TB or not to be? Kikuchi-Fujimoto disease: a rare but important differential for TB.

A 29-year-old British Pakistani woman presented with a 2-month history of drenching fevers, night sweats, lethargy and tender cervical and axillary lymphadenopathy. Initial investigations, bloods and imaging were unremarkable. Fever persisted during her admission, and treatment for tuberculosis (TB) lymphadenitis was started postbiopsy until histology confirmed a diagnosis of Kikuchi-Fujimoto's disease (KFD). KFD has a non-specific presentation of fever, night sweats and lymphadenopathy and commonly raises a clinical suspicion of a number of other serious conditions such as TB, lymphoma, HIV, systemic lupus erythematous, toxoplasmosis and infectious mononucleosis. Although rare, KFD should be considered to be a differential diagnosis for fever of unknown origin and tender lymphadenopathy in otherwise well individuals. This case demonstrates the importance of a timely histological biopsy diagnosis to prevent an incorrect diagnosis and administration of unnecessary medications.

Methods to study the development, anatomy, and function of the zebrafish inner ear across the life course.

The inner ear is a remarkably intricate structure able to detect sound, motion, and gravity. During development of the zebrafish embryo, the ear undergoes dynamic morphogenesis from a simple epithelial vesicle into a complex labyrinth, consisting of three semicircular canals and three otolithic sensory organs, each with an array of differentiated cell types. This microcosm of biology has led to advances in understanding molecular and cellular changes in epithelial patterning and morphogenesis, through to mechanisms of mechanosensory transduction and the origins of reflexive behavior. In this chapter, we describe different methods to study the zebrafish ear, including high-speed imaging of otic cilia, confocal microscopy, and light-sheet fluorescent microscopy. Many dyes, antibodies, and transgenic lines for labeling the ear are available, and we provide a comprehensive review of these resources. The developing ear is amenable to genetic, chemical, and physical manipulations, including injection and transplantation. Chemical modulation of developmental signaling pathways has paved the way for zebrafish to be widely used in drug discovery. We describe two chemical screens with relevance to the ear: a fluorescent-based screen for compounds that protect against ototoxicity, and an in situ-based screen for modulators of a signaling pathway involved in semicircular canal development. We also describe methods for dissection and imaging of the adult otic epithelia. We review both manual and automated methods to test the function of the inner ear and lateral line, defects in which can lead to altered locomotor behavior. Finally, we review a collection of zebrafish models that are generating new insights into human deafness and vestibular disorders.

The cutlery effect: do designed products for people with disabilities stigmatise them?

The purpose of this study was to investigate of how assistive cutlery design effects perception of the user. Studies regarding the usage and development of assistive cutlery have primarily focused on the ergonomics, whereas research into the aesthetics of assistive cutlery has been minimal. A method based on Canter's "Room Inference Protocol" from the field of environmental psychology was used to evaluate the aesthetics of the assistive cutlery. A series of images were digitally composited and a survey was deployed online, with an outcome of 562 usable responses. The results demonstrated that the female model with assistive cutlery was perceived to be less attractive, less stylish and less sporty in comparison with the male model that was utilising identical pieces of assistive cutlery. The research contributes to the existing literature in the field, complimenting the study by Torrens and Smith and validating the need for greater aesthetic consideration in addition to an ergonomically acceptable response for assistive cutlery. This in turn highlights the importance of industrial design for the context and adaptations of use, rather than just a design response given to the physical manifestation of a product. Implications for Rehabilitation Reduced grip can be not only physically debilitating but also socially isolating through stigmatisation. Current assistive cutlery may be ergonomically sound, but aesthetically lacking. Large, multinational study demonstrates significant gender effect relating to the perception of women using these devices.

The mere exposure effect for consumer products as a consequence of existing familiarity and controlled exposure.

The finding that repeated exposure to a stimulus enhances attitudes directed towards it is a well-established phenomenon. Despite this, the effects of exposure to products are difficult to determine given that they could have previously been exposed to participants any number of times. Furthermore, factors other than simple repeated exposure can influence affective evaluations for stimuli that are meaningful. In our first study, we examined the influence of existing familiarity with common objects and showed that the attractiveness of shapes representing common objects increases with their rated commonness. In our second study, we eliminated the effects of prior exposure by creating fictitious yet plausible products; thus, exposure frequency was under complete experimental control. We also manipulated the attention to be drawn to the products' designs by placing them in contexts where their visual appearance was stressed to be important versus contexts in which it was indicated that little attention had been paid to their design. Following mere exposure, attractiveness ratings increased linearly with exposure frequency, with the slope of the function being steeper for stimuli presented in an inconspicuous context-indicating that individuals engage in more deliberate processing of the stimuli when attention is drawn to their visual appearance.

Towards a visual recognition threshold: new instrument shows humans identify animals with only 1ms of visual exposure.

The human visual system is very adept at extracting categorical information from complex scenes with only the briefest of exposure. Here we show that information from visual scenes can be processed to the level of identification with formally unattainable, ultra-brief (1ms) presentations. This brief presentation time is afforded by a new instrument, the light-emitting diode (LED) tachistoscope, in which a liquid crystal display (LCD) is illuminated externally by a brief LED flash after LCD steady-state is reached, such that image onset and offset timing can be precisely controlled. Photographs of animals were presented with or without backgrounds for 1ms and 10ms. The results indicate that visual recognition of objects benefits from presenting them in isolation rather than with a background at smaller (1ms) durations. In both conditions, however, animals could be recognised at 1ms at least 83% of the time, possibly due to iconic memory and top-down, feedback mechanisms.

Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets.

AIMS/HYPOTHESIS: Aldosterone concentrations increase in obesity and predict the onset of diabetes. We investigated the effects of aldosterone on glucose homeostasis and insulin secretion in vivo and in vitro. METHODS: We assessed insulin sensitivity and insulin secretion in aldosterone synthase-deficient (As [also known as Cyp11b2](-/-)) and wild-type mice using euglycaemic-hyperinsulinaemic and hyperglycaemic clamps, respectively. We also conducted studies during high sodium intake to normalise renin activity and potassium concentration in As (-/-) mice. We subsequently assessed the effect of aldosterone on insulin secretion in vitro in the presence or absence of mineralocorticoid receptor antagonists in isolated C57BL/6J islets and in the MIN6 beta cell line. RESULTS: Fasting glucose concentrations were reduced in As (-/-) mice compared with wild-type. During hyperglycaemic clamps, insulin and C-peptide concentrations increased to a greater extent in As (-/-) than in wild-type mice. This was not attributable to differences in potassium or angiotensin II, as glucose-stimulated insulin secretion was enhanced in As (-/-) mice even during high sodium intake. There was no difference in insulin sensitivity between As (-/-) and wild-type mice in euglycaemic-hyperinsulinaemic clamp studies. In islet and MIN6 beta cell studies, aldosterone inhibited glucose- and isobutylmethylxanthine-stimulated insulin secretion, an effect that was not blocked by mineralocorticoid receptor antagonism, but was prevented by the superoxide dismutase mimetic tempol. CONCLUSIONS/INTERPRETATION: We demonstrated that aldosterone deficiency or excess modulates insulin secretion in vivo and in vitro via reactive oxygen species and in a manner that is independent of mineralocorticoid receptors. These findings provide insight into the mechanism of glucose intolerance in conditions of relative aldosterone excess.

Spectroscopic noninvasive measurement of hemoglobin compared with capillary and venous values in neonates.

BACKGROUND: Venepuncture-related blood loss is a common cause of neonatal anemia. Currently, this is the only way to obtain hemoglobin levels. This causes distress for the infant but can also lead to the need for blood transfusions. Recently, a new technique for measuring hemoglobin levels non-invasively has been developed to reduce iatrogenic blood loss and pain. OBJECTIVE: To compare hemoglobin levels obtained using a transcutaneous spectroscopic device (Mediscan 2000, MBR Optical Systems, Wuppertal, Germany) with venous or capillary blood samples in neonates. METHODS: Single-center prospective cohort study of term and preterm infants. The white light spectroscopic device was placed on the forearm for 60 s to measure hemoglobin content within 4 h of venous or capillary blood sampling. Pain reactions of the infants were assessed by using a neonatal pain assessment tool. Results were analyzed by Bland-Altman comparison and Wilcoxon signed-rank test. RESULTS: 80 infants (mean gestational age 29.8 +/- 3.8 weeks, mean birth weight 1,300 +/- 690 g) were enrolled into the study. A total of 313 spectroscopic recordings within 2 h of a clinically indicated blood sample (181 capillary, 142 venous) were taken. The correlation coefficient R(2) was 0.96 for capillary/spectroscopic and 0.99 for venous/spectroscopic pairs. Pain scores were significantly less for the spectroscopic measurements (p < 0.01). CONCLUSION: The results show good correlation between the hemoglobin blood levels and spectroscopic measurements. The slightly lower correlation coefficient for the capillary samples demonstrates a naturally higher variance in these values due to the laboratory method.

Development of a light-emitting diode tachistoscope.

This paper describes a new method for rapid visual stimulus delivery, the light-emitting diode (LED) tachistoscope. An array of white LEDs provided a luminous intensity greater than 1,000,000 mcd. This array was placed behind a liquid crystal display (LCD) to function as a backlight; switching it on and off determined the visibility of the display. Commands to illuminate for periods from 1 ms to continuously on were relayed from a computer to the LED array. Changes in luminous intensity at the surface of a LED and the LCD were recorded via oscilloscope. The required duration of light pulses consistently matched the durations displayed, with only microsecond discrepancies due to turn-on and turn-off delays. Images were illuminated on the LCD screen for as little as 1 ms, with the amplitude of the luminance consistent across trials. The LED tachistoscope can be used with any computer to display images extremely briefly, potentially at the submillisecond level, providing superior performance to traditional and computer monitor tachistoscopes.

Maternal depression and medication exposure during pregnancy: comparison of maternal retrospective recall to prospective documentation.

OBJECTIVE: Outcome investigations of prenatal maternal depression and psychotropic exposure rely extensively on maternal retrospective recall. This study compared postnatal recall to prospective documentation of illness and medication exposures. DESIGN: Prospective cohort and retrospective case-control studies. SETTING: Emory Women's Mental Health Program (prospective study) and Emory University Department of Psychology (retrospective study). SAMPLE: A total of 164 women who participated in both the prospective and retrospective studies. METHODS: Women with a history of mental illness were followed during pregnancy for prospective prenatal assessments of depression and medication exposures. At 6 months postpartum, some of these women also participated in a retrospective study during which they were asked to recall prenatal depression and medication use. Agreement between prospective and retrospective documentation of exposures was analysed. MAIN OUTCOME MEASURES: Occurrence of maternal depression during pregnancy and maternal use of pharmacological agents during pregnancy. RESULTS: There was only moderate agreement (k = 0.42) in prospective versus retrospective reporting of prenatal depression. Positive predictive value for recalling depression was 90.4%; however, negative predictive value for denying depression was only 53.8%. Participants accurately recalled psychotropic use but significantly underreported use of nonpsychotropic medications. CONCLUSIONS: Studies using retrospective data collection may be susceptible to systematic recall bias with underreporting of maternal depression and use of nonpsychotropic agents during pregnancy.

Day-surgery laparoscopic cholecystectomy: factors influencing same-day discharge.

BACKGROUND: Day-surgery laparoscopic cholecystectomy (LC) should be the procedure of choice in patients with symptomatic gallstone disease. This article assesses feasibility, patient outcome and predictive factors for successful day-case laparoscopic cholecystectomy. METHOD: A retrospective analysis of our prospective database of 176 patients following laparoscopic cholecystectomy in a day-surgery unit was performed. A telephone interview was conducted within 24 h after discharge and again after 3 weeks. RESULTS: Of the 176 cases included in this study, 74% had biliary colic, cholecystitis (16%), pancreatitis (8%), and jaundice (2%). In addition to LC, nine patients (5.1%) underwent laparoscopic bile duct exploration and ten (5.7%) had an additional procedure performed. Eighty-six percent of the patients were discharged the same day. Multivariate analysis identified risk factors affecting same-day discharge, including age greater than 50 years and intraoperative complications. Bile duct exploration reduced the odds of discharge but did not reach significance. Postoperative telephone interviews identified high patient satisfaction with 86% of respondents recommending LC as a day-surgery procedure. CONCLUSION: Day-surgery LC is a safe procedure with an acceptable rate of patient discharge. However, intraoperative complications or age over 50 years adversely affected the same-day discharge rate and as such should be taken into consideration when planning day-case laparoscopic cholecystectomy.

Structural properties of liquid N-methylacetamide via ab initio, path integral, and classical molecular dynamics.

In order to better understand the physical interactions that stabilize protein secondary structure, the neat liquid state of a peptidic fragment, N-methylacetamide (NMA), was studied using computer simulation. Three different descriptions of the molecular liquid were examined: an empirical force field treatment with classical nuclei, an empirical force field treatment with quantum mechanical nuclei, and an ab initio density functional theory (DFT) treatment. The DFT electronic structure was evaluated using the BLYP approximate functional and a plane wave basis set. The different physical effects probed by the three models, such as quantum dispersion, many-body polarization, and nontrivial charge distributions on the liquid properties, were compared. Much of the structural ordering in the liquid is characterized by hydrogen bonded chains of NMA molecules. Modest structural differences are present among the three models of liquid NMA. The average molecular dipole in the liquid under the ab initio treatment, however, is enhanced by 60% over the gas phase value.

Structure and hydrogen bonding in neat N-methylacetamide: classical molecular dynamics and Raman spectroscopy studies of a liquid of peptidic fragments.

The results of classical molecular dynamics (MD) simulations and Raman spectroscopy studies of neat liquid N-methylacetamide (NMA), the simplest model system relevant to the peptides, are reported as a function of temperature and pressure. The MD simulations predict that near ambient conditions, the molecules form a hydrogen bond network consisting primarily of linear chains. Both the links between molecules within the hydrogen-bonded chains and the associations between chains are stabilized by weak methyl-donated "improper" hydrogen bonds. The three-dimensional structural motifs observed in the liquid show some similarity to protein beta-sheets. The temperature and pressure dependence of the hydrogen bond network, as probed by the mode frequency of the experimentally determined amide-I Raman band, blue shifts on heating and red shifts under compression, respectively, suggesting weakened and enhanced hydrogen bonding in response to temperature and pressure increases. Disruption of the hydrogen-bonding network is clearly observed in the simulation data as temperature is increased, whereas the improper hydrogen bonding is enhanced under compression to reduce the energetic cost of increasing the packing fraction. Because of the neglect of polarizability in the molecular model, the computed dielectric constant is underestimated compared to the experimental value, indicating that the simulation may underestimate dipolar coupling in the liquid.

Vanadogermanate cluster anions.

Three novel vanadogermanate cluster anions have been synthesized by hydrothermal reactions. The cluster anions are derived from the (V(18)O(42)) Keggin cluster shell by substitution of V=O(2+) "caps" by Ge(2)O(OH)(2)(4+) species. In Cs(8)[Ge(4)V(16)O(42)(OH)(4)].4.7H(2)O, 1, (monoclinic, space group C2/c (No. 15), Z = 8, a = 44.513(2) A, b = 12.7632(7) A, c = 22.923(1) A, beta = 101.376(1) degrees ) and (pipH(2))(4)(pipH)(4)[Ge(8)V(14)O(50).(H(2)O)] (pip = C(4)N(2)H(10)), 2 (tetragonal, space group P4(2)/nnm (No. 134), Z = 2, a = 14.9950(7) A, c = 18.408(1) A), two and four VO(2+) caps are replaced, respectively, and each cluster anion encapsulates a water molecule. In K(5)H(8)Ge(8)V(12)SO(52).10H(2)O, 3, (tetragonal, space group I4/m (No. 87), Z = 2, a = 15.573(1) A, c = 10.963(1) A), four VO(2+) caps are replaced by Ge(2)O(OH)(2)(4+) species, and an additional two are omitted. The cluster ion in 3 contains a sulfate anion disordered over two positions. The cluster anions are analogous to the vanadoarsenate anions [V(18)(-)(n)()As(2)(n)()O(42)(X)](m)(-) (X = SO(3), SO(4), Cl; n = 3, 4) previously reported.

Reproductive decisions by women with bipolar disorder after prepregnancy psychiatric consultation.

OBJECTIVE: This study ascertained family planning decisions by women with bipolar disorder after psychiatric consultation. METHOD: The authors surveyed 116 women with DSM-IV bipolar disorder after specialized consultation about treatment options and risks regarding pregnancy. RESULTS: Of 70 respondents, 45% had been advised to avoid pregnancy by a health care professional before consultation. After consultation, 63% decided to pursue pregnancy. CONCLUSIONS: Women with bipolar disorder often encounter obstacles from health care professionals regarding pregnancy. Individualized comprehensive review of risks and benefits of treatment options during specialized preconception consultation can support thoughtful clinical planning.

Gravitational smoothing as a global optimization strategy.

An optimization scheme for atomic cluster structures, based on exaggerating the importance of the gravitational force, is introduced. Results are presented for calculations on Lennard-Jones clusters of 13, 38, and 55 atoms, and the 13-atom Morse cluster.

Enhanced sampling in numerical path integration: an approximation for the quantum statistical density matrix based on the nonextensive thermostatistics.

Here we examine a proposed approximation for the quantum statistical density matrix motivated by the nonextensive thermostatistics of Tsallis and co-workers. The approximation involves replacing the physical potential energy with an effective one, corresponding to a generalized nonextensive statistical ensemble. We examine the convergence properties of averages calculated using the effective potential, and introduce a related method for enhanced sampling in numerical path integration. As a necessary measure, path integral energy estimators are introduced for potentials that involve explicit temperature dependence. This sampling method is found to be effective for path integral simulations involving broken ergodicity.

Expression of BMP signalling pathway members in the developing zebrafish inner ear and lateral line.

In this paper we describe the mRNA expression patterns of members of the bone morphogenetic protein (BMP) signalling pathway in the developing zebrafish ear. bmp2b, 4, and 7 are expressed in discrete areas of otic epithelium, some of which correspond to sensory patches. bmp2b and 4 mark the developing cristae before and during the appearance of differentiated hair cells. bmp4 is also expressed in a dorsal, non-sensory region of the ear. Expression of bmps in cristae is conserved between zebrafish, chick, and mouse, but there are also notable differences in ear expression patterns between these species. Of five zebrafish BMP antagonists, only one (follistatin) shows significant expression in the otic epithelium. The type I receptor bmpr-IB shows localised expression in the ear epithelium. Mediators of BMP signalling, smad1 and smad5, are expressed in statoacoustic and lateral line ganglia; smad5 is also expressed at low levels throughout the ear epithelium. An inhibitory smad, smad6, is expressed laterally in the ear epithelium. Lateral line primordia and neuromasts also express bmp2b, 4, follistatin, smad1, and smad5. The conservation of bmp expression in cristae among different species adds weight to the growing evidence that BMPs are required for the development of the vertebrate ear.

Zebrafish sparse corresponds to an orthologue of c-kit and is required for the morphogenesis of a subpopulation of melanocytes, but is not essential for hematopoiesis or primordial germ cell development.

The relative roles of the Kit receptor in promoting the migration and survival of amniote melanocytes are unresolved. We show that, in the zebrafish, Danio rerio, the pigment pattern mutation sparse corresponds to an orthologue of c-kit. This finding allows us to further elucidate morphogenetic roles for this c-kit-related gene in melanocyte morphogenesis. Our analyses of zebrafish melanocyte development demonstrate that the c-kit orthologue identified in this study is required both for normal migration and for survival of embryonic melanocytes. We also find that, in contrast to mouse, the zebrafish c-kit gene that we have identified is not essential for hematopoiesis or primordial germ cell development. These unexpected differences may reflect evolutionary divergence in c-kit functions following gene duplication events in teleosts.

Hair cells without supporting cells: further studies in the ear of the zebrafish mind bomb mutant.

Each sensory hair cell in the ear is normally surrounded by supporting cells, which separate it from the next hair cell. In the mind bomb mutant, as a result of a failure of lateral inhibition, cells that would normally become supporting cells differentiate as hair cells instead, creating sensory patches that consist of hair cells only. This provides a unique opportunity to pinpoint the functions for which supporting cells are required in normal hair cell development. We find that hair cells in the mutant develop an essentially normal cytoskeleton, with a correctly structured hair bundle and well-defined planar polarity, and form apical junctional complexes with one another in standard epithelial fashion. They fail, however, to form a basal lamina or to adhere properly to the adjacent non-sensory epithelial cells, which overgrow them. The hair cells are eventually expelled from the ear epithelium into the underlying mesenchyme, losing their hair bundles in the process. It is not clear whether they undergo apoptosis: many cells staining strongly with the TUNEL procedure are seen but do not appear apoptotic by other criteria. Supporting cells, therefore, are needed to hold hair cells in the otic epithelium and, perhaps, to keep them alive, but are not needed for the construction of normal hair bundles or to give the hair bundles a predictable polarity. Moreover, supporting cells are not absolutely required as a source of materials for otoliths, which, though small and deformed, still develop in their absence.

Intercellular signals and cell-fate choices in the developing inner ear: origins of global and of fine-grained pattern.

The major regions of the inner ear begin to be distinguishable by their patterns of gene expression very early, before the otocyst has closed. Later, individual cells within a neurogenic or sensory patch become committed to specific pathways of differentiation. Insights gained from homologies with invertebrates and from studies of tissues other than the ear, combined with discoveries from screens for mutations affecting development in the zebrafish, are beginning to reveal the genes and signalling mechanisms that control these cell-fate choices in the developing inner ear.