Increasing evidence supports the association between hyperuricemia and incident chronic kidney disease (CKD); however, there are conflicting data regarding the role of hyperuricemia in the ...progression of CKD. This study retrospectively assessed the longitudinal association between uric acid (UA) level and CKD progression in a Chinese population lived in Taiwan.
Patients with physician diagnosis of hyperuricemia or receiving urate-lowering therapy between 2003 and 2005 were identified in the electronic medical records (EMR) of a tertiary medical center and were followed up until December 31, 2011. Patients were divided into four UA categories at the cut-off 6, 8, and 10 mg/dL. CKD progression was estimated by the change of estimated glomerular filtration rate (eGFR) in the linear mixed models. Kidney failure was defined as an eGFR less than 15 mL/min/1.73 m2 or requiring renal replacement therapy.
A total of 739 patients were analyzed. In the full-adjusted model, patients with a baseline UA level ≥6 mg/dL had greater decline in eGFR ((β = -9.6, 95% CI -16.1, -3.1), comparing to those with a UA level less than 6 mg/dL. When stratifying patients into four UA categories, all three hyperuricemia categories (UA6-8, 8-10, ≥10 mg/dL) associated with a greater decline in eGFR over the follow-up period with an increasing dose-response, comparing to the lowest UA category. The risk of progression to renal failure increased 7% (hazard ratio 1.07, 95% CI 1.00, 1.14) for each 1mg/dL increase in baseline UA level. The influences of hyperuricemia on eGFR decline and the risk of kidney failure were more prominent in patients without proteinuria than those with proteinuria.
Our study showed a higher uric acid level is associated with a significant rapid decline in eGFR and a higher risk of kidney failure, particularly in patients without proteinuria. Our findings suggest hyperuricemia is a potential modifiable factor of CKD progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A patient with progressive metastatic pancreatic cancer was treated with a single infusion of 16.2×10
9
autologous T cells that had been genetically engineered to clonally express two allogeneic ...HLA-C*08:02–restricted T-cell receptors (TCRs) targeting mutant KRAS G12D expressed by the tumors. The patient had regression of visceral metastases (overall partial response of 72% according to the Response Evaluation Criteria in Solid Tumors, version 1.1); the response was ongoing at 6 months. The engineered T cells constituted more than 2% of all the circulating peripheral-blood T cells 6 months after the cell transfer. In this patient, TCR gene therapy targeting the KRAS G12D driver mutation mediated the objective regression of metastatic pancreatic cancer. (Funded by the Providence Portland Medical Foundation.)
A 71-year-old woman with progressive pancreatic adenocarcinoma containing a mutated
KRAS
oncogene was given adoptive cellular therapy of her own T cells that had been altered to express two different T-cell receptors specific for her HLA type and the mutated
KRAS
in the tumor. Six months after treatment, the tumor burden had decreased by 72%, and the response was ongoing.
Public awareness of health-related topics is increasing, and an increase in average life expectancy has increased the senior citizen population in Taiwan. Furthermore, because of the high cost of ...raising young children, people's willingness to give birth has decreased. Taiwan's aging population and declining birth rate are key challenges for its population development, and the promotion of interactions between young children and senior citizens is also a crucial topic for scholars. Therefore, intergenerational learning has been proposed, and several Taiwanese preschools have attempted to develop intergenerational learning courses. This study explored the perceptions of young children and senior citizens during the implementation of intergenerational learning courses in a preschool. The results revealed that the implementation of such courses allowed young children and senior citizens to influence each other's life experiences and develop positive feelings. The interactions also promoted their psychological well-being. Through this study, we clarified the effectiveness of intergenerational learning courses. Finally, we proposed that intergenerational learning courses with the themes of 'caring' and 'love' should be developed and integrated into intergenerational learning courses.
This study explored Richard Shusterman's somaesthetics to understand the rationale for his view on enhancing the body experience of older adults and increasing their participation in art; it also ...examined methods or successful aging to enhance the theoretical foundation for educational gerontology. Accordingly, the research objectives were to (1) analyze the definition of successful aging; (2) clarify the role of body experience and participation in art in promoting successful aging among older adults; (3) explore and discuss Shusterman's somaesthetics; and (4) explore methods for successful aging derived from Shusterman's somaesthetics. This study mainly explored educational philosophy by collecting, reading, analyzing, logically reviewing, and interpreting the literature on this topic. During this exploration, methods for successful aging were reviewed. The findings are as follows: (1) shifting focus of successful aging to the bodies of older adults; (2) cultivating the body consciousness of older adults enables them to understand themselves and pursue virtue, happiness, and justice; (3) popular art can be integrated to promote the aesthetic ability of older adults and encourage their physical participation in the aesthetic process; (4) older adult education should cultivate the somaesthetic sensitivity of older adults; (5) older adult education should incorporate the physical training of older adults to help them enhance their self-cultivation and care for their body, cultivate virtue, and live a better life; and (6) older adult education should integrate the body and mind of older adults.
About 40% of the world's population is overweight or obese and exist at risk of developing type 2 diabetes mellitus (T2D). Obesity is a leading pathogenic factor for developing insulin resistance ...(IR). It is well established that IR and a progressive decline in functional β-cell mass are hallmarks of developing T2D. In order to mitigate the global prevalence of T2D, we must carefully select the appropriate animal models to explore the cellular and molecular mechanisms of T2D, and to optimize novel therapeutics for their safe use in humans. Flavonoids, a group of polyphenols, have drawn great interest for their various health benefits, and have been identified in naturally occurring anti-diabetic compounds. Results from many clinical and animal studies demonstrate that dietary intake of flavonoids might prove helpful in preventing T2D. In this review, we discuss the currently available rodent animal models of T2D and analyze the advantages, the limitations of each T2D model, and highlight the potential anti-diabetic effects of flavonoids as well as the mechanisms of their actions.
Probiotic supplements are potential therapeutic agents for age-related disorders due to their antioxidant and anti-inflammatory properties. However, the effect of probiotics on age-related brain ...dysfunction remains unclear. To investigate the effects of
PS23 (LPPS23) on the progression of age-related cognitive decline, male and female senescence-accelerated mouse prone 8 (SAMP8) mice were divided into two groups (
= 6 each): the control and PS23 groups. From the age of 16 weeks, these groups were given saline and LPPS23, respectively, because SAMP8 mice start aging rapidly after four months of age. After 12 weeks of treatment, we evaluated the effect of LPPS23 by analyzing their appearance, behavior, neural monoamines, anti-oxidative enzymes, and inflammatory cytokines. The PS23 group showed lower scores of senescence and less serious anxiety-like behaviors and memory impairment compared to the control group. The control mice also showed lower levels of neural monoamines in the striatum, hippocampus, and serum. Moreover, LPPS23 induced the anti-oxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). Higher levels of tumor necrosis factor (TNF)-α and monocyte chemotactic protein-1 (MCP1) and lower levels of interleukin (IL)-10 indicated that LPPS23 modulated the inflammation. Our results suggest that LPPS23 supplements could delay age-related cognitive decline, possibly by preventing oxidation and inflammation and modulating gut⁻brain axis communication.
Background On the basis of evidence from studies showing the antidepressant effects of omega-3 polyunsaturated fatty acids and the inverse relation between fish consumption and the prevalence of ...depression, the phospholipid hypothesis seems promising in ascertaining the etiology and treatment of depression. Although several studies have shown lower levels of omega-3 (n-3) polyunsaturated fatty acids in depressive patients, the results of individual polyunsaturated fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and the omega-6 (n-6) polyunsaturated fatty acid arachidonic acid (AA), were inconsistent. Methods We conducted the meta-analyses of 14 studies comparing the levels of polyunsaturated fatty acids between depressive patients and control subjects. The effect size of each study was synthesized by using a random effects model. Results Compared with control subjects, the levels of EPA, DHA, and total n-3 polyunsaturated fatty acids were significantly lower in depressive patients. There was no significant change in AA or total n-6 polyunsaturated fatty acids. Conclusions The results showed lower levels of EPA, DHA, and total n-3 polyunsaturated fatty acids in patients with depression, thus implying that n-3 polyunsaturated fatty acids play a role in the pathogenesis of depression. Our findings provide further support to the phospholipid hypothesis of depression and a rationale for using n-3 polyunsaturated fatty acids as an alternative treatment for depression. With these results, future studies examining specific roles of DHA and EPA in different clusters of depressive symptoms are warranted.
Introduction The primary aim of social studies education is to convey knowledge about cultural and social systems while fostering inquiry, participation, practice, reflection, and innovation. Social ...studies education plays a pivotal role in raising awareness about various ethnic groups, societies, localities, countries, and the world at large. Furthermore, it instills in students a sense of responsibility, leading them to embrace diversity, value human rights, and promote global sustainability. The current elementary social studies curriculum in Taiwan strongly aligns with these principles and is a vehicle for sustainable development in society. Methods The researcher used qualitative research methods and adopted a case study design to review the pedagogical design of the elementary social studies curriculum in Taiwan as a means of sustainability education and enriching children’s cultural learning in the context of sustainability. Children’s learning related to sustainability in an elementary school was investigated, and a social studies teaching design was developed. Finally, the developed teaching approach was implemented in a classroom setting. Results and discussion The study yielded the following findings: (1) The social studies curriculum development in Taiwan is connected to the pulse of life, a sense of care for local communities, and cultivation of local thinking. (2) This social studies curriculum adopts a child-centered and problem-oriented approach and integrates students’ interests and the local environment into the learning process. (3) It effectively enhances students’ sustainability-related competencies and skills. These findings offer valuable insights for teachers and can enable them to shape the direction of their social studies courses and cultivate children’s concept of sustainable development for their living environment.
A brief gonadotropin-releasing hormone analogues (GnRHa) stimulation test which solely focused on LH 30-minute post-stimulation was considered to identify girls with central precocious puberty (CPP). ...However, it was tested using traditional statistical methods. With advanced computer science, we aimed to develop a machine learning-based diagnostic model that processed baseline CPP-related variables and a brief GnRHa stimulation test for CPP diagnosis.
We recruited girls suspected of precocious puberty and underwent a GnRHa stimulation test at Children Hospital 2, Vietnam, and Cathay General Hospital, Taiwan. Clinical data, bone age measurement, and 30-min post-stimulation blood test were used to build up the predictive model. The candidate model was developed by different machine learning algorithms that were mainly evaluated by sensitivity, specificity, the area under the receiver operator characteristic curve (AUC), and F1-score in internal and external validation data to classify girls as CPP and non-CPP at different time-points (0-min, 30-min, 60-min, and 120-min post-stimulation).
Among the 614 girls diagnosed with PP, 524 (85.3%) had CPP. The random forest algorithm yielded the highest value of F1-score (0.976), specificity (0.893), positive predicted value (0.987), and relatively high value of AUC (0.972) that contributed to high probability to identify CPP. The performance metrics of the 30-min post-stimulation diagnostic model including sensitivity and specificity surpassed those of the 0-minute model (0-min) and were equivalent to those of the model obtained 60-min and 120-min post-stimulation. Hence, our machine learning-based model helps shorten the stimulation test to 30 minutes after GnRHa injection, in general, it requires 120 minutes for a completed GnRHa stimulation test.
We developed a diagnostic model based on clinical features and a single sample 30-minute post-stimulation to identify CPP in girls that can reduce distress for children caused by multiple blood samplings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genistein, a major isoflavone compound in soybeans, has been shown to have biological activities including anti‐cancer activates. In the present, we investigated the anti‐leukemia activity of ...genistein on HL‐60 cells in vitro. The percentage of viable cell, cell cycle distribution, apoptotic cell death, reactive oxygen species (ROS), and Ca2+ production and the level of ΔΨm were measured by flow cytometric assay. Cell apoptosis and endoplasmic reticulum (ER) stress associated protein expressions were examined by Western blotting assay. Calpain 1, GRP78, and GADD153 expression were measured by confocal laser microscopy. Results indicated that genistein‐induced cell morphological changes, decreased the total viable cells, induced G2/M phase arrest and DNA damage and fragmentation (cell apoptosis) in HL‐60 cells. Genistein promoted ROS and Ca2+ productions and decreased the level of ΔΨm in HL‐60 cells. Western blotting assay demonstrated that genistein increased ER stress‐associated protein expression such as IRE‐1α, Calpain 1, GRP78, GADD153, caspase‐7, caspase‐4, and ATF‐6α at 20‐50 μM treatment and increased apoptosis associated protein expression such as pro‐apoptotic protein Bax, PARP‐cleavage, caspase‐9, and ‐3, but decreased anti‐apoptotic protein such as Bcl‐2 and Bid in HL‐60 cells. Calpain 1, GRP78, and GADD153 were increased in HL‐60 cells after exposure to 40 μM of genistein. In animal xenografted model, mice were intraperitoneally injected with genistein (0, 0.2, and 0.4 mg/kg) for 28 days and the body weight and tumor volume were recorded. Results showed that genistein did not affect the body weights but significantly reduced the tumor weight in 0.4 mg/kg genistein‐treated group. Genistein also increased the expressions of ATF‐6α, GRP78, Bax, Bad, and Bak in tumor. In conclusion, genistein decreased cell number through G2/M phase arrest and the induction of cell apoptosis through ER stress‐ and mitochondria‐dependent pathways in HL‐60 cells and suppressed tumor properties in vivo.
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