Intracranial EEG correlates of implicit relational inference within the hippocampus.

Drawing inferences from past experiences enables adaptive behavior in future situations. Inference has been shown to depend on hippocampal processes. Usually, inference is considered a deliberate and effortful mental act which happens during retrieval, and requires the focus of our awareness. Recent fMRI studies hint at the possibility that some forms of hippocampus-dependent inference can also occur during encoding and possibly also outside of awareness. Here, we sought to further explore the feasibility of hippocampal implicit inference, and specifically address the temporal evolution of implicit inference using intracranial EEG. Presurgical epilepsy patients with hippocampal depth electrodes viewed a sequence of word pairs, and judged the semantic fit between two words in each pair. Some of the word pairs entailed a common word (e.g., "winter-red," "red-cat") such that an indirect relation was established in following word pairs (e.g., "winter-cat"). The behavioral results suggested that drawing inference implicitly from past experience is feasible because indirect relations seemed to foster "fit" judgments while the absence of indirect relations fostered "do not fit" judgments, even though the participants were unaware of the indirect relations. A event-related potential (ERP) difference emerging 400 ms post-stimulus was evident in the hippocampus during encoding, suggesting that indirect relations were already established automatically during encoding of the overlapping word pairs. Further ERP differences emerged later post-stimulus (1,500 ms), were modulated by the participants' responses and were evident during encoding and test. Furthermore, response-locked ERP effects were evident at test. These ERP effects could hence be a correlate of the interaction of implicit memory with decision-making. Together, the data map out a time-course in which the hippocampus automatically integrates memories from discrete but related episodes to implicitly influence future decision making.

Cytoskeletal motor-driven active self-assembly in in vitro systems.

Molecular motor-driven self-assembly has been an active area of soft matter research for the past decade. Because molecular motors transform chemical energy into mechanical work, systems which employ molecular motors to drive self-assembly processes are able to overcome kinetic and thermodynamic limits on assembly time, size, complexity, and structure. Here, we review the progress in elucidating and demonstrating the rules and capabilities of motor-driven active self-assembly. We focus on the types of structures created and the degree of control realized over these structures, and discuss the next steps necessary to achieve the full potential of this assembly mode which complements robotic manipulation and passive self-assembly.

Controlling self-assembly of microtubule spools via kinesin motor density.

Active self-assembly, in which non-thermal energy is consumed by the system to put together building blocks, allows the creation of non-equilibrium structures and active materials. Microtubule spools assembled in gliding assays are one example of such non-equilibrium structures, capable of storing bending energies on the order of 10(5) kT. Although these structures arise spontaneously in experiments, the origin of microtubule spooling has long been debated. Here, using a stepwise kinesin gradient, we demonstrate that spool assembly can be controlled by the surface density of kinesin motors, showing that pinning of microtubules due to dead motors plays a dominant role in spool initiation.

The effect of oxidative stress on the bursopentin peptide structure: a theoretical study.

Bursopentin (BP(5), H-Cys(1)-Lys(2)-Arg(3)-Val(4)-Tyr(5)-OH), found in the bursa Fabricius of the chicken, is a pentapeptide that protects the organism from oxidative stress by reducing the intracellular generation of reactive oxygen species. Hydrogen abstraction, a common oxidative reaction occurring in proteins, often results in the formation of d amino acid residues. To study the effect of this phenomenon on the structure of bursopentin, each of its residues were converted from the l configuration to the d configuration, and the structures of these peptide epimers were compared to that of the wild-type bursopentin. The conformations, secondary structures, compactness and hydrogen bonding of bursopentin were compared to its epimers using molecular dynamics simulations and first principles quantum chemical computations. It was discovered that the repulsion between the side chains of Lys(2) and Arg(3) influenced the conformation of the peptide regardless of the configuration of these residues. Epimerisation of the Val(4) and Tyr(5) caused a reduction in the compactness of bursopentin. In all cases, the occurrence of a turn structure was relatively high, especially when Arg(3) was in the d configuration. Thermodynamic analysis of the epimerisation process showed that the formation of d amino acid residues is favourable.

Patterns of antihypertensive prescribing, discontinuation and switching among a Hong Kong Chinese population from over one million prescriptions.

To evaluate the prescription, discontinuation and switching profiles of antihypertensive agents, we studied computerized records for patients prescribed antihypertensive drugs in government primary care clinics of Hong Kong between January 2004 and June 2007, which include 1069836 antihypertensive drug visits (representing 67028 patients). The most commonly prescribed drugs were calcium channel blockers (CCBs, 49%), beta-blockers (BBs, 46%) and angiotensin-converting enzyme inhibitors (ACEIs, 19%). Although thiazide diuretic prescribing was low (13%) and on the decline (from 14% in 2004 to 12% in 2007), prescription of ACEIs was rising (from 16% in 2004 to 23% in 2007); drug discontinuation was highest for BBs (21%) and lowest for CCBs (12%) and the high rates of discontinuation in BBs remained apparent after controlling for confounders. CCBs may be particularly favourable antihypertensive drugs in Chinese and the low use of thiazide diuretics warrants further clinical and cost effectiveness studies among Chinese.

Effectiveness of a Chinese herbal medicine preparation in the treatment of cough in uncomplicated upper respiratory tract infection: a randomised double-blinded placebo-control trial.

BACKGROUND: Rigorous scientific and well-designed clinical trials to evaluate the effect of traditional Chinese medicine (TCM) is lacking. We, therefore, designed this study to evaluate the effectiveness of a commonly used TCM preparation in treating acute cough of uncomplicated URTI in adults and to search for a safe, effective and affordable alternative treatment for this common condition. METHODS: A randomised, double-blinded, placebo-control study comparing this TCM preparation with a placebo was conducted in 82 patients who attended the Family Medicine Training Centre, Prince of Wales Hospital, Hong Kong between November and December, 2003. The TCM herbal preparation includes nine commonly used TCM herbs for cough such as chuanbei, fangfeng, jiegeng, gancao and baibu (see Table 1). The treatment lasted for 5 days and patients were followed-up for another 6 days. Patients were asked to fill in a cough score and validated Leicester cough questionnaire (LCQ). RESULTS: 62 patients (75.6%) had completed the trial and no adverse effects were reported. Both intervened and control groups had improved in cough score and LCQ in the follow-up period, despite no overall statistical significance was observed in the differences of scores between the two groups. Women taking TCM had significantly fewer problems with sputum production (p = 0.03) and older subjects (>35 years of age) reported a significant improvement in hoarseness (p = 0.05) when compared to those using placebo. CONCLUSION: TCM was well-tolerated and received among the Hong Kong Chinese population. This TCM preparation appeared to have some benefits in the treatment of cough. Future research on TCM should concentrate more on commonly encountered conditions such as UTRI and cough. Our experience on the sensitivity of assessment tools used in detecting subtle differences in an otherwise self-limiting illness and clinical trial methodology when applying the underlying theory of how TCM works in disease management was invaluable.

A comparison of soft-tissue anchors in tendo achilles reattachment.

This prospective study evaluated four soft-tissue fixation modalities, used in seven different combinations, to reattach the tendo Achilles in 34 cadaveric specimens. Ultimate loads, elastic moduli, and modes of failure were evaluated by loading the specimen in a cantilevered fashion on an Instron. Mann-Whitney U tests were performed to compare the failure load data for statistical significance. Although the use of two Mitek SuperAnchors showed better load resistance than one anchor (p < .01), there was no significant improvement between using two or three anchors (one anchor 116 +/- 24 N, two anchors 234 +/- 21 N, three anchors 277 +/- 80 N). Two Bionx Bankart Tacks demonstrated no significant difference over using a single tack (one tack 178 +/- 57 N, two tacks 214 +/- 86 N). No statistical difference was observed between the screw and washer systems (screw with polyacetal resin washer 307 +/- 80 N, screw with metal washer 290 +/- 81 N). Both screw and washer systems did show greater stability when compared with a single Mitek SuperAnchor (p < .01) or a single Bionx Bankart Tack (p < .05). Similar analyses using the Mann-Whitney U tests were performed on the elastic modulus data. Analysis of the displacement data among all groups showed no statistical difference. Observations of the mode of failure exhibited 86% of Mitek SuperAnchor failed secondary to suture, and 70% of the Bionx Bankart Tack and 90% of the screw and washer systems failed because of the tendon shearing around the fixation. The comparisons of cost-effectiveness among the fixations showed the Synthes screw and polyacetal resin spiked washer to have the lowest cost to load ratio ($0.15/N).

First metatarsophalangeal joint arthrodesis: quantitative mechanical testing of six-hole dorsal plate versus crossed screw fixation in cadaveric specimens.

Quantitative strength analysis of first metatarsophalangeal joint arthrodesis was performed using two fixation techniques: a small 6-hole plate with an interfragmentary screw or two crossed lag screws. Twelve matched-pair fresh-frozen cadaveric specimens (24 trials) were used for direct comparison of each of the two fixation techniques. All joint surfaces were prepared with power conical reamers utilizing a standard technique. The fixation construct was stressed to failure on each specimen using a computer-integrated materials tester. Fixation stiffness defined as force (load) over displacement and point of ultimate failure was evaluated. The six-hole plate and interfragmentary screw fixation method was a statistically stiffer form of fixation (p > .01) and displayed a greater point of ultimate failure (p > .002) under the laboratory conditions.

Retrospective analysis of Silastic implant arthroplasty of the first metatarsophalangeal joint.

The purpose of this study was to evaluate the outcome of implant arthroplasty according to subjective, biomechanic, and radiographic parameters over a long period of time. Implants in 40 feet (27 patients) were analyzed at an average follow-up time of 8.25 years and a mean patient age of 63. The results were consistent with the subjective findings of previous studies that demonstrated that most patients were satisfied with the procedure. Ninety-six percent of the patients in this study confirmed they would undergo the procedure a second time. The radiographic results did not demonstrate a high incidence of implant fracture as previously reported. This review suggests that implants can be effective when used with patients who are carefully selected according to age, activity level, and diagnosis.

Retrospective analysis of first metatarsal phalangeal arthrodesis.

A retrospective evaluation of first metatarsophalangeal joint arthrodesis was performed on nine patients (12 feet) using two fixation techniques: a small compression plate and screws or two crossed lag screws. The joint surfaces were prepared with power conical reamers to allow for joint alignment and subsequent fusion. The average follow-up time was 6.9 months (range, 1.3 to 15 months) and, to date, all feet are successfully fused. No major postoperative complications or removal of internal fixation devices were noted in our retrospective study. This surgical technique was effective and reliable in achieving first metatarsophalangeal joint fusion, and it may serve as an alternative procedure to silicone implant or resection joint arthroplasty.

Design, biological activity and NMR-solution structure of a DNA analogue of yeast tRNA(Phe) anticodon domain.

Design of biologically active DNA analogues of the yeast tRNA(Phe) anticodon domain, tDNAPheAC, required the introduction of a d(m5C)-dependent, Mg(2+)-induced structural transition and the d(m1G) disruption of an intra-loop dC.dG base pair. The modifications were introduced at residues corresponding to m5C-40 and wybutosine-37 in tRNA(Phe). Modified tDNAPheAC inhibited translation by 50% at a tDNAPheAC:ribosome ratio of 8:1. The molecule's structure has been determined by NMR spectroscopy and restrained molecular dynamics with an overall r.m.s.d. of 2.8 A and 1.7 A in the stem, and is similar to the tRNA(Phe) anticodon domain in conformation and dimensions. The tDNAPheAC structure may provide a guide for the design of translation inhibitors as potential therapeutic agents.

Modified nucleoside-dependent transition metal binding to DNA analogs of the tRNA anticodon stem/loop domain.

Biologically active DNA analogs of tRNAPhe (tDNAPhe) were used to investigate metal ion interaction with tRNA-like structures lacking the 2'OH. Binding of Mg2+ to the 76 oligonucleotide tDNAPhe, monitored by circular dichroism spectroscopy, increased base stacking and thus the conformational stability of the molecule. Mg2+ binding was dependent on a d(m5C) in the anticodon region. In contrast to Mg2+, Cd2+ decreased base stacking interactions, thereby destabilizing the molecule. Since alterations in the anticodon region contributed to most of the spectral changes observed, detailed studies were conducted with anticodon hairpin heptadecamers (tDNAPheAC). The conformation of tDNAPheAC-d(m5C) in the presence of 1 mM Cd2+, Co2+, Cr2+, Cu2+, Ni2+, Pb2+, VO2+ or Zn2+ differed significantly from that of the biologically active structure resulting from interaction with Mg2+, Mn2+ or Ca2+. Nanomolar concentrations of the transition metals were sufficient to denature the tDNAPheAC-d(m5C) structure without catalyzing cleavage of the oligonucleotide. In the absence of Mg2+ and at [Cd2+] to [tDNAPheAC-d(m5C)] ratios of approximately 0.2-1.0, tDNAPheAC-d(m5C40) formed a stable conformation with one Cd2+ bound with a Kd = 3.7 x 10(-7) M. In contrast to Mg2+, Cd2+ altered the DNA analogs without discriminating between modified and unmodified tDNAPheAC. This ability of transition metals to disrupt higher order DNA structures, and possibly RNA, at microM concentrations, in vitro, demonstrates that these structures are potential targets in chronic metal exposure, in vivo.