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1.
Opt Express ; 32(12): 20915-20930, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859460

RESUMO

Channeled spectropolarimetry enables real-time measurement of the polarimetric spectral information of the target. A crucial aspect of this technology is the accurate reconstruction of Stokes parameters spectra from the modulated spectra obtained through snapshot measurements. In this paper, a learnable sparse dictionary compressed sensing method is proposed for channeled spectropolarimeter (CSP) spectral reconstruction. Grounded in the compressive sensing framework, this method defines a variable sparse dictionary. It can learn prior knowledge from the measured modulated spectra, continuously optimizing its own structure and parameters iteratively by removing redundant basis functions and refining the matched basis functions. The learned sparse dictionary, post-training, can provide a more accurate sparse representation of the Stokes parameters spectra, enabling the proposed method to achieve more precise reconstruction results. To assess the efficacy of the proposed method, simulations and experiments were conducted, both of which consistently demonstrated the superior performance of the proposed approach. The suggested method is well-positioned to enhance the efficiency and accuracy of polarimetric spectral information retrieval in CSP applications.

2.
J Nat Prod ; 87(2): 322-331, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38334086

RESUMO

A strategy integrating in silico molecular docking with LXRα and phenotypic assays was adopted to discover anti-hypercholesterolemia agents in a small library containing 205 marine microorganism-derived natural products, collected by our group in recent years. Two fumitremorgin derivatives, 12R,13S-dihydroxyfumitremorgin C (1) and tryprostatin A (3), were identified as potential LXRα agonists, by real-time qPCR and Western blot (WB) analysis, together with a surface plasmon resonance (SPR) assay. The anti-hypercholesterolemic effects of 1 and 3, together with their mechanisms, were investigated in depth using different cell and mouse models, among which the study of LXRα is of crucial importance. Compound 1 or 3 exhibited the capacity to effectively reverse excessive lipid accumulation in a hepatic steatosis cell model and significantly reduce liver damage and blood cholesterol levels in high cholesterol diet (HCD)-fed wild-type mice, whereas those beneficial effects were completely nullified in HCD-fed LXRα-knockout mice. Furthermore, 1 and 3 outperformed common LXRα agonists by suppressing the expression of sterol regulatory element-binding protein 1 (SREBP1) in HCD-fed mice, mitigating lipotoxicity. Thus, this study highlights the discovery of two marine microorganism-derived anti-hypercholesterolemia agents targeting LXRα.


Assuntos
Hipercolesterolemia , Receptores Nucleares Órfãos , Animais , Camundongos , Colesterol/metabolismo , Hipercolesterolemia/tratamento farmacológico , Fígado , Receptores X do Fígado/metabolismo , Camundongos Knockout , Simulação de Acoplamento Molecular , Receptores Nucleares Órfãos/metabolismo , Receptores Nucleares Órfãos/farmacologia
3.
Med Sci Monit ; 30: e944314, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865287

RESUMO

BACKGROUND Hyperuricemia, which is common in chronic kidney disease and diabetes mellitus patients, raises health concerns. Febuxostat, a first-line urate-lowering agent, prompts cardiovascular risk questions, especially in high-risk patients. This study compared the effects of febuxostat and allopurinol on cardiovascular risk in diabetes mellitus and chronic kidney disease patients. MATERIAL AND METHODS This retrospective observational cohort study, conducted using Taiwan's National Health Insurance Research Database, focused on patients diagnosed with chronic kidney disease and diabetes between January 2012 and December 2017. The study population was divided into 2 groups: allopurinol users (n=12 901) and febuxostat users (n=2997). We performed 1: 1 propensity score matching, resulting in subgroups of 2997 patients each. The primary outcomes were assessed using a competing risk model, estimating hazard ratios (HR) for long-term outcomes, including the risks of all-cause hospitalization, hospitalization for heart failure, and hospitalization for cardiovascular interventions. RESULTS Febuxostat users, compared to allopurinol users, had higher all-cause hospitalization (HR: 1.33; 95% confidence interval [CI]: 1.25 to 1.42; P<.001), hospitalization for heart failure (HR: 1.62; 95% CI: 1.43 to 1.83; P<.001), and hospitalization for cardiovascular interventions (HR: 1.51; 95% CI: 1.32 to 1.74; P<.001). Moreover, the adverse effects of febuxostat on cardiac health were consistent across most subgroups. CONCLUSIONS Use of febuxostat in patients with diabetes mellitus and chronic kidney disease is associated with higher cardiovascular risks compared to allopurinol. Prudent evaluation is essential when recommending febuxostat for this at-risk group.


Assuntos
Alopurinol , Doenças Cardiovasculares , Febuxostat , Supressores da Gota , Hiperuricemia , Insuficiência Renal Crônica , Humanos , Febuxostat/uso terapêutico , Febuxostat/efeitos adversos , Alopurinol/uso terapêutico , Alopurinol/efeitos adversos , Masculino , Feminino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Taiwan/epidemiologia , Hiperuricemia/tratamento farmacológico , Hiperuricemia/complicações , Supressores da Gota/uso terapêutico , Supressores da Gota/efeitos adversos , Diabetes Mellitus/tratamento farmacológico , Fatores de Risco , Adulto , Hospitalização
4.
Opt Express ; 31(6): 9608-9619, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157527

RESUMO

Here we propose a metasurface consisting of symmetry-broken dielectric tetramer arrays, which can generate polarization-selective dual-band toroidal dipole resonances (TDR) with ultra-narrow linewidth in the near-infrared region. We found, by breaking the C4v symmetry of the tetramer arrays, two narrow-band TDRs can be created with the linewidth reaching ∼ 1.5 nm. Multipolar decomposition of scattering power and electromagnetic field distribution calculations confirm the nature of TDRs. A 100% modulation depth in light absorption and selective field confinement has been demonstrated theoretically by simply changing the polarization orientation of the exciting light. Intriguingly, it is also found that absorption responses of TDRs on polarization angle follow the equation of Malus' law in this metasurface. Furthermore, the dual-band toroidal resonances are proposed to sense the birefringence of an anisotropic medium. Such polarization-tunable dual toroidal dipole resonances with ultra-narrow bandwidth offered by this structure may find potential applications in optical switching, storage, polarization detection, and light emitting devices.

5.
Med Sci Monit ; 29: e941321, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37807497

RESUMO

BACKGROUND Circulating calcium mainly carries out its physiologic function in its ionized form (iCa). Clinically, iCa is usually estimated by multiplying the total calcium (TCa) level by 0.5 in the general population, but this method is not accurate when applied to patients on long-term hemodialysis (CHD). Accordingly, this study aimed to develop a predictive function for iCa in patients on CHD by incorporating TCa and other additional variables. MATERIAL AND METHODS This was a retrospective cross-sectional study consisting of 2 cross-sectional datasets: a derivation set including 469 CHD patients in June 2019, and a validation set including 446 CHD patients in September 2019. The derivation set's data were analyzed using the stepwise model selection of machine learning with 10-fold cross-validation to develop a predictive function for iCa. This predictive function was then applied to the validation set's data, and the predictive function's estimated iCa was compared with the actual laboratory iCa by using the paired-samples t test and intraclass correlation coefficient. RESULTS After analyzing the routine laboratory data parameters of patients in the derivation set, the following 5 variables were included in the predictive function of iCa: blood urea nitrogen, creatinine, phosphate, TCa, and albumin. This predictive function was applied to the validation set to yield an estimated iCa level that was not significantly different from the laboratory-measured iCa level of the validation dataset (P=0.676) with an excellent ICC of 0.905. CONCLUSIONS We developed a new predictive function that accurately measures the iCa in patients on CHD by using routine laboratory data.


Assuntos
Cálcio , Hipercalcemia , Diálise Renal , Insuficiência Renal Crônica , Humanos , Cálcio/sangue , Estudos Transversais , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia
6.
Med Sci Monit ; 29: e940959, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37525452

RESUMO

BACKGROUND Hyperparathyroidism poses significant risks for patients prior to kidney transplantation. However, the outcomes of patients who undergo parathyroidectomy before renal transplantation compared to those without such a procedure remain uncertain. This real-world data study aimed to examine the clinical outcomes of both patient groups. MATERIAL AND METHODS Using the Taiwan National Health Insurance Research Database, we conducted a retrospective cohort study on patients who underwent renal transplantation between January 2005 and December 2015. The patients were divided into two groups: a case group (n=294) with parathyroidectomy and a control group (n=588) without the need for parathyroidectomy before kidney transplantation. The groups were matched based on age, sex, dialysis vintage, and baseline characteristics at a 1:2 ratio. Hazard ratios (HR) were estimated using the Cox regression model. The main outcomes assessed were graft failure, mortality, and major adverse cardiovascular events (MACE) recorded until December 2019. RESULTS During a mean follow-up period of 6 years, a significant difference was observed in graft failure (HR 1.40; 95% confidence interval 1.10-1.79, p=0.007) between the two groups. After further adjustment, graft failure remained significant (HR 1.52; 95% CI 1.07-2.15, p=0.019). Additionally, machine learning-based feature selection identified the importance of parathyroidectomy (ranked 9 out of 11) before kidney transplantation in predicting subsequent graft failure. CONCLUSIONS Our study demonstrates that severe hyperparathyroidism requiring parathyroidectomy before kidney transplantation may contribute to poor post-transplant graft outcomes compared to patients who do not require parathyroidectomy.


Assuntos
Hiperparatireoidismo , Transplante de Rim , Humanos , Transplante de Rim/métodos , Estudos Retrospectivos , Paratireoidectomia/efeitos adversos , Hiperparatireoidismo/cirurgia , Hiperparatireoidismo/etiologia , Diálise Renal , Sobrevivência de Enxerto
7.
Opt Express ; 30(7): 10367-10386, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35473006

RESUMO

Channeled spectropolarimetry is a snapshot technique for measuring the spectra of Stokes parameters of light by demodulating the measured spectrum. As an indispensable part of the channeled spectropolarimeter, the spectrometer module is far from being perfect to reflect the real modulation spectrum, which further reduces the polarimetric reconstruction accuracy of the channeled spectropolarimeter. Since the modulation spectrum is composed of many continuous narrow-band spectra with high frequency, it is a challenging work to reconstruct it effectively by existing methods. To alleviate this issue, a convolutional neural network (CNN)-based spectral reconstruction solver is proposed for channeled spectropolarimeter. The key idea of the proposed method is to first preprocess the measured spectra using existing traditional methods, so that the preprocessed spectra contain more spectral features of the real spectra, and then these spectral features are employed to train a CNN to learn a map from the preprocessed spectra to the real spectra, so as to further improve the reconstruction quality of the preprocessed spectra. A series of simulation experiments and real experiments were carried out to verify the effect of the proposed method. In simulation experiments, we investigated the spectral reconstruction accuracy and robustness of the proposed method on three synthetic datasets and evaluate the effect of the proposed method on the demodulation results obtained by the Fourier reconstruction method. In real experiments, system matrices are constructed by using measured spectra and reconstructed spectra respectively, and the spectra of Stokes parameters of incident light are estimated by the linear operator method. Several other advanced demodulation methods are also used to demodulate the measured spectrum in both simulation and real experiments. The results show that compared with other methods, the accuracy of the demodulation results can be much more improved by employing the CNN-based solver to reconstruct the measured spectrum.

8.
Medicina (Kaunas) ; 57(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916080

RESUMO

Background and Objectives: Identifying risk factors associated with psychiatrist-confirmed anxiety and depression among young lung cancer patients is very difficult because the incidence and prevalence rates are obviously lower than in middle-aged or elderly patients. Due to the nature of these rare events, logistic regression may not successfully identify risk factors. Therefore, this study aimed to propose a novel algorithm for solving this problem. Materials and Methods: A total of 1022 young lung cancer patients (aged 20-39 years) were selected from the National Health Insurance Research Database in Taiwan. A novel algorithm that incorporated a k-means clustering method with v-fold cross-validation into multiple correspondence analyses was proposed to optimally determine the risk factors associated with the depression and anxiety of young lung cancer patients. Results: Five clusters were optimally determined by the novel algorithm proposed in this study. Conclusions: The novel Multiple Correspondence Analysis-k-means (MCA-k-means) clustering algorithm in this study successfully identified risk factors associated with anxiety and depression, which are considered rare events in young patients with lung cancer. The clinical implications of this study suggest that psychiatrists need to be involved at the early stage of initial diagnose with lung cancer for young patients and provide adequate prescriptions of antipsychotic medications for young patients with lung cancer.


Assuntos
Depressão , Neoplasias Pulmonares , Adulto , Idoso , Algoritmos , Ansiedade/epidemiologia , Depressão/epidemiologia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Taiwan , Adulto Jovem
9.
Int J Mol Sci ; 21(5)2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32111067

RESUMO

Vascular calcification (VC) is highly associated with cardiovascular disease and all-cause mortality in patients with chronic kidney disease. Dysregulation of endothelial cells and vascular smooth muscle cells (VSMCs) is related to VC. Sirtuin-1 (Sirt1) deacetylase encompasses a broad range of transcription factors that are linked to an extended lifespan. Sirt1 enhances endothelial NO synthase and upregulates FoxOs to activate its antioxidant properties and delay cell senescence. Sirt1 reverses osteogenic phenotypic transdifferentiation by influencing RUNX2 expression in VSMCs. Low Sirt1 hardly prevents acetylation by p300 and phosphorylation of ß-catenin that, following the facilitation of ß-catenin translocation, drives osteogenic phenotypic transdifferentiation. Hyperphosphatemia induces VC by osteogenic conversion, apoptosis, and senescence of VSMCs through the Pit-1 cotransporter, which can be retarded by the sirt1 activator resveratrol. Proinflammatory adipocytokines released from dysfunctional perivascular adipose tissue (PVAT) mediate medial calcification and arterial stiffness. Sirt1 ameliorates release of PVAT adipokines and increases adiponectin secretion, which interact with FoxO 1 against oxidative stress and inflammatory arterial insult. Conclusively, Sirt1 decelerates VC by means of influencing endothelial NO bioavailability, senescence of ECs and VSMCs, osteogenic phenotypic transdifferentiation, apoptosis of VSMCs, ECM deposition, and the inflammatory response of PVAT. Factors that aggravate VC include vitamin D deficiency-related macrophage recruitment and further inflammation responses. Supplementation with vitamin D to adequate levels is beneficial in improving PVAT macrophage infiltration and local inflammation, which further prevents VC.


Assuntos
Sirtuína 1/metabolismo , Calcificação Vascular/metabolismo , Adipocinas , Tecido Adiposo/metabolismo , Animais , Apoptose , Doenças Cardiovasculares/metabolismo , Transdiferenciação Celular , Células Endoteliais/metabolismo , Proteína Forkhead Box O1/metabolismo , Humanos , Miócitos de Músculo Liso/metabolismo , Óxido Nítrico/metabolismo , Osteogênese/fisiologia , Fatores de Transcrição , Calcificação Vascular/prevenção & controle , Rigidez Vascular , beta Catenina/metabolismo
10.
BMC Endocr Disord ; 19(1): 80, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349821

RESUMO

BACKGROUND: Myasthenia gravis (MG) is the most common disorder of neuromuscular transmission, and it is typified by fluctuating degrees and variable combinations of weakness in the ocular, bulbar, limb, and respiratory muscles. Under rare circumstances, MG can be accompanied by Addison's disease. CASE PRESENTATION: Here, we reported the case of a 57-year-old Chinese woman with MG. She experienced progressive muscle weakness for 1 week. MG with acute exacerbation was initially suspected. However, further biochemistry tests found mild hyperkalemia (5.6 mEq/L) and a lower renal potassium excretion rate. Consequently, low aldosterone action was highly suspected. Further findings included a suppressed cortisol level, a higher adrenocorticotropic hormone concentration, and 21-hydroxylase antibody positivity, supporting a diagnosis of primary adrenal insufficiency due to autoimmune adrenalitis. CONCLUSION: We successfully demonstrated that adrenal insufficiency could be diagnosed, due to the presence of hyperkalemia. This case suggested a need for clinicians to consider the possible coincidence of adrenal insufficiency in a patient with MG and hyperkalemia. Early hormone supplementation should be begun.


Assuntos
Hiperpotassemia/patologia , Miastenia Gravis/complicações , Feminino , Humanos , Hiperpotassemia/etiologia , Pessoa de Meia-Idade , Prognóstico
11.
Med Sci Monit ; 25: 691-699, 2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30674864

RESUMO

BACKGROUND Rapid shifting between extracellular and intracellular phosphorus can occur during dialysis sessions, which can cause aberrant intracellular signaling in long-term hemodialysis (LTHD) patients. However, the effect of these intra-dialysis fluctuations of phosphorus on clinical outcomes has not been examined. Therefore, we investigated the relationship between intradialysis serum phosphorus reduction ratio (IDSPRR) and mortality in LTHD patients. MATERIAL AND METHODS This was a retrospective, observational cohort study to assess the predictive power of IDSPRR (>0.63 vs. ≤0.63) on mortality in a total of 805 LTHD patients. All these fatal events were analyzed using the Cox proportional hazards regression model. RESULTS After multivariable analysis, baseline IDSPRR higher than 0.63 was significantly predictive of all-cause mortality (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.10-2.26), but not for cardiovascular (CV) mortality (HR: 1.41; 95% CI: 0.91-2.18). However, when time-varied IDSPRRs were applied, a value greater than 0.63 was not only significantly predictive of all-cause mortality (HR: 1.74, 95% CI: 1.16-2.63), but also CV mortality (HR: 2.04, 95% CI: 1.23-3.40). CONCLUSIONS High IDSPRR (>0.63) is independently associated with increased all-cause and CV mortality, which shows the negative effect of rapid intracellular phosphorus-shifting on LTHD patients.


Assuntos
Fósforo/análise , Diálise Renal/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/efeitos adversos , Fósforo/sangue , Prognóstico , Modelos de Riscos Proporcionais , Diálise Renal/efeitos adversos , Estudos Retrospectivos
12.
Appl Opt ; 58(16): 4345-4351, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31251239

RESUMO

Dual-wavelength operation of grating-tuned dye laser systems was demonstrated in this paper. We used the second harmonic generation of a Q-switched Nd:YAG laser to pump the Nile red solvent (dissolved in ethanol) in the Littrow configuration and the Littman-Metcalf configuration. By rotating the grating 3.6° in the Littrow configuration and the tuning mirror 3.9° in the Littman-Metcalf configuration, we obtained a 72 and 46 nm tuning-range dye laser output, respectively. Meanwhile by parallelly moving the grating in the Littrow configuration and the tuning mirror in the Littman-Metcalf configuration, we achieved the separation of dual wavelength from 0.7 to 5 nm in the former and 1.5 to 4 nm in the latter, which were in the terahertz range and could find applications in the terahertz source after using difference frequency technology. Finally, after considering the laser trajectories in the two configurations, we theoretically analyzed the reasons for overall tuning and separation tuning of dual wavelength.

13.
BMC Nephrol ; 19(1): 160, 2018 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-29973184

RESUMO

BACKGROUND: Hypokalemia is one of the most common clinical electrolyte imbalance problems, and thyrotoxic periodic paralysis (TPP) is a leading cause of presentation to the emergency department. Low renal potassium secretion rates, a normal acid-base balance in the blood, and hyperthyroidism are the hallmarks of suspected TPP. CASE PRESENTATION: Here we report the case of a 36-year-old man who presented to the emergency department with a sudden onset of acute muscle weakness at 5 h prior to admission. Biochemistry tests revealed hypokalemia with hyperthyroidism and renal potassium wasting. TPP was initially not favored due to the presence of renal potassium wasting. However, his serum potassium level rebounded rapidly within several hours after potassium supplementation, indicating that the intracellular shifting of potassium ions was the main etiology for his hypokalemia. The early stage of TPP development may have contributed to this paradox. CONCLUSION: Therefore, it is premature to rule out TPP based on the presentation of high renal potassium secretion rates alone. This finding may result in an incorrect impression being made in the early stage of TTP and may consequently lead to an inappropriate potassium supplementation policy.


Assuntos
Hipertireoidismo/sangue , Hipopotassemia/sangue , Debilidade Muscular/sangue , Paralisia/sangue , Potássio/sangue , Adulto , Diagnóstico Diferencial , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/diagnóstico , Hipopotassemia/complicações , Hipopotassemia/diagnóstico , Masculino , Debilidade Muscular/complicações , Debilidade Muscular/diagnóstico , Paralisia/complicações , Paralisia/diagnóstico
14.
Ren Fail ; 37(1): 88-95, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25350835

RESUMO

BACKGROUND: The ankle-brachial index (ABI) is associated with peripheral vascular atherosclerosis, adverse cardiovascular outcomes, and all-cause mortality. However, there were limited data available on studying the effect of interleg ABI difference. METHODS: We investigated the association of the interleg ABI difference with overall and cardiovascular mortality in chronic hemodialysis in a retrospective observational cohort of 369 Taiwanese patients undergoing chronic hemodialysis. RESULTS: An interleg ABI difference of ≥0.15 in hemodialysis patients had significant predictive power for all-cause and cardiovascular mortality in crude analysis. The hazard ratio (HR) for all-cause mortality was 3.00 [95% confidence interval (CI), 1.91-4.71]; the HR for cardiovascular mortality was 3.13 (95% CI, 1.82-5.38). After adjustment for confounding variables, this difference continued to have significant predictive power for all-cause mortality but lost its predictive power for fatal cardiac outcome. ABI <0.9 and high brachial-ankle pulse wave velocity were independently associated with an interleg ABI difference of ≥0.15 in hemodialysis patients. Moreover, in the subgroup analysis, we found that this difference was an independent factor for overall and cardiovascular mortality, particularly in elder patients, female patients, or those with ABI <0.9. CONCLUSION: Detection of an interleg ABI difference of ≥0.15 was an independent risk factor for overall mortality in hemodialysis patients but it may affect cardiovascular mortality through the effect of peripheral vascular disease.


Assuntos
Perna (Membro) , Doença Arterial Periférica , Diálise Renal/efeitos adversos , Fatores Etários , Idoso , Índice Tornozelo-Braço/métodos , Índice Tornozelo-Braço/estatística & dados numéricos , Causas de Morte , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Perna (Membro)/irrigação sanguínea , Perna (Membro)/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Diálise Renal/métodos , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Taiwan/epidemiologia
15.
J Am Soc Nephrol ; 24(10): 1587-97, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23833262

RESUMO

A T60M mutation in the thiazide-sensitive sodium chloride cotransporter (NCC) is common in patients with Gitelman's syndrome (GS). This mutation prevents Ste20-related proline and alanine-rich kinase (SPAK)/oxidative stress responsive kinase-1 (OSR1)-mediated phosphorylation of NCC and alters NCC transporter activity in vitro. Here, we examined the physiologic effects of NCC phosphorylation in vivo using a novel Ncc T58M (human T60M) knock-in mouse model. Ncc(T58M/T58M) mice exhibited typical features of GS with a blunted response to thiazide diuretics. Despite expressing normal levels of Ncc mRNA, these mice had lower levels of total Ncc and p-Ncc protein that did not change with a low-salt diet that increased p-Spak. In contrast to wild-type Ncc, which localized to the apical membrane of distal convoluted tubule cells, T58M Ncc localized primarily to the cytosolic region and caused an increase in late distal convoluted tubule volume. In MDCK cells, exogenous expression of phosphorylation-defective NCC mutants reduced total protein expression levels and membrane stability. Furthermore, our analysis found diminished total urine NCC excretion in a cohort of GS patients with homozygous NCC T60M mutations. When Wnk4(D561A/+) mice, a model of pseudohypoaldosteronism type II expressing an activated Spak/Osr1-Ncc, were crossed with Ncc(T58M/T58M) mice, total Ncc and p-Ncc protein levels decreased and the GS phenotype persisted over the hypertensive phenotype. Overall, these data suggest that SPAK-mediated phosphorylation of NCC at T60 regulates NCC stability and function, and defective phosphorylation at this residue corrects the phenotype of pseudohypoaldosteronism type II.


Assuntos
Rim/metabolismo , Receptores de Droga/metabolismo , Simportadores de Cloreto de Sódio/metabolismo , Animais , Estudos de Casos e Controles , Cães , Feminino , Técnicas de Introdução de Genes , Síndrome de Gitelman/genética , Síndrome de Gitelman/metabolismo , Humanos , Células Madin Darby de Rim Canino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Fenótipo , Fosforilação/genética , Proteínas Serina-Treonina Quinases/metabolismo , Pseudo-Hipoaldosteronismo/metabolismo , Receptores de Droga/genética , Simportadores de Cloreto de Sódio/genética , Membro 1 da Família 12 de Carreador de Soluto/genética , Membro 1 da Família 12 de Carreador de Soluto/metabolismo
16.
ScientificWorldJournal ; 2014: 486781, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25489602

RESUMO

As a low-molecular-weight heparin, tinzaparin has effectively been used as an anticoagulant during hemodialysis sessions. However, the impact of different heparin types on dyslipidemia is still controversial. In our study, 434 chronic hemodialysis patients were evaluated. The mean age was 65 ± 13. Forty-eight patients (11%) and 386 patients (89%) were in the tinzaparin and unfractionated heparin (UFH) groups, respectively. Triglyceride had significant difference between the two groups (P = 0.001) but total cholesterol, HDL, or LDL did not. In the univariate analysis, the triglyceride level was significantly associated with tinzaparin use [ß: -39.9, 95% confidence interval (CI): -76.7 to -3.0], and this association remained following the multivariate analysis (ß: -40.8, 95% CI: -75.1 to -6.5). The difference in serum total cholesterol level between tinzaparin and UFH became significant (ß: -13, 95% CI: -24.5 to -1.56) after adjustment in the multivariate analysis. Moreover, in a subgroup analysis, male diabetic patients showed lower serum triglyceride levels with the use of tinzaparin, while older, nondiabetic, male patients showed significant advantages in total cholesterol levels with the use of tinzaparin. Based on our findings, tinzaparin shows a significant association with a lower lipid profile in patients with chronic hemodialysis when compared to UFH.


Assuntos
Heparina de Baixo Peso Molecular/farmacologia , Lipídeos/sangue , Diálise Renal , Idoso , Colesterol/sangue , Estudos Transversais , Demografia , Feminino , Humanos , Modelos Lineares , Masculino , Análise Multivariada , Tinzaparina , Triglicerídeos/sangue
17.
Kidney Res Clin Pract ; 43(2): 216-225, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37165616

RESUMO

BACKGROUND: This study reports the outcomes of a collaborative program between dialysis clinics and a referral hospital, which consisted of clinical monitoring and supplementary routine surveillance, for improving the quality of vascular access care. METHODS: This retrospective observational study was performed at five dialysis clinics as part of a 2-year collaborative program (2019-2020) in conjunction with a hospital-based dialysis access management center. A total of 392 hemodialysis patients (arteriovenous fistula [AVF], n = 339 and arteriovenous graft [AVG], n = 53) were included. Outcome measures included the prognosis of vascular access, clinic satisfaction, and referral rate to the hospital. RESULTS: Increased vascular access flow was observed and critical flow events decreased from the first to the second year (AVF: 18.3% vs. 12.7%, p < 0.001; AVG: 26.2% vs. 20.1%, p = 0.30). There were fewer percutaneous transluminal angioplasty events in the AVG group (0.77 per person-year vs. 0.51 per person-year, p = 0.005). New AVF or AVG creation events also remained low. All dialysis clinics were satisfied with the program. The overall referral rate from the participating clinics increased (65.7% vs. 72.0%) during the study period independently of the physical distance between the dialysis clinic and the hospital. CONCLUSION: The collaboration between dialysis clinics and a referral hospital for improving the quality of vascular access care was successful in this study, and the model can be used by other clinics and hospitals looking to improve care coordination in dialysis patients.

18.
Front Public Health ; 12: 1352570, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38450138

RESUMO

Introduction: Glyphosate, a widely utilized herbicide globally, has been linked to various health issues, including cancer, birth abnormalities, and reproductive issues. Additionally, there is growing experimental support indicating potential harm to skeletal muscles. Despite this, the impact of glyphosate on human muscle health remains unclear. Methods: We examined information gathered from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), which included 1466 adults aged 18 or older. Our primary aim was to investigate the relationship between glyphosate exposure and hand grip strength, as well as its influence on lean muscle mass. Results and discussion: Our investigation uncovered a detrimental correlation between glyphosate exposure and all measures of grip strength, except for the second test of the first hand. Specifically, we observed a statistically significant adverse association between glyphosate exposure and combined grip strength, which is calculated as the sum of the highest readings from both hands (ß coefficient of -2.000, S.E. = 0.891, p = 0.040). We did not observe a significant correlation between glyphosate levels, lean muscle mass, and the likelihood of reaching maximum grip strength meeting sarcopenia criteria. Additionally, we observed an interaction between age and glyphosate, as well as between body mass index (BMI) and glyphosate, concerning the association with combined grip strength. In this comprehensive analysis of NHANES data, our study reveals a potential association between glyphosate exposure and hand grip strength in the adult population. Our findings suggest the need for deeper exploration into the health effects of glyphosate exposure and its impact on muscle strength, shedding light on possible public health concerns.


Assuntos
Glifosato , Força da Mão , Adulto , Humanos , Inquéritos Nutricionais , Força Muscular , Músculos
19.
Front Med (Lausanne) ; 10: 1155426, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37859858

RESUMO

Background and objectives: Chronic kidney disease (CKD) is a global health concern. This study aims to identify key factors associated with renal function changes using the proposed machine learning and important variable selection (ML&IVS) scheme on longitudinal laboratory data. The goal is to predict changes in the estimated glomerular filtration rate (eGFR) in a cohort of patients with CKD stages 3-5. Design: A retrospective cohort study. Setting and participants: A total of 710 outpatients who presented with stable nondialysis-dependent CKD stages 3-5 at the Shin-Kong Wu Ho-Su Memorial Hospital Medical Center from 2016 to 2021. Methods: This study analyzed trimonthly laboratory data including 47 indicators. The proposed scheme used stochastic gradient boosting, multivariate adaptive regression splines, random forest, eXtreme gradient boosting, and light gradient boosting machine algorithms to evaluate the important factors for predicting the results of the fourth eGFR examination, especially in patients with CKD stage 3 and those with CKD stages 4-5, with or without diabetes mellitus (DM). Main outcome measurement: Subsequent eGFR level after three consecutive laboratory data assessments. Results: Our ML&IVS scheme demonstrated superior predictive capabilities and identified significant factors contributing to renal function changes in various CKD groups. The latest levels of eGFR, blood urea nitrogen (BUN), proteinuria, sodium, and systolic blood pressure as well as mean levels of eGFR, BUN, proteinuria, and triglyceride were the top 10 significantly important factors for predicting the subsequent eGFR level in patients with CKD stages 3-5. In individuals with DM, the latest levels of BUN and proteinuria, mean levels of phosphate and proteinuria, and variations in diastolic blood pressure levels emerged as important factors for predicting the decline of renal function. In individuals without DM, all phosphate patterns and latest albumin levels were found to be key factors in the advanced CKD group. Moreover, proteinuria was identified as an important factor in the CKD stage 3 group without DM and CKD stages 4-5 group with DM. Conclusion: The proposed scheme highlighted factors associated with renal function changes in different CKD conditions, offering valuable insights to physicians for raising awareness about renal function changes.

20.
J Clin Med ; 12(4)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36836085

RESUMO

(1) Background: Fibroblast growth factor 23 (FGF23) is predominantly secreted from bone and plays an important role in mineral balance in chronic kidney disease. However, the relationship between FGF23 and bone mineral density (BMD) in chronic hemodialysis (CHD) patients remains unclear. (2) Methods: This was a cross-sectional observational study that involved 43 stable outpatients on CHD. A linear regression model was used to determine risk factors for BMD. Measurements included serum hemoglobin, intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23), sclerostin, Dickkopf-1, α-klotho, 1,25-hydroxyvitamin D, intact parathyroid hormone levels and dialysis profiles. (3) Results: Study participants had a mean age of 59.4 ± 12.3 years, and 65% were male. In the multivariable analysis, cFGF23 levels showed no significant associations with the BMD of the lumbar spine (p = 0.387) nor that of the femoral head (p = 0.430). However, iFGF23 levels showed a significant negative association with the BMD of the lumbar spine (p = 0.015) and that of the femoral neck (p = 0.037). (4) Conclusions: Among patients on CHD, higher serum iFGF23 levels, but not serum cFGF23 levels, were associated with lower BMD values of the lumbar spine and femoral neck. However, further research is required to validate our findings.

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