How Much Is Too Much? Estimating Effective Price-Hikes to Affect Smoking Behavior in Vietnam.

INTRODUCTION: Raising the price of cigarettes is one of the most effective strategies to reduce cigarette smoking. The Vietnamese government is working toward the tobacco control goal of a 10% reduction in smoking prevalence by 2020. However, cigarette prices in Vietnam have not increased in the last two decades. The aim of this study was to estimate what cigarette prices would make smokers attempt to quit smoking, and to identify predictors of the price to quit and the intention to quit. METHODS: A cross-sectional survey was conducted with 822 male current smokers in Da Nang, Vietnam. A structured questionnaire was adapted from the International Tobacco Control project survey. Bayesian quantile regression was applied to predict factors associated with expected cigarette price. RESULTS: Fifty-six percent of smokers suggested a price to quit. Their median suggested price to quit per pack, 62 000 VND (2.8 USD), was 2.8 times higher than the actual current price, 22 000 VND (1.01 USD). Suggesting a lower price to quit was significantly associated with awareness of warning labels and smoke-free policies. In contrast, being a heavy smoker was significantly associated with a higher suggested price to quit across all quantiles. CONCLUSIONS: There may be sufficient room to increase cigarette prices in Vietnam. The price to quit is associated with various factors, including non-pricing policies. IMPLICATIONS: Evidence suggests that a steep increase in cigarette prices, setting a high minimum tax, and introducing a large specific tax, which are policy-induced price increases that can raise prices substantially in Vietnam, are preferable strategies. In addition to increasing price and taxes, the government should also strengthen non-pricing policies.

Occlusal features and need for orthodontic treatment in persons with osteogenesis imperfecta.

The aim of the study was to (a) analyse dental occlusion and determine the need for orthodontic treatment of persons with osteogenesis imperfecta (OI) in comparison with the healthy population and (b) investigate the associations between OI and malocclusion. A case-control study included 26 OI persons and 400 healthy participants (control group). Occlusal features and the need for orthodontic treatment were defined according to Dental Health Component-Index of Orthodontic Treatment Need and Dental Aesthetic Index. Results showed that Angle Class I, II, and III relationship was found in 23.1%, 3.8%, and 73.1% of OI group, and in the control group, it was 67%, 17.5%, and 15.5%, respectively. OI group had significantly higher prevalence of reverse overjet >1 mm (76.9%), missing teeth (42.3%), posterior crossbite (34.6%), and open bite >2 mm (19.2%) compared to the control group (8.5%, 2.2%, 6.2%, and 3.5%, respectively). OI group had less incisal segment crowding and more incisal segment spacing than the control group (p < 0.05). The need for orthodontic treatment of OI group according to Dental Health Component-Index of Orthodontic Treatment Need and Dental Aesthetic Index was 88.5% and 61.5%, respectively, while in the control group, it was 24.8% and 51.8%. The malocclusion in OI persons was associated with reverse overjet > 1 mm (OR = 13.3, 95% CI = 3.9-44.7, p < .001), Angle Class III malocclusion (OR = 8.0, 95% CI = 2.0-30.8, p = .003), and missing teeth (OR = 4.7, 95% CI = 1.0-22.4, p = .049). In conclusion, there is the high probability of malocclusion in OI persons. Persons with OI require early orthodontic treatment because of significant correlation of OI disease with Angle Class III malocclusion, reverse overjet, and missing teeth.

Constitutive activation of casein kinase 2 in glioblastomas: Absence of class restriction and broad therapeutic potential.

Casein kinase II contributes to the growth and survival of malignant gliomas and attracts increasing attention as a therapeutic target in these tumors. Several reports have suggested that this strategy might be most relevant for specific subgroups of patients, namely Verhaak's classical and TP53 wild-type tumors. Using kinase assays and microarray genetic profiling in a series of 27 proprietary fresh frozen surgical glioma samples, we showed that constitutive CK2 kinase activation is not restricted to tumors that present increased copy numbers or mRNA expression of its catalytic or regulatory subunits, and can result from a functional activation by various cytokines from the glioma microenvironment. Using corresponding primary tumor and human astrocyte cell cultures as well as glioma cell lines, we confirmed that CK2 inhibition is selectively toxic to malignant glial tumors, without any restriction to tumor class or to TP53 status. We finally showed that while the contribution of CK2 to the constitutive NF-κB hyperactivation in malignant gliomas is at best moderate, a delayed activation of NF-κB may associate with the therapeutic resistance of glioma cells to CK2 inhibition.

A bioinspired catalytic aerobic oxidative C-H functionalization of primary aliphatic amines: synthesis of 1,2-disubstituted benzimidazoles.

Aerobic oxidative CH functionalization of primary aliphatic amines has been accomplished with a biomimetic cooperative catalytic system to furnish 1,2-disubstituted benzimidazoles that play an important role as drug discovery targets. This one-pot atom-economical multistep process, which proceeds under mild conditions, with ambient air and equimolar amounts of each coupling partner, constitutes a convenient environmentally friendly strategy to functionalize non-activated aliphatic amines that remain challenging substrates for non-enzymatic catalytic aerobic systems.

Regiospecific synthesis of neuroprotective 1,4-benzoxazine derivatives through a tandem oxidation-Diels-Alder reaction.

The tandem oxidation-inverse electron demand Diels-Alder reaction of o-aminophenol derivatives and enamines has been accomplished at room temperature using a stoichiometric amount of manganese dioxide as the oxidant to furnish highly substituted 1,4-benzoxazine cycloadducts with complete regiochemical control. Because of its efficiency in introducing diverse elements in both cycloaddition partners, this one-pot process should allow the assembly of libraries of biologically relevant 1,4-benzoxazine derivatives. In this respect, the 3,3-diphenyl-substituted-1,4-benzoxazine derivative 3n was found to be a potent neuroprotective agent in an animal model of excitotoxic lesions in newborn mice.

Connexin 30 expression inhibits growth of human malignant gliomas but protects them against radiation therapy.

BACKGROUND: Glioblastomas remain ominous tumors that almost invariably escape treatment. Connexins are a family of transmembrane, gap junction-forming proteins, some members of which were reported to act as tumor suppressors and to modulate cellular metabolism in response to cytotoxic stress. METHODS: We analyzed the copy number and expression of the connexin (Cx)30 gene gap junction beta-6 (GJB6), as well as of its protein immunoreactivity in several public and proprietary repositories of glioblastomas, and their influence on patient survival. We evaluated the effect of the expression of this gap junction protein on the growth, DNA repair and energy metabolism, and treatment resistance of these tumors. RESULTS: The GJB6 gene was deleted in 25.8% of 751 analyzed tumors and mutated in 15.8% of 158 tumors. Cx30 immunoreactivity was absent in 28.9% of 145 tumors. Restoration of Cx30 expression in human glioblastoma cells reduced their growth in vitro and as xenografts in the striatum of immunodeficient mice. Cx30 immunoreactivity was, however, found to adversely affect survival in 2 independent retrospective cohorts of glioblastoma patients. Cx30 was found in clonogenic assays to protect glioblastoma cells against radiation-induced mortality and to decrease radiation-induced DNA damage. This radioprotection correlated with a heat shock protein 90-dependent mitochondrial translocation of Cx30 following radiation and an improved ATP production following this genotoxic stress. CONCLUSION: These results underline the complex relationship between potential tumor suppressors and treatment resistance in glioblastomas and single out GJB6/Cx30 as a potential biomarker and target for therapeutic intervention in these tumors.

Casein kinase 2 inhibition modulates the DNA damage response but fails to radiosensitize malignant glioma cells.

Inhibitors of casein kinase 2 (CK2), a regulator of cell proliferation and mediator of the DNA damage response, are being evaluated in clinical trials for the treatment of cancers. Apigenin was capable of inhibiting the activation of CK2 following γ irradiation in LN18 and U87 malignant glioma cells. Apigenin and siRNA-mediated CK2 protein depletion further inhibited NF-κB activation and altered the Tyr68 phosphorylation of Chk2 kinase, a DNA damage response checkpoint kinase, following irradiation. However, CK2 inhibition did not decrease the ability of these glioma cells to repair double-strand DNA breaks, as assessed by COMET assays and γ-H2Ax staining. Likewise, apigenin and siRNA-induced depletion of CK2 failed to sensitize glioma cells to the cytotoxic effect of 2 to 10 G-rays of γ irradiation, as assessed by clonogenic assays. These results contrast with those found in other cancer types, and urge to prudence regarding the inclusion of malignant glioma patients in clinical trials that assess the radiosensitizing role of CK2 inhibitors in solid cancers.

Post-traumatic thoracic outlet syndrome.

BACKGROUND: To evaluate the clinical presentation, diagnostic and therapeutic management and outcome of 27 cases of post-traumatic thoracic outlet syndrome (PT TOS). METHODS: Retrospective chart analysis. RESULTS: Nineteen women and eight men were included in this study. Involvement in a traffic accident was the most common scenario. Fracture of either the first rib or the clavicle was reported in eight patients at the time of injury; in others, the diagnosis was cervical or shoulder soft tissue trauma. Upon presentation at our clinic at a mean 41 months after injury, four patients had bilateral symptoms and 17 reported decreased function of either the arm or hand. Two patients presented with severe lower trunk deficits including one who had received surgical intervention at both the cervical spine and elbow before diagnosis of TOS was made. Sixteen and 15 patients were suffering from some degree of anxiety and/or depression. Upon diagnosis of neurogenic TOS, the two patients with atrophy of the hand musculature were treated surgically. Conservative treatment was applied to all other patients. Six months after presentation to our clinic, nine patients demonstrated a significant improvement. The remainder that reported incapacitating symptoms were offered surgical treatment. Three patients declined the latter. Fifteen patients received surgical treatment via an anterior supraclavicular approach with resection of the anterior scalene muscles. Eleven patients had resection of the middle scalene muscle while five had resection of an osseous structure (partial claviculectomy, C7 transverse process or a cervical rib). The two patients with atrophy of the hand only slightly improved their motor deficit but had a notable relief of symptoms of pain. Postoperative improvement occurred in 80% of surgically treated patients. CONCLUSIONS: The majority of patients suffering from a post-traumatic TOS present a neurogenic, usually subjective syndrome. Prompt therapeutic management is necessary, addressing both physical and psychological complaints. Most patients are cured or well improved by conservative and/or surgical treatment.

Structural role of counterions adsorbed on self-assembled peptide nanotubes.

Among noncovalent forces, electrostatic ones are the strongest and possess a rather long-range action. For these reasons, charges and counterions play a prominent role in self-assembly processes in water and therefore in many biological systems. However, the complexity of the biological media often hinders a detailed understanding of all the electrostatic-related events. In this context, we have studied the role of charges and counterions in the self-assembly of lanreotide, a cationic octapeptide. This peptide spontaneously forms monodisperse nanotubes (NTs) above a critical concentration when solubilized in pure water. Free from any screening buffer, we assessed the interactions between the different peptide oligomers and counterions in solutions, above and below the critical assembly concentration. Our results provide explanations for the selection of a dimeric building block instead of a monomeric one. Indeed, the apparent charge of the dimers is lower than that of the monomers because of strong chemisorption. This phenomenon has two consequences: (i) the dimer-dimer interaction is less repulsive than the monomer-monomer one and (ii) the lowered charge of the dimeric building block weakens the electrostatic repulsion from the positively charged NT walls. Moreover, additional counterion condensation (physisorption) occurs on the NT wall. We furthermore show that the counterions interacting with the NTs play a structural role as they tune the NTs diameter. We demonstrate by a simple model that counterions adsorption sites located on the inner face of the NT walls are responsible for this size control.

Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of sulfasalazine for the treatment of progressing malignant gliomas in adults.

BACKGROUND: Sulfasalazine, a NF-kappaB and x(c)-cystine/glutamate antiport inhibitor, has demonstrated a strong antitumoral potential in preclinical models of malignant gliomas. As it presents an excellent safety profile, we initiated a phase 1/2 clinical study of this anti-inflammatory drug for the treatment of recurrent WHO grade 3 and 4 astrocytic gliomas in adults. METHODS: 10 patients with advanced recurrent anaplastic astrocytoma (n = 2) or glioblastoma (n = 8) aged 32-62 years were recruited prior to the planned interim analysis of the study. Subjects were randomly assigned to daily doses of 1.5, 3, 4.5, or 6 grams of oral sulfasalazine, and treated until clinical or radiological evidence of disease progression or the development of serious or unbearable side effects. Primary endpoints were the evaluation of toxicities according to the CTCAE v.3.0, and the observation of radiological tumor responses based on MacDonald criteria. RESULTS: No clinical response was observed. One tumor remained stable for 2 months with sulfasalazine treatment, at the lowest daily dose of the drug. The median progression-free survival was 32 days. Side effects were common, as all patients developed grade 1-3 adverse events (mean: 7.2/patient), four patients developed grade 4 toxicity. Two patients died while on treatment or shortly after its discontinuation. CONCLUSION: Although the proper influence of sulfasalazine treatment on patient outcome was difficult to ascertain in these debilitated patients with a large tumor burden (median KPS = 50), ISRCTN45828668 was terminated after its interim analysis. This study urges to exert cautiousness in future trials of Sulfasalazine for the treatment of malignant gliomas. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45828668.

Sulfasalazine unveils a contact-independent HSV-TK/ganciclovir gene therapy bystander effect in malignant gliomas.

The efficacy of HSV-TK/ganciclovir-based gene therapy on malignant gliomas largely relies on the amplitude of the bystander effect. In these experiments, the anti-inflammatory drug Sulfasalazine increased the HSV-TK/ganciclovir bystander effect in C6, 9L and LN18 cells but not in U87 glioma cells. Using bi-compartmental culture devices and conditioned medium transfer experiments, we showed that in C6, 9L and LN18 cells but not in U87 cells, Sulfasalazine also unveiled a new, contact-independent mechanism of HSV-TK/ganciclovir bystander effect. Upon treatment with ganciclovir, human LN18-TK but not U87-TK cells synthetized and released TNF-alpha in the culture medium. Sulfasalazine sensitized glioma cells to the toxic effect of TNF-alpha and enhanced its secretion in LN18-TK cells in response to GCV treatment. The caspase-8 inhibitor Z-IETD-FMK and a blocking antibody to TNF-alpha both inhibited the contact-independent bystander effect in LN18 cells. Taken together, these results suggest that TNF-alpha mediates the contact-independent bystander effect in LN18 cells. The treatment with GCV and/or Sulfasalazine of tumor xenografts consisting of a mix of 98% C6 and 2% C6-TK cells shows that Sulfasalazine is also a potent adjunct to the in vivo treatment of gliomas.

Dexamethasone inhibits the HSV-tk/ ganciclovir bystander effect in malignant glioma cells.

BACKGROUND: HSV-tk/ ganciclovir (GCV) gene therapy has been extensively studied in the setting of brain tumors and largely relies on the bystander effect. Large studies have however failed to demonstrate any significant benefit of this strategy in the treatment of human brain tumors. Since dexamethasone is a frequently used symptomatic treatment for malignant gliomas, its interaction with the bystander effect and the overall efficacy of HSV-TK gene therapy ought to be assessed. METHODS: Stable clones of TK-expressing U87, C6 and LN18 cells were generated and their bystander effect on wild type cells was assessed. The effects of dexamethasone on cell proliferation and sensitivity to ganciclovir were assessed with a thymidine incorporation assay and a MTT test. Gap junction mediated intercellular communication was assessed with microinjections and FACS analysis of calcein transfer. The effect of dexamethasone treatment on the sensitivity of TK-expressing to FAS-dependent apoptosis in the presence or absence of ganciclovir was assessed with an MTT test. Western blot was used to evidence the effect of dexamethasone on the expression of Cx43, CD95, CIAP2 and BclXL. RESULTS: Dexamethasone significantly reduced the bystander effect in TK-expressing C6, LN18 and U87 cells. This inhibition results from a reduction of the gap junction mediated intercellular communication of these cells (GJIC), from an inhibition of their growth and thymidine incorporation and from a modulation of the apoptotic cascade. CONCLUSION: The overall efficacy of HSV-TK gene therapy is adversely affected by dexamethasone co-treatment in vitro. Future HSV-tk/ GCV gene therapy clinical protocols for gliomas should address this interference of corticosteroid treatment.

Situation on gynecological infections of the lower reproductive track among ever married women of reproductive age in Thien Phuoc district, Quang Nam province in 2004

A gynecological study on 548 married women at reproductive ages living in Tien Phuoc district, Quang Nam province showed that: among them 207 women had infections of the lower congenital-urinary tract (37.77%). Pathogenic agents: 99.52% of the cases were a single agent with such as bacteria 70.53%, Candida albicans 25.12%; Trichomonas vaginalis 3.86%. There was one case of infection caused by two different agents, bacteria and Candida albicans. There were 117 cases (56.53%) with clinical lesions including: 30.91% cervicitis with glandular epithelial eversion, 21.26% purely cervicitis, 36.68% of the women had abnormal leukorrhea of which 21.90% was pus-like leukorrhea.