STAT4 expression and activation is increased during mitosis in vitro and in vivo in skin- and mucosa-derived cell types: implications in neoplastic and inflammatory skin diseases.

BACKGROUND: The signal transducer and activator of transcription-4 (STAT4/Stat4) is a transcription factor known to convey signals from interleukin-12, interleukin-23, and interferon-alpha/beta to the nucleus, resulting in activation of dendritic cells, T-helper cell differentiation and production of interferon-gamma. OBJECTIVE: To demonstrate a novel role for STAT4 in cell mitosis. RESULTS: Phosphoserine STAT4 (pSerSTAT4) is increased in cells undergoing mitosis and is distributed throughout the cytoplasm during this stage of the cell cycle, whilst phosphotyrosine STAT4 (pTyrSTAT4) is confined to the chromosomal compartment. This distinct pattern of pSerSTAT4 during mitosis is seen in vitro in human keratinocytes and in other cell types. This is also present in vivo in cells undergoing mitosis in normal skin, psoriasis and squamous cell carcinoma. Inhibition of STAT4 phosphorylation by lisofylline and depletion of STAT4 by RNA interference results in a delay in progression of mitosis and leads to a reduction in cells completing cytokinesis. CONCLUSION: Our data demonstrate that STAT4 plays a role in enabling the normal and timely division of cells undergoing mitosis.

In vitro diagnostic assays are effective during the acute phase of delayed-type drug hypersensitivity reactions.

BACKGROUND: Previous reports have suggested that drug-specific lymphocyte proliferation assays (LPA) can be used retrospectively to confirm the culprit drug following delayed-type drug hypersensitivity reactions (DHR). However, only limited evidence supports their use in aiding acute clinical management. The aim of this study was to compare the LPA against combination cytokine assays for potential use in the acute setting. METHODS: A total of 43 patients with DHR (19 during the acute reaction, 20 after recovery, four during acute and after recovery) and 14 control subjects without DHR were investigated using ex vivo analysis of drug-specific proliferation, and interferon (IFN)-γ and interleukin (IL)-4 production. RESULTS: Healthy controls showed negative drug-specific proliferation and cytokine release in contrast to individuals with a known sensitivity (P < 0·0001). The assays demonstrated a test specificity of 95% (LPA), 83% (IFN-γ) and 92% (IL-4). The sensitivity of combined measurement of drug-specific IFN-γ and IL-4 cytokines during acute DHR was better than LPA (82% vs. 50%), but all assays were less sensitive during the recovery phase. The correlation between LPA and IFN-γ assays was strong (r = 0·7, P < 0·0001), whereas the IL-4 assay did not correlate as well with either of these assays. In contrast to LPA, drug enzyme-linked immunosorbent spot assays showed positive responses in patients concurrently taking immunosuppressive medication. CONCLUSIONS: In vitro assays of drug-specific IFN-γ and IL-4 production offer potential for use as rapid diagnostic tests. Cytokine detection offers distinct advantages over the LPA, including a shorter assay time, a greater sensitivity and effectiveness in testing immunosuppressed patients.

Quantum Monte Carlo study of a positron in an electron gas.

Quantum Monte Carlo calculations of the relaxation energy, pair-correlation function, and annihilating-pair momentum density are presented for a positron immersed in a homogeneous electron gas. We find smaller relaxation energies and contact pair-correlation functions in the important low-density regime than predicted by earlier studies. Our annihilating-pair momentum densities have almost zero weight above the Fermi momentum due to the cancellation of electron-electron and electron-positron correlation effects.

Crystal structures of dense lithium: a metal-semiconductor-metal transition.

Ab initio random structure searching and single-crystal x-ray diffraction have been used to determine the full structures of three phases of lithium, recently discovered at low temperature above 60 GPa. A structure with C2mb symmetry, calculated to be a poor metal, is proposed for the oC88 phase (60-65 GPa). The oC40 phase (65-95 GPa) is found to have a lowest-enthalpy structure with C2cb symmetry, in excellent agreement with the x-ray data. It is calculated to be a semiconductor with a band gap of ∼1 eV at 90 GPa. oC24, stable above 95 GPa, has the space group Cmca, and refined atomic coordinates are in excellent agreement with previous calculations.

Repeated low-dose skin exposure is an effective sensitizing stimulus, a factor to be taken into account in predicting sensitization risk.

BACKGROUND: Contact sensitization by ingredients in personal products is an important clinical problem. It is not clear how sensitization is induced by the generally low concentrations at which they occur but it might be the result of repeated exposure. OBJECTIVES: To compare the strength of contact sensitization induced by a single exposure to 2,4-dinitrochlorobenzene (DNCB) (60 microg cm(-2)) or three repeated exposures to a subsensitizing dose (10 microg cm(-2)). METHODS: Two groups (n = 10) of healthy adult volunteers were randomized to receive either a single patch of DNCB 60 microg cm(-2) or three once-weekly applications to the same site of 10 microg cm(-2) DCNB. Four weeks after the last application, sensitization was quantified by measurement of responses (skinfold thickness) to a graded series of four challenge doses. RESULTS: All the volunteers were sensitized and the strength of the responses was virtually identical between the groups. CONCLUSIONS: The same degree of sensitization was induced by three exposures to DNCB 10 microg cm(-2) as by one exposure to 60 microg cm(-2) of DNCB. Thus repeated exposure to low doses of contact sensitizers may increase the sensitizing potency. This must be taken into account in future risk assessments.

Speed of sound from fundamental physical constants.

Two dimensionless fundamental physical constants, the fine structure constant α and the proton-to-electron mass ratio [Formula: see text], are attributed a particular importance from the point of view of nuclear synthesis, formation of heavy elements, planets, and life-supporting structures. Here, we show that a combination of these two constants results in a new dimensionless constant that provides the upper bound for the speed of sound in condensed phases, vu We find that [Formula: see text], where c is the speed of light in vacuum. We support this result by a large set of experimental data and first-principles computations for atomic hydrogen. Our result expands the current understanding of how fundamental constants can impose new bounds on important physical properties.

A quality improvement intervention to increase palliative care in nursing homes.

CONTEXT: Death is common in nursing homes, but access to palliative care is limited. OBJECTIVE: To test whether a quality improvement (QI) intervention in nursing homes increases hospice, pain management, and advance care planning. DESIGN AND SETTING: The QI intervention was tested in seven nursing homes using a prepoststudy design. Two additional nursing homes served as control sites. PARTICIPANTS: Nine nursing homes serving 1169 residents. INTERVENTION: The intervention included recruitment and training of Palliative Care Leadership Teams in each facility, followed by six technical assistance meetings for team members. Hospice providers delivered six educational sessions for all nursing home staff using a structured curriculum. Teams received feedback of performance data on hospice enrollment, pain management, and advance care planning at 0, 3, and 6 months. MAIN OUTCOME MEASURES: Percentage of residents receiving hospice or palliative services, pain assessment, pain treatment among residents in pain, and documented advance care planning discussions. RESULTS: Intervention facilities increased hospice enrollment from 4.0% of residents at baseline to 6.8% postintervention (p = .01) and increased pain assessments from 18% to 60% (p < .001). Among resident in pain, orders for nonpharmacologic pain treatments increased from 15% to 35% (p < .001), but pain medication use did not change. Residents with in-depth discussions about end-of-life care increased from 4% to 17% (p < .001). There were no significant changes in control sites. CONCLUSIONS: A quality improvement intervention was effective in increasing hospice enrollment, pain assessment, nonpharmacologic pain treatment, and advance care planning discussions.

Differentiation of gluteus medius and minimus activity in weight bearing and non-weight bearing exercises by M-mode ultrasound imaging.

BACKGROUND: Knowledge on task-specific activity of the deep hip abductor muscles is limited and is required for determining appropriate hip abductor exercises. OBJECTIVES: To assess the temporal differentiation of activity of gluteus minimus and the deep and the superficial regions of gluteus medius during weight bearing and non-weight bearing exercises. DESIGN: Repeated measures design on a single recording occasion. METHOD: M-mode ultrasound was used to capture activity-related muscle motion of the gluteus minimus and medius muscles in 20 healthy volunteers during weight shift, hip hitch, side-lying abduction and active leg lengthening exercises. M-mode traces were computer-processed for detecting muscle motion onsets. Mean onset differences between muscle regions and their intra-individual variability were assessed. RESULTS: In contrast to side-lying abduction, the weight shift and hip hitch exercises resulted in larger onset variability between the gluteus minimus and deep gluteus medius (P < 0.001) and also between the deep and superficial regions of the gluteus medius (P < 0.05). CONCLUSIONS: Weight bearing exercises promoted a greater functional differentiation between deep and superficial hip abductor muscles.

Experimental evidence of new tetragonal polymorphs of silicon formed through ultrafast laser-induced confined microexplosion.

Ordinary materials can transform into novel phases at extraordinary high pressure and temperature. The recently developed method of ultrashort laser-induced confined microexplosions initiates a non-equilibrium disordered plasma state. Ultra-high quenching rates overcome kinetic barriers to the formation of new metastable phases, which are preserved in the surrounding pristine crystal for subsequent exploitation. Here we demonstrate that confined microexplosions in silicon produce several metastable end phases. Comparison with an ab initio random structure search reveals six energetically competitive potential phases, four tetragonal and two monoclinic structures. We show the presence of bt8 and st12, which have been predicted theoretically previously, but have not been observed in nature or in laboratory experiments. In addition, the presence of the as yet unidentified silicon phase, Si-VIII and two of our other predicted tetragonal phases are highly likely within laser-affected zones. These findings may pave the way for new materials with novel and exotic properties.

Interleukin-10 (IL10) promoter polymorphisms and multiple sclerosis.

Interleukin-10 (IL10) is an anti-inflammatory cytokine which may modulate disease expression in multiple sclerosis (MS). Three dimorphic polymorphisms within the IL10 promoter region at positions - 1082, -819 and -519 have previously been identified. The - 1082*A allele has been associated with low and the - 1082*G allele with high in vitro IL10 production. We have genotyped 185 Caucasian MS patients and 211 ethnically matched controls for each of these three dimorphisms. MS patients were stratified for severity of disease outcome. No associations were found for any IL10 promoter polymorphisms when the MS cases were compared with controls or with disease outcome with regards to disability. IL10 polymorphism does not appear to be associated with MS or to influence disease progression.

Custodial nursing home care. Setting realistic goals.

Despite concerted effort to rehabilitate and return patients to their homes, the majority of nursing home patients are destined to spend the remainder of their days in institutional settings. These custodial care patients are elderly, have many functional disabilities, and are often demented. The traditional medical approach to care, which emphasizes diagnosis and treatment of specific diseases, is often not appropriate for these patients. Instead, physicians should focus their attention on functional assessment and treatment, nontechnologic management of acute problems, humane terminal care, and the development of an efficient caregiving system within the nursing home.

Diagnostic role of tests for T cell receptor (TCR) genes.

Rapid advances in molecular biological techniques have made it possible to study disease pathogenesis at a genomic level. T cell receptor (TCR) gene rearrangement is an important event in T cell ontogeny that enables T cells to recognise antigens specifically, and any dysregulation in this complex yet highly regulated process may result in disease. Using techniques such as Southern blot hybridisation, polymerase chain reaction, and flow cytometry it has been possible to characterise T cell proliferations in malignancy and in diseases where T cells have been implicated in the pathogenesis. The main aim of this article is to discuss briefly the process of TCR gene rearrangement and highlight the disorders in which expansions or clonal proliferations of T cells have been recognised. It will also describe various methods that are currently used to study T cell populations in body fluids and tissue, their diagnostic role, and current limitations of the methodology.

A rapid HPLC method for monitoring plasma levels of caffeine and theophylline using solid phase extraction columns.

A simple HPLC method for the determination of caffeine and theophylline in plasma is described. Separation of theobromine, paraxanthine, theophylline, beta-hydroxyethyltheophylline and caffeine is obtained using a mobile phase of 1% acetic acid/methanol (83:17, v/v) and a Waters Associates NOVA-PAK C18 column protected by a Guard-PAK precolumn module containing a Guard-PAK CN cartridge. Rapid sample preparation is achieved by solid-phase extraction columns (Bond-Elut C18, 1 mL capacity) which provide excellent recovery values for both drugs. The cost per sample using this approach can be minimised by column regeneration and re-use. Results obtained for theophylline are in good agreement with values determined by other techniques.

Cutaneous signs of systemic disease.

In this article we have discussed briefly some of the important diseases in which a thorough skin examination is of help in evaluation and diagnosis of patients in an emergency department. Changes in the skin, for instance, may be the first clue of an internal malignancy. Disorders associated with gastrointestinal bleeding, endocrine abnormalities, and/or epilepsy can have prominent cutaneous manifestations. Thus, an awareness of the unusual findings is of value to the emergency medicine physician.

Long-term care organizational challenges and strategies art vs. regulation.

1. Long-term residents of nursing homes, especially those with chronic deteriorating illnesses, may be at risk of overly rigorous treatment or abandonment because they do not fit the typical rehabilitative or terminal care planning models. 2. A proactive approach to care planning once rehabilitation is no longer an option emphasizes ongoing dialogue with the resident and family to determine their values and wishes for care, not merely determining the treatments they want withheld. 3. Although staff are enthusiastic about proactive, individualized, interdisciplinary planning for the care of residents, in actuality it is extremely difficult given current organizational constraints.

Superconducting graphene sheets in CaC6 enabled by phonon-mediated interband interactions.

There is a great deal of fundamental and practical interest in the possibility of inducing superconductivity in a monolayer of graphene. But while bulk graphite can be made to superconduct when certain metal atoms are intercalated between its graphene sheets, the same has not been achieved in a single layer. Moreover, there is a considerable debate about the precise mechanism of superconductivity in intercalated graphite. Here we report angle-resolved photoelectron spectroscopy measurements of the superconducting graphite intercalation compound CaC6 that distinctly resolve both its intercalant-derived interlayer band and its graphene-derived π* band. Our results indicate the opening of a superconducting gap in the π* band and reveal a substantial contribution to the total electron-phonon-coupling strength from the π*-interlayer interband interaction. Combined with theoretical predictions, these results provide a complete account for the superconducting mechanism in graphite intercalation compounds and lend support to the idea of realizing superconducting graphene by creating an adatom superlattice.

Oxygen K-edge electron energy loss spectra of hydrous and anhydrous compounds.

First-principles calculations have been employed to examine the possible use of electron energy loss spectroscopy (EELS) as a tool for determining the presence of OH groups and hence hydrogen content in compounds. Our density functional theory (DFT) based calculations describe accurately the experimental EELS results for forsterite (Mg2SiO4), hambergite (Be2BO3(OH)), brucite (Mg(OH)2) and diaspore (α-AlOOH). DFT calculations were complemented by an experimental time resolved study of the oxygen K-edge in diaspore. The results show unambiguously that there is no connection between a pre-edge feature in the oxygen K-edge spectrum of diaspore and the presence of OH groups in the structure. Instead, the experimental study shows that the pre-edge feature in diaspore is transient. It can be explained by the presence of molecular O2, which is produced as a result of the electron irradiation.