Urinary levels of organophosphate flame retardants metabolites in a young population from Southern Taiwan and potential health effects

BackgroundOrganophosphate flame retardants (OPFRs) are widely distributed in the environment and their metabolites are observed in urine, but little is known regarding OPFRs in a broad-spectrum young population from newborns to those aged 18 years.ObjectivesInvestigate urinary levels of OPFRs and OPFR metabolites in Taiwanese infants, young children, schoolchildren, and adolescents within the general population.MethodsDifferent age groups of subjects (n=136) were recruited from southern Taiwan to detect 10 OPFR metabolites in urine samples. Associations between urinary OPFRs and their corresponding metabolites and potential health status were also examined.ResultsThe mean level of urinary Σ10 OPFR in this broad-spectrum young population is 2.25 μg/L (standard deviation (SD) of 1.91 μg/L). Σ10 OPFR metabolites in urine are 3.25 ± 2.84, 3.06 ± 2.21, 1.75 ± 1.10, and 2.32 ± 2.29 μg/L in the age groups comprising of newborns, 1-5 year-olds, 6-10 year-olds, and 11-18 year-olds, respectively, and borderline significant differences were found in the different age groups (p=0.125). The OPFR metabolites of TCEP, BCEP, DPHP, TBEP, DBEP, and BDCPP predominate in urine and comprise more than 90% of the total. TBEP was highly correlated with DBEP in this population (r=0.845, p<0.001). The estimated daily intake (EDI) of Σ5OPFRs (TDCPP, TCEP, TBEP, TNBP, and TPHP) was 2,230, 461, 130, and 184 ng/kg bw/day for newborns, 1-5 yr children, 6-10 yr children, and 11-17 yr adolescents, respectively. The EDI of Σ5OPFRs for newborns was 4.83-17.2 times higher than the other age groups. Urinary OPFR metabolites are significantly correlated with birth length and chest circumference in newborns.ConclusionTo our knowledge, this is the first investigation of urinary OPFR metabolite levels in a broad-spectrum young population. There tended to be higher exposure rates in both newborns and pre-schoolers, though little is known about their exposure levels or factors leading to exposure in the young population. Further studies should clarify the exposure levels and factor relationships

CLIPCAM: A Simple Baseline For Zero-Shot Text-Guided Object And Action Localization

The key for the contemporary deep learning-based object and action localization algorithms to work is the large-scale annotated data. However, in real-world scenarios, since there are infinite amounts of unlabeled data beyond the categories of publicly available datasets, it is not only time- and manpower-consuming to annotate all the data but also requires a lot of computational resources to train the detectors. To address these issues, we show a simple and reliable baseline that can be easily obtained and work directly for the zero-shot text-guided object and action localization tasks without introducing additional training costs by using Grad-CAM, the widely used class visual saliency map generator, with the help of the recently released Contrastive Language-Image Pre-Training (CLIP) model by OpenAI, which is trained contrastively using the dataset of 400 million image-sentence pairs with rich cross-modal information between text semantics and image appearances. With extensive experiments on the Open Images and HICO-DET datasets, the results demonstrate the effectiveness of the proposed approach for the text-guided unseen object and action localization tasks for images

SLC9A3 Protein Is Critical for Acrosomal Formation in Postmeiotic Male Germ Cells

Solute carrier family 9 isoform 3 (SLC9A3), a Na+/H+ exchanger, regulates the transepithelial absorption of Na+ and water and is primarily expressed on the apical membranes of the intestinal epithelium, renal proximal tubule, epididymis, and vas deferens. Loss of the Slc9a3 allele in mice enhances intestinal fluid and causes diarrhoea as a consequence of diminished Na+ and HCO3− absorption. Hence, the loss also causes male infertility and reveals the abnormal dilated lumen of the rete testis and calcification in efferent ductules. However, whether loss of Slc9a3 alleles also disrupts mammalian spermatogenesis remains unknown. First, through immunoblotting, we determined that SLC9A3 is highly expressed in the murine testis compared with the small intestine, epididymis, and vas deferens. During murine spermatogenesis, SLC9A3 is specifically expressed in the acrosome region of round, elongating, and elongated spermatids through immunostaining. Furthermore, SLC9A3 signals are enriched in the acrosome of mature sperm isolated from the vas deferens. In Slc9a3 knockout (KO) mice, compared with the same-aged controls, the number of spermatids on the testicular section of the mice progressively worsened in mice aged 20, 35, and 60 days. Sperm isolated from the epididymis of Slc9a3 KO mice revealed severe acrosomal defects. Our data indicated that SLC9A3 has a vital role in acrosomal formation during spermiogenesis

Long-Term Neuropsychological Sequelae in HIV-Seronegative Cryptococcal Meningoencephalitis Patients with and without Ventriculoperitoneal Shunts: A Cine MRI Study

Background. Hydrocephalus in cryptococcal meningoencephalitis is most commonly managed with a ventriculoperitoneal shunt. This study applied cine magnetic resonance imaging (MRI) to evaluate initial disease severity on long-term cerebrospinal fluid (CSF) flow dynamics and associated neuropsychological sequelae in cryptococcal meningoencephalitis patients with and without ventriculoperitoneal shunts. Methods. Eighteen human immunodeficiency virus-seronegative cryptococcal meningoencephalitis patients (10 with shunts versus 8 without shunts) were compared with 32 age- and sex-matched healthy volunteers. All subjects underwent complete neurologic examination and neuropsychological testing. Cine MRI was conducted to evaluate CSF flow parameters. Initial CSF laboratory analysis and imaging findings were correlated with present CSF flow parameters and neuropsychological scores. Results. Patients without shunts had higher average flow than controls, suggesting chronic hydrocephalus. Initial Evans ratios and CSF glucose levels were associated with CSF peak velocity and flow. Worsening CSF flow parameters correlated with decreased neuropsychological performance. Conclusions. CSF flow parameter differences between the cryptococcal meningoencephalitis patients both with and without ventriculoperitoneal shunts could be detected by cine MRI and correlated with acute stage disease severity and chronic stage neuropsychological results. Cine MRI is useful for assessing the chronic hydrocephalus that may lead to neuropsychological deficits in cryptococcal meningoencephalitis patients

The associations between renal disease severity and exposure to organophosphate flame retardants in patients with chronic kidney disease

Organophosphate flame retardants (OPFRs) are emerging and widespread environmental pollutants with potential health hazards, including nephrotoxicity. However, the exposure patterns and nephrotoxic potential of OPFRs are yet to be investigated in patients with chronic kidney disease (CKD). We conducted a cross-sectional study involving 166 patients with CKD stratified by estimated glomerular filtration rate (eGFR) and severity of proteinuria. The urinary concentrations of 10 OPFR compounds were measured to evaluate the exposure patterns. Clinical and urinary OPFR profiles were compared among subgroups to identify whether the OPFR compounds were independently correlated with eGFR and proteinuria. Additionally, lifestyle factors were compared among subgroups stratified by median concentrations of urinary OPFR compounds associated with renal disease severity. This study revealed universal exposure to OPFRs in the CKD population, with an overall urinary detection rate of 98.80 %. Furthermore, after adjusting for covariates, the urinary concentration of bis(2-chloroethyl) phosphate (BCEP) was identified as an independent predictor of lower eGFR (low vs high eGFR, odds ratio (OR) (95 % confidence interval (CI)), 1.761 (1.032–3.005) per log μg/g creatinine, p = 0.038), and the urinary concentration of bis(2-butoxyethyl) phosphate (BBOEP) was independently correlated with overt proteinuria in CKD patients (with vs without overt proteinuria, OR (95 % CI), 1.813 (1.065–3.086) per log μg/g creatinine, p = 0.028). Moreover, frequent seafood consumption was negatively correlated with urinary BCEP concentration (high vs low BCEP, OR (95 % CI), 0.455 (0.228–0.908), p = 0.025), and age was inversely associated with urinary BBOEP concentration (high vs low BBOEP, OR (95 % CI), 0.968 (0.937–0.999) per year, p = 0.048). In conclusion, our investigation highlights the extensive exposure to OPFRs and the independent association between renal disease severity and urinary BCEP/BBOEP concentrations in the CKD population, indicating the nephrotoxic potential of these pollutants

Peripheral Leukocyte Apoptosis in Patients with Parkinsonism: Correlation with Clinical Characteristics and Neuroimaging Findings

Apoptosis of both brain neurons and peripheral blood leukocyte is believed to be an important biomarker for evaluating the functional status of Parkinson’s disease (PD). However, their correlation remains unknown. A better understanding of the pathophysiology of neurodegeneration is essential for the treatment and prevention of PD. The present study demonstrated that leukocyte apoptosis is significantly higher in PD patients and is associated with central dopamine neuron loss by using Tc99m-TRODAT-1 SPECT. The leukocyte apoptosis and striatal dopamine transporter uptake ratios were further associated with increased severity and longer duration of disease. The interaction between brain and systemic inflammation may be responsible for the neurodegenerative disease progression

Genome-wide CRISPR/Cas9 knockout screening uncovers a novel inflammatory pathway critical for resistance to arginine-deprivation therapy

Arginine synthesis deficiency due to the suppressed expression of ASS1 (argininosuccinate synthetase 1) represents one of the most frequently occurring metabolic defects of tumor cells. Arginine-deprivation therapy has gained increasing attention in recent years. One challenge of ADI-PEG20 (pegylated ADI) therapy is the development of drug resistance caused by restoration of ASS1 expression and other factors. The goal of this work is to identify novel factors conferring therapy resistance. Methods: Multiple, independently derived ADI-resistant clones including derivatives of breast (MDA-MB-231 and BT-549) and prostate (PC3, CWR22Rv1, and DU145) cancer cells were developed. RNA-seq and RT-PCR were used to identify genes upregulated in the resistant clones. Unbiased genome-wide CRISPR/Cas9 knockout screening was used to identify genes whose absence confers sensitivity to these cells. shRNA and CRISPR/Cas9 knockout as well as overexpression approaches were used to validate the functions of the resistant genes both in vitro and in xenograft models. The signal pathways were verified by western blotting and cytokine release. Results: Based on unbiased CRISPR/Cas9 knockout screening and RNA-seq analyses of independently derived ADI-resistant (ADIR) clones, aberrant activation of the TREM1/CCL2 axis in addition to ASS1 expression was consistently identified as the resistant factors. Unlike ADIR, MDA-MB-231 overexpressing ASS1 cells achieved only moderate ADI resistance both in vitro and in vivo, and overexpression of ASS1 alone does not activate the TREM1/CCL2 axis. These data suggested that upregulation of TREM1 is an independent factor in the development of strong resistance, which is accompanied by activation of the AKT/mTOR/STAT3/CCL2 pathway and contributes to cell survival and overcoming the tumor suppressive effects of ASS1 overexpression. Importantly, knockdown of TREM1 or CCL2 significantly sensitized ADIR toward ADI. Similar results were obtained in BT-549 breast cancer cell line as well as castration-resistant prostate cancer cells. The present study sheds light on the detailed mechanisms of resistance to arginine-deprivation therapy and uncovers novel targets to overcome resistance. Conclusion: We uncovered TREM1/CCL2 activation, in addition to restored ASS1 expression, as a key pathway involved in full ADI-resistance in breast and prostate cancer models

Variometric approach for real-time GNSS navigation: First demonstration of Kin-VADASE capabilities

The use of Global Navigation Satellite Systems (GNSS) kinematic positioning for navigational applications dramatically increased over the last decade. Real-time high performance navigation (positioning accuracy from one to few centimeters) can be achieved with established techniques such as Real Time Kinematic (RTK), and Precise Point Positioning (PPP). Despite their potential, the application of these techniques is limited mainly by their high cost. This work proposes the Kinematic implementation of the Variometric Approach for Displacement Analysis Standalone Engine (Kin-VADASE) and gives a demonstration of its performances in the field of GNSS navigation. VADASE is a methodology for the real-time detection of a standalone GNSS receiver displacements. It was originally designed for seismology and monitoring applications, where the receiver is supposed to move for few minutes, in the range of few meters, around a predefined position. Kin-VADASE overcomes the aforementioned limitations and aims to be a complete methodology with fully kinematic capabilities. Here, for the first time, we present its application to two test cases in order to estimate high rate (i.e., 10 Hz) kinematic parameters of moving vehicles. In this demonstration, data are collected and processed in the office, but the same results can be obtained in real-time through the implementation of Kin-VADASE in the firmware of a GNSS receiver. All the Kin-VADASE processing were carried out using double and single frequency observations in order to investigate the potentialities of the software with geodetic class and low-cost single frequency receivers. Root Mean Square Errors in 3D with respect to differential positioning are at the level of 50 cm for dual frequency and better than 1 meter for single frequency data. This reveals how Kin-VADASE features the main advantage of the standalone approach and the single frequency capability and, although with slightly lower accuracy with respect to the established techniques, can be a valid alternative to estimate kinematic parameters of vehicle in motions