prostate cell lines. Lycopene, phytoene, and β-carotene uptakes were similar in LNCaP and PC-3 cells, whereas RWPE-1 cells absorbed a smaller portion of the phytoene dose than lycopene or β-carotene doses. The clearance rates of carotenoids from LNCaP cells did not differ. Intestinal cell uptake of phytoene was greatest, followed by β-carotene and lycopene. SR-BI inhibitor treatment did not significantly reduce the uptake or efflux of carotenoids by LNCaP or Caco-2 cells at the dose concentration provided. ConclusionsOverall, this study suggests that greater bioavailability at the point of the intestine and greater stability of phytoene are determinants of the relative enrichment of phytoene in prostate tissue.

Insulin Regulation of Lysine and α-Aminoadipic Acid Dynamics and Amino Metabolites in Women With and Without Insulin Resistance.

Insulin is a key regulator of amino acids (AAs) metabolism. Many plasma AAs, including lysine and its metabolite, α-aminoadipic acid (α-AA), a predictor for developing diabetes, are elevated in insulin resistance. In 18 insulin-resistant (IR) over-weight women with polycystic ovary syndrome compared to 12 lean controls, high physiological insulin during a euglycemic clamp failed to normalize many elevated AA metabolites, including branched-chain and aromatic AA, alphaamino- butyric acid, and lysine, but normalized α-AA. To understand the underpinning of differential responses of lysine and its metabolic product α-AA to high physiological insulin in IR compared to controls, we developed a kinetic model utilizing [α-15N1] lysine and [13C1] α-AA as tracers and measured the two tracers simultaneously in α-AA by innovative mass spectrometry. High insulin increased lysine conversion to α-AA in IR and controls but failed to normalize plasma lysine concentrations in IR due to a decrease in lysine metabolic clearance rate (MCR). In contrast, despite higher conversion rates of lysine to α-AA by high insulin, α-AA concentration decreased in IR because of the sustained greater MCR of α-AA. The abnormal AAs and metabolites, even while on high physiological insulin, could potentially explain many functional derangements in IR.

Predictive analysis of lactate clearance on the prognosis of patients with large burns

Aims: To examine burn shock monitoring and the connection between lactate clearance and shock prognosis in individuals with severe burns. Materials and methods: This retrospective analysis comprised 100 patients with significant burns treated in our hospital between August 2017 and August 2021. The patients were split into two groups based on whether they survived or not: 50 cases each in the survival and death groups. Both groups had their blood lactate levels, partial pressure of oxygen, and other relevant indices tested. Analysis was done on the correlation between lactate level, lactate clearance, and death as well as the association between lactate clearance and prognosis at each time and point. Results: The lactate clearance rates at 6 h, 12 h, 24 h and 24 h in the survival group were greater than those in the death group, and the differences were significant (p &lt; 0.05). The lactate clearance rates at each time point were compared at a cut-off of 20%, and patients with 6 h and 12 h blood lactate clearance rates ≥20.0% had lower prognostic morbidity and mortality rates than those &lt;20.0%, with a significant difference (p &lt; 0.05). Conclusion: Lactate clearance is directly correlated with the prognosis of patients with severe burns, and survivors also have a high clearance rate. As a result, in patients with severe burns, lactate clearance monitoring during the shock phase can improve prognostic prediction and enable early treatment plan modification based on outcomes.

Chronic Viral Infections and Hepatic Oncogenesis

Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) are major contrib¬utors to chronic liver disease and hepatocellular carcinoma (HCC) worldwide. Discovered in the 1960s and 1980s, these viruses are associated with significant global health burdens. HBV, a member of the He¬padnaviridae family, is a partially double-stranded DNA virus responsible for chronic liver infections that can lead to HCC. Despite the success of HBV vaccination, challenges such as vaccine escape mutants and non-responders persist. HCV, a member of the Flaviviridae family and a positive-sense single-stranded RNA virus, affects millions globally. While direct-acting antivirals (DAAs) can achieve high rates of viral clearance, vaccine development remains hindered by genetic diversity and immune evasion. HDV, the smallest known human virus, relies on HBV for its propagation. It exacerbates liver disease and increases HCC risk, particularly in co-infected individuals. HDV does not integrate into the host genome, suggesting indirect mechanisms of carcinogenesis, potentially through interactions with HBV. Addressing these chal¬lenges requires enhanced vaccination strategies, improved antiviral therapies, and continued research to understand the complex interplay between these viruses and liver cancer development.