BMP9‐ID1 signaling promotes EpCAM‐positive cancer stem cell properties in hepatocellular carcinoma

The malignant nature of hepatocellular carcinoma (HCC) is closely related to the presence of cancer stem cells (CSCs). Bone morphologic protein 9 (BMP9), a member of the transforming growth factor‐beta (TGF‐β) superfamily, was recently reported to be involved in liver diseases including cancer. We aimed to elucidate the role of BMP9 signaling in HCC‐CSC properties and to assess the therapeutic effect of BMP receptor inhibitors in HCC. We have identified that high BMP9 expression in tumor tissues or serum from patients with HCC leads to poorer outcome. BMP9 promoted CSC properties in epithelial cell adhesion molecule (EpCAM)‐positive HCC subtype via enhancing inhibitor of DNA‐binding protein 1 (ID1) expression in vitro. Additionally, ID1 knockdown significantly repressed BMP9‐promoted HCC‐CSC properties by suppressing Wnt/β‐catenin signaling. Interestingly, cells treated with BMP receptor inhibitors {"type":"entrez-nucleotide","attrs":{"text":"K02288","term_id":"191391"}}K02288 and LDN‐212854 blocked HCC‐CSC activation by inhibiting BMP9‐ID1 signaling, in contrast to cells treated with the TGF‐β receptor inhibitor galunisertib. Treatment with LDN‐212854 suppressed HCC tumor growth by repressing ID1 and EpCAM in vivo. Our study demonstrates the pivotal role of BMP9‐ID1 signaling in promoting HCC‐CSC properties and the therapeutic potential of BMP receptor inhibitors in treating EpCAM‐positive HCC. Therefore, targeting BMP9‐ID1 signaling could offer novel therapeutic options for patients with malignant HCC.     

Need for improved antimicrobial and infection control stewardship in Vietnamese intensive care units

Objective Survey of antibiotic consumption, microbial resistance and hygiene precautions in the intensive care units of three hospitals in northern Vietnam. Methods Observational study. Data were collected from the microbiological laboratories. Antibiotic consumption was determined based on quantities of drugs delivered from the pharmacy. A protocol to observe the application of hygiene precautions was developed and used. Bacteria were typed and tested for drug susceptibility using the disc‐diffusion method. Results The mean antibiotic consumption was 811 defined daily doses per 1000 occupied bed days. The most commonly used antibiotics were third‐generation cephalosporins, followed by carbapenems, amoxicillin and ampicillin. Eighty per cent of bacterial isolates were Gram‐negative. The most common pathogens found in blood cultures were Escherichia coli and Klebsiella spp., Pseudomonas spp., Acinetobacter spp., Staphylococcus aureus and Enterococcus faecalis. Acinetobacter and Pseudomonas spp. were the two most frequently isolated bacteria from the respiratory tract and all other sources together. Seventy per cent of Acinetobacter species showed reduced susceptibility to imipenem, 80% to ciprofloxacin and 89% to ceftazidime. Forty‐four per cent of Pseudomonas spp. showed reduced susceptibility to imipenem, 49% to ciprofloxacin and 49% to ceftazidime. Escherichia coli was fully susceptible to imipenem, but 57% of samples were resistant to both ciprofloxacin and cefotaxime. Hygiene precautions were poor, and fewer than 50% of patient contacts incorporated appropriate hand hygiene. Conclusion Low antibiotic consumption, poor hygiene precautions and the high level of antibiotic resistance indicate that there is room for improvement regarding antibiotic use and infection control.     

Ethical Attitudes of Nurse, Physician, and Unaffiliated Members of Institutional Review Boards

PURPOSE: To evaluate the recommendation for adding unaffiliated members to institutional review boards (IRB) by comparing the attitudes and influence of IRB members of different backgrounds, primarily nurses, physicians, and unaffiliated members. DESIGN: Survey. METHOD: A closed-ended self-administered questionnaire concerning ethical issues in human subjects research was completed by 284 IRB members in a nonprobability sample of 27 IRBs in 12 U.S. states. The attitudes and influence of IRB members with different backgrounds were compared. FINDINGS: Nurses rated most of the issues as more important than did all other members; physicians rated most of the issues as less important than did all other members; and unaffiliated IRB members rated the issues similar to the whole. Nurses and unaffiliated members were ranked the least influential IRB members, and IRB chairs and physicians were ranked the most influential. CONCLUSIONS: The responses of the IRB members in this study indicate that adding more unaffiliated members to IRBs is unlikely to increase IRB concerns with ethical issues. Adding more nurse members to IRBs might increase IRB concerns with ethical issues if the level of influence of the nurses is increased.     

Randomised primary health center based interventions to improve the diagnosis and treatment of undifferentiated fever and dengue in Vietnam

Background  

Fever is a common reason for attending primary health facilities in Vietnam. Response of health care providers to patients with fever commonly consists of making a presumptive diagnosis and proposing corresponding treatment. In Vietnam, where malaria was brought under control, viral infections, notably dengue, are the main causes of undifferentiated fever but they are often misdiagnosed and inappropriately treated with antibiotics.     

Selection of the most promising 2-substituted quinoline as antileishmanial candidate for clinical trials

The antileishmanial evaluation of more than one hundred 2-substituted quinolines led us to identify three compounds for further studies: compound 1 (2-n-propylquinoline), compound 2 (2-(2methoxyethenyl)quinoline) and compound 3 (2-(2-hydroxyprop-2-enyl)quinoline). The final selection of a potential drug candidate was mainly based on chemical stability and acute oral toxicity as discriminating criteria. The most stable compound in various conditions was 2-n-propylquinoline (compound 1). Only reversible toxicity signs were observed for compound 1 at 1000 mg/kg after a treatment by oral route at a single dose and no sign was detected at 100 mg/kg. Interestingly, 2-substituted quinolines were active on a Leishmania donovani line, resistant to sitamaquine, a 8-aminoquinoline, suggesting that 2-substituted quinolines and 8-aminoquinoline probably affect a different target in L. donovani.     

Hepatitis B vaccination coverage of Vietnamese children in south-western Sydney

Vaccination coverage since the selective hepatitis B vaccination of neonates of highrisk group program introduced in 1987, was measured in 658 children from 301 Vietnamese families living in the southwestern Sydney. The vaccination rate of children born after the introduction of the program was twice that of children born before its implementation (OR=2.00, 95% Cl 1.65–2.42). The shorter the mother's duration of residency in Australia, the more likely her children were to be fully vaccinated (OR=2.49, 95% Cl 2.43-2.62). A catch-up vaccination program of older siblings is required to assist the public health strategy to reduce the morbidity and mortality from hepatitis B viral infection.     

Hypothesis of the cause and development of neoplasms.

Cancer, in general, is considered a disease of genetic mutation. Many questions are, however, unanswered. How exactly do mutations occur in the cells? How do gene mutations interface with the cell microenvironment and macroenvironment to create cancer phenotypes? Is mutation the cause of cancer or the consequence of special adaptive responses to aging; hormonal imbalance; physical, chemical and biologic stresses and damage? What makes cancer spread in the body and invade other organs causing death to the patient? In this paper, we hypothesize that the cellular hyperexcitability via stimulation of mineral channels (e.g. sodium voltage-gated channels) and ligand excitatory receptors (e.g. glutamate and other neuron and non-neuronal excitatory receptors) could be a significant causative and pathogenic factor of cancer. Managing hyperexcitatory states of the cells through lifestyle, nutritional changes, phytochemical and pharmaceutical medications theoretically could be a prospective direction in cancer prevention and therapy.     

Effects of repeated exposure of diazinon on cholinesterase activity and growth in snakehead fish (Channa striata)

The organophosphate insecticide diazinon is widely used in the Mekong river delta and often applied several times per rice crop. In the present study, juvenile snakehead fish Channa striata, which is a commercially important inhabitant of rice fields, were exposed twice to 4-day pulses of 0.016, 0.079 or 0.35 mg/L of diazinon, separated by a 2 week interval to imitate the exposure conditions in the field. After the 4-day exposures to these environmentally realistic concentrations, the fish were moved to clean water for recovery. During this experiment, which lasted a total of 2 months, the individual growth rates and brain cholinesterase levels were measured. We show not only that diazinon caused long term inhibition of brain ChE activity, which was still significantly depressed at the termination of the experiment, but also that the highest of these realistic concentrations caused a significant 30% growth inhibition.     

An evaluation of total parenteral nutrition in the management of steroid-dependent and steroid-resistant patients with Crohn's disease

This study is an evaluation of short- and long-term benefits of total parenteral nutrition (TPN) in 20 patients with active Crohn's disease but without fistulae. TPN was done during 42 (14-80) days (median-range) after failure of medical therapy including patients with steroid-resistant (11 SR) or steroid-dependent (9 SD) active Crohn's disease. Efficacy of short-term TPN was demonstrated by nutritional repair and achievement of clinical remission in all but one patients. Follow-up was 28 (8-78) months in the 19 patients (10 SR, 9 SD) discharged improved after the end of TPN. At 1 yr, the cumulative recurrence rate was 26% (5/19). During the follow-up, three patients (2 SR, 1 SD) remained symptom-free, 13 (6 SR, 7 SD) had a partial remission defined as relapse controlled by medication, and only three patients (2 SR, 1 SD) had a relapse uncontrolled by medical therapy leading to surgery. Therefore in our selected population without fistula or abscess, after failure of medical therapy TPN was obviously an effective therapy which avoided surgery. Furthermore follow-up indicated that SD and SR were only transient events in the course of Crohn's disease patients.