LiOtBu-promoted synthesis of bis(3-indolyl)methanes by the alkylation of indoles with alcohols under air.

Bis(3-indolyl)methanes (BIMs) are known for their important bioactivities, which include anti-cancer, anti-inflammatory, antibacterial, and antioxidant properties. In this study, we are disclosing a metal catalyst-free synthesis of BIMs in high yields via the alkylation reaction of indoles and alcohols in the presence of lithium tert-butoxide base. Notably, oxygen in air played an important role as an oxidant for the facilitation of this transformation. Interestingly, unactivated aliphatic alcohols could be successfully used as alkylating reagents in the alkylation reactions of indole. Especially, several chemical intermediates detected by GC-MS gave important information about the mechanism insights. This method demonstrated cost and environmental advantages for the development of green processes.

Feasibility of monitoring Global Breast Cancer Initiative Framework key performance indicators in 21 Asian National Cancer Centers Alliance member countries.

Background: The Global Breast Cancer Initiative (GBCI) Framework, launched by the World Health Organisation (WHO) in 2023, emphasises assessing, strengthening, and scaling up services for the early detection and management of breast cancer. This study aims to determine the feasibility of monitoring the status of breast cancer control in the 21 Asian National Cancer Centers Alliance (ANCCA) countries based on the three GBCI Framework key performance indicators (KPIs): stage at diagnosis, time to diagnosis, and treatment completion. Methods: We reviewed published literature on breast cancer control among 21 ANCCA countries from May to July 2023 to establish data availability and compiled the latest descriptive statistics and sources of the indicators using a standardised data collection form. We performed bivariate Pearson's correlation analysis to measure the strength of correlation between stage at diagnosis, mortality and survival rates, and universal health coverage. Findings: Only 12 (57%) ANCCA member countries published national cancer registry reports on breast cancer age-standardised incidence rate (ASIR) and age-standardised mortality rate (ASMR). Indonesia, Myanmar, and Nepal had provincial data and others relied on WHO's Global Cancer Observatory (GLOBOCAN) estimates. GLOBOCAN data differed from the reported national statistics by 5-10% in Bhutan, Indonesia, Iran, the Republic of Korea, Singapore, and Thailand and >10% in China, India, Malaysia, Mongolia, and Sri Lanka. The proportion of patients diagnosed in stages I and II strongly correlated with the five-year survival rate and with the universal health coverage (UHC) index. Three countries (14%) reported national data with >60% of invasive breast cancer patients diagnosed at stages I and II, and a five-year survival rate of >80%. Over 60% of the ANCCA countries had no published national data on breast cancer staging, the time interval from presentation to diagnosis, and diagnosis to treatment. Five (24%) countries reported data on treatment completion. The definition of delayed diagnosis and treatment completion varied across countries. Interpretation: GBCI's Pillar 1 KPI correlates strongly with five-year survival rate and with the UHC index. Most ANCCA countries lacked national data on cancer staging, timely diagnosis, and treatment completion KPIs. While institutional-level data were available in some countries, they may not represent the nationwide status. Strengthening cancer surveillance is crucial for effective breast cancer control. The GBCI Framework indicators warrant more detailed definitions for standardised data collection. Surrogate indicators which are measurable and manageable in country-specific settings, could be considered for monitoring GBCI indicators. Ensuring UHC and addressing health inequalities are essential to early diagnosis and treatment of breast cancer. Funding: Funding for this research article's processing fee (APC) will be provided by the affiliated institution to support the open-access publication of this work. The funding body is not involved in the study design; collection, management, analysis and interpretation of data; or the decision to submit for publication. The funding body will be informed of any planned publications, and documentation provided.

Intraoperative cell salvage: The impact on immune cell numbers.

BACKGROUND: Patient outcomes are influenced by many confounding factors peri-operatively, including the type of surgery, anaesthesia, transfusion, and immune competence. We have previously demonstrated (in-vitro) that compared to allogeneic blood transfusion (ABT), intraoperative cell salvage (ICS) improves immune competence. The peri-operative immune response is complex. Altered or impaired immune responses may predispose patients to develop adverse outcomes (i.e., post-operative wound infection, pneumonia, urinary tract infection etc.) Surgical patients may develop infection, even without the confirmed presence of a definite microbiological pathogen. With all these factors in mind it is important to consider changes in immune cell numbers (and sub-populations) and functional capacity during peri-operative transfusion. METHODS: In this TRIMICS-Cell (Transfusion Related Immune Modulation and Intraoperative Cell Salvage-Cell numbers) study (n = 17, October 2018-November 2019) we prioritized and analysed peri-operative changes in the number and proportions of immune cell populations and sub-populations (B cells (CD20+), NK (natural killer) cells (CD56+), monocytes (CD14+), T cells (total CD3+ and sub-populations: T helper cells (CD4+), cytotoxic T cells (CD8+), effector T cells (CD4+ CD127+), activated effector T cells (CD4+ CD25+ CD127+) and regulatory T cells (CD4+ CD25+ CD127-)), plasmacytoid dendritic cells (pDC; Lineage-, HLA-DR+, CD11c-, CD123+), classical dendritic cell (cDC) (Lineage-, HLA-DR+, CD11c+), and cDC activation (Lineage-, HLA-DR+, CD11c+), co-stimulatory/adhesion molecules and pDC (CD9+, CD38+, CD80+, CD83+, CD86+, CD123+). Firstly we analysed the whole cohort of study patients and secondly according to the relevant transfusion modality (i.e., three study groups: those who received no transfusion, received ICS only (ICS), or both ICS and allogeneic packed red blood cells (pRBC) (ICS&RBC)), during major orthopaedic surgery. RESULTS: For the whole study cohort (all patients), changes in immune cell populations were significant: leucocytes and specifically neutrophils increased post-operatively, returning towards pre-operative numbers by 48h post-operatively (48h), and lymphocytes reduced post-operatively returning to pre-operative numbers by 48h. When considering transfusion modalities, there were no significant peri-operative changes in the no transfusion group for all immune cell populations studied (cell numbers and proportions (%)). Significant changes in cell population numbers (i.e., leucocytes, neutrophils and lymphocytes) were identified in both transfused groups (ICS and ICS&RBC). Considering all patients, changes in immune cell sub-populations (NK cells, monocytes, B cells, T cells and DCs) and functional characteristics (e.g., co-stimulation markers, adhesion, activation, and regulation) were significant peri-operatively and when considering transfusion modalities. Interestingly DC numbers and functional capacity were specifically altered following ICS compared to ICS&RBC and pDCs were relatively preserved post-operatively following ICS. CONCLUSION: A transient peri-operative alteration with recovery towards pre-operative numbers by 48h post-surgery was demonstrated for many immune cell populations and sub-populations throughout. Immune cell sub-populations and functional characteristics were similar peri-operatively in those who received no transfusion but changed significantly following ICS and ICS&RBC. Interesting changes that require future study are a post-operative monocyte increase in the ICS&RBC group, changes in cDC considering transfusion modalities, and possibly preserved pDC numbers post-operatively following ICS. Future studies to assess changes in immune cell sub-populations, especially during peri-operative transfusion, while considering post-operative adverse outcomes, is recommended.

Mutation spectrum of retinoblastoma patients in Vietnam.

BACKGROUND: Retinoblastoma (RB), an intraocular malignancy commonly diagnosed in children, is mostly caused by inactivating mutations of both alleles of the RB1 gene. Early genetic screening for RB1 gene mutations would greatly improve treatment outcomes and patient management. METHODS: In this study, both somatic and germline mutations were detected in blood and tumour samples of 42 RB patients using direct sequencing and multiplex ligation-dependent probe amplification. RESULTS: In total, 34 different mutations were found in 36 patients, including 1 SNP, 4 large deletions, 5 splicing sites, 1 missense, 7 frameshifts and 17 nonsense mutations. There were five novel mutations and one unreported which have not been found in large databases such as Leiden Open Variation Database (LOVD) and ClinVar. CONCLUSION: A higher rate of RB patients carrying heterozygous germline mutation and highly prevalent with pathogenic truncated mutation, hence, early detection of RB is essential for vision salvation and genetic counselling.

New Dibenzocyclooctadiene Lignans and Phenolics from Kadsura heteroclite with Anti-Inflammatory Activity.

A chemical investigation of K. heteroclite led to isolation of two new dibenzocyclooctadienes (1 and 2) together with 14 known compounds (3-16) by using multiple chromatographic techniques. New compounds (1 and 2) were obtained and identified by spectroscopic methods (HR-ESI-MS, 1D and 2D NMR, and ECD) as well as by comparison of their experimental data with those reported in the literatures. All the isolates were evaluated for their ability to modulate TNF-α production in lipopolysaccharide (LPS) stimulated RAW264.7 cells. Among them, compound 5 displayed the most inhibition against tumor necrosis factor (TNF)-α production with IC50 value of 6.16±0.14 µM. Whereas, compounds (1, 3, and 6) showed the significant inhibition (IC50 values ranging from 9.41 to 14.54 µM), and compounds (2, 4, 9, 10, 13, 15, and 16) exhibited moderate inhibition (IC50 values ranging from 19.27 to 40.64 µM) toward TNF-α production, respectively.

Repurposing thioridazine for inducing immunogenic cell death in colorectal cancer via eIF2α/ATF4/CHOP and secretory autophagy pathways.

BACKGROUND: Colorectal cancer (CRC) is a highly prevalent cancer type with limited targeted therapies available and 5-year survival rate, particularly for late-stage patients. There have been numerous attempts to repurpose drugs to tackle this problem. It has been reported that autophagy inducers could augment the effect of certain chemotherapeutic agents by enhancing immunogenic cell death (ICD). METHODS: In this study, we employed bioinformatics tools to identify thioridazine (THD), an antipsychotic drug, and found that it could induce autophagy and ICD in CRC. Then in vitro and in vivo experiments were performed to further elucidate the molecular mechanism of THD in CRC. RESULTS: THD was found to induce endoplasmic reticulum (ER) stress in CRC cells by activating the eIF2α/ATF4/CHOP axis and facilitating the accumulation of secretory autophagosomes, leading to ICD. In addition, THD showed a remarkable ICD-activating effect when combined with oxaliplatin (OXA) to prevent tumor progression in the mouse model. CONCLUSIONS: Together, our findings suggest that the repurposed function of THD in inhibiting CRC involves the upregulation of autophagosomes and ER stress signals, promoting the release of ICD markers, and providing a potential candidate to enhance the clinical outcome for CRC treatment. Video Abstract.

Anti-Alzheimer's Activity of Polyphenolic Stilbene-Rich Acetone Fraction of the Oil-Removed Seeds of Passiflora edulis: in Vivo and in Silico Studies.

The stilbene-rich acetone fraction in high yield (6.6 %, PEAS) of Passiflora edulis Sims was prepared and evaluated for neuroprotective activity in murine Alzheimer's disease model induced by aluminum chloride and D-galactose. The phytochemical and HPLC-DAD-MS analysis of the polyphenolic stilbene-rich acetone fraction showed that it contained different stilbenes including trans-piceatannol, scirpusins A-B and cassigarol E. The total phenolic content (TPC) of PEAS was 413.87±1.71 mg GAE eqv/g. The neuroprotective activity of PEAS is typically presented in the Morris water maze-reference Spatial Memory test, where the Alzheimer's mice treated at 100 mg/kg (Alz-ED1) and 200 mg/kg (Alz-ED2) spent less than 47 % and 66 % of the time, respectively, than the Alzheimer's model mice (Alz). Two simple stilbenes, trans-piceatannol and trans-resveratrol, showed selectively inhibitory activity in silico against acetylcholinesterase (AChE). Two stilbene dimers, cassigarol E and scirpusin A, exhibited low nanomolar inhibitory potential against AChE and butyrylcholinesterase (BChE), significantly lower than those of the positive control, donepezil and tacrine. These findings suggest that the stilbenes from P. edulis seeds, particularly the stilbene dimers, warrant further investigation as potential neuroprotective candidates in the prevention of cognitive deficits associated with Alzheimer's disease.

Budget impact analysis of a home-based colorectal cancer screening programme in Malaysia.

OBJECTIVES: The 2020-2022 research project 'Colorectal Cancer Screening Intervention for Malaysia' (CRC-SIM) evaluated the implementation of a home-based CRC screening pilot in Segamat District. This budget impact analysis (BIA) assessed the expected changes in health expenditure of the Malaysian Ministry of Health budget in the scenario where the pilot programme was implemented nationwide vs current opportunistic screening. DESIGN: Budget impact analysis. Assumptions and costs in the opportunistic and novel CRC screening scenarios were derived from a previous evaluation of opportunistic CRC screening in community health clinics across Malaysia and the CRC-SIM research project, respectively. SETTING: National level (with supplement analysis for district level). The BIA was conducted from the viewpoint of the federal government and estimated the annual financial impact over a period of 5 years. RESULTS: The total annual cost of the current practice of opportunistic screening was RM1 584 321 (~I$1 099 460) of which 80% (RM1 274 690 or ~I$884 587) was expended on the provision of opportunistic CRC to adults who availed of the service. Regarding the implementation of national CRC screening programme, the net budget impact in the first year was estimated to be RM107 631 959 (~I$74 692 546) and to reach RM148 485 812 (~I$103 043 589) in the fifth year based on an assumed increased uptake of 5% annually. The costs were calculated to be sensitive to the probability of adults who were contactable, eligible and agreeable to participating in the programme. CONCLUSIONS: Results from the BIA provided direct and explicit estimates of the budget changes to when implementing a population-based national CRC screening programme to aid decision making by health services planners and commissioners in Malaysia about whether such programme is affordable within given their budget constraint. The study also illustrates the use and value of the BIA approach in low-income and middle-income countries and resource-constrained settings.

Synthesis of Multifunctional Eu(III) Complex Doped Fe3O4/Au Nanocomposite for Dual Photo-Magnetic Hyperthermia and Fluorescence Bioimaging.

In this paper, the luminescent complex Eu(3-thenoyltrifluoroacetonate)3 was integrated with Fe3O4 and gold (Au) nanoparticles to form a multifunctional nanocomposite, Fe3O4/Au/Eu(TTA)3 (FOASET NC), for dual magnetic-photothermal therapy and biomedical imaging. Upon functionalization with amine-NH2, the FOASET NC exhibits a small size of 60-70 nm and strong, sharp emission at λmax = 614 nm, enhanced by surface plasmon resonance (SPR) of Au nanoparticles that provided an effective label for HT29 colorectal cancer cells by fluorescence microscopy imaging. In addition, a hyperthermia temperature (42-46 °C) was completely achieved by using these FOASET NCs in an aqueous solution with three heating modes for (i) Magnetic therapy (MT), (ii) Photothermal therapy (PT), and (iii) Dual magnetic-photothermal therapy (MPT). The heating efficiency was improved in the dual magnetic-photothermal heating mode.

BMX, a specific HDAC8 inhibitor, with TMZ for advanced CRC therapy: a novel synergic effect to elicit p53-, ß-catenin- and MGMT-dependent apoptotic cell death.

BACKGROUND: Despite advances in treatment, patients with refractory colorectal cancer (CRC) still have poor long-term survival, so there is a need for more effective therapeutic options. METHODS: To evaluate the HDAC8 inhibition efficacy as a CRC treatment, we examined the effects of various HDAC8 inhibitors (HDAC8i), including BMX (NBM-T-L-BMX-OS01) in combination with temozolomide (TMZ) or other standard CRC drugs on p53 mutated HT29 cells, as well as wild-type p53 HCT116 and RKO cells. RESULTS: We showed that HDAC8i with TMZ cotreatment resulted in HT29 arrest in the S and G2/M phase, whereas HCT116 and RKO arrest in the G0/G1 phase was accompanied by high sub-G1. Subsequently, this combination approach upregulated p53-mediated MGMT inhibition, leading to apoptosis. Furthermore, we observed the cotreatment also enabled triggering of cell senescence and decreased expression of stem cell biomarkers. Mechanistically, we found down-expression levels of ß-catenin, cyclin D1 and c-Myc via GSK3ß/ß-catenin signaling. Intriguingly, autophagy also contributes to cell death under the opposite status of ß-catenin/p62 axis, suggesting that there exists a negative feedback regulation between Wnt/ß-catenin and autophagy. Consistently, the Gene Set Enrichment Analysis (GSEA) indicated both apoptotic and autophagy biomarkers in HT29 and RKO were upregulated after treating with BMX. CONCLUSIONS: BMX may act as a HDAC8 eraser and in combination with reframed-TMZ generates a remarkable synergic effect, providing a novel therapeutic target for various CRCs. Video Abstract.

Laparoscopic Surgery for Intestinal Obstruction Caused by an Internal Paracecal Hernia.

Paracecal hernia is rarely associated with ischemia and has seldom been reported in the few published studies in the review literature. We present a case of incarcerated paracecal hernia with intestinal obstruction that was effectively treated with laparoscopic intervention. A 64-year-old woman who had not previously undergone any intestinal surgery arrived complaining of abdominal pain and vomiting at our hospital. Abdominal computed tomography suggested intestinal obstruction. A laparoscopic emergency procedure demonstrated an incarcerated small bowel loop in the paracecal region. The confined small bowel was removed from the paracecal area. On the fourth postoperative day, the patient was discharged. This case is unusual because the patient presented with small bowel strangulation, leading to intestinal obstruction. Laparoscopic surgery is beneficial for diagnosing internal hernias and curing small-bowel obstructions caused by paracecal hernias.

Dual roles of oxostephanine as an Aurora kinase inhibitor and angiogenesis suppressor.

The Aurora kinases, including Aurora A, B and C, play critical roles in cell division. They have been found overexpressed in a number of types of cancer and may thus be potential targets in cancer therapy. Several Aurora kinase inhibitors have been identified and developed. Some of these have been used in clinical trials and have exhibited certain efficacy in cancer treatment. However, none of these has yet been applied clinically due to the poor outcomes. Oxostephanine is an aporphine alkaloid isolated from several plants of the genus Stephania. This compound has been reported to inhibit Aurora kinase activity in kinase assays and in cancer cells. The present study aimed to investigate the real­time effects of oxostephanine extracted from Stephania dielsiana Y.C. Wu leaves on the growth of an ovarian cancer cell line (OVCAR­8, human ovarian carcinoma); these effects were compared to those of the well­known Aurora kinase inhibitor, VX­680. The effects of oxostephanine on stromal cells, as well as endothelial cells were also examined. The results demonstrated that oxostephanine was an Aurora kinase inhibitor through the prevention of histone H3 phosphorylation at serine 10, the mislocalization of Aurora B and the induction of aneuploidy. Moreover, this substance was selectively cytotoxic to human umbilical vein endothelial cells (hUVECs), whereas it was less cytotoxic to human fibroblasts and umbilical cord­derived mesenchymal stem cells. In addition, this compound significantly attenuated the migration and tube formation ability of hUVECs. Taken together, the present study demonstrates that oxostephanine plays dual roles in inhibiting Aurora kinase activity and angiogenesis. Thus, it may have potential for use as a drug in cancer treatment.

A ruptured pancreatic pseudocyst causes acute peritonitis with clinical characteristics of a gastrointestinal tract perforation.

Intraperitoneal air in pancreatic pseudocysts is a rare complication that can jeopardize hemodynamic stability and requires emergency surgery. A 61-year-old man was admitted to our hospital after abdominal pain, vomiting and diarrhea. Computed tomography showed a hollow visceral perforation with intraperitoneal air and two pseudocysts close to the pancreas. The patient was transferred to the emergency operating room with symptoms of septic shock. We histopathologically diagnosed a ruptured pancreatic pseudocyst combined with an intracystic haemorrhage. We resected a portion of the pseudocyst wall using surface electrocautery inside the lumen, cholecystectomy and peritoneal toilet and maintained adequate external drainage. The patient was discharged on postoperative Day 12. The patient achieved relapse-free survival for 12 months postoperatively. Ruptured pancreatic pseudocysts with extraluminal gas are dangerous if effective medical interventions are not performed. Emergency surgery should be completed as soon as possible to drain the pancreatic cyst and cleanse the abdomen.

Breast cancer screening practices among Vietnamese women and factors associated with clinical breast examination uptake.

BACKGROUND: This study examined current breast cancer (BC) screening practices among Vietnamese women and the factors associated with the uptake of clinical breast examination (CBE). METHODS: A total of 508 women aged 30-74 years in Hanoi completed a knowledge-attitude-practice (KAP) survey in 2019 including validated measures of breast cancer awareness (Breast-CAM) and health beliefs (Champion's Health Belief Model Scale). Descriptive statistics, χ2, and ANOVA tests were used to analyse KAP responses across groups with different sociodemographic characteristics. A logistic regression model assessed the associations of knowledge, beliefs, and sociodemographic characteristics with CBE uptake. RESULTS: Only 18% of respondents were aware of BC signs, risk factors, and screening modalities although 63% had previously received BC screening. CBE was the most common screening modality with an uptake of 51%. A significantly higher proportion of urban residents compared with rural residents (32% vs 18%, Chi-square test, p = 0.04) received mammography. Unlike mammography, CBE uptake was not associated with sociodemographic characteristics (i.e., residence area/education level/occupation/household monthly income/possession of health insurance). CBE uptake was associated with BC knowledge (OR = 2.44, 95%CI: 1.37-4.32), perceived susceptibility to BC (OR = 1.15, 95%CI: 1.05-1.25), and perceived barriers to accessing CBE (OR = 0.88, 95%CI: 0.84-0.92). CONCLUSION: The study points to the need for public health education and promotion interventions to address low levels of awareness about BC and to increase uptake of BC screening in Vietnam in advance of screening programme planning and implementation. It also suggests that screening programmes using CBE are promising given current engagement and the absence of socio-demographic disparities.

Allopurinol-induced severe cutaneous adverse reactions in Vietnamese: the role of HLA alleles and other risk factors.

Aim: To reveal the association of three class I HLA alleles, including HLA-A*33:03, HLA-B*58:01 and HLA-C*03:02, and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese patients. Methods: A case-control study on 100 allopurinol-induced SCARs patients, 183 tolerant controls and 810 population controls was performed. The HLA-A*33:03 and HLA-C*03:02 alleles were detected with the nested allele-specific PCR method; the HLA-B*58:01 allele was detected with the sequence-specific primer PCR method. Results: There were strong associations between HLA-B*58:01 and HLA-C*03:02 and allopurinol-induced SCARs. Specific associations were found between HLA-B*58:01 and Stevens-Johnson syndrome/toxic epidermal necrolysis and between HLA-C*03:02 and drug reaction with eosinophilia and systemic symptoms, with a gene dosage effect. The multivariate regression analysis indicated two significant independent risk factors: HLA-B*58:01/HLA-C*03:02 and estimated glomerular filtration rate <60 ml/min/1.73 m2. The specificity, positive predictive value and negative predictive value of HLA-B*58:01 testing were higher than the HLA-C*03:02 or the multiplex testing, especially in patients with impaired renal function. Conclusion: The results supported pre-treatment HLA-B*58:01 testing in Vietnamese patients with declined renal function to prevent SCARs.

Cytotoxic and nitric oxide inhibitory activities of triterpenoids from Lycopodium clavatum L.

Using combined chromatographic separation techniques, three new triterpenoids named lycomclavatols A-C (1-3), a new natural product, methyl lycernuate-A (4), as well as seven known compounds (5-11), were isolated from the methanol extract of the whole plants of Lycopodium clavatum. Their chemical structures were established based on 1 D/2D NMR and HR-ESI-MS spectroscopic analyses. Among the isolates, compound 1 exhibited inhibitory activity on NO production in LPS-stimulated BV2 cells (IC50 = 36.0 µM). In addition, 1 was cytotoxic against both HepG2 and A549 cancer cell lines, with IC50 values of 40.7 and 87.0 µM, respectively. Compounds 10 and 11 showed cytotoxicity on only HepG2 and A549 cells, with IC50 values of 91.2 and 57.6 µM, respectively. Our results contribute to understanding more the secondary metabolites produced by L. clavatum and provide a scientific rationale for further investigations of anti-inflammatory and anticancer effects for this valuable medicinal plant.

Costs of breast cancer treatment incurred by women in Vietnam.

BACKGROUND: There is a paucity of research on the cost of breast cancer (BC) treatment from the patient's perspective in Vietnam. METHODS: Individual-level data about out-of-pocket (OOP) expenditures on use of services were collected from women treated for BC (n = 202) using an online survey and a face-to-face interview at two tertiary hospitals in 2019. Total expenditures on diagnosis and initial BC treatment were presented in terms of the mean, standard deviation, and range for each type of service use. A generalised linear model (GLM) was used to assess the relationship between total cost and socio-demographic characteristics. RESULTS: 19.3% of respondents had stage 0/I BC, 68.8% had stage II, 9.4% had stage III, none had stage IV. The most expensive OOP elements were targeted therapy with mean cost equal to 649.5 million VND ($28,025) and chemotherapy at 36.5 million VND ($1575). Mean total OOP cost related to diagnosis and initial BC treatment (excluding targeted therapy cost) was 61.8 million VND ($2667). The mean OOP costs among patients with stage II and III BC were, respectively, 66 and 148% higher than stage 0/I. CONCLUSIONS: BC patients in Vietnam incur significant OOP costs. The cost of BC treatment was driven by the use of therapies and presentation stage at diagnosis. It is likely that OOP costs of BC patients would be reduced by earlier detection through raised awareness and screening programmes and by providing a higher insurance reimbursement rate for targeted therapy.

Chemical constituents from Lycopodiella cernua and their anti-inflammatory and cytotoxic activities.

Phytochemical investigation of the whole plants of Lycopodiella cernua resulted in the isolation and identification of three new compounds (1-3), namely lycocernuaside E (1), lycernuic ketone F (2), and lycernuic B (3) and 12 known ones (4-15). Their chemical structures were established based on 1 D/2D NMR spectroscopic and HR-ESI-MS data analyses. Compounds 5, 12, and 13 displayed NO inhibitory effects in LPS-stimulated BV2 cells, with IC50 values of 21.2 ± 1.1, 28.5 ± 1.4, and 21.9 ± 1.1 µM, respectively. In addition, cytotoxic activity of the isolated compounds against MCF7 (breast carcinoma), HepG2 (hepatocarcinoma), and SK-Mel2 (melanoma) cancer cell lines were also reported.

Health-related quality of life among breast cancer patients compared to cancer survivors and age-matched women in the general population in Vietnam.

PURPOSE: This study compared the health-related quality of life (HRQoL) of breast cancer (BC) patients, survivors, and age-matched women from the general population in Vietnam to address the paucity of HRQoL research and contribute to the robust assessment of BC screening and care in Vietnam. METHODS: The standardised EQ-5D-5L instrument was incorporated in an online survey and a hospital-based face-to-face survey, and together with data from the Vietnam EQ-5D-5L norms study. χ2 tests assessed EQ-5D health profile associations and a Tobit regression model investigated the association between overall health status (EQ-VAS/utility scores) and sociodemographic and clinical characteristics. RESULTS: A total of 309 participants (107 patients undergoing treatment and 202 survivors who had completed treatment) provided usable responses. The dimensions that affected mostly the HRQoL of women with BC were pain/discomfort and anxiety/depression. Current patients and survivors differed significantly regarding HRQoL dimensions of mobility, self-care, usual activities, and anxiety/depression. Their health utilities were 0.74 and 0.84, respectively, compared with 0.91 for age-matched Vietnamese women in the general population (p < 0.001). Treatment status (survivor vs patient), younger age, higher monthly household income, and higher education levels were associated with higher health utility. CONCLUSIONS: The results point to unmet needs in mental health support and well-being and for attention to be given to the development of a biopsychosocial system of cancer diagnosis, treatment, and care. The results will also inform future assessments of the comparative value for money of interventions intended to impact on breast cancer in Vietnam.

Effect of Valproic Acid on the Metabolic Spectrum of Clozapine in Patients With Schizophrenia.

BACKGROUND: Valproic acid (VPA) is frequently used with clozapine (CLZ) as mood stabilizer and/or seizure prophylaxis. Valproic acid is known to reduce N-desmethylclozapine (N-DMC) but not CLZ levels. This leads to the hypothesis that VPA induces the CLZ metabolism via non-N-desmethylation pathways. Therefore, we aimed to investigate the effect of concurrent VPA use on the serum concentrations of a spectrum of CLZ metabolites in patients, adjusting for smoking. METHODS: In total, 288 patients with an overall number of 737 serum concentration measurements of CLZ and metabolites concurrently using VPA (cases, n = 22) or no interacting drugs (controls, n = 266) were included from a routine therapeutic drug monitoring service. Linear mixed model analyses were performed to compare the dose-adjusted concentrations (C/D) of CLZ, N-DMC, CLZ 5N/N+-glucuronides, and metabolite-to-parent ratios in cases versus controls. RESULTS: After adjusting for covariates, the N-DMC (-40%, P < 0.001) and N+-glucuronide C/Ds (-78%, P < 0.001) were reduced in cases versus controls, while the CLZ C/D was unchanged (P > 0.7). In contrast, the 5N-glucuronide C/D (+250%, P < 0.001) and 5N-glucuronide-to-CLZ ratios (+120%, P = 0.01) were increased in cases versus controls. CONCLUSIONS: Our findings show that complex changes in CLZ metabolism underly the pharmacokinetic interaction with VPA. The lower levels of N-DMC seem to be caused by VPA-mediated induction of CLZ 5N-glucuronide formation, subsequently leading to reduced substrate availability for N-desmethylation. Whether the changes in CLZ metabolism caused by VPA affects the clinical outcome warrants further investigation.