Oral health behaviors and bone mineral density in South Korea: the 2008-2010 Korean National Health and Nutrition Examination Survey.

The purpose of this study was to examine the association between oral health behaviors and bone mineral density (BMD) by using data from the Korean National Health and Nutrition Examination Survey conducted in 2008-2010. We included 6,620 subjects (3,140 men aged more than 50 years and 3,480 postmenopausal women). BMD was measured at three sites-namely, the lumbar spine, total femur, and femur neck. Oral health behaviors were assessed by use of a self-administered questionnaire in the Korean National Health and Nutrition Examination Survey. After adjustment for all covariates, BMD of the lumbar spine and femur neck tended to increase as the frequency of tooth brushing increased in men (p trend = 0.020 and p trend = 0.028, respectively). Women using secondary oral products had increased lumbar spine BMD compared with women who did not use secondary oral products. However, after adjustment for all covariates, no significant relationship was observed between BMD and the use of secondary oral products. As the frequency of tooth brushing and the number of secondary oral products used increased, the prevalence of osteoporosis decreased. The frequency of tooth brushing is associated with increased lumbar spine and femur neck BMD in South Korean men.

Quality of life discordance between terminal cancer patients and family caregivers: a multicenter study.

BACKGROUND: Research studies on quality of life (QOL) discordance between cancer patients and family caregivers are limited, and the results are inconsistent. The objective of this study was to examine QOL discordance between patients and family caregivers in a hospice setting and to identify factors associated with the discordance. METHODS: We enrolled 178 patient-family caregiver pairs from six tertiary hospital hospice palliative care units in South Korea in this cross-sectional study. To establish groupings based on patient and family caregiver QOL levels, we measured the QOL of patient and family caregiver pairs using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care and the Caregiver QOL Index-Cancer, respectively. Pairs were categorized into the following three groups: both good QOL pairs, only poor patient QOL, and only poor family caregiver QOL. Factors associated with only poor patient or only poor family caregiver QOL were compared to both good QOL pairs. A stepwise multivariate regression model was used to identify relevant factors. RESULTS: The QOL of family caregivers did not correlate significantly (P = 0.227) with QOL in terminally ill cancer patients. As well, poor emotional function in patients was the only significant factor associated with the only poor patient QOL group [adjusted odds ratio (aOR), 4.1; 95 % confidence interval (CI), 1.5-11.5]. However, emotionally distressed family caregivers (aOR, 10.2; 95 % CI, 2.8-37.5), family caregivers who professed a religion (aOR, 4.1; 95 % CI, 1.5-11.3), and family caregivers with low social support (aOR, 3.9; 95 % CI, 1.5-10.6) were independent predictors for the only poor family caregiver QOL group. CONCLUSIONS: Assessing the respective emotional status of both the patient and family caregiver is needed in hospice care to reduce the gap in QOL between the two groups. Further, more attention should be paid to the lack of social support for family caregivers.

N-Glycosylation with synthetic undecaprenyl pyrophosphate-linked oligosaccharide to oligopeptides by PglB oligosaccharyltransferase from Campylobacter jejuni.

The oligosaccharyltransferase PglB from Campylobacter jejuni catalyses the N-glycosylation reaction with undecaprenyl-pyrophosphate-linked Glc1 GalNAc5 Bac1 (Und-PP-Glc1 GalNAc5 Bac1 ). Experiments using chemically synthesized donors coupled to fluorescently tagged peptides confirmed that biosynthetic intermediate Und-PP-Bac1 and Und-PP-GalNAc2 Bac1 are transferred efficiently to the Asn residue in the consensus sequence (D/E-X'-N-X-T/S, X',X≠P). The products were analyzed in detail by tandem MS to confirm their chemical structures.

Hyponatremia as an independent prognostic factor in patients with terminal cancer.

PURPOSE: Hyponatremia is a common and associated with poor clinical outcome in cancer patients. But little is known regarding hyponatremia in terminal cancer patients. The purpose of this study is to investigate the prognostic role of the hyponatremia in terminal cancer patients. METHODS: A retrospective observational study was conducted between January 2010 and December 2012 in a tertiary hospital palliative care unit. Medical records were collected from hospitalized patients who were eligible for obtaining serum sodium level. Hyponatremia was defined as serum sodium <136 mEq/L. And we classified patients into three groups; eunatremia (sodium 136-145 mEq/L), mild to moderate hyponatremia (sodium 126-135 mEq/L), and severe hyponatremia (sodium ≤125 mEq/L). Univariate and multivariate Cox regression analyses were performed to determine factors affecting survival time. RESULTS: Of the 576 patients, hyponatremia was present in 367 individuals (63.7 %). In the univariate analysis, serum CRP, PPS, and sodium ≤125 mEq/L were associated with survival time (HR = 1.22; p < 0.001, HR = 0.69; p < 0.001, HR = 1.91; p < 0.001). In the multivariate analysis, serum CRP, PPS, sodium 126-135 mEq/L, and sodium ≤125 mEq/L were associated with survival time (HR = 1.16; p < 0.001, HR = 0.70; p < 0.001, HR = 1.19; p = 0.048, HR = 1.75; p < 0.001). CONCLUSIONS: Hyponatremia is an independent prognostic factor in terminal cancer patients and careful clinical concern is needed. In the future, large prospective study is warranted in terminal cancer patients.

Association between the duration of palliative care service and survival in terminal cancer patients.

PURPOSE: Preliminary studies of early palliative care showed improved quality of life, less medical cost, and better survival time. But, most terminal cancer patients tend to be referred to palliative care late. For the proper care of terminal cancer patients, it is necessary to refer to hospice and palliative care timely. The aim of this study is to analyze the effect of the duration of palliative care services on the survival in terminal cancer patients. METHODS: We reviewed 609 patients who had died from terminal cancer between January 2010 and December 2012. We analyzed correlations of age, first Palliative Performance Scale (PPS) level, duration of palliative care service, and survival time. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. RESULTS: Duration of palliative care services was significantly correlated with survival time. In univariate Cox regression analysis, age, and each group of duration of palliative care service showed significant associations with survival. Final multivariate Cox regression model retained four parameters as independent prognostic factors for survival (age HR = 0.99 (p = 0.002), 1∼10 days HR = 2.64 (p < 0.001), 11∼30 days HR = 2.43 (p < 0.001), 31∼90 days HR = 1.87 (p < 0.001)). CONCLUSIONS: Shorter duration of palliative care services showed poor prognostic factor. Timely referral system from the end of chemotherapy is warranted.

Serum and urine concentrations of morphine and morphine metabolites in patients with advanced cancer receiving continuous intravenous morphine: an observational study.

BACKGROUND: The feasibility and clinical implication of drug monitoring of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) need further investigation. This study aimed to determine what predicts serum concentrations of morphine in cancer patients receiving continuously intravenous morphine, the relationships between serum concentration of morphine/its metabolites and urinary concentrations, and the relation between morphine concentrations and with clinical outcomes. METHODS: We collected serum and urine samples from 24 patients with advanced cancer undergoing continuously intravenous morphine therapy. Serum samples were obtained at day one. Spot urine samples were collected once daily on three consecutive days. Pain and adverse drug events were assessed using the Korean version of MD Anderson Symptom Inventory. RESULTS: A total of 96 samples (72 urine and 24 serum samples) were collected. Median dose of morphine was 82.0 mg/24 h. In a multivariate analysis, total daily morphine dose was the most significant predictors of both serum and urine concentration of morphine. Morphine, M6G, and M3G in serum and urine were statistical significantly correlated (correlation coefficient = 0.81, 0.44, 0.56; p values < 0.01, 0.03, 0.01, respectively). CONCLUSION: Spot urine concentrations of morphine and its metabolites were highly correlated to those of serum. Total dose of daily morphine was related to both serum and urine concentration of morphine and its metabolites.

Agrammatic primary progressive aphasia in two dextral patients with right hemispheric involvement.

Agrammatic primary progressive aphasia (PPA-G) has been known to be associated with focal brain atrophy involving the left posterior frontal and anterior insular regions. However, aphasia can also rarely result from right hemispheric lesions in right-handed patients, so-called crossed aphasia in dextrals (CAD). We report two right-handed patients with PPA-G whose 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) showed hypometabolism predominantly in the right hemisphere, implicating "crossed PPA-G."

EORTC QLQ-C15-PAL quality of life score as a prognostic indicator of survival in patients with far advanced cancer.

PURPOSE: Quality of life (QoL) and performance status predict survival in advanced cancer patients; these relationships have not been explored in the hospice palliative care setting. The aim of this study was to examine the survival predictability of patient-reported QoL using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL questionnaire in far advanced cancer inpatients at the very end of life. METHODS: This is a retrospective cohort study. Patients reported QoL using the EORTC QLQ-C15-PAL. One hundred sixty-two inpatients in hospice palliative wards of six hospitals in South Korea were followed until death or the end of the study. Additional symptoms and performance status were assessed by the MD Anderson Symptom Inventory-Korean (MDASI-K), Palliative Performance Scale (PPS) and Eastern Cooperative Oncology Group (ECOG) performance status. Correlations between EORTC QLQ-C15-PAL, MDASI-K, PPS, and ECOG were assessed. Survival analyses were performed using Cox proportional hazard models. RESULTS: Patients' median survival was less than 1 month. Physician-reported PPS significantly predicted survival (hazard ratio [HR] 0.493; p<0.001). From the EORTC QLQ-C15-PAL, patient-reported physical functioning predicted survival (HR=0.65; p<0.001). Other six domains of EORTC QLQ-C15-PAL were significantly related to survival after adjustment. Those domains were global health status, emotional functioning, fatigue, nausea/vomiting, appetite loss, and constipation. CONCLUSIONS: EORTC QLQ-C15-PAL can be an independent prognostic factor in inpatients with far advanced cancer. Patient-reported physical functioning showed survival predictability as good as physician-reported performance status. It is notable that the QLQ instrument is useful even for patients in their final month of life. Cancer anorexia-cachexia syndrome-related symptoms may be independent prognostic symptoms. Prospective study is warranted.

Involvement of GDH3-encoded NADP+-dependent glutamate dehydrogenase in yeast cell resistance to stress-induced apoptosis in stationary phase cells.

Glutamate metabolism is linked to a number of fundamental metabolic pathways such as amino acid metabolism, the TCA cycle, and glutathione (GSH) synthesis. In the yeast Saccharomyces cerevisiae, glutamate is synthesized from α-ketoglutarate by two NADP(+)-dependent glutamate dehydrogenases (NADP-GDH) encoded by GDH1 and GDH3. Here, we report the relationship between the function of the NADP-GDH and stress-induced apoptosis. Gdh3-null cells showed accelerated chronological aging and hypersusceptibility to thermal and oxidative stress during stationary phase. Upon exposure to oxidative stress, Gdh3-null strains displayed a rapid loss in viability associated with typical apoptotic hallmarks, i.e. reactive oxygen species accumulation, nuclear fragmentation, DNA breakage, and phosphatidylserine translocation. In addition, Gdh3-null cells, but not Gdh1-null cells, had a higher tendency toward GSH depletion and subsequent reactive oxygen species accumulation than did WT cells. GSH depletion was rescued by exogenous GSH or glutamate. The hypersusceptibility of stationary phase Gdh3-null cells to stress-induced apoptosis was suppressed by deletion of GDH2. Promoter swapping and site-directed mutagenesis of GDH1 and GDH3 indicated that the necessity of GDH3 for the resistance to stress-induced apoptosis and chronological aging is due to the stationary phase-specific expression of GDH3 and concurrent degradation of Gdh1 in which the Lys-426 residue plays an essential role.

Alpha-synuclein functions in the nucleus to protect against hydroxyurea-induced replication stress in yeast.

Hydroxyurea (HU) inhibits ribonucleotide reductase (RNR), which catalyzes the rate-limiting synthesis of deoxyribonucleotides for DNA replication. HU is used to treat HIV, sickle-cell anemia and some cancers. We found that, compared with vector control cells, low levels of alpha-synuclein (α-syn) protect S. cerevisiae cells from the growth inhibition and reactive oxygen species (ROS) accumulation induced by HU. Analysis of this effect using different α-syn mutants revealed that the α-syn protein functions in the nucleus and not the cytoplasm to modulate S-phase checkpoint responses: α-syn up-regulates histone acetylation and RNR levels, maintains helicase minichromosome maintenance protein complexes (Mcm2-7) on chromatin and inhibits HU-induced ROS accumulation. Strikingly, when residues 2-10 or 96-140 are deleted, this protective function of α-syn in the nucleus is abolished. Understanding the mechanism by which α-syn protects against HU could expand our knowledge of the normal function of this neuronal protein.

Interleukin-6 but not tumour necrosis factor-alpha predicts survival in patients with advanced cancer.

PURPOSE: The purpose of this study was to evaluate the prognostic role of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in the survival of patients with advanced cancer. METHODS: In this prospective cohort study between three hospice and palliative care centres in South Korea, we followed 98 advanced cancer patients until death or the end of the study. Approximately 60 % of the patients had poor functional status (Eastern Cooperative Oncology Group score ≥3). We investigated the symptoms of cancer cachexia anorexia syndrome, possible cytokine-related confounders such as infection and medication records. Influence from clinical variables was adjusted using the Cox proportional hazard model. RESULTS: The median survival time was 27 days. On multivariate analysis, elevated IL-6 (hazard ratio, 2.139; p = 0.003) was found to be an independent significant prognostic factor. TNF-α was not a significant factor. Poor performance status and male gender were also independently related to shortened survival. CONCLUSIONS: IL-6 level can be a useful indicator of survival time of patients with advanced cancer at the very end of life. In contrast, the prognostic role of TNF-α requires further study.

Less healthy dietary pattern is associated with smoking in Korean men according to nationally representative data.

The relationship between smoking and nutrient intake has been widely investigated in several countries. However, Korea presents a population with a smoking rate of approximately 50% and dietary consumption of unique foods. Thus, the aim of this study was to evaluate the association of dietary patterns with smoking in Korean men using a nationally representative sample. The study subjects were comprised of 4,851 Korean men over 19 yr of age who participated in the fourth Korean National Health and Nutrition Examination Survey. Dietary data were assessed by the 24-hr recall method. The smoking group comprised 2,136 men (46.6%). Five dietary patterns were derived using factor analysis: 'sugar & fat', 'vegetables & seafood', 'meat & drinks', 'grains & eggs', and 'potatoes, fruits and dairy products.' Current smokers showed a more significant 'sugar & fat' pattern (P = 0.001) while significantly less of the 'vegetables & seafood' and 'potatoes, fruits and dairy products' patterns (P = 0.011, P < 0.001, respectively). As found in similar results from Western studies, Korean male smokers showed less healthy dietary patterns than nonsmokers. Thus, the result of this study underlines the need for health professionals to also provide advice on dietary patterns when counseling patients on smoking cessation.

Phosphate and succinate use different mechanisms to inhibit sugar-induced cell death in yeast: insight into the Crabtree effect.

Stationary-phase Saccharomyces cerevisiae cells transferred from spent rich media into water live for weeks, whereas the same cells die within hours if transferred into water with 2% glucose in a process called sugar-induced cell death (SICD). Our hypothesis is that SICD is due to a dysregulated Crabtree effect, which is the phenomenon whereby glucose transiently inhibits respiration and ATP synthesis. We found that stationary-phase cells in glucose/water consume 21 times more O(2) per cell than exponential-phase cells in rich media, and such excessive O(2) consumption causes reactive oxygen species to accumulate. We also found that inorganic phosphate and succinate protect against SICD but by different mechanisms. Phosphate protects by triggering the synthesis of Fru-1,6-P(2), which inhibits respiration in isolated mitochondria. Succinate protects in wild-type cells but fails to protect in dic1Δ cells. DIC1 codes for a mitochondrial inner membrane protein that exchanges cytosolic succinate for matrix phosphate. We propose that succinate depletes matrix phosphate, which in turn inhibits respiration and ATP synthesis. In sum, restoring the Crabtree effect, whether with phosphate or succinate, protects cells from SICD.

Triclabendazole protects yeast and mammalian cells from oxidative stress: identification of a potential neuroprotective compound.

The Prestwick and NIH chemical libraries were screened for drugs that protect baker's yeast from sugar-induced cell death (SICD). SICD is triggered when stationary-phase yeast cells are transferred from spent rich medium into water with 2% glucose and no other nutrients. The rapid, apoptotic cell death occurs because reactive oxygen species (ROS) accumulate. We found that triclabendazole, which is used to treat liver flukes in cattle and man, partially protects against SICD. Characterization of triclabendazole revealed that it also protects yeast cells from death induced by the Parkinson's disease-related protein alpha-synuclein (α-syn), which is known to induce the accumulation of ROS.

TCA cycle-independent acetate metabolism via the glyoxylate cycle in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, the accepted theory is that due to TCA cycle dysfunction, the Δcit1 mutant lacking the mitochondrial enzyme citrate synthase (Cit1) cannot grow on acetate, regardless of the presence of the peroxisomal isoenzyme (Cit2). In this study, we re-evaluated the roles of Cit1 and Cit2 in acetate utilization and examined the pathway of acetate metabolism by analysing mutants defective in TCA or glyoxylate cycle enzymes. Although Δcit1 cells showed significantly reduced growth on rich acetate medium (YPA), they exhibited growth similar to Δcit2 and the wild-type cells on minimal acetate medium (YNBA). Impaired acetate utilization by Δcit1Δcit2 cells on YNBA was restored by ectopic expression of either Cit2 or its cytoplasmically localized variants. Deletion of any of the genes for the enzymes solely involved in the TCA cycle (IDH1, KGD1 and LSC1), except for SDH1, caused little defect in acetate utilization on YNBA but resulted in significant growth impairment on YPA. In contrast, cells lacking any of the genes involved in the glyoxylate cycle (ACO1, FUM1, MLS1, ICL1 and MDH2) did not grow on either YNBA or YPA. Deletion of SFC1 encoding the succinate-fumarate carrier also caused similar growth defects on YNBA. Our results suggest that in S. cerevisiae the glyoxylate cycle functions as a competent metabolic pathway for acetate utilization on YNBA, while both the TCA and glyoxylate cycles are essential for growth on YPA.

Recent advances in stereoselective glycosylation through intramolecular aglycon delivery.

Methodology toward the stereoselective 1,2-cis glycoside linkage using intramolecular aglycon delivery (IAD) has been extensively developed. In the last two decades, progress has been made using various mixed acetal linkages and a number of glycosyl donor moieties to develop novel IAD strategies, mainly based on formation of acetal linkages. This account summarizes the newest naphthylmethyl (NAP) ether-mediated IAD as well as all the types of mediations for stereospecific construction of various 1,2-cis linkages, not only for beta-mannopyranoside, but also for other linkages almost without exception, including beta-L-rhamnoside.

Yeast cells lacking the CIT1-encoded mitochondrial citrate synthase are hypersusceptible to heat- or aging-induced apoptosis.

In Saccharomyces cerevisiae, the initial reaction of the tricarboxylic acid cycle is catalyzed by the mitochondrial citrate synthase Cit1. The function of Cit1 has previously been studied mainly in terms of acetate utilization and metabolon construction. Here, we report the relationship between the function of Cit1 and apoptosis. Yeast cells with cit1 deletion showed a temperature-sensitive growth phenotype, and they displayed a rapid loss in viability associated with typical apoptotic hallmarks, i.e., reactive oxygen species (ROS) accumulation and nuclear fragmentation, DNA breakage, and phosphatidylserine translocation, when exposed to heat stress. On long-term cultivation, cit1 null strains showed increased potentials for both aging-induced apoptosis and adaptive regrowth. Activation of the metacaspase Yca1 was detected during heat- or aging-induced apoptosis in cit1 null strains, and accordingly, deletion of YCA1 suppressed the apoptotic phenotype caused by cit1 null mutation. Cells with cit1 deletion showed higher tendency toward glutathione (GSH) depletion and subsequent ROS accumulation than the wild type, which was rescued by exogenous GSH, glutamate, or glutathione disulfide (GSSG). These results led us to conclude that GSH deficiency in cit1 null cells is caused by an insufficient supply of glutamate necessary for biosynthesis of GSH rather than the depletion of reducing power required for reduction of GSSG to GSH.

Stereoselective synthesis of beta-L-rhamnopyranosides.

Stereoselective construction of 1,2-cis-beta-L-rhamnopyranoside was achieved by our effective methodology using naphthylmethyl (NAP) ether-mediated intramolecular aglycon delivery (IAD). The complete stereoselective synthesis of the bacterial extracellular polysaccharide, alpha-L-Rhap-(1-->3)-beta-L-Rhap-(1-->4)Glcp from Sphaerotilus natans, was successfully accomplished, clearly demonstrating that the NAP-IAD methodology is highly versatile.

Synthesis of a tetrasaccharide phosphate from the linkage region of the arabinogalactan-peptidoglycan complex in the mycobacterial cell wall.

The synthesis of dibenzyl 6-O-naphthylmethyl-2,3,5-tri-O-benzoyl-beta-D-galactofuranosyl-(1-->5)-2,3-di-O-benzoyl-6-O-benzyl-beta-D-galactofuranosyl-(1-->4)-3-O-benzyl-2-O-pivaloyl-alpha-l-rhamnopyranosyl-(1-->3)-2-acetamido-2-deoxy-4,6-di-O-benzoyl-alpha-D-glucopyranosyl phosphate (1), a protected form of the tetrasaccharide phosphate of the linkage region of the arabinogalactan-peptidoglycan complex in the mycobacterial cell wall, has been accomplished. Key steps include the coupling of four monosaccharide building blocks with complete stereoselectivity by glycosylations employing thioglycosides, 2'-carboxybenzyl glycosides, and glycosyl fluorides as glycosyl donors. The alpha-glycosyl phosphate linkage was also stereoselectively elaborated by reaction of a tetrasaccharide hemiacetal with tetrabenzyl pyrophosphate in the presence of a base.