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1.
J Nucl Cardiol ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415628

RESUMO

OBJECTIVES: We aimed to develop a dynamic imaging technique for a novel PET superoxide tracer, [18F]DHMT, to allow for absolute quantification of myocardial reactive oxygen species (ROS) production in a large animal model. METHODS: Six beagle dogs underwent a single baseline dynamic [18F]DHMT PET study, whereas one animal underwent three serial dynamic studies over the course of chronic doxorubicin administration (1 mg·kg-1·week-1 for 15 weeks). During the scans, sequential arterial blood samples were obtained for plasma metabolite correction. The optimal compartment model and graphical analysis method were identified for kinetic modeling. Values for the left ventricular (LV) net influx rate, Ki, were reported for all the studies and compared with the LV standard uptake values (SUVs) and the LV-to-blood pool SUV ratios from the 60 to 90 minute static images. Parametric images were also generated. RESULTS: [18F]DHMT followed irreversible kinetics once oxidized within the myocardium in the presence of superoxide, as evidenced by the fitting generated by the irreversible two-tissue (2Ti) compartment model and the linearity of Patlak analysis. Myocardial Ki values showed a weak correlation with LV SUV (R2 = 0.27), but a strong correlation with LV-to-blood pool SUV ratio (R2 = 0.92). Generation of high-quality parametric images showed superior myocardial to blood contrast compared to static images. CONCLUSIONS: A dynamic PET imaging technique for [18F]DHMT was developed with full and simplified kinetic modeling for absolute quantification of myocardial superoxide production in a large animal model.

2.
J Food Biochem ; : e13278, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32412117

RESUMO

Betulinic acid (BA) was verified to possess plenty of biological activities including anti-tumor, anti-inflammatory and so on. In our research, we studied the growth inhibition, apoptosis promotion and metastasis resistance of ovarian cancer cells by BA. The result showed that BA showed a time- and dose-dependent inhibitory effect on ovarian cancer cell lines. SKOV3 cell line proliferation has a concentration- and time-dependently, which may be inhibited by BA. Furthermore, BA inhibited the metastasis of tumor cells remarkably by inhibiting epithelial-mesenchymal transition process. Beyond that, the weight and volume of subcutaneous tumor was distinctly suppressed by administration of BA in tumor-bearing mice of SKOV3 cells. Pathological and immunohistochemical tests showed that Ki-67+ and MMP-2+ cells were dramatically decreased after BA administration, indicating that BA can not only suppress proliferation, but also inhibit migration of tumor cells. Taken together, BA can be a valuable candidate drug for the treatment of ovarian cancer. PRACTICAL APPLICATIONS: Betulinic acid (BA) isolated from natural plants such as fenugreek, eucalyptus bulb and mulberry has been reported with many biological activities. Results from this study revealed that in vitro and in vivo BA-induced apoptosis and inhibited migration and invasion of human ovarian cancer cells. Therefore, BA from natural plants may be developed as a potential drug for inhibition the development of ovarian cancer cells.

3.
Chem Commun (Camb) ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32373827

RESUMO

The three component hydroxyletherification and hydroxylazidation reactions of (trifluoromethyl)alkenes are reported, providing various useful α-trifluoromethyl ß-heteroatom substituted tertiary alcohols in high yields. The ipso-defluorooxylation of (trifluoromethyl)alkenes with oximes is completely inhibited. A pesticidal active compound could be synthesized with our method.

4.
iScience ; 23(5): 101128, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32422594

RESUMO

Single-molecule sequencing technologies produce much longer reads compared with next-generation sequencing, greatly improving the contiguity of de novo assembly of genomes. However, the relatively high error rates in long reads make it challenging to obtain high-quality assemblies. A computationally intensive consensus step is needed to resolve the discrepancies in the reads. Efficient consensus tools have emerged in the recent past, based on partial-order alignment. In this study, we discovered that the spatial relationship of alignment pileup is crucial to high-quality consensus and developed a deep learning-based consensus tool, CONNET, which outperforms the fastest tools in terms of both accuracy and speed. We tested CONNET using a 90× dataset of E. coli and a 37× human dataset. In addition to achieving high-quality consensus results, CONNET is capable of delivering phased diploid genome consensus. Diploid consensus on the above-mentioned human assembly further reduced 12% of the consensus errors made in the haploid results.

5.
J Mol Endocrinol ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32302969

RESUMO

miR-146b-5p is overexpressed in papillary thyroid carcinoma (PTC) and is thought to be a related diagnostic marker. Previous studies have indicated the effects of iodine on oncogenic activation. However, the effect of iodine on the proliferation of PTC cells and the associated underlying mechanisms remain unclear. We found that miR-146b-5p was downregulated and smad4 was upregulated in patients exposed to high iodine concentration by in situ hybridisation (ISH) and immunohistochemical (IHC). NaI (10-3 M) treatment downregulated miR-146b-5p and upregulated Smad4 in PTC cell lines. Luciferase assay was used to confirm that Smad4 is a target of miR-146b-5p. Furthermore, MTT assay and cell cycle analysis indicated that 10-3 M NaI suppressed cell proliferation and caused G0/G1 phase arrest. Real-time PCR and western blotting demonstrated that 10-3 M NaI increased p21, p27, and p57 levels and reduced cyclin D1 levels in PTC cells. Our findings suggest that 10-3 M NaI increases Smad4 levels through repression of miR-146b-5p expression, curbing the proliferation in PTC.

6.
Cell Biochem Funct ; 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32283563

RESUMO

Gastric cancer (GC) is one of the most prevalent types of malignancies. Betulinic acid (BA) is a natural pentacyclic triterpene with a lupine structure. However, to the best of our knowledge, there is no research study on the anti-tumour and anti-metastasis effect of BA on GC. In this study, we assessed the anti-cancer effect of BA on human GC cells in vitro and in vivo. We first investigated the cytotoxicity and anti-proliferation effect of BA on GC cells of SNU-16 and NCI-N87. The results indicated that BA had significant cytotoxic and inhibitory effects on GC cells in a dose- and time-dependent manner. To further study the cytotoxic action of BA on GC cells, we assessed the apoptotic induction effect of BA on SNU-16 cells and found that BA distinctly induced apoptosis in SNU-16 cells. In addition, BA inhibited the migratory and invasive abilities of SNU-16 cells. Western-blot analysis revealed that BA suppressed the migration and invasion of GC cells by impairing epithelial-mesenchymal transition progression. Furthermore, in vivo experiments showed that BA could delay tumour growth and inhibit pulmonary metastasis, which is consistent with the results of in vitro studies. Overall, we evaluated the anti-cancer effect of BA on human GC cells in vivo and in vitro, and the present study provides new evidence on the use of BA as a potential anti-cancer drug for GC treatment. SIGNIFICANCE OF THE STUDY: BA significantly suppressed proliferation and triggered apoptosis in GC cells. Additionally, BA remarkably inhibited migration and invasion of GC cells by impairing the epithelial-mesenchymal transition signalling pathway. It is worth noting that BA drastically retarded tumour growth in the xenograft mouse model of GC. Our results indicated that BA can be considered a candidate drug for GC therapy.

7.
Support Care Cancer ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32215735

RESUMO

An important aspect of breast cancer survivorship is finding comfortable undergarments that work for women's post-treatment bodies. Patients who undergo mastectomy, including both those who do and do not receive reconstruction, need bras that can accommodate new breast shape, size, and feel, as well as scarring and skin sensitivity. Our research with breast cancer patients and the literature reveal that ready-to-wear bras are inadequate for the variety of patients' needs, and many women lack support and guidance to make decisions about undergarments after cancer. This commentary describes a major quality-of-life challenge for breast cancer survivors and makes recommendations for future research. Healthcare providers need more guidance and resources to be able to help their patients prepare for this aspect of survivorship. New technologies, such as biomechanical modeling, 3D body scanning, and manufacturing techniques, should be pursued in collaboration with patients, healthcare providers, and clothing designers to ease this burden for breast cancer patients.

8.
Angiogenesis ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32140799

RESUMO

To examine whether free fatty acid receptor 4 (FFAR4) activation can protect against choroidal neovascularization (CNV), which is a common cause of blindness, and to elucidate the mechanism underlying the inhibition, we used the mouse model of laser-induced CNV to mimic angiogenic aspects of age-related macular degeneration (AMD). Laser-induced CNV was compared between groups treated with an FFAR4 agonist or vehicle, and between FFAR4 wild-type (Ffar4+/+) and knock out (Ffar4-/-) mice on a C57BL/6J/6N background. The ex vivo choroid-sprouting assay, including primary retinal pigment epithelium (RPE) and choroid, without retina was used to investigate whether FFAR4 affects choroidal angiogenesis. Western blotting for pNF-ĸB/NF-ĸB and qRT-PCR for Il-6, Il-1ß, Tnf-α, Vegf, and Nf-ĸb were used to examine the influence of FFAR4 on inflammation, known to influence CNV. RPE isolated from Ffar4+/+ and Ffar4-/- mice were used to assess RPE contribution to inflammation. The FFAR4 agonist suppressed laser-induced CNV in C57BL/6J mice, and CNV increased in Ffar4-/- compared to Ffar4+/+ mice. We showed that the FFAR4 agonist acted through the FFAR4 receptor. The FFAR4 agonist suppressed mRNA expression of inflammation markers (Il-6, Il-1ß) via the NF-ĸB pathway in the retina, choroid, RPE complex. The FFAR4 agonist suppressed neovascularization in the choroid-sprouting ex vivo assay and FFAR4 deficiency exacerbated sprouting. Inflammation markers were increased in primary RPE cells of Ffar4-/- mice compared with Ffar4+/+ RPE. In this mouse model, the FFAR4 agonist suppressed CNV, suggesting FFAR4 to be a new molecular target to reduce pathological angiogenesis in CNV.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32219492

RESUMO

PURPOSE: Attenuation correction using CT transmission scanning increases the accuracy of single-photon emission computed tomography (SPECT) and enables quantitative analysis. Current existing SPECT-only systems normally do not support transmission scanning and therefore scans on these systems are susceptible to attenuation artifacts. Moreover, the use of CT scans also increases radiation dose to patients and significant artifacts can occur due to the misregistration between the SPECT and CT scans as a result of patient motion. The purpose of this study is to develop an approach to estimate attenuation maps directly from SPECT emission data using deep learning methods. METHODS: Both photopeak window and scatter window SPECT images were used as inputs to better utilize the underlying attenuation information embedded in the emission data. The CT-based attenuation maps were used as labels with which cardiac SPECT/CT images of 65 patients were included for training and testing. We implemented and evaluated deep fully convolutional neural networks using both standard training and training using an adversarial strategy. RESULTS: The synthetic attenuation maps were qualitatively and quantitatively consistent with the CT-based attenuation map. The globally normalized mean absolute error (NMAE) between the synthetic and CT-based attenuation maps were 3.60% ± 0.85% among the 25 testing subjects. The SPECT reconstructed images corrected using the CT-based attenuation map and synthetic attenuation map are highly consistent. The NMAE between the reconstructed SPECT images that were corrected using the synthetic and CT-based attenuation maps was 0.26% ± 0.15%, whereas the localized absolute percentage error was 1.33% ± 3.80% in the left ventricle (LV) myocardium and 1.07% ± 2.58% in the LV blood pool. CONCLUSION: We developed a deep convolutional neural network to estimate attenuation maps for SPECT directly from the emission data. The proposed method is capable of generating highly reliable attenuation maps to facilitate attenuation correction for SPECT-only scanners for myocardial perfusion imaging.

10.
Org Lett ; 22(6): 2246-2250, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32115955

RESUMO

Kijanose is one of the most highly functionalized deoxysugars found in nature and a challenging synthetic target. We found that the ring opening of trisubstituted, 2-oxazolidinone-fused aziridines is regio- and stereoselective, and the azide adduct has the same stereochemistry as that of kijanose after converting the azido to a nitro group. Therefore, both α- and ß-methyl l-kijanosides were prepared from ethyl l-lactate in 14% total yield.

11.
J Chem Phys ; 152(4): 044105, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32007075

RESUMO

The Bethe-Salpeter equation (BSE) based on GW quasiparticle levels is a successful approach for calculating the optical gaps and spectra of solids and also for predicting the neutral excitations of small molecules. We here present an all-electron implementation of the GW+BSE formalism for molecules, using numeric atom-centered orbital (NAO) basis sets. We present benchmarks for low-lying excitation energies for a set of small organic molecules, denoted in the literature as "Thiel's set." Literature reference data based on Gaussian-type orbitals are reproduced to about one millielectron-volt precision for the molecular benchmark set, when using the same GW quasiparticle energies and basis sets as the input to the BSE calculations. For valence correlation consistent NAO basis sets, as well as for standard NAO basis sets for ground state density-functional theory with extended augmentation functions, we demonstrate excellent convergence of the predicted low-lying excitations to the complete basis set limit. A simple and affordable augmented NAO basis set denoted "tier2+aug2" is recommended as a particularly efficient formulation for production calculations. We finally demonstrate that the same convergence properties also apply to linear-response time-dependent density functional theory within the NAO formalism.

12.
Cell Biochem Funct ; 38(3): 249-256, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32107809

RESUMO

Hinokiflavone is a natural product, isolated from Selaginella P. Beauv, Juniperus phoenicea and Rhus succedanea. Even though hinokiflavone was reported to possess cytotoxicity to many cancer cells, and has potential in cancer treatment, the anti-proliferation and anti-metastasis efficacy of hinokiflavone on human breast cancer cells has not a further research. In this study, we investigated the anti-cancer activity of hinokiflavone in human breast cancer cells in vitro and in vivo. Hinokiflavone exhibited a time- and dose-dependent manner apoptosis induction by upregulating expression of Bax and downregulating Bcl-2 in breast cancer cells. Furthermore, hinokiflavone significantly inhibited the migration and invasion of breast cancer cells by impairing the process of epithelial-to-mesenchymal transition. In addition, the tumour growth was distinctly inhibited by treatment of hinokiflavone in a xenograft tumour mouse model of MDA-MB-231 cells. Immunohistochemical analysis of tumour sections showed that MMP-2+ cells and Ki-67+ cells were remarkably decreased in tumour tissues of mice after treatment of hinokiflavone, indicating that hinokiflavone inhibits not only proliferation but also metastasis of breast cancer cells. Our study suggested that hinokiflavone can be a potential drug to breast cancer. SIGNIFICANCE OF THE STUDY: Hinokiflavone significantly inhibited proliferation and induced apoptosis in breast cancer cells. In addition, hinokiflavone remarkably inhibited migration and invasion of breast cancer cells via EMT signalling pathway. It is worth noting that hinokiflavone possesses anti-tumour effect in tumour mouse xenograft model of breast cancer. Overall, our results indicated that hinokiflavone may be a potential anticancer drug for breast cancer treatment.

13.
Gene Expr Patterns ; 35: 119096, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32027977

RESUMO

Glomerular capillary formation is one of the fundamental mysteries in renal developmental biology. However, there are still debates on this issue, and its detailed formation process has not been clarified. To resolve this problem, we performed antibody staining with ultra-thick section on embryonic and postnatal mouse kidneys. We obtained the expression patterns of several genes that play an important role in the development of glomerular capillaries. We found that blood vessel of the fetal kidneys expanded through proliferation and sprouting. During the comma-stage and S-shaped stage, 3-4 capillaries began to bud and migrate into the glomerular cleft, forming a capillary bed in the Bowman's capsule. Then, the capillary bed expanded into mature glomerular capillary by intussusceptive angiogenesis. The afferent and efferent arterioles were formed through pruning. The distribution of VEGFA in the nephron epithelial cells but not only in podocytes, induced multiple capillaries sprouted into the glomerular cleft. And CXCR4 played an important role in the differentiation and expansion of capillary bed into glomerular capillary. Immunofluorescence performed with ultra-thick section allowed us to investigate the development of complex structure tissues systematically and comprehensively.

14.
Phys Chem Chem Phys ; 22(9): 4967-4973, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32073010

RESUMO

Nowadays identifying a high-performance catalyst for converting methane to methanol is crucial because methanol serves as an excellent energy source and has wide chemical applications. In the present study, we used DFT, a computational chemistry method, to investigate the reaction mechanism of methanol production by conversion of methane on Pt5 nanoparticles supported on graphene oxide (GO) substrates. Computational results predicted that the Pt5/GO system exhibits excellent catalysis efficiency, compared with those of the previously examined Pt2/GO and Pt2O2/GO systems. Energetics of examined molecular species and the reaction mechanism showed that the Pt5/GO system exhibits high stability in this catalysis reaction and catalyzes the reaction efficiently. Moreover, between the two investigated surfaces GO and UGO, GO performed better and should be a promising catalyst support to convert methane into methanol.

15.
Cerebrovasc Dis ; 49(1): 62-69, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32023610

RESUMO

INTRODUCTION: The multiphase computed tomography angiography (mCTA) is superior to the noncontrast computed tomography (NCCT) in selecting patients that would benefit from mechanical thrombectomy following an acute ischemic stroke (AIS). It remains unclear whether the longer examination time of mCTA worsens outcomes of intravenous recombinant tissue plasminogen activator (IV r-tPA) or increases the risk of hemorrhagic transformation (HT) compared to NCCT in Asian stroke patients. METHODS: Between January 2011 and December 2017, 199 AIS patients receiving IV r-tPA with initial National Institute of Health Stroke Scale (NIHSS) scores between 6 and 25 were enrolled in a single medical center. Onset-to-needle time (ONT), door-to-needle time (DNT), and creatinine levels before and after thrombolysis were recorded. We evaluated NIHSS scores 2, 24 h after treatment, and at discharge, the modified Rankin Scale (mRS) at discharge, and mortality rate. The presence of HT was reviewed within 7 days after thrombolysis. RESULTS: DNT, perithrombolysis creatinine levels, NIHSS, and mRS scores at the emergency room were similar between the NCCT and mCTA groups. ONT was shorter in the mCTA group. AIS patients got more significant neurologic improvement (NIHSS decrease ≥4) after thrombolysis and physically independent (mRS ≤2) at discharge in the mCTA group. Mortality rates, symptomatic, and total HT rates were similar between the NCCT and mCTA groups. CONCLUSION: Comparing to NCCT, mCTA-based IV r-tPA would not delay DNT nor worsen the outcome. Furthermore, mCTA provides more information for early identification of candidates for mechanical thrombectomy in Asian AIS patients.

16.
Nat Commun ; 11(1): 939, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094358

RESUMO

The island of Sardinia has been of particular interest to geneticists for decades. The current model for Sardinia's genetic history describes the island as harboring a founder population that was established largely from the Neolithic peoples of southern Europe and remained isolated from later Bronze Age expansions on the mainland. To evaluate this model, we generate genome-wide ancient DNA data for 70 individuals from 21 Sardinian archaeological sites spanning the Middle Neolithic through the Medieval period. The earliest individuals show a strong affinity to western Mediterranean Neolithic populations, followed by an extended period of genetic continuity on the island through the Nuragic period (second millennium BCE). Beginning with individuals from Phoenician/Punic sites (first millennium BCE), we observe spatially-varying signals of admixture with sources principally from the eastern and northern Mediterranean. Overall, our analysis sheds light on the genetic history of Sardinia, revealing how relationships to mainland populations shifted over time.


Assuntos
DNA Antigo , DNA Mitocondrial/genética , Genética Populacional/história , Migração Humana , Modelos Genéticos , Arqueologia/métodos , Restos Mortais , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Conjuntos de Dados como Assunto , Feminino , História do Século XV , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , História Medieval , Humanos , Itália , Masculino , Análise de Sequência de DNA
17.
Int J Mol Sci ; 21(4)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098361

RESUMO

The tightly structured neural retina has a unique vascular network comprised of three interconnected plexuses in the inner retina (and choroid for outer retina), which provide oxygen and nutrients to neurons to maintain normal function. Clinical and experimental evidence suggests that neuronal metabolic needs control both normal retinal vascular development and pathological aberrant vascular growth. Particularly, photoreceptors, with the highest density of mitochondria in the body, regulate retinal vascular development by modulating angiogenic and inflammatory factors. Photoreceptor metabolic dysfunction, oxidative stress, and inflammation may cause adaptive but ultimately pathological retinal vascular responses, leading to blindness. Here we focus on the factors involved in neurovascular interactions, which are potential therapeutic targets to decrease energy demand and/or to increase energy production for neovascular retinal disorders.

18.
J Nucl Cardiol ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32043239

RESUMO

2-deoxy-2- [18F] fluoro-D-glucose (FDG) PET is commonly used for the assessment of vessel wall inflammation. Guidelines for analysis of arterial wall FDG signal recommend the use of the average of maximal standardized uptake value (mean SUVmax) and target-to-blood (mean TBRmax) ratio. However, these methods have not been validated against a gold standard such as tissue activity ex vivo or net uptake rate of FDG (Ki) obtained using kinetic modeling. We sought to evaluate the accuracy of mean SUVmax and mean TBRmax for aortic wall FDG signal quantification in comparison with the net uptake rate of FDG. METHODS: Dynamic PET data from 13 subjects without prior history of cardiovascular disease who enrolled in a study of vascular inflammation were used for this analysis. Ex vivo measurement of plasma activity was used as the input function and voxel-by-voxel Patlak analysis was performed with t* = 20 minute to obtain the Ki image. The FDG signal in the ascending aortic wall was quantified on PET images following recent guidelines for vascular imaging to determine mean SUVmax and mean TBRmax. RESULTS: The Ki in the ascending aortic wall did not correlate with mean SUVmax (r = 0.10, P = NS), but correlated with mean TBRmax (r = 0.82, P < 0.001) (Figure 1B). Ki and Ki_max strongly correlated (R = 0.96, P < 0.0001) and similar to Ki, Ki_max did not correlate with mean SUVmax (r = 0.17, P = NS), but correlated with mean TBRmax (r = 0.83, P < 0.001). CONCLUSIONS: Kinetic modeling supports the use of mean TBRmax as a surrogate for the net uptake rate of FDG in the arterial wall. These results are relevant to any PET imaging agent, regardless of the biological significance of the tracer uptake in the vessel wall.

19.
Laryngoscope ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045010

RESUMO

OBJECTIVE: To assess the risk of Alzheimer's disease (AD) in patients with obstructive sleep apnea (OSA) with or without treatment based on real-world evidence. STUDY DESIGN: Retrospective cohort study. METHODS: Patients newly diagnosed with OSA during 1997-2012 were identified using the National Health Insurance Research Database of Taiwan. Patients without OSA were randomly selected and matched in a 1:4 ratio by age, sex, urbanization level, and income. All patients were followed up until death or the end of 2013. The primary outcome was AD occurrence. RESULTS: This study included 3,978 OSA patients and 15,912 non-OSA patients. OSA was independently and significantly associated with a higher incidence of AD in an adjusted Cox proportional hazard model (adjusted hazard ratio: 2.12; 95% confidence interval [CI], 1.27-3.56). The average period of AD detection from the time of OSA occurrence was 5.44 years (standard deviation: 2.96). Subgroup analyses revealed that the effect of OSA remained significant in patients aged ≥60 years, male subgroups, patients without CPAP or surgical treatment, and patients without pharmacological therapies. Patients with OSA who received treatment (continuous positive airway pressure or surgery) exhibited a significantly reduced risk of AD compared with those without treatment (incidence rate ratio 0.23, 95% CI, 0.06-0.98). CONCLUSION: OSA is independently associated with an increased risk of AD. Treatment for OSA reduces the AD risk in OSA patients. AD irreversibility renders OSA as a potential modifiable target for slowing or preventing the process of AD development. LEVEL OF EVIDENCE IV: Laryngoscope, 2020.

20.
Cardiovasc Diabetol ; 19(1): 2, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910836

RESUMO

BACKGROUND AND AIM: Peroxisome proliferator-activated receptor-γ (PPAR-γ) modulating treatment may have cardiovascular benefits in type 2 diabetes mellitus (T2DM) patients after ischemic stroke (IS). However, whether there are additional benefits from intensive PPAR-γ modulating treatments in Asian patients with T2DM and hypertension (HTN) after IS remains unknown. METHODS: Between 2001 and 2013, patients admitted due to IS were identified from the National Health Insurance Research Database of Taiwan. Patients with T2DM and HTN using angiotensin receptor blockers were further included. Eligible patients were divided into two groups: (1) pioglitazone and (2) non-pioglitazone oral anti-diabetic agent groups. Propensity score matching (1:2) was used to balance the distribution of baseline characteristics, stroke severity and medications. The primary outcome was recurrent IS. Subgroup analysis for recurrent IS in pioglitazone and/or telmisartan users, the trend of IS risks across different PPAR-γ intensity treatments, and dose-dependent outcomes across different pioglitazone possession ratios were further studied. Statistical significance was set at p < 0.05 and p < 0.1 for clinical outcomes and interaction of subgroup analyses, respectively. RESULTS: There were 3190 and 32,645 patients in the pioglitazone and non-pioglitazone groups. Patients of the pioglitazone group had a lower risk of recurrent IS (subdistribution hazard ratio, 0.91; 95% confidence interval 0.84-0.99). Pioglitazone was also associated with reduced recurrent IS in patients who also used telmisartan (p for interaction = 0.071). A graded correlation was found a borderline significant trend between the intensity of PPAR-γ therapy and following IS (p = 0.076). The dose-dependent outcome also showed that a borderline significant trend that higher pioglitazone possession ratio was associated with a lower risk of recurrent IS (p = 0.068). CONCLUSIONS: The current study suggests that the use of pioglitazone in type 2 diabetic and hypertensive IS patients is associated with fewer recurrent IS events in an Asian population. Concurrent telmisartan use or a higher pioglitazone possession ratio may have a trend of increased pleiotropic effects, which could possibly be related to higher PPAR-γ effects. Future studies are warranted to confirm or refute the clinical effects and the possible mechanism of more intensive PPAR-γ-modulating treatments.

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