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1.
Environ Geochem Health ; 46(8): 270, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954122

ABSTRACT

Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.


Subject(s)
Cesium Radioisotopes , Mining , Soil Pollutants, Radioactive , Risk Assessment , China , Soil Pollutants, Radioactive/analysis , Cesium Radioisotopes/analysis , Humans , Strontium Radioisotopes/analysis , Cesium/analysis , Cities , Soil/chemistry , Monte Carlo Method , Radiation Monitoring
2.
Clin Kidney J ; 17(3): sfae037, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38455522

ABSTRACT

Background: Disruptions in gene expression associated with the glomerular basement membrane (GBM) could precipitate glomerular dysfunction. Nevertheless, a comprehensive understanding of the characterization of GBM components within pediatric glomerular diseases and their potential association with glomerular function necessitates further systematic investigation. Methods: We conducted a systematic analysis focusing on the pathological transformations and molecular attributes of key constituents within the GBM, specifically Collagen IV α3α4α5, Laminin α5ß2γ1, and Integrin α3ß1, across prevalent pediatric glomerular diseases. Results: We observed upregulation of linear expression levels of COL4A3/4/5 and Laminin 5α proteins, along with a partial reduction in the linear structural expression of Podocin in idiopathic nephrotic syndrome (INS), encompassing minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), but showing a reduction in IgA nephropathy (IgAN), IgA vasculitis nephritis (IgAVN) and lupus nephritis (LN). Furthermore, our study revealed reductions in Laminin ß2γ1 and Integrin α3ß1 in both primary and secondary childhood glomerular diseases. Conclusion: In INS, notably MCD and FSGS, there is a notable increase in the linear expression levels of COL4A3/4/5 and Laminin 5α proteins. In contrast, in IgAN, IgAVN, and LN, there is a consistent reduction in the expression of these markers. Furthermore, the persistent reduction of Laminin ß2γ1 and Integrin α3ß1 in both primary and secondary childhood glomerular diseases suggests a shared characteristic of structural alterations within the GBM across these conditions.

3.
Eur Urol Focus ; 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38195354

ABSTRACT

BACKGROUND: Accurate primary staging of renal cancer with conventional imaging is challenging. Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) may serve to improve the accuracy of renal cancer staging. OBJECTIVE: To determine clinicopathological and management differences for primary renal cancer staged with PSMA PET/CT in comparison to conventional imaging. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study of PSMA PET/CT scans performed for primary staging of renal cancer and incidental renal lesions at three sites in Brisbane, Australia between June 2015 and June 2020. Clinical characteristics, imaging, and histopathology were reviewed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinicopathological and management differences according to staging modality (PSMA PET/CT, conventional imaging) were assessed. Descriptive statistics were used to report demographics and clinical parameters. Nonparametric methods were used for statistical analysis. Fisher's exact test was used for comparison of small-cell size categorical variables. RESULTS AND LIMITATIONS: From a total of 120 PSMA PET/CT scans, 61 were included (52 staging, 9 incidental) for predominantly males (74%) with a mean age of 65.1 yr (standard deviation 12.0). Most primary lesions (40/51) were clear-cell renal cell carcinoma (ccRCC; 98% PSMA-avid), eight were non-ccRCC (75% PSMA-avid), and three were non-RCC (oncocytoma; 67% PSMA-avid). PSMA PET identified a greater number of presumed metastatic lesions than conventional imaging (195 vs 160). A management change was observed for 32% of patients (20% major, 12% minor). Limitations include the retrospective design and selection bias, lack of blinding to PSMA reporting, and the use of different PSMA radiotracers. CONCLUSIONS: PSMA PET/CT detected more metastases than conventional imaging and most renal cancers were PSMA-avid, resulting in a management change for one-third of the patients. PATIENT SUMMARY: We looked at a newer type of scan called PSMA PET/CT for first staging of kidney cancer. We found that this detects more metastasis and helps in decisions on changes in treatment for some patients. This type of imaging is a useful addition to conventional scans in tricky cases and may help in better selection of suitable treatments, but more studies are required.

4.
BMC Med ; 21(1): 461, 2023 11 23.
Article in English | MEDLINE | ID: mdl-37996906

ABSTRACT

BACKGROUND: High-power short-duration (HPSD) ablation strategy has emerged as a popular approach for treating atrial fibrillation (AF), with shorter ablation time. The utilized Smart Touch Surround Flow (STSF) catheter, with 56 holes around the electrode, lowers electrode-tissue temperature and thrombus risk. Thus, we conducted this prospective, randomized study to investigate if the HPSD strategy with STSF catheter in AF ablation procedures reduces the silent cerebral embolism (SCE) risk compared to the conventional approach with the Smart Touch (ST) catheter. METHODS: From June 2020 to September 2021, 100 AF patients were randomized 1:1 to the HPSD group using the STSF catheter (power set at 50 W) or the conventional group using the ST catheter (power set at 30 to 35 W). Pulmonary vein isolation was performed in all patients, with additional lesions at operator's discretion. High-resolution cerebral diffusion-weighted magnetic resonance imaging (hDWI) with slice thickness of 1 mm was performed before and 24-72 h after ablation. The incidence of new periprocedural SCE was defined as the primary outcome. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test. RESULTS: All enrolled AF patients (median age 63, 60% male, 59% paroxysmal AF) underwent successful ablation. Post-procedural hDWI identified 106 lesions in 42 enrolled patients (42%), with 55 lesions in 22 patients (44%) in the HPSD group and 51 lesions in 20 patients (40%) in the conventional group (p = 0.685). No significant differences were observed between two groups regarding the average number of lesions (p = 0.751), maximum lesion diameter (p = 0.405), and total lesion volume per patient (p = 0.669). Persistent AF and CHA2DS2-VASc score were identified as SCE determinants during AF ablation procedure by multivariable regression analysis. No significant differences in MoCA scores were observed between patients with SCE and those without, both immediately post-procedure (p = 0.572) and at the 3-month follow-up (p = 0.743). CONCLUSIONS: Involving a small sample size of 100 AF patients, this study reveals a similar incidence of SCE in AF ablation procedures, comparing the HPSD strategy using the STSF catheter to the conventional approach with the ST catheter. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04408716. AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.


Subject(s)
Ablation Techniques , Atrial Fibrillation , Catheter Ablation , Intracranial Embolism , Humans , Male , Middle Aged , Female , Atrial Fibrillation/epidemiology , Atrial Fibrillation/surgery , Atrial Fibrillation/complications , Prospective Studies , Intracranial Embolism/diagnostic imaging , Intracranial Embolism/epidemiology , Intracranial Embolism/prevention & control , Incidence , Ablation Techniques/adverse effects , Treatment Outcome , Catheter Ablation/adverse effects , Catheter Ablation/methods , Recurrence
5.
Bull Environ Contam Toxicol ; 111(5): 59, 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37903975

ABSTRACT

Vanadium (V) contamination in soil has received extensive attention due to its high toxicity. The change of mobility and bioavailability of soil V and the effects of V on the soil microbial community were studied under conditions of different V(V) spiking concentrations (0, 100, 250, and 500 mg kg-1) and aging time (1, 7, 14, 30, 45, and 60 d). The results showed that soil V mainly presented as V(IV) of all treatments throughout the aging process. At high levels of V(V) loading (250 and 500 mg kg-1), soil V(V) showed a downward trend, while bioavailable V did not change significantly within 60 d's aging. The analysis of soil bacterial community showed that Proteobacteria was the most abundant phylum in all soils, and the dominant genera Sphingomonas and Lysobacter can well adapt to high concentration V. These microorganisms exhibited great potential for bioremediation of V-contaminated soils.


Subject(s)
Microbiota , Soil Pollutants , Vanadium/toxicity , Vanadium/analysis , Soil/chemistry , Soil Pollutants/toxicity , Soil Pollutants/analysis , High-Throughput Nucleotide Sequencing , Soil Microbiology
6.
Cardiovasc Diabetol ; 22(1): 293, 2023 10 27.
Article in English | MEDLINE | ID: mdl-37891556

ABSTRACT

OBJECTIVE: Diabetic kidney disease (DKD) is characterized by the abnormal deposition of oxidized low-density lipoprotein (ox-LDL), which contributes to podocyte damage. Klotho, an aging suppressor that plays a critical role in protecting podocytes in DKD, is mainly expressed in kidney tubular epithelium and secreted in the blood. However, it has not been established whether Klotho can alleviate podocyte injury by inhibiting renal ox-LDL deposition, and the potential molecular mechanisms require further investigation. METHODS: We conducted a comprehensive analysis of serum and kidney biopsy samples obtained from patients diagnosed with DKD. Additionally, to explore the underlying mechanism of Klotho in the deposition of ox-LDL in the kidneys, we employed a mouse model of DKD with the Klotho genotype induced by streptozotocin (STZ). Furthermore, we conducted meticulous in vitro experiments on podocytes to gain further insights into the specific role of Klotho in the deposition of ox-LDL within the kidney. RESULTS: Our groundbreaking study unveiled the remarkable ability of the soluble form of Klotho to effectively inhibit high glucose-induced ox-LDL deposition in podocytes affected by DKD. Subsequent investigations elucidated that Klotho achieved this inhibition by reducing the expression of the insulin/insulin-like growth factor 1 receptor (IGF-1R), consequently leading to a decrease in the expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) and an enhancement of mitochondrial function. Ultimately, this series of events culminated in a significant reduction in the expression of the oxidized low-density lipoprotein receptor (OLR1), thereby resulting in a notable decrease in renal ox-LDL deposition in DKD. CONCLUSION: Our findings suggested that Klotho had the potential to mitigate podocyte injury and reduced high glucose-induced ox-LDL deposition in glomerulus by modulating the IGF-1R/RAC1/OLR1 signaling. These results provided valuable insights that could inform the development of novel strategies for diagnosing and treating DKD.


Subject(s)
Diabetic Nephropathies , Klotho Proteins , Podocytes , Animals , Humans , Mice , Diabetes Mellitus/metabolism , Diabetic Nephropathies/etiology , Diabetic Nephropathies/prevention & control , Glucose/metabolism , Kidney/metabolism , Lipoproteins, LDL/metabolism , Podocytes/metabolism , Podocytes/pathology , rac1 GTP-Binding Protein/metabolism , rac1 GTP-Binding Protein/pharmacology , Scavenger Receptors, Class E/metabolism , Klotho Proteins/metabolism , Signal Transduction
7.
Eur J Nucl Med Mol Imaging ; 51(1): 295-303, 2023 12.
Article in English | MEDLINE | ID: mdl-37592084

ABSTRACT

PURPOSE: There is an emerging role of the use of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in renal cell carcinoma. Herein, we report our experience in use of PSMA PET in recurrent or metastatic renal cell carcinoma (RCC). METHODS: A retrospective analysis of all patients who underwent PSMA PET for suspected recurrent or de-novo metastatic RCC between 2015 and 2020 at three institutions was performed. The primary outcome was change in management (intensification or de-intensification) following PSMA PET scan. Secondary outcomes included histopathological correlation of PSMA avid sites, comparison of sites of disease on PSMA PET to diagnostic CT and time to systemic treatment.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Prostatic Neoplasms , Male , Humans , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/therapy , Carcinoma, Renal Cell/pathology , Prostate/pathology , Retrospective Studies , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/therapy , Kidney Neoplasms/pathology , Positron Emission Tomography Computed Tomography/methods , Positron-Emission Tomography , Prostate-Specific Antigen/metabolism , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/therapy , Prostatic Neoplasms/pathology , Gallium Radioisotopes
8.
Int J Dev Disabil ; 69(4): 568-577, 2023.
Article in English | MEDLINE | ID: mdl-37346250

ABSTRACT

Limited efforts have been made in middle- and low-income countries to raise public awareness of autism spectrum disorders (ASD) over the past ten years. We report data from a general population survey exploring the relationship between awareness, knowledge, and attitudes regarding autism in Malaysia. A questionnaire consisting of items related to awareness, knowledge, and attitudes regarding ASD was distributed. The scores of knowledge of ASD and attitude towards ASD were 6.87 (SD = 4.17; with a total possible score of 12) and 6.39 (SD = 2.77; with a total possible score of 9), respectively, indicating that, on average, the participants had moderate levels of knowledge and attitude. Structural equation modeling showed that improving awareness and knowledge about ASD will enhance more positive attitudes towards ASD. Efforts should be geared towards disseminating information about ASD, in order to increase acceptance of the disorder.

9.
Chemosphere ; 336: 139222, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37343642

ABSTRACT

Hitherto, the effect of vanadium on higher plant growth remains an open topic. Therefore, nontargeted metabolomic and RNA-Seq profiling were implemented to unravel the possible alteration in alfalfa seedlings subjected to 0.1 mg L-1 (B group) and 0.5 mg L-1 (C group) pentavalent vanadium [(V(V)] versus control (A group) in this study. Results revealed that vanadium exposure significantly altered some pivotal transcripts and metabolites. The number of differentially expressed genes (DEGs) markedly up- and down-regulated was 21 and 23 in B_vs_A, 27 and 33 in C_vs_A, and 24 and 43 in C_vs_B, respectively. The number for significantly up- and down-regulated differential metabolites was 17 and 15 in B_vs_A, 43 and 20 in C_vs_A, and 24 and 16 in C_vs_B, respectively. Metabolomics and transcriptomics co-analysis characterized three significantly enriched metabolic pathways in C_vs_A comparing group, viz., α-linolenic acid metabolism, flavonoid biosynthesis, and phenylpropanoid biosynthesis, from which some differentially expressed genes and differential metabolites participated. The metabolite of traumatic acid in α-linolenic acid metabolism and apigenin in flavonoid biosynthesis were markedly upregulated, while phenylalanine in phenylpropanoid biosynthesis was remarkably downregulated. The genes of allene oxide cyclase (AOC) and acetyl-CoA acyltransferase (fadA) in α-linolenic acid metabolism, and chalcone synthase (CHS), flavonoid 3'-monooxygenase (CYP75B1), and flavonol synthase (FLS) in flavonoid biosynthesis, and caffeoyl-CoA O-methyltransferase (CCoAOMT) in phenylpropanoid biosynthesis were significantly downregulated. While shikimate O-hydroxycinnamoyltransferase (HCT) in flavanoid and phenylpropanoid biosynthesis were conspicuously upregulated. Briefly, vanadium exposure induces a readjustment yielding in metabolite and the correlative synthetic precursors (transcripts/unigenes) in some branched metabolic pathways. This study provides a practical and in-depth perspective from transcriptomics and metabolomics in investigating the effects conferred by vanadium on plant growth and development.


Subject(s)
Medicago sativa , Transcriptome , Medicago sativa/genetics , Seedlings/genetics , Vanadium/toxicity , alpha-Linolenic Acid , Gene Expression Profiling , Flavonoids , Metabolomics , Gene Expression Regulation, Plant
10.
Sci Total Environ ; 894: 165068, 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37355119

ABSTRACT

Due to the long-term open stockpile, the release of vanadium (V) from V-containing tailings will cause continuous V pollution in the mining area. Previous studies on the concentration and speciation of V primarily focused on surface tailings at a regional scale. However, the mobilization and redistribution of V within the tailing profile during the mineral transformation of tailings remain unclear. Herein, a series of concentrations of V(V) (0-200 mg L-1) solutions were added to the vanadium­titanium magnetite tailings at different depths separately to simulate the redistribution of dissolved V released from tailings in the solid phase of tailings. During the 56-day incubation, the concentrations of aqueous V in the surface tailings were significantly lower than those in the deep tailings under the same level of V(V) treatment, indicating that the shallow tailings had a stronger immobilization capacity for V than the deep tailings. Morphological analysis and color overlays of the elements demonstrated that most of V was immobilized into the tailings and adsorbed or precipitated by the Fe (hydr)oxides in the tailings in 200 mg L-1 V(V) treatment. This portion of V mainly occurred in acid-soluble and reducible fractions in the tailings after a 7-day incubation, accounting for >71.7 % of the total V. However, these two factions of V with high bioavailability were gradually mineralized over time and transferred to residual V, which is difficult to move and has low bioavailability. Mineral phase analysis revealed that additional V(V) favored the formation of melanovanadite (Ca2V8O20·10H2O) and chromium vanadium oxide (Cr2V4O13) in the tailings. This study reveals that the dissolved V influenced the fractionation and redistribution of solid-phase V during tailing weathering, improving the understanding of the geochemical processes of V in tailing profiles and providing important guidance for the management of V-containing tailings.

11.
Environ Geochem Health ; 45(7): 5343-5356, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37138141

ABSTRACT

Fluorine (F) is not an essential element for vegetation and excessive F can be phytotoxic to plant growth, which can cause fluorosis to human beings by ingesting F-contaminated plant. Although there have been some studies focusing on the toxicity of F to plants and the retarding effect of Ca to F-stress plant, atmospheric F contamination to vegetation and the role of the application of foliar Ca are scantly reported. This study investigated several biochemical parameters to evaluate F toxicity under both F-exposure (root and leaf F-exposure) and the remedial effects of foliar Ca. The results showed that F concentration of pakchoi leaves was correlated with exogenous F level positively in both foliar and root F-exposure series, and F concentration of pakchoi roots was only changed under root F-exposure treatments. Ca supplement (0.5 g/L and 1 g/L) significantly decreased plant F concentration. Both F-exposure treatments caused lipid peroxidation in plants and exogenous Ca alleviated the toxicity of F to pakchoi. Meanwhile, chlorophyll-a concentration was decreased by foliar and root F, whereas chlorophyll-b concentration was only affected by foliar F, and chlorophyll-a concentration could be elevated by exogenous Ca but chlorophyll-b could not. It was concluded that both atmospheric and root F can impair pakchoi growth and disturb photosynthesis, and foliar Ca showed an ameliorative effect to F toxicity of pakchoi through alleviating chlorophyll decomposition, increasing protein content and alleviating oxidative damage.


Subject(s)
Chlorophyll , Fluorine , Humans , Fluorine/toxicity , Chlorophyll/metabolism , Photosynthesis , Oxidative Stress , Plant Leaves/metabolism , Plant Roots/metabolism
12.
Environ Pollut ; 330: 121743, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37149251

ABSTRACT

Vanadium-titanium (V-Ti) magnetite tailings contain toxic metals that could potentially pollute the surrounding environment. However, the impact of beneficiation agents, an integral part of mining activities, on the dynamics of V and the microbial community composition in tailings remains unclear. To fill this knowledge gap, we compared the physicochemical properties and microbial community structure of V-Ti magnetite tailings under different environmental conditions, including illumination, temperature, and residual beneficiation agents (salicylhydroxamic acid, sodium isobutyl xanthate, and benzyl arsonic acid) during a 28-day reaction. The results revealed that beneficiation agents exacerbated the acidification of the tailings and the release of V, among which benzyl arsonic acid had the greatest impact. The concentration of soluble V in the leachate of tailings with benzyl arsonic acid was 6.4 times higher than that with deionized water. Moreover, illumination, high temperatures, and beneficiation agents contributed to the reduction of V in V-containing tailings. High-throughput sequencing revealed that Thiobacillus and Limnohabitans adapted to the tailings environment. Proteobacteria was the most diverse phylum, and the relative abundance was 85.0%-99.1%. Desulfovibrio, Thiobacillus, and Limnohabitans survived in the V-Ti magnetite tailings with residual beneficiation agents. These microorganisms could contribute to the development of bioremediation technologies. The main factors affecting the diversity and composition of bacteria in the tailings were Fe, Mn, V, SO42-, total nitrogen, and pH of the tailings. Illumination inhibited microbial community abundance, while the high temperature (39.5 °C) stimulated microbial community abundance. Overall, this study strengthens the understanding of the geochemical cycling of V in tailings influenced by residual beneficiation agents and the application of inherent microbial techniques in the remediation of tailing-affected environments.


Subject(s)
Soil Pollutants , Vanadium , Vanadium/analysis , Titanium/analysis , Temperature , Ferrosoferric Oxide , Lighting , Bacteria , Soil Pollutants/analysis
13.
J Hazard Mater ; 451: 131077, 2023 06 05.
Article in English | MEDLINE | ID: mdl-36871469

ABSTRACT

The microbially- and chemically-mediated redox process is critical in controlling the fate of vanadium (V) in tailing environment. Although the microbial reduction of V has been widely studied, the coupled biotic reduction mediated by beneficiation reagents and the underlying mechanism remain unclear. Herein, the reduction and redistribution of V in V-containing tailings and Fe/Mn oxide aggregates mediated by Shewanella oneidensis MR-1 and oxalic acid were explored. The dissolution of Fe-(hydr)oxides by oxalic acid promoted the microbe-mediated V release from solid-phase. After 48-day of reaction, the dissolved V concentrations in the bio-oxalic acid treatment reached maximum values of 1.72 ± 0.36 mg L-1 and 0.42 ± 0.15 mg L-1 in the tailing system and the aggregate system, respectively, significantly higher than those in control (0.63 ± 0.14 mg L-1 and 0.08 ± 0.02 mg L-1). As the electron donor, oxalic acid enhanced the electron transfer process of S. oneidensis MR-1 for V(V) reduction. The mineralogical characterization of final products indicates that S. oneidensis MR-1 and oxalic acid promoted solid-state conversion from V2O5 to NaV6O15. Collectively, this study demonstrates that microbe-mediated V release and redistribution in solid-phase were promoted by oxalic acid, suggesting that the role of organic agents for the V biogeochemical cycle in natural systems deserves greater attention.


Subject(s)
Shewanella , Vanadium , Ferric Compounds/chemistry , Oxalic Acid , Oxidation-Reduction , Oxides
14.
Pathology ; 55(4): 498-507, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36774238

ABSTRACT

The glomerular basement membrane (GBM) consists of laminins, collagen IV, nidogens, and fibronectin and is essential for filtration barrier integrity in the kidney. Critically, structural and functional abnormalities in the GBM are involved in chronic kidney disease (CKD) occurrence and development. Fibronectin is encoded by FN1 and is essential for podocyte-podocyte and podocyte-matrix interactions. However, disrupted or disordered fibronectin occurs in many kidney diseases. In this study, we identified a novel mutation (c.3415G>A) in FN1 that causes glomerular fibronectin-specific deposition in a gain-of-function manner, that may be associated with thin basement membrane nephropathy (TBMN) and expand the spectrum of phenotypes seen in glomerulopathy with fibronectin deposits (GFND). Our studies confirmed this variant increased fibronectin's ability to bind to integrin, thereby maintaining podocyte adhesion. Also, we hypothesised that TBMN arose as the fibronectin variant exhibited a decreased capacity to bind COL4A3/4. Our study is the first to identify and link this novel pathogenic mutation (c.3415G>A) in FN1 to GFND as well as TBMN, which may broaden the phenotype and mutation spectrums of the FN1 gene. We believe our data will positively impact genetic counselling and prenatal diagnostics for GFND with TBMN and other associated conditions that may be commonly benign conditions in humans, and may not require proteinuria-lowering treatments or renal biopsy.


Subject(s)
Collagen Type IV , Kidney Diseases , Humans , Collagen Type IV/genetics , Fibronectins/genetics , Kidney/pathology , Kidney Diseases/genetics , Kidney Diseases/pathology
15.
J Autism Dev Disord ; 53(2): 795-807, 2023 Feb.
Article in English | MEDLINE | ID: mdl-34247302

ABSTRACT

Sibling relationships remain understudied in typically developing adolescents who have siblings with autism spectrum disorder (ASD). This study explored the lived experiences and perceptions of adolescents who have a brother or a sister with a diagnosis of ASD using semi-structured interviews. Using thematic analysis, the participants reported having difficulties communicating with their siblings. Feeling a mixture of emotions was common when interacting with their siblings with ASD and emotional self-regulation was a typical coping strategy utilized by these adolescents. Despite the challenges, having a sibling with ASD led to closer relationships between the siblings. These findings offer insights into these adolescents' needs and how they may be best supported, informing the practice of speech-language pathology and other health professions.


Subject(s)
Autism Spectrum Disorder , Siblings , Male , Humans , Child , Adolescent , Siblings/psychology , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/psychology , Malaysia , Sibling Relations , Emotions
16.
Mol Genet Genomic Med ; 11(1): e2090, 2023 01.
Article in English | MEDLINE | ID: mdl-36369907

ABSTRACT

BACKGROUND: Hereditary tyrosinemia type 1 (HT1) is a rare inherited metabolic disease characterized by severe liver and renal dysfunction. Early identification in affected children is critical for improved treatment options and prognosis. METHODS: In this study, we identified novel compound heterozygous mutations (NM_000137: c.657delC (p.K220Rfs*12) and c.607G>A (p.A203T)) in the fumarylacetoacetate hydrolase (FAH) gene in a family. We also characterized the clinical phenotype of the proband and verified the pathogenic effects of the mutations. Furthermore, we explored the pathogenic mechanism of renal injury through renal biopsy pathology and cell-based in vitro assays. Our study aims to verify the association between novel fumarylacetoacetate hydrolase (FAH) variants and HT1, confirm the pathogenic effects of the mutations and explore the pathogenic mechanism of renal injury. RESULTS: We showed these FAH mutations were inherited in an autosomal recessive manner and resulted in abnormal FAH protein expression and dysfunction, leading to fumarylacetoacetate (FAA) accumulation. The proband also showed apparent renal injury, including glomerular filtration barrier dysfunction and abnormal tubular protein reabsorption. CONCLUSIONS: These observations may provide deeper insights on disease pathogenesis and identify potential therapeutic approaches for HT1 from a genetic perspective. Similarly, we hope to provide valuable information for genetic counseling and prenatal diagnostics.


Subject(s)
Tyrosinemias , Humans , Tyrosinemias/genetics , Mutation , Kidney/metabolism , Liver/pathology
17.
Disabil Rehabil ; 45(24): 4035-4047, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36541160

ABSTRACT

OBJECTIVE: To examine the relationship between affiliate stigma, stress, and perceived quality of life among parents of children with cerebral palsy (CP). METHOD: Surveys (Study 1) and semi-structured interviews (Study 2) were used to collect data. Thirty-eight respondents completed the Affiliate Stigma Scale (ASS), Caregiver Burden Inventory (CBI), and Care-related Quality of Life (CarerQol) scales (GMFCS). Eleven respondents took part in semi-structured interviews, which were then thematically evaluated. RESULTS: Parents did not feel stigmatized because they had a child with CP. However, parents needed some form of short-term relief from caregiving. After controlling for demographics, high stress respondents experienced high affiliate stigma whereas low stress respondents had better quality of life. Although the respondents with less stigma had a better quality of life, this effect was moderate. Three major themes emerged from the interviews. CONCLUSION: Counseling, support groups, and helper services should be offered to parents. Also, healthcare professionals participating in CP rehabilitation, community-based rehabilitation, and health institutions should be educated on how to better help parents of children with CP.


There is a need in Malaysia to offer counseling, support groups, and assistance programs for parents of children with cerebral palsy.Healthcare professionals, who offer rehabilitation services to children with cerebral palsy, need greater awareness of the needs of families and caregivers and should be educated about how to best support them.There should be greater recognition of the importance of respite and relief from caregiving among Malaysian parents of children with cerebral palsy.


Subject(s)
Cerebral Palsy , Quality of Life , Child , Humans , Quality of Life/psychology , Cerebral Palsy/rehabilitation , Malaysia , Caregivers/psychology , Parents/psychology
18.
Clin Genitourin Cancer ; 21(1): 55-62, 2023 02.
Article in English | MEDLINE | ID: mdl-36411184

ABSTRACT

BACKGROUND: In patients with renal cell carcinoma (RCC) on cabozantinib, venous thromboembolism (VTE) management remains challenging due to limited safety data regarding direct oral anticoagulants (DOACs) use in conjunction with cabozantinib. We investigated the safety of cabozantinib with different anticoagulants in patients with RCC. METHODS: In this retrospective multicenter study (9 sites), patients with advanced RCC were allocated into 4 groups: (1) cabozantinib without anticoagulation, cabozantinib with concomitant use of (2) DOACs, (3) low molecular weight heparin (LMWH), or (4) warfarin. The primary safety endpoint was the proportion of major bleeding events (defined per International Society on Thrombosis and Hemostasis criteria). The primary efficacy endpoint was the proportion of new/recurrent VTE while anticoagulated. RESULTS: Between 2016 and 2020, 298 patients with RCC received cabozantinib (no anticoagulant = 178, LMWH = 41, DOAC = 64, and warfarin = 15). Most patients had clear cell histology (78.5%) and IMDC intermediate/poor disease (78.2%). Cabozantinib was first, second, or ≥ third line in 21.8%, 31.9%, 43.3% of patients, respectively. Overall, there was no difference in major bleeding events between the no anticoagulant, LMWH, and DOAC groups (P = .088). Rate of new/recurrent VTE was similar among anticoagulant groups. Patients with a VTE had a statistically significantly worse survival than without a VTE (HR 1.48 [CI 95% 1.05-2.08, P = .02]). CONCLUSION: This real-world cohort provides first data on bleeding and thrombosis complications in patients with RCC treated with cabozantinib with or without concurrent anticoagulation. DOACs appear safe for VTE treatment for patients with RCC on cabozantinib, but optimized anticoagulation management, including individualized risk-benefit discussion, remains important in clinical practice.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neoplasms , Venous Thromboembolism , Humans , Anticoagulants/adverse effects , Warfarin/adverse effects , Heparin, Low-Molecular-Weight/adverse effects , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/complications , Venous Thromboembolism/drug therapy , Neoplasms/chemically induced , Neoplasms/complications , Neoplasms/drug therapy , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Hemorrhage/complications , Kidney Neoplasms/drug therapy , Kidney Neoplasms/complications , Administration, Oral
19.
Eur Urol ; 83(2): 145-151, 2023 02.
Article in English | MEDLINE | ID: mdl-36272943

ABSTRACT

BACKGROUND: The role of upfront cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of immune checkpoint inhibitors is unclear. OBJECTIVE: To evaluate the relationship between upfront CN and clinical outcomes in the setting of mRCC treated with immune checkpoint inhibitors or targeted therapy. DESIGN, SETTING, AND PARTICIPANTS: Using the International Metastatic RCC Database Consortium, we retrospectively identified patients diagnosed with de novo mRCC treated with immune checkpoint inhibitors or targeted therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) was compared between the two groups using the Kaplan-Meier method and multivariable Cox regressions adjusting for known prognostic factors. RESULTS AND LIMITATIONS: We identified a total of 4639 eligible patients with mRCC. Among the 4202 patients treated with targeted therapy and 437 patients treated with immune checkpoint inhibitors, 2326 (55%) and 234 (54%) patients received upfront CN prior to treatment start. In multivariable analyses, CN was associated with significantly better OS in both the immune checkpoint inhibitor-treated (hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.41-0.90, p = 0.013) and the targeted therapy treatment (HR: 0.72; 95% CI, 0.67-0.78, p < 0.001) group. There was no difference in OS benefit of CN between the immune checkpoint inhibitor and targeted therapy treatment groups (interaction p = 0.6). Limitations include selection of patients from large academic centers and the retrospective nature of the study. CONCLUSIONS: Upfront CN is associated with a significant OS benefit in selected patients treated by either immune checkpoint inhibitors or targeted therapy, and still has a role in selected patients in the era of immune checkpoint inhibitors. PATIENT SUMMARY: Before effective systemic therapies were available for metastatic kidney cancer, surgical removal of the primary (kidney) tumor was the mainstay of treatment. The role of removing the primary tumor has recently been called into question given that more effective systemic therapies have become available. In this study, we find that removal of the primary kidney tumor still has a benefit for selected patients treated with highly effective modern systemic therapies, including targeted therapies and immune checkpoint inhibitors.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/drug therapy , Kidney Neoplasms/surgery , Immune Checkpoint Inhibitors/therapeutic use , Retrospective Studies , Cytoreduction Surgical Procedures/methods , Nephrectomy/methods
20.
Environ Pollut ; 316(Pt 1): 120590, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36336187

ABSTRACT

The stockpiling of vanadium-containing tailings allows vanadium to migrate into the surrounding area, resulting in toxic metal contamination. By using the vanadium-bearing iron/manganese (Fe/Mn) oxide agglomerates as the simulated tailings, the feasibility of photo-induced reduction of vanadium by oxalic acid was investigated. Batch effects of the available light and the reducing agents on agglomerates were investigated. Results showed that oxalic acid (5 mmol L-1) can convert V(V) to V(IV) and convert Fe(III) released from the Fe/Mn oxide agglomerates to Fe(II) under both light and dark conditions. After 45 d of reaction in the dark, oxalic acid converted 33.54% Fe(III) and 100% V(V) in the leachate into Fe(II) and V(IV). The Fenton reaction occurred by light irradiation significantly increased the redox potential in the solution, and also caused V(IV) to be oxidized. Overall, oxalic acid can rapidly reduce V(V) to V(IV), but sunlight may have an inhibitory effect on the reduction reaction. Present study can deepen the understanding of the mechanism for valence transformation of elements in minerals by sunlight, and can help in implementing tailings treatment and environmental remediation by using oxalic acid and avoiding light.


Subject(s)
Iron , Vanadium , Manganese , Ferric Compounds , Oxalic Acid , Oxides , Oxidation-Reduction , Ferrous Compounds
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