Investigating the Anti-Tumor Effects of Two Novel B-Catenin Inhibitors in Ovarian Cancer Cells

Epithelial ovarian cancer (EOC) is the deadliest female malignancy. The development of chemoresistance and relapse becomes a major challenge in treating ovarian cancer. The Wnt/-catenin pathway, which plays a critical role in developmental and physiological processes, have been indicated to contribute to EOC development. Aberrant activation of this pathway was reported to promote cancer stem cell self-renewal, metastasis, and chemoresistance in all subtypes of EOC, suggesting the Wnt/-catenin pathway is a strong candidate for the development of targeted therapies. In this study, we have identified and investigated the anti-tumor effects of two novel -catenin inhibitors, referred to as compound 2 (C2) and C10. Results from functional assays showed that C2 and C10 inhibited EOC cell proliferation, anchorage-independent growth, and spheroid formation. In addition, C10 treatment inhibited the expression of stem cell markers of EOC cells, suggesting the small molecule inhibitors target ovarian cancer stem cells. Using TOPflash reporter assays, we found that C2 and C10 inhibited the transcriptional activity of -catenin/TCF complex. Finally, preliminary results suggest that C2 and C10 bind directly to recombinant -catenin. Taken together, this study identified two novel potent -catenin inhibitors that have strong anti-tumor effects. These compounds could be potentially developed into targeted therapies for ovarian cancer patients who harbor abnormal activation of Wnt/-catenin signaling

Measuring banking efficiency in Vietnam: parametric and non-parametric methods

The article aims to evaluate the business efficiency of commercial banks in Vietnam using both parametric and non-parametric approaches. In this study, the Stochastic Frontier Analysis (SFA), which belongs to a parametric method, and Data Envelopment Analysis (DEA), a non-parametric approach, are applied to a sample of 30 joint stock commercial banks in Vietnam in the period of 2011–2015. Applying Tobit regression model, the impact of bank size, bank age, and the ownership feature on the efficiency of bank service industry in Vietnam is also investigated. The analysis results show that in general, the Vietnamese banking efficiency is improving during the selected period regardless of techniques used. However, there is small level of similarity in efficiency rankings identified from the SFA and DEA models. In terms of efficiency determinants, the results show that all three variables of size, age, and state ownership have a positive impact on bank efficiency

Optimizing the ratios of standardized ileal digestible (SID) methionine plus SID cystine and SID threonine to SID lysine in low-protein diets for working boars

This study aimed to optimize the ratios of standardized ileal digestible (SID) methionine (Met) plus cystine (Cys), and threonine (Thr) to SID lysine (Lys) in low-protein diets for working boars. Forty-eight working Duroc boars were randomly allocated to one of 12 dietary treatments in a 3x4 factorial experimental design in which factor 1 was the ratios of SID Met plus Cys to SID Lys (50, 60, 70%), factor 2 was the ratios of SID Thr to SID Lys (40, 50, 60, 70%). Semen was collected at a 4 days interval for 6 weeks for 10 ejaculates. Semen volume (V), percentage of sperm with progressive motility (A), sperm concentration (C), and the total number of motile sperm per ejaculate (VAC) were measured. The results of the study revealed that the ratios of SID Met plus Cys to SID Lys in the diets affected the C and VAC. Values of C and VAC were highest at the ratios of SID Met plus Cys to SID Lys of 70% and lowest at 50% (P<0.05). Similarly, the ratios of SID Thr to SID Lys affected the C and VAC. Further, the values of C and VAC were highest at the ratio of SID Thr to SID Lys of 60% and lowest at 40% (P<0.05). There was no interaction effect between the two factors. In conclusion, the ratios of SID Met plus Cys to SID Lys of 70% and SID Thr to SID Lys of 60% in a 13.5% CP diet are optimal for working boars

Acidifiers as Alternatives for Antibiotics Reduction and Gut Health Improvement for Poultry and Swine

Using antibiotics of low doses as feed additives could support to improve poultry and swine performances. However, these applications have caused resistance of bacteria and antibiotic residues in foods of animal origins. Therefore, efforts were focused on solutions to replace antibiotics as growth promoters (AGPs). There are many alternatives for AGPs, in which organic acids are one of the important alternatives. The aim of this chapter is to review publications on these acids and their other forms namely as acidifiers using as feed additives including their names and forms, mode of actions, spectrum against bacteria, combinations among them, and latest updates on their effects on swine and poultry production. The scientific findings show that acidifiers can inhibit pathogenic bacteria growth, improve nutrient digestibility, enhance immunity and overall gut health, consequently increase performances of poultry and swine. Several acids and their salts in both liquid and solid forms have been studied and applied as poultry and swine feed additives; however, the efficacy levels and the mode of actions are dependent on the single acidifiers, their salts, and combinations among them. The uses of acidifiers in their salts and derivative forms and mixtures of different acidifiers seem to be more favorable

Undergraduate Medical Education Reform in Viet Nam for a Primary Health Care Workforce

Strong primary health care (PHC) systems require a robust PHC workforce. Traditionally, medical education takes place in academic medical centres that favour subspecialty care rather than PHC settings. This may undervalue primary care as a career and contribute to a shortage of PHC workers. However, designing undergraduate medical education curricula that incorporate early experiences in clinical care delivery at PHC sites remains a challenge, including in many low- and middle-income countries (LMICs). This paper describes how a collaboration between Harvard Medical School and five medical schools in Vietnam, and in-country collaborations among the Vietnamese medical schools, facilitated curricular innovation and co-creation of coursework relevant to PHC through the development of a Practice of Medicine (POM) course. The collaboration implemented a technical assistance strategy consisting of in-person workshops, focused virtual consultations, on-site ‘office hours’, site visits and observations to each of the five medical universities, and immersion trips to support the creation and implementation of the POM course. A pilot program was started at a single site and then scaled nationally using local customisation, experience, and expertise utilising a train-the-trainers approach. As a result, five new POM courses have been developed by five Vietnamese institutions. Fifty Vietnamese faculty received training to lead the POM course development, and 228 community-based preceptors have been trained to teach students at PHC sites. A total of 52 new PHC and community-based clinical training sites have been added, and 3,615 students have completed or are currently going through a POM course. This experience can serve as a model for future academic collaborations to support the development of a robust PHC workforce for the 21st century

Host Transcription Profile in Nasal Epithelium and Whole Blood of Hospitalized Children Under 2 Years of Age With Respiratory Syncytial Virus Infection.

BACKGROUND: Most insights into the cascade of immune events after acute respiratory syncytial virus (RSV) infection have been obtained from animal experiments or in vitro models. METHODS: In this study, we investigated host gene expression profiles in nasopharyngeal (NP) swabs and whole blood samples during natural RSV and rhinovirus (hRV) infection (acute versus early recovery phase) in 83 hospitalized patients <2 years old with lower respiratory tract infections. RESULTS: Respiratory syncytial virus infection induced strong and persistent innate immune responses including interferon signaling and pathways related to chemokine/cytokine signaling in both compartments. Interferon-α/β, NOTCH1 signaling pathways and potential biomarkers HIST1H4E, IL7R, ISG15 in NP samples, or BCL6, HIST2H2AC, CCNA1 in blood are leading pathways and hub genes that were associated with both RSV load and severity. The observed RSV-induced gene expression patterns did not differ significantly in NP swab and blood specimens. In contrast, hRV infection did not as strongly induce expression of innate immunity pathways, and significant differences were observed between NP swab and blood specimens. CONCLUSIONS: We conclude that RSV induced strong and persistent innate immune responses and that RSV severity may be related to development of T follicular helper cells and antiviral inflammatory sequelae derived from high activation of BCL6

A Multi-Center Randomized Trial to Assess the Efficacy of Gatifloxacin versus Ciprofloxacin for the Treatment of Shigellosis in Vietnamese Children

The bacterial genus Shigella is the most common cause of dysentery (diarrhea containing blood and/or mucus) and the disease is common in developing countries with limitations in sanitation. Children are most at risk of infection and frequently require hospitalization and antimicrobial therapy. The WHO currently recommends the fluoroquinolone, ciprofloxacin, for the treatment of childhood Shigella infections. In recent years there has been a sharp increase in the number of organisms that exhibit resistance to nalidixic acid (an antimicrobial related to ciprofloxacin), corresponding with reduced susceptibility to ciprofloxacin. We hypothesized that infections with Shigella strains that demonstrate resistance to nalidixic acid may prevent effective treatment with ciprofloxacin. We performed a randomized controlled trial to compare 3 day ciprofloxacin therapy with 3 days of gatifloxacin, a newer generation fluoroquinolone with greater activity than ciprofloxacin. We measured treatment failure and time to the cessation of individual disease symptoms in 249 children with dysentery treated with gatifloxacin and 245 treated with ciprofloxacin. We could identify no significant differences in treatment failure between the two groups or in time to the cessation of individual symptoms. We conclude that, in Vietnam, ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute dysentery

Ventilator-associated respiratory infection in a resource-restricted setting: impact and etiology.

BACKGROUND: Ventilator-associated respiratory infection (VARI) is a significant problem in resource-restricted intensive care units (ICUs), but differences in casemix and etiology means VARI in resource-restricted ICUs may be different from that found in resource-rich units. Data from these settings are vital to plan preventative interventions and assess their cost-effectiveness, but few are available. METHODS: We conducted a prospective observational study in four Vietnamese ICUs to assess the incidence and impact of VARI. Patients ≥ 16 years old and expected to be mechanically ventilated > 48 h were enrolled in the study and followed daily for 28 days following ICU admission. RESULTS: Four hundred fifty eligible patients were enrolled over 24 months, and after exclusions, 374 patients' data were analyzed. A total of 92/374 cases of VARI (21.7/1000 ventilator days) were diagnosed; 37 (9.9%) of these met ventilator-associated pneumonia (VAP) criteria (8.7/1000 ventilator days). Patients with any VARI, VAP, or VARI without VAP experienced increased hospital and ICU stay, ICU cost, and antibiotic use (p < 0.01 for all). This was also true for all VARI (p < 0.01 for all) with/without tetanus. There was no increased risk of in-hospital death in patients with VARI compared to those without (VAP HR 1.58, 95% CI 0.75-3.33, p = 0.23; VARI without VAP HR 0.40, 95% CI 0.14-1.17, p = 0.09). In patients with positive endotracheal aspirate cultures, most VARI was caused by Gram-negative organisms; the most frequent were Acinetobacter baumannii (32/73, 43.8%) Klebsiella pneumoniae (26/73, 35.6%), and Pseudomonas aeruginosa (24/73, 32.9%). 40/68 (58.8%) patients with positive cultures for these had carbapenem-resistant isolates. Patients with carbapenem-resistant VARI had significantly greater ICU costs than patients with carbapenem-susceptible isolates (6053 USD (IQR 3806-7824) vs 3131 USD (IQR 2108-7551), p = 0.04) and after correction for adequacy of initial antibiotics and APACHE II score, showed a trend towards increased risk of in-hospital death (HR 2.82, 95% CI 0.75-6.75, p = 0.15). CONCLUSIONS: VARI in a resource-restricted setting has limited impact on mortality, but shows significant association with increased patient costs, length of stay, and antibiotic use, particularly when caused by carbapenem-resistant bacteria. Evidence-based interventions to reduce VARI in these settings are urgently needed

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Investigating the Anti-Tumor Effects of Two Novel B-Catenin Inhibitors in Ovarian Cancer Cells

Epithelial ovarian cancer (EOC) is the deadliest female malignancy. The development of chemoresistance and relapse becomes a major challenge in treating ovarian cancer. The Wnt/-catenin pathway, which plays a critical role in developmental and physiological processes, have been indicated to contribute to EOC development. Aberrant activation of this pathway was reported to promote cancer stem cell self-renewal, metastasis, and chemoresistance in all subtypes of EOC, suggesting the Wnt/-catenin pathway is a strong candidate for the development of targeted therapies. In this study, we have identified and investigated the anti-tumor effects of two novel -catenin inhibitors, referred to as compound 2 (C2) and C10. Results from functional assays showed that C2 and C10 inhibited EOC cell proliferation, anchorage-independent growth, and spheroid formation. In addition, C10 treatment inhibited the expression of stem cell markers of EOC cells, suggesting the small molecule inhibitors target ovarian cancer stem cells. Using TOPflash reporter assays, we found that C2 and C10 inhibited the transcriptional activity of -catenin/TCF complex. Finally, preliminary results suggest that C2 and C10 bind directly to recombinant -catenin. Taken together, this study identified two novel potent -catenin inhibitors that have strong anti-tumor effects. These compounds could be potentially developed into targeted therapies for ovarian cancer patients who harbor abnormal activation of Wnt/-catenin signaling