Socioecological differences in factors associated with inconsistent condom use with female sex workers and casual partners: an observational study of heterosexual men attending an anonymous HIV testing clinic in Singapore.

Sexual practices among heterosexual men may differ between female sex workers (FSWs) and casual partners. We surveyed 203 heterosexual men and investigated the attributes associated with inconsistent condom use among them. Lower educational attainment was positively associated with inconsistent condom use with FSWs (adjusted prevalence ratio (aPR) 2.63; P = 0.018) and casual partners (aPR 1.55; P = 0.022), whereas early age of sexual debut (aPR 3.00; P = 0.012) and alcohol use during sex (aPR 7.95; P < 0.001) were positively associated with inconsistent condom use with FSWs. Socioecological factors may explain such differences.

A web-based educational intervention module to improve knowledge and attitudes towards thalassaemia prevention in Malaysian young adults.

BACKGROUND: Thalassaemia is a public health burden in Malaysia and its prevention faces many challenges. In this study, we aimed to assess the effectiveness of a web-based educational module in improving knowledge and attitudes about thalassaemia prevention amongst Malaysian young adults. METHODS: We designed an interactive web-based educational module in the Malay language wherein videos were combined with text and pictorial visual cues. Malaysians aged 18-40 years old who underwent the module had their knowledge and attitudes assessed at baseline, post-intervention and at 6-month follow-up using a selfadministered validated questionnaire. RESULTS: Sixty-five participants: 47 Malays (72.3%), 15 Chinese (23.1%), three Indians (4.6%) underwent the module. Questionnaires were completed at baseline (n=65), postintervention (n=65) and at 6-month follow-up (n=60). Out of a total knowledge score of 21, significant changes were recorded across three time-points- median scores were 12 at pre-intervention, 19 at post-intervention and 16 at 6-month follow-up (p<0.001). Post-hoc testing comparing preintervention and 6-month follow-up scores showed significant retention of knowledge (p<0.001). Compared to baseline, attitudes at 6-month follow-up showed an increased acceptance for "marriage avoidance between carriers" (pre-intervention 20%, 6-month follow-up 48.3%, p<0.001) and "prenatal diagnosis" (pre-intervention 73.8%, 6-month follow-up 86.2%, p=0.008). Acceptance for selective termination however, remained low without significant change (pre-intervention 6.2%, 6-month follow-up 16.7%, p=0.109). CONCLUSION: A web-based educational module appears effective in improving knowledge and attitudes towards thalassaemia prevention and its incorporation in thalassaemia prevention programs is potentially useful in Malaysia and countries with a high internet penetration rate.

High-resolution outpatient imaging of the wrist.

The authors describe their experience with magnetic resonance imaging (MRI) in the evaluation of pathologic conditions of the wrist in an outpatient setting. In that setting, because time and quality are both important factors, they have concentrated on developing protocols that will allow effective, time-efficient, high-resolution MRI of the wrist. With these wrist imaging protocols, they have evaluated the majority of commonly encountered pathologic conditions of the wrist. They have found that high-resolution images, which can be acquired in a very timely fashion when fast spin echo sequences are used in imaging protocols, will demonstrate the most common pathologic conditions, including triangular fibrocartilage and ligament tears in the wrist. They present the practical issues of patient position and imaging sequences as well as the imaging findings in those pathologic conditions.

Two-photon absorption-induced self-phase modulation in GaAs-AlGaAs waveguides for surface-emitted second-harmonic generation.

Performance-limiting asymmetric distortion is observed in the spectra of fundamental pulses transmitted through GaAs-Al(0.9)Ga(0.1)As multilayer waveguides designed for surface-emitted second-harmonic generation. This behavior is attributed to refractive-index changes resulting from the accumulation of free carriers created by two-photon absorption in the GaAs layers. Numerical simulations of the intensity-dependent spectra by use of the separately measured two-photon absorption coefficient are shown to be in good agreement with the observed spectra.

A review of the role of magnetic resonance imaging in the evaluation of shoulder impingement syndrome and rotator cuff tendon tears.

The objective of this paper is to present a review of the role of magnetic resonance imaging in the evaluation of shoulder impingement syndrome and rotator cuff tendon tears. This imaging modality is effective in demonstrating both the soft tissue and bony abnormalities associated with structural shoulder impingement which include subacromial-subdeltoid bursitis, supraspinatus tendinopathy, rotator cuff tendon tears, subacromial osteophytic spurs and acromioclavicular joint capsular hypertrophy and osteophytosis. The detection of a subacromial osteophytic spur is considered specific for shoulder impingement syndrome. The 3 most accurate magnetic resonance imaging signs of a full thickness supraspinatus tendon tear reported are: tendon discontinuity, musculotendinous junction retraction and supraspinatus tendon thinning. The most specific sign is tendon discontinuity and the most sensitive is subacromial-subdeltoid bursal fluid.

Molecular modeling of closed circular DNA thermodynamic ensembles.

Many modeling studies of supercoiled DNA are based on equilibrium structures from theoretical calculations or energy minimization. Since closed circular DNAs are flexible, it is possible that errors are introduced by calculating properties from a single minimum energy structure, rather than from a complete thermodynamic ensemble. We have investigated this question using molecular dynamics simulations on a low resolution molecular mechanics model in which each base pair is represented by three points (a plane). This allows the inclusion of sequence-dependent variations of tip, inclination, and twist. Three kinds of sequences were tested: (1) homogeneous DNA, in which all base pairs have the helicoidal parameters of an ideal, average B-DNA; (2) random sequence DNA; and (3) curved DNA. We examined the rate of convergence of various structural parameters. Convergence for most of these is slowest for homogeneous sequences, more rapid for random sequences, and most rapid for curved sequences. The most slowly converging parameter is the antipodes profile. In a plasmid with N base pairs (bp), the antipodes distance is the distance dij from base pair i to base pair j halfway around the plasmid, j = i + N/2. The antipodes profile at time tau is a plot of dij over the range i = 1, N/2. In a homogeneous plasmid, convergence requires that the antipodes profile averaged over time must be flat. Even in the small plasmids examined here, the average properties of the ensembles were found to differ from those of static equilibrium structures. These effects will be even more dramatic for larger plasmids. Further, average and dynamic properties are affected by both plasmid size and sequence.

Molecular dynamics simulations of small DNA plasmids: effects of sequence and supercoiling on intramolecular motions.

Small (600 base pair) DNA plasmids were modeled with a simplified representation (3DNA) and the intramolecular motions were studied using molecular mechanics and molecular dynamics techniques. The model is detailed enough to incorporate sequence effects. At the same time, it is simple enough to allow long molecular dynamics simulations. The simulations revealed that large-scale slithering occurs in a homogeneous sequence. In a heterogeneous sequence, containing numerous small intrinsic curves, the centers of the curves are preferentially positioned at the tips of loops. With more curves than loop tips (two in unbranched supercoiled DNA), the heterogeneous sequence plasmid slithers short distances to reposition other curves into the loop tips. However, the DNA is immobilized most of the time, with the loop tips positioned over a few favored curve centers. Branching or looping also appears in the heterogeneous sequence as a new method of repositioning the loop tips. Instead of a smooth progression of increasing writhing with increasing linking difference, theoretical studies have predicted that there is a threshold between unwrithed and writhed DNA at a linking difference between one and two. This has previously been observed in simulations of static structures and is demonstrated here for dynamic homogeneous closed DNA. Such an abrupt transition is not found in the heterogeneous sequence in both the static and dynamic cases.

DNA topological context affects access to eukaryotic DNA topoisomerase I.

We have analyzed the reactivity of a 217 base pair segment of the intrinsically curved Crithidia fasciculata kinetoplast DNA towards eukaryotic DNA topoisomerase I. The substrates were open [linear fragment and nicked circle] and closed minidomains [closed relaxed circle and circles with linking differences of -1 and -2]. We interpreted the results with the aid of a model that was used to predict the structures of the topoisomers. The modelling shows that the delta Lk(-1) form is unusually compact because of the curvature in the DNA. To determine the role of sequence-directed curvature in both the experimental and modeling studies, controls were examined in which the curved Crithidia sequence was replaced by an uncurved sequence obtained from the plasmid pBR322. Reactivity of the Crithidia DNA [as analyzed both by the cleavage and topoisomerization reactions] markedly varied among the DNA forms: (i) the hierarchy of overall reactivity observed is: linear fragment > nicked circular, closed circular [delta Lk(0)], interwound [delta Lk(-2)] > bent interwound [delta Lk(-1)]; (ii) the intensity of several cleavage positions differs among DNA forms. The results show that eukaryotic DNA topoisomerase I is very sensitive to the conformation of the substrates and that its reactivity is modulated by the variation of the compactness of the DNA molecule. The C. fasciculata sequence contains a highly curved segment that determines the conformation of the closed circle in a complex way.

Anaplastic carcinoma of the thyroid: a 24-year experience.

BACKGROUND: Anaplastic carcinoma of the thyroid gland is a lethal entity; few patients live more than 12 months following diagnosis. We retrospectively reviewed the experience with this entity at our cancer institute and identified a subgroup of patients with complete resection who have a 60% 5-year survival. METHODS: Twenty-one cases of anaplastic carcinoma of the thyroid gland were analyzed retrospectively with respect to prognostic factors influencing survival. This represents 2.7% of 771 cases of thyroid cancer seen at our institution from 1968 to 1992. The median age at presentation was 65.1 years; male/female ratio was 1:1.1; and the most common symptom was a rapidly enlarging neck mass (76%). RESULTS: Estimated 5-year survival was 10% (median: 4.5 months). Tumor size less than 6.0 cm (p = .004) and female gender (p = .02) were significant prognostic factors. Five patients who underwent complete resection had an estimated 5-year survival of 60% (median: 131 months). Four of these patients had postoperative radiotherapy with or without sequential chemotherapy. Two of these patients survived more than 10 years, and a third remains alive without disease at 26 months.

Modeling large RNAs and ribonucleoprotein particles using molecular mechanics techniques.

There is a growing body of low-resolution structural data that can be utilized to devise structural models for large RNAs and ribonucleoproteins. These models are routinely built manually. We introduce an automated refinement protocol to utilize such data for building low-resolution three-dimensional models using the tools of molecular mechanics. In addition to specifying the positions of each nucleotide, the protocol provides quantitative estimates of the uncertainties in those positions, i.e., the resolution of the model. In typical applications, the resolution of the models is about 10-20 A. Our method uses reduced representations and allows us to refine three-dimensional structures of systems as big as the 16S and 23S ribosomal RNAs, which are about one to two orders of magnitude larger than nucleic acids that can be examined by traditional all-atom modeling methods. Nonatomic resolution structural data--secondary structure, chemical cross-links, chemical and enzymatic footprinting patterns, protein positions, solvent accessibility, and so on--are combined with known motifs in RNA structure to predict low-resolution models of large RNAs. These structural constraints are imposed on the RNA chain using molecular mechanics-type potential functions with parameters based on the quality of experimental data. Surface potential functions are used to incorporate shape and positional data from electron microscopy image reconstruction experiments into our models. The structures are optimized using techniques of energy refinement to get RNA folding patterns. In addition to providing a consensus model, the method finds the range of models consistent with the data, which allows quantitative evaluation of the resolution of the model. The method also identifies conflicts in the experimental data. Although our protocol is aimed at much larger RNAs, we illustrate these techniques using the tRNA structure as an example and test-bed.

Use of skeletal surveys in the radiological assessment of renal osteodystrophy--a study in the Singapore General Hospital.

The aims of this review on the use of skeletal surveys in the radiological assessment of renal osteodystrophy were threefold: to describe the radiological pattern of renal osteodystrophy in a local cohort of patients with chronic renal failure, to assess whether serial radiographs of the hands may effectively replace full radiological skeletal surveys in the long-term follow-up assessment of renal bone disease, and to formulate a grading system for bone resorption due to hyperparathyroidism. A radiological study of 61 patients with chronic renal failure revealed 20 (32.8%) patients with unequivocal radiological signs of renal osteodystrophy. The main abnormal radiological features observed in descending order of frequency were: osteopenia with associated cortical thinning and coarsened bone trabecular pattern (75%), subperiosteal resorption (60%), osteosclerosis (50%), extraosseous calcification (30%) and periosteal new bone formation (15%). A five-grade method of assessing the severity and extent of bone resorption was formulated. The study showed that 40% of the patients with a radiological diagnosis of renal osteodystrophy did not show changes in the hand radiographs. This finding precluded a recommendation of hand radiographs being used alone in the long-term radiological follow-up of patients with renal bone disease. An alternative was proposed and this was a limited radiological skeletal survey of three projections: radiographs of both hands, chest including the clavicles and the pelvis. This limited study would result in a cost saving of 62% as compared to a full study.

Teaching macromolecular modeling.

Training newcomers to the field of macromolecular modeling is as difficult as is training beginners in x-ray crystallography, nuclear magnetic resonance, or other methods in structural biology. In one or two lectures, the most that can be conveyed is a general sense of the relationship between modeling and other structural methods. If a full semester is available, then students can be taught how molecular structures are built, manipulated, refined, and analyzed on a computer. Here we describe a one-semester modeling course that combines lectures, discussions, and a laboratory using a commercial modeling package. In the laboratory, students carry out prescribed exercises that are coordinated to the lectures, and they complete a term project on a modeling problem of their choice. The goal is to give students an understanding of what kinds of problems can be attacked by molecular modeling methods and which problems are beyond the current capabilities of those methods.

Prediction of the three-dimensional structure of Escherichia coli 30S ribosomal subunit: a molecular mechanics approach.

We introduce a computer-assisted procedure for folding large RNA chains into three-dimensional conformations consistent with their secondary structure and other known experimental constraints. The RNA chain is modeled using pseudoatoms at different levels of detail--from a single pseudoatom per helix to a single pseudoatom for each nucleotide. A stepwise procedure is used, starting with a simple representation of the macromolecule that is refined and then extrapolated into higher resolution for further refinement. The procedure is capable of folding different random-walk chains by using energy minimization, allowing generation of a range of conformations consistent with given experimental data. We use this procedure to generate several possible conformations of the 16S RNA in the 30S ribosomal subunit of Escherichia coli by using secondary structure and the neutron-scattering map of the 21 proteins in the small subunit. The RNA chain is modeled using a single pseudoatom per helix. RNA-RNA and RNA-protein crosslinks, reported in current literature, are included in our model. Footprinting data for different ribosomal proteins in the 16S RNA are also used. Several conformations of the 16S RNA are generated and compared to predict gross structural features of the 30S subunit as well as to identify regions of the 16S RNA that cannot be well-defined with current experimental data.

Molecular mechanics model of supercoiled DNA.

We describe a pseudo-atomic model of supercoiled DNA. Each base-pair of the DNA is represented in the model by three particles placed in a plane. The particle triplets are stacked to model stacked base-pairs in double-helical DNA, and closed circular conformations are generated to investigate supercoiling. This model is less detailed than all-atom models, which are too computationally demanding to be used to study supercoiling. On the other hand, this model contains details at the base-pair level and is therefore more elaborate than elastomechanical models. A potential energy function is written in terms of a set of internal co-ordinates defined to resemble a limited number of helical parameters. The modeled helical parameters, helical twist, base-roll, tilt and rise, are the most important parameters of the global shape of DNA. Experimentally measured mechanical properties of DNA are used to define the forces holding the particles together. We then use a procedure incorporating energy minimization and molecular dynamics to locate low energy conformations of the model DNA. The model was found to behave very much like rubber-tubing and elastomechanical models. The conformations and the effects of supercoiling pressure (a number proportional to the degree to which the total twist of the DNA has been altered from its natural value) on these conformations are all very similar to those observed in the latter two models. We also used this model to examine the effects of supercoiling pressure, base-sequence and mechanical properties on the conformations and energies of five sequences. The sequences studied include models of naturally straight DNA and DNA with static or natural bends.

AUGUR: a program to predict, display and analyze the tertiary structure of B-DNA.

AUGUR is a program to predict, display and analyze the three-dimensional structure of B-DNA. The user can choose one of six models to predict the helical parameters of a given sequence. These parameters are then used to generate the coordinates of the DNA model in three-dimensional space (trajectory). The trajectory can be displayed and rotated on a graphics terminal. The trajectory and helical parameters can also be searched for bends and structural homologues.

A comparison of six DNA bending models.

The predictions of six DNA bending models were compared with experimental relative mobility data. The study showed that all the models are reasonably accurate in predicting bending in synthetic sequences and in a natural sequence. The least accurate of these models is the Calladine-Dickerson model. The most consistent model is the ApA Wedge, possibly because it distributes the bends into base-roll and base-tilt components.

Stability of the accommodative dark focus after periods of maintained accommodation.

The behavior of the accommodative system at rest was investigated following short- (5 min) and long-term (1 hr) accommodative stimuli of either 0.00 D or 3.00 D. The resting position of accommodation changed in the direction of the accommodative stimulus presented. After the 5 min stimulus, the resting position slowly returned toward the pre-stimulus level. After the 1 hr stimulus, the resting state remained significantly different from the pre stimulus level over the subsequent 6 hr. These results suggest that the equilibrium level of accommodation in the dark is determined by a balance of the previous accommodative stimuli.

Steady-state accommodation response to different Snellen letter sizes.

The steady-state accommodation response to Snellen letters of different sizes was measured with a laser-Badal optometer. It was found that the accommodation response was least when viewing the 6/9 letter size for both monocular and binocular observation at 6 m and increased when the letter size got smaller or larger. The mean accommodation response for the monocular viewing state was significantly higher than the binocular state for Snellen letter sizes between 6/4.7 and 6/12. At 40 cm the accommodation response for different letter sizes showed no obvious trend. However, the lag in binocular accommodation was significantly less than the monocular lag.