Role of PPARα and Its Agonist in Renal Diseases

Peroxisome proliferator-activated receptor (PPAR)-α, a member of a large nuclear receptor superfamily, plays a major role in the regulation of lipid metabolism. Recently, PPARα activation has been shown to confer additional benefits on endothelial function, kidney function, and anti-inflammation, suggesting that PPARα agonists may be good candidates for treating acute renal failure. In clinical application, PPAR-α activators, such as hypolipidemic drugs in fibric acid class, were proven to have therapeutic effects on metabolic syndrome and cardiovascular disease. This paper focuses on signaling pathways, ligand selectivity, and physio-pathological roles of PPARα in kidney diseases and the therapeutic utility of PPARα modulators in the treatment of diabetes and inflammation-induced nephropathy. Implication of new and more potent PPAR-α activators could provide important insights into the overall benefits of activating PPAR-α clinically for the treatment of dyslipidemia and the prevention of diabetic or inflammation-induced nephropathy in the future

Lightly Weighted Automatic Audio Parameter Extraction for the Quality Assessment of Consensus Auditory-Perceptual Evaluation of Voice

The Consensus Auditory-Perceptual Evaluation of Voice is a widely employed tool in clinical voice quality assessment that is significant for streaming communication among clinical professionals and benchmarking for the determination of further treatment. Currently, because the assessment relies on experienced clinicians, it tends to be inconsistent, and thus, difficult to standardize. To address this problem, we propose to leverage lightly weighted automatic audio parameter extraction, to increase the clinical relevance, reduce the complexity, and enhance the interpretability of voice quality assessment. The proposed method utilizes age, sex, and five audio parameters: jitter, absolute jitter, shimmer, harmonic-to-noise ratio (HNR), and zero crossing. A classical machine learning approach is employed. The result reveals that our approach performs similar to state-of-the-art (SOTA) methods, and outperforms the latent representation obtained by using popular audio pre-trained models. This approach provide insights into the feasibility of different feature extraction approaches for voice evaluation. Audio parameters such as jitter and the HNR are proven to be suitable for characterizing voice quality attributes, such as roughness and strain. Conversely, pre-trained models exhibit limitations in effectively addressing noise-related scorings. This study contributes toward more comprehensive and precise voice quality evaluations, achieved by a comprehensively exploring diverse assessment methodologies.Comment: Published in IEEE 42th International Conference on Consumer Electronics (ICCE 2024

Epilepsy and Neurodevelopmental Outcomes in Children With Etiologically Diagnosed Central Nervous System Infections: A Retrospective Cohort Study

Background: Central nervous system (CNS) infection in childhood can lead to neurological sequelae, including epilepsy, and neurodevelopmental disorders, such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). This study investigated the association of etiologically diagnosed childhood brain infections with the subsequent risks of epilepsy and neurodevelopmental disorders.Objectives: We retrospectively analyzed the data of children aged <18 years who had definite brain infections with positive cerebrospinal fluid cultures from January 1, 2005, to December 31, 2017. These patients were followed to evaluate the risks of epilepsy and neurodevelopmental disease (ADHD and ASD) after brain infections (group 1) in comparison with the risks in those without brain infections (group 2).Results: A total of 145 patients with an average age of 41.2 months were included in group 1. Enterovirus accounted for the majority of infections, followed by group B Streptococcus, S. pneumoniae, and herpes simplex virus. A total of 292 patients with an average age of 44.8 months were included in group 2. The 12-year risk of epilepsy in group 1 was 10.7 (95% confidence interval [CI], 2.30–49; p < 0.01). Compared with group 2 (reference), the risk of ASD in the age interval of 2–5 years in group 1 was 21.3 (95% CI, 1.33–341.4; p = 0.03). The incidence of ADHD in group 1 was not significantly higher than that in group 2.Conclusions: This study identified the common etiological causes of brain infections in Taiwanese children. The highest-risk neurodevelopmental sequelae associated with brain infections was epilepsy. Children who had a diagnosis of brain infection (specially Enterovirus) should be followed since they are at greater risk of developing epilepsy and ASD

Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug

Ultrasound (US) sonication with microbubbles (MBs) has the potential to disrupt blood vessels and enhance the delivery of drugs into the sonicated tissues. In this study, mouse ear tumors were employed to investigate the therapeutic effects of US, MBs, and pegylated liposomal doxorubicin (PLD) on tumors. Tumors started to receive treatments when they grew up to about 15 mm3 (early stage) with injection of PLD 10 mg/kg, or up to 50 mm3 (medium stage) with PLD 6 (or 4) mg/kg. Experiments included the control, PLD alone, PLD + MBs + US, US alone, and MBs + US groups. The procedure for the PLD + MBs + US group was that PLD was injected first, MB (SonoVue) injection followed, and then US was immediately sonicated on the tumor. The results showed that: (1) US sonication with MBs was always able to produce a further hindrance to tumor growth for both early and medium-stage tumors; (2) for the medium-stage tumors, 6 mg/kg PLD alone was able to inhibit their growth, while it did not work for 4 mg/kg PLD alone; (3) with the application of MBs + US, 4 mg/kg PLD was able to inhibit the growth of medium-stage tumors; (4) for early stage tumors after the first treatment with a high dose of PLD alone (10 mg/kg), the tumor size still increased for several days and then decreased (a biphasic pattern); (5) MBs + US alone was able to hinder the growth of early stage tumors, but unable to hinder that of medium stage tumors. The results of histological examinations and blood perfusion measurements indicated that the application of MBs + US disrupts the tumor blood vessels and enhances the delivery of PLD into tumors to significantly inhibit tumor growth

Maternal autoimmune disease and risk of offspring autism spectrum disorder – a nationwide population-based cohort study

IntroductionAutism spectrum disorder (ASD) is a group of neurodevelopmental disorders which cause long term social and behavior impairment, and its prevalence is on the rise. Studies about the association between maternal autoimmune diseases and offspring ASD have controversial results. The aim of this study was to investigate whether maternal autoimmune diseases increase the risk of ASD in offspring from a population-based perspective.MethodsThe data sources were Taiwan’s National Health Insurance Research Database (NHIRD) and Taiwan’s Maternal and Child Health Database (MCHD), which were integrated and used to identify newborns whose mothers were diagnosed with autoimmune disease. Newborns were matched by maternal age, neonatal gender, and date of birth with controls whose mothers were without autoimmune disease using a ratio of 1:4 between 2004 and 2019. Data on diagnoses of autoimmune disease and autism spectrum disorders were retrieved from NHIRD. Patients who had at least 3 outpatient visits or at least 1 admission with a diagnosis of autoimmune disease and autism spectrum disorders were defined as incidence cases. The risks of ASD in offspring were compared between mothers with or without autoimmune disorders.ResultsWe identified 20,865 newborns whose mothers had been diagnosed with autoimmune disease before pregnancy and matched them at a ratio of 1:4 with a total of 83,460 newborn whose mothers were without autoimmune disease, by maternal age, neonatal gender, and date of birth. They were randomly selected as the control group. The cumulative incidence rates of autism spectrum disorders (ASD) were significantly higher among the offspring of mothers with autoimmune diseases. After adjusting for cofactors, the risk of ASD remained significantly higher in children whose mother had autoimmune diseases. Regarding to specific maternal autoimmune disease, Sjögren’s syndrome and rheumatoid arthritis were both associated with elevated risks of ASD in offspring.ConclusionMother with autoimmune disease might be associated with increasing the risk of autism spectrum disorder in offspring

The Incidence and Prevalence of Thromboangiitis Obliterans in Taiwan: A Nationwide, Population-based Analysis of Data Collected from 2002 to 2011

OBJECTIVE: To estimate the incidence and prevalence of thromboangiitis obliterans in Taiwan in the period spanning from 2002 to 2011. METHODS: We identified all incident and prevalent cases with a diagnosis of thromboangiitis obliterans (International Classification of Diseases, Ninth Revision code 443.1) in the period spanning from 2002 to 2011 using Taiwan’s National Health Insurance Research Database. We calculated the age- and sex-specific incidence and prevalence rates of thromboangiitis obliterans during the study period. RESULTS: From 2002 to 2011, 158 patients were diagnosed with thromboangiitis obliterans; of these, 76% were men. Most (63%) of the patients wer

Association Between Thyroid Disorders and Colorectal Cancer Risk in Adult Patients in Taiwan

IMPORTANCE Thyroid hormones have been shown to affect several important pathways in cancer development, including colorectal cancer (CRC). Clinical studies examining the association between thyroid disorders and colorectal cancer have conflicting results and have predominantly involved white populations. OBJECTIVE To determine if a diagnosis of hyperthyroidism or hypothyroidism is associated with the risk of developing colorectal cancer in an East Asian population. DESIGN, SETTING, AND PARTICIPANTS This nationwide population-based case-control study was conducted from April 27, 2018, to November 8, 2018, using the Taiwanese National Health Insurance Research Database. Participants were adults (n = 139 426) either with a new diagnosis (between 2008 and 2013) of primary colorectal cancer without a history of cancer, or without cancer. Cases and controls were matched 11 by age, sex, and index date. Diagnosis of hyperthyroidism or hypothyroidism prior to the diagnosis of colorectal cancer (or the same index date in controls) was then determined. MAIN OUTCOMES AND MEASURES Risk differences in developing colorectal cancer among patients with a medical history of hyperthyroidism or hypothyroidism. RESULTS A total of 139 426 patients were included in the study, and 69 713 individuals made up each case and control group, which were both predominantly male (39 872 [57.2%]). The mean (SD) age for those with CRC was 65.8 (13.7) years and for those without CRC was 66.0 (13.6) years. Both hyperthyroidism (adjusted odds ratio [aOR], 0.77; 95% CI, 0.69-0.86; P < .001) and hypothyroidism (aOR, 0.78; 95% CI, 0.65-0.94; P = .008) were associated with a decreased risk of being diagnosed with colorectal cancer. An inverse association of rectal cancer was found among patients aged 50 years or older with a history of hypothyroidism despite treatment (aOR, 0.54; 95% CI, 0.39-0.74; P < .001). A history of hyperthyroidism in all age groups was associated with a lower risk of colon cancer (aOR, 0.74; 95% CI, 0.64-0.85; P < .001), with a stronger association seen among those younger than 50 years (aOR, 0.55; 95% CI, 0.36-0.85; P = .007). CONCLUSIONS AND RELEVANCE In this study, hypothyroidism appeared to be associated with a lower risk of rectal cancer, whereas hyperthyroidism appeared to be associated with a lower risk of colon cancer. Because of this, biochemical in vivo research and epidemiologic studies appear to be needed to further clarify the nature of these associations.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]