Serotonin receptor 1A promoter polymorphism, rs6295, modulates human anxiety levels via altering parasympathetic nervous activity.

OBJECTIVE: The G-allele of the -1019C/G (rs6295) promoter polymorphism of the serotonin receptor 1A (HTR1A) gene has been implicated in anxiety; however, the underlying neurophysiological processes are still not fully understood. Recent evidence indicates that low parasympathetic (vagal) tone is predictive of anxiety. We thus conducted a structural equation model (SEM) to examine whether the HTR1A rs6295 variant can affect anxiety by altering parasympathetic nervous activity. METHOD: A sample of 1141 drug-free healthy Han Chinese was recruited for HTR1A genotyping. Autonomic nervous function was assessed by short-term spectral analysis of heart rate variability (HRV). Anxiety and stress levels were evaluated by the Beck Anxiety Inventory (BAI) and the Perceived Stress Scale (PSS) respectively. RESULTS: The number of the HTR1A G allele was inversely correlated with high-frequency power (HF), a parasympathetic index of HRV. The HF index was negatively associated with BAI scores. Furthermore, the good-fitting SEM, adjusting for confounding variables (e.g., age and PSS levels), revealed a significant pathway linking rs6295 variant to BAI scores via HF index modulation. CONCLUSION: These results are the first to show that HTR1A -1019C/G polymorphism influences anxiety levels by modulating parasympathetic tone, providing a neurophysiological insight into the role of HTR1A in human anxiety.

Continuing weight-loss effect after topiramate discontinuation in obese persons with schizophrenia: a pilot open-label study.

INTRODUCTION: Few studies have investigated the likelihood of weight maintenance in obese persons with schizophrenia after their initial successful weight loss. This pilot open-label study examined the efficacy of topiramate in weight loss and the trajectory of weight changes after topiramate discontinuation. METHODS: This study enrolled 10 obese persons with schizophrenia. A 4-month treatment phase was started, followed by a 12-month discontinuation phase. Body weight was measured as the primary outcome every month. Secondary outcomes included leptin levels, fasting glucose, lipid profiles, and insulin resistance index. RESULTS: After the 4-month addition of topiramate, participants lost 1.79 kg of their body weight (95% CI=-3.03 to -0.56, p=0.005). The maximum weight reduction was 4.32 kg, occurring when topiramate had been discontinued for 12 months (95% CI=-6.41 to -2.24, p<0.001). DISCUSSION: The continuing weight-loss effect after topiramate discontinuation might have resulted from topiramate's potential to improve leptin functioning. These findings demonstrate that topiramate's weight-loss effect could not only persist during its administration, but also continue to improve after its discontinuation.

Chewing ability, nutritional status and quality of life.

In the literature, most researchers evaluate individuals' nutritional status and chewing ability by types of foods chosen or blood test. However, most of previous researches enrolled small sample size and the results might be influenced by personal preference of foods as well as the individuals' response to invasive examination. In this study, researchers assessed individuals' nutritional status and chewing ability with non-invasive test and excluded the personal preference of foods. This study had two aims: first, to explore associations between chewing ability, edentulous or dentulous, self-perceived oral health and individuals' nutritional status and quality of life; second, to assess whether the association proposed by Locker's model is valid. This study used the database of Phase I 'Publicly-funded Denture Installation Plan for the Elderly' of Kaohsiung City Government. Nine hundred and fifty-four subjects aged 65 years and older completed the questionnaires for data analysis. The research results supported and verified the theoretical model proposed by Locker. Individual's chewing ability associated significantly with his/her nutritional status and quality of life. The results demonstrated that better chewing ability of the elderly leads to better nutritional status and quality of life. The appropriateness of the indicators and measurements of individual's chewing ability and nutritional status used in this study has been evaluated and presented. These indicators and measurements are suggested to be generally used for clinical or research application on future-related issues. Consequently, the maintenance or improvement in the chewing ability of the elderly is extremely beneficial to healthy ageing.

Role of gender disparity of circulating high-sensitivity C-reactive protein concentrations and obesity on asthma in Taiwan.

BACKGROUND: Several studies have suggested that the association between obesity and asthma may be stronger in females than in males, but the reason is still unclear. OBJECTIVE: The aim of this study was to investigate whether differences in high-sensitivity C-reactive protein (hs-CRP) levels explain why obesity is associated with asthma in females but not in males. METHODS: This study prospectively enrolled 754 subjects ≥ 18 years old from hospital-based asthma patients and population-based controls. We measured adiposity factors [body mass index (BMI), waist circumference and waist-hip ratio], hs-CRP and total IgE levels. RESULTS: After adjusting for potential confounding factors, we found a significant association between BMI and asthma in females with a significant interaction of gender and BMI on asthma (χ(2) =10.2, P=0.004). If hs-CRP was added to the logistic model, the interaction was attenuated but still significant (χ(2) =7.02, P=0.03). After adjusting for BMI, we did not find that circulating hs-CRP concentrations were significantly associated with asthma in males and females. CONCLUSION: We found that BMI was associated with asthma in females, but our results do not support the suggestion that hs-CRP levels contribute significantly to the link between obesity and asthma with respect to gender disparity.

The Association between health-related quality of life and prosthetic status and prosthetic needs in Taiwanese adults.

The objective of this study was to describe aspects of prosthetic statuses and needs and to evaluate their relationship with health-related quality of life in Taiwan. The study participants, aged 18 years and above, were recruited from a community survey, and each of the total 2469 participants received a dental examination and completed a questionnaire. Multivariable analysis was used to assess the adjusted means of health-related quality of life (SF-36) in both prosthetic status and need. The results showed that 12.6% of those aged 65 years and above were edentulous. The proportion of prosthetic need increased as age increased (39.7% to 61.3%). Multivariate analysis revealed that participants with 'removable prosthesis' had higher physical health scores than those with 'non-removable prosthesis'. The scores of mental health measurement decreased in people with need for full prostheses in relation to people without need for any prosthesis. Therefore, fulfilling prosthetic needs is not only about recovering oral masticatory function, but also concerns improvement of both physical and mental health-related quality of life.

Ethnic differences in the occurrence of oropharyngeal cancer in Taiwan.

OBJECTIVE: The purpose of this study was to examine the oropharyngeal cancer pattern among different ethnic groups in Taiwan. METHODS: The sample population was divided into three ethnic groups: the Fukkien, Hakka, and aboriginal communities. Age-standardized mortality rates (SMRs) and age-standardized incidence rates (SIRs) were estimated among these ethnic groups for the period 1979-1996/1997. RESULTS: Our study found that the higher oropharyngeal cancer mortality and incidence rates in females of aboriginal groups are statistically significant, and higher than reference groups for both genders (SMR=3.76, SIR=2.18). However, in the lower areca quid chewing aboriginal groups, the higher pattern was not seen in females, and the lower pattern was even found in males. The incidence and mortality rate of oropharyngeal cancer in Hakkas was significantly lower than in the reference group. CONCLUSIONS: The pattern of oropharyngeal cancer in Taiwan showed ethnic differences. The differences may be due to variation in exposure to different risk factors; however, in our study, we found that genetic differences might also be considered when explaining the different oropharyngeal cancer patterns among ethnic groups.

The effects of chewing areca/betel quid with and without cigarette smoking on oral submucous fibrosis and oral mucosal lesions.

OBJECTIVES: The purpose of this study was to investigate the risk of areca/betel quid chewing with or without cigarette smoking on oral submucous fibrosis (OSF) and other oral mucosal lesions. METHODS: A stratified case-control study was designed. There were in total 102 patients with oral mucosal lesions or OSF (confirmed pathologically) in the case group. OSF (n = 62) and oral mucosal lesions (n = 62) in 102 subjects were separately analyzed for men and women investigating their risks. RESULTS: For OSF, people with both smoking and chewing habits had a statistically significant odds ratio (OR) 8.68 (95% CI = 1.87, 40.23). For the group of people with chewing habit only and without any lifetime cigarette smoking habit, the OR was 4.51 (95% CI = 1.20, 16.94). For other oral mucosal lesions, people with mixed habits and chewing only had also significant risks (OR = 8.37 and 3.95, respectively). For both OSF and other oral lesions, the ORs of mixed habits and chewing only were both higher in women than in men. CONCLUSIONS: The areca/betel quid used in Taiwan does not contain any tobacco product. The only way of areca/betel quid could synergize with any tobacco product is through cigarette smoking. A statistically significant association with oral mucosal lesions and OSF was still found in the group of areca/betel quid chewing only.

Intragastric administration of Lactobacillus casei expressing transmissible gastroentritis coronavirus spike glycoprotein induced specific antibody production.

Lactobacillus casei strain Shirota was selected as a bacterial carrier for the development of live mucosal vaccines against coronavirus. A 75 kDa fragment of transmissible gastroenteritis coronavirus (TGEV) spike glycoprotein S was used as the model coronavirus antigen. The S glycoprotein was cloned into a Lactobacillus/E. coli shuttle vector (pLP500) where expression and secretion of the glycoprotein S from the recombinant lactobacilli was detected via immunoblotting. Oral immunization of BALB/c mice with recombinant LcS that constitutively expresses the 75 kDa fragment of the glycoprotein S, induced both local mucosal and systemic immune responses against TGEV. Maximum titers of IgG (8.38+/-0.19 ng/ml of serum) and IgA (64.82+/-2.9 ng/ml of intestinal water) were attained 32 days post oral inturbation. The induced antibodies demonstrated neutralizing effects on TGEV infection.

Permanent colonization by Lactobacillus casei is hindered by the low rate of cell division in mouse gut.

Long residence times of probiotics in the intestinal tract would prolong their potential beneficial health effects and assist colonization. This study investigated the colonization potential of Lactobacillus casei Shirota in mouse intestine by using 5 (and 6)-carboxyfluorescein diacetate, succinimidyl ester (cFDA-SE) for assessment of doubling times in different parts of the intestine. The amounts of intestinal water overlying the surfaces of the duodenum, jejunum, ileum, and colon in BALB/c mice were 34.4 +/- 2.9, 58.8 +/- 6.8, 21.6 +/- 2.2, and 8.0 +/- 1.0 mg, respectively. Based on the residual concentrations of cFDA-SE-labeled lactobacilli on intestinal mucosal surfaces, the average half times for the wash-out of lactobacilli fed were estimated at 3.98, 1.55, 1.34, and 2.48 days in the duodenum, jejunum, ileum, and colon, respectively. The average doubling times of the lactobacilli, estimated from the residual fluorescent levels of surface-adhered cells, were 4.10, 4.78, 4.56, and 5.59 days in the duodenum, jejunum, ileum, and colon, respectively. It is estimated that the lactobacilli would have to achieve an average doubling time of 1.03 to 2.04 days to colonize the various sections of the mouse intestinal tract more permanently.

Intramolecular interactions in chemically modified Escherichia coli thioredoxin monitored by hydrogen/deuterium exchange and electrospray ionization mass spectrometry.

Site specific amide hydrogen/deuterium content of oxidized and reduced Escherichia colithioredoxin, and alkylated derivatives, Cys-32-ethylglutathionylated and Cys-32-ethylcysteinylated thioredoxins are measured, after exposure for 20 s to D(2)O/phosphate buffer (pH 5.7), by electrospray mass spectrometry. The degree of deuteration of Oxi-TRX and Red-TRX correlated with the rates of H/D exchange measured previously by NMR. The ethylcysteinyl modification was shown to minimally perturb the active site of the reduced protein, but showed more global effects on structures of alpha-helices and beta-strands distant from the site of modification. In contrast, the larger ethylglutathionyl group had little effect on the protein's overall conformation, but significantly affected the structure of loops close to the active site. A molecular model of GS-ethyl-TRX derived from molecular simulation allowed the H/D exchange results to be interpreted in terms of specific interactions between the alkyl chain and the protein surface. The specific conformation of the ethylglutathione modification was predicted to be fixed by salt bridges between the carboxylates of the gamma-Glu and Gly of glutathione and the guanidinium of Arg-73 and epsilon-amino group of Lys-90 of the protein. Specific hydrogen bonding interactions between the glutathione carbonyl oxygens and the amide protons of thioredoxin residues Ile-75 and Ala-93 were predicted. The H/D exchange studies showed low levels of deuterium incorporation at backbone nitrogens of these residues. The data also provided evidence for an unusual amide proton-amide nitrogen hydrogen bond within the ethylglutathionylated chain. These same sets of electrostatic and hydrogen bonding interactions were not predicted or observed for the smaller alkyl modification in Cys-ethyl-TRX.

The crystal structures of DNA Holliday junctions.

Nearly 40 years ago, Holliday proposed a four-stranded complex or junction as the central intermediate in the general mechanism of genetic recombination. During the past two years, six single-crystal structures of such DNA junctions have been determined by three different research groups. These structures all essentially adopt the antiparallel stacked-X conformation, but can be classified into three distinct categories: RNA-DNA junctions; ACC trinucleotide junctions; and drug-induced junctions. Together, these structures provide insight into how local and distant interactions help to define the detailed and general physical features of Holliday junctions at the atomic level.

A crystallographic map of the transition from B-DNA to A-DNA.

The transition between B- and A-DNA was first observed nearly 50 years ago. We have now mapped this transformation through a set of single-crystal structures of the sequence d(GGCGCC)2, with various intermediates being trapped by methylating or brominating the cytosine bases. The resulting pathway progresses through 13 conformational steps, with a composite structure that pairs A-nucleotides with complementary B-nucleotides serving as a distinct transition intermediate. The details of each step in the conversion of B- to A-DNA are thus revealed at the atomic level, placing intermediates for this and other sequences in the context of a common pathway.

The crystal structures of psoralen cross-linked DNAs: drug-dependent formation of Holliday junctions.

The single-crystal structures are presented for two DNA sequences with the thymine bases covalently cross-linked across the complementary strands by 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT). The HMT-adduct of d(CCGCTAGCGG) forms a psoralen-induced Holliday junction, showing for the first time the effect of this important class of chemotheraputics on the structure of the recombination intermediate. In contrast, HMT-d(CCGGTACCGG) forms a sequence-dependent junction. In both structures, the DNA duplex is highly distorted at the thymine base linked to the six-member pyrone ring of the drug. The psoralen cross-link defines the intramolecular interactions of the drug-induced junction, while the sequence-dependent structure is nearly identical to the native Holliday junction of d(CCGGTACCGG) alone. The two structures contrast the effects of drug- and sequence-dependent interactions on the structure of a Holliday junction, suggesting a role for psoralen in the mechanism to initiate repair of psoralen-lesions in mammalian DNA.

Intrinsically bent DNA in the promoter regions of the yeast GAAL1-10 and GAL80 genes.

Circular permutation analysis has detected fairly strong sites of intrinsic DNA bending on the promoter regions of the yeast GAL1-10 and GAL80 genes. These bends lie in functionally suggestive locations. On the promoter of the GAL1-10 structural genes, strong bends bracket nucleosome B, which lies between the UAS(G) and the GAL1 TATA. These intrinsic bends could help position nucleosome B. Nucleosome B plus two other promoter nucleosomes protect the TATA and start site elements in the inactive state of expression but are completely disrupted (removed) when GAL1-10 expression is induced. The strongest intrinsic bend ( approximately 70 degrees ) lies at the downstream edge of nucleosome B; this places it approximately 30 base pairs upstream of the GAL1 TATA, a position that could allow it to be involved in GAL1 activation in several ways, including the recruitment of a yeast HMG protein that is required for the normally robust level of GAL1 expression in the induced state (Paull, T., Carey, M., and Johnson, R. (1996) Genes Dev. 10, 2769-2781). On the regulatory gene GAL80, the single bend lies in the non-nucleosomal hypersensitive region, between a GAL80-specific far upstream promoter element and the more gene-proximal promoter elements. GAL80 promoter region nucleosomes contain no intrinsically bent DNA.

A body-mind-spirit model in health: an Eastern approach.

Under the division of labor of Western medicine, the medical physician treats the body of patients, the social worker attends to their emotions and social relations, while the pastoral counselor provides spiritual guidance. Body, mind, cognition, emotion and spirituality are seen as discrete entities. In striking contrast, Eastern philosophies of Buddhism, Taoism and traditional Chinese medicine adopt a holistic conceptualization of an individual and his or her environment. In this view, health is perceived as a harmonious equilibrium that exists between the interplay of 'yin' and 'yang': the five internal elements (metal, wood, water, fire and earth), the six environmental conditions (dry, wet, hot, cold, wind and flame), other external sources of harm (physical injury, insect bites, poison, overeat and overwork), and the seven emotions (joy, sorrow, anger, worry, panic, anxiety and fear). The authors have adopted a body-mind-spirit integrated model of intervention to promote the health of their Chinese clients. Indeed, research results on these body-mind-spirit groups for cancer patients, bereaved wives and divorced women have shown very positive intervention outcomes. There are significant improvements in their physical health, mental health, sense of control and social support.

Differences in physician utilization between Aboriginal and non-Aboriginal children.

OBJECTIVE: In the present study, we examined the factors affecting Aboriginal children's visits to a medical practitioner and compared them with non-Aboriginal children. METHODS: We selected five Aboriginal communities and four neighbouring non-Aboriginal communities, and conducted a door-to-door survey, covering all children born after 1983. Of an initial sample of 1013 children, 896 (response rate 89.92% for non-Aboriginal children and 85.87% for Aboriginal children) completed the questionnaire for analysis. RESULTS: In all, 896 children of non-mixed lineage with an age range of 0-12 years were collected into the study, including 316 Aborigines and 580 non-Aborigines. A higher percentage of non-Aboriginal children had more national health insurance coverage than Aboriginal children. The ratio of parents using the services of an out of community medical practitioner when their children were sick was higher for Aboriginal parents than for non-Aborigines. Medical injection frequency was higher in Aboriginal children. Linear regression was used to examine the factors affecting the frequency of physician utilization in the preceding month. CONCLUSION: A lower national health insurance coverage rate, and a higher rate of intramuscular injections for Aboriginal children plus difficulties in access to medical resources due to travel time and travel distance are still major problems for the Aborigines.

The extended and eccentric E-DNA structure induced by cytosine methylation or bromination.

Cytosine methylation or bromination of the DNA sequence d(GGCGCC)2 is shown here to induce a novel extended and eccentric double helix, which we call E-DNA. Like B-DNA, E-DNA has a long helical rise and bases perpendicular to the helix axis. However, the 3'-endo sugar conformation gives the characteristic deep major groove and shallow minor groove of A-DNA. Also, if allowed to crystallize for a period of time longer than that yielding E-DNA, the methylated sequence forms standard A-DNA, suggesting that E-DNA is a kinetically trapped intermediate in the transition to A-DNA. Thus, the structures presented here chart a crystallographic pathway from B-DNA to A-DNA through the E-DNA intermediate in a single sequence. The E-DNA surface is highly accessible to solvent, with waters in the major groove sitting on exposed faces of the stacked nucleotides. We suggest that the geometry of the waters and the stacked base pairs would promote the spontaneous deamination of 5-methylcytosine in the transition mutation of dm5C-dG to dT-dA base pairs.