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1.
Nanoscale ; 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36723054

RESUMO

The emerging two-dimensional (2D) semiconductors hold a promising prospect for sustaining Moore's law benefitting from the excellent device electrostatics with narrowed channel length. Here, the performance limits of sub-5 nm InSe and In2SSe metal-oxide-semiconductor field-effect transistors (MOSFETs) are explored by ab initio quantum transport simulations. The van der Waals heterostructures prepared by assembling different two-dimensional materials have emerged as a new design of artificial materials with promising physical properties. In this study, device performance was investigated utilizing InSe/In2SSe van der Waals heterostructure as the channel material. Both the monolayer and heterostructure devices can scale Moore's law down to 5 nm. A heterostructure transistor exhibits a higher on-state current and faster switching speed compared with isolated monolayer transistors. This work proves that the sub-5 nm InSe/In2SSe MOSFET can satisfy both the low power and high-performance requirements for the international technology roadmap for semiconductors in the next decade and can provide a feasible approach for enhancing device performance.

2.
J Mater Chem B ; 11(4): 905-913, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36598076

RESUMO

High performance hydrogels have essential applications in many fields such as tissue engineering and soft robot. Herein, we develop an impact resistant hydrogel composed of bicontinuous structures of polymer-hard phase and polymer-soft phase. This unique bicontinuous phase structure is formed by modulating various hydrogen bonding interactions. During loading, the polymer-hard phase is broken accompanied by the dissociation of hydrogen bonds to dissipate energy, while the polymer-soft phase distributes the load to avoid stress concentration, thus enabling the bicontinuous hydrogel to achieve excellent strength and toughness simultaneously. Furthermore, the fracture of hierarchical energy dissipation structures efficiently reduces impact strength and increases buffer time. Owing to the synergy of the bicontinuous phase structure and hierarchical energy dissipation, the resulting bicontinuous hydrogel remains intact even if it undergoes impact at a strain rate of ∼13 000 s-1. Based on these findings, it is expected that the bicontinuous hydrogel has a potential application in the field of articular cartilage repair.

3.
BMC Endocr Disord ; 23(1): 2, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597099

RESUMO

BACKGROUND: Iron-overloaded patients are recognized as presenting an increased risk of osteoporosis. However, studies on the correlation between osteoporosis and organ iron overload are controversial or scarce. The aim of this study is to assess bone mineral density (BMD) and trabecular bone score (TBS) in correlation with hepatic and pancreatic iron overload. METHODS: Forty-one patients diagnosed with hemoglobinopathies, were studied. BMDs of the lumbar spine (LS), femoral neck (FN), and total hip (TH) were analyzed by Dual-energy X-ray absorptiometry (DXA) scan. LS bone quality was derived from each spine DXA examination using the TBS analysis. Hepatic and pancreatic iron overload were obtained with a multi-echo gradient echo T2* technique. RESULTS: Abnormal microarchitecture and abnormal bone mass were observed in 19/41 (46.3%) and 9/41 (22.0%) patients, respectively. For 26 males, BMD, T-score and Z-score of LS were significantly lower among subjects with moderate-severe hepatic iron-overload than their counterparts, as it is between no- and pancreatic iron-overload groups. For 15 females, patients with moderate-severe hepatic iron-overload had significantly lower BMD and T-score of FN and TH, and patients with pancreatic iron-overload had significantly lower BMD, T-score of FN, and lower BMD, T-score and Z-score of TH than their counterparts. Moreover, pancreatic T2*-value was positively correlated with BMD and T-score at all analyzed sites and Z-score at TH. CONCLUSION: These data showed lower bone mass in patients with organ iron overload, particularly for LS in males, FN and TH in females. TBS may well represent a complementary tool for the evaluation of bone quality and the risk of fracture in iron-overloaded patients.


Assuntos
Sobrecarga de Ferro , Osteoporose , Fraturas por Osteoporose , Masculino , Feminino , Humanos , Densidade Óssea , Osso Esponjoso , Osteoporose/etiologia , Osteoporose/complicações , Absorciometria de Fóton/efeitos adversos , Absorciometria de Fóton/métodos , Colo do Fêmur , Vértebras Lombares/diagnóstico por imagem , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/diagnóstico por imagem , Imageamento por Ressonância Magnética , Ferro
4.
Immunol Cell Biol ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36630591

RESUMO

There is growing evidence that programmed death ligand-1 (PD-L1) has exciting therapeutic efficacy in hematological malignancy and partial solid tumors. However, many patients still face failure with the treatment of immune checkpoint blockade because of PD-L1 expression regulation during transcription and post-transcription processes, including N6-methyladenosine (m6A). Similar to the epigenetic regulation in DNA and histones, recent research has revealed the essential regulation of m6A modification in RNA nuclear export, metabolism and translation. Recent studies have shown that m6A-induced PD-L1 expression emerges as one of the main reasons for the immunological alteration in this process and contributes to the failure of T cell-induced anti-tumor immunity. The results of preclinical studies demonstrate the potential of m6A-targeted therapy in combination with immune checkpoint blockade. Meanwhile, the comprehensive expression of m6A-related genes has provided the possibility to indicate the prognosis and optimize the treatment for patients of various cancer types. In this review, we focus on the m6A modification in PD-L1 mRNA as well as the regulation of PD-L1 expression in cancer cells and summarize its clinical value in anti-PD-L1 cancer immune therapy.

5.
Sci Adv ; 9(4): eabp8943, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36696496

RESUMO

Exceptional points (EPs), at which more than one eigenvalue and eigenvector coalesce, are unique spectral features of non-Hermiticity (NH) systems. They exist widely in open systems with complex energy spectra. We experimentally demonstrate the appearance of paired EPs in a periodical-driven degenerate optical cavity along the synthetic orbital angular momentum dimension with a tunable parameter. The complex-energy band structures and the key features of EPs, i.e., their bulk Fermi arcs, parity-time symmetry breaking transition, energy swapping, and half-integer band windings, are directly observed by detecting the wavefront angle-resolved transmission spectrum. Our results demonstrate the flexibility of using the photonic synthetic dimensions to implement NH systems beyond their geometric dimension and EP-based sensing.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36700551

RESUMO

Near-infrared (NIR) small-molecule acceptors that absorb at wavelengths of up to 1000 nm are attractive for applications in organic photodetectors (OPDs) and biometrics. In this study, we incorporated IEICO-4F as the third component for PffBT4T-2OD:PC71BM-based OPDs to provide an efficient NIR response while greatly suppressing the leakage current at reverse bias. By varying the blend ratio and thickness (250-600 nm), we obtained an NIR OPD displaying an ultralow dark-current density (JD = 2.62 nA cm-2), ultrahigh detectivity [D* = 7.2 × 1012 Jones (850 nm)], high sensitivity, and photoresponsivity covering the region from the ultraviolet to the NIR. We used tapping-mode atomic force microscopy, optical microscopy, grazing-incidence wide-angle X-ray scattering, and contact angle measurements to investigate the effect of IEICO-4F on the performance of the ternary OPDs. The low compatibility of PffBT4T-2OD and IEICO-4F, originating from weak intermolecular interactions, allowed us to manipulate the degree of phase separation between the donor and acceptor in the ternary blends, leading to an optimized blend morphology featuring efficient charge separation, transport, and collection. To demonstrate its applicability, we integrated our OPD with two light-emitting diodes and used the system for precisely calculated transmissive pulse oximetry.

7.
Comput Struct Biotechnol J ; 21: 769-779, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36698972

RESUMO

Understanding genes and their underlying mechanisms is critical in deciphering how antimicrobial-resistant (AMR) bacteria withstand detrimental effects of antibiotic drugs. At the same time the genes related to AMR phenotypes may also serve as biomarkers for predicting whether a microbial strain is resistant to certain antibiotic drugs. We developed a Cross-Validated Feature Selection (CVFS) approach for robustly selecting the most parsimonious gene sets for predicting AMR activities from bacterial pan-genomes. The core idea behind the CVFS approach is interrogating features among non-overlapping sub-parts of the datasets to ensure the representativeness of the features. By randomly splitting the dataset into disjoint sub-parts, conducting feature selection within each sub-part, and intersecting the features shared by all sub-parts, the CVFS approach is able to achieve the goal of extracting the most representative features for yielding satisfactory AMR activity prediction accuracy. By testing this idea on bacterial pan-genome datasets, we showed that this approach was able to extract the most succinct feature sets that predicted AMR activities very well, indicating the potential of these genes as AMR biomarkers. The functional analysis demonstrated that the CVFS approach was able to extract both known AMR genes and novel ones, suggesting the capabilities of the algorithm in selecting relevant features and highlighting the potential of the novel genes in expanding the antimicrobial resistance gene databases.

8.
Chem Commun (Camb) ; 59(8): 1022-1025, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36598113

RESUMO

Ulcerative colitis (UC) is an inflammatory disease of the colon with an unmet need for therapeutic targets. Ethyl gallate (EG) is a natural small molecule for UC treatment, but its cellular target is unknown. By labelling EG with a diazirine photocrosslinker and a click chemistry handle, we identified phosphatidyl-ethanolamine binding protein1 (PEBP1) as a direct cellular target of EG by forming hydrogen bonds with Asp70 and Tyr120. In particular, hydrogen/deuterium exchange mass spectrometry indicated that EG induced the sequence (residues 141-153) embedding to inhibit S153 phosphorylation of PEBP1. Additionally, the EG-mediated sequence (residues 108-122) exposure significantly enhanced PEBP1-Raf-1 interaction to block the downstream NF-κB inflammatory pathway in macrophages. Moreover, PEBP1 siRNA substantially reversed the EG-dependent down-regulation of the phosphorylation of IKKß, IκBα and NF-κB, demonstrating that the NF-κB signal functioned as an essential anti-inflammation mechanism of PEBP1. Collectively, we revealed PEBP1 as a previously undescribed cellular target in macrophages for UC therapy and identified a new allosteric site for PEBP1 biology study using EG as a chemical probe.


Assuntos
Colite Ulcerativa , NF-kappa B , Humanos , NF-kappa B/metabolismo , NF-kappa B/uso terapêutico , Ativação de Macrófagos , Quinase I-kappa B/metabolismo , Proteína de Ligação a Fosfatidiletanolamina/química , Proteína de Ligação a Fosfatidiletanolamina/metabolismo
9.
AMB Express ; 13(1): 10, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36683079

RESUMO

Bacillus, an excellent organic-degrading agent, can degrade lignocellulose. Notably, some B. velezensis strains encode lignocellulases. However, their ability to degrade lignocellulose in fermented feed is not much appreciated. This study performed a comparative genomic analysis of twenty-three B. velezensis strains to find common carbohydrate-active enzymes (CAZymes) encoding genes and evaluated their potential to degrade lignocellulose. The comparative genomic and CAZyme database-based analyses identified several potential CAZymes genes that degrade cellulose (GH1, GH4, GH5, GH13, GH16, GH32, PL1, and PL9), hemicellulose (GH11, GH26, GH43, GH51, and CE3) and lignin (AA4, AA6, AA7, and AA10). Furthermore, Illumina RNA-seq transcriptome analysis revealed the expression of more than 1794 genes in B. velezensis CL-4 fermented corn germ meal at 48 h (FCGM 48 h). Gene ontology analysis of expressed genes revealed their enrichment in hydrolase activity (breaking the glycosyl bonds during carbohydrate metabolism), indicating the upregulation of CAZymes. In total, 58 differentially upregulated CAZymes-encoding genes were identified in FCGM 48 h compared to FCGM 0 h. The upregulated CAZymes-encoding genes were related to cellulose (6-phospho-ß-galactosidase and 6-phospho-α-glucosidase), starch (α-glucosidase and α-amylase), pectin (pectin lyase), and hemicellulose (arabinan endo-1,5-α-L-arabinosidase, xylan 1,4-beta-xylosidase, α-N-arabinofuranosidase, and acetyl xylan esterase). Importantly, arabinoxylan degradation mainly occurred in FCGM 48 h, followed by partial degradation of cellulose, pectin, and starch. This study can support the development of enzymatic cocktails for the solid-state fermented feed (SFF).

10.
J Ethnopharmacol ; 305: 116125, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36603786

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a major cause of morbidity and mortality due to repetitive remissions and relapses, and many severe complications, including colitis-associated cancer (CAC). The San-Qi-Xue-Shang-Ning (SQ) formula has been utilized in clinical practice to treat gut diseases, but its pharmacological evidence is limited and awaits elucidation. AIM OF THE STUDY: Here, we elucidated the molecular mechanisms of the SQ formula. MATERIALS AND METHODS: Its therapeutic value in combating UC and CAC was predicted from network pharmacology and weighted gene co-expression network analysis (WGCNA). Experimental colitis models were established by feeding dextran sodium sulfate (DSS) to C57BL/6N mice for 7 days, and they were subjected to the SQ formula for 14 days. High-throughput technologies and biochemical investigations were executed to corroborate the anti-colitis effect. RESULTS: Network pharmacology and WGCNA demonstrated that the targets of the SQ formula were associated with interleukin-17 (IL-17), tumor necrosis factor (TNF), IL-1b and peroxisome proliferators-activated receptor (PPAR) signaling pathways, and correlated with the survival in patients with colorectal cancer. In mice with colitis, the SQ treatment hindered colitis progression in a dose-dependent manner, as evidenced by the rescued colon length and weight loss, improved colonic epithelial integrity, and abolished crypt loss. In addition to the suppressed serum IL-17, TNFα, and IL-1b levels, the SQ-treated colitis mice exhibited decreased colonic protein abundance of hypoxia-inducible factor-1α (HIF-1 α), PPARα, and Caspase3 (Casp3) with an increased PPARγ expression. Concurrently, the high dose of SQ promoted the alternative activation of peritoneal macrophages by increasing Arg1 and inhibiting iNOS2, thereby facilitating the migration of NCM460 cells and controlling TNF-induced reactive oxygen species production and apoptosis in intestinal organoids. In colitis-accompanied dysbiosis, the SQ formula reversed the decreased microbiota diversity indexes and restored the microbiome profile in the murine colitis models. CONCLUSION: The SQ formula is a potent anti-colitis drug that facilitates inflammation resolution and restores gut microbiota homeostasis.


Assuntos
Colite Ulcerativa , Colite , Microbiota , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Interleucina-17/metabolismo , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colo , Homeostase , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças
11.
Chemosphere ; 315: 137791, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36623602

RESUMO

The oily water treatment is becoming one of the hottest topics due to that increase of offshore oil transportation and the various accident oil leakages. In this study, a functional TiO2-ABS composite membrane was generated through the three-dimensional (3D) printing strategy for the first time and was conducted to simulated oily water treatment. The TiO2-ABS composite membrane demonstrated a significant promotion in hydrophilicity and oleophobicity which were evidenced by the water contact angle of 14.8° and the underwater oil contact angle of 144.7°, respectively. The optimal modified membrane had both exceedingly high flux (1.8 × 105 L m-2·h-1) and oil rejection rate (99.5%). Moreover, the results of filtration cycles of 10 days and extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory demonstrated that the modified membranes took possession of excellent stability and antifouling property. What was more, the TiO2-ABS composite membrane revealed over 99% rejection to all five types of oil/water systems. The interestingly experimental results indicated that the prepared membrane possessed a broad development trend and application prospect in the field of oily water treatment.


Assuntos
Acrilonitrila , Butadienos , Estireno , Titânio , Óleos
12.
Foods ; 12(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36673415

RESUMO

Soft sensors work as predictive frameworks encapsulating a set of easy-to-collect input data and a machine learning method (ML) to predict highly related variables that are difficult to measure. The machine learning method could provide a prediction of complex unknown relations between the input data and desired output parameters. Recently, soft sensors have been applicable in predicting the prices and vintages of New Zealand Pinot noir wines based on chemical parameters. However, the previous sample size did not adequately represent the diversity of provenances, vintages, and price points across commercially available New Zealand Pinot noir wines. Consequently, a representative sample of 39 commercially available New Zealand Pinot noir wines from diverse provenances, vintages, and price points were selected. Literature has shown that wine phenolic compounds strongly correlated with wine provenances, vintages and price points, which could be used as input data for developing soft sensors. Due to the significance of these phenolic compounds, chemical parameters, including phenolic compounds and pH, were collected using UV-Vis visible spectrophotometry and a pH meter. The soft sensor utilising Naive Bayes (belongs to ML) was designed to predict Pinot noir wines' provenances (regions of origin) based on six chemical parameters with the prediction accuracy of over 75%. Soft sensors based on decision trees (within ML) could predict Pinot noir wines' vintages and price points with prediction accuracies of over 75% based on six chemical parameters. These predictions were based on the same collected six chemical parameters as aforementioned.

13.
Int J Biol Macromol ; 229: 1054-1068, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36627036

RESUMO

The crucial need for quality refined sugar has led to the development of advanced adsorbents, with a focus on the decolorization of remelt syrup. In this study, (3-chloro-2-hydroxypropyl) trimethylammonium chloride and polyethyleneimine co-modified pomelo peel cellulose-derived aerogel (CP-PPA) was fabricated, and synthetic melanoidins were used as model colorants of remelt syrup to evaluate the validity and practicality of CP-PPA for eliminating colored impurities. Integrating abundant amine-functionalized groups (quaternary ammonium and protonated amine) within the pomelo peel-derived aerogel directionally captured electronegative melanoidins via electrostatic interactions. Furthermore, the active sites, types, and relative strength of the weak interactions between CP-PPA and melanoidins were determined using density functional theory simulations. CP-PPA exhibited an excellent equilibration adsorbing capacity for capturing melanoidins of 749.51 mg/g, and a removal efficiency of 93.69 %. Additionally, the adsorption mechanism was thoroughly examined in an effort to improve the economy of the sugar refinement industry.

14.
Artigo em Inglês | MEDLINE | ID: mdl-36715824

RESUMO

Hyperuricemia is a metabolic disease caused by purine nucleotide metabolism disorder. The prevalence of hyperuricemia is increasing worldwide, with a growing trend in the younger populations. Although numerous studies have indicated that hyperuricemia may be an independent risk factor for insulin resistance, the causal relationship between the two is controversial. There are few reviews, however, focusing on the relationship between uric acid (UA) and insulin resistance from experimental studies. In this review, we summarized the experimental models related to soluble UA-induced insulin resistance in pancreas and peripheral tissues, including skeletal muscles, adipose tissue, liver, heart/cardiomyocytes, vascular endothelial cells and macrophages. In addition, we summarized the research advances about the key mechanism of UA-induced insulin resistance. Moreover, we attempt to identify novel targets for the treatment of hyperuricemia-related insulin resistance. Lastly, we hope that the present review will encourage further researches to solve the chicken-and-egg dilemma between UA and insulin resistance, and provide strategies for the pathogenesis and treatment of hyperuricemia related metabolic diseases.

15.
Anal Bioanal Chem ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36719439

RESUMO

Erhuangquzhi granules (EQG) have been clinically proven to be effective in nonalcoholic steatohepatitis (NASH) treatment. However, the active components and molecular mechanisms remain unknown. This study aimed to screen active components targeting tumor necrosis factor α (TNF-α) in EQG for the treatment of NASH by a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). The amine-coupling method was used to immobilize recombinant TNF-α protein on an SPR chip, the specificity of the TNF-α-immobilized chip was validated, and nine medicinal herbs in EQG were prescreened. Nuciferine (NF), lirinidine (ID), and O-nornuciferine (NNF) from lotus leaves were found and identified as TNF-α ligands by UPLC‒MS/MS, and the affinity constants of NF, ID, and NNF to TNF-α were determined by SPR experiments (Kd = 61.19, 31.02, and 20.71 µM, respectively). NF, ID, and NNF inhibited TNF-α-induced apoptosis in L929 cells, the levels of secreted IL-6 and IL-1ß were reduced, and the phosphorylation of IKKß and IκB was inhibited in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In conclusion, a class of new active small-molecule TNF-α inhibitors was discovered, which also provides a valuable reference for the material basis and mechanism of EQG action in NASH treatment.

16.
Mol Neurobiol ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633805

RESUMO

Astroglial-fibrotic scars resulted from spinal cord injury affect motor and sensory function, leading to paralysis. In particular, the fibrotic scar is a main barrier that disrupts neuronal regeneration after spinal cord injury. However, the association between astrocytes and fibrotic scar formation is not yet understood. We have previously demonstrated that the transcriptional factor Cebpd contributes to astrogliosis, which promotes glial scar formation after spinal cord injury. Herein, we show that fibrotic scar formation was decreased in the epicenter region in Cebpd-/- mice after contusive spinal cord injury and astrocytic Cebpd promoted fibroblast migration through secretion of Ptx3. Furthermore, the expression of Mmp3 was increased under recombinant protein Ptx3 treatment in fibroblasts by observing microarray data, resulting in fibroblast migration. In addition, regulation of Mmp3 occurs through the NFκB signaling pathway by using an irreversible inhibitor of IκBα phosphorylation in pretreated fibroblasts. Of note, we used the synthetic peptide RI37, which blocks fibroblast migration and decreases fibroblast Mmp3 expression in IL-1ß-treated astrocyte conditioned media. Collectively, our data suggest that fibroblast migration can be affected by astrocytic Cebpd through the Ptx3/NFκB/Mmp3 axis pathway and that the RI37 peptide may act as a therapeutic medicine to inhibit fibrotic scar formation after spinal cord injury.

17.
Eur J Nutr ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36651989

RESUMO

PURPOSE: We re-explored the basal iodine requirement based on healthy Chinese female and a new iodine overflow theory was proposed for iodine balance study. METHODS: Thirty-six Chinese healthy female adults (age 20.7 ± 1.1) were recruited for this study, which included 40 days low iodine depletion period and six stages of 30 days supplementation period. Uniform diets with low iodine were provided and the content of iodine in the diet was regulated by dairy products. The total iodine intake from food and the total iodine excretion through 24-h urine and staged feces were completely gathered and monitored. The incremental (Δ) intake and excretion over the range were calculated. RESULTS: The iodine intake and excretion were 13.6 µg/day and 48.6 µg/day at the first stage, respectively. The incremental iodine intakes and excretions were 21.1 µg/day to 120.3 µg/day and 25.8 µg/day to 105.4 µg/day for the supplementation stages, respectively. According to the 'iodine overflow theory', the zero iodine balance (Δ iodine intake = Δ iodine excretion) derived from a mixed effect model indicated a mean iodine intake of 52.2 µg/d (1.0 µg/d kg). The RNI for iodine to healthy Chinese female adult was 73.1 µg/d (1.4 µg/d kg). CONCLUSION: A daily iodine intake of 52.2 µg/d may meet the basal iodine requirement for healthy Chinese female adults, and Chinese female may need more than 20% iodine intake than male based on the 'iodine overflow theory'. The trial was registered at the Chinese Clinical Trial Registry in May 2018 (No: ChiCTR1800016184).

18.
Kidney Med ; 5(2): 100585, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36712315

RESUMO

Rationale & Objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, single-center renal genetics clinic experience. Study Design: Retrospective cohort. Setting & Participants: Outpatient cases referred to the renal genetics clinic of the Cleveland Clinic between January 2019 and March 2022 were reviewed. Analytical Approach: Clinical and laboratory characteristics were analyzed. All genetic testing was performed in clinical labs. Results: 309 new patients referred from 15 specialties were evaluated, including 118 males and 191 females aged 35.1 ± 20.3 years. Glomerular diseases were the leading presentation followed by cystic kidney diseases, electrolyte disorders, congenital anomalies of kidneys and urinary tract, nephrolithiasis, and tubulointerstitial kidney diseases. Dysmorphic features were noted in 27 (8.7%) patients. Genetic testing was recommended in 292 (94.5%) patients including chromosomal microarray (8.9%), single-gene tests (19.5%), multigene panels (77.3%), and exome sequencing (17.5%). 80.5% of patients received insurance coverage for genetic testing. 45% (115/256) of patients had positive results, 25% (64/256) had variants of unknown significance, and 22.3% (57/256) had negative results. 43 distinct monogenic disorders were diagnosed. Family history of kidney disease was present in 52.8% of patients and associated with positive genetic findings (OR, 2.28; 95% CI, 1.40-3.74). 69% of patients with positive results received a new diagnosis and/or a change in the diagnosis. Among these, 39.7% (31/78) of patients received a significant change in disease management. Limitations: Retrospective and single-center study. Conclusions: The renal genetics clinic plays important roles in the diagnosis and management of patients with genetic kidney diseases. Multigene panels are the most frequently used testing modality with a high diagnostic yield. Family history of kidney disease is a strong indication for renal genetics clinic referral.

19.
Ther Adv Chronic Dis ; 14: 20406223221143233, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36687666

RESUMO

Background: Elevated arterial stiffness in patients with primary aldosteronism (PA) can be reversed after adrenalectomy; however, the effect of medical treatment with mineralocorticoid receptor antagonist (MRAs) is unknown. Objectives: The aim of this study was to evaluate the effect of MRAs and compare both treatment strategies on arterial stiffness in PA patients. Design: Prospective cohort study. Methods: We prospectively enrolled PA patients from 2006 to 2019 who received either adrenalectomy or MRA treatment (spironolactone). We compared their baseline and 1-year post-treatment biochemistry characteristics and arterial pulse wave velocity (PWV) to verify the effects of treatment and related determinant factors. Results: A total 459 PA patients were enrolled. After 1:1 propensity score matching for age, sex and blood pressure (BP), each group had 176 patients. The major determinant factors of baseline PWV were age and baseline BP. The adrenalectomy group had greater improvements in BP, serum potassium level, plasma aldosterone concentration, and aldosterone-to-renin ratio. The MRA group had a significant improvement in PWV after 1 year of treatment (1706.2 ± 340.05 to 1613.6 ± 349.51 cm/s, p < 0.001). There were no significant differences in post-treatment PWV (p = 0.173) and improvement in PWV (p = 0.579) between the adrenalectomy and MRA groups. The determinant factors for an improvement in PWV after treatment were hypertension duration, baseline PWV, and the decrease in BP. Conclusion: The PA patients who received medical treatment with MRAs had a significant improvement in arterial stiffness. There was no significant difference in the improvement in arterial stiffness between the two treatment strategies.

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