Supplementary Material for: The Effect of Prostaglandin Analogues on Central Corneal Thickness of Patients with Glaucoma or Ocular Hypertension: a systematic review

Purpose: A meta-analysis of observational studies was conducted to evaluate the effect of prostaglandin analogues (PGAs) on central cornea thickness (CCT) of patients with glaucoma and ocular hypertension (OHT). Methods: A literature search was performed through Pubmed, Embase, Cochrane Library, the System for Information on Grey Literature in Europe (Open Grey), ClinicalTrials.gov, and reference lists of retrieved studies. Observational studies were included in our meta-analysis. The final CCT of patients and 95% confidence interval (CI) from each study were extracted. Study quality was assessed using The Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ). A fixed-effects model was used to calculate the weighted mean difference (WMD) and 95% confidence interval (CI). Subgroup analyses based on several stratified factors were also performed. Results: Five cohort studies, five case-control, three cross-sectional studies involving 2722 subjects were included. The pooled effect of all thirteen studies showed PGAs can reduce CCT of patients with glaucoma or OHT slightly but significantly (WMD, -9.37; 95% CI [-12.18, -6.57], P =0.00; I2 = 45.5%). And significant results were observed in all specific study design ( WMD, -5.17; 95% CI [-9.52, -0.82] for cohort study; WMD, -15.31; 95% CI [-22.66, -7.97] for case–control study; WMD, -8.65; 95% CI [-17.30, -0.01] for cross-sectional study). Also, subgroup analysis of exposure time showed the effect of PGAs was more obvious in the first two years (WMD, -5.81; 95% CI [-9.49, -2.14] for 1 year; WMD, -13.02; 95% CI [-20.03, -6.01] for 2 years). Conclusions: The pooled effects from current literature suggest that PGAs use could reduce CCT of patients with glaucoma or OHT slightly but significantly, and this effect is more pronounced in the first two years. This reminds us that we need to pay attention to the changes in CCT during the first two years of PGA use in case we misestimate intraocular pressure (IOP) and the efficacy of the PGA

Supplementary Material for: Loss of Pten in renal tubular cells leads to water retention by upregulating AQP2

Introduction: Phosphatase and tensin (PTEN) is a multifunctional gene associated with the normal development and physiological function of various tissues including the kidney. However, its role in renal tubular reabsorption function has not been well elucidated. Methods: We generated a renal tubule-specific Pten knockout mouse model by crossing Ptenfl/fl mice with Ksp-Cre transgenic mice, evaluated the effect of Pten loss on renal tubular function, and investigated the underlying mechanisms. Results: Pten loss resulted in abnormal renal structure and function and water retention in multiple organs. Our results also demonstrated that aquaporin-2 AQP2, an important water channel protein, was upregulated and concentrated on the apical plasma membrane of collecting duct cells, which could be responsible for the impaired water balance in Pten loss mice. The regulation of Pten loss on AQP2 was mediated by Protein kinase B (AKT) activation. Discussion/Conclusions: Our results reveal a connection between PTEN gene inactivation and water retention, suggesting the importance of PTEN in normal kidney development and function

Supplementary Material for: Early Cognitive Impairment after Intracerebral Hemorrhage in the INTERACT1 Study

<b><i>Background:</i></b> Data on cognitive impairment after acute intracerebral hemorrhage (ICH) are limited. This study is aimed at determining the frequency and predictors of cognitive impairment among participants of the pilot phase, Intensive Blood Pressure (BP) Reduction in Acute Cerebral Hemorrhage Trial (INTERACT1). <b><i>Methods:</i></b> INTERACT1 was an open randomized trial of early intensive (target systolic BP <140 mm Hg) compared with contemporaneous guideline-recommended BP lowering in 404 patients with elevated systolic BP (150–220 mm Hg) within 6 h of ICH onset. Cognitive impairment was defined by scores ≤24 on the Mini-Mental State Examination (MMSE) assessed by interview on follow-up at 90 days. <b><i>Results:</i></b> A total of 231 (64.5%) of 358 90-day survivors had MMSE scores for analyses, and 75 (32.5%) had cognitive impairment. In multivariable analysis, older age (OR 2.48, 95% CI 1.73–3.56 per 10-year increase; <i>p</i> < 0.001), female sex (OR 2.06, 95% CI 1.00–4.23; <i>p</i> = 0.049), prior ICH (OR 2.87, 95% CI 1.08–7.65; <i>p</i> = 0.035), high baseline National Institute of Health Stroke Scale score (OR 1.06, 95% CI 1.00–1.13; <i>p</i> = 0.044), and high mean systolic BP over the first 24 h post-randomization (OR 1.34, 95% CI 1.07–1.68/10 mm Hg increase; <i>p</i> = 0.011) were independently associated with cognitive impairment. <b><i>Conclusions:</i></b> One third of patients have significant cognitive impairment early after ICH, which is more frequent in the elderly, females, those with prior ICH, and more severe initial neurological deficit and with persistently high early systolic BP

Supplementary Material for: Flagellins of <b><i>Salmonella</i></b> Typhi and Nonpathogenic <b><i>Escherichia coli</i></b> Are Differentially Recognized through the NLRC4 Pathway in Macrophages

Flagellin is recognized by both Toll-like receptor (TLR)5 and NAIP5/NLRC4 inflammasome receptors. We hypothesized that the flagellins derived from different bacteria might differentially activate TLR5 and/or NAIP5/NLRC4 signal pathways. To test this, the immune recognition of recombinant flagellins derived from pathogenic <i>Salmonella</i> Typhi (SF) and the nonpathogenic <i>Escherichia coli</i> K12 strain MG1655 (KF) were examined by the activation of TLR5 and NLRC4 pathways in various cell types. While flagellins SF and KF were not distinguishable in activating the TLR5 pathway, KF induced significantly less interleukin-1β production and pyroptotic cell death in peritoneal macrophages than SF, and showed markedly lower efficiency in activating caspase-1 through the NLRC4 pathway than SF. Macrophages may differentially recognize flagellins by intracellular sensors and thereby initiate the immune response to invading pathogenic bacteria. Our findings suggest an active role of flagellin as an important determinant in host differential immune recognition and for the control of bacteria infection

Supplementary Material for: Gross Hematuria Is More Common in Male and Older Patients with Renal Tuberculosis in China: A Single-Center 15-Year Clinical Experience

<p><b><i>Objectives:</i></b> This study aimed to investigate the clinical features of renal tuberculosis and identify the age- and gender-related differences. <b><i>Methods:</i></b> A total of 419 patients at the Peking University First Hospital from January 2000 to July 2015 were retrospectively reviewed. Data on demographic characteristics, clinical presentation, complications, laboratory results, radiologic imaging, surgical procedures, and pathology features were collected and compared between genders and 3 different age groups (under 40 years, 41-60, years and over 60 years). <b><i>Results:</i></b> The most common local presentations were lower urinary tract symptoms (65.2%), flank pain (37.9%), and gross hematuria (26.3%). Constitutional symptoms were also observed in 38.9% of the patients. Gross hematuria was more common in male patients (32.2%) and older patients (45.5%). Flank pain was more common in female patients (43.6%). Patients younger than 40 years of age had lower frequencies of calcification of the urinary tract (22.2%) and kidney atrophy (4.2%) in CT. In the postoperative pathological reports, atrophy (35.9%) and fibrosis (38.5%) were found to be significantly more common in older patients. <b><i>Conclusions:</i></b> While gross hematuria is more prevalent in older patients and male patients, flank pain is more common in female patients. Radiological and pathological features including calcification of the urinary tract, fibrosis, and kidney atrophy are more common in older patients.</p

Supplementary Material for: Admission Low Magnesium Level Is Associated with In-Hospital Mortality in Acute Ischemic Stroke Patients

<p><b><i>Background:</i></b> Low magnesium levels are associated with an elevated risk of stroke. In this study, we investigated the association between magnesium levels on hospital admission and in-hospital mortality in acute ischemic stroke (AIS) patients. <b><i>Methods:</i></b> A total of 2,485 AIS patients, enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city, were included in this study. The patients were divided into 4 groups according to their level of admission magnesium: Q1 (<0.82 mmol/L), Q2 (0.82-0.89 mmol/L), Q3 (0.89-0.98 mmol/L), and Q4 (≥0.98 mmol/L). Cox proportional hazard model was used to estimate the effect of magnesium on all-cause in-hospital mortality in AIS patients. <b><i>Results:</i></b> During hospitalization, 92 patients (3.7%) died from all causes. The lowest serum magnesium level (Q1) was associated with a 2.66-fold increase in the risk of in-hospital mortality in comparison to Q4 (hazard ratio [HR] 2.66; 95% CI 1.55-4.56; <i>p</i>-trend < 0.001). After adjusting for age, sex, time from onset to hospital admission, baseline National Institutes of Health Stroke Scale score, and other potential covariates, HR for Q1 was 2.03 (95% CI 1.11-3.70; <i>p</i>-trend = 0.014). Sensitivity and subgroup analyses further confirmed a significant association between lower magnesium levels and a high risk of in-hospital mortality. <b><i>Conclusions:</i></b> Decreased serum magnesium levels at admission were independently associated with in-hospital mortality in AIS patients.</p

Supplementary Material for: Serum Anti-PLA2R Antibody Predicts Treatment Outcome in Idiopathic Membranous Nephropathy

<strong><em>Background:</em></strong> M-type phospholipase A₂ receptor (PLA₂R) has been identified as the major target antigen in idiopathic membranous nephropathy (IMN). However, the role of glomerular PLA₂R (gPLA₂R) and the associations of serum anti-PLA₂R antibody (sPLA₂R-Ab) titre with diagnosis, treatment and prognosis in IMN need to be further investigated. <b><i>Methods:</i></b> We screened 148 consecutive patients with biopsy-proven membranous nephropathy (MN; 113 with IMN and 35 with secondary MN (SMN)) who were followed up for ≤20 months. Serum and urine samples were simultaneously collected at different time points. The levels of sPLA₂R-Ab were detected using immunofluorescence and enzyme-linked immunosorbent assay. gPLA₂R was assessed by immunofluorescence. <b><i>Results:</i></b> Most patients with IMN displayed both gPLA₂R and sPLA₂R-Ab positive (85.8 and 82.3%, respectively). In contrast, very few patients with SMN showed either gPLA₂R or sPLA₂R-Ab positive. The sPLA₂R-Ab titre, not gPLA₂R, was significantly correlated with proteinuria. Surprisingly, changes in sPLA₂R-Ab titre occurred earlier and faster than proteinuria in patients who were followed up for ≤20 months during the whole period of observation. Survival analysis of IMN patients indicated a significant association between sPLA₂R-Ab titre and outcome, whereas, no significant difference was observed between the gPLA₂R intensity and outcome. <b><i>Conclusions:</i></b> These data indicate that sPLA₂R-Ab might be a better biomarker for IMN diagnosis and treatment outcome. In addition, monitoring sPLA₂R-Ab titre may assist in determining when to initiate the administration of immunosuppressive agents and in evaluating treatment efficacy.<br