Neonatal jaundice is associated with increased risks of congenital anomalies of the kidney and urinary tract and concomitant urinary tract infection.

The link between neonatal jaundice and urinary tract infection (UTI) remains debated, with congenital kidney and urinary tract anomalies (CAKUT) potentially playing a role. This population-based study aimed to analyze the correlations between neonatal jaundice, CAKUT, and concomitant UTI. The study cohort consisted of 2,078,122 live births from 2004 to 2014. We linked several population-based datasets in Taiwan to identify infants with unexplained neonatal jaundice and their mothers. The primary outcome was the rate of CAKUT occurring within 3 years after delivery, and the presence of concomitant UTI during neonatal jaundice hospitalization. Infants with neonatal jaundice had a significantly higher risk of CAKUT (adjusted odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.11-1.39) during early childhood. Among the subtypes of CAKUT, obstructive uropathy, vesicoureteral reflux and other CAKUT were associated with an increased risk of neonatal jaundice. Infants who underwent intensive phototherapy, had a late diagnosis (> 14 days of postnatal age) or underwent a prolonged duration of phototherapy (> 3 days) exhibited a higher risk of concomitant UTI compared to other infants with jaundice. Our findings indicate a notable association between neonatal jaundice and increased risks of UTIs in the context of CAKUT. This study underscore the importance of vigilant monitoring and timely interventions for neonates presenting with jaundice, while acknowledging the complexity and variability in the progression of CAKUT and its potential connection to UTIs.

Systematic Myostatin Expression Screening Platform for Identification and Evaluation of Myogenesis-Related Phytogenic in Pigs.

Skeletal muscle growth in livestock impacts meat quantity and quality. Concerns arise because certain feed additives, like beta-agonists, may affect food safety. Skeletal muscle is a specialized tissue consisting of nondividing and multinucleated muscle fibers. Myostatin (MSTN), a protein specific to skeletal muscle, is secreted and functions as a negative regulator of muscle mass by inhibiting the proliferation and differentiation of myoblasts. To enhance livestock muscle growth, phytogenic feed additives could be an alternative as they inhibit MSTN activity. The objective of this study was to establish a systematic screening platform using MSTN activity to evaluate phytogenics, providing scientific evidence of their assessment and potency. In this study, we established a screening platform to monitor myostatin promoter activity in rat L8 myoblasts. Extract of Glycyrrhiza uralensis (GUE), an oriental herbal medicine, was identified through this screening platform, and the active fractions of GUE were identified using a process-scale liquid column chromatography system. For in vivo study, GUE as a feed additive was investigated in growth-finishing pigs. The results showed that GUE significantly increased body weight, carcass weight, and lean content in pigs. Microbiota analysis indicated that GUE did not affect the composition of gut microbiota in pigs. In summary, this established rodent myoblast screening platform was used to identify a myogenesis-related phytogenic, GUE, and further demonstrated that the active fractions and compounds inhibited MSTN expression. These findings suggest a novel application for GUE in growth performance enhancement through modulation of MSTN expression. Moreover, this well-established screening platform holds significant potential for identifying and assessing a diverse range of phytogenics that contribute to the process of myogenesis.

Associations between neonatal jaundice and autism spectrum disorder or attention deficit hyperactivity disorder: Nationwide population based cohort study.

BACKGROUND/PURPOSE: Neonatal jaundice might result brain insults. Both autistic spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are developmental disorders, which might result from early brain injury at neonatal period. We aimed to explore the association between neonatal jaundice treated with phototherapy and the ASD or ADHD. METHODS: This retrospective nationwide population cohort study was based on a nationally representative database of Taiwan, and neonates born from 2004 to 2010 were enrolled. All eligible infants were divided into 4 groups, without jaundice, jaundice with no treatment, jaundice with simple phototherapy only and jaundice with intensive phototherapy or blood exchange transfusion (BET). Each infant was follow-up until the date of incident primary outcomes, death, or 7-year-old, whichever occurred first. Primary outcomes were ASD, ADHD. Using cox proportional hazard model to analyze their associations. RESULTS: In total, 118,222 infants with neonatal jaundice were enrolled, including diagnosed only (7260), simple phototherapy (82,990), intensive phototherapy or BET (27,972 infants). The cumulative incidences of ASD in each group was 0.57%, 0.81%, 0.77%, and 0.83%, respectively. The cumulative incidences of ADHD in each group was 2.83%, 4.04%, 3.52% and 3.48%, respectively. Jaundice groups were significantly associated with ASD, ADHD, or either one, even after all other extraneous maternal and neonatal variables were adjusted. After stratification, the associations were still existed in subgroup with birth weights ≥2500 grams and in male subgroup. CONCLUSION: Neonatal jaundice correlated with the ASD and ADHD. The associations were significant in infants of both sexes and with birth weights larger than 2500 grams.

Chemometric-guided chemical marker selection: A case study of the heat-clearing herb Scrophularia ningpoensis.

The selection of medicinal plants' chemical markers focuses on bioactivity as the primary goal, followed by the nature of secondary metabolites, their stability, and availability. However, herbal medicines are valued for their complex and holistic pharmacological effects. A correct chemical marker can be carefully selected by a systematic clarification of their chemical-biological relationships. In the current study, the multi-informative molecular networking (MIMN) approach was employed to construct the anti-inflammatory metabolomic pattern of a heat-clearing herb, Scrophularia ningpoensis Hemsl. (S. ningpoensis). The MIMN molecular families characterized by cinnamic acid glycosides showed a higher bioactivity score compared with the other two major chemical classes (iridoid glycosides and iridoid-cinnamic acid glycosides). The Global Natural Product Social Molecular Networking (GNPS) and Reaxys database were used to assist in the putative annotation of eighteen metabolites from the bioactive and non-bioactive molecular families. The anti-inflammatory validation step was based on the detection of reactive oxygen species (ROS) generation by activated human neutrophils. All compounds from the bioactive MIMN molecular families dose-dependently inhibited the total ROS generation promoted by fMLF (IC50: 0.04-0.42 µM), while the compounds from non-bioactive MIMN clusters did not show any significant anti-inflammatory effect. The ROS-dependent anti-inflammatory activity of these cinnamic acid glycosides was attributed to their oxygen radical scavenging ability. The most abundant cinnamic acid glycoside, angoroside C (IC50: 0.34 µM) was suggested to be selected as a chemical marker for S. ningpoensis. In this study, the MIMN platform was applied to assist in the chemical marker selection of S. ningpoensis. The correct selection of markers will aid in the compilation and revision of herbal monographs and pharmacopeias resulting in the precise analysis and classification of medicinal plants on a scientific basis.

Anti-inflammatory and antiviral activities of flavone C-glycosides of Lophatherum gracile for COVID-19.

Lophatherum gracile (L. gracile) has long been used as a functional food and herbal medicine. Previous studies have demonstrated that extracts of L. gracile attenuate inflammatory response and inhibit SARS-CoV-2 replication; however, the underlying active constituents have yet to be identified. This study investigated the bioactive components of L. gracile. Flavone C-glycosides of L. gracile were found to dominate both anti-inflammatory and antiviral effects. A simple chromatography-based method was developed to obtain flavone C-glycoside-enriched extract (FlavoLG) from L. gracile. FlavoLG and its major flavone C-glycoside isoorientin were shown to restrict respiratory bursts and the formation of neutrophil extracellular traps in activated human neutrophils. FlavoLG and isoorientin were also shown to inhibit SARS-CoV-2 pseudovirus infection by interfering with the binding of the SARS-CoV-2 spike on ACE2. These results provide scientific evidence indicating the efficacy of L. gracile as a potential supplement for treating neutrophil-associated COVID-19.

Lonicerae Japonicae Flos Attenuates Neutrophilic Inflammation by Inhibiting Oxidative Stress.

Lonicerae japonicae flos (LJ) is an Asian traditional herb that is used as a dietary supplement, tea, and beverage to clear heat and quench thirst. However, no studies investigated its effect on activated human neutrophils, which played a crucial role in the bad prognosis of coronavirus disease of 2019 (COVID-19) patients by aggravating lung inflammation and respiratory failure. Herein, we evaluated the anti-inflammatory effect of LJ ethanol extract (LJEE) on human neutrophils activated by N-formyl-methionyl-leucyl-phenylalanine (fMLF). Our experimental results indicated that LJEE suppressed fMLF-activated superoxide anion (O2•-) generation, the expression of CD11b, and cell adhesion and migration, as well as the formation of neutrophil extracellular traps in human neutrophils. Further in-depth mechanical investigation revealed that pretreatment with LJEE accelerated the Ca2+ clearance, but did not affect the phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) in activated human neutrophils. In addition, LJEE displayed a dose-dependent reactive oxygen species (ROS) scavenger activity, which assisted its anti-inflammatory activity. From the bioassay-coupled chromatographic profile, chlorogenic acids were found to dominate the anti-inflammatory effects of LJEE. Moreover, LJ water extract (LJWE) demonstrated an interrupting effect on the severe acute respiratory syndrome coronavirus-2 spike protein (SARS-CoV-2-Spike)/angiotensin-converting enzyme 2 (ACE2) binding. In conclusion, the obtained results not only supported the traditional use of LJ for heat-clearance, but also suggested its potential application in daily health care during the COVID-19 pandemic.

Untargeted LC-MS/MS-Based Multi-Informative Molecular Networking for Targeting the Antiproliferative Ingredients in Tetradium ruticarpum Fruit.

The fruit of Tetradium ruticarpum (TR) is commonly used in Chinese herbal medicine and it has known antiproliferative and antitumor activities, which can serve as a good source of functional ingredients. Although some antiproliferative compounds are reported to be present in TR fruit, most studies only focused on a limited range of metabolites. Therefore, in this study, the antiproliferative activity of different extracts of TR fruit was examined, and the potentially antiproliferative compounds were highlighted by applying an untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based multi-informative molecular networking strategy. The results showed that among different extracts of TR fruit, the EtOAc fraction F2-3 possessed the most potent antiproliferative activity against HL-60, T24, and LX-2 human cell lines. Through computational tool-aided structure prediction and integrating various data (sample taxonomy, antiproliferative activity, and compound identity) into a molecular network, a total of 11 indole alkaloids and 47 types of quinolone alkaloids were successfully annotated and visualized into three targeted bioactive molecular families. Within these families, up to 25 types of quinolone alkaloids were found that were previously unreported in TR fruit. Four indole alkaloids and five types of quinolone alkaloids were targeted as potentially antiproliferative compounds in the EtOAc fraction F2-3, and three (evodiamine, dehydroevodiamine, and schinifoline) of these targeted alkaloids can serve as marker compounds of F2-3. Evodiamine was verified to be one of the major antiproliferative compounds, and its structural analogues discovered in the molecular network were found to be promising antitumor agents. These results exemplify the application of an LC-MS/MS-based multi-informative molecular networking strategy in the discovery and annotation of bioactive compounds from complex mixtures of potential functional food ingredients.

Lophatherum gracile Brongn. attenuates neutrophilic inflammation through inhibition of JNK and calcium.

ETHNOPHARMACOLOGICAL RELEVANCE: Lophatherum gracile Brongn. (L. gracile) has been long used in traditional herbal medicine to clinically clear heat, disinhibit dampness, and treat inflammation. However, the effect of L. gracile on the activation of human neutrophils remains unclear. AIM OF THE STUDY: The aim of current study is to investigate the anti-inflammatory properties of L. gracile extract (LGE) in N-formyl-methionyl-leucyl-phenylalanine (fMLF)-induced activation of human neutrophils. MATERIALS AND METHODS: Superoxide anion generation and elastase release were estimated by spectrophotometry. A series of signaling pathways including mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt), as well as calcium mobilization were studied by Western blot analysis and spectrofluorometry. RESULTS: Our experimental results indicated that the nontoxic dosage of LGE does-dependently inhibited the fMLF-induced superoxide anion (O2•-) generation, elastase release, CD11b expression, adhesion, and chemotactic migration in human neutrophils. LGE selectively inhibited the fMLF-induced phosphorylation of JNK but not p38, ERK, or Akt in human neutrophils. LGE also decreased the intracellular Ca2+ levels ([Ca2+]i) in fMLF-activated human neutrophils. However, a specific JNK inhibitor inhibited the fMLF-induced O2•- generation and CD11b expression, but it had no effect on [Ca2+]i in human neutrophils. CONCLUSIONS: LGE exhibited anti-inflammatory activities in fMLF-activated human neutrophils. The pharmacological mechanisms of LGE-repressed neutrophilic inflammation were through two independent pathways, JNK signaling and calcium mobilization. Our results suggested that LGE holds the potential to be developed as an anti-inflammatory botanical medicine.

Pubinernoid A and Apo-9'-fucoxanthinone, Secondary Metabolites from a Gorgonian Coral Pinnigorgia sp.

The structures of pubinernoid A (1) and apo-9'-fucoxanthinone (2), isolated from a gorgonian coral Pinnigorgia sp., were elucidated on the basis of spectroscopic analysis and by comparison of their spectroscopic data with those of known compounds. This is the first report of 1 and 2 from an animal source. Apo-9'-fucoxanthinone (2) displayed a significant inhibitory effect on the release of elastase by human neutrophils, with an IC50 value of 5.75 µM.

Oxytoxin-2, An Algal-Derived Molecule from a Cultured Mollusc Volvatella vigourouxi.

A natural caulerpenyne-derived sesquiterpene, oxytoxin-2 (1), was isolated from a cultured mollusc Volvatella vigourouxi. The structure of 1 was elucidated on the basis of spectroscopic analysis and this compound was suggested to be a diet-derived metabolite from the green alga Caulerpa sertularioides.-This is the first study on the chemical constituents of V. vigourouxi. Oxytoxin-2 (1) was found to inhibit significantly the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) protein of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells.

Outpatient physical therapy utilization for children and adolescents with intellectual disabilities in Taiwan: a population-based nationwide study.

This study analyzed the utilization and utilization determinants of outpatient physical therapy (PT) among children and adolescents with intellectual disabilities (ID) in Taiwan. A cross-sectional study was conducted to analyze 2007 national health insurance (NHI) claim data from 35,802 eighteen-year-old and younger persons with intellectual disabilities. A total of 3944 (11.02%) claimants received outpatient physical therapy. Variables that affected PT utilization included age, residence urbanization level, ID level, copayment status and major co-morbidity. The average annual PT visit frequency was 25.4 ± 33.0; pre-school children, claimants suffering from catastrophic disease and ID co-occurring with cerebral palsy had a higher mean cost per visit. Age, ID level, copayment status and co-morbidity were factors that influenced expenditure. Pre-school children, males, individuals who resided in the lowest urbanization areas and individuals with a catastrophic disease tended to use hospital services. The point prevalence of epilepsy and cerebral palsy were 12.10% and 19.80%, respectively. Despite the NHI program and government regulations to provide special services, the use of physical therapy for children and adolescents with intellectual disabilities was low, and the utilization decreased as the subjects aged.

Predictive value of plasma (D)-dimer levels for cancer-related stroke: a 3-year retrospective study.

BACKGROUND: Cerebrovascular disease is the second leading cause of central nervous system pathology in cancer patients. Cancer-associated hypercoagulation plays an important role in cancer-related stroke. The present study aims to test whether plasma d-dimer levels could predict comorbid malignancy in patients with ischemic stroke. METHODS: Five hundred sixteen stroke patients with measured d-dimer levels and who were consecutively admitted to our stroke center from 2009 to 2012 were included. Cancer status was determined by medical chart, and 59 patients were identified to have active cancer. An additional 48 cancer patients with stroke were identified from the hospital database. Several d-dimer cutoff levels were used to predict cancer-related stroke. RESULTS: Stroke patients with active cancer had significantly higher d-dimer levels than those without cancer (P < .001). The average d-dimer level in stroke patients without cancer was .66 ± 1.83 mg/L, whereas the levels for active cancer patients from the stroke center and hospital database were 5.70 ± 9.63 mg/L and 10.47 ± 12.31 mg/L, respectively. When using d-dimer of .55 mg/L or more and multiple territory infarctions as criteria, the specificity and positive predictive value (PPV) for cancer-related stroke were 99.7% and 92.9%, respectively. When using d-dimer of 5.5 mg/L or more as the cutoff value, the test had a high specificity and PPV regardless the brain magnetic resonance imaging (MRI) findings. Six stroke patients fitting our criteria were confirmed to have occult malignancy after comprehensive cancer survey. CONCLUSIONS: Extraordinary high d-dimer levels or combining d-dimer and MRI findings may be used as a screening tool to detect malignancy in stroke patients.

Healthcare utilization and expenditure analysis between individuals with intellectual disabilities and the general population in Taiwan: a population-based nationwide child and adolescent study.

This study examines differences in outpatient-visit frequency and medical expenditures between (1) children and adolescents in Taiwan with intellectual disabilities and (2) children and adolescents in Taiwan's general population. A cross-sectional study was conducted to analyze data from 2007 provided by Taiwan's National Health Insurance program. A total of 236,045 beneficiaries younger than 19 years made use of outpatient services; among them, 35,802 had a principal diagnosis of mental retardation (intellectual disability). The average number of ambulatory visits was 14.9 ± 12.4, which is much higher than in the United States and other developed countries. The mean number of annual visits of the individuals with intellectual disabilities was significantly higher than that of the general population in Taiwan (20.1 ± 20.0 vs. 14.0 ± 12.2); age, gender, urbanization level of residential area, and copayment status affected outpatient visit frequency. The mean annual outpatient costs were NTD6371.3 ± NTD11989.1 for the general population and NTD19724.9 ± NTD40469.9 for those with intellectual disabilities (US $1 equals approximately NTD30). Age, gender, urbanization level of residential area, and copayment status were the determinants that accounted for this difference in cost. Children and adolescents with intellectual disabilities had higher use rates of rehabilitative and psychiatric services than the general population. We conclude that individuals with intellectual disabilities had higher demands than the general population for healthcare services, especially for rehabilitative and psychiatric services.

Comparison of outpatient services between elderly people with intellectual disabilities and the general elderly population in Taiwan.

This study aims to analyze the ambulatory visit frequency and medical expenditures of the general elderly population versus the elderly with intellectual disabilities in Taiwan, while examining the effects of age, gender, urbanization and copayment status on ambulatory utilization. A cross-sectional study was conducted to analyze data from 103,183 national health insurance claimants aged 65 or older. A total of 1469 had a principal diagnosis of mental retardation (intellectual disability) and claimed medical outpatient services in 2007. The average number of ambulatory visits was 30.1 ± 23.1, which is much higher than in the United States and other developed countries, and the mean annual visits of the elderly with intellectual disabilities was significantly higher than the general population in Taiwan (35.2 ± 28.7 vs. 30.0 ± 23.1). Age and copayment status affected outpatient visit frequency. The mean medical expenditure per visit and the mean annual outpatient cost were 1146.5 ± 4497.7 NT$ and 34,533.7 ± 115,891.7 NT$, respectively. Male beneficiaries tended to have higher average annual medical expenses and mean medical expenses per visit than female beneficiaries. The three most frequent principal diagnoses at ambulatory visits were circulatory system diseases, musculoskeletal system and connective tissue diseases and digestive system diseases. We conclude that the elderly with intellectual disabilities had higher demand than the general population for healthcare services, and the NHI program lowers the barrier to care for populations with special needs.