Health Disparity Still Exists in an Economically Well-Developed Society in Asia

Background

The socioeconomic inequalities in child health continue to widen despite improved economy.

Objective

To investigate the correlation between socio-economic factors and health risk behaviors and psychosocial well-being of children in Hong Kong.

Hypothesis

The null hypothesis is that for this particular developed region, there exists little or no correlation between social-economic factors and health risk behaviors and psychosocial well-being of children.

Design

Cross sectional territory wide survey.

Participants

Caregivers of 7,000 children in kindergartens in Hong Kong.

Measuring tools

Youth Risk Behavior Surveillance questionnaire, health-related knowledge and hygienic practice questionnaire, and Children Behavior Checklist (CBCL).

Results

Children were less likely to have somatic complaints and anxiety/depression as reflected by CBCL scores coming from families of higher income, not being recipients of social assistance, with fathers in employment, and with higher parental education. Children with only mother or father as caretakers had lower odds ratios (ORs) 0.71 (95% CI 0.58-0.89) and 0.53 (95% CI 0.33-0.84) respectively to have the habit of eating breakfast, whilst parental education at post-secondary level and higher family income had higher ORs 1.91 (95% CI 1.31-2.78), and 1.63 (95% CI 1.11-2.39). Fathers unemployed, relatives as main caretakers and living in districts with low median household inome incurred higher ORs, as 1.46 (95% CI 1.10-1.94),1.52 (95% CI 1.27-1.83) and 1.17 (95% CI 1.02-1.34) respectively, of watching television over two hours daily, whilst children with parental education at secondary level or above incurred lower OR 0.33 (95% CI 0.24-0.45). Children with parental education at post-secondary level and higher family income had lower ORs of 0.32 (95% CI 0.48-0.97) and 0.52 (95% CI 0.34-0.79) respectively, with regard to exposing to passive smoking, and reversed for those living in districts with lower median household income, lower family income and recipient of CSSA with ORs 1.24 (95% CI 1.06-1.44) and 1.6 (95% CI 1.09-2.37) respectively.

Conclusion

Null hypothesis was not supported. A strong gradient was still found to exist among different socio-economic groups for various health-related behaviors in developed society like Hong Kong.     

CD40 ligand induces RIP1-dependent,necroptosis-like cell death in low-grade serous but not serous borderline ovarian tumor cells

Ovarian high-grade serous carcinomas (HGSCs) and invasive low-grade serous carcinomas (LGSCs) are considered to be distinct entities. In particular, LGSCs are thought to arise from non-invasive serous borderline ovarian tumors (SBOTs) and show poor responsiveness to conventional chemotherapy. The pro-apoptotic effects of CD40 ligand (CD40L) have been demonstrated in HGSC, though the underlying mechanisms are not fully understood. Conversely, the therapeutic potential of the CD40L-CD40 system has yet to be evaluated in LGSC. We now show that CD40 protein is focally expressed on tumor cells in two of five primary LGSCs compared with no expression in eight primary SBOTs. Treatment with CD40L or agonistic CD40 antibody decreased the viability of LGSC-derived MPSC1 and VOA1312 cells, but not SBOT3.1 cells. Small interfering RNA (siRNA) targeting CD40 was used to show that it is required for these reductions in cell viability. CD40L treatment increased cleaved caspase-3 levels in MPSC1 cells though, surprisingly, neither pan-caspase inhibitor nor caspase-3 siRNA reversed or even attenuated CD40L-induced cell death. In addition, CD40-induced cell death was not affected by knockdown of the mitochondrial proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG). Interestingly, CD40L-induced cell death was blocked by necrostatin-1, an inhibitor of receptor-interacting protein 1 (RIP1), and attenuated by inhibitors of RIP3 (GSK''872) or MLKL (mixed lineage kinase domain-like; necrosulfonamide). Our results indicate that the upregulation of CD40 may be relatively common in LGSC and that CD40 activation induces RIP1-dependent, necroptosis-like cell death in LGSC cells.Epithelial ovarian cancer accounts for approximately 90% of all ovarian malignancies and is the leading cause of gynecological cancer death in developed countries.^{1, 2} Recently, differences in molecular alterations and clinicopathological features have established a dualistic model dividing ovarian serous carcinomas into high-grade serous carcinoma (HGSC) and low-grade serous carcinoma (LGSC) subtypes. HGSCs are more common and are thought to develop directly from the ovarian surface epithelium or from serous tubal intra-epithelial carcinomas in the fallopian tube. In contrast, LGSCs are rare and are generally considered to develop from benign serous cystadenomas through serous borderline ovarian tumors (SBOT). SBOTs are slow-growing, non-invasive epithelial neoplasms that have a better prognosis compared with other types of ovarian cancer.^{3, 4, 5} Our previous studies have shown that the inhibition of p53 or treatment of epidermal growth factor or transforming growth factor-β1 increases SBOT cell invasion by inducing epithelial–mesenchymal transition, which suggests a possible mechanism that mediates the progression from SBOT to LGSC.^{6, 7, 8, 9} However, many of SBOTs recur as LGSCs that display poor responsiveness to conventional chemotherapy and for which survival rates are <50%.^{1, 3, 10} Thus, the development of novel, targeted therapeutic strategies is likely required to significantly improve patient survival.CD40, a transmembrane glycoprotein belonging to the tumor necrosis factor receptor superfamily, is expressed by a wide range of cell types including immune, endothelial and epithelial cells. Engagement of CD40 with its ligand, CD40L, has been shown to have important roles in a variety of physiological and pathological processes, especially in immunity.^{11, 12} In addition, CD40 expression has been demonstrated in several types of cancer, including colon, lung, cervical, bladder and prostate cancer.¹³ However, reported functions of CD40 in tumor cells vary, with both pro-apoptotic and anti-proliferative effects observed depending on the cellular context.^{14, 15, 16} Alternatively, some studies have shown that CD40 activation may promote the neoplastic transformation and growth of normal cells.^{17, 18, 19} Expression of CD40 has been demonstrated in ovarian cancer cell lines and tumor samples, but not in normal ovarian tissue, suggesting that CD40 may have an important role in ovarian tumors.^{20, 21, 22, 23, 24} Indeed, CD40L-CD40 signaling has been shown to induce growth-inhibitory effects in HGSC cells,^{20, 21, 23, 24, 25} however, the therapeutic potential of CD40 in LGSC and SBOT has not been evaluated.In the present study, we report for the first time elevated CD40 expression in a significant proportion of LGSCs compared with SBOTs. Moreover, CD40 expression is elevated in LGSC-derived MPSC1 and VOA1312 cells compared with SBOT3.1 cells, and CD40 activation induces cell death via CD40 only in LGSC-derived cells. Neither pan-caspase inhibitor nor caspase-3 small interfering RNA (siRNA) has any effect on CD40L-induced MPSC1 cell death. Moreover, CD40L-induced cell death was unaffected by individual or combined knockdown of the mitochondrial proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG). Interestingly, our results suggest that receptor-interacting protein 1 (RIP1), RIP3 and MLKL are involved in CD40-induced MPSC1 cell death. These results demonstrate that CD40 induces RIP1-dependent, necroptosis-like cell death in LGSC cells.     

Tumor necrosis factor-alpha stimulates gastric epithelial cell proliferation

TNF-alpha is a cytokine produced during gastric mucosal injury. We examined whether TNF-alpha could promote mucosal repair by stimulation of epithelial cell proliferation and explored further the underlying mechanisms in a rat gastric mucosal epithelial cell line (RGM-1). TNF-alpha treatment (1-10 ng/ml) for 12 or 24 h significantly increased cell proliferation but did not induce apoptosis in RGM-1 cells. TNF-alpha treatment significantly increased cytosolic phospholipase A(2) and cyclooxygenase-2 (COX-2) protein expression and PGE(2) level but did not affect the protein levels of EGF, basic fibroblast growth factor, and COX-1 in RGM-1 cells. The mRNA of TNF receptor (TNF-R) 2 but not of TNF-R1 was also increased. Dexamethasone dose dependently inhibited the stimulatory effect of TNF-alpha on cell proliferation, which was associated with a significant decrease in cellular COX-2 expression and PGE(2) level. A selective COX-2 inhibitor 3-(3-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-5,5-dimethyl-(5)H-furan-2-one (DFU) by itself had no effect on basal cell proliferation but significantly reduced the stimulatory effect of TNF-alpha on RMG-1 cells. Combination of dexamethasone and DFU did not produce an additive effect. PGE(2) significantly reversed the depressive action of dexamethasone on cell proliferation. These results suggest that TNF-alpha plays a regulatory role in epithelial cell repair in the gastric mucosa via the TNF-alpha receptor and activation of the arachidonic acid/PG pathway.     

Increased survival of mesothelial cells from the peritoneum in peritoneal dialysis fluid

Peritonitis remains the most important factor in patient morbidity and technical failure associated with continuous ambulatory peritoneal dialysis (CAPD). In vitro examination of bacterial infection of cultured human peritoneal mesothelial cells (HPMC) is an attractive approach to the study of peritonitis in CAPD, yet there are few reports on this subject. Previous studies have shown two limitations: (i) cell cultures of HPMC lasted for days only when incubated in culture medium and (ii) short-term studies of <30 min were done in HPMC when incubated with peritoneal dialysis fluid (PDF). Human peritoneal mesothelial cells, maintained in a conventional single chamber culture system with PDF alone, were unable to survive more than 40 min. The present study was designed to prolong the viability of HPMC cultured in PDF, with the object of using cells under different conditions, such as that of simulating CAPD. HPMC were cultured using plastic microtiter plates, where they were grown to confluence and growth was arrested. PDF containing different concentrations of NaHCO3and human serum albumin was added. Cell viability after exposure for up to 24 h was measured by trypan blue, Cell Death Detection ELISA and Annex-V flow cytometry. The data confirmed the 'toxic' effect of PDF, with cell viability being <40% after 2 h incubation in 4.25% glucose in PDF. However, the survival time of HPMC increased significantly in 4.25% glucose PDF at a physiological pH and even further after the addition of human albumin. These experimental conditions simulating CAPD may allow future in vitro studies of mesothelial physiology and peritonitis related to CAPD treatment.     

Whole-genome sequences of four Mycobacterium bovis BCG vaccine strains

Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only vaccine available against tuberculosis (TB). A number of BCG strains are in use, and they exhibit biochemical and genetic differences. We report the genome sequences of four BCG strains representing different lineages, which will help to design more effective TB vaccines.     

SARS coronavirus 8b reduces viral replication by down-regulating E via an ubiquitin-independent proteasome pathway

The severe acute respiratory syndrome coronavirus (SARS-CoV) 8b protein, which is not expressed by other known coronaviruses, can down-regulate the envelope (E) protein via a proteasome-dependent pathway. Here, we showed that the down-regulation of E is not dependent on the lysine residues on 8b and the reduction of polyubiquitination of E mutants is not correlated with their down-regulation by 8b, suggesting an ubiquitin-independent proteasome pathway is involved. A time-course study revealed that 8b was expressed at late-stages of SARS-CoV infection. By using Vero E6 cells stably expressing green fluorescence protein-tagged 8b, ectopic expression of 8b was shown to significantly reduce the production of progeny virus and down-regulate E expression. Taken together, these results suggest that 8b negatively modulates virus replication by down-regulating E via an ubiquitin-independent proteasome pathway.     

Mouse model of male germ cell apoptosis in response to a lack of hormonal stimulation

As a prerequisite for studies using mutant mice, we established a mouse model for induction of male germ cell apoptosis after deprivation of gonadotropins and intratesticular testosterone (T). We employed a potent long acting gonadotropin-releasing hormone antagonist (GnRH-A), acyline, alone or in combination with an antiandrogen, flutamide for effective induction of germ cell apoptosis in mice. Combined treatment with continuous release of acyline (3 mg/kg BW/day) with flutamide (in the form of sc pellets of 25 mg) resulted in almost the same level of suppression of spermatogenesis, as judged by testis weight and by germ cell apoptotic index, in 2 weeks as that reported for rats after treatment with 1.25 mg/kg BW Nal-Glu GnRH-A for the same time period. Within the study paradigm, the maximum suppression of spermatogenesis occurred after a single sc injection of high (20 mg/kg BW) dose of acyline with flutamide. The combined treatment resulted in complete absence of elongated spermatids. Germ cell counts at stages VII-VIII showed a significant (P < 0.05) reduction in the number of preleptotene (27.1%) and pachytene spermatocytes (81.9%), and round spermatids (96.6%) in acyline + flutamide group in comparison with controls. In fact, treatment with a single high (20 mg/kg BW) dose of acyline combined with flutamide in mice achieved same or greater level of suppression, measured by germ cell counts at stages VII-VIII, in two weeks when compared with those reported after daily treatment with Nal-Glu GnRH-A for 4 weeks in rats. Both plasma and testicular T levels were markedly suppressed after administration of acyline alone either by miniosmotic pump or by a single sc injection. Addition of flutamide to acyline had no discernible effect on plasma or intratesticular T levels when compared with acyline alone. These results demonstrate that optimum suppression of spermatogenesis through increased germ cell death is only possible in mice if total abolition of androgen action is achieved and further emphasize the usefulness of acyline + flutamide treated mice as a suitable model system to study hormonal regulation of testicular germ cell apoptosis.     

Cdc42 antagonizes inductive action of cAMP on cell shape,via effects of the myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) on myosin light chain phosphorylation

Rho GTPases play pivotal roles in regulating cell morphology. We previously showed that RhoA acts via ROKalpha to counteract the effects of the classical second messenger cyclic AMP on cell shape changes. Here we show that active Cdc42V12 also competes against the cAMP-induced stellate morphology in SH-EP cells. This Cdc42 effect is not mediated by the RhoA/ ROK pathway but rather the related MRCKalpha, a myotonic dystrophy kinase-related Cdc42-binding kinase. Co-expression of a dominant inhibitory MRCKalpha mutant with Cdc42V12 blocks the ability of the GTPase to counteract cAMP, suggesting that MRCK acts downstream of Cdc42 in this process. Cdc42V12 enhances the phosphorylation of myosin light chain (MLC) at the cell periphery and sustains focal adhesion complexes, while MLC kinase inhibitors destroy focal adhesion complexes and impair the Cdc42V12 protective effect. The data suggest that the maintenance of focal adhesion complexes via the regulation of myosin II activity underlies the ability of Cdc42 to protect against the effect of elevated cAMP.     

Influence of Phosphate on the Growth and Nodulation Characteristics of Rhizobium trifolii

The growth and nodulating characteristics of Rhizobium trifolii 6 and 36 differed under different external phosphate conditions. Under growth conditions designed to deplete the internal phosphate content of the rhizobia, strain 6 maintained a generation time of 5 h during the exponential phase over two cycles of growth in phosphate-depleted medium. In contrast, the generation time of strain 36 was extended from 3.5 to 9.8 h over two cycles of phosphate-depleted growth, although the organism eventually achieved the same cell density and cellular phosphate content as that of strain 6 at stationary phase. Phosphate-depleted strain 6 required 0.51 ± 0.08 μM phosphate to commence proliferation, whereas phosphate-depleted strain 36 required 0.89 ± 0.04 μM phosphate under the same conditions. Phosphate-depleted strain 6 maintained viability when exposed to external phosphate concentrations subcritical for growth to occur, whereas phosphate-depleted strain 36 lost viability within 48 h when exposed to medium containing phosphate at concentrations subcritical for growth. Phosphate-depleted strain 36 was inferior to phosphate-depleted strain 6 at nodulating subterranean clover (Trifolium subterraneum L. cv. Mt. Barker) by taking 2 to 4 days longer to develop nodules in phosphatedepleted plant grown medium at pH 5.5. Nodulation by phosphate-depleted strain 36 was accelerated either by including phosphate in the plant growth medium at pH 5.5 or by raising the solution pH of phosphate-depleted plant growth medium to pH 6.5. External phosphate and pH effects were not observed on the nodulating capabilities of phosphate-depleted strain 6 or on luxury phosphate-grown cells of either strain. Phosphatedepleted strains 6 and 36 proliferated to a similar extent on the rhizoplanes even under stringently low external P_i concentrations. The phosphatase activities of both phosphate-depleted strains were significantly (P = 0.05) higher at pH 6.5 than at pH 5.5, and the activity of strain 6 was significantly higher (P = 0.05) than that of strain 36 at pH 5.5 and 5.0.