Morgancho3577

Osteoporosis is an age-related complex disease clinically diagnosed with bone mineral density (BMD). Although several genomewide association studies (GWASs) have discovered multiple noncoding genetic variants at 11p15 influencing osteoporosis risk, the functional mechanisms of these variants remain unknown. Through integrating bioinformatics and functional experiments, a potential functional single-nucleotide polymorphism (SNP; rs1440702) located in an enhancer element was identified and the A allele of rs1440702 acted as an allelic specificities enhancer to increase its distal target gene SOX6 (~600 Kb upstream) expression, which plays a key role in bone formation. We also validated this long-range regulation via conducting chromosome conformation capture (3C) assay. Furthermore, we demonstrated that SNP rs1440702 with a risk allele (rs1440702-A) could increase the activity of the enhancer element by altering the binding affinity of the transcription factor TCF4, resulting in the upregulation expression of SOX6 gene. Collectively, our integrated analyses revealed how the noncoding genetic variants (rs1440702) affect osteoporosis predisposition via long-range gene regulatory mechanisms and identified its target gene SOX6 for downstream biomarker and drug development. © 2022 American Society for Bone and Mineral Research (ASBMR).Relative abundance of fibroblast growth factor-23 (FGF23) measured by the C-terminal (cFGF23, which measures both intact FGF23 and C-terminal fragments) versus intact (iFGF23, measures only intact hormone) assays varies by kidney function in humans. Differential kidney clearance may explain this finding. We measured cFGF23 and iFGF23 in the aorta and bilateral renal veins of 162 patients with essential hypertension undergoing renal angiography. Using multivariable linear regression, we examined factors associated with aorta to renal vein reduction of FGF23 using both assays. Similar parameters and with addition of urine concentrations of cFGF23 and iFGF23 were measured in six Wistar rats. Mean ± standard deviation (SD) age was 54 ± 12 years, 54% were women, and mean creatinine clearance was 72 ± 48 mL/min/100 g. The human kidney reduced the concentrations of both cFGF23 (16% ± 12%) and iFGF23 (21% ± 16%), but reduction was higher for iFGF23. Greater kidney creatinine and PTH reductions were each independently associated with greater reductions of both cFGF23 and iFGF23. The greater kidney reduction of iFGF23 compared to cFGF23 appeared stable and consistent across the range of creatinine clearance evaluated. Kidney clearance was similar, and urine concentrations of both assays were low in the rat models, suggesting kidney metabolism of both cFGF23 and iFGF23. Renal reduction of iFGF23 is higher than that of creatinine and cFGF23. Our data suggest that FGF23 is metabolized by the kidney. However, the major cell types involved in metabolization of FGF23 requires future study. Kidney clearance of FGF23 does not explain differences in C-terminal and intact moieties across the range of kidney function. © 2022 American Society for Bone and Mineral Research (ASBMR).

We aimed to investigate the clinical features and prognosis of posterior reversible encephalopathy syndrome (PRES) in children.

Clinical data of children with PRES diagnosed at the Children's Hospital of Chongqing Medical University from June 2015 to May 2019 were retrospectively analyzed.

The study enrolled 47 patients with a mean age at diagnosis of 8.79 ± 3.72 years (range, 2-15 years). PRES causes included renal disorder (29/47), hematological disease (13/47), and hypertension (5/47). PRES manifested as seizure (43/47), headache (28/47), visual impairment (18/47), dizziness (18/47), vomiting (18/47), and mental and behavioral abnormalities (17/47). Forty-six children had hypertension (46/47) at PRES onset. Magnetic resonance imaging (MRI) mainly involved the parietal and occipital lobes (42/47), 38 cases were mild (38/47), seven were moderate (7/47), and two were severe (2/47). The clinical symptoms of 41 patients (41/47) were relieved within 1-2weeks. Thirty-seven children were followed up for 7-54 months (modified Rankin Scale). Twenty-five children had favorable outcomes (25/37). Twelve children had adverse outcomes (12/37), including epilepsy, disorders of consciousness, visual impairment, and mental decline. Analysis of single factors revealed that severity on MRI, length of in-hospital stay, and mental and behavioral abnormalities were related to adverse outcomes after PRES. Analysis of multiple factors revealed that severity on MRI and length of in-hospital stay were independent risk factors for PRES.

Pediatric PRES is a clinical radiographic syndrome with multiple etiologies. Most patients have a good prognosis. Severity on MRI and length of in-hospital stay are independent risk factors.

Pediatric PRES is a clinical radiographic syndrome with multiple etiologies. Most patients have a good prognosis. Severity on MRI and length of in-hospital stay are independent risk factors.

To evaluate the feasibility of motion correction for sodium (

Na) MRI based on interleaved acquired 3D proton (

H) navigator images.

A 3D radial density-adapted sequence for interleaved

Na/

H MRI was implemented on a 7 Tesla whole-body MRI system. The

H data obtained during the

Na acquisition were used to reconstruct 140 navigator image volumes with a nominal spatial resolution of (2.5 mm)

and a temporal resolution of 6 s. The motion information received from co-registration was then used to correct the

Na image dataset, which also had a nominal spatial resolution of (2.5 mm)

. The approach was evaluated on six healthy volunteers, whose motion during the scans had different intensities and characteristics.

Interleaved acquisition of two nuclei did not show any relevant influence on image quality (SNR of 13.0 for interleaved versus 13.2 for standard

Na MRI and 176.4 for interleaved versus 178.0 for standard

H MRI). The applied motion correction increased the consistency between two consecutive scans for all examined volunteers and improved the image quality for all kinds of motion. The SD of the differences ranged between 2.30% and 6.96% for the uncorrected and between 2.13% and 2.67% for the corrected images.

The feasibility of interleaved acquired

H navigator images to be used for retrospective motion correction of

Na images was successfully demonstrated. The approach neither affected the

Na image quality nor elongated the scan time and can therefore be an important tool to improve the accuracy of quantitative

Na MRI.

The feasibility of interleaved acquired 1 H navigator images to be used for retrospective motion correction of 23 Na images was successfully demonstrated. The approach neither affected the 23 Na image quality nor elongated the scan time and can therefore be an important tool to improve the accuracy of quantitative 23 Na MRI.When combined with nalbuphine, local anesthetics show a longer duration of nerve block without increasing complications. However, no evidence is available concerning the effect of nalbuphine on the cardiotoxicity of local anesthetics. The objective of this work is to investigate whether nalbuphine pretreatment can increase the lethal dose threshold of ropivacaine in rats. Anesthetized Sprague Dawley rats were pretreated with different doses of nalbuphine (0.4, 0.8, 1.5, 3.0, 5.0 mg/kg) or NS (normal saline, negative control) or 30% LE (lipid emulsion, positive control) 2 ml/kg/min for 5 min (n = 6). Then 0.5% ropivacaine was infused at a rate of 2.5 mg/kg/min until asystole occurs. Time of arrhythmia, 50% mean arterial pressure- and 50% heart rate-reduction, and asystole were recorded, and ropivacaine doses were calculated. Nalbuphine (0.4-5.0 mg/kg) did not affect ropivacaine-induced arrhythmia, 50% mean arterial pressure-reduction and 50% heart rate-reduction, and asystole in rats compared with NS pre-treatment. The asystole dose threshold (in milligrams per kilogram) of group LE was higher than that of group NS (NS 28.25(6.32) vs. LE, 41.58(10.65); P = 0.04; 95% confidence interval 0.23 to 26.45), while thresholds of arrhythmia, 50% mean arterial pressure-reduction, and 50% heart rate-reduction were not affected by LE. Nalbuphine doses of 0.4-5.0 mg/kg pretreatment did not increase the threshold of ropivacaine cardiotoxicity compared with NS control; 30% LE increases the lethal dose threshold of ropivacaine in rats.

We aimed to investigate the effectiveness and safety of mirabegron for adult and child patients with neurogenic lower urinary tract dysfunction (NLUTD).

A comprehensive search for articles about mirabegron treatment of NLUTD patients was conducted in PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov databases. Retrospective studies and randomized-controlled studies were included if they met the inclusion criteria and were evaluated by different quality evaluation methods according to study types. Mean difference (MD) and 95% confidence intervals (CIs) were calculated using fixed-effects models or random models depending on heterogeneity. Clinical and urodynamic parameters were pooled to evaluate the efficacy, and safety was measured by adverse events rate.

A total of 10 studies with 314 participants were finally included. Four retrospective and six prospective studies containing two randomized-control trials met the inclusion criteria with moderate and high evidence levels. Compared to the baseline date, the pooled results suggested that patients who underwent mirabegron treatment presented less urinary frequency (MD = -0.70; 95% CI -1.08 to -0.32; p < 0.01) and less incontinence (MD = -1.62; 95% CI-2.20 to -1.03; p < 0.01), showed conspicuous improvements in adult and child patients' urodynamic parameters, while the incidence of adverse events (10.0% on average, 0%-31.25%) also demonstrated the safety of mirabegron.

Mirabegron can significantly improve urodynamic parameters and quality of life in adult and child patients with NLUTD, and increase patient compliance with a smaller complication rate.

Mirabegron can significantly improve urodynamic parameters and quality of life in adult and child patients with NLUTD, and increase patient compliance with a smaller complication rate.The menopause transition in women is a period of significant bone loss, with rapid declines in bone mineral density (BMD) commencing a year before the final menstrual period (FMP). Changes in menstrual bleeding patterns cannot reliably tell us if this rapid bone loss has begun or is imminent. We hypothesized that low circulating levels of anti-Mullerian hormone (AMH), which decline as women approach the FMP, would be associated with future and ongoing rapid bone loss. We used data from The Study of Women's Health Across the Nation, a multisite, multi-ethnic, prospective cohort study of the menopause transition to test this hypothesis. Adjusted for age, body mass index, race/ethnicity, and study site, every 50% decrement in AMH level in premenopause and early perimenopause was associated with 0.14% per year faster decline over the following 3 to 4 years in lumbar spine BMD and 0.11% per year faster decline in femoral neck BMD (p  less then  0.001 for both). AMH in late perimenopause was not associated with the rate of future BMD decline.