Efficacy of rehabilitation interventions in rheumatic conditions

All industrialized nations are facing a crisis in health care financing. Rising expectations coupled with increasing specialization and technologic capacities have forced health care payers to examine their assumptions and to seek data on the outcomes of medical interventions. Clinical investigators who have been taught to use randomized controlled trials that evaluate efficacy under experimental conditions have been redirected toward studies that can help answer health policy questions. Such studies examine the effectiveness of interventions in more realistic settings on a richer array of patient-centered outcomes such as function and consider cost effectiveness and relative cost effectiveness. Rehabilitation interventions, which are by and large pragmatic, have never had a strong scientific basis grounded in controlled trials, and this lack of evidence has put tremendous pressure on clinicians to justify their practices. In this article, we review the recent literature on effectiveness of rehabilitation interventions in rheumatic disorders

Internal structure and origin of the double reefs of North Bohol and the Olango reef flat (Philippines)

Nine holes were drilled with a submersible hydraulic drill into the slopes and reef flats of the Caubyna and Calituban reefs as well as of Olango Flat. The maximum depth of core penetration was 11 m. 14C ages showed that the Caubyan and Caltituban reefs were formed within the last 6,000 years. Corals settled on a pre-existing relief prallel to the island of Bohol, building a framework for other carbonate-producing organisms. The reef flat south of Olango has a different structure. Formation took place during a Pleistocene high sea level, e.g. 125,000 years ago

Is Misoprostol Cost-effective in the Prevention of Nonsteroidal Anti-inflammatory Drug—Induced Gastropathy in Patients With Chronic Arthritis?

Whether misoprostol, a synthetic prostaglandin E1 analogue, should be routinely prescribed along with nonsteriodal anti-inflammatory drugs (NSAIDS) to prevent gastric damage is of great clinical importance and has profound cost implications. No consensus exists on whether misoprostol cotherapy results in a cost-saving, is cost-effective, or is costly. The different conclusions reached by five economic evaluations of misoprostol can be explained solely by the assumed absolute risk reduction of symptomatic ulcer, which was more than seven times greater in the studies that concluded that misoprostol was cost-effective than in a study that concluded misoprostol to be costly. Since no study has directly shown the effectiveness of misoprostol cotherapy in preventing clinically significant ulcer disease (ie, hemorrhage and preforation), it is impossible to judge which assumptions are most appropriate. The absence of firm data on the rate of NSAID-induced gastric ulcers reduced by misoprostol makes it impossible to conclude whether it is cost-effective in patients with chronic arthritis who use NSAIDS

Melatonin synthesis in the human pineal gland

Poster presentation: The mammalian pineal organ is a peripheral oscillator, depending on afferent information from the so-called master clock in the suprachiasmatic nuclei of the hypothalamus. One of the best studied outputs of the pineal gland is the small and hydrophobic molecule melatonin. In all vertebrates, melatonin is synthesized rhythmically with high levels at night, signalling the body the duration of the dark period. Changes or disruptions of melatonin rhythms in humans are related to a number of pathophysiological disorders, like Alzheimer's disease, seasonal affective disorder or the Smith-Magenis-Syndrome. To use melatonin in preventive or curative interferences with the human circadian system, a complete understanding of the generation of the rhythmic melatonin signal in the human pineal gland is essential. Melatonin biosynthesis is best studied in the rodent pineal gland, where the activity of the penultimate and rate-limiting enzyme, the arylalkylamine N-acetyltransferase (AA-NAT), is regulated on the transcriptional level, whereas the regulatory role of the ultimate enzymatic step, achieved by the hydroxyindole O-methyltransferase (HIOMT), is still under debate. In rodents, Aa-nat mRNA is about 100-fold elevated during the night in response to adrenergic stimulation of the cAMP-signalling pathway, with AA-NAT protein levels closely following this dynamics. In contrast, in all ungulates studied so far (cow, sheep), a post-transcriptional regulation of the AA-NAT is central to determine rhythmic melatonin synthesis. AA-NAT mRNA levels are constantly elevated, and lead to a constitutive up-regulation of AA-NAT protein, which is, however, rapidly degraded via proteasomal proteolysis during the day. AA-NAT proteolysis is only terminated upon the nocturnal increase in cAMP levels. Similar to ungulates, a post-transcriptional control of this enzyme seems evident in the pineal gland of the primate Macaca mulatta. Studies on the molecular basis of melatonin synthesis in the human being are sparse and almost exclusively based on phenomenological data, derived from non-invasive investigations. Yet the molecular mechanisms underlying the generation of the hormonal message of darkness can currently only be deciphered using autoptic material. We therefore analyzed in human post-mortem pineal tissue Aa-nat and Hiomt mRNA levels, AA-NAT and HIOMT enzyme activity, and melatonin levels for the first time simultaneously within tissue samples of the same specimen. Here presented data show the feasibility of this approach. Our results depict a clear diurnal rhythm in AA-NAT activity and melatonin content, despite constant values for Aa-nat and Hiomt mRNA, and for HIOMT activity. Notably, the here elevated AA-NAT activity during the dusk period does not correspond to a simultaneous elevation in melatonin content. It is currently unclear whether this finding may suggest a more important role of the ultimate enzyme in melatonin synthesis, the HIOMT, for rate-limiting the melatonin rhythm, as reported recently for the rodent pineal gland. Thus, our data support for the first time experimentally that post-transcriptional mechanisms are responsible for the generation of rhythmic melatonin synthesis in the human pineal gland

Internal wave kinematics in the upper tropical Atlantic

Horizontal velocity and temperature measurements observed from a two-dimensional array of moored instruments, mooring Fl, are analysed to describe the near-surface internal wave field in the GATE (GARP Atlantic Tropical Experiment) C-scale area. Spectral properties indicate strong deviations from the Garrett and Munk (1972, 1975) deep ocean internal wave models. The frequency spectrum in the upper pycnocline is dominated by three energetic bands centered at 0.0127 (inertial frequency), 0.08 (M2-tidal frequency) and 3 cph. The latter frequency band does not correspond to the local Brunt Väisälä frequency (< 10 cph) and contains about one half of the total internal wave energy of fluctuations with periods less than 10 hours. Cross-spectral analysis of the high frequency internal waves yields corresponding wavelengths of order 1 km consistent with westward propagating first mode wave groups, if the effect of Doppler shift due to a strong mean current is taken into accoun

Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data

BACKGROUND: Over the past decade our laboratory has focused on understanding how soluble cytoskeleton-associated proteins interact with membranes and other lipid aggregates. Many protein domains mediating specific cell membrane interactions appear by fluorescence microscopy and other precision techniques to be partially inserted into the lipid bilayer. It is unclear whether these protein-lipid-interactions are dependent on shared protein motifs or unique regional physiochemistry, or are due to more global characteristics of the protein. RESULTS: We have developed a novel computational program that predicts a protein's lipid-binding site(s) from primary sequence data. Hydrophobic labeling, Fourier transform infrared spectroscopy (FTIR), film balance, T-jump, CD spectroscopy and calorimetry experiments confirm that the interfaces predicted for several key cytoskeletal proteins (alpha-actinin, Arp2, CapZ, talin and vinculin) partially insert into lipid aggregates. The validity of these predictions is supported by an analysis of the available three-dimensional structural data. The lipid interfaces predicted by our algorithm generally contain energetically favorable secondary structures (e.g., an amphipathic alpha-helix flanked by a flexible hinge or loop region), are solvent-exposed in the intact protein, and possess favorable local or global electrostatic properties. CONCLUSION: At present, there are few reliable methods to determine the region of a protein that mediates biologically important interactions with lipids or lipid aggregates. Our matrix-based algorithm predicts lipid interaction sites that are consistent with the available biochemical and structural data. To determine whether these sites are indeed correctly identified, and whether use of the algorithm can be safely extended to other classes of proteins, will require further mapping of these sites, including genetic manipulation and/or targeted crystallography