Optical design and performance of the biological small-angle X-ray scattering beamline at the Taiwan Photon Source.

The optical design and performance of the recently opened 13A biological small-angle X-ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high-flux X-rays in the energy range 4.0-23.0 keV. MoB4C double-multilayer and Si(111) double-crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high-flux beam of ∼4 × 1014 photons s-1 to a high-energy-resolution beam of ΔE/E ≃ 1.5 × 10-4; both modes share a constant beam exit. With a set of Kirkpatrick-Baez (KB) mirrors, the X-ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four-bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra-SAXS with a minimum scattering vector q down to 0.0004 Å-1, which allows resolving ordered d-spacing up to 1 µm. A microbeam, of 10-50 µm beam size, is tailored by a combined set of high-heat-load slits followed by micrometre-precision slits situated at the front-end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in-vacuum X-ray pixel detectors is installed to perform synchronized small- and wide-angle X-ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra-SAXS in one beamline.

Parathyroidectomy slows renal function decline in patients with primary hyperparathyroidism.

PURPOSE: Primary hyperparathyroidism has deleterious effects on health and causes nephrolithiasis and osteoporosis. However, it remains unclear whether parathyroidectomy benefits kidney function among patients with primary hyperparathyroidism. METHODS: In this retrospective study, patients with primary hyperparathyroidism receiving parathyroidectomy in a tertiary medical center between 2003 and 2017 were followed up until December 31 2017, death, or requiring renal replacement therapy. Impact of parathyroidectomy on kidney function was examined using longitudinal estimated glomerular filtration rate (eGFR) change scales: single, average, absolute difference, percent change, annual decline rate, and slope. We applied linear mixed-effect model to determine the effect of parathyroidectomy on kidney function. RESULTS: During study period, 167 patients with primary hyperparathyroidism were identified from 498 parathyroidectomized patients, and finally, 27 patients fulfilled our stringent criteria. Median follow-up duration was 1.50 years (interquartile range 1.05-1.81) before surgery and 2.47 years (1.37-6.43) after surgery. Although parathyroidectomy did not affect amount of proteinuria and distribution of eGFR, parathyroidectomy significantly slowed decline rate of eGFR compared with that before surgery (- 1.67 versus - 2.73 mL/min/1.73 m2/year, p < 0.001). More importantly, parathyroidectomy made more beneficial effects on kidney function in patients with age < 65 years and those without chronic kidney disease or hypertension. CONCLUSIONS: Our study showed that parathyroidectomy slows renal function decline irrespective of age or comorbidities, which offers novel insight into the revision of guidelines for surgical indications in primary hyperparathyroidism. Given small sample size, further large-scale controlled studies are warranted to confirm our findings.

Proton pump inhibitor use and the risk of osteoporosis and fracture in stroke patients: a population-based cohort study.

A considerable proportion of stroke survivors are prescribed with proton pump inhibitors (PPIs). Our study indicated that PPI use is associated with an increased risk of osteoporosis, hip fracture, and vertebral fracture in stroke patients. The risk tends to increase as the cumulative doses of PPIs increase. INTRODUCTION: A considerable proportion of stroke survivors are prescribed with proton pump inhibitors (PPIs). Our study investigated the association between PPI use and the risk of osteoporosis and fracture among stroke survivors. METHODS: A population-based propensity-matched retrospective cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients diagnosed with a new stroke between 2000 and 2012 were identified. After propensity score matching, 10,596 patients were enrolled, and 5298 patients were each assigned to the PPI user and non-user groups. Hazard ratios (HRs) were calculated for the risk of osteoporosis, hip fracture, and vertebral fractures according to PPI use or non-use. Sensitivity analyses were conducted to evaluate the dose effects of PPI. RESULTS: PPI use after stroke was associated with an increased risk of osteoporosis, hip fracture, or vertebral fracture, with an adjusted HR (aHR) of 1.28 (P < 0.001). The aHRs were also significant for each outcome: osteoporosis, 1.26 (P < 0.001); hip fracture, 1.18 (P = 0.048); vertebral fracture, 1.33 (P < 0.001). A pattern of dose effect was identified. For any event (osteoporosis/hip fracture/vertebral fracture), the aHR for PPI use of 1-90, 91-365, and > 365 cDDDs was 1.22 (P < 0.001), 1.27 (P < 0.001), and 1.66 (P < 0.001), respectively. For each outcome, the highest dose was associated with the highest risk, with aHR of 1.79 (P < 0.001), 1.41 (P = 0.039), and 1.82 (P < 0.001) for osteoporosis, hip fracture, and vertebral fracture, respectively. Age- and sex-stratified analyses revealed similar patterns. CONCLUSIONS: PPI use is associated with an increased risk of osteoporosis, hip fracture, and vertebral fracture in stroke patients.

Angiotensin II receptor blocker prevents upper gastrointestinal bleeding in hypertensive patients with chronic kidney disease not on dialysis.

AIMS: Investigate if angiotensin II receptor blocker (ARB) decreases risk of upper gastrointestinal bleeding (UGIB) in hypertensive patients with chronic kidney disease (CKD) not on dialysis. METHODS: All hypertensive patients with CKD not on dialysis in outpatient department of China Medical University Hospital from 2003 to May 2013 were enrolled. The risk of UGIB was analysed using Cox proportional hazard regression. RESULTS: A total of 2744 hypertensive CKD patients including 1515 male and 1229 female, aged 64.9 ± 13.8 years old in a median of 1.9 (0.9-3.9) years were analysed. The incidence of UGIB was 4.5 per 100 patient-years. ARB was associated with a decreased risk of UGIB (p < 0.001) with an adjusted hazard ratio (HR) of 0.533 [95% confidence interval (CI) 0.404-0.703]. A history of UGIB, Helicobacter pylori infection, diabetes, lower estimated glomerular filtration rate, elevated blood urea nitrogen and decreased serum albumin were independently associated with an increased risk of UGIB. CONCLUSIONS: Angiotensin II receptor blocker is associated with a decreased risk of UGIB in hypertensive CKD patients not on dialysis, independent of their renal function, history of gastrointestinal bleeding and nutrition status.

Intentional examination of esophagus by narrow-band imaging endoscopy increases detection rate of cervical inlet patch.

Foci of heterotopic gastric mucosa have been identified at different sites in the human body and the most common location is the proximal esophagus which is referred to as cervical inlet patch (CIP). The true prevalence of CIP varies and it is usually incidental findings during endoscopy. Because CIP is always asymptomatic, it was believed to be of little clinical relevance. However, emerging studies have described the acid-secreting characteristics of heterotopic gastric mucosa and associations of CIP with gastroesophageal reflux disease (GERD). In addition, complications such as stricture, fistula, infection, mucosal hyperplasia, and malignant transformation have been reported. In this study, we investigated the prevalence of CIP, its associations with clinical manifestations, and the effect of intentional screening upper esophagus by magnifying endoscopy-narrow-band imaging (ME-NBI) system. Consecutive healthy adults who underwent panendoscopy were separated into two groups. Patients in group I (n = 471) were examined by an endoscopist who intended to find CIPs by ME-NBI. Patients in group II (n = 428) were examined by two endoscopists who were unaware of the study and performed white-light imaging endoscopy. Participants provided questionnaires on GERD-related symptoms. Higher CIP prevalence (11.7% vs. 1.9%, P < 0.0001) and longer duration of esophageal examination (mean ± standard deviation, 17.50 ± 12.40 vs. 15.24 ± 10.78 seconds, P = 0.004) were noted in group I than in group II. Analyzing group I patients revealed the higher prevalences of reflux symptoms (32.7% vs. 18.3%, P = 0.013) and erosive esophagitis (43.6% vs. 25.5%, P = 0.005) in patients with CIP than in those without. CIP was not associated with globus or dysphagia symptoms. More small CIPs (< 5 mm) were detected by ME-NBI than by white-light imaging (85.3% vs. 41.4%, P = 0.001). In conclusion, CIP prevalence was not low under intentional ME-NBI examination of the upper esophagus. The clinical relevance of CIP and its association with GERD require further investigation.

Aliskiren attenuates proteinuria in mice with lupus nephritis by a blood pressure-independent mechanism.

This study revealed that low-dose aliskiren treatment could attenuate proteinuria by interrupting the renin-angiotensin system in mice with lupus nephritis, and the beneficial effect was beyond blood pressure control. An in and ex vivo fluorescence imaging (using a non-invasion in vivo imaging system) showed intense labeling of renin in the kidneys of female MRL/lpr mice. In the study, Alzet mini-osmotic pumps were implanted into 6-week-old female MRL/lpr mice. Pumps were filled with either phosphate-buffered saline or a solution of aliskiren dissolved in phosphate-buffered saline (20 mg/kg/day) and replaced at 28-day intervals. Mice were sacrificed at four and eight weeks. To label cells for DNA synthesis, bromodeoxyuridine (BrdU) (50 mg/kg) was injected intraperitoneally an hour prior to sacrifice. The level of renin inhibition was adequate, as aliskiren-treated mice demonstrated higher renal renin mRNA expression than controls (p < 0.05). Although there were no significant differences in the systolic blood pressure (control versus aliskiren-treated: 127.20 ± 4.44 mmHg versus 103.80 ± 7.40 mmHg, p > 0.05) and heart rate (control versus aliskiren-treated: 680.50 ± 11.71 versus 647.80 ± 13.90, p > 0.05) of both groups after eight weeks, there was significant reduction of inflammatory cytokines (transforming growth factor-beta1, regulated on activation normal T cell expressed, monocyte chemoattractant protein-1 and osteopontin, p < 0.05), reduction of innate immunity (toll-like receptor 7, p < 0.05), as well as a reduction of glomerular proliferation and inflammation (BrdU-, CD45-, CD3- and F4/80-positive glomerular cells, p < 0.01) after aliskiren infusion, which might translate into an improvement in proteinuria (control versus aliskiren-treated: 493.7 versus 843.7 mg/g, p < 0.01) or weight gain (control versus aliskiren-treated: 5.65 ± 1.61 versus 8.67 ± 0.97%, p < 0.05).

Performance of the new biological small- and wide-angle X-ray scattering beamline 13A at the Taiwan Photon Source.

Recent developments in the instrumentation and data analysis of synchrotron small-angle X-ray scattering (SAXS) on biomolecules in solution have made biological SAXS (BioSAXS) a mature and popular tool in structural biology. This article reports on an advanced endstation developed at beamline 13A of the 3.0 GeV Taiwan Photon Source for biological small- and wide-angle X-ray scattering (SAXS-WAXS or SWAXS). The endstation features an in-vacuum SWAXS detection system comprising two mobile area detectors (Eiger X 9M/1M) and an online size-exclusion chromatography system incorporating several optical probes including a UV-Vis absorption spectrometer and refractometer. The instrumentation and automation allow simultaneous SAXS-WAXS data collection and data reduction for high-throughput biomolecular conformation and composition determinations. The performance of the endstation is illustrated with the SWAXS data collected for several model proteins in solution, covering a scattering vector magnitude q across three orders of magnitude. The crystal-model fittings to the data in the q range ∼0.005-2.0 Å-1 indicate high similarity of the solution structures of the proteins to their crystalline forms, except for some subtle hydration-dependent local details. These results open up new horizons of SWAXS in studying correlated local and global structures of biomolecules in solution.

Impetigo herpetiformis with gestational hypertension: a case report and literature review.

BACKGROUND: Impetigo herpetiformis (IH) is a rare skin disorder that occurs during pregnancy. It was previously associated with high maternal and fetal mortality and morbidity, but now has a better prognosis. CASE REPORT: We report a case of a pregnant woman with IH who presented with generalized erythematous pustular eruptions in the 32nd week of gestation. The IH progressed rapidly, and gestational hypertension was observed in the 36th week. The lesions did not subside, despite treatment with corticosteroids and phototherapy. She delivered a healthy male baby via cesarean section in the 37th week. One month after her delivery, her skin returned to normal, except for residual pigmentation, with complete recovery 3 months postpartum. CONCLUSION: An experienced medical team comprising obstetricians, dermatologists, perinatologists and neonatologists is critical to aggressively treat this life-threatening specific dermatosis of pregnancy and to prevent ensuing complications, such as fluid and electrolyte imbalance, secondary infection and placental insufficiency.

Influence of predialysis comorbidity and damage accrual on mortality in lupus patients treated with peritoneal dialysis.

OBJECTIVE: Although there have been many studies on systemic lupus erythematosus (SLE) patients, there are few data about survival analysis of lupus patients receiving dialysis. Therefore, the objective of this study is to analyze risk factors predicting mortality in lupus patients treated with peritoneal dialysis (PD). In addition, we also delineate the relationship between predialysis comorbid illnesses, damage accrual, and mortality in lupus patients undergoing PD. METHODS: This longitudinal cohort study included 38 lupus patients undergoing PD between 1990 and 2008. The clinical parameters, disease activity (non-renal SLEDAI, nrSLEDAI), comorbid illnesses, and damage accrual were collected. We applied the Charlson Comorbidity Index (CCI), Khan Index, and Davies Index to elucidate the impact of predialysis comorbidity on mortality. Moreover, we examined prognostic value of predialysis SDI (Systemic Lupus International Collaborating Clinics Disease Damage Index) for lupus PD patients. RESULTS: There were 33 women and five men included for analysis. The mean age at PD entry was 32.2 +/- 10.4 years and mean duration of PD was 39.7 +/- 22.4 months. The nrSLEDAI score during PD significantly decreased, compared to the predialysis one (2.13 +/- 2.09 vs. 4.00 +/- 3.08, p < 0.001). All comorbidity indices and SDI scores were significantly and positively correlated with each other (p < 0.001). Univariate Cox regression analysis showed that serum creatinine level, date at PD entry, and the CCI were predictors for mortality. The predialysis nrSLEDAI and SDI scores did not have roles in predicting mortality of lupus PD patients. CONCLUSIONS: The predialysis CCI, instead of SDI, determines an increased risk for mortality in lupus patients treated with PD. The prognosis of lupus patients treated with PD largely depends on the severity of predialysis comorbidity, especially cardiovascular diseases.

COX-2 and iNOS are critical in advanced glycation end product-activated chondrocytes in vitro.

BACKGROUND: The advanced glycation end products (AGEs) accumulate in joints of osteoarthritis patients. This study aimed to investigate the roles of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) pathways in AGE-mediated cartilage damage. MATERIALS AND METHODS: Methylglyoxal-modified albumin was used as the source of AGE. Porcine and human chondrocytes were prepared from the joint cartilage of pigs and osteoarthritis patients. The activation of COX-2, iNOS, nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and protein kinases was determined by Western blotting, kinase assay, electrophoretic mobility shift assay (EMSA) or transfection assay. Prostaglandin E(2) (PGE(2)) and NO concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and Griess reaction respectively. The enzymatic activity of COX was determined by measuring the conversion of arachidonic acid to PGE(2). The release of sulphated glycosaminoglycan and the intensity of Safranin O staining were used to measure cartilage degradation. RESULTS: AGE potently induced COX-2-PGE(2) and iNOS-NO activation in porcine and human chondrocytes. Meanwhile, the upstream molecules regulating COX-2/iNOS activation, such as AP-1, NF-kappaB, extracellular signal regulated protein kinase (ERK) and c-jun N-terminal kinase (JNK), were activated by AGE. Although AGE could not activate p38 directly, by measuring COX enzyme activity, the inhibition of p38 resulted in suppressing AGE-induced conversion of arachidonic acid to PGE(2). Furthermore, successful blockage of either COX-2 or NOS activity significantly reduced AGE-mediated proteoglycan release and cartilage degradation. CONCLUSIONS: This study highlights the significance of COX-2 and iNOS pathways in AGE-mediated OA pathogenesis and their potential as therapeutic targets that are beyond pain killing for OA treatment.

Pegylated interferon alpha-2a versus standard interferon alpha-2a for treatment-naive dialysis patients with chronic hepatitis C: a randomised study.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is prevalent in dialysis patients, and standard interferon monotherapy is the current standard of care for such patients. AIM: To investigate whether pegylated interferon has a better therapeutic efficacy and safety profile than standard interferon in dialysis patients with chronic hepatitis C. METHODS: 50 such patients were randomly assigned to receive either pegylated interferon alpha-2a 135 microg subcutaneously once per week or standard interferon alpha-2a 3 million units subcutaneously thrice per week for 24 weeks. The primary efficacy and safety end points were sustained virological response (SVR) by intention-to-treat analysis and treatment-related withdrawal rate during the study. RESULTS: In univariate analysis, patients receiving pegylated interferon alpha-2a tended to have a higher sustained virological response (SVR) than those receiving standard interferon alpha-2a (48% vs 20%, p = 0.07). By using multivariate analysis, treatment with pegylated interferon alpha-2a (p = 0.02) and pretreatment HCV RNA level <800 000 IU/ml (p = 0.007) were independently predictive of an SVR. All patients failing to achieve a rapid virological response (RVR) could not achieve an SVR. In addition, patients receiving pegylated interferon alpha-2a had a significantly lower treatment-related withdrawal rate than those receiving standard interferon alpha-2a (0% vs 20%, p = 0.04). CONCLUSIONS: Pegylated interferon alpha-2a once weekly provides more effective and safer therapy than standard interferon alpha-2a thrice weekly for treatment-naive dialysis patients with chronic hepatitis C.

Candida parapsilosis peritonitis complicated with infected pancreatic pseudocysts in a peritoneal dialysis patient: a challenge for nephrologists.

In continuous ambulatory peritoneal dialysis (CAPD)-related cases of fungal peritonitis, Candida parapsilosis (C. parapsilosis) has become as common as Candida albicans (C. albicans) in fungal isolates. This report describes a 74-year-old male CAPD patient who received bypass surgery for coronary artery disease, followed by an episode of bacterial peritonitis. The peritonitis was successfully treated with intraperitoneal antibiotics. However, C. parapsilosis peritonitis with concomitant pancreatitis and infected pseudocysts occurred one month later. Despite surgical drainage and intravenous administration of fluconazole, fungal peritonitis persisted. Finally, he died of nosocomial pneumonia. This case demonstrates the poor outcome of C. parapsilosis peritonitis, suggesting a more aggressive treatment in peritoneal dialysis patients.

Postpartum urinary retention after cesarean delivery.

OBJECTIVE: To investigate the incidence of postpartum urinary retention (PUR) after cesarean delivery and determine which obstetric factors contribute to this problem. METHOD: A prospective study recruited 605 pregnant women who had a cesarean delivery. Each patient's postvoid residual bladder volume (PVRBV) was estimated with an ultrasound scan after first micturition. The women were divided into 2 groups: PUR (PVRBV > or =150 mL) and normal. Patients' characteristics, obstetric parameters, and prevalence of lower urinary tract symptoms at 3 months postpartum were compared. RESULT: The overall incidence of PUR was 24.1%. The incidence of overt and covert PUR was 7.4% and 16.7%, respectively. Morphine-related postoperative analgesia, multiple pregnancy, and low body mass index were significantly associated with PUR. At 3-month follow-up, 5.0% of patients had obstructive voiding symptoms and 9.1% had irritative voiding symptoms. CONCLUSION: Our results revealed PUR was a common phenomenon in patients who had a cesarean delivery, and morphine-related postoperative analgesia was the main contributing factor.

Stroke complicating pregnancy and the puerperium.

Stroke complicating pregnancy and the puerperium in Taiwan and the comparison between Western and Eastern countries have not been well studied. We identified retrospectively 32 cases of stroke from 66,781 deliveries, including 21 intracranial hemorrhages and 11 cerebral infarctions from 1992 to 2004. The most common causes of intracranial hemorrhage were vascular anomaly (29%), pre-eclampsia/eclampsia (24%), undetermined (24%) and coagulopathy (19%). The most common causes of cerebral infarction were cardioembolism (36%), cerebral venous thrombosis (27%) and pre-eclampsia/eclampsia (18%). Perinatal adverse outcome included two stillbirths, nine premature deliveries and four abortions. The compiled results of previous studies and ours revealed that intracranial hemorrhage appeared to be slightly more common in Taiwan (43-69%) than in the Western countries (33-52%). The average maternal mortality rate was 17.8% (range 9-38) with 77.8% due to intracranial hemorrhage. The average incidence of stroke associated with pregnancy and the puerperium was 21.3 per 100,000 deliveries (range 8.9-67.1). Our study, different from the Western countries, showed that intracranial hemorrhage is slightly more common than cerebral infarction. Pre-eclampsia/eclampsia is an important cause of stroke, however, the possibility of cardioembolism in cerebral infarction and vascular anomaly in intracranial hemorrhage should be studied.

New insight into the molecular mechanisms of MLL-associated leukemia.

Rearrangements of the MLL gene (ALL1, HRX, and Hrtx) located at chromosome band 11q23 are commonly involved in adult and pediatric cases of primary acute leukemias and also found in cases of therapy-related secondary leukemias. Studies on mouse models of MLL translocation and cell lines containing MLL rearrangements showed that the MLL gene linked chromosomal rearrangements to cellular differentiation and tumor tropism. Moreover, recent structural/functional studies on MLL and aberrant MLL proteins provided new clues and suggested that different mechanisms might be included in leukemogenesis by MLL rearrangements. The connection between these different mechanisms will help us understand globally how aberrant MLL oncogenes affect the normal cellular processes at molecular level.

Early Detection of a Hepatic Artery Pseudoaneurysm After Liver Transplantation Is the Determinant of Survival.

BACKGROUND: Hepatic artery pseudoaneurysm (PA) after liver transplantation (LT) is a rare but potentially fatal complication. Among a series of 50 patients of LT, we experienced 3 such cases. Some authors also have reported cases of PA, either intrahepatic or extrahepatic. The aim of this study was to investigate the important factors that affect the treatment outcome. METHODS: Three patients were presented. To analyze the factors, not only our patients but also the patients with PA reported in the literature (including 10 case series and 23 case reports) were enrolled for analysis. The possible factors probably affecting the survival were compared statistically, including age, sex, clinical manifestation as bleeding (including gastrointestinal bleeding, hemobilia, or intra-abdominal bleeding), treatment (with embolization or surgical exploration or stent), diagnosis establishment before or after bleeding, and so forth. RESULTS: From univariate analysis, the significant factors that affect survival are sex (female) (P = .036), stent treatment (P = .006), and early detection (P = .036), whereas age (P = .493) and presentation with hemorrhage (P = .877) are not significant factors. However, according to multivariate analysis, stent treatment has a borderline significance (P = .056). CONCLUSIONS: Early detection of such a life-threatening complication is a key determinant of survival. "Early" does not refer to early postoperative days but means the detection prior to the rupture of the pseudoaneurysm. Postoperative imaging studies such as computed tomographic scan or magnetic resonance cholangiopancreatography early and periodically to follow up the graft status is recommended, especially for those who had received other interventions before or after the liver transplantation.