Evaluation of Intrarenal Blood Flow by Doppler Ultrasonography Immediately after Extracorporeal Shock Wave Lithotripsy on Hydronephrotic Kidney

Extracorporeal shock wave lithotripsy (ESWL) is an effective and relatively noninvasive mode of treatment for urinary calculi. The aim of this study was to test whether therapeutic ESWL induces changes in renal parenchymatous blood flow and to evaluate shock wave side effects on the renal parenchyma. A total of 45 patients who underwent ESWL for ureteropelvic stone between January 2002 and July 2003 were included in this prospective study. Color Doppler sonography before and 30 minutes after ESWL showed no significant morphologic change. Resistive index (RI) was used to estimate renovascular resistance. The RI significantly increased in obstructed hydronephrotic kidneys. However, no significant change was observed in both treated and untreated kidneys before and after treatment. Hydronephrotic kidneys do not have a higher risk of post-ESWL renovascular resistance interference. The measurement of changes in RI with Doppler ultrasonography may provide useful information for clinical diagnosis of renal tubulointerstitial and vascular damage

Prevalence of intestinal parasitic infections among school children in capital areas of the Democratic Republic of São Tomé and Príncipe, West Africa

Background: Although the Democratic Republic of Sao Tome and Principe (DRSTP) has undertaken school children-based deworming programs against intestinal parasitic infections (IPIs) using a single dose of mebendazole annually since 2005, it remains unclear as to the outcome to date. The present study intends to  investigate the recent IPIs status among school children living in capital areas of the DRSTP.Methods: A total of 252 school children (121 boys and 131 girls) of grades 4 and 5 from 4 primary schools located in the capital areas participated in the present study and their fresh fecal specimens were examined for the presence of any parasites using the merthiolate- iodine-formaldehyde concentration method as conducted.Results: The overall prevalence of IPIs was 64.7% (163/ 252). No significant gender difference in prevalence between boys (67.8%) and girls (61.8%) was found (p = 0.3). The majority of school children were infected with a single species of parasite (55.8%). Altogether, 12 different intestinal parasite species were identified in DRSTP school children, of which 9 species were pathogenic and the remaining 3 were non-pathogenic.Conclusion: Improving the detection method, sanitation facilities and personal hygiene as well as utilizing combined drugs are all important measures to greatly reduce IPIs in DRSTP school children.Keywords: Democratic Republic of Sao Tome and Principe, school children, intestinal parasitic infection

NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50 ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1, p21(Waf1/Cip1) gene expression had markedly increased while cyclin B1 and D1 gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor gene p53 in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activity in vitro and in vivo

Targeting PML-RARα and Oncogenic Signaling Pathways by Chinese Herbal Mixture Tien-Hsien Liquid in Acute Promyelocytic Leukemia NB4 Cells

Tien-Hsien Liquid (THL) is a Chinese herbal mixture that has been used worldwide as complementary treatment for cancer patients in the past decade. Recently, THL has been shown to induce apoptosis in various types of solid tumor cells in vitro. However, the underlying molecular mechanisms have not yet been well elucidated. In this study, we explored the effects of THL on acute promyelocytic leukemia (APL) NB4 cells, which could be effectively treated by some traditional Chinese remedies containing arsenic trioxide. The results showed THL could induce G2/M arrest and apoptosis in NB4 cells. Accordingly, the decrease of cyclin A and B1 were observed in THL-treated cells. The THL-induced apoptosis was accompanied with caspase-3 activation and decrease of PML-RARα fusion protein. Moreover, DNA methyltransferase 1 and oncogenic signaling pathways such as Akt/mTOR, Stat3 and ERK were also down-regulated by THL. By using ethyl acetate extraction and silica gel chromatography, an active fraction of THL named as EAS5 was isolated. At about 0.5–1% of the dose of THL, EAS5 appeared to have most of THL-induced multiple molecular targeting effects in NB4 cells. Based on the findings of these multi-targeting effects, THL might be regarding as a complementary and alternative therapeutic agent for refractory APL

Phenotypes and Genotypes of Patients with Pantothenate Kinase-Associated Neurodegeneration in Asian and Caucasian Populations: 2 Cases and Literature Review

Objectives. Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disease caused by pantothenate kinase 2 (PANK2, OMIM 606157) mutations. This study is aimed to investigate clinical presentations, pathologies, and genetics in patients with PKAN. Methods. Two patients with PKAN were reported. We reviewed the literature to include additional 19 patients with PKAN in Eastern Asia. These patients were divided into classic and atypical groups by the age of onset. We compared the data on PKAN patients of Asian and Caucasian populations. Results. We found iron deposits in the globus pallidus in our Patient 1 and a heterozygous truncating mutation (c.1408insT) in Patient 2. Literature review shows that generalized dystonia and bulbar signs are more common in classic PKAN patients, whereas segmental dystonia and tremors are more specific to atypical ones. Asian patients have less complex presentations-lower prevalence of pyramidal signs, mental impairment, and parkinsonism-than Caucasians. D378G in exon 3 is the most frequent mutation (28%) in Asians. Conclusions. Our study demonstrates that the distribution of dystonia is the major distinction between subgroups of PKAN. Caucasian patients have more complex presentations than Asians. Exon 3 and 4 are hot spots for screening PANK2 mutations in Asian patients

Effects of and satisfaction with short message service reminders for patient medication adherence: a randomized controlled study

BACKGROUND: Medication adherence is critical for patient treatment. This study involved evaluating how implementing Short Message Service (SMS) reminders affected patient medication adherence and related factors. METHODS: We used a structured questionnaire to survey outpatients at three medical centers. Patients aged 20 years and older who were prescribed more than 7 days of a prescription medication were randomized into SMS intervention or control groups. The intervention group received daily messages reminding them of aspects regarding taking their medication; the control group received no messages. A phone follow-up was performed to assess outcomes after 8 days. Data were collected from 763 participants in the intervention group and 435 participants in the control group. RESULTS: After participants in the intervention group received SMS reminders to take medication or those in the control group received no messages, incidences of delayed doses were decreased by 46.4 and 78.8% for those in the control and intervention groups, respectively. The rate of missed doses was decreased by 90.1% for participants in the intervention group and 61.1% for those in the control group. We applied logistic regression analysis and determined that participants in the intervention group had a 3.2-fold higher probability of having a decrease in delayed doses compared with participants in the control group. Participants in the intervention group also showed a 2.2-fold higher probability of having a decrease in missed doses compared with participants in the control group. CONCLUSIONS: Use of SMS significantly affected the rates of taking medicine on schedule. Therefore, daily SMS could be useful for reminding patients to take their medicine on schedule

The Taiwan Birth Panel Study: a prospective cohort study for environmentally- related child health

<p>Abstract</p> <p>Background</p> <p>The Taiwan Birth Panel Study (TBPS) is a prospective follow-up study to investigate the development of child health and disease in relation to in-utero and/or early childhood environmental exposures. The rationale behind the establishment of such a cohort includes the magnitude of potential environmental exposures, the timing of exposure window, fatal and children's susceptibility to toxicants, early exposure delayed effects, and low-level or unknown neurodevelopmental toxicants.</p> <p>Methods</p> <p>A total of 486 mother-infant paired was enrolled from April 2004 to January 2005 in this study. Maternal blood before delivery, placenta and umbilical cord blood at birth, and mothers' urine after delivery were collected. The follow-up was scheduled at birth, 4, 6 months, and 1, 2, 3 and 5 years. The children's blood, urine, hair, and saliva were collected at 2 years of age and children's urine was collected at 5 years of age as well. The study has been approved by the ethical committee of National Taiwan University Hospital. All the subjects signed the inform consent on entering the study and each of the follow up.</p> <p>Results</p> <p>Through this prospective birth cohort, the main health outcomes were focused on child growth, neurodevelopment, behaviour problem and atopic diseases. We investigated the main prenatal and postnatal factors including smoking, heavy metals, perfluorinated chemicals, and non-persistent pesticides under the consideration of interaction of the environment and genes.</p> <p>Conclusions</p> <p>This cohort study bridges knowledge gaps and answers unsolved issues in the low-level, prenatal or postnatal, and multiple exposures, genetic effect modification, and the initiation and progression of "environmentally-related childhood diseases."</p

High versus standard doses interferon-alpha in the treatment of naïve chronic hepatitis C patients in Taiwan: a 10-year cohort study

BACKGROUND: Interferon-alpha monotherapy is effective in less than one-third patients with chronic hepatitis C. The dose-effect, tolerability and durability of interferon-alpha treatment and its long-term effect on the prevention of cirrhosis and hepatocellular carcinoma in naïve Taiwanese patients with chronic hepatitis C have not been well investigated. We conducted the present cohort study treated with high and standard interferon-alpha to illustrate the issues. METHODS: We performed a long-term virologic and histological follow-up of 214 chronic hepatitis C patients treated with interferon-alpha, 3 million units (3-MU, n = 80) or 6-MU (n = 134) thrice weekly for 24 weeks, in Taiwan between 1992 and 2001. RESULTS: There was no difference in the incidence of discontinuation between 3-MU and 6-MU groups (4/80, 5.0% versus 10/134. 7.5%). The 6-MU group had similar incidence of adverse events with the 3-MU group, except that 6-MU group had significantly higher incidence of psychological manifestations, mainly presented as irritability. The rates of sustained virological response (SVR) were significantly higher in 6-MU regimen (37.1%) than in 3-MU regimen (23.7%, p < 0.05) in per protocol analysis. Based on multivariate analysis, baseline viral load was strongly associated with SVR, followed by hepatitis C virus genotype, interferon-alpha regimen, and liver fibrosis. A histological improvement in necroinflammatory activity, but not in fibrosis was observed in the follow-up biopsy performed 0.5–5.5 years (mean: 1.9 years, n = 51) after end-of-treatment. Among patients without SVR, there was more activity improvement in 6-MU group. The durability of SVR was 100% (18/18) and 97.8% (45/46) for 3-MU and 6-MU group, respectively, in a mean follow-up period of 6.81 years (5.25–9.18 years). For 163 baseline non-cirrhotic patients, 9 of 84 (10.7%) non-responders and 3 of 79 (3.8%) sustained responders progressed to cirrhosis during a mean follow-up period of 5.52 and 5.74 years, respectively (p = 0.067, Kaplan-Meier survival analysis, log-rank test). For all 200 patients, hepatocellular carcinoma was detected in 12 of 113 (10.6%) non-responders and one of 87 (1.1%) sustained responders during a mean follow-up period of 5.67 and 5.73 years, respectively (p < 0.01, Kaplan-Meier survival analysis, log-rank test). CONCLUSION: We confirm the dose effect of interferon-alpha in chronic hepatitis C. Six-MU regimen had better efficacy than 3-MU regimen in virologic and histological responses. Both regimens had good tolerability and durability in Taiwan. Sustained response could reduce the incidence of cirrhotic change and hepatocarcinogenesis

Afatinib Exerts Immunomodulatory Effects by Targeting the Pyrimidine Biosynthesis Enzyme CAD

13 páginas, 7 figurasCurrent clinical trials of combined EGFR-tyrosine kinase inhibitors (TKI) and immune checkpoint blockade (ICB) therapies show no additional effect. This raises questions regarding whether EGFR-TKIs attenuate ICB-enhanced CD8+ T lymphocyte function. Here we show that the EGFR-TKI afatinib suppresses CD8+ T lymphocyte proliferation, and we identify CAD, a key enzyme of de novo pyrimidine biosynthesis, to be a novel afatinib target. Afatinib reduced tumor-infiltrating lymphocyte numbers in Lewis lung carcinoma (LLC)-bearing mice. Early afatinib treatment inhibited CD8+ T lymphocyte proliferation in patients with non-small cell lung cancer, but their proliferation unexpectedly rebounded following long-term treatment. This suggests a transient immunomodulatory effect of afatinib on CD8+ T lymphocytes. Sequential treatment of afatinib with anti-PD1 immunotherapy substantially enhanced therapeutic efficacy in MC38 and LLC-bearing mice, while simultaneous combination therapy showed only marginal improvement over each single treatment. These results suggest that afatinib can suppress CD8+ T lymphocyte proliferation by targeting CAD, proposing a timing window for combined therapy that may prevent the dampening of ICB efficacy by EGFR-TKIs. SIGNIFICANCE: This study elucidates a mechanism of afatinib-mediated immunosuppression and provides new insights into treatment timing for combined targeted therapy and immunotherapy. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3270/F1.large.jpg.This study was supported by Taiwan Ministry of Science and Technology grants MOST 104-2320-B-002-044-MY3, MOST 106-2320-B-002-046-MY3, and MOST 108-2320-B-002-024-MY3, National Health Research Institutes grants NHRI-EX106-10401BI and NHRI-EX109-10725BI, National Taiwan University grants NTU107L890504 and NTU110L893503 to M.-S. Lee, and National Taiwan University Hospital grants 106-003451, 107-003849, 108-004269, and 109-004720 to C.-C. Ho. This work was also supported by MINECO grants BFU2016-80570-R and RTI2018-098084-B-I00 (AEI/FEDER, UE). The authors would like to thank the Laboratory Animal Core Facility at the College of Medicine, National Taiwan University for their servicesPeer reviewe