No genetic causal association between iron status and pulmonary artery hypertension: Insights from a two-sample Mendelian randomization.

To explore the genetic causal association between pulmonary artery hypertension (PAH) and iron status through Mendelian randomization (MR), we conducted MR analysis using publicly available genome-wide association study (GWAS) summary data. Five indicators related to iron status (serum iron, ferritin, total iron binding capacity (TIBC), soluble transferrin receptor (sTfR), and transferrin saturation) served as exposures, while PAH was the outcome. The genetic causal association between these iron status indicators and PAH was assessed using the inverse variance weighted (IVW) method. Cochran's Q statistic was employed to evaluate heterogeneity. We assessed pleiotropy using MR-Egger regression and MR-Presso test. Additionally, we validated our results using the Weighted median, Simple mode, and Weighted mode methods. Based on the IVW method, we found no causal association between iron status (serum iron, ferritin, TIBC, sTfR, and transferrin saturation) and PAH (p ß > 0.05). The Weighted median, Simple mode, and Weighted mode methods showed no potential genetic causal association (p ß > 0.05 in the three analyses). Additionally, no heterogeneity or horizontal pleiotropy was detected in any of the analyses. Our results show that there are no genetic causal association between iron status and PAH.

ROS-responsive thermosensitive polypeptide hydrogels for localized drug delivery and improved tumor chemoimmunotherapy.

In this study, we developed a ROS-responsive thermosensitive poly(ethylene glycol)-polypeptide hydrogel loaded with a chemotherapeutic drug, doxorubicin (Dox), an antiviral imidazoquinoline, resiquimod (R848), and antibody targeting programmed cell death protein 1 (aPD-1) for local chemoimmunotherapy. The hydrogel demonstrated controllable degradation and sustained drug release behavior according to the concentration of ROS in vitro. Following intratumoral injection into mice bearing B16F10 melanoma, the Dox/R848/aPD-1 co-loaded hydrogel effectively inhibited tumor growth, prolonged animal survival time and promoted anti-tumor immune responses with low systemic toxicity. In the postoperative model, the Dox/R848/aPD-1 co-loaded hydrogel exhibited enhanced tumor recurrence prevention and long-term immune memory effects. Thus, the hydrogel-based local chemoimmunotherapy system demonstrates potential for effective anti-tumor treatment and suppression of tumor recurrence.

Daurisoline inhibits proliferation, induces apoptosis, and enhances TRAIL sensitivity of breast cancer cells by upregulating DR5.

Daurisoline (DS) is an isoquinoline alkaloid that exerts anticancer activities in various cancer cells. However, the underlying mechanisms through which DS affects the survival of breast cancer cells remain poorly understood. Therefore, the present study was undertaken to investigate the potential anticancer effect of DS on breast cancer cells and reveal the mechanism underlying the enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis by DS. Cell counting kit-8 (CCK-8) and 5-ethynyl-2-deoxyuridine (EdU) assay were used to evaluate the ability of cell proliferation. Flow cytometry was selected to examine the cell cycle distribution. TUNEL assay was used to detect the cell apoptosis. The protein expression was measured by Western blot analysis. DS was found to reduce the cell viability and suppress the proliferation of MCF-7 and MDA-MB-231 cells by causing G1 phase cell cycle arrest. DS could trigger apoptosis by promoting the cleavage of caspase-8 and PARP. The phosphorylation of ERK, JNK, and p38MAPK was upregulated clearly following DS treatment. Notably, SP600125 (JNK inhibitor) pretreatment significantly abrogated DS-induced PARP cleavage. DS inactivated Akt/mTOR and Wnt/ß-catenin signaling pathway and upregulated the expression of ER stress-related proteins. Additionally, DS amplified TRAIL-caused viability reduction and apoptosis in breast cancer cells. Mechanismly, DS upregulated the protein level of DR4 and DR5, and knockdown of DR5 attenuated the cotreatment-induced cleavage of PARP. Inhibition of JNK could block DS-induced upregulation of DR5. This study provides valuable insights into the mechanisms of DS inhibiting cell proliferation, triggering apoptosis, and enhancing TRAIL sensitivity of breast cancer cells.

Inhibition of acyl-CoA binding protein (ACBP) by means of a GABAARγ2-derived peptide.

Acyl-CoA binding protein (ACBP) encoded by diazepam binding inhibitor (DBI) is an extracellular inhibitor of autophagy acting on the gamma-aminobutyric acid A receptor (GABAAR) γ2 subunit (GABAARγ2). Here, we show that lipoanabolic diets cause an upregulation of GABAARγ2 protein in liver hepatocytes but not in other major organs. ACBP/DBI inhibition by systemically injected antibodies has been demonstrated to mediate anorexigenic and organ-protective, autophagy-dependent effects. Here, we set out to develop a new strategy for developing ACBP/DBI antagonists. For this, we built a molecular model of the interaction of ACBP/DBI with peptides derived from GABAARγ2. We then validated the interaction between recombinant and native ACBP/DBI protein and a GABAARγ2-derived eicosapeptide (but not its F77I mutant) by pull down experiments or surface plasmon resonance. The GABAARγ2-derived eicosapeptide inhibited the metabolic activation of hepatocytes by recombinant ACBP/DBI protein in vitro. Moreover, the GABAARγ2-derived eicosapeptide (but not its F77I-mutated control) blocked appetite stimulation by recombinant ACBP/DBI in vivo, induced autophagy in the liver, and protected mice against the hepatotoxin concanavalin A. We conclude that peptidomimetics disrupting the interaction between ACBP/DBI and GABAARγ2 might be used as ACBP/DBI antagonists. This strategy might lead to the future development of clinically relevant small molecules of the ACBP/DBI system.

Sub-Nanometer Mono-Layered Metal-Organic Frameworks Nanosheets for Simulated Flue Gas Photoreduction.

The dilemma between the thickness and accessible active site triggers the design of porous crystalline materials with mono-layered structure for advanced photo-catalysis applications. Here, a kind of sub-nanometer mono-layered nanosheets (Co-MOF MNSs) through the exfoliation of specifically designed Co3 cluster-based metal-organic frameworks (MOFs) is reported. The sub-nanometer thickness and inherent light-sensitivity endow Co-MOF MNSs with fully exposed Janus Co3 sites that can selectively photo-reduce CO2 into formic acid under simulated flue gas. Notably, the production efficiency of formic acid by Co-MOF MNSs (0.85 mmol g-1 h-1) is ≈13 times higher than that of the bulk counterpart (0.065 mmol g-1 h-1) under a simulated flue gas atmosphere, which is the highest in reported works up to date. Theoretical calculations prove that the exposed Janus Co3 sites with simultaneously available sites possess higher activity when compared with single Co site, validating the importance of mono-layered nanosheet morphology. These results may facilitate the development of functional nanosheet materials for CO2 photo-reduction in potential flue gas treatment.

CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to prevent DNA hypermethylation and ensure normal transcription in growing oocytes.

The DNA methylation is gradually acquired during oogenesis, a process sustained by successful follicle development. However, the functional roles of methyl-CpG-binding protein 2 (MeCP2), an epigenetic regulator displaying specifical binding with methylated DNA, remains unknown in oogenesis. In this study, we found MeCP2 protein was highly expressed in primordial and primary follicle, but was almost undetectable in secondary follicles. However, in aged ovary, MeCP2 protein is significantly increased in both oocyte and granulosa cells. Overexpression of MeCP2 in growing oocyte caused transcription dysregulation, DNA hypermethylation, and genome instability, ultimately leading to follicle growth arrest and apoptosis. MeCP2 is targeted by DCAF13, a substrate recognition adaptor of the Cullin 4-RING (CRL4) E3 ligase, and polyubiquitinated for degradation in both cells and oocytes. Dcaf13-null oocyte exhibited an accumulation of MeCP2 protein, and the partial rescue of follicle growth arrest induced by Dcaf13 deletion was observed following MeCP2 knockdown. The RNA-seq results revealed that large amounts of genes were regulated by the DCAF13-MeCP2 axis in growing oocytes. Our study demonstrated that CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to ensure normal DNA methylome and transcription in growing oocytes. Moreover, in aged ovarian follicles, deceased DCAF13 and DDB1 protein were observed, indicating a potential novel mechanism that regulates ovary aging.

The Risk of Cervical Cancer in Women Among Han, Bai, Dai and Hani Ethnic Minorities in Yunnan Province of China.

Background: Research on the risk factors for cervical cancer in Yunnan Province's four characteristic ethnic groups (Han, Bai, Dai, and Hani) is lacking. Objective: To study the risk factors of cervical cancer in four ethnic women in Yunnan Province, and to provide evidence for its prevention. Methods: The cervical cancer patients of Han, Bai, Dai and Hani ethnic groups in Yunnan Province who were first diagnosed in the Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center) from January 2011 to December 2020 were selected as the research objects. The 1:1 matched case-control study method was used, and single factor and conditional logistic regression were used for statistical analysis. Results: HPV types 16, 18 and 58 are mostly related with cervical cancer, the younger the age of the last pregnancy, the more times of pregnancy, childbirth and abortion, especially the younger the first marriage age of Bai and Dai, are the risk factors of cervical cancer; the infection of genital tract bacteria, mycoplasma and chlamydia is closely related to the incidence of cervical cancer in four ethnicities. Multifactorial analysis showed that demographic characteristics and environment/behavior were not included in the influencing factors of cervical cancer; among Han, Bai, Dai and Hani ethnic minorities, contraception (OR=0.29, OR=0.03, OR=0.09, OR=0.16, P<0.05) was positive factor, HPV infection (OR=64.77, OR=128.71, OR=71.89, OR=40.07, P<0.01) was a causative factor of cervical cancer. Conclusion: Risk of high parity with cervical cancer could be due to a complex interplay of factors, it is very important to formulate prevention strategies and measures in line with the cervical cancer of Han, Bai, Dai and Hani ethnic groups women in Yunnan Province.

Injectable, Adhesive Albumin Nanoparticle-Incorporated Hydrogel for Sustained Localized Drug Delivery and Efficient Tumor Treatment.

Injectable hydrogels are receiving increasing attention as local depots for sustained anticancer drug delivery. However, most current hydrogel-based carriers lack tissue-adhesive ability, a property that is important for the immobilization of drug-loaded systems at tumor sites to increase local drug concentration. In this study, we developed a paclitaxel (PTX)-loaded injectable hydrogel with firm tissue adhesion for localized tumor therapy. PTX-loaded bovine serum albumin (BSA) nanoparticles (PTX@BN) were prepared, and the drug-loaded hydrogel was then fabricated by cross-linking PTX@BN with o-phthalaldehyde (OPA)-terminated 4-armed poly(ethylene glycol) (4aPEG-OPA) via a condensation reaction between OPA and the amines in BSA. The hydrogel showed firm adhesion to various organs and tumor tissues ex vivo due to the condensation reaction of unreacted OPA groups and amines in the tissues. The PTX-loaded nanocomposite hydrogels sustained PTX release over 30 days following the Korsmeyer-Peppas model and exhibited notable inhibition activities against mouse C26 colon and 4T1 breast cancer cells in vitro. Following peritumoral injection into mice with C26 or 4T1 tumors, the PTX@BN-loaded hydrogel significantly enhanced the antitumor efficacy and prolonged animal survival time compared to free PTX solutions with low systemic toxicity. Therefore, the adhesive, PTX-loaded nanocomposite hydrogels have the potential for efficient localized tumor therapy.

From Multiple Myeloma to Acute Myeloid Leukemia: A Case Report of a 61-year-old Woman after 8 Years of Chemotherapy and Immunotherapy.

BACKGROUND: As the second most prevalent hematologic malignancy, multiple myeloma (MM) affects plasma cells and is characterized by chromosomal abnormalities, particularly involving the immunoglobulin heavy chain switch region. MM represents a biologically and clinically heterogeneous hematological malignancy that serves as a clonal evolution model, exhibiting clonal heterogeneity throughout all stages from monoclonal gammopathy undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to MM. Although significant progress has been made in the treatment of MM, leading to improved patient outcomes, concerns are arising regarding disease relapse due to the presence and selection of pre-existing resistant clones or selective pressure during therapy. CASE PRESENTATION: We present a case of multiple myeloma (MM) in a female patient, who underwent an 8-year course of treatment, including chemotherapy, immunomodulators, hematopoietic stem cell transplantation, CD38 monoclonal antibody, and chimeric antigen receptor T-cell (CAR-T), and was recently diagnosed with concurrent progressive MM and acute myeloid leukemia (AML). This patient has witnessed the evolution of MM treatment paradigms. CONCLUSION: In this course, disease relapses occurred twice, one of which was manifested by a light chain escape (LCE). Moreover, through the course of the disease in this patient, we review the process of clonal evolution that may be relevant.

Effect of pre-admission "quasi-collective" education on health education for patients with ophthalmic day surgery.

BACKGROUND: Day surgery is a new surgical model in which patients complete the admission, surgery, and discharge on the same day. OBJECTIVE: The present study aimed to explore the effect of pre-admission "quasi-collective" health education for patients with ophthalmic day surgery. METHODS: For this study, a total of 200 patients undergoing ophthalmic day surgery from February 2019 to December 2019 were enrolled as the research subjects. The patients were divided randomly into the observation group and the control group, with 100 cases in each group. For the control group, conventional health education was conducted after admission. On the day of admission, the admission education and peri-operative health education were performed. For the observation group, pre-admission health education was provided to the patients, and detailed education on the admission instructions, pre-operative precautions, and simulation of the intra-operative process were given by the medical staff. On the day of admission, the understanding of the education was evaluated, and any weaknesses in the health education were addressed. The anxiety status, method of handwashing, method of administering the drug to the eye, preoperative preparations, intra-operative training, preoperative medication, diet guidance, and postoperative care were compared between the two groups of patients. RESULTS: Before discharge, there were significant differences in the anxiety scores, impact, and satisfaction of health education between the two groups of patients, all of which were statistically significant (P< 0.05). CONCLUSION: The pre-admission "quasi-collective" health education for patients undergoing day surgery in ophthalmology was better than conventional health education.

The EZH2-H3K27me3 axis modulates aberrant transcription and apoptosis in cyclophosphamide-induced ovarian granulosa cell injury.

Chemotherapy-induced ovarian damage and infertility are significant concerns for women of childbearing age with cancer; however, the underlying mechanisms are still not fully understood. Our study has revealed a close association between epigenetic regulation and cyclophosphamide (CTX)-induced ovarian damage. Specifically, CTX and its active metabolite 4-hydroperoxy cyclophosphamide (4-HC) were found to increase the apoptosis of granulosa cells (GCs) by reducing EZH2 and H3K27me3 levels, both in vivo and in vitro. Furthermore, RNA-seq and CUT&Tag analyses revealed that the loss of H3K27me3 peaks on promoters led to the overactivation of genes associated with transcriptional regulation and apoptosis, indicating that stable H3K27me3 status could help to provide a safeguard against CTX-induced ovarian damage. Administration of the H3K27me3-demethylase inhibitor, GSK-J4, prior to CTX treatment could partially mitigate GC apoptosis by reversing the reduction of H3K27me3 and the aberrant upregulation of specific genes involved in transcriptional regulation and apoptosis. GSK-J4 could thus potentially be a protective agent for female fertility when undergoing chemotherapy. The results provide new insights into the mechanisms for chemotherapy injury and future clinical interventions for fertility preservation.

Screening and early diagnosis of chronic obstructive pulmonary disease: a population study.

BACKGROUND AND OBJECTIVE: Although chronic obstructive pulmonary disease (COPD) is a common disease leading to further morbidity and significant mortality, there is still limited data on screening for COPD. The purpose of this study was to establish an early chronic obstructive pulmonary disease (COPD) screening system for the community and hospitals in Nanshan District in Shenzhen City, to improve the rate of early diagnosis and treatment of patients with COPD. METHODS: We identified individuals at high risk of COPD using a questionnaire survey and analyzed the relevant influencing factors in the early stages of COPD in high-risk groups. RESULTS: We collected a total of 5,000 COPD screening questionnaires, and a total of 449 patients were diagnosed with COPD by pulmonary function examination. The prevalence of COPD in people aged 20 and above in Nanshan District of Shenzhen City was estimated to be 8.98%, with a base of 5000. The severity classification as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria was as follows: GOLD I accounted for 34.74%; GOLD II accounted for 37.64%; GOLD III accounted for 16.04%; and GOLD IV accounted for 11.58%. Common features of early COPD that we identified were: (1) patients were mainly males, accounting for 68.0%; (2) COPD was common among people aged 50-59 years, comprising 31%; (3) 96.0% of patients often had severe respiratory symptoms and had frequent coughs when they did not have a cold; (4) 57.2% of patients experienced shortness of breath when walking quickly on level ground or climbing gentle slopes; (5) 72.6% of patients had a family history of bronchial asthma and COPD. Multivariate ordinal multi-classification logistic regression showed that gender, age, shortness of breath, and the use of firewood, grass, and coal stoves were all influencing factors in pulmonary function grading. CONCLUSION: A screening questionnaire combined with a pulmonary function test should be adopted as a COPD screening strategy to be implemented at the primary level as a public health priority in China to reduce the incidence, disability, and mortality from COPD.

Optimal Rituximab Monotherapy in Splenic Marginal Zone Lymphoma (SMZL): A Case Report and Brief Review.

INTRODUCTION: Splenic marginal zone Lymphoma (SMZL) is a rare, chronic B lymphocyte proliferative disease. Generally, SMZL is accompanied by circulating atypical villous lymphocytes, known as SMZL with villous lymphocytes. Rituximab is a chimeric monoclonal antibody to CD20; recent but limited studies have confirmed its effectiveness in treating SMZL. Given the low incidence and selection of treatment, statistical comparisons of rituximab monotherapy with other available treatment options with the full range of data from previous clinical studies remain sparse. Here, we report a case of SMZL with villous lymphocytes treated by rituximab monotherapy, which is especially infrequently reported. CASE REPORT: A 63-year-old Chinese female was presented to the hospital with complaints of splenomegaly and pain in the spleen area. Immunohistochemistry analysis was positive for IGH, IGK, and IGL clonal rearrangement. Villous lymphocytes were found in peripheral blood and bone marrow, along with further immunotyping results. The case was considered as SMZL with villous lymphocytes. Based on the SMZLSG prognosis assessment, we applied rituximab monotherapy. After eight cycles of rituximab treatment, the patient's condition improved markedly, with blood constituent and size of the spleen returning to normal levels, achieving complete response, with no significant side effect observed. DISCUSSION: The patient provides a typical SMZL with villous lymphocytes case treated with rituximab monotherapy. Currently, the main treatment options include splenectomy and rituximab. After synthesizing a series of current views, we put forward our opinion about the selection of therapy for SMZL patients in order to gain maximum benefits for patients in need of treatment. CONCLUSION: Our analysis found no statistically significant difference between rituximab monotherapy and rituximab combined with chemotherapy, while rituximab treatments resulted in better therapeutic effects than chemotherapy. Rituximab monotherapy has favorable therapeutic effects and minor adverse effects (AEs) in treating SMZL.

Biotransformed bear bile powder ameliorates diet-induced nonalcoholic steatohepatitis in mice through modulating arginine biosynthesis via FXR/PXR-PI3K-AKT-NOS3 axis.

NASH is a highly prevalent metabolic syndrome that has no specific approved agents up to now. BBBP, which mainly contains bile acids, possess various pharmacological properties and some bile acids are available for NASH treatment. Herein, the therapeutic effects and underlying mechanisms of BBBP against NASH were systemically evaluated. In this study, mice received an HFHS diet over a 20-week period to induce NASH with or without BBBP intervention were used to evaluate the effect and underlying mechanisms of BBBP against NASH. Our results demonstrated that BBBP attenuated hepatic steatosis, reduced body weight gain and lipid concentrations, and improved sensitivity to insulin and tolerance to glucose in mice fed an HFHS diet. Metabolomics and transcriptomic analysis revealed that BBBP suppressed the arginine biosynthesis by up-regulating NOS3 expression and the PI3K-Akt signaling pathway was also regulated by BBBP, as indicated by 55 DEGs. Bioinformatic analysis predicted the regulatory effect of the FXR/PXR-PI3K-AKT-NOS3 axis on arginine biosynthesis-related metabolites. These results were further confirmed by the significantly increased mRNA and protein levels of NOS3, PI3K (Pik3r2), and AKT1. And the increased levels of arginine biosynthesis related-metabolites, such as urea, aspartic acid, glutamic acid, citrulline, arginine, and ornithine, were confirmed accurately based on targeted metabolomics analysis. Together, our study uncoded the complicated mechanisms of anti-NASH activities of BBBP, and provided critical evidence inspiring the discovery of innovative therapies based on BBBP in the treatment of NASH.

Association between gut microbiota and endometriosis: a two-sample Mendelian randomization study.

Background: Recent studies have shown that an imbalance in gut microbiota (GM) may not always be associated with endometriosis (EMS). To investigate this further, we conducted a two-sample Mendelian randomization study. Methods: MR analysis was performed on genome-wide association study (GWAS) summary statistics of GM and EMS. Specifically, the MiBioGen microbiota GWAS (N = 18,340) was used as exposure. The FinnGen study GWAS (8,288 EMS cases and 68,969 controls) was used as outcome. We primarily used the inverse variance weighted (IVW) method to analyze the correlation and conducted a sensitivity analysis to verify its reliability. Results: (1) MR analysis: The results of the IVW method confirmed that a total of 8 GM taxa were related to the risk of EMS. Class-Melainabacteria (p = 0.036), family-Ruminococcaceae (p = 0.037), and genus-Eubacteriumruminantium (p = 0.015) had a protective effect on EMS, whereas order-Bacillales (p = 0.046), family-Prevotellaceae (p = 0.027), genus-Anaerotruncus (p = 0.025), genus-Olsenella (p = 0.036) and genus-RuminococcaceaeUCG002 (p = 0.035) could increase the risk of EMS. (2) Sensitivity analysis: Cochrane's Q test (p > 0.05), MR-Egger intercept method (p > 0.05), and leave-one-out method confirmed the robustness of MR results. Conclusion: This study performed a MR analysis on two large national databases and identified the association between 8 GM taxa and EMS. These taxa could potentially be utilized for indirectly diagnosing EMS and could lead to novel perspectives in research regarding the pathogenesis, diagnosis, and treatment of EMS.

Hypervirulent Klebsiella pneumoniae detection methods: a minireview.

Hypervirulent Klebsiella pneumoniae (hvKp), characterized by high virulence and epidemic potential, has become a global public health challenge. Therefore, improving the identification of hvKp and enabling earlier and faster detection in the community to support subsequent effective treatment and prevention of hvKp are an urgent issue. To address these issues, a number of assays have emerged, such as String test, Galleria mellonella infection test, PCR, isothermal exponential amplification, and so on. In this paper, we have collected articles on the detection methods of hvKp and conducted a retrospective review based on two aspects: traditional detection technology and biomarker-based detection technology. We summarize the advantages and limitations of these detection methods and discuss the challenges as well as future directions, hoping to provide new insights and references for the rapid detection of hvKp in the future. The aim of this study is to focus on the research papers related to Hypervirulent Klebsiella pneumoniae involving the period from 2012 to 2022. We conducted searches using the keywords "Hypervirulent Klebsiella pneumoniae, biomarkers, detection techniques" on ScienceDirect and Google Scholar. Additionally, we also searched on PubMed, using MeSH terms associated with the keywords (such as Klebsiella pneumoniae, Klebsiella Infections, Virulence, Biomarkers, diagnosis, etc.).

Exploring the option of student-run free health clinics to support people living with type 2 diabetes mellitus: a scoping review.

Diabetes is a major cause of morbidity and premature mortality worldwide and now identified as a 'public health emergency' and a 'modern and preventable pandemic'. Indigenous populations are disproportionately affected by type 2 diabetes mellitus (T2DM) and associated complications. Student run free clinics (SRFCs) may play an important role in the prevention and management of T2DM. The primary objective of this scoping review was to investigate the opportunity for curriculum enhancement through the role and effectiveness of SRFCs in managing T2DM. Electronic databases such as PubMed, CINAHL, Science Direct and Cochrane Library were searched from inception to October 2022. Identified records from database literature searches were imported into Covidence®. Two independent reviewers screened and extracted the data. The research team collectively created a data charting table/form to standardize data collection. A narrative synthesis was used to summarize the evidence. Six studies (total of 319 participants) that met our eligibility criteria were included in this scoping review. SRFCs can provide high-quality diabetic care, especially for uninsured and economically weaker population. Preliminary evidence further indicate that shared medical appointments and telehealth may facilitate diabetic care especially during times where access to care may be difficult (e.g., COVID lockdown). However, no study included in the review explored or discussed family centred/culturally sensitive interventions. Hence, such interventions should be made part of the curriculum in the future with students in SRFCs exposed to such an approach.

Significant Effects of Renal Function on Mycophenolic Acid Total Clearance in Pediatric Kidney Transplant Recipients with Population Pharmacokinetic Modeling.

BACKGROUND AND OBJECTIVES: Mycophenolic acid (MPA) is an immunosuppressant commonly prescribed in pediatric kidney transplantation to prevent graft rejection. Large variabilities in MPA plasma exposures have been observed in this population, which could result in severe adverse effects. The majority of the MPA pharmacokinetic data have been reported in adult populations, whereas information in pediatric patients is still very limited. The objective of this study was to establish a novel, nonlinear mixed-effects model for MPA and investigate the clinical variables affecting MPA population pharmacokinetics in pediatric kidney transplant recipients. METHODS: Data were collected retrospectively from pediatric kidney transplant patients (≤ 18 years when MPA concentrations were initially collected; on oral administration of mycophenolate mofetil) in Calgary, Alberta, Canada. Nonlinear mixed-effect modeling was conducted using stochastic approximation expectation-maximization in Monolix 2021R2 (Lixoft SAS, France) to determine population pharmacokinetic estimates, interindividual variabilities, and interoccasional variabilities. Covariate models were constructed using the Model Proposal function in Monolix in conjunction with a systematic stepwise inclusion/elimination protocol. The best model was selected based on objective function values, relative standard errors, goodness-of-fit plots, prediction-corrected visual predictive checks, and numerical predictive checks. RESULTS: A total of 50 pediatric kidney transplant patients (25 female) with 219 MPA plasma concentration-time profiles were included. The average age (± standard deviation) and posttransplant time for the sample population were 12.8 ± 4.8 years and 762 ± 1160 days, respectively. The majority of study subjects (i.e., > 85% based on all occasions) were co-administered tacrolimus. A two-compartment, first-order absorption with lag time and linear elimination structural model with lognormal distributed proportional residual errors best described the MPA concentration-time data. The absorption rate constant (2.52 h-1 or 0.042 min-1), lag time (0.166 h or 9.96 min), volumes of distributions of the central (22.8 L) and peripheral (216 L) compartments, and intercompartment clearance (17.6 L h-1 or 0.293 L min-1) were consistent with literature values; whereas total MPA clearance (0.72 L h-1 or 0.012 L min-1) was relatively reduced, likely due to the general lack of cyclosporine interactions and the stabilized graft functions from significantly longer posttransplant time in our sample population. Of the clinical variables tested, only estimated glomerular filtration rate (eGFR) was identified a significant covariate affecting total MPA clearance with a positive, exponential relationship. The final population pharmacokinetic model was successfully evaluated/validated using a variety of complementary methods. CONCLUSION: We have successfully constructed and validated a novel population pharmacokinetic model of MPA in pediatric kidney transplant patients. A positive, nonlinear relationship between eGFR and total MPA clearance identified in our model is likely attributed to multiple concurrent mechanisms, which warrant further systematic investigations.

Preparation of DES lignin-chitosan aerogel and its adsorption performance for dyes, catechin and epicatechin.

Herein, DES lignin was obtained by pretreatment of grapevine with a deep eutectic solvent (ChCl-LA). A novel chitosan-DES lignin composite aerogel material (CS-LIG aerogel) was prepared to adsorb methylene blue (MB), Congo red (CR), catechin (C), and epicatechin (EC). The CS-LIG aerogel was systematically characterized by modern technological instruments. It was demonstrated that the DES lignin was successfully incorporated and had an important effect on the morphological structure and adsorption of dyes and natural products in the aerogel. The adsorption kinetic models for both adsorbed CR and MB are pseudo-second-order models. Adsorption isotherms followed Langmuir for the adsorption of CR and Freundlich for the adsorption of MB. The π-π interaction and hydrogen bonding of DES lignin aromatic groups in CS-LIG aerogels were responsible for the adsorption of C and EC with 86.42 % and 90.85 % removal rates, respectively. This study opens a new avenue for the high-value utilization of DES lignin and the preparation of chitosan-based composites for the adsorption of dyes and purification of natural products.

Eggshell translucency in late-phase laying hens and its effect on egg quality and physiological indicators.

Eggshell translucency severely affects external egg quality, and variations in the eggshell or eggshell membrane are considered the structural basis of the trait. Research has shown that 1.85% additional mixed fatty acids in the diet would greatly decrease the occurrence of eggshell translucency. Only a few studies have examined the phenotypic regularity of eggshell translucency with the increasing age of hens. Therefore, two strains, 1139 Rhode Island Red-White (RIR-White) and 836 Dwarf Layer-White (DWL-White), were used, and from each strain, 30 hens each that consecutively laid translucent or opaque eggs at 67 wks of age were selected. Subsequently, eggshell translucency, internal quality and external quality of eggs, and total cholesterol, albumin, calcium binding protein and other physiological indicators related to lipid, lipoprotein, and calcium metabolisms at the 75th, 79th, and 83rd wks of age in the late phase of the laying cycle were determined. Results: (1) In terms of flocks, for both strains, the translucency scores of the translucent groups were significantly higher than those of the opaque groups (P < 0.05); in terms of individuals, 81.1% RIR-White and 82.8% DWL-White hens consecutively laid eggs of the same or similar translucency, indicating the stability of the trait with increasing hen age; (2) In RIR-White, the eggshell strength of the translucent group at 75 weeks was significantly higher than that of the opaque group (P < 0.05); in DWL-White, the eggshell membrane thickness of the translucent group at the 75th and 83rd weeks was significantly lower than that of the opaque group (P < 0.05); (3) Compared to the opaque groups, the translucent groups had lower total cholesterol content in both RIR-White and DWL-White, lower albumin content in DWL-White at the 79th weeks (P < 0.05), and higher calcium-binding protein (CALB1) in RIR-White at the 83rd weeks (P < 0.05). In summary, this study illustrates the stability of eggshell translucency in late-phase laying hens and provides a reference of physiological indicators for exploring the formation of translucent eggs.