BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.
Adult ; Anti-HIV Agents/adverse effects* ; Antiretroviral Therapy, Highly Active ; China ; Drug Therapy, Combination ; HIV Infections/drug therapy* ; HIV-1 ; Humans ; Maleimides ; Peptides ; Ritonavir/therapeutic use* ; Treatment Outcome ; Viral Load

pantothenic acid, sodium, animal iron, zinc, selenium, and cholesterol (negative trends), and carbohydrate rate, fiber, water-soluble fiber, vitamin K, vitamin C, and plant calcium (positive trends). Multivariate analysis revealed that animal fat, animal iron, and niacin (negative trends) and animal protein, fiber, and vitamin C (positive trends) were statistically significant. Pantothenic acid and sodium showed non-significant negative trends (P < 0.1), and vitamin B₁₂ showed a non-significant positive trend.CONCLUSION: This study provided a nutritional basis and extended the utility of ACFS, which is a bridgehead for future cancer-preventive clinical trials using ACFS.]]>
Animals ; Ascorbic Acid ; Asian Continental Ancestry Group ; Calcium ; Cholesterol ; Diet ; Humans ; Iron ; Multivariate Analysis ; Niacin ; Pantothenic Acid ; Plants ; Riboflavin ; Selenium ; Sodium ; Vegetarians ; Vitamin D ; Vitamin K ; Vitamins ; Zinc

Humans ; Male ; Minerals ; Miners ; Niacinamide ; Pantothenic Acid ; Recommended Dietary Allowances ; Testosterone ; United States Food and Drug Administration ; Vitamin B 12 ; Vitamin B 6 ; Vitamins ; Zinc

OBJECTIVE: Synaptic vesicle mobilization and neurite outgrowth regulation molecules were examined in modulation of effects of methylphenidate (MPH) in Spontaneous Hypertensive Rats (SHRs), a model for attention-deficit hyperactivity disorder (ADHD). METHODS: We compared the changes in the protein expression level of Cyclin dependent kinase 5 (Cdk5) and molecular substrates of Cdk5; tropomyosin receptor kinase B (TrkB), syntaxin 1A (STX1A) and synaptosomal-associated protein 25 (SNAP25). Comparisons were made in prefrontal cortex of vehicle (distilled water i.p. for 7 days)-treated SHRs, vehicle-treated Wistar Kyoto Rats (WKYs) and MPH (2 mg/kg i.p. for 7 days) treated SHRs. RESULTS: The Cdk5 level of vehicle-treated SHRs was significantly decreased compared to the Cdk5 level of vehicle-treated WKY rats, but was restored to the expression level of vehicle-treated WKYs in MPH-treated SHR. The ratio of p25/p35 was significantly decreased in MPH-treated SHR compared to vehicle-treated SHR. Moreover, TrkB, STX1A and SNAP25 of vehicle-treated SHRs were significantly decreased compared to vehicle-treated WKY rats, but were restored to the expression level of vehicle-treated WKYs in MPH-treated SHR. CONCLUSION: The results show that Cdk5, TrkB, STX1A, and SNAP25 were involved in the modulation of MPH effects in prefrontal cortex of SHRs and play important role in treatment of ADHD.
Animals ; Cyclin-Dependent Kinase 5 ; Methylphenidate ; Neurites ; Phosphotransferases ; Prefrontal Cortex ; Rats ; Rats, Inbred WKY ; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins ; Synaptic Vesicles ; Synaptosomal-Associated Protein 25 ; Syntaxin 1 ; Tropomyosin ; Water

Aplastic anemia may develop secondary to environmental exposure to entities such as chemicals, medical drugs, and infectious agents. Fatal complications from antiepileptic medications may occur despite careful and appropriate use. We report the case of a 9-year-old girl with a presenting diagnosis of aplastic anemia following treatment with ethosuximide for absence seizures. Aplastic anemia can now be cured with stem cell transplantation or immunosuppressive therapy. In this case, however, because of the impossibility of bone marrow transplantation and the specific needs of the patient's parents, three courses of methylprednisolone pulse therapy were administered. Following the therapy, there was improvement in pancytopenia and complete remission in the bone marrow. No adverse side effects of therapy were observed. The authors suggest that methylprednisolone pulse therapy may be a treatment for acquired aplastic anemia.
Anemia, Aplastic* ; Anticonvulsants ; Bone Marrow ; Bone Marrow Transplantation ; Child ; Diagnosis ; Environmental Exposure ; Epilepsy, Absence ; Ethosuximide ; Female ; Humans ; Methylprednisolone* ; Pancytopenia ; Parents ; Stem Cell Transplantation

PURPOSE: Vesicle-associated membrane protein 8 (VAMP8) is a soluble N-ethylmaleimide-sensitive factor receptor protein that participates in autophagy by directly regulating autophagosome membrane fusion and has been reported to be involved in tumor progression. Nevertheless, the expression and prognostic value of VAMP8 in breast cancer (BC) remain unknown. This study aimed to evaluate the clinical significance and biological function of VAMP8 in BC. METHODS: A total of 112 BC samples and 30 normal mammary gland samples were collected. The expression of VAMP8 was assessed in both BC tissues and normal mammary gland tissues via a two-step immunohistochemical detection method. RESULTS: The expression of VAMP8 in BC tissues was significantly higher than that in normal breast tissues. Furthermore, increased VAMP8 expression was significantly correlated with tumor size (p=0.007), lymph node metastasis (p=0.024) and recurrence (p=0.001). Patients with high VAMP8 expression had significantly lower cumulative recurrence-free survival and overall survival (p < 0.001 for both) than patients with low VAMP8 expression. In multivariate logistic regression and Cox regression analyses, lymph node metastasis and VAMP8 expression were independent prognostic factors for BC. CONCLUSION: VAMP8 is significantly upregulated in human BC tissues and can thus be a practical and potentially effective surrogate marker for survival in BC patients.
Autophagy ; Biomarkers ; Breast Neoplasms* ; Breast* ; Humans ; Logistic Models ; Lymph Nodes ; Mammary Glands, Human ; Membrane Fusion ; Methods ; N-Ethylmaleimide-Sensitive Proteins ; Neoplasm Metastasis ; Prognosis ; R-SNARE Proteins* ; Recurrence

OBJECTIVE: MicroRNA-155 (miR-155) is significantly highly expressed in breast cancer, lung cancer, liver cancer and other malignant tumors. This study was to design and construct a radiolabeled probe targeting miR-155 for in vivo imaging in breast cancer. METHODS: Anti-miR-155 oligonucleotide (AMO-155) was chemically synthesized with 2' OMe modification. Its 5' end was linked with acetyl amine group. After chelated with a bifunctional chelator NHS-MAG3, AMO-155 was radiolabeled with ^99mTc using stannous chloride. The serum stability was evaluated at cellular level. In vivo imaging was performed in MCF-7 tumor bearing mice after the administration of ^99mTc radiolabeled AMO-155 and scramble control probes, respectively. Furthermore, the blocked imaging of tumor bearing mice was obtained after the injection of unlabeled AMO-155 2 hours ahead. MCF-7 and MDA-MB-231 tumor bearing mice with different expression level of miR-155 were imaged, respectively. Quantitative real-time PCR (qRT-PCR) was used to identify the expression level of miR-155 in the bearing tumors. RESULTS: ^99mTc-AMO-155 was prepared with high radiolabeled efficiency (97%), radiochemical purity (greater than 98%), and radioactive specific activity (3.75 GBq/μg). ^99mTc-AMO-155 was stable in fresh human serum for 12 hours. After the administration via tail vein, ^99mTc-AMO-155 displayed significant accumulation in MCF-7 bearing tumors with high expression level of miR-155, whereas ^99mTc-control showed little accumulation. After blocked with unlabeled AMO-155, the tumor could not be visualized clearly after the administration of ^99mTc-AMO-155. Furthermore, ^99mTc-AMO-155 could show the differential expression of miR-155 in vivo. MCF-7 tumor was shown with significantly higher radioactive accumulation than MDA-MB-231, based on its higher expression level of miR-155, which was verified by qRT-PCR. CONCLUSION ^99mTc-labeled AMO-155 with chemical modification showed good serum stability and in vivo tumor targeting ability. This study provides a potential probe for in vivo imaging of breast cancer.
Animals ; Breast Neoplasms/diagnostic imaging* ; Cell Line, Tumor ; Female ; Humans ; Mice ; MicroRNAs/analysis* ; Oligonucleotides, Antisense ; Oligopeptides ; Radiopharmaceuticals ; Succinimides ; Technetium ; Tissue Distribution

BACKGROUND: Twenty-nail dystrophy (TND) is an acquired idiopathic disease characterized by dull, thin, lusterless, and fragile nails with fissuring, small regular pits, and excessive longitudinal ridging. Although various treatment modalities have been performed in order to treat TND, the effects of these treatments are controversial. OBJECTIVE: To evaluate the effectiveness of oral cyclosporine in TND. METHODS: A total of 38 patients with TND were treated with combination therapy using oral cyclosporine with a pantothenic acid complex-based dietary supplement (Pantogar®; Merz Pharmaceuticals GmbH, Germany), whereas 44 patients were treated with the pantothenic acid complex-based dietary supplement alone. The therapeutic efficacy in each group was retrospectively evaluated using medical records and clinical photographs. RESULTS: The cyclosporine therapy group had significantly more patients whose improvement was rated as almost clear, marked, or moderate compared to the control group (p<0.001). While the mean CHATS (Color, Hyperkeratosis, Area, Thickness, Separation) score of the cyclosporine therapy group was decreased by 13.45 (from 30.95 to 17.5) after treatment, the mean CHATS score of the control group was only decreased by 8 (from 29.43 to 21.43, p<0.001). Moreover, greater Dermatology Life Quality Index changes after treatment were observed in the cyclosporine therapy group (p=0.085). CONCLUSION: Oral cyclosporine can be a valuable therapeutic option in patients with TND.
Cyclosporine* ; Dermatology ; Dietary Supplements* ; Humans ; Medical Records ; Pantothenic Acid ; Quality of Life ; Retrospective Studies

This study examined the characteristics of the foodservice menu items offered at senior welfare centers to provide information on Korean senior menu development. A total of 514 lunch menu items were collected from 27 senior welfare centers in April, July, October and January. The most frequently served staple foods, soups, and side dishes were multi-grain rice, seaweed soup, Bulgogi, Kimchi, and liquid yogurt. The proportions of carbohydrate, protein, and lipids of total energy serving of senior welfare centers were 59.8%: 16.7%: and 22.8%, respectively. The nutrients served at less than 40% of the Recommended Nutrient Intake (RNI) and Adequate Intake (AI) of Dietary Reference Intakes for Koreans (KDRIs) were chloride (1.0%), vitamin D (1.3%), biotin (1.7%), magnessium (4.5%), Iodine (7.5%), pantothenic acid (8.0%), vitamin E (12.5%), vitamin B6 (20.0~21.4%), vitamin K (21.1~24.3%), and water (35.7~39.7%). The nutrients served in excess of the daily intake goal and RNI were iron (98.9~127.1%), sodium (104.9%), and copper (1,100.0%).
Aged* ; Biotin ; Copper ; Humans ; Iodine ; Iron ; Lunch ; Pantothenic Acid ; Recommended Dietary Allowances ; Seaweed ; Sodium ; Vitamin B 6 ; Vitamin D ; Vitamin E ; Vitamin K ; Vitamins ; Water ; Yogurt

BACKGROUND AND PURPOSE: Childhood absence epilepsy (CAE) is one of the most common types of pediatric epilepsy. It is generally treated with ethosuximide (ESM), valproic acid (VPA), or lamotrigine (LTG), but the efficacy and adverse effects of these drugs remain controversial. This study compared initial therapy treatment outcomes, including VPA-LTG combination, and assessed clinical factors that may predict treatment response and prognosis. METHODS: Sixty-seven patients with typical CAE were retrospectively enrolled at the Korea University Medical Center. We reviewed patients' clinical characteristics, including age of seizure onset, seizure-free interval, duration of seizure-free period, freedom from treatment failure, breakthrough seizures frequency, and electroencephalogram (EEG) findings. RESULTS: The age at seizure onset was 7.9±2.7 years (mean±SD), and follow-up duration was 4.4±3.7 years. Initially, 22 children were treated with ESM (32.8%), 23 with VPA (34.3%), 14 with LTG (20.9%), and 8 with VPA-LTG combination (11.9%). After 48 months of therapy, the rate of freedom from treatment failure was significantly higher for the VPA-LTG combination therapy than in the three monotherapy groups (p=0.012). The treatment dose administrated in the VPA-LTG combination group was less than that in the VPA and LTG monotherapy groups. The shorter interval to loss of 3-Hz spike-and-wave complexes and the presence of occipital intermittent rhythmic delta activity on EEG were significant factors predicting good treatment response. CONCLUSIONS: This study showed that low-dose VPA-LTG combination therapy has a good efficacy and fewer side effects than other treatments, and it should thus be considered as a firstline therapy in absence epilepsy.
Academic Medical Centers ; Child ; Electroencephalography ; Epilepsy ; Epilepsy, Absence* ; Ethosuximide ; Follow-Up Studies ; Freedom ; Humans ; Korea ; Prognosis ; Retrospective Studies ; Seizures ; Treatment Failure ; Valproic Acid