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.

Prediction of a crystallization pathway for Z-DNA hexanucleotides.

Crystallization of macromolecules for structural studies has long been a hit-or-miss process. The crystallization of hexanucleotides as Z-DNA was studied, and it was shown that the cation concentration for crystal formation could be predicted from solvation free energy (SFE) calculations. Solution studies on the conformation and solubilities of the hexanucleotides showed that a critical concentration of the DNA in the Z-conformation must be present in solution to effect crystallization. The SFE calculations therefore predict the propensity of the hexanucleotides to adopt the left-handed conformation and the driving force required to reach this critical concentration relative to the intrinsic solubility of Z-DNA for crystallization.

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.

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.

The structures and relative stabilities of d(G x G) reverse Hoogsteen, d(G x T) reverse wobble, and d(G x C) reverse Watson-Crick base-pairs in DNA crystals.

We have solved the structures of the homoduplex d(Gm5CGCGCG)2, and the heteroduplexes d(GCGCGCG)/d(TCGCGCG) and d(GCGCGCG)/d(CCGCGCG). The structures form six base-pairs of identical Z-DNA duplexes with single nucleotides overhanging at the 5'-ends. The overhanging nucleotide from one strand remains stacked and sandwiched between the blunt-ends of two adjacent Z-DNA duplexes, while the overhanging base of the opposing strand is extra-helical. The stacked and the extra-helical bases from adjacent duplexes pair to form a distorted d(G x G) reverse Hoogsteen base-pair in the d(Gm5CGCGCG)2 homoduplex, and d(G x T) reverse wobble and d(G x C) reverse Watson-Crick base-pairs in the d(GCGCGCG)/d(TCGCGCG) and d(GCGCGCG)/d(CCGCGCG) heteroduplexes, respectively. Interestingly, only the d(G,T) and d(G x C) base-pairs were observed in the heteroduplexes, suggesting that both the d(G x T) reverse wobble and d(G x C) reverse Watson-Crick base-pairs are more stable in this crystal environment than the d(G x G) reverse Hoogsteen base-pair. To estimate the relative stability of the three types of reverse base-pairs, crystals were grown using various mixtures of sequences and their strand compositions analyzed by mass spectrometry. The d(G x C) reverse Watson-Crick base-pair was estimated to be more stable by approximately 1.5 kcal/mol and the d(G x T) reverse wobble base-pair more stable by approximately 0.5 kcal/mol than the d(G x G) reverse Hoogsteen base-pair. The step during crystallization responsible for discriminating between the strands in the crystal is highly cooperative, suggesting that it occurs during the initial nucleating event of crystal growth.

Alternating and non-alternating dG-dC hexanucleotides crystallize as canonical A-DNA.

We have solved the single-crystal X-ray structures of two different hexanucleotides: the alternating sequence d(Gm5CGm5CGC), and the non-alternating sequence d(Gm5CCGGC). Both of these hexamers crystallize readily as A-DNA in the orthorhombic space group C222(1). Although hexanucleotides have been previously crystallized as Z-DNA, and in one case as B-DNA, this is the first time hexanucleotides have been crystallized as A-DNA. Both hexamers adopt a typical A-conformation, which is surprisingly more similar to the structure of A-DNA fibers than to other A-DNA single crystals. The structure of d(Gm5CGm5CGC) was solved to a resolution of 2.1 A (R-factor = 19.6%). This structure has all of the features characteristic of canonical A-DNA, including it's helical repeat (11.2 bp/turn), helical rise (2.6 A/bp), base-pair displacement (-4.7 A), base inclination angle (16.9 degrees), and sugar puckers that are predominantly 3'-endo. The lower resolution, non-alternating structure has similar overall average values for these parameters. We observed several sequence-dependent correlations in these parameters, especially in the d(CG) base step. These steps have lower twist and rise values, coupled with high roll angles as compared to d(GC) steps. The molecular interactions involved in crystal packing and the detailed structure of the bound water in the crystals, however, are similar to those of longer 8 and 10 bp A-DNA crystal structures. Although the structural effect of cytosine methylation on A-DNA appears to be minimal, this modification significantly affects the ability of these sequences to crystallize as A-DNA. In conclusion, we present the A-DNA forming class of hexanucleotides, a new crystallographic system for studying DNA structure at near atomic resolution.

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.

Tears of the anulus fibrosus: correlation between MR and pathologic findings in cadavers.

Tears of the anulus fibrosus, which have been implicated in back pain, have not been studied systematically with MR imaging. We correlated MR images with cryomicrotome sections to study the lumbar anulus fibrosus in 20 cadavers. Three distinct types of tears of the anulus were identified: concentric tears, characterized by fluid-filled spaces between adjacent lamellae; radial tears, characterized by a rupture of all layers in the anulus between the nucleus and the surface of the disk; and transverse tears, characterized by a rupture of Sharpey's fibers in the periphery of the anulus, near the ring apophysis. In each type, fluid or mucoid material was present in the tear. MR demonstrated the transverse and radial tears. We conclude that MR imaging provides an accurate means for investigating tears of the anulus.

MR and cryomicrotomy of C1 and C2 roots.

Paramedian sagittal MR images and cryotome sections in four cadavers were correlated with eight clinical MR studies to analyze the appearance of the C1 and C2 nerve roots and adjacent tissue. The C2 nerve roots and anatomically related venous plexus were identified. The C1 root, although not visualized by MR, could be localized by its relation to the vertebral artery, C1 lateral mass, and posterior arch.

The MR appearance of gray and white matter in the cervical spinal cord.

Artifacts that can distort the appearance of the cervical spinal cord are caused by data truncation during MR image reconstruction. We used a phantom and then correlated anatomic sections with MR images in cadavers and normal volunteers to evaluate the effect of truncation artifacts on the MR appearance of the spinal cord. When truncation artifacts are minimized, the gray matter and major white-matter columns in the cervical cord can be recognized. T2-weighted gradient-echo MR techniques can best differentiate gray from white matter.

Truncation artifact in MR images of the intervertebral disk.

A cadaver's vertebral column, a phantom, and a volunteer were imaged on a 1.5-T MR scanner to study the thin, uniform, dark, transverse lines that characterize some intervertebral disks. An artifactual dark line appears when the field of view (FOV) and matrix steps (n) are chosen so that d = FOV/n, where d equals the intervertebral disk height, or spacing between phantom vertebrae. The artifact is caused by the truncation effect. An artifactual dark line is differentiated from a dark line caused by anatomic variables, and means for reducing such lines by modifying imaging parameters are discussed.

MR appearance of gray and white matter at the cervicomedullary region.

To study the appearance of gray and white matter in the cervicomedullary region, six fresh cadavers were imaged with a 1.5-T MR scanner and then sectioned with a cryomicrotome. The pyramidal tracts, fasciculus cuneatus and gracilis, inferior olivary nuclei, supraspinal nuclei, spinal trigeminal nuclei, and medial lemnisci were identified by MR in the cervicomedullary region.

The interactions of ruthenium hexaammine with Z-DNA: crystal structure of a Ru(NH3)6+3 salt of d(CGCGCG) at 1.2 A resolution.

A crystal of d(CGCGCG) in the Z-DNA lattice was soaked with ruthenium(III) hexaammine and its structure refined at 1.2 A resolution. Three unique metal complexes were found absorbed to each hexamer duplex. In addition, two symmetry-related binding sites were located, yielding a total of five ruthenium complexes bound to each d(CGCGCG) duplex. One unique site and its symmetry related site are nearly identical to the binding site of cobalt(III) hexaammine on Z-DNA. At that position, the metal complex bridges the convex surfaces of two adjacent Z-DNA strands by hydrogen bonds to the N7 and O6 functional groups of the guanine bases. The remaining three ruthenium three ruthenium(III) hexaammine binding sites are not present in the cobalt(III) hexaammine Z-DNA structure. Of these, two are related by symmetry and span the gap between the convex outer surface of one Z-DNA strand and the helical groove crevice of a neighboring strand. The third ruthenium site has no symmetry mate and involves interactions with only the deep groove. In this interaction, the metal complex hydrogen bonds to both the phosphate backbone and to a set of primary shell water molecules that extend the hydrogen bonding potential of the deep groove crevice out to the surface of the molecule. Solution studies comparing the circular dichroism spectra of low salt poly(dG-dC).poly(dG-dC) samples in the presence of ruthenium(III) and cobalt(III) hexammine show that the ruthenium complex does stabilize Z-DNA in solution, but not as effectively as the cobalt analogue. This suggests that some of the interactions available for the larger ruthenium complex may not be important for stabilization of the left-handed DNA conformation.

Aetiology, morphology and body composition of infants born small for gestational age.

Infants born small for gestational age (SGA) are a heterogeneous group. Both the timing and duration of the intrauterine insult determine the physical condition and body composition of the infant at birth. Infants with symmetrical intrauterine growth retardation (IUGR) have a similar body composition at birth to weight-matched infants born appropriate for gestational age. However, these infants are more likely to remain shorter and lighter than normal infants. In contrast, infants with asymmetrical IUGR have reduced fat deposition but are more likely to exhibit catch-up growth during the first few months of life. The low mortality and morbidity rates in infants born SGA observed in recent studies are linked to their appropriate perinatal management, including adequate early nutritional support.