A marker-free registration method for standing X-ray panorama reconstruction for hip-knee-ankle axis deformity assessment.

Accurate measurement of knee alignment, quantified by the hip-knee-ankle (HKA) angle (varus-valgus), serves as an essential biomarker in the diagnosis of various orthopaedic conditions and selection of appropriate therapies. Such angular deformities are assessed from standing X-ray panoramas. However, the limited field-of-view of traditional X-ray imaging systems necessitates the acquisition of several sector images to capture an individual's standing posture, and their subsequent 'stitching' to reconstruct a panoramic image. Such panoramas are typically constructed manually by an X-ray imaging technician, often using various external markers attached to the individual's clothing and visible in two adjacent sector images. To eliminate human error, user-induced variability, improve consistency and reproducibility, and reduce the time associated with the traditional manual 'stitching' protocol, here we propose an automatic panorama construction method that only relies on anatomical features reliably detected in the images, eliminating the need for any external markers or manual input from the technician. The method first performs a rough segmentation of the femur and the tibia, then the sector images are registered by evaluating a distance metric between the corresponding bones along their medial edge. The identified translations are then used to generate the standing panorama image. The method was evaluated on 95 patient image datasets from a database of X-ray images acquired across 10 clinical sites as part of the screening process for a multi-site clinical trial. The panorama reconstruction parameters yielded by the proposed method were compared to those used for the manual panorama construction, which served as gold-standard. The horizontal translation differences were 0:43 ± 1:95 mm 0:26 ± 1:43 mm for the femur and tibia respectively, while the vertical translation differences were 3:76 ± 22:35 mm and 1:85 ± 6:79 mm for the femur and tibia, respectively. Our results showed no statistically significant differences between the HKA angles measured using the automated vs. the manually generated panoramas, and also led to similar decisions with regards to the patient inclusion/exclusion in the clinical trial. Thus, the proposed method was shown to provide comparable performance to manual panorama construction, with increased efficiency, consistency and robustness.

Image-Guided Interventions: We've come a long way, but are we there?

While the term "image-guided surgery" has gained popularity fairly recently, the use of imaging for medical interventions dates as far back as the beginning of the 20th century. Dr. George H. Gray of Lynn, Massachusetts, reported in his 1908 article "X-rays in Surgical Work," published in volume 2 of the Journal of Therapeutics and Dietetics, that "the one great stride in the handling of difficult cases was the accurate diagnosis made possible by the use of the X-rays." His story points to the day when a seamstress presented to his office with a broken sewing needle embedded in her hand. Thanks to the use of the recently discovered X-rays by Wilhelm Conrad Roentgen, the father of diagnostic radiology, Gray was able not only to confirm that the needle was indeed embedded in her hand but also to locate its parts, saving "an hour's hunting as some had previously done and then often failed."

The effect of the nano-silica support on the catalytic reduction of water by gold, silver and platinum nanoparticles--nanocomposite reactivity.

Pt°-NPs, prepared by the reduction of Pt(IV) salts with borohydride, do not catalyse the reduction of water in the presence of the strongly-reducing ˙C(CH3)2OH radicals. However, supporting the same metal nanoparticles (M°-NPs) with SiO2 alters the catalytic properties enabling the reaction. This effect depends both on the nature of M° and concentration of the composite nanoparticles. At low nanocomposite concentration: for M = Au nearly no effect is observed; for M = Ag the support decreases the catalytic reduction of water and for M = Pt the support initiates the catalytic process. At high nanocomposite concentration: for M = Au the reactivity is considerably lower and for M = Ag or Pt no catalysis is observed. Furthermore, for M = Ag or Pt H2 reduces the ˙C(CH3)2OH radicals.

Comparison of electrically evoked cortical potential thresholds generated with subretinal or suprachoroidal placement of a microelectrode array in the rabbit.

The aim of the study was to directly compare the threshold electrical charge density of the retina (retinal threshold) in rabbits for the generation of electrical evoked potentials (EEP) by delivering electrical stimulation with a custom-made microelectrode array (MEA) implanted into either the subretinal or suprachoroidal space. Nine eyes of seven Dutch-belted rabbits were studied. The electroretinogram (ERG), visual evoked potentials (VEP) and EEP were recorded. Electrodes for the VEP and EEP were placed on the dura mater overlying the visual cortex. The EEP was recorded following electrical stimulation of the MEA placed either subretinally beneath the visual streak of the retina or in the suprachoroidal space in the rabbit eye. An ab externo approach was used for placement of the MEA. Liquid perfluorodecaline (PFCL; 0.4 ml) was placed within the vitreous cavity to flatten the neurosensory retina on the MEA after subretinal implantation. The retinal threshold for generation of an EEP was determined for each MEA placement by three consecutive measurements consisting of 100 computer-averaged recordings. Animals were sacrificed at the conclusion of the experiment and the eyes were enucleated for histological examination. The retinal threshold to generate an EEP was 9 +/- 7 nC (0.023 +/- 0.016 mC cm(-2)) within the subretinal space and 150 +/- 122 nC (0.375 +/- 0.306 mC cm(-2)) within the suprachoroidal space. Histology showed disruption of the outer retina with subretinal but not suprachoroidal placement. The retinal threshold to elicit an EEP is significantly lower with subretinal placement of the MEA compared to suprachoroidal placement (P < 0.05). The retinal threshold charge density with a subretinal MEA is well below the published charge limit of 1 mC cm(-2), which is the level below which chronic stimulation of the retina is considered necessary to avoid tissue damage (Shannon 1992 IEEE Trans. Biomed. Eng. 39 424-6).

Effects of DNA sequence and structure on binding of RecA to single-stranded DNA.

Fluorescence anisotropy is used to follow the binding of RecA to short single-stranded DNA (ssDNA) sequences (39 bases) at low DNA and RecA concentration where the initial phase of polymerization occurs. We observe that RecA condensation is extremely sensitive to minute changes in DNA sequences. RecA binds strongly to sequences that are rich in pyrimidines and that lack significant secondary structure and base stacking. We find a correlation between the DNA folding free energy and the onset concentration for RecA binding. These results suggest that the folding of ssDNA and base stacking represent a barrier for RecA binding. The link between secondary structure and binding affinity is further analyzed with two examples: discrimination between two naturally occurring polymorphisms differing by one base and RecA binding on a molecular beacon. A self-assembly model is introduced to explain these observations. We propose that RecA may be used to sense ssDNA sequence and structure.

Repetitive transcranial magnetic stimulation is as effective as electroconvulsive therapy in the treatment of nondelusional major depressive disorder: an open study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS), a new method for the stimulation of the central nervous system, is being proposed as a potential new treatment in patients with major depressive disorder (MDD). We tested the hypothesis that rTMS would be as effective as electroconvulsive therapy (ECT) in patients with MDD. METHODS: Forty patients with MDD referred for ECT were randomly assigned to either ECT or rTMS. Repetitive transcranial magnetic stimulation was performed at 90% power of the motor threshold. The stimulation frequency was 10 Hz for either 2 sec (first eight patients) or 6 sec (final 12 patients) for 20 trains. Patients were treated for up to 20 treatment days. Electroconvulsive therapy was performed according to standard protocols. RESULTS: Overall patients responded best to ECT (chi(2) = 3.8, p <.05). Patients with MDD and psychosis responded significantly better to ECT (chi(2) = 9.2, p <. 01), whereas MDD patients without psychosis responded similarly to both treatments (chi(2) = 0.0, ns). The analysis of variance with repeated measures of clinical variables for the whole sample revealed significant treatment effects for both groups; however, interaction between group and treatment was seen only for the Global Assessment of Function and the Sleep assessment. When the psychosis-nonpsychosis grouping was considered, patients with psychosis responded dramatically better to ECT in all assessments, whereas those without psychosis responded similarly to both treatments. CONCLUSIONS: Overall ECT was a more potent treatment for patients with MDD, this being particularly evident in patients with MDD and psychosis; however, in patients with MDD without psychosis the effects of rTMS were similar to those of ECT. The results we report are encouraging and support an important role for rTMS in the treatment of severe MDD; however, additional blinded studies are needed to precisely define this role.

Pearling in cells: a clue to understanding cell shape.

Gradual disruption of the actin cytoskeleton induces a series of structural shape changes in cells leading to a transformation of cylindrical cell extensions into a periodic chain of "pearls." Quantitative measurements of the pearling instability give a square-root behavior for the wavelength as a function of drug concentration. We present a theory that explains these observations in terms of the interplay between rigidity of the submembranous actin shell and tension that is induced by boundary conditions set by adhesion points. The theory allows estimation of the rigidity and thickness of this supporting shell. The same theoretical considerations explain the shape of nonadherent edges in the general case of untreated cells.

The treatment of kleptomania with serotonin reuptake inhibitors.

Kleptomania is characterized by an irresistible impulse to steal objects not needed for personal use or for their monetary value. Several recent case reports have shown that Serotonin Specific Reuptake Inhibitors (SSRIs) could be effective in the treatment of kleptomania just as it is in other obsessive-compulsive spectrum disorders. We report five cases of kleptomania patients who were successfully treated with fluoxetine or paroxetine in combination with a psychotherapeutic intervention. In one case, the discontinuation of the medication repeatedly led to the resurgence of the kleptomanic behavior. Our case series illustrates the effectiveness of SSRIs in kleptomania. It thus supports the assumption that this syndrome involves a dysfunctional serotoninergic mechanism.

Dynamic excitations in membranes induced by optical tweezers.

We present the phenomenology of transformations in lipid bilayers that are excited by laser tweezers. A variety of dynamic instabilities and shape transformations are observed, including the pearling instability, expulsion of vesicles, and more exotic ones, such as the formation of passages. Our physical picture of the laser-membrane interaction is based on the generation of tension in the bilayer and loss of surface area. Although tension is the origin of the pearling instability, it does not suffice to explain expulsion of vesicles, where we observe opening of giant pores and creeping motion of bilayers. We present a quantitative theoretical framework to understand most of the observed phenomenology. The main hypothesis is that lipid is pulled into the optical trap by the familiar dielectric effect, is disrupted, and finally is repackaged into an optically unresolvable suspension of colloidal particles. This suspension, in turn, can produce osmotic pressure and depletion forces, driving the observed transformations.

Localized dynamic light scattering: a new approach to dynamic measurements in optical microscopy.

We present a new approach to probing single-particle dynamics that uses dynamic light scattering from a localized region. By scattering a focused laser beam from a micron-size particle, we measure its spatial fluctuations via the temporal autocorrelation of the scattered intensity. We demonstrate the applicability of this approach by measuring the three-dimensional force constants of a single bead and a pair of beads trapped by laser tweezers. The scattering equations that relate the scattered intensity autocorrelation to the particle position correlation function are derived. This technique has potential applications for measurement of biomolecular force constants and probing viscoelastic properties of complex media.

Valproic acid in ultra-rapid cycling: a case report.

Valproic acid has been proven to be efficient in the treatment of bipolar affective disorders as an adjunctive agent to lithium and carbamazepine. Recently, its efficacy in rapid cycling states has attracted interest. We present the case of a male patient with bipolar affective disorder who developed an extreme state of ultra-rapid cycling (48-h cycles). Only the addition of valproic acid therapy to prior lithium treatment succeeded in curtailing the ultra-rapid cycling. Several issues regarding ultra-rapid cycling and valproate's efficacy in bipolar disorder are discussed.

Nightmares related to fluoxetine treatment.

Sleep disturbances are found in most depressive patients. Serotonin reuptake inhibitors, such as fluoxetine hydrochloride, seem to improve sleep by changing the depressive affect and the underlying biological mechanisms. Insomnia is an occasional adverse effect of the medication, but it was shown that only 2-3% of the patients with fluoxetine-induced insomnia discontinued the drug for this reason. We could not find any report of nightmares or night terrors under fluoxetine treatment. We report on four patients who experienced nightmares on fluoxetine monotherapy.

Tyrphostins inhibit follicle-stimulating hormone-mediated functions in cultured rat ovarian granulosa cells.

FSH induces the expression of cholesterol side-chain cleavage cytochrome P450 (P450scc) in rat ovarian granulosa cells. The present study reveals that the tyrphostin AG18, a member of novel protein tyrosine kinase inhibitors, can arrest the FSH-induced synthesis of P450scc with an apparent IC50 of 30 microM. Total inhibition of P450scc expression was achieved at 80 microM AG18. AG18-mediated inhibition of P450scc was also observed when the enzyme was induced by prostaglandin E2, forskolin, or 8-bromo-cAMP. Studies examining functional LH receptors showed that the tyrphostin inhibits the expression of FSH-induced LH receptors. The drug did not affect FSH-induced cAMP accumulation, suggesting that it may interfere with the flow of FSH signal transduction at a site distal intracellular accumulation of cAMP. Control experiments demonstrated that the inhibitory action of AG18 was reversible, did not hamper total protein synthesis in the cells, and did not change the adenine nucleotide (ATP:ADP:AMP) ratio or their levels in the treated cells. A cell-free assay of cAMP-dependent protein kinase showed that the tyrphostin AG18 does not affect this enzyme activity up to concentrations above 200 microM. These results suggest that a putative tyrosine kinase activity is involved in the gonadotropin signal transduction pathway leading to expression of functional genes in ovarian cells.