Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer.

The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, the externally thiolated hollow mesoporous silica nanoparticles (MSN-SH(E)) is fabricated to serve as a platform for improved bladder intravesical therapy. Enhanced mucoadhesive effect of the thiolated nanovector is confirmed with porcine bladder. The permeation-enhancing effect is also verified, and a fragmented distribution pattern of a tight junction protein, claudin-4, indicates the opening of tight junction. Moreover, MSN-SH(E)-associated reprogramming of M2 macrophages to M1-like phenotype is observed in vitro. The antitumor activity of the mitomycin C (MMC)-loaded nanovector (MMC@MSN-SH(E)) is more effective than that of MMC alone in both in vitro and in vivo. In addition, IHC staining is used to analyze IFN-γ, TGF-ß1, and TNF-α. These observations substantiated the significance of MMC@MSN-SH(E) in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non-muscle invasive bladder cancer (NMIBC) due to its mucoadhesivity, enhanced permeation, immunomodulation, and prolonged and very efficient drug exposure.

Association of Prenatal Maternal Anemia with Tics and Tourette's Syndrome in Offspring.

Iron deficiency anemia (IDA) accounts for most of the anemia in pregnancy, and iron is essential for neurodevelopment. Tics and Tourette's syndrome (TS) are neurodevelopmental disorders that manifest in childhood. A few studies reported an inconclusive association between iron deficiency and tics in children. No study has investigated the relationship between prenatal maternal anemia and tics in children. We aimed to assess the relationship between prenatal anemia exposure and the incidence of tics or TS in offspring. We linked the Taiwan National Health Insurance Research Database to the Maternal and Child Health Database for the analysis and identified 153,854 children with prenatal anemia exposure and 2,014,619 children without prenatal anemia exposure from 2004 to 2016 and followed them through 2017. Cox regression models were applied to compare the risk of tics or TS between the exposed and nonexposed groups. Among the exposed group, 37,832 were exposed at ≤12 weeks of gestational age (GA) and 116,022 at >12 weeks of GA. We observed an increased risk of tics and TS in those exposed at ≤12 weeks compared with the nonexposed group (adjusted hazard ratio (aHR) = 1.23, 95% confidence interval (CI): 1.12-1.34). The result remained consistent after adjusting for birth year, sex, birth order, maternal age, low-income levels, gestational age, birth weight, and alcohol use and smoking during pregnancy (aHR = 1.16, CI: 1.04-1.28). Fetuses exposed to maternal anemia at ≤12 weeks of GA are at high risk of tics or TS. However, this effect was attenuated to insignificance in the sibling comparison. Our study highlights the importance of detection of anemia during pregnancy and proper timing of iron supplementation.

Routine admission to step-down unit as an alternative to intensive care unit after pediatric supraglottoplasty.

OBJECTIVE: To evaluate the feasibility and the outcomes for step-down (SD) unit admission as an alternative to intensive care unit (ICU) admission after supraglottoplasty in the pediatric patient. METHODS: A review of 98 patients who underwent supraglottoplasty from 2012 to 2017 at a tertiary referral pediatric hospital was performed. An SD unit had 1-to-3 nurse-to-patient ratio with noninvasive positive pressure ventilation capability. Data variables included demographics, comorbidities, preoperative and postoperative respiratory requirements, and length of stay. RESULTS: Routine admission to SD occurred for 85% patients while 15% patients were selectively admitted to ICU due to intubation requirement or perioperative respiratory distress. In SD, noninvasive respiratory support was required for 28 (34%) patients. Three (4%) required re-intubation and ICU transfer without delay in care. Patients at high risk for requiring respiratory support after surgery have a neurologic condition (OR 7.0, 95% 2.4-20.2, p < 0.01) or intrinsic pulmonary disease (OR 4.5, 95% CI 1.5-13.3, p < 0.01). Median length of stay was shorter for patients in step-down (1 day, IQR 1-2). CONCLUSION: Patients can be managed safely in a SD unit after supraglottoplasty supporting de-escalation of care. Patients with neurologic and pulmonary comorbidities may have higher respiratory needs postoperatively. Prospective studies are warranted to further optimize resource allocation.

Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid.

PURPOSE: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. METHODS AND MATERIALS: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. RESULTS: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). CONCLUSIONS: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

Factors related to nephrotic-range proteinuria in late-stage chronic kidney disease patients with diabetes mellitus.

PURPOSE: Diabetic nephropathy and proteinuria are important risk factors for both end-stage renal disease and cardiovascular events. The present study aimed to identify the factors associated with nephrotic-range proteinuria in patients with advanced diabetic nephropathy. METHODS: This cross-sectional study enrolled 386 diabetic patients with chronic kidney disease (CKD) stages 3-5, from our outpatient Department of Nephrology. Urinary protein-to-creatinine ratio was recorded. Additionally, other laboratory parameters, body mass index, blood pressure, comorbidities, and medications were also reviewed. RESULTS: The mean age of the patients was 65.1 ± 11.6 years. Among patients with CKD stage 3 and 4, the odds ratio (OR) for nephrotic-range proteinuria in relation with systolic blood pressure significantly increased starting from 121 mmHg (OR 7.04 and 11.79 for systolic blood pressure of 121-140 and ≥141 mmHg, respectively, in comparison with systolic blood pressure below 121 mmHg). In addition, serum phosphorus ≥4.7 mg/dl was associated with significantly higher risk (OR 15.45) for severe proteinuria, compared with a phosphorus level ≤2.6 mg/dl. Finally, hypertriglyceridemia ≥241 mg/dl was also associated with higher OR for severe proteinuria, compared with a triglyceride level ≤200 mg/dl. Similar associations were found in patients with CKD stage 5. CONCLUSIONS: Higher systolic blood pressure, serum phosphorus, and triglyceride levels are associated with nephrotic-range proteinuria in patients with diabetic nephropathy and CKD stage 3-5. Further studies should clarify whether a reduction in serum phosphorus would lead to a decrease in proteinuria in these patients.

Hyperphosphatemia is associated with overt proteinuria in non-diabetic patients with late-stage chronic kidney disease: a cross-sectional study.

PURPOSE: Proteinuria plays an important role in the progression of chronic kidney disease (CKD), as well as a powerful predictor of cardiovascular morbidity and mortality. The aim of our study was to investigate the potential determinants associated with overt proteinuria in non-diabetic patients with late-stage CKD. METHODS: Between January 2006 and September 2011, a total of 418 non-diabetic patients with CKD stage 3-5 were enrolled from the outpatient department of nephrology. Urinary protein-to-creatinine ratio and serum phosphorus were determined. Other laboratory parameters, associated comorbidities, medication use, body mass index, and blood pressure were also assessed. RESULTS: The mean age of the patients was 66.7 ± 14.0 years. In multiple logistic regression analysis and adjusting for established risk factors, the odds ratios for overt proteinuria were 3.96 (95 % confidence interval, 1.80-8.76; p = 0.001) for higher serum phosphorus level (≥4.3 mg/dl) and 3.56 (95 % confidence interval, 1.47-8.63; p = 0.005) for hypercholesterolemia (≥217 mg/dl), compared to subjects with serum phosphorus <3.3 mg/dl and cholesterol level 158-184 mg/dl. The similar significant findings remained robust in individuals not receiving phosphate binder. CONCLUSIONS: Hyperphosphatemia and high serum cholesterol are associated with overt proteinuria in non-diabetic patients with late-stage CKD. Further studies should clarify whether this relation is causal and whether serum phosphorus level should be a new therapeutic target for proteinuria reduction.

Anti-enterovirus 71 activity screening of chinese herbs with anti-infection and inflammation activities.

Antipyretic and toxin-eliminating traditional Chinese herbs are believed to possess antiviral activity. In this study, we screened extracts of 22 herbs for activity against enterovirus 71 (EV71). We found that only extracts of Houttuynia cordata Thunb. could neutralize EV71-induced cytopathic effects in Vero cells. The 50% inhibitory concentration of H. cordata extract for EV71 was 125.92 +/- 27.84 mug/ml. Antiviral screening of herb extracts was also conducted on 3 genotypes of EV71, coxsackievirus A16 and echovirus 9. H. cordata extract had the highest activity against genotype A of EV71. A plaque reduction assay showed that H. cordata extract significantly reduced plaque formation. Viral protein expression, viral RNA synthesis and virus-induced caspase 3 activation were inhibited in the presence of H. cordata extract, suggesting that it affected apoptotic processes in EV71-infected Vero cells by inhibiting viral replication. The antiviral activity of H. cordata extract was greater in cells pretreated with extract than those treated after infection. We conclude that H. cordata extract has antiviral activity, and it offers a potential to develop a new anti-EV71 agent.

House dust mite Dermatophagoides farinae augments proinflammatory mediator productions and accessory function of alveolar macrophages: implications for allergic sensitization and inflammation.

In this study, we examine the effects of Dermatophagoides farinae (Der f), a major source of airborne allergens, on alveolar macrophages (AMs), and we also test its contribution to allergic responses in mice. Der f activated NF-kappaB of AMs and, unlike OVA or LPS stimulation, up-regulated IL-6, TNF-alpha, and NO. In addition, it down-regulated antioxidants, but affected neither the expression nor production of IL-12. Der f-stimulated AMs expressed enhanced levels of costimulatory B7 molecules, supported T cell proliferation, and promoted Th2 cell development. The enhanced accessory function was suppressed by blockade mAbs to B7.2, IL-6, and TNF-alpha and by N-monomethyl-L-arginine, an NO synthase inhibitor, and N-acetylcysteine, a thiol antioxidant, whereas it was augmented by (+/-)-S-nitroso-N-acetylpenicillamine, an NO donor. Arg-Gly-Asp-Ser peptide and neo-glycoproteins galactose-BSA and mannose-BSA inhibited the Der f-induced IL-6 and TNF-alpha productions and enhanced accessory function of AMs. Der f was more potent than OVA for inducing pulmonary eosinophilic inflammation, NO, and serum allergen-specific IgG1 Ab production in mice. AMs from Der f-challenged mice expressed enhanced levels of B7 and augmented T cell proliferation ex vivo. In Der f-challenged mice, respiratory syncytial virus infection (5 x 10(5) pfu; 3 days before Der f instillation) augmented Der f-specific Ab production, whereas dexamethasone (50 mg/kg; 1 h before Der f instillation) diminished the allergic airway inflammation and Ab response. We conclude that AMs are sensitive targets for Der f and that the Der f-induced proinflammatory responses may represent an important mechanism in mediating the development of allergic sensitization and inflammation.